0% found this document useful (0 votes)

71 views35 pages

Sulfone Synthesis Advances

Uploaded by

Ana Dhar

We take content rights seriously. If you suspect this is your content, claim it here.

Available Formats

Download as PDF, TXT or read online on Scribd

0% found this document useful (0 votes)

71 views35 pages

Sulfone Synthesis Advances

Uploaded by

Ana Dhar

We take content rights seriously. If you suspect this is your content, claim it here.

Available Formats

Download as PDF, TXT or read online on Scribd

SYNTHESIS0039-78 1 437-210X

© Georg Thieme Verlag Stuttgart · New York

2016, 48, 1939–1973 1939
review

Syn thesis N.-W. Liu et al. Review

Recent Advances in the Synthesis of Sulfones

Nai-Wei Liu traditional approaches
Shuai Liang S R2-X
R1 R2 R1-X + SO2 +
Georg Manolikakes* 3-component procedures
O
O O
S S 2
Institut für Organische Chemie und Chemische Biologie, R1 O R1 R
Goethe-Universität Frankfurt, Max-von-Laue-Str. 7, 60438 R1-H
O O
Frankfurt, Germany
S synthesis by C–H activation
[Link]@[Link] R1 X

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Received: 04.03.2016 transformation.1,4 In addition, sulfone groups can stabilize
Accepted after revision: 04.04.2016
adjacent carbanions.1,5 Classical reactions of sulfones in or-
Published online: 07.06.2016
DOI: 10.1055/s-0035-1560444; Art ID: ss-2016-e0158-r ganic synthesis include the Ramberg–Bäcklund reaction of
α-halo sulfones6 or the Julia–Lythgoe as well as the modi-
Abstract Sulfones are versatile intermediates in organic synthesis and fied Julia olefination (Scheme 1).7
important building blocks in the construction of biological active mole-
cules or functional materials. This review provides a summary of recent
O O
developments in the synthesis of sulfones. R1 S 2
1 Introduction sulfonyl R good
group
2 Classical Methods and Variants facilitates H leaving
group
2.1 Oxidation of Sulfides deprotonation
O O
2.2 Aromatic Sulfonylation
S 2
2.3 Alkylation/Arylation of Sulfinates good Michael R
acceptor
2.4 Addition to Alkenes and Alkynes
R1
2.5 Miscellaneous Methods
3 Metal-Catalyzed Coupling Reactions Ramberg–Bäcklund reaction

4 Sulfone Synthesis by C–H Functionalization O O

Base
R1 S R2
5 Sulfur Dioxide Based Three-Component Approaches
– SO2 R1 R2
6 Biological Synthesis of Sulfones X
7 Conclusion
Julia–Lythgoe olefination

Key words sulfone, addition, coupling, catalysis, medicinal chemistry, 1) base OAc
R2
SO2Ph 2) R2-CHO Na(Hg)
multicomponent reaction R2
R1
R1 3) Ac2O R1
SO2Ph

1 Introduction modified Julia olefination

O O O base R2
Sulfones (R-SO2-R) are versatile synthetic intermediates S R1 +
Het R2 H R1
in organic chemistry, and molecules bearing a sulfone unit
have found various applications in diverse fields such as ag- Het = benzothiazole, 1-phenyl-1H-tetrazole,
1-tert-butyl-1H-tetrazole
rochemicals, pharmaceuticals and polymers.1 The sulfone
group can be employed as a temporary modulator of chem- Scheme 1

ical reactivity. Therefore a variety of different transforma-

tions are feasible with this functional group, leading to the Apart from these classical transformations, sulfones
description of sulfones as ‘chemical chameleons’.2 Sulfone have been employed as versatile intermediates for the
groups can function as activating, electron-withdrawing preparation of various product classes, for example the
substituents in Michael acceptors1,3 or as good leaving van Leusen synthesis of oxazoles and imidazoles8 or the
groups producing a sulfinate anion, a reactivity that often synthesis of quinolines (Scheme 2).9
facilitates removal of the sulfone moiety after the desired

Syn thesis N.-W. Liu et al. Review

van Leusen synthesis Due to their distinct electronic and structural features,
O
N oxazole
sulfones play a prominent role in various fields of applica-
Me
X
base
R tions. A large number of biologically active molecules con-
S NC
+
R H R'
or tain this functional group.10 The sulfone scaffold is thus of
O O N
N imidazole
particular relevance in medicinal chemistry. Molecules
X = O, NR'
R used against diverse medical indications such as eletrip-
tan11 (treatment of migraine), bicalutamide12 (treatment of
prostate cancer) or the antibacterial dapsone13 feature a
O
sulfone unit (Figure 1). The sulfone group is also embedded
NHBoc O O
O O O
S in various important agrochemicals, for example mesotri-

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
R3 R2
R3
S
R2 +
t-BuLi one,14 pyroxasulfone15 or cafenstrole16 (Figure 1). Sulfone-
R4
CuCN, LiCl R1 containing polymers display interesting properties and bis-
R1
R4
NHBoc phenol S (Figure 1) is used replacement for bisphenol A.17
O
Considering this plethora of possible applications, it is
O O
S
R1 not surprising that a number of efficient methods for the
R3 R2 TFA, Δ R4 synthesis of sulfones have been developed. Indeed, the first
R4
R 1
methods were reported in the 19th century. The constant
R2 N
NHBoc
demand for efficient, robust and more sustainable ap-
quinoline
proaches for the preparation of sulfones has led to a resur-
Scheme 2 gence of research activities in this field in recent years. This
review highlights advances in the synthesis of sulfones un-
til the end of 2015.

Biographical Sketches

Georg Manolikakes was born ized organometallics and cross- search group leader at the
in Ebersberg (Germany) in coupling reactions. From Goethe-Universität Frankfurt.
1979. He studied chemistry at 2009–2010 he worked as a His research interests are multi-
the LMU Munich (Germany) postdoctoral fellow with Prof. component and one-pot reac-
where he received his Diploma Phil S. Baran at the Scripps Re- tions, synthesis of sulfonyl-
in 2005. In 2009 he obtained his search Institute (La Jolla, USA) group-containing molecules
PhD from the same university on synthesis of cortistatin A. At and asymmetric synthesis.
under the guidance of Prof. Paul the end of 2010 he took up his
Knochel working on functional- current position as junior re-

Shuai Liang was born in Qing- versity under the supervision of research interest focuses on
dao (P. R. of China) in 1988. He Prof. Xiaoqi Yu. Since November novel methods for the synthesis
earned his BS degree in 2011 2014 he is a PhD student at the of sulfones via selective C–H
from Sichuan University. In Goethe-Universität Frankfurt, functionalization.
2014 he received his MS degree under the supervision of Dr.
in chemistry from Sichuan Uni- Georg Manolikakes. His current

Nai-Wei Liu was born in Taipei Universität Frankfurt (Germa- veloping new methods for the
(Taiwan R.O.C.) in 1987. He ob- ny). He is currently working on fixation of sulfur dioxide into
tained his [Link]. and [Link]. de- his PhD thesis in the group of small molecules.
grees from the Goethe- Dr. Georg Manolikakes and de-

Syn thesis N.-W. Liu et al. Review

O O General reaction:
H HO Me O O
S H
Ph N S O O O
S oxidizing conditions
N S 2 via
R1 R2 S 2
O R1 R R1 R
Me NC F
sulfide sulfone sulfoxide
N CF3
H Recent examples
eletriptan bicalutamide
O O NO2 O O
O O S oxidant
Ph Me S
S Ph Me

Me
O S
H2N NH2
O O Oxidant:
dapsone mesotrione

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O urea-H2O2, neat, 85 °C 87%
N
Me O
O S Me H2O2, NbC (4 mol%), 92%
Me CHF2 N
O O O N EtOH, 60 °C
S
O Me
N NEt2 KMnO4/MnO2, neat, rt 83–93%
N
N Me
pyroxasulfone cafenstrole Me 30% aq H2O2, 75 °C 68%

O O NaOCl, cyanuric acid (10 mol%) 96%

S toluene, rt

Scheme 3
HO OH
bisphenol S

Figure 1 2.2 Aromatic Sulfonylation

Another widely used strategy for the synthesis of sul-

2 Classical Methods and Variants fones involves the reaction between a (hetero)arene and a
sulfonyl halide or sulfonic acid in the presence of a suitable
The four traditional and still most common approaches Lewis or Brønsted acid catalyst (Scheme 4).1 Sulfonyl chlo-
for the synthesis of sulfones are the oxidation of the corre- rides are most commonly employed in these Friedel–Crafts-
sponding sulfides or sulfoxides, alkylation of sulfinate salts, type reactions and substituents on the (hetero)arene exert
Friedel–Crafts-type sulfonylation of arenes, and addition activating/deactivating as well as directing effects as ex-
reactions to alkenes and alkynes.1 Although all four reac- pected for electrophilic aromatic substitutions.23 Typically,
tion types were discovered several decades ago, new vari- these reactions are performed in the presence of stoichio-
ants with improved substrate scope, functional group toler- metric amounts of conventional Lewis or Brønsted acid,
ance and efficiency, as well as new reagents, are constantly such as aluminum trichloride, iron(III) chloride or phos-
being developed. Other methods, such as rearrangements, phoric acid.24
reactions of sulfonic acid derivatives with nucleophiles, or
O O catalyst O O
cycloaddition reactions, although known for decades, are
S S
rarely used. R X Ar-H R Ar
sulfonyl halide sulfone
(X = Cl, F, Br)
2.1 Oxidation of Sulfides
catalyst
and/or
The oxidation of sulfides is perhaps still the most fa- O O activating agent O O
vored method for the synthesis of sulfones. While a variety S Ar-H S
R OH R Ar
of oxidants can be used for this transformations,1 peracids
sulfonic acid sulfone
or hydrogen peroxide in combination with acetic acid are
most frequently employed (Scheme 3).18 In general, excess Scheme 4

oxidizing agent, high temperatures and/or long reaction

times are necessary to achieve complete conversion of the In general, these reactions suffer from the typical draw-
intermediate sulfoxide to the sulfone. In most cases, exist- backs of Friedel–Crafts-type processes, such as harsh reac-
ing procedures will furnish the desired sulfones in accept- tion conditions, low regioselectivity, the need for stoichio-
able yields. Current research focuses mainly on safe oxida- metric amounts of the catalyst, and the generation of sub-
tion reagents, such as urea–hydrogen peroxide,19 catalytic stantial quantities of hazardous waste. Therefore, a variety
systems for milder and faster oxidations20 and solvent-free of more efficient catalysts have been developed throughout
systems21 or highly sustainable methods.22 the last decades.25 Special emphasis was placed on more
sustainable methods such as reusable solid acids,25e sol-
vent-free25i or ionic-liquid-based25d,f systems and reactions

Syn thesis N.-W. Liu et al. Review

with low catalyst loadings.25i The direct sulfonylation of An unusual process is the sulfonylation of arenes with
arenes with sulfonic acids in the presence of acid catalysts sulfonamides in the presence of triflic anhydride as activat-
has also been reported.25e,26 Activation of the sulfonic acid ing agent.32 This method provides an alternative access to
with suitable reagents, such as phosphorus pentoxide or aryl sulfones using a stable primary sulfonamide as sulfo-
triflic anhydride, leads to the in situ formation of reactive nylating agent (Scheme 7).
mixed anhydrides and an efficient sulfonylation of arenes at
O O
room temperature.27 Ar-H +
Tf2O O O
S S
DCE, 80–120 °C
Sulfones are frequently encountered side-products in R NH2 R Ar

the sulfonation of arenes with sulfuric acid.28 They are 42–95% yield

formed by the reaction of the intermediate sulfonic acid O O O O Me

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
with an excess of the arene. Removal of water during the re- S S
action furnishes the symmetrical diaryl sulfone as the ma-
jor product (Scheme 5).29 In a similar manner, symmetrical Me
89%
Br O2N
42%
Me
diaryl sulfones can be prepared by the reaction of an arene Me O O O O
with dimethyl pyrosulfate in the presence of sulfuric acid.30 S S S
Me

Method A Ph
H2SO4 O O
Ar-H Me 86% 58%
S
Method B Ar Ar
MeO-SO2-O-SO2-OMe Scheme 7
sulfone
H2S2O7

2.3 Alkylation/Arylation of Sulfinates

O O O O
S S
The salts of sulfinic acids are useful precursors for the
synthesis of sulfones. Sulfinates are powerful nucleophiles
80% 41%
Method A Method A and react with a variety of different electrophiles at the sul-
O O O O
fur atom to form sulfones.1,33 Only in the case of hard al-
S S kylating agents, such as dimethyl sulfate or diazomethane,
does O-alkylation occur, and the corresponding sulfinate
83% 80% Me esters are produced predominantly (Scheme 8).34
Method B Method B

Scheme 5 O O O
S S
R M R O M
31
Rao and co-workers reported a similar method. Their sulfinate
procedure enables the one-pot synthesis of symmetrical as
well as unsymmetrical diaryl sulfones starting from arenes, O O O
+ E+ sulfone
a persulfate salt, trifluoromethanesulfonic acid (TfOH) and R
S
O M R
S
E
trifluoroacetic acid anhydride (TFAA) (Scheme 6). The reac- sulfinate electrophile O
sulfinate ester
tion is presumed to proceed via a sulfonic acid which is ac- S
R O E
tivated to the corresponding anhydride with TFAA. minor product or
not formed at all
K2S2O8 O O
Ar1-H + Ar2-H S Scheme 8
TfOH, TFAA Ar1 Ar2
35–98% yield

Me O O Me Me O O Me Typical electrophiles include alkyl halides,34,35 epox-

S O S O
N N ides,36 Michael acceptors,37 and aryl halides activated to-
F3C CF3 wards nucleophilic aromatic substitution (Scheme 9).38 Al-
Me Me
91% 80%
though the reactions are generally high-yielding, simple to
Me
O O
Me O O perform and suitable for a broad scope of alkylating agents,
S
S S this approach is limited owing to the modest availability of
F
sulfinate salts.
60% Me 47%
Me

Scheme 6

Syn thesis N.-W. Liu et al. Review

O O tions, this method is not limited to activated arenes, and

R
S
Alkyl
unsymmetrical diaryliodonium salts can transfer one aryl
moiety with high degrees of chemoselectivity (Scheme 11).
Alkyl-X
alkyl hailde X
O O O O O I
Ar-X EWG
S O Ar2 Ar3 O O
R Ar activated S S
R O M Michael acceptor R EWG S S
aryl halide Ar1 O Na DMF, 90 °C Ar1 Ar2
sulfinate
X = Cl, PF6, BF4, 17–96% yield
O OTs, OTf
epoxide O O O O

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
S S S
O O
S
R OH
94% 83%
Scheme 9 Me
O O O O
S S CF3

Recent developments in this field include the sulfonyla- Me Me

tion of five- and six-membered heterocycles with sodium 88% 78%
sulfinates by way of nucleophilic aromatic substitution Scheme 11
(Scheme 10).39 Both methods enable the transition-metal-
free synthesis of heterocyclic sulfones, of particular rele-
vance for medicinal chemistry. Mhaske and Pandya developed a transition-metal-free
process for the synthesis of aryl sulfones based on the addi-
Y
tion of sodium sulfinates to in situ generated arynes
X
Z
Y
(Scheme 12).42
SO2R
DMSO, 110 °C
Z
38–98% yield O TMS TBAF (1.1 equiv) SO2R1
O +
S
S X R1 O Na OTf
MeCN, rt
R O Na
R2 R2
N
X = Cl, Br, I, OTf, NO2 TBACl (0.3 equiv) aryne precursor 45–96% yield
Y = O, S, NH (HCl)
Z = N, CH SO2R
DMAc, 100 °C
N O O
O O
75–98% yield
S O S

O O O
O O
S S S 95% 96%
S

N N O O
Me O O
84% 89% S
S S
CN O O Br
O O
S NO2
S
73% 74%
N
N Me
Me Scheme 12
97% Me 91%

Scheme 10
Chen, Yu and co-workers extended the transition-
In a similar manner, diaryliodonium salts, powerful ary- metal-free coupling of sodium sulfinates to employ vinyl
lating reagents,40 react with sodium sulfinates in the ab- halides (Scheme 13).43 The reaction proceeds in water with
sence of any catalyst.41 In contrast to classical SNAr reac- catalytic amounts of an acid and a phase-transfer catalyst.
An addition–elimination mechanism is proposed for this
transformation.

Syn thesis N.-W. Liu et al. Review

O X HCl (30 mol%) SO2R1 O Br Br SO2R1

+ TBAB (5 mol%) +
S S
R1 O Na R1 O Na DMF, 80 °C
R2 H2O, 100 °C R2 R2 R2

65–88% yield
X = Br, Cl 40–99% yield

O
O2
S Me CN Ph
O2 S NH2 S S
S Me O O O O O O
OMe Me
80% 80% 65%

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
99% 40%
Pent
O2 O2 Pent
S S S S
HOOC Me O O O O

Me 66% (5:1)

59% 53% Scheme 15

Scheme 13
Sreedhar and co-workers reported an iron(III) chloride
The lithium bromide catalyzed reaction of sodium sulfi- catalyzed direct sulfonylation of activated alcohols with so-
nates with terminal epoxides in water provides a sustain- dium sulfinates (Scheme 16).46 The reaction proceeds
able approach for the preparation of vinyl sulfones (Scheme through an activation of the alcohol and formation of a sta-
14).44 A mixture of the internal and the terminal regioiso- bilized carbocation.
mer is obtained in most cases. The regioselectivity is gov-
FeCl3 (15 mol%)
erned by electronic and steric effects of the expoxide sub- O HO
TMSCl (1.2 equiv)
SO2R1
+ R3 R2
stituent. The reaction is presumed to proceed through ini- R1
S
R2
O Na CH2Cl2, 45 °C R3
tial expoxide opening with the sulfinate followed by
R2, R3 = alkyl, aryl, allyl 35–96% yield
dehydration of the formed β-hydroxy sulfone.

SO2R1 Me

O2 O2
R2 internal O2S S S
O vinylsulfone
O
LiBr (10 mol%) +
S +
R1 O Na Me Me
R2 H2O, 80–90 °C
R1O2S
75% 71% 65%
R2 terminal Me
combined yield: 71–93%
regioselectivity: 100:0 to 9:91 vinylsulfone
Me
O2S
Me
Me S Me
O2
F Br
O2S O2S O2S
38% 60%
O2S
O
Scheme 16
Me

OMe
The Ji group developed a one-pot synthesis of allylic sul-
72% 84% 78% 71%
84:16 91:9 0:100 0:100 fones, β-keto sulfones or triflic alcohols from allylic alco-
hols and sulfinic acids.47 Substitution of the allylic alcohol
Scheme 14
yields the allyl sulfone. Direct treatment of the reaction
mixture with phenyliodine(III) diacetate (PIDA) and sulfuric
Liang and co-workers developed a synthesis of vinyl sul- acid leads to an oxidative rearrangement of the allyl sulfone
fones starting from sodium sulfinates and 1,2-dibromides and formation of β-keto sulfones. For triflated intermedi-
in the absence of any catalyst.45 The method provides the ates, no migration is observed and triflic alcohols are ob-
(E)-vinyl sulfone as the major stereoisomer or sole product tained instead (Scheme 17).
(Scheme 15).

Syn thesis N.-W. Liu et al. Review

O sponding salt.1,49 If unmasking of the sulfinate is performed

R1
S
OH
in the presence of a suitable electrophile, formation of a
HO Me O2 (balloon)
Ar sulfone occurs. Exploiting this reactivity, Petrini and co-
Ar
workers reported the synthesis of sulfones from alkyl and
DCE, 120 °C R2 SO2R1
R2 activated aryl halides and p-toluenesulfonyl hydrazide with
33–97% yield
sodium acetate as base (Scheme 19).50
R2 = Ar
R1 = Ar O Ar
Ar O NaOAc O
Ar SO2R1 Me S NHNH2 + R X Me S R
PIDA, H2SO4 EtOH, reflux
R2 SO2R1 O O
Ar OH R = alkyl, benzyl,

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
80–95% yield
allyl, aryl
R1 = CF3 R2 SO2R1 X = Cl, Br, I

O O Me Me
O O Me
S S Me S Me S
O O O O
Br O O
Me
85% 92%

O2N Me
69% 75% (1:1)

S S
OH O CF3
S O O NO2 O O
O
F 84% 95%

Scheme 19

68%

Scheme 17 In a similar manner, sulfonyl hydrazides react with

Michael acceptors to yield the corresponding ethyl sul-
fones.51 The reaction proceeds in water without any catalyst
Tian and co-workers reported a catalyst-free alkylation (Scheme 20).
of sulfinic acids with allylic and benzylic sulfonamides.48
O
Cleavage of the C–N bond takes place even at room tem- O
O
R NaOAc
perature (Scheme 18). Ar
H
S N NH2 + Ar S R
H2O, 65 °C
O O O
O NHTs SO2R1
+ R2 R2 R = OR', NHR' 70–98% yield
S
R1 OH R3 CHCl3, rt R3
56–99% yield OMe NO2
O O

MeO EtO S EtO S

O O
O O O O O O
Ph S
S Ph 91%
Ph 93%
Ph Me Me
H
O O
67% 56%
PhO S PhHN S
O O O O
MeO MeO
O O 70% 99%
O O
S S
Me Scheme 20
Me Me
OMe
72% 99%
Tang and co-workers reported a sulfonylation of allylic
Scheme 18 acetates with sulfonyl hydrazides in water.52 The reaction is
catalyzed by tetrabutylammonium iodide (TBAI), and tert-
Sulfonyl hydrazides can be considered as masked sulfi- butyl hydroperoxide (TBHP) is employed as cooxidant
nates, as treatment of a hydrazide with base or with water (Scheme 21).
and heating can liberate the free sulfinic acid or the corre-

Syn thesis N.-W. Liu et al. Review

OAc TBAI (20 mol%) O OH iPr NEt R2

O TBHP (2.0 equiv) EWG 2 R1
H EWG
Ph Ar S CN + R2
Ar S N NH2 + Ph R1 CH2Cl2, rt
H2O, 80 °C O
SO2Ar SO2Ar
O
72–95% yield
EWG = CO2R, CN 44–72% yield
COOMe COOMe
Me
CO2Me O2N CO2Et
O SO2Ph SO2Ph
O
Cl S 95% 72%
S
O O Me
Br Me
54% 63%

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Z/E = 97:3 Z/E = 99:1 SO2Ph SO2

CO2Me CN Br
O O
S O2N
S S
O 81% 84%
O

72%
Me Scheme 23
69%
Z/E = 89:11 Z/E = 1:99

Scheme 21
O OH SO2R1
S +
R1 Cl R2 R3 CHCl3, 25–60 °C R2 R3
Li and co-workers reported an interesting approach 53–99% yield
starting from 1,2-bis(phenylsulfonyl)ethane as sulfinate
precursor.53 In the presence of a palladium catalyst, cleav- SO2Ph SO2Me
COMe
age of one C–S bond and formation of a palladium–sulfinate Ph
Ph
complex occurs. Transfer of the sulfinate to an activated
SO2Ph
alkyne affords the (E)-vinyl sulfone in good yields (Scheme MeO
77%
Ph
75% 78%
22).
Scheme 24
Pd-mediated
C–S bond cleavage
2.4 Addition to Alkenes and Alkynes
Ph Pd(OAc)2 (10 mol%) O
O
DMEDA (20 mol%) Ph R
O S Ph + The addition of sulfonyl radicals to alkenes and alkynes
Ph S t O
O KO Bu, DMF/MeCN S is an important method for the synthesis of sulfones
O 120 °C O
Ph
R O (Scheme 25).1,56 Since the first reports on addition of sulfo-
R = OR, NHR 43–79% yield nyl halides to alkenes in the presence of radical initiators,
light or copper(I) chloride,57 various improvements and
O Me modifications of this atom-transfer radical addition (ATRA)
O Me O
Ph N
Ph OMe
process have been developed. Sulfonyl radicals can be gen-
H11C5 N
O erated from sulfonyl haldes, sulfonyl selenides, sulfonyl hy-
S O O
Ph
O S S
O
drazides, sulfonyl azides, or by the oxidation of sulfinates.58
O Ph
Ph
OMe
O X
64% 54% 43% initiator or catalyst O R2
R1 S X + R2
Scheme 22 O
R1 S
O
O
via R1 S
radical precursor
O
Allylic alcohols react with arenesulfonyl cyanides to af- sulfonyl radical
ford trisubstituted allyl sulfones (Scheme 23).54
Scheme 25
Tian and co-workers developed a method to convert
benzylic and allylic alcohols into the corresponding sul-
fones using sulfinyl chlorides (Scheme 24).55 The reaction Ruthenium complexes are amongst the most efficient
proceeds through in situ formation of a sulfinic acid or a catalysts for the ATRA of sulfonyl chlorides to olefins. Cata-
sulfinate ester and is catalyzed by the by-product HCl. lyst loadings as low as 0.1 mol% and high turnover frequen-
cies are observed for modified cyclopentadienyl–rutheni-
um complexes.59,60

Syn thesis N.-W. Liu et al. Review

Addition of sulfonyl halides to alkynes affords haloge- The ATRA of tosyl bromide to bisallenes leads to the for-
nated vinyl sulfones. In general, the (E)-β-halovinyl sulfones mation of five-membered rings bearing an exocyclic vinyl
are obtained as either the major or the sole diastereomer sulfone via a 5-exo-trig cyclization (Scheme 28).64
(Scheme 26).1,57 Nakamura and co-workers reported an
Ts
iron-catalyzed regio- and stereoselective addition of sulfo- AIBN
O
nyl chlorides to terminal alkynes (Scheme 26).61 A bromo- (20 mol%)
Tol S X Y Y
sulfonylation of terminal alkynes was achieved with a tri- O
toluene, 90 °C
ethylborane-initiated sulfonyl radical generation.62 X
X = Br, SePh Y = O, NR, CR2 48–73% yield
R2
Fe(acac)3 (10 mol%)

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O
(p-Tol)3P (10 mol%) Cl Ts Ts Ts
R1 S H H H
O toluene Ph
O TsN O
R1 S X R2
Ph
O
Br H H H
O R2
R1 S Br SePh Br
Et3B, O2 73%
O 55% 63%

Scheme 28
O O
O nBu
O
Ph S S
1,6-Diynes react with tosyl bromide in a similar man-
Cl Me Cl Me ner, affording bromo-substituted sulfonylated methylcyclo-
O pentenes via a 5-endo-dig cyclization (Scheme 29).65
83% 67%

R3 R3 Br
O R1 R1
O hν
O O Tol S Br +
Ph S O benzene, rt
S O R2 R2
Me R4 R4
Br Ts
Me Br 51–72% yield

99% 91%
Me Br Me Br Me Br
HO O O
Scheme 26
HO O O
Me Me Me
Ts Ts Ts
The Kang group developed methods for the synthesis of 68% 72% 51%
heterocyclic compounds based on the radical additions of Scheme 29
tosyl bromide or iodide to allenes.63 Treatment of the re-
sulting allylic halides with base furnished the correspond-
ing heterocycles (Scheme 27). Generation of sulfonyl radicals from the corresponding
azides is also possible. For example, Mantrand and Renaud
O
developed a radical-mediated azidosulfonylation of alkenes,
Tol S X
O
dienes and enynes with phenylsulfonyl azide (Scheme
AIBN Ts
+ n YH 30).66 The reaction is limited to 1,6-dienes, 1-en-6-ynes, or
toluene, 90 °C
YH
X alkenes that are able to undergo a rapid radical rearrange-
n
ment. In the case of simple alkenes, no reaction is observed
X = Br, I
Y = O, NTs owing to the reversibility of the sulfonyl radical addition
Ts and the low reaction rate of the final azidation of secondary
Ts (base)
n YH n alkyl radicals.
X Y Sulfinic acids and their salts are competent radical pre-
Ts cursors and yield the corresponding sulfonyl radicals upon
Ts
OH O single-electron oxidation. Various methods have been re-
ported for the generation of sulfonyl radicals from sulfi-
Br
67% 70%
nates or the free acids.1,56,58 Addition to an alkene or alkyne
Ts can yield the formal hydrosulfonylation product as well as
K2CO3
Ts
n YH
various other sulfonylated products arising from different
DMF
HN trapping processes. Two-electron oxidation of sulfinic acids
Br
51% 78% can yield a sulfonyl cation, which can undergo similar reac-
Scheme 27 tions with double or triple bonds.

Syn thesis N.-W. Liu et al. Review

Jiang and co-workers reported a palladium-catalyzed

PhO2S
X tBuN=NtBu addition of sodium sulfinates to alkynes affording (E)-vinyl
O
Ph S N3 + R1 R3
(0.5 equiv)
X sulfones (Scheme 32).69
sun lamp R2
O R2
R3
R1 X
X = O, NR, CR2 N3 O O
PdCl2 (5 mol%) R2
41–89% yield S
R1 O Na R1 S
DMSO
R2 O
PhO2S PhO2S 65–93% yield
X = H, COOH

MeO2C
Ts N O2
Me Me O2
MeO2C S

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
S O
Me Me S NO2
N3 N3 OMe
82% 83%
76% 89% X=H X=H

O2 O2
SO2Ph SO2Ph F3C S S
Ph Ph
O O
H H H H 73% 93%
Me Me X = COOH X = COOH
N3 N3
Scheme 32
82% 80%

Scheme 30
Kuhakarn and co-workers developed a PIDA and potas-
sium iodide mediated synthesis of vinyl sulfones and β-io-
Taniguchi reported a copper-catalyzed addition of sodi- dovinyl sulfones (Scheme 33).70 The reaction of sodium sul-
um sulfinates to alkenes and alkynes.67 Addition to alkenes finates with alkenes furnishes β-iodo sulfones, which elimi-
affords (E)-vinyl sulfones via an addition–elimination pro- nate to the corresponding vinyl sulfones under the reaction
cess. Reaction of alkynes in the presence of potassium ha- conditions or upon treatment with base. In the case of
lides furnishes (E)-β-haloalkenyl sulfones (Scheme 31). This alkynes, (E)-β-iodovinyl sulfones are obtained as products.
method was later extended to a formal hydrosulfonylation An in situ formation of sulfonyl iodides as reactive species is
of alkynes.68 proposed.

Method A R2 O R2
CuI/bpy (8 mol%) PIDA, KI
O X R1 S
KX (1.1 equiv) MeCN, rt
R1 S H O
O AcOH, air O (then DBU)
O R3 for alkenes
S 100 °C S
R1 O Na R1 O Na
for alkynes
Method A R2 R2
PIDA, KI
CuI/bpy (8 mol%) O R2 O I
R3 R2
KI (50 mol%) MeCN, rt
R1 S R1 S
AcOH, air
O R3 O
100 °C
for alkenes for alkynes

X/H O2N
Method B
O R2
CuCl/ligand (5 mol%)
R1 S
AcOH, DMI
O R3 C6H13
H2O or MX, 60 °C
O O I
for alkynes I
Me S Me S

Br SO2Tol O O
77% 64%
Ph SO2Me

74% 68%
Method A Method A OMe
O
O O
SO2Tol Me S Me S O
Br
O O
N
SO2Tol 75% 62%
91% 35%
Method B Method B Scheme 33

Scheme 31 DMI = 1,3-Dimethyl-2-imidazolidinone

Syn thesis N.-W. Liu et al. Review

The potassium persulfate promoted direct sulfonylation Visible-light-photocatalyzed oxidation of sulfinates or

of N-phenylmethacrylamides with sulfinic acids leads to sulfinic acids provides an attractive alternative for the gen-
the formation of sulfonylated oxindoles (Scheme 34).71 eration of sulfonyl radicals. König and co-workers devel-
oped a visible-light-mediated addition of sodium sulfinates
SO2R1 to alkenes.73 This method provides a general and simple
Me R3
O N O K2S2O8
procedure for the synthesis of vinyl sulfones (Scheme 36).
+ R2 R2 O
1
S MeCN, H2O
R OH N
R3 80 °C R1 Eosin Y (10 mol%) R1
Me O PhNO2 (1.0 equiv)
54–93% yield R2 green LED ArO2S
S + R2
Ar O Na EtOH, 40 °C

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
SO2Ph 51–99% yield
SO2Ph Me
O
Me
O O O O
O S
Me S
O N
N
F Me
Me
79% 74%
70% 76%
F3C O O O O
OH S S
SO2Ph Me O2
S

O OMe
O
N 88% 90%
N
Me
Me Scheme 36
92% 81%

Scheme 34
Visible-light-initiated addition of sulfinic acids to N-
arylacrylamides furnishes sulfonylated oxindoles via an ad-
In general, the addition of sulfinic acids or sulfinates to dition/cyclization cascade (Scheme 37).74
alkynes leads to the regioselective formation of the anti-
Markovnikov-type products. Shi and co-workers reported a Me SO2R1
Na2-Eosin Y R3
gold-catalyzed synthesis of α-substituted vinyl sulfones.72 O N O (2 mol%)
white LED
In the presence of a suitable gold catalyst and gallium(III) S + R2 R2 O
R1 OH TBHP (1 equiv) N
R3
triflate, regioselective Markovnikov addition to terminal H2O, rt
Me
alkynes takes place (Scheme 35). 60–91% yield

[BrettPhosAu(TA)]OTf Me Me O2
(5 mol%) SO2Ph Sn
O O Bu
Ga(OTf)3 (10 mol%)
+ R2 R1 S O O
S
R1 OH DCE, rt to 45 °C N N
O R2
Me Me
50–91% yield
85% 65%
O
Me Me Me
O Cl SO2Tol N SO2Tol
Ph S O2N
S
O O O
Cl
S N
O
Me
tBu Ph
70% 70%
80% 82%

O
Scheme 37

H
Under similar reaction conditions, sulfinic acids react
H H
with phenyl propiolates to afford coumarins (Scheme 38).75
S
O Ph
O
86%

Scheme 35

Syn thesis N.-W. Liu et al. Review

O The oxidative addition of sodium sulfinates to terminal

S alkenes can be catalyzed by molecular iodine in the pres-
R1 OH R3
+ Eosin Y (1 mol%) ence of air.77 Oxygen acts as terminal oxidant, while iodine
visible light SO2R1
O O R2
serves as radical initiator and reducing agent for the initial-
TBHP (1 equiv) ly formed β-hydroperoxo sulfone (Scheme 40).
R2 O O
MeCN/H2O, rt

55–77% yield O I2 (10 mol%) OH

R3 O2 (air)
S + SO2R1
R1 O Na R2 R2
Ph Ph MeCN, AcOH
O2 O2 61–93% yield
S I S
OH OH HO Me

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O O Me O O Me SO2Ph SO2Ph SO2Ph

71% 65%
Me Br
93% 72% 79%
Ph
O2 O2 Scheme 40
S CF3 S

O O Cl O O Me Interestingly, addition of sulfinic acids to alkenes can be

58% 77% mediated by oxygen alone.78 A basic additive, such as pyri-
dine, enhances the reaction rate considerably (Scheme 41).
Scheme 38
The reaction proceeds through the initial formation of a β-
hydroperoxo sulfone, which is reduced to the correspond-
In the presence of oxygen or another oxidant as radical ing hydroxysulfone upon workup with triphenylphospine.
trapping reagent, the addition of sulfonyl radicals to
alkenes and alkynes yields the corresponding hydroxy or O R3 3
pyridine, O2 (air) HO R
R4
keto sulfones. Taniguchi reported a nickel-catalyzed hy- R1
S
OH
+
R 2
R2
R4
CHCl3, 45 °C
droxysulfonylation of alkenes with sodium sulfinates in the then Ph3P SO2R1
presence of air.76 Addition to disubstituted alkenes leads to 60–98% yield
the formation of trans-substituted β-hydroxy sulfones in- Me
Me
dependent of the olefin configuration (Scheme 39). OH
O2 HO O2
Me S S
NiBr2-TEEDA Ph
(5 mol%) OMe
NH4PF6 OH Me
O 83% 66%
Ar2 (30 mol%) R
S R Ar2 OH
Ar1 O Na AcOH, DMF O2
H2O, air, 60 °C SO2Ar1 S Me OH
O2
62–88% yield EtO S

OH OH F Me
O2 O
O2 Me
S S 95% 82%

OMe Br Me Scheme 41
80% 74%
HO Me O OH
2 O2
S S Yadav and co-workers reported a silver nitrate and po-
tassium persulfate promoted synthesis of β-keto sulfones
Me Me starting from alkenes and sodium sulfinates.79 The same
73% 67%
keto sulfones can be also prepared by the oxygen-initiated
Scheme 39
addition of sulfinic acids to alkynes (Scheme 42).80

Syn thesis N.-W. Liu et al. Review

Method A Interestingly, in the presence of stoichiometric amounts

O O
AgNO3 Method B of iodine, the TBHP-mediated reaction of sulfonyl hydra-
S K2S2O8 O pyridine S
R1 ONa O2 R1 OH zides with alkenes yields the corresponding β-iodo sulfones
O2 (air)
+ SO2R1 +
H2O R2 CHCl3 (Scheme 44).83 Performing the same reaction with alkynes
R2 25 °C 45 °C R2
furnishes (E)-β-vinyl sulfones (Scheme 45).84
OMe O O O O
O I
S S H I2, TBHP
R1 S N NH2 + R2 SO2R1
O O 0–20 °C R2
O
F 71–95% yield
71% 75%
Method A Method A

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O O O O I
I
S S O2 O2
S S Me
O O
S
Me
76% 67%
MeO
Method B Method B 89% 88%

Scheme 42 I
I O2
O2 S
S
Br
O
Sulfonyl hydrazides can be employed as stable and easi- Me
Me
ly accessible starting materials for the sulfonylation of 72% 84%

double and triple bonds. Jiang and co-workers reported a Scheme 44

copper-catalyzed synthesis of vinyl sulfones based on the
oxidative cleavage of a hydrazide, followed by reaction of a O R2
H I2, TBHP
R1 S N NH2 + R2 SO2R1
reactive sulfonyl species with the alkene (Scheme 43).81 Lei 0–20 °C I
O
and co-workers were able to achieve the generation of sul- 22–94% yield
fonyl radicals from sulfonyl hydrazides with catalytic
I I
amounts of potassium iodide and TBHP (Scheme 43).82
O2S O2S Me
Method A S
CuCl (10 mol%)
O LiBr (30 mol%)
H DMSO, 100 °C, air SO2R1 94% 83%
R1 S N NH2 + R2 R2
Method B
O KI (20 mol%) I I
TBHP
DMSO/AcOH, 25–30 °C O2S Me Pent
F3C O2S
O2 F
N S O2 CF3 Me
S Br
94% 22%
S
Me
Me Scheme 45
88% 76%
Method A Method B

O2 O2 In the presence of catalytic amounts of copper acrylate

S S
NC and iron(II) chloride, the reaction of sulfonyl hydrazides
Me Me
Me with alkynes affords (E)-vinyl sulfones (Scheme 46).85 The
54% 79%
iron-catalyzed reaction of sulfonyl hydrazides with alkenes
Method A Method B in the presence of air yields β-hydroxy sulfones (Scheme
Scheme 43 47).86 With Cu(OAc)2 as catalyst, the reaction of sulfonyl hy-
drazides with alkenes affords the corresponding β-keto sul-
fones (Scheme 48).87

Syn thesis N.-W. Liu et al. Review

O [Rh(COD)Cl]2 (2.5 mol%)

H Fe/Cu catalyst R1 DPEphos (10 mol%)
R1 S N NH2 + R2 X SO2R1 SO2R1
R2 PhCO2H (50 mol%)
DTBP, DMSO O S O
O +
X = H, COOH 100 °C R2
30–84% yield NHNH2 DCE, 80 °C
R2
79–98% yield

O2 O2 SO2Tol
S S SO2Tol SO2Bz

Ph Pent
Me OMe 82% 87% 90%
81% 72%
X = COOH X = COOH
Scheme 49

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O2
S O2
S
Another approach to allylic sulfones is the TBAI/TBHP-
Br Me
N Me mediated reaction of sulfonyl hydrazides with α-substitut-
80%
ed styrenes (Scheme 50).89 Generation of a sulfonyl radical,
75%
X=H X=H followed by addition to the double bond and elimination
Scheme 46 leads to the formation of nonconjugated sulfones.

OH TBAI (20 mol%) Ts

R1 FeCl3, air TBHP (2.0 equiv)
R1 SO2Tol TsNHNH2 +
TsNHNH2 + R R
R2 THF, 80 °C R2 Ar MeCN, 80 °C Ar
21–90% yield
21–95% yield

SO2Tol SO2Tol SO2Tol

OH
OH
OH SO2Tol
SO2Tol Me
SO2Tol Ph
Ph
Me F3C MeO
21% 60% 90%
N
95% 54% 48% Scheme 50
Scheme 47
Qu, Chen and co-workers developed a copper-catalyzed
Cu(OAc)2 (5 mol%) O
R1SO2NHNH2
O2 SO2R1
sulfonylation of alkynes with tert-butylsulfinamide
+
EtOH, 70 °C
Ar
(Scheme 51).90 Phosphorous acid serves as terminal reduc-
R2 R2
Ar ing agent and the oxidation of the sulfinyl (SO) to the sulfo-
50–72% yield
nyl (SO2) moiety takes place under the reaction conditions.
O O
O CuSO4 (20 mol%)
SO2Ph SO2Ph H3PO3 (2.0 equiv)
O
SO2Ph Ph TFA (2.0 equiv) SO2tBu
Ph S +
Me tBu
MeO NH2 R2 DMF, 100 °C R2
70% 70% 52% 51–81% yield

Scheme 48 SO2tBu SO2tBu

81% MeO 66%

Breit and co-workers reported a rhodium-catalyzed S SO2tBu
SO2tBu
synthesis of branched allylic sulfones starting from termi-
nal alkynes and sulfonyl hydrazides (Scheme 49).88 The re-
53% 69%
action proceeds via a benzoic acid mediated formation of a
rhodium–allyl species, which undergoes nucleophilic dis- Scheme 51
placement with a sulfinic acid generated in situ from the
sulfonyl hydrazide. Widely available dimethyl sulfoxide (DMSO) is a suit-
able starting material for the methylsulfonylation of alkenes
and alkynes. The ammonium iodide induced addition of
DMSO to alkenes yields (E)-vinyl methyl sulfones (Scheme

Syn thesis N.-W. Liu et al. Review

52).91 The authors propose that the reaction proceeds via any catalyst at high temperatures in DMSO97 (Scheme 55). A
the generation of thiomethyl radicals and water serves as mechanism consisting of sulfonyl radical formation fol-
the source of the second sulfonyl oxygen. lowed by addition to the alkene and decarboxylation is pro-
posed for all transformations.
O NH4I (4.0 equiv) SO2Me
S +
R DMSO/H2O O HO2C
Me Me R conditions SO2R
130 °C S +
46–99% yield R O Na – CO2 Ar
Ar
SO2Me Ph
SO2Me conditions: yield (for R, Ar = Ph)
MeO Ph

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
75% 68% PIDA (2.0 equiv), DMF, 100 °C 73%
Me
SO2Me CuCl (20 mol%), KI (1.5 equiv), DMSO, air, 100 °C 74%
SO2Me
Ph N I2 (2.0 equiv), TBHP (2.0 equiv), toluene, 90 °C 92%
S
46% 87%
I2 (1.0 equiv), K2CO3 (1.0 equiv), H2O, 60 °C 78%
Scheme 52
K2CO3 (0.50 equiv), DMSO, 100 °C 82%

The groups of Chen and Qu and the group of Loh report- Scheme 55
ed two procedures for the copper-catalyzed synthesis of
(E)-vinyl methyl sulfones from alkynes in DMSO.92 Diethyl Liu and Li reported a copper/silver-mediated domino
H-phosphonate acts as terminal reducing agent (Scheme reaction for the synthesis of 2-sulfonylbenzofurans based
53). Loh showed that under identical conditions, the reac- on a cyclization–decarboxylation sequence (Scheme 56).98
tion of alkenes affords β-keto sulfones (Scheme 54).92b
HO2C SO2R1
CuCl2 (0.5 equiv)
Method A AgTFA (2.5 equiv)
O O
CuSO4 (25 mol%) OH Cs2CO3 (2.0 equiv)
(EtO)2P(O)H (1.1 equiv) S +
R1 TFA (2.0 equiv) R1 O Na DMF, 80–100 °C
O 120 °C SO2Me – CO2
R2 R2
+
S
Me Me Method B R1 R2 20–79% yield
R2 CuBr (10 mol%), O2
(EtO)2P(O)H (3.0 equiv) O O O O
120 °C S
S
O
SO2Me
SO2Me Ph O O
Ph Me N Me
Me H
79% 72%
89% Method A 68% Method A
85% Method B 70% Method B O O O O
SO2Me SO2Me S MeO S
Tol Et
O O
MeO F
60% Method A 55% Method A
81% 31%
80% Method B 82% Method B

Scheme 53 Scheme 56

CuBr (10 mol%) O

O R (EtO)2P(O)H (3.0 equiv)
+ SO2Me Interestingly, palladium-catalyzed69 as well as phos-
S Ar
Me Me
Ar
O2, 90 °C
R
phoric acid mediated99 decarboxylative coupling reactions
43–84% yield of sodium sulfinates with aryl propiolic acids affords (E)-vi-
O O O nyl sulfones (Scheme 57).
Ph
SO2Me
Ph
SO2Me S SO2Me As mentioned previously, sulfonyl hydrazides are at-
Me tractive alternatives to sulfinates in various transforma-
82% 71% 75% tions. Accordingly, the iodine-mediated reaction of sulfonyl
Scheme 54 hydrazides with cinnamic acids yields (E)-vinyl sulfones via
a radical addition and carbon dioxide extrusion (Scheme
Several groups have developed decarboxylative cou- 58).100 The copper-101 or copper/iron-catalyzed86 decarbox-
plings of sodium sulfinates and cinnamic acids for the syn- ylative hydrosulfonylation of phenyl propiolic acids with
thesis of vinyl sulfones. These reactions can be mediated by sulfonyl hydrazides furnishes the corresponding vinyl sul-
PIDA,93 catalytic ammounts of copper(I) chloride,94 iodine fones (Scheme 59).
and TBHP,95 or iodine96 and even proceed in the absence of

Syn thesis N.-W. Liu et al. Review

Method A Lei and co-workers developed a copper-catalyzed decar-

CO2H PdCl2 (5 mol%)
O
DMSO, 100 °C
boxylative oxosulfonylation of arylacrylic acids with sulfin-
SO2R
R
S
O Na
+ ic acids (Scheme 60).102 Evidence for a single-electron-
Method B
Ar H3PO4
Ar transfer process between copper and the sulfinic acid was
DMSO, 80 °C provided by extensive spectroscopic studies.

CO2H CuBr2 (10 mol%) O

PhO2S MeO2S O air
Ph Ph + Ar SO2R1
S Ar
R1 OH DMF, rt
83% Method A 91% Method A R2 R2
92% Method B 82% Method B
38–92% yield

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O O O O O O O
S S SO2Ph SO2Ph SO2Me
Ph Ph Ph Ph Ph
Me
F3C
92% 38% 61%
73% Method A 73% 87% Method A
64% Method B 64% 80% Method B O O

Scheme 57 SO2Ph MeO SO2Ph

F MeO
I2 (40 mol%) 81% 63%
O O HO2C DBU, TBHP SO2R
S + Scheme 60
R NHNH2 MeCN, H2O, rt Ar
Ar
57–88% yield

Vinyl acetates are suitable olefins for the synthesis of β-

Ph
SO2Tol S SO2Tol keto sulfones. Sulfonylation of vinyl acetates with sulfonyl
87% 78% hydrazides mediated by either iron(III) chloride in the pres-
ence of air103 or TBAI and TBHP104 affords the oxidative cou-
SO2Ph Ph SO2Tol
Ph pling products via a radical addition (Scheme 61).
68% 61%

Scheme 58 Method A
FeCl3 (10 mol%), air
O O OAc THF, 70 °C O
Method A S + SO2R1
CO2H CuI/bpy (10 mol%) R1 NHNH2 R2 Method B R2
O O DMF, air, 100 °C SO2R TBAI (20 mol%)
+ TBHP (2.0 equiv)
S
R NHNH2 Method B MeCN, 80 °C
copper acrylate (20 mol%) Ar
Ar
FeCl2 (15 mol%)
DTBP
DMSO,100 °C O O
SO2Tol SO2Tol
Ph Ph
SO2Tol SO2Tol
Ph Tol Me
91% Method A 53% Method A
85% Method A 60% Method A 70% Method B 40% Method B
81% Method B 73% Method B
O O O O
SO2Tol O O S SO2Tol S
S Ph
Ph
F F
OMe 40% Method A 80% Method A
43% Method A 71% Method A 45% Method B 51% Method B
72% Method B 72% Method B
Scheme 61
Scheme 59

A photoredox-catalyzed addition of sulfonyl chlorides to

vinyl acetates for the synthesis of β-keto sulfones was de-
veloped by Zhang, Yu and co-workers (Scheme 62).105

Syn thesis N.-W. Liu et al. Review

AcO O SO2R1 Katritzky reported on N-sulfonylbenzotriazoles as ad-

O O fac-IrIII(ppy)3 (1 mol%) vantageous reagents for the sulfonylation of lithiated het-
S +
R1 Cl CH2Cl2, white LED erocycles or lithium enolates (Scheme 65).110
N2, rt
R2 R2
46–98% yield R3
O O
S O O
N
O O O O O O R1 N R2O OLi S R3
N R1
S S
R2O O
F3C
69% 98% O O

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O S N
O O O SO2Tol R N Het-Li O O
N
S S
R Het

N
71% 46%
O O O O
Scheme 62 S Bn
S Ph

O
Me Et O Et O
The TBAI-mediated oxidative coupling of enamides with
60% 71%
sulfonyl hydrazides yields β-keto sulfones in a similar fash-
ion (Scheme 63).106 O O O O
S S S
Me
NHAc TBAI (20 mol%) O O
O O THBP (2.0 equiv) Me
+ SO2R1 73% 47%
S R2 R2
R1 NHNH2 MeCN, 80 °C
R3 R3 Scheme 65
13–80% yield

O O O O O
SO2Tol
Ph
S In the presence of Lewis or Brønsted acid, aryl sulfon-
Ph
ates and aryl sulfonamides will rearrange to the corre-
SO2Tol
Cl
sponding hydroxyaryl and aminoaryl sulfones, respectively
80% 27% 63%
(Scheme 66).24a,111 This exetension of the classical Fries re-
Scheme 63 arrangement affords a mixture of ortho and para isomers.
Solvents and substituents on the aromatic ring can affect
the ortho/para ratio.
2.5 Miscellaneous Methods
O O XH
S Lewis or XH
Apart from these first four important approaches for the R1 X Brønsted acid
SO2R1
+
preparation of sulfones, several other synthetic routes exist. Δ
R2
The reaction of sulfonic acid derivatives, such as sulfonate R2 SO2R1
R2
esters, or sulfonyl chlorides, with organometallic reagents
X = O, NR
produces sulfones (Scheme 64).1,107 Generally, these reac-
tions are low-yielding and limited to certain substrate com- Scheme 66
binations. For example, reactions with sulfonyl chlorides
frequently afford the corresponding sulfoxides as the major Wang and co-workers reported a copper-catalyzed rear-
products.108 It has been shown that sulfonyl fluorides are rangement of N-tosylhydrazones to (E)-vinyl sulfones.112
superior electrophiles for reactions with organomagnesium Prabhu and Ojha developed a similar reaction mediated by
or organolithium reagents.109 cyanogen bromide and a phase-transfer catalyst (Scheme
67).113
O O O O O
S + R2 M S 2 + S
R1 X R1 R R1 R2
X = OR, Cl, F M = Li, Mg, Hg

Scheme 64

Syn thesis N.-W. Liu et al. Review

R1 Method A Dienediones react with sulfonamides in an acid-mediat-

O S O
Cu(OAc)2 (15 mol%) SO2R1 ed cascade process furnishing sulfonated cyclopentanes
xylene, 90–140 °C
NH R2 with three contiguous stereocenters (Scheme 70).116
N Method B
R3 CNBr (1.1 equiv), TBAB (2.5 equiv) R3
R2 K2CO3 (3.0 equiv), dioxane, 100 °C R2
O O
SO2R1
R2
TolSO2 TolSO2 TolSO2 O HBF4 (1.0 equiv)
S +
Ph SO2(p-Tol) R1 NH2 MeCN/CH2Cl2, rt
Ph Ph Me Ph
O R2
93% Method A 87% Method A 81% Method A

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
93% Method B 69% Method B 84% Method B O 64–83% yield
R2 1,2-syn/2,3-anti major
Scheme 67 1,2-anti/2,3-anti minor

O O
SO2tBu SO2tBu
In the presence of a copper catalyst, sulfonyl hydrazones Me
Ph
can undergo nitrogen extrusion to yield sulfones (Scheme
68).114
O Ph O Me
R1
80% (75:25) 66% (68:32)
O S O
CuI (20 mol%)
NH SO2R1
N K2CO3 O
SO2Ph O
R2 R3 SO2Tol
dioxane, 110 °C
R2 R3 Ph
46–90% yield Me

SO2Tol SO2Tol SO2Tol

O Ph
O Me
Ph Me 73% (70:30) 64% (83:17)

Br OMe Scheme 70
88% 46 % 76%

Scheme 68
The reaction of sulfur dioxide with dienes yields sulfo-
lenes in a chelotropic reaction. Although this [4+1] cycload-
Jiang and Tu reported a THBP/TBAI-mediated synthesis dition is one of the classical textbook examples for a ste-
of allenyl sulfones starting from propargylic alcohols and reospecific, pericyclic reaction, it is rarely used in organic
sulfonyl hydrazides (Scheme 69).115 The authors propose synthesis.1,117,118 Vogel and Sordo showed that the reaction
the formation of a sulfonyl hydrazone followed by a radical of dienes with sulfur dioxide can indeed produce not only
fragmentation/coupling process to afford the final product. one but two products.119 Under kinetic control (< –60 °C), a
hetero-Diels–Alder reaction takes place and the corre-
Ar
TBAI (20 mol%) Ar SO2R3 sponding sultine is formed. Under thermodynamic control
O O TBHP (2.0 equiv)
+
(> –40 °C), the sulfolene is formed (Scheme 71).
S C
R3 NHNH2 AcOH, MeCN
HO R2 60 °C
R2 R1 [4+2] O
R1 SO2 +
42–84% yield < –60 °C S
O
Ph SO2Tol Ph SO2(2-Np) sultine

C C
[4+1] O
SO2 + S
Ph Ph Ph Ph > –40 °C O
84% 69%
Me sulfolene
Cl
SO2C6H4-4-Cl Scheme 71
SO2Ph
C
C
3 Metal-Catalyzed Coupling Reactions
Ph Ph
F F
73% 63% In the last 15 years, transition-metal-catalyzed coupling
Scheme 69 reactions of either sulfinates as nucleophilic or sulfonyl ha-
lides as electrophilic coupling partners have emerged as at-

Syn thesis N.-W. Liu et al. Review

tractive alternatives to the traditional procedures. They al- CuI (15 mol%)
N2+BF4– DMEDA (15 mol%)
low the synthesis of sulfones in a regiospecific manner, of- Ar
TBAI (1.3 equiv) O O
ten under milder reaction conditions compared to those + K2CO3
Tol
S
Ar
used in sulfide oxidation or electrophilic sulfonylation reac- O DMSO, N2, 100 °C
72–91% yield
tions. Therefore metal-catalyzed coupling reactions can ex- Tol
S
O Na
pand the functional group compatibility considerably.
Since the first report by Suzuki and Abe on the copper- O O
O O S
assisted coupling of sodium sulfinates with non-activated S Tol
Tol Ph
iodoarenes,120 various improvements have been developed. OMe
The introduction of ligands such as proline,121 N,N-di- 91% 89%

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
methyethylenediamine (DMEDA),122 D-glucosamine,123 O O
Me
S O O
functionalized ionic liquids124 or 1,10-phenanthroline125 Tol S
Tol
enables the copper-catalyzed coupling of sulfinic acid sodi- NO2
um salts with aryl iodides or bromides (Scheme 72). How- 84% 72% Me

ever, there is only one report for copper-catalyzed cross-

Scheme 73
couplings with aryl chlorides,126 and this procedure is limit-
ed to activated, electron-poor (hetereo)aromatic chlorides,
which should undergo a direct, uncatalyzed nucleophilic Xu and Qing employed arenediazonium salts as starting
aromatic substitution.1,38 materials in a copper-catalyzed coupling with sodium tri-
fluoromethylsulfinate.128 This method allows the mild syn-
O
O conditions thesis of trifluoromethanesulfonyl-substituted arenes, of
S + Ar X R S Ar
R O Na particular interest for medicinal chemistry, in good yields
X = Br, I O
(Scheme 74).

O Cu2O (10 mol%) O

N2+BF4–
conditions yield + F3C S Ar
S Ar
(for R = Ph, Ar = Tol, X = I) F3C O Na DMSO, N2, rt
O
45–90% yield
CuI (10 mol%), L-proline sodium salt (20 mol%) 77%
DMSO, 90 °C
O O O O
S S
(CuOTf)[Link] (5 mol%), DMEDA (10 mol%) 70% CF3 CF3
DMSO, 110 °C
HO2C NO2
52% 85%
CuI (10 mol%), D-glucosamine (20 mol%) 94%
KOAc, DMSO/H2O, 100 °C O O
O O
S
CF3 S
CuI (10 mol%), [enim][Val] (20 mol%) 81% H CF3
N
DMSO, 95 °C Tol S
N
O O
CuFe2O4 (10 mol%), 1,10-phenanthroline (10 mol%) 78% 59% 45%
DMF, 110 °C
Scheme 74
Scheme 72

Cacchi and co-workers developed a palladium-catalyzed

Nagarkar and co-workers developed a copper-catalyzed coupling of sodium sulfinates with aryl and vinyl halides
cross-coupling of sodium p-toluenesulfinate with arenedi- for the synthesis of diaryl and aryl vinyl sulfones.129 The
azonium salts as an alternative to aryl halides.127 The best yields were obtained with Pd2(dba)3–Xantphos as the
authors propose a TBAI-mediated in situ formation of aryl catalyst system. The reaction is strongly influenced by the
iodides as coupling partners by way of a Sandmeyer-type addition of tetraalkylammonium salts, such as tetrabu-
reaction (Scheme 73). tylammonium chloride (Scheme 75). The palladium-cata-
lyzed coupling of vinyl tosylates with aryl sulfonate salts
gives aryl vinyl sulfones in a similar manner (Scheme 76).130

Syn thesis N.-W. Liu et al. Review

Pd2(dba)3 (2.5 mol%) The groups of Beaulieu and Evans developed a copper-
Xantphos (5 mol%)
X TBACl (0 or 1.2 equiv) SO2R 1 mediated cross-coupling of boronic acids and sodium sulfi-
O Cs2CO3 (1.5 equiv) nates (Scheme 78).132 This oxidative coupling reaction pro-
+
S
R1 O Na toluene, argon vides a useful and mild alternative to the just-described
60–120 °C
coupling reactions.
X = I, Br, OTf 20–96% yield

O O NO2 O O Cu(OAc)2 (1.1 equiv)

O B(OH)2 K2CO3 (2.0 equiv) O O
S S
+ S 2
S R2
R 1
O Na DMSO, 4 Å MS R1 R
rt to 60 °C
Me Me Me 19–97% yield
96% 89%

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O O O O Me O O O O
Me O O
S S S S
Me S Me Me Me

Me N Ph Me N
Me
Me Me 52%
80%
97% 63% 19%
Scheme 75
Scheme 78
Pd2(dba)3 (2.5 mol%)
OTs Xantphos (5 mol%) SO2R1
O K3PO4 (1.5 equiv)
+ R3 R3
Later, several catalytic versions of these Chan–Evans–
S R3 R3
R1 O Na toluene, N2,100 °C Lam-type couplings were reported (Scheme 79), including
methods with imidazole133 or phenanthroline134 ligands, in
40–75% yield
ionic liquids135 or water136 and utilizing magnetically sepa-
SO2Tol SO2Tol rable copper ferrite nanoparticles.125
BocN O B(OH)2 conditions O O
69% 75% S + S 2
R1 O Na R2 R1 R
O O
Ph conditions yield
S
SO2Tol (for R1 = Me , R2 = 4-MeOC6H4)
Ph
Cu(OAc)2 (20 mol%) 68%
74% 40%
1-benzylimidazole (40 mol%)
4 Å MS, DMSO, air, 60 °C
Scheme 76
Cu(OAc)2 (10 mol%) 60%
Yu and Wu reported an interesting palladium-catalyzed 1,10-phenanthroline (20 mol%)
4 Å MS, CH2Cl2/DMSO, O2, 40 °C
synthesis of sulfones by a denitrative coupling of ni-
troarenes with sulfinic acid salts (Scheme 77).131 Cu2O (10 mol%), NH3, H2O, air, rt 76%

Scheme 79
palladacycle (0.75 mol%)
O NO2 K2CO3 (1.0 equiv)
S + Ar SO2R
R O Na Ar DMSO, N2, 110 °C
48–90%
Xu, Liang and co-workers developed a palladium-cata-
lyzed coupling of sulfonyl hydrazones with aryl iodides for
N
Pd Cl the synthesis of allylic sulfones.137 Base-mediated decom-
Fe
2 position of the hydrazine leads to the simultaneous forma-
palladacycle tion of a diazo compound and a sulfinate as nucleophilic
coupling partners (Scheme 80).
O O O O SO2R Pd2dba3 (2.5 mol%)
S Me S Ph3P (15 mol%) Ar1
NH BnNEt3Cl (1.0 equiv)
N
I + Na2CO3 (2.5 equiv) SO2R
N Ar1
O2N Me Me
MeCN, 50 °C
85% 90% Ar 2

O O O O Ar2 40–93% yield

O S S Me
S
2-Tol Ph Ph
O O
O
Me SO2Tol SO2Ph S S
68% 48%
2-Tol Ph Ph
Scheme 77
40% 93% 78%

Scheme 80

Syn thesis N.-W. Liu et al. Review

A common method for the regio- and stereoselective more recent example is the iridium-catalyzed regio- and
preparation of allylic sulfones is the transition-metal-cata- enantioselective allylic substitution with sodium sulfi-
lyzed coupling of allylic electrophiles with sulfinate salts or nates.146 Branched allylic sulfones are obtained in high
sulfininic acids.138 Allylic carboxylates,139 carbonates,140 al- regio- and enantioselectivities (Scheme 85).
cohols141 or nitro compounds142 can undergo substitution
Pd catalyst
reactions with sulfinic acids and their salts (Scheme 81). O OAc
chiral ligand
SO2R1
+
Reactivities and regioselectivities can differ significantly R1
S
O Na R 2 R2 R2 R2
depending on the structure of the allyl electrophile and the
Scheme 84
catalyst system.
R2

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O Pd catalyst O Ir catalyst (2 mol%) R2 SO2R1
+ LG SO2R2 +
S 1
S
1 R O Na dioxane, N2, 50 °C
R O Y
Y = metal or H LG = OAc, OCO2Et, OCO2Me
OH, NO2, etc. 77–99% yield
86–98% ee
Scheme 81

Tian, Gu and co-workers reported a stereospecific sub-

stitution of enantioenriched allylic alcohols with sodium
sulfinates that proceeds with complete retention of config-
O
uration (Scheme 82).141b Palladium-catalyzed direct substi- Ir P O
tution of allylic amines with sulfinate salts is also possible, N
furnishing allyl sulfones with almost complete retention of
Ph Ph
configuration (Scheme 83).143 Ir catalyst

Pd(OAc)2 (5 mol%)
HO rac-BINAP (5 mol%) R1O2S SO2Ph SO2Tol
O B(OH)3 (4 equiv)
R3 R3
+ nPr
S Ph
R1 O Na dioxane, N2, 100 °C
R2 R2 92%, 94% ee 92%, 94% ee
51–97% yield
SO2Me SO2iPr
PhO2S
PhO2S Me PhO2S
Me Me

O MeO MeO
Ph Cy 95%, 92% ee 99%, 93% ee

Scheme 85
90%, 97% ee 72%, 97% ee 51%, 97% ee

Scheme 82
Plietker and Jegelka showed that low-valent iron(II)
complexes can catalyze the allylation of sodium sulfi-
H2N
[Pd(allyl)Cl]2 (0.1 mol%)
R1O2S
nates.147 The sulfonylation of allylic carbonates proceeds
rac-BINOL (0.4 mol%)
O R3 B(OH)3 (4.0 equiv) R3 with excellent retention of configuration (Scheme 86). They
S +
R1 O Na dioxane, N2, 100 °C later extended their work to include α-sulfonyl succinimid-
R2 R4 R2 R4
es as sulfonyl donors.148
86–93% yield

OR2
TolO2S TBAFe (5 mol%)
TolO2S BnO2S
(4-MeOAr)3P
Me Me Me O O O SO2R1
(6 mol%)
S
R1 O Na R3 R3
Ph H Cy H Ph H R4 DMF/MeOC2H4OH R4
80 °C
93% 82% 88% 31–86% yield

Scheme 83 Me
SO2Ph SO2Ph N Me SO2Ph

In addition, various efficient chiral catalyst systems for Me

O MeO2C Me
Me Me Me
the asymmetric allylic sulfonylation were developed in the
83% 62% 77%
1980s and 1990s (Scheme 84).144 In general, these methods
enable the highly enantioselective synthesis of allylic sul- Scheme 86
fones, which are useful asymmetric building blocks.145 A

Syn thesis N.-W. Liu et al. Review

The transition-metal-catalyzed coupling of sulfonyl The copper-catalyzed reaction of silyl dienol ethers
chlorides with various organometallic reagents is another with sulfonyl chlorides affords γ-sulfonylated α,β-unsatu-
approach for the synthesis of sulfones. Crucial for the suc- rated carbonyl compounds (Scheme 89).154
cess of these transformations is the reaction temperature.
OTMS O
Vogel and co-workers showed that, at higher temperatures, CuCl (10 mol%)
O
desulfinylative carbon–carbon bond formation via sulfur R S Cl +
MeCN, 80 °C

dioxide extrusion takes place.149 Palladium-catalyzed reac- O

tion of organostannes150 or organoboronic acids151 with sul- SO2R
fonyl chlorides at low temperatures yields the desired sul- 38–87% yield

fones (Scheme 87). O2

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
S S
Method A (M = SnR3):
O O
Pd(PPh3)4, THF, 65–70 °C O
R1 S Cl + R2 M R1 S R2 O Me
Method B (M = B(OH)2): 87% 70%
O PdCl2, K2CO3 O
acetone/H2O, 0–25 °C O2 O2
M = SnR3, B(OH)2 S S

Me O Me O N Me
O2 CO2Me
S 75%
Me S dr = 15:1 56%
O2
MeO Scheme 89
90% 57%
Method A Method A

O2 O2
4 Sulfone Synthesis by C–H Functionaliza-
S S
tion
MeO N Me

98% 82% The selective functionalization of C–H bonds plays a key

Method B Method B role in the development of efficient and sustainable meth-
Scheme 87 ods for organic synthesis.155 Regioselective metal-catalyzed
as well as metal-free activations of C–H bonds have
emerged as valuable tools for the preparation of carbon–
Hu and Lei reported copper-catalyzed coupling reac- carbon and carbon–heteroatom bonds. In recent years, syn-
tions of sulfonyl chlorides with arylboronic acids152 or or- thesis of sulfones by selective functionalization of C–H
ganozinc reagents,153 respectively (Scheme 88). bonds has become an important area of research. Although
the established Friedel–Crafts-type sulfonylation can be
Method A (M = ZnX): considered as C–H functionalization, recent research efforts
O CuI (5 mol%), TMEDA (2.0 equiv) O
R1 S Cl + R2 M
THF, rt focus on different reactivity profiles.
R1 S R2
O
Method B (M = B(OH)2):
O
Dong and co-workers reported the first palladium-cata-
(phen)CuBr (10 mol%), K2CO3
CH2Cl2/H2O, rt lyzed C–H bond sulfonylation of phenylpyridines with sul-
M = ZnX, B(OH)2 fonyl chlorides (Scheme 90).156 Mechanistic studies indicate
a Pd(II)/Pd(IV) catalytic cycle.157
O2 O2
S O2
S S
Me Pd(MeCN)2Cl2
N (10 mol%) N
Br S O
K2CO3
+ R S Cl SO2R
H 4 Å MS
O
86% 74% 76% dioxane, 120 °C
Method A Method A Method A
41–88% yield
O2 O2
S S OMe
Ph N N
O N N
Me
SO2Tol SO2Tol SO2Tol
OMe
88% 73%
Method B Method B

Scheme 88 82% 78% 42%

Scheme 90

Syn thesis N.-W. Liu et al. Review

Palladium-catalyzed sulfonylation of 2-aryloxypyridines DG O Pd(PhCN)2Cl2 (10 mol%) DG

K2CO3, 4 Å MS
with sulfonyl chlorides proceeds in the ortho-position rela- + R1 S Cl SO2R1
R2 dioxane, 120 °C R2
tive to the directing group.158 Removal of the pyridyl group R3
O R3
thus gives access to ortho-sulfonylated phenols, which are 25–70% yield
difficult to synthesize otherwise (Scheme 91). Me Me Cl
O2 O2
S S

N N
O N O Pd(OAc) (8 mol%) Cl Cl
O N
K2CO3
H + R S Cl SO2R 67% Me 61%
4 Å MS O
O O
dioxane, 120 °C

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
NH Me NH
29–67% yield O2 O2
Me
S S

N N O Me
O O 61% 33%
O2 O2
S S Scheme 93

Me Cl
62% Cl 46%
Palladium-catalyzed coupling of quinones with arylsul-
fonyl chlorides gives rise to arylsulfonyl quinones via a
N N Heck-type coupling (Scheme 94).161
O O
O2 O2
S S O O

O O Pd(OAc)2 (5 mol%)
Me + R S Cl
Me K2CO3
H O DCE, 90 °C SO2R
47% 57% O O
52–91% yield
Scheme 91
O O OMe O
Two independent reports describe the ortho-sulfonyla-
Me
tion of azobenzenes with arylsulfonyl chlorides via palladi-
um-catalyzed C–H activation (Scheme 92).159 Loh and co- S S S
O2 O2 O2
workers developed a palladium-catalyzed alkenyl C–H bond O O OMe O
sulfonylation of vinyl pyridines and enamides with sulfonyl 89% 81% 63%
chlorides (Scheme 93).160
Scheme 94
Ph
N
N Method A:
N
Ph Regioselective ortho-sulfonylation of quinolone N-ox-
Pd(OAc)2 (5 mol%)
K2S2O5 (1.1 equiv) N ides was achieved via copper-catalyzed C–H bond activa-
H DCE, air, 110 °C
+ tion (Scheme 95).162
Method B:
O Pd(MeCN)2Cl2 (10 mol%) SO2R
R S Cl K2CO3, 4 Å MS O
CuI (10 mol%)
O dioxane, 130 °C + R S Cl
N H K2CO3 N SO2R
O
Ph Ph O DCE, 100 °C O
N N
N Me N F 28–91% yield

Me
S S OMe
O2 O2

90% 86%
N S N S
Method A Method B O2 O2
O O
Ph Ph 80% 84%
N N
Me
N N Me Me F
Me
N
S S N S N S
O2 O2 O O2
CN O2
O O
Me
71% 90% 53% 65%
Method A Method B
Scheme 95
Scheme 92

Syn thesis N.-W. Liu et al. Review

Kambe and co-workers reported a nickel-mediated C–H

bond sulfonylation of benzamides enabled by the 8-amino- N O
[Ru(p-cymene)Cl2]2 N
(2.5 mol%)
quinoline (AQ) directing group (Scheme 96). 163 + R S Cl
K2CO3
O MeCN, 115 °C
H H
O N O N H SO2R
AQ O AQ
NiCl2 (50 mol%)
H + SO2R1 23–74% yield
R1 S Cl
R2 Na2CO3
O R2
dioxane, 140 °C

N N N
AQ = 33–57% yield
N
Br Me

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
AQ
AQ
O NH SO2Ph S S
O NH O2 O2
O2
O2
S
Me S
70% 74% 40%

42% Cl 38%
OMe Scheme 98

Scheme 96
Several groups reported copper-mediated ortho-sulfo-
Interestingly, the copper-catalyzed reaction of benz- nylations of benzoic acid derivatives with sodium sulfinates
amides bearing the 8-aminoquinoline moiety with sulfonyl employing the 8-aminoquinoline (AQ),166 the 2-pyridinyl
chlorides leads to a remote functionalization of the quino- isopropyl (PIP),167 or the amide-oxazoline (Oxa)168 directing
line (Scheme 97).164 groups (Scheme 99). These oxidative coupling reactions uti-
lize sulfinates as the coupling partner.
H
O N
H H
O N O N
R2 DG DG
N H H
O N O H
conditions SO2R
CuCl (10 mol) S
R2 R O Na
+ Na2CO3 N SO2R 2

O toluene, 110 °C
R1 S Cl
27–89% yield Me Me
O
O2 N
SO2Ph S N H NH
S H O
O O N
N N
Ph N Ph N AQ PIP Oxa
H H
N N

86% 86%
Ts Ts conditions:
O O yield (for R = Ph)

N DG = AQ Cu(OAc)2 (1.0 equiv), K2CO3 76%

N
H H DMF, 80 °C
S N N
78% 70% DG = PIP Cu(OAc)2 (10 mol%), Ag2CO3 73%
DCE, 120 °C
Scheme 97
DG = Oxa Cu(OAc)2 (2.0 equiv), K2CO3 69%
TFE, 80 °C

Scheme 99
A ruthenium-catalyzed regioselective meta-sulfonyla-
tion of 2-phenylpyridines with sulfonyl chlorides was de-
veloped by Frost and co-workers.165 The observed switch in Shi and co-workers described a palladium-catalyzed di-
regioselectivity is attributed to a change in the mechanistic rect sulfonylation of non-activated C(sp3)–H bonds with so-
pathway via a para-directing Ru–C bond (Scheme 98). dium sulfinates enabled by the 8-aminoquinoline moiety
(Scheme 100).169 Late-stage sulfonylation of complex mole-
cules can be achieved with this method.

Syn thesis N.-W. Liu et al. Review

Pd(OAc)2 Qu, Zhao and co-workers developed a metal-free, H-

(10 mol%)
O MesCO2H
O phosphonate-mediated direct sulfonylation of heteroaro-
O
R2 AQ (20 mol%) R2 AQ matic N-oxides with sulfonyl chlorides,172 wherein 2-sulfo-
S N N
R1 H
O Na H Ag2CO3 nyl-N-heterocycles are obtained as products (Scheme 103).
H CH2Cl2, 90 °C SO2R1
26–72% yield
O HP(O)(OiPr)2 (1 equiv)
O + KOH
R S Cl N SO2R
O O
N H O THF, rt
N
N N O 35–87% yield
H H
O N N
SO2Ph SO2Ph

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Me
72% 53% N O2
Me Me S
O
H
N S
O N O2
H
Me OMe N
SO2Ph 86% 65%

44% N Me

Scheme 100 N S
O2 N S
O2

60% 35%
The copper-catalyzed oxidative coupling of oxime ace-
Scheme 103
tates with sodium sulfinates provides access to sulfonylvi-
nylamines and keto sulfones via a formal C(sp3)–H bond ac-
tivation (Scheme 101).170 The groups of Deng and Kuhakarn described methods
for the regioselective C2-sulfonylation of indoles with sodi-
NH2
um sulfinates catalyzed or mediated by iodine (Scheme
SO2R1
O R2 104).173 Both authors propose an addition–elimination
S
R1 O Na Cu(OAc)2 (10 mol%) direct product mechanism for this transformation. Later, an extension to
toluene, 100 °C or the coupling of azetidine and oxetane sulfinate salts was re-
HO (hydrolysis with SiO2) O ported.174
N
SO2R1
H R2
R2 O
after hydrolysis Method A:
S
R1 O Na I2 (10 mol%), TBHP
AcOH, rt
R2 SO2R1
O O
NH2 O2 Method B: N
SO2Tol S I2 (1.5 equiv), MeOH, rt H
SO2Tol Ph R2
Ph H
S N
H
92% 78% 97%
Me
Scheme 101
SO2Ph SO2Me
N N
H
Kamijo and co-workers reported a photoinduced sulfo- H

nylation of ethereal C–H bonds with sulfonyl chlorides.171 84% 90%

Method A Method A
The C–H bond activation is achieved by hydrogen abstrac-
tion with photoexcited benzophenone (Scheme 102). SO2
N SO2
O O Ph2C=O, hν O Me N
H
H + R1 S Cl SO2R1
acetone, rt NBoc
n O n Cl
44–100% yield 75% 94%
Method B Method B
Ts Scheme 104
H
Ts
O O O2
O S
Oct TBHP/TBAI-mediated oxidative coupling of C2/C3-un-
substituted indoles with sulfonyl hydrazides leads to the
H
formation of 3-sulfonyl-2-sulfonyldiazenyl-1H-indoles
44% 100% 74%
(Scheme 105).175
Scheme 102

Syn thesis N.-W. Liu et al. Review

O Of course, sulfur dioxide (SO2) would be an obvious

H
R1 S N NH2 SO2R1 choice as reagent for the installation of a sulfonyl (-SO2-)
TBAI (30 mol%)
O
TBHP moiety. Sulfur dioxide is produced on an enormous scale
R2 N
H and has been utilized by mankind since ancient times.
MeCN, 40 °C N N SO2R1
H However, it is a toxic and corrosive gas. The associated safe-
R2 H
N 42–87% yield ty considerations and the difficult handling can limit the
H
use of sulfur dioxide in the laboratory-scale synthesis of
SO2Tol SO2Tol
fine chemicals. Despite this, sulfur dioxide has found vari-
Cl ous applications in organic synthesis.178 Important exam-
N N ples include the sulfur dioxide ene reaction and the associ-

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
N N SO2Tol N N SO2Tol
H H ated sulfur dioxide induced alkene isomerization,179 as well
87% 72% as copolymerizations with alkenes to produce polysul-
Scheme 105 fones.180
Vogel and co-workers were among the first to investi-
gate the potential of sulfur dioxide as a reagent in the syn-
Xiao, Deng and co-workers reported a metal-free direct thesis of complex molecules.177d They reported a Lewis acid
sulfonylation of 2-methylquinolines with sodium sulfinates promoted ene reaction of enoxysilanes and allylsilanes or
mediated by potassium iodide and TBHP (Scheme 106).176 allylstannanes.181 The formed sulfinates can be trapped in
situ with a variety of electrophiles, enabling a one-pot,
O
three-componenet synthesis of polyfunctional sulfones
S KI (1.0 equiv)
R O Na
TBHP (1.0 equiv)
X (Scheme 107).
DMSO/AcOH SO2R
X N SO2
air, 80 °C R1 O
OSiMe3 TBSOTf R1 O
H 37–94% yield (cat.) R3-X
N O
R1 R2 S TBAF R2 SO2R3
R2 OSiMe3
N Ph
SO2
R1 TBSOTf R1 R1
SO2Ph SO2Ph
F N N (cat.) R3-X
O (TBAF)
R2 M R2 S R2 SO2R3
94% 69%
OM
O2 M = SiMe3, SnBu3
S O2 50–88% yield
N S
N

Me O O O O
51% 56%
S CO2Et S
Scheme 106
60% 65%

5 Sulfur Dioxide Based Three-Component O O O

O
Approaches
O O
S CO2Et
MeO S Ph
Me
Me
Almost all hitherto-described methods for the synthesis
of sulfones utilize starting materials that already contain a 50% 70%
sulfur functionality. Only a few of these sulfur-containing Scheme 107
starting materials are commercially available, and their
synthesis can be quite cumbersome. Therefore, efficient
methods for the incorporation of the sulfonyl moiety from Unfunctionalized alkenes can react with sulfur dioxide
simple, readily available sources offer a very attractive ap- in the presence of stoichiometric amounts of boron trichlo-
proach for the preparation of sulfones. In the last 10 to 15 ride to form sulfinic acid–boron trichloride adducts, which
years, the development of new one-pot and multicompo- can be hydrolyzed with base to generate sulfinates.182 Reac-
nent processes for the synthesis of sulfones from two tion of the latter with alkyl halides yields α,β-unsaturated
sulfur-free starting materials and a simple sulfonyl source sulfones in a one-pot transformation (Scheme 108).
has become a very active area of research.177

Syn thesis N.-W. Liu et al. Review

The reaction of organometallic compounds with sulfur

R1
R1
R3 SO2 R 3 dioxide gas for the preparation of sulfinates is well docu-
R2 R4-X R3
R1 BCl3
R2 mented.1,178a Direct trapping of these salts without prior
CH2Cl2 O NaOH
R2 –20 °C
S
SO2R4
isolation provides a convenient one-pot approach for the
OH.BCl3
80–91% yield
synthesis of sulfones. Since various efficient procedures for
the preparation of a plethora of highly functionalized or-
O
ganometallic reactions are known,185 this process offers an
O O
O O
Me S attractive approach for the synthesis of complex sulfones.
S Ph Ph
A group from Boehringer Ingelheim developed a practi-
Me
83% 87% cal three-step protocol for the transformation of (hetero)ar-

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
omatic halides into sulfones (Scheme 110).186 Their proce-
O O O O O dure consists of (1) generation of a Grignard reagent via
S
Ph
S Ph magnesium–halide exchange; (2) reaction of the Grignard
Me
reagent with sulfur dioxide to afford the corresponding
magnesium sulfinate; and (3) trapping of the sulfinate with
80% 85%
an alkylating agent.
Scheme 108
1) cPentMgBr
O O O
THF, –40 °C R-X
Vogel and co-workers pioneered the use of sulfur diox- Ar X S S
2) SO2 Ar OMgBr Ar R
ide in Lewis acid mediated hetero-Diels–Alder processes as
60–91% yield
a novel method to construct C–C bonds via an umpolung of
electron-rich 1,3-dienes.183 A typical example is depicted in
Scheme 109. Reaction of a mixture of an electron-rich diene O O O O
with sulfur dioxide and a silyl enol ether in the presence of S S
(CH2)4OAc
a Lewis acid affords a silyl sulfinate. The Lewis acid catalyz-
es the initial formation and heterolysis of the hetero-Diels– EtO2C EtO2C

Alder adduct to from a zwitterionic sulfinate, which is 91% 65%

trapped by the enoxy silane as terminal nucleophile. Treat-

O O
ment of the sulfinate with tetrabutylammonium fluoride O O
S
S (CH2)4OAc
(TBAF) and methyl iodide affords the corresponding sulfone N (CH2)4OAc
S
in 63% yield and high stereoselectivity. This method allows
Me
the one-pot, four-component synthesis of polyfunctional
60% 94%
sulfones and sulfonamides and has found application in the
total synthesis of complex molecules and natural prod- Scheme 110
ucts.183,184
A similar one-pot sequence has been reported with a di-
OSiMe3
aryliodonium salt as terminal electrophile (Scheme 111).187
Me SO2 OMe OMe
Et TBSOTf LA
This procedure allows the efficient synthesis of aryl sul-
(cat.) O
+
O fones starting from (hetero)aromatic or aliphatic halides as
S S
O O well as non-prefunctionalized (hetero)arenes. The lithium,
OMe
magnesium and zinc reagents were prepared via metal in-
sertion, exchange or deprotonation.
OSiMe3
It has been shown that lithium sulfinates, prepared in
Me
Et situ from the reaction of organolithium compounds with
sulfur dioxide, can undergo oxidative coupling with benzoic
acids bearing the amide-oxazoline (Oxa) directing group
O
via copper-mediated C–H bond activation (Scheme 112).168
SO2Me TBAF S
O OMe MeI O OMe OSiMe3

Et Et
Me Me

63%, dr = 81:19
100% Z

Scheme 109

Syn thesis N.-W. Liu et al. Review

R X O O Pd(OAc)2
1) metalation Ar2I+Y– O O O
or R SO2M S Ph3P, 1,10-phenanthroline R-X
2) SO2 R Ar Ar X S S
R H Ar O Ar R
K2S2O5, NaO2CH
17–97% yield 31–79% yield
X = Br, I TBAB
M = Li, MgX, ZnX DMSO, 70 °C

O O O O O O O O
S S S S CO2tBu
NC N Me

EtO2C MeO MeO

85% 64%
58% 56%
O O O O Me

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
O O O O
S S
N Ph S S
Me MeO2C Me
Me Me
N
51% 80%
68% 57%
Scheme 111
Scheme 113

H
O N
DG DG Ar B(OH)2 [Pd(MeCN)2Cl2] (10 mol%)
H t O O
O NH BuXPhos (10 mol%)
+ S
O K2S2O5, TBAB Ar R
SO2R R X
SO2 DMF, 85 °C
R Li S 39–96% yield
R OLi
Cu(OAc)2
K2CO3 O O O O
TFE, 80 °C 81% (R = Ph) Sn Sn
Pr O Pr
O 44% (R = nBu) N
DG = N
Me N
N Me H
58% 96%

Scheme 112 O O O O NHBoc

S CO2Et S
CO2Me

Despite its potential utility, there are some drawbacks MeO MeO

associated with the toxic, corrosive and gaseous nature of 94% 51%
sulfur dioxide. A popular strategy to overcome this limita-
Scheme 114
tion is the use of solid, easy-to-handle surrogates.10c,177 Sim-
ple, commercially available metal sulfites (MSO3) or meta-
bisulfites (M2S2O5) can release sulfur dioxide upon the addi- The gold-catalyzed reaction of (hetero)arylboronic acids
tion of Brønsted acids or upon heating to high with K2S2O5 and alkyl halides yields the corresponding sul-
temperatures. Researchers from Pfizer described a palladi- fones in a similar fashion (Scheme 115).190
um-catalyzed sulfonylation of (hetero)aryl halides with po-
tassium metabisulfite (K2S2O5) and sodium formate tBuP AuCl
3
(Scheme 113).188 Direct reaction of the generated sulfinates (10 mol%)
K2S2O5 O O
with alkyl halides enables the one-pot synthesis of sul- + S
Ar B(OH)2 R X
fones. DIPEA Ar R
MeOH/toluene
They later reported a palladium-catalyzed three-com- 100 °C 46–66% yield

ponent synthesis of sulfones from (hetero)arylboronic O O O O

Me O O
acids, alkyl halides and potassium metabisulfite (Scheme S Ph S Ph
S Ph
114).189 The authors propose an in situ formation of a palla- N
N
dium sulfinate, which then reacts with the alkyl halide.
Me Me

56% 49% 53%

Scheme 115

Syn thesis N.-W. Liu et al. Review

Willis and co-workers pioneered the use of the 1,4-di- Pd(OAc)2 O O

1) tBuLi Ar1 SO2 ligand
azabicyclo[2.2.2]octane–bis(sulfur dioxide) adduct DABSO Ar1 Br S
2) DABSO Ar1 Ar2
as very useful, solid and bench-stable sulfur dioxide surro- Li Ar2-Br, Cs2CO3
dioxane, 110 °C 35–98% yield
gate.191 The addition of organolithium or organomagnesium
reagents to DABSO generates the corresponding sulfinates, Me Me

which can be directly trapped with a variety of different

ligand [R = 3,5-(F3C)2C6H3)]
electrophiles, such as alkyl halides, epoxides or diaryliodo- O
nium salts (Scheme 116).192 This method enables the one- PR2 PR2
pot synthesis of a diverse set of sulfones. Organozinc re-
agents react with DABSO in a similar manner, and the gen- O O O O

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
S S
erated zinc sulfinates can be alkylated to form sulfones
(Scheme 117).193 CO2Me N OMe
Me Me
DABSO O O O 81% 95%
E+
R M R S S
THF, –40 °C R E
OM O O O O
M = Li, MgX 46–94% yield F3C S Me S
O O
O O
S Ph Cl
S S Ph
OMe Me OMe
MeO2C 92% 93%
83% 46%
Scheme 118
O O OH
O O O S
n
S
Bu Ph
O Pd(OAc)2 O O
Me E+
PAd2Bu Ar SO2
90% 56% Ar I S
DABSO, Et3N Ar E
HNEt3
Scheme 116 iPrOH, 75 °C
38–90% yield

O O O O
DABSO O O O
R2-X S CO2tBu S CO2tBu
R1 ZnX R1 S S 2
THF, 21 °C DMSO R1 R
OZnx
70 °C MeO2C S
25–90% yield
O O O O 74% 64%
O O
S Ph S CO2tBu
S S CO2tBu
O O O O OH
N CO2Et BocHN CO2Me Me S Ph Me S
58% 89 % 77%

Scheme 117
Me Me
85% 76%
Reaction of organolithium reagents with DABSO, fol- Scheme 119
lowed by palladium-catalyzed cross-coupling of the formed
lithium sulfinate with (hetero)aryl halides allows the three-
component synthesis of aryl sulfones (Scheme 118).194 The Waser and Chen reported a one-pot, three-component
lithium reagents can be prepared in situ through halogen– synthesis of aryl alkynyl sulfones through the reaction of in
lithium exchange. situ generated sulfinates with ethynyl-benziodoxolone
Palladium-catalyzed coupling of aryl halides with (EBX).196 The sulfinates were prepared from DABSO and an
DABSO in the presence of triethylamine yields ammonium organomagnesium reagent or aryl iodide and a palladium
sulfinates. These salts can be directly converted into a vari- catalyst (Scheme 120).
ety of sulfones by trapping with different electrophiles
(Scheme 119).195

Syn thesis N.-W. Liu et al. Review

Ar-Br + Mg O O Wu and co-workers extended this approach to the syn-

R-EBX
or
DABSO
Ar-SO2
S thesis of diaryl sulfones utilizing diaryliodonium salts as
Ar
R
electrophiles.199 In this study, the intermediate sulfonyl hy-
Ar-I + cat. Pd(0)
39–85% yield drazines were prepared by reaction of diazonium salts with
DABSO and hydrazines (Scheme 122).200
R I O
Ar1 N2+BF4–
O 1) DABSO, MeCN, rt O O
+ S
2) (Ar2)2I+BF4– Ar1 Ar2

R-EBX O 2-methylbutan-2-ol
42–88% yield
N 90 °C

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
H2N
O O O O
S S
O O
SiiPr3 O SiiPr3 O O O O
MeO2C S
Ph S S
56% 70% Ph Ph

Cl OMe
O O O O CO2Me
S S
t
74% 88% 42%
Bu SiiPr3
Me
Scheme 122
79% 46%

Scheme 120
Feng and co-workers reported an iodide-catalyzed
three-component synthesis of vinyl sulfones from aryldi-
Building on their previous results with the palladium- azonium salts, DABSO and alkenes (Scheme 123).201
catalyzed aminosulfonylation of aryl halides,197 the Willis
(Het)Ar N2+BF4– TBAI (10 mol%) O
group developed a different approach for the one-pot syn- TBHP O
(Het)Ar S
thesis of aryl sulfones based on in situ generated sulfonyl +
DABSO
hydrazines.198 Key steps in this transformation are the pal- R1
MeCN, 80 °C R1
58–88% yield
ladium-catalyzed aminosulfonylation of the aryl halide
with DABSO and the hydrazine, degradation of the generat- O O
O O
ed sulfonyl hydrazine to the corresponding sulfinate, and Cl S S
S
sulfinate alkylation to yield the desired sulfone (Scheme
Ph Ph
121). 82% 75%
O O O
O
Ph S S N
O O Ph
Pd(OAc)2 (10mol%)
I tBu [Link] (20 mol%) S NR22
3 4 N CO2Me
R1 R1 H 71% 83%
DABSO, H2N-NR22
Scheme 123
K2CO3 BnBr

O O O 6 Biological Synthesis of Sulfones

S 3 R3-X S
R O K
R1 R1
Considering the biological activity profile of sulfones,
36–91% yield
and especially their antibacterial activities, it is very sur-
O O O O prising that there are only three known examples of natu-
S Ph S Ph rally occurring sulfones (Figure 2). The diaryl sulfone echi-
N
nosulfone A, a bromoindole derivative, was isolated from
H MeS
36% 89% the marine sponge Echinodictyum sp.202 So far nothing is
known about the biosynthesis of echinosulfone A. Only as
O O O O
S S CO2Et
recently as 2015 did Hertweck and co-workers report the
Me
isolation of two more diaryl sulfones, sulfadixiamycins B
Me Me
EtO EtO and C, from recombinant Streptomyces species harboring
55% 57%
the entire xiamycin biosynthesis gene cluster.203 The au-
thors propose a flavoprotein-mediated incorporation of
Scheme 121
sulfur dioxide, via a radical copolymerization of two carba-

Syn thesis N.-W. Liu et al. Review

zoles with sulfur dioxide. This report might provide useful References
insights for biomimetic synthesis of sulfones in organic lab-
(1) (a) Whitham, G. H. Organosulfur Chemistry; Oxford University
oratories.
Press: Oxford/New York, 1995. (b) Oae, S. Organic Chemistry of
Sulfur; Plenium Press: New York, 1977. (c) Stirling, C. J. M.
O O Organic sulphur chemistry: Structure, mechanism, and synthesis;
Br Br
S Butterworths: London/Boston, 1975. (d) Patai, S.; Rappoport, Z.;
HO2C
Me
H Stirling, C. J. M. The Chemistry of Sulphones and Sulphoxides;
N NH
HO Wiley: New York, 1988.
HO2C
echinosulfone A
(2) Trost, B. M.; Chadiri, M. R. J. Am. Chem. Soc. 1984, 106, 7260.
Me NH (3) (a) Simpkins, N. S. Tetrahedron 1990, 46, 6951. (b) Forristal, I.
J. Sulfur Chem. 2005, 26, 163.

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
(4) (a) Alonso, D. A.; Ájera, C. N. Org. React. 2009, 72, 367. (b) Gui, J.;
OH
Zhou, Q.; Pan, C.-M.; Yabe, Y.; Burns, A. C.; Collins, M. R.;
Me
O S Me Ornelas, M. A.; Ishihara, Y.; Baran, P. S. J. Am. Chem. Soc. 2014,
O CO2H 136, 4853. (c) Ku, Y.-Y.; Patel, R. R.; Roden, B. A.; Sawick, D. P.
H
N Tetrahedron Lett. 1994, 35, 6017. (d) Brown, A. C.; Carpino, L. A.
H J. Org. Chem. 1985, 50, 1749. (e) Kumar, V.; Ramesh, N. G. Chem.
sulfadixiamycin B
Commun. 2006, 4952. (f) Abrunhosa, I.; Gulea, M.; Masson, S.
OH Synthesis 2004, 928.
Me Me (5) (a) Seeliger, F.; Mayr, H. Org. Biomol. Chem. 2008, 6, 3052.
(b) Magnus, P. D. Tetrahedron 1977, 33, 2019.
CO2H
H (6) (a) Ramberg, L.; Bäcklund, B. Ark. Chim., Mineral Geol. 1940, 27,
OH
N
Me
1. (b) Taylor, R. J. K.; Casy, G. Org. React. 2004, 62, 359.
H
O S Me (7) (a) Julia, M.; Paris, J.-M. Tetrahedron Lett. 1973, 14, 4833.
O CO2H (b) Kocienski, P. J.; Lythgoe, B.; Ruston, S. J. Chem. Soc., Perkin
H
N Trans. 1 1978, 829. (c) Aïssa, C. J. Org. Chem. 2006, 71, 360.
H
(d) Blakemore, P. R. J. Chem. Soc., Perkin Trans. 1 2002, 2563.
sulfadixiamycin C (8) (a) Li, J. J. Name Reactions in Heterocyclic Chemistry; John Wiley
Figure 2 & Sons: Hoboken, 2005. (b) van Leusen, A. M.; Hoogenboom, B.
E.; Siderius, H. Tetrahedron Lett. 1972, 13, 2369. (c) van Leusen,
A. M.; Wildeman, J.; Oldenziel, O. H. J. Org. Chem. 1977, 42, 1153.
(9) Swenson, R. E.; Sowin, T. J.; Zhang, H. Q. J. Org. Chem. 2002, 67,
9182.
7 Conclusion (10) (a) Acton, Q. A. Sulfones—Advances in Research and Application;
Scholarly Editions: Atlanta, 2013. (b) Meadows, D. C.; Gervay-
Sulfones (R-SO2-R) have been known for over 100 years, Hague, J. Med. Res. Rev. 2006, 26, 793. (c) Bisseret, P.; Blanchard,
and they have found widespread application in organic syn- N. Org. Biomol. Chem. 2013, 11, 5393.
thesis and as pharmaceuticals, agrochemicals and poly- (11) (a) Goadsby, P. J.; Ferrari, M. D.; Olesen, J.; Stovner, L. J.; Senard,
mers. Indeed, the first sulfone-based drug, sulfonal, dates J. M.; Jackson, N. C.; Poole, P. H. Neurology 2000, 54, 156.
(b) Sandrini, G.; Farkkila, M.; Burgess, G.; Forster, E.; Haughie, S.
back to 1888.204 The chemistry of sulfones has been subject
Neurology 2002, 59, 1210.
to a formidable evolution since their initial discovery and (12) (a) Iversen, P.; Tyrrell, C. J.; Kaisary, A. V.; Anderson, J. B.; van
experienced a considerable growth in the last 15 years. The Poppel, H.; Tammela, T. L.; Chamberlain, M.; Carroll, K.;
transition-metal-catalyzed reactions, selective C–H func- Melezinek, I. J. Urol. 2000, 164, 1579. (b) Le, Y.; Ji, H.; Chen, J.-F.;
tionalizations, and methods based on sulfur dioxide and Shen, Z.; Yun, J.; Pu, M. Int. J. Pharm. 2009, 370, 175. (c) Kanfer, I.
sulfur dioxide surrogates, in particular, have led to major J. Pharm. Pharm. Sci. 2000, 5, 1.
improvements for the synthetic preparation of sulfones and (13) (a) Yazdanyar, S.; Boer, J.; Ingvarsson, G.; Szepietowski, J. C.;
Jemec, G. B. E. Dermatology 2011, 222, 342. (b) Lopez de Compa-
related applications. Nevertheless, there is a constant high
dre Rosa, L.; Pearlstein, R. A.; Hopfinger, A. J.; Seydel, J. K. J. Med.
demand for novel general and sustainable methods for the Chem. 1987, 30, 900. (c) Zhang, F.-R.; Liu, H.; Irwanto, A.; Fu, X.-
synthesis of sulfones. Regioselective C–H functionaliza- A.; Li, Y.; Yu, G.-Q.; Yu, Y.-X.; Chen, M.-F.; Low, H.-Q.; Li, J.-H.;
tions, sulfur dioxide based introductions of the sulfonyl Bao, F.-F.; Foo, J.-N.; Bei, J.-X.; Jia, X.-M.; Liu, J.; Liany, H.; Wang,
moiety and biomimetic syntheses remain largely unex- N.; Niu, G.-Y.; Wang, Z.-Z.; Shi, B.-Q.; Tian, H.-Q.; Liu, H.-X.; Ma,
plored and new innovative possibilities still lie ahead. S.-S.; Zhou, Y.; You, J.-B.; Yang, Q.; Wang, C.; Chu, T.-S.; Liu, D.-
C.; Yu, X.-L.; Sun, Y.-H.; Ning, Y.; Wei, Z.-H.; Chen, S.-L.; Chen,
X.-C.; Zhang, Z.-X.; Liu, Y.-X.; Pulit, S. L.; Wu, W.-B.; Zheng, Z.-Y.;
Acknowledgment Yang, R.-D.; Long, H.; Liu, Z.-S.; Wang, J.-Q.; Li, M.; Zhang, L.-H.;
Wang, H.; Wang, L.-M.; Xiao, P.; Li, J.-L.; Huang, Z.-M.; Huang, J.-
We thank Prof. Michael Göbel for his support. Funding by the Fonds X.; Li, Z.; Xiong, L.; Yang, J.; Wang, X.-D.; Yu, D.-B.; Lu, X.-M.;
der Chemischen Industrie (Liebig Fellowship to G.M.), the Deutsche Zhou, G.-Z.; Yan, L.-B.; Shen, J.-P.; Zhang, G.-C.; Zeng, Y.-X.; de
Forschungsgemeinschaft (DFG), and the Chinese Scholarship Council Bakker, P.; Chen, S.-M.; Liu, J.-J. N. Engl. J. Med. 2013, 369, 1620.
(PhD fellowship to S.L.) is gratefully acknowledged.

Syn thesis N.-W. Liu et al. Review

(14) (a) Mitchell, G.; Bartlett, D. W.; Fraser, T. E. M.; Hawkes, T. R.; (27) (a) Mirjalali, M. B.; Zolfigol, M. A.; Bamoniri, A.; Khazdooz, L.
Holt, D. C.; Townson, J. K.; Wichert, R. A. Pest. Manag. Sci. 2001, Bull. Korean Chem. Soc. 2003, 24, 1009. (b) Alizadeh, A.; Khodaei,
57, 120. (b) Beaudegnies, R.; Edmunds, A. J. F.; Fraser, T. E. M.; M. M.; Nazari, E. Tetrahedron Lett. 2007, 48, 6805.
Hall, R. G.; Hawkes, T. R.; Mitchell, G.; Schaetzer, J.; Wendeborn, (28) Rueggerberg, W. H. C.; Sauls, T. W.; Norwood, S. L. J. Org. Chem.
S.; Wibley, J. Bioorg. Med. Chem. 2009, 17, 4134. 1955, 20, 455.
(15) Tanetani, Y.; Kaku, K.; Kawai, K.; Fujioka, T.; Shimizu, T. Pest. (29) (a) Fouque, G.; Lacroix, J. Bull. Soc. Chim. Fr. 1923, 33, 180.
Biochem. Physiol. 2009, 95, 47. (b) Kozlov, V. V.; Vol’fson, T. I.; Kozlova, N. A.; Tubyarskaya, G. S.
(16) Takahashi, H.; Ohki, A.; Kanzaki, M.; Tanaka, A.; Sato, Y.; J. Gen. Chem. USSR 1962, 32, 3373.
Matthes, B.; Böger, P.; Wakabayashi, K. Z. Naturforsch. C 2001, (30) Joly, R.; Bucourt, R.; Mathieu, J. Recl. Trav. Chim. Pays-Bas 1959,
56, 781. 78, 527.
(17) El-Hibri, M. J.; Weinberg, S. A. In Encyclopedia of Polymer Science (31) Yang, Y.; Chen, Z.; Rao, Y. Chem. Commun. 2014, 50, 15037.
and Technology; Mark, H. F., Ed.; Wiley: New York, 2014, 179. (32) Yao, B.; Zhang, Y. Tetrahedron Lett. 2008, 49, 5385.

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
(18) (a) Pritzius, A. B.; Breit, B. Angew. Chem. Int. Ed. 2015, 54, 3121. (33) Aziz, J.; Messaoudi, S.; Alami, M.; Hamze, A. Org. Biomol. Chem.
(b) Griffin, R. J.; Henderson, A.; Curtin, N. J.; Echalier, A.; 2014, 12, 9743.
Endicott, J. A.; Hardcastle, I. R.; Newell, D. R.; Noble, M. E. M.; (34) Meek, J. S.; Fowler, J. S. J. Org. Chem. 1968, 33, 3422.
Wang, L.-Z.; Golding, B. T. J. Am. Chem. Soc. 2006, 128, 6012. (35) Oxley, P.; Partridge, M. W.; Robson, T. D.; Short, W. F. J. Chem.
(c) Catarinella, M.; Grüner, T.; Strittmatter, T.; Marx, A.; Mayer, Soc. 1946, 763.
T. U. Angew. Chem. Int. Ed. 2009, 48, 9072. (d) Posner, G. H.; (36) Culvenor, C. C. J.; Davies, W.; Heath, N. S. J. Chem. Soc. 1949, 278.
Maxwell, J. P.; O’Dowd, H.; Krasavin, M.; Xie, S.; Shapiro, T. A. (37) (a) Achmatowicz, O.; Michalski, J. Rocz. Chem. 1956, 30, 243.
Bioorg. Med. Chem. 2000, 8, 1361. (e) Tozkoparan, B.; Küpeli, E.; (b) Hansen, O. R.; Hammer, R.; Vister, T. Acta Chem. Scand. 1953,
Yeşilada, E.; Ertan, M. Bioorg. Med. Chem. 2007, 15, 1808. 7, 1331.
(19) Varma, R. S.; Naicker, K. P. Org. Lett. 1999, 1, 189. (38) Roblin, R. O.; Williams, J. H.; Anderson, G. W. J. Am. Chem. Soc.
(20) (a) Kirihara, M.; Itou, A.; Noguchi, T.; Yamamoto, J. Synlett 2010, 1941, 63, 1930.
1557. (b) Bahrami, K.; Khodaei, M. M.; Sheikh Arabi, M. J. Org. (39) (a) Maloney, K. M.; Kuethe, J. T.; Linn, K. Org. Lett. 2011, 13, 102.
Chem. 2010, 75, 6208. (c) Karimi, B.; Ghoreishi-Nezhad, M.; (b) Liang, S.; Zhang, R.-Y.; Xi, L.-Y.; Chen, S.-Y.; Yu, X.-Q. J. Org.
Clark, J. H. Org. Lett. 2005, 7, 625. (d) Jana, N. K.; Verkade, J. G. Chem. 2013, 78, 11874.
Org. Lett. 2003, 5, 3787. (e) Fukuda, N.; Ikemoto, T. J. Org. Chem. (40) (a) Merritt, E. A.; Olofsson, B. Angew. Chem. Int. Ed. 2009, 48,
2010, 75, 4629. 9052. (b) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299.
(21) Shaabani, A.; Mirzaei, P.; Naderi, S.; Lee, D. G. Tetrahedron 2004, (c) Olofsson, B. Arylation with Diaryliodonium Salts, In Topics in
60, 11415. Current Chemistry; Springer: Berlin/Heidelberg, 2015, 1.
(22) Jereb, M. Green Chem. 2012, 14, 3047. (d) Silva, L. F. Jr.; Olofsson, B. Nat. Prod. Rep. 2011, 28, 1722.
(23) Olah, G. A. Friedel–Crafts and Related Reactions; Wiley-Inter- (41) Umierski, N.; Manolikakes, G. Org. Lett. 2013, 15, 188.
science: New York, 1964. (42) Pandya, V. G.; Mhaske, S. B. Org. Lett. 2014, 16, 3836.
(24) (a) Jensen, F. R.; Goldman, G. In Friedel–Crafts and Related Reac- (43) Liang, S.; Zhang, R.-Y.; Wang, G.; Chen, S.-Y.; Yu, X.-Q. Eur. J. Org.
tions; Olah, G. A., Ed.; Wiley-Interscience: New York, 1964, Chem. 2013, 7050.
1319. (b) Olah, G. A.; Kobayashi, S.; Nishimura, J. J. Am. Chem. (44) Chawla, R.; Kapoor, R.; Singh, A. K.; Yadav, L. D. S. Green Chem.
Soc. 1973, 95, 564. (c) Olah, G. A.; Lin, H. C. Synthesis 1974, 342. 2012, 14, 1308.
(d) Hyatt, J. A.; White, A. W. Synthesis 1984, 214. (e) Effenberger, (45) Guan, Z.-H.; Zuo, W.; Zhao, L.-B.; Ren, Z.-H.; Liang, Y.-M. Synthe-
F.; Huthmacher, K. Angew. Chem. Int. Ed. 1974, 13, 409. sis 2007, 1465.
(f) Répichet, S.; Le Roux, C.; Hernandez, P.; Dubac, J.; Desmurs, (46) Reddy, M. A.; Reddy, P. S.; Sreedhar, B. Adv. Synth. Catal. 2010,
J.-R. J. Org. Chem. 1999, 64, 6479. (g) Graybill, B. M. J. Org. Chem. 352, 1861.
1967, 32, 2931. (h) Sipe, H. J. Jr; Clary, D. W.; White, S. B. Synthe- (47) Chu, X.-Q.; Meng, H.; Xu, X.-P.; Ji, S.-J. Chem. Eur. J. 2015, 21,
sis 1984, 283. (i) Ueda, M.; Uchiyama, K.; Kano, T. Synthesis 11359.
1984, 323. (j) Effenberger, F.; Huthmacher, K. Chem. Ber. 1976, (48) Liu, C.-R.; Li, M.-B.; Cheng, D.-J.; Yang, C.-F.; Tian, S.-K. Org. Lett.
109, 2315. (k) Ono, M.; Nakamura, Y.; Sato, S.; Itoh, I. Chem. Lett. 2009, 11, 2543.
1988, 395. (49) (a) Dornow, A.; Bartsch, W. Liebigs Ann. Chem. 1957, 602, 23.
(25) (a) Choudary, B. M.; Chowdari, N.; Kantam, M.; Kannan, R. Tet- (b) Powell, B. F.; Overberger, C. G.; Anselme, J.-P. J. Heterocycl.
rahedron Lett. 1999, 40, 2859. (b) Singh, R. P.; Kamble, R. M.; Chem. 1983, 20, 121. (c) Carter, P.; Stevens, T. S. J. Chem. Soc.
Chandra, K. L.; Saravanan, P.; Singh, V. K. Tetrahedron 2001, 57, 1961, 1743. (d) Lemal, D. M.; Rave, T. W.; McGregor, S. D. J. Am.
241. (c) Jang, D. O.; Moon, K. S.; Cho, D. H.; Kim, J.-G. Tetrahe- Chem. Soc. 1963, 85, 1944. (e) Lemal, D. M.; Menger, F.; Coats, E.
dron Lett. 2006, 47, 6063. (d) Bahrami, K.; Khodei, M. M.; J. Am. Chem. Soc. 1964, 86, 2395. (f) Carpino, L. A. Chem. Ind.
Shahbazi, F. Tetrahedron Lett. 2008, 49, 3931. (e) Choudary, B. 1957, 172. (g) Carpino, L. A. J. Am. Chem. Soc. 1957, 79, 4427.
M.; Chowdari, N. S.; Kantam, M. L. J. Chem. Soc., Perkin Trans. 1 (h) Baker, W.; McOmie, J. F. W.; Preston, D. R. J. Chem. Soc. 1961,
2000, 2689. (f) Nara, S. J.; Harjani, J. R.; Salunkhe, M. M. J. Org. 2971.
Chem. 2001, 66, 8616. (g) Noronha, R. G.; Fernandes, A. C.; (50) Ballini, R.; Marcantoni, E.; Petrini, M. Tetrahedron 1989, 45,
Romão, C. C. Tetrahedron Lett. 2009, 50, 1407. (h) Borujeni, K. P.; 6791.
Tamami, B. Catal. Commun. 2007, 8, 1191. (i) Marquié, J.; (51) Yang, Y.; Tang, L.; Zhang, S.; Guo, X.; Zha, Z.; Wang, Z. Green
Laporterie, A.; Dubac, J.; Roques, N.; Desmurs, J.-R. J. Org. Chem. Chem. 2014, 16, 4106.
2001, 66, 421. (52) Li, X.; Xu, X.; Tang, Y. Org. Biomol. Chem. 2013, 11, 1739.
(26) (a) Olah, G. A.; Mathew, T.; Surya Prakash, G. K. Chem. Commun. (53) Song, R.-J.; Liu, Y.; Liu, Y.-Y.; Li, J.-H. J. Org. Chem. 2011, 76, 1001.
2001, 1696. (b) Li, H.-Z.; Xiao, L.-W.; Li, H.-Y.; Wang, K.-F.; Li, X. (54) Reddy, L. R.; Hu, B.; Prashad, M.; Prasad, K. Angew. Chem. Int. Ed.
J. Chem. Res., Synop. 2003, 493. 2009, 48, 172.

Syn thesis N.-W. Liu et al. Review

(55) Li, H.-H.; Dong, D.-J.; Jin, Y.-H.; Tian, S.-K. J. Org. Chem. 2009, 74, (85) Rong, G.; Mao, J.; Yan, H.; Zheng, Y.; Zhang, G. J. Org. Chem. 2015,
9501. 80, 4697.
(56) Pan, X.-Q.; Zou, J.-P.; Yi, W.-B.; Zhang, W. Tetrahedron 2015, 71, (86) Taniguchi, T.; Idota, A.; Ishibashi, H. Org. Biomol. Chem. 2011, 9,
7481. 3151.
(57) (a) Asscher, M.; Vofsi, D. J. Chem. Soc. 1964, 4962. (b) Skell, P. S.; (87) Wei, W.; Liu, C.; Yang, D.; Wen, J.; You, J.; Suo, Y.; Wang, H.
Woodworth, R. C.; McNamara, J. H. J. Am. Chem. Soc. 1957, 79, Chem. Commun. 2013, 49, 10239.
1253. (c) Cristol, S. J.; Davies, D. I. J. Org. Chem. 1964, 29, 1282. (88) Xu, K.; Khakyzadeh, V.; Bury, T.; Breit, B. J. Am. Chem. Soc. 2014,
(58) (a) Dénès, F.; Pichowicz, M.; Povie, G.; Renaud, P. Chem. Rev. 136, 16124.
2014, 114, 2587. (b) Dénès, F.; Schiesser, C. H.; Renaud, P. Chem. (89) Li, X.; Xu, X.; Zhou, C. Chem. Commun. 2012, 48, 12240.
Soc. Rev. 2013, 42, 7900. (c) Majumdar, K. C.; Debnath, P. Tetra- (90) Liu, Z.; Chen, X.; Chen, J.; Qu, L.; Xia, Y.; Wu, H.; Ma, H.; Zhu, S.;
hedron 2008, 64, 9799. (d) Hart, D. J. In Radicals in Organic Syn- Zhao, Y. RSC Adv. 2015, 5, 71215.
thesis; Renaud, P.; Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001, (91) Gao, X.; Pan, X.; Gao, J.; Huang, H.; Yuan, G.; Li, Y. Chem.

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
279. (e) Bertrand, M. P.; Ferreri, C. In Radicals in Organic Synthe- Commun. 2015, 51, 210.
sis; Renaud, P.; Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001, (92) (a) Chen, J.-Y.; Chen, X.-L.; Li, X.; Qu, L.-B.; Zhang, Q.; Duan, L.-
485. (f) Alfassi, Z. B. S-Centered Radicals; Wiley: Chichester, K.; Xia, Y.-Y.; Chen, X.; Sun, K.; Liu, Z.-D.; Zhao, Y.-F. Eur. J. Org.
1999. Chem. 2015, 314. (b) Jiang, Y.; Loh, T.-P. Chem. Sci. 2014, 5, 4939.
(59) (a) Quebatte, L.; Thommes, K.; Severin, K. J. Am. Chem. Soc. 2006, (93) Katrun, P.; Hlekhlai, S.; Meesin, J.; Pohmakotr, M.; Reutrakul, V.;
128, 7440. (b) Nair, R. P.; Kim, T. H.; Frost, B. J. Organometallics Jaipetch, T.; Soorukram, D.; Kuhakarn, C. Org. Biomol. Chem.
2009, 28, 4681. 2015, 13, 4785.
(60) Kamigata, N.; Shimizu, T. Rev. Heteroat. Chem. 1997, 17, 1. (94) Jiang, Q.; Xu, B.; Jia, J.; Zhao, A.; Zhao, Y.-R.; Li, Y.-Y.; He, N.-N.;
(61) Zeng, X.; Ilies, L.; Nakamura, E. Org. Lett. 2012, 14, 954. Guo, C.-C. J. Org. Chem. 2014, 79, 7372.
(62) Gilmore, K.; Gold, B.; Clark, R. J.; Alabugin, I. V. Aust. J. Chem. (95) Chen, J.; Mao, J.; Zheng, Y.; Liu, D.; Rong, G.; Yan, H.; Zhang, C.;
2013, 66, 336. Shi, D. Tetrahedron 2015, 71, 5059.
(63) (a) Kang, S.-K.; Ko, B.-S.; Ha, Y.-H. J. Org. Chem. 2001, 66, 3630. (96) Gao, J.; Lai, J.; Yuan, G. RSC Adv. 2015, 5, 66723.
(b) Kang, S.-K.; Ko, B.-S.; Lee, D.-M. Synth. Commun. 2006, 32, (97) Xu, Y.; Tang, X.; Hu, W.; Wu, W.; Jiang, H. Green Chem. 2014, 16,
3263. (c) Kang, S.-K.; Seo, H.-W.; Ha, Y.-H. Synthesis 2001, 1321. 3720.
(64) Kang, S.-K.; Ha, Y.-H.; Kim, D.-H.; Lim, Y.; Jung, J. Chem. (98) Li, H.-S.; Liu, G. J. Org. Chem. 2014, 79, 509.
Commun. 2001, 1306. (99) Rong, G.; Mao, J.; Yan, H.; Zheng, Y.; Zhang, G. J. Org. Chem. 2015,
(65) Alabugin, I. V.; Timokhin, V. I.; Abrams, J. N.; Manoharan, M.; 80, 7652.
Abrams, R.; Ghiviriga, I. J. Am. Chem. Soc. 2008, 130, 10984. (100) Singh, R.; Allam, B. K.; Singh, N.; Kumari, K.; Singh, S. K.; Singh,
(66) Mantrand, N.; Renaud, P. Tetrahedron 2008, 64, 11860. K. N. Org. Lett. 2015, 17, 2656.
(67) Taniguchi, N. Synlett 2011, 1308. (101) Li, S.; Li, X.; Yang, F.; Wu, Y. Org. Chem. Front. 2015, 2, 1076.
(68) Taniguchi, N. Tetrahedron 2014, 70, 1984. (102) Lu, Q.; Zhang, J.; Peng, P.; Zhang, G.; Huang, Z.; Yi, H.; Miller, J.
(69) Xu, Y.; Zhao, J.; Tang, X.; Wu, W.; Jiang, H. Adv. Synth. Catal. T.; Lei, A. Chem. Sci. 2015, 6, 4851.
2014, 356, 2029. (103) Yadav, V. K.; Srivastava, V. P.; Yadav, L. D. S. Synlett 2016, 27,
(70) Katrun, P.; Chiampanichayakul, S.; Korworapan, K.; Pohmakotr, 427.
M.; Reutrakul, V.; Jaipetch, T.; Kuhakarn, C. Eur. J. Org. Chem. (104) Tang, Y.; Fan, Y.; Gao, H.; Li, X.; Xu, X. Tetrahedron Lett. 2015, 56,
2010, 5633. 5616.
(71) Wei, W.; Wen, J.; Yang, D.; Du, J.; You, J.; Wang, H. Green Chem. (105) Jiang, H.; Cheng, Y.; Zhang, Y.; Yu, S. Eur. J. Org. Chem. 2013,
2014, 16, 2988. 5485.
(72) Xi, Y.; Dong, B.; McClain, E. J.; Wang, Q.; Gregg, T. L.; Akhmedov, (106) Tang, Y.; Zhang, Y.; Wang, K.; Li, X.; Xu, X.; Du, X. Org. Biomol.
N. G.; Petersen, J. L.; Shi, X. Angew. Chem. Int. Ed. 2014, 53, 4657. Chem. 2015, 13, 7084.
(73) Meyer, A. U.; Jäger, S.; Prasad Hari, D.; König, B. Adv. Synth. Catal. (107) (a) Gilman, H.; Beaber, N. J.; Myers, C. H. J. Am. Chem. Soc. 1925,
2015, 357, 2050. 47, 2047. (b) Burton, H.; Davy, W. A. J. Chem. Soc. 1948, 528.
(74) Xia, D.; Miao, T.; Li, P.; Wang, L. Chem. Asian J. 2015, 10, 1919. (c) Whitmore, F. C.; Thurman, N. J. Am. Chem. Soc. 1923, 45,
(75) Yang, W.; Yang, S.; Li, P.; Wang, L. Chem. Commun. 2015, 51, 1068.
7520. (108) Gilman, H.; Fothergill, R. E. J. Am. Chem. Soc. 1929, 51, 3501.
(76) Taniguchi, N. J. Org. Chem. 2015, 80, 7797. (109) Shirota, Y.; Nagai, T.; Tokura, N. Tetrahedron 1969, 25, 3193.
(77) Kariya, A.; Yamaguchi, T.; Nobuta, T.; Tada, N.; Miura, T.; Itoh, A. (110) Katritzky, A. R.; Abdel-Fattah, A. A.; Vakulenko, A. V.; Tao, H. J.
RSC Adv. 2014, 4, 13191. Org. Chem. 2005, 70, 9191.
(78) Lu, Q.; Zhang, J.; Wei, F.; Qi, Y.; Wang, H.; Liu, Z.; Lei, A. Angew. (111) (a) Gerasimova, T. N.; Bushmelev, V. A.; Koptyug, V. A. Russ.
Chem. Int. Ed. 2013, 52, 7156. J. Org. Chem. 1965, 1, 1667. (b) Bradley, W.; Hannon, J. D. Chem.
(79) Singh, A. K.; Chawla, R.; Yadav, L. D. S. Tetrahedron Lett. 2014, 55, Ind. 1959, 540.
4742. (112) Mao, S.; Gao, Y. R.; Zhu, X. Q.; Guo, D. D.; Wang, Y. Q. Org. Lett.
(80) Lu, Q.; Zhang, J.; Zhao, G.; Qi, Y.; Wang, H.; Lei, A. J. Am. Chem. 2015, 17, 1692.
Soc. 2013, 135, 11481. (113) Ojha, D. P.; Prabhu, K. R. Org. Lett. 2015, 17, 18.
(81) Li, X.; Xu, Y.; Wu, W.; Jiang, C.; Qi, C.; Jiang, H. Chem. Eur. J. 2014, (114) Feng, X. W.; Wang, J.; Zhang, J.; Yang, J.; Wang, N.; Yu, X. Q. Org.
20, 7911. Lett. 2010, 12, 4408.
(82) Tang, S.; Wu, Y.; Liao, W.; Bai, R.; Liu, C.; Lei, A. Chem. Commun. (115) Yang, Z.; Hao, W. J.; Wang, S. L.; Zhang, J. P.; Jiang, B.; Li, G.; Tu, S.
2014, 50, 4496. J. J. Org. Chem. 2015, 80, 9224.
(83) Sun, K.; Lv, Y.; Zhu, Z.; Jiang, Y.; Qi, J.; Wu, H.; Zhang, Z.; Zhang, (116) Gigant, N.; Drège, E.; Retailleau, P.; Joseph, D. Chem. Eur. J. 2015,
G.; Wang, X. RSC Adv. 2015, 5, 50701. 21, 15544.
(84) Li, X.; Xu, X.; Shi, X. Tetrahedron Lett. 2013, 54, 3071. (117) Mock, W. L. J. Am. Chem. Soc. 1966, 88, 2857.

Syn thesis N.-W. Liu et al. Review

(118) Smith, M. March's Advanced Organic Chemistry. Reactions, Mech- (141) (a) Chandrasekhar, S.; Jagadeshwar, V.; Saritha, B.; Narsihmulu,
anisms, and Structure; Wiley: Hoboken, 2013. C. J. Org. Chem. 2005, 70, 6506. (b) Ma, X.-T.; Dai, R.-H.; Zhnag, J.;
(119) (a) Deguin, B.; Vogel, P. J. Am. Chem. Soc. 1992, 114, 9210. Gu, Y.; Tian, S.-K. Adv. Synth. Catal. 2014, 356, 2984.
(b) Vogel, P.; Sordo, J. A. Curr. Org. Chem. 2006, 10, 2007. (142) (a) Ono, N.; Hamamoto, I.; Kawai, T.; Kaji, A.; Tamura, R.;
(c) Suarez, D.; Sordo, T. L.; Sordo, J. A. J. Org. Chem. 1995, 60, Kakihana, M. Bull. Chem. Soc. Jpn. 1986, 59, 405. (b) Tamura, R.;
2848. (d) Suarez, D.; Gonzalez, J.; Sordo, T. L.; Sordo, J. A. J. Org. Kai, Y.; Kakihana, M.; Hayashi, K.; Tsuji, M.; Nakamura, T.; Oda,
Chem. 1994, 59, 8058. (e) Suarez, D.; Sordo, T. L.; Sordo, J. A. J. D. J. Org. Chem. 1986, 51, 4375.
Am. Chem. Soc. 1994, 116, 763. (143) Wu, X. S.; Chen, Y.; Li, M. B.; Zhou, M. G.; Tian, S. K. J. Am. Chem.
(120) Suzuki, H.; Abe, H. Tetrahedron Lett. 1995, 36, 6239. Soc. 2012, 134, 14694.
(121) Zhu, W.; Ma, D. J. Org. Chem. 2005, 70, 2696. (144) (a) Hiroi, K.; Kurihara, Y. J. Chem. Soc., Chem. Commun. 1989,
(122) Baskin, J. M.; Wang, Z. Org. Lett. 2002, 4, 4423. 1778. (b) Hiroi, K.; Makino, K. Chem. Pharm. Bull. 1988, 36, 1744.
(123) Yang, M.; Shen, H.; Li, Y.; Shen, C.; Zhang, P. RSC Adv. 2014, 4, (c) Hiroi, K.; Makino, K. Chem. Lett. 1986, 617. (d) Hiroi, K.;

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
26295. Kitayama, R.; Sato, S. J. Chem. Soc., Chem. Commun. 1984, 303.
(124) Bian, M.; Xu, F.; Ma, C. Synthesis 2007, 2951. (e) Hiroi, K.; Kitayama, R.; Sato, S. Chem. Pharm. Bull. 1984, 32,
(125) Srinivas, B. T. V.; Rawat, V. S.; Konda, K.; Sreedhar, B. Adv. Synth. 2628. (f) Hiroi, K.; Kitayama, R.; Sato, S. J. Chem. Soc., Chem.
Catal. 2014, 356, 805. Commun. 1983, 1470. (g) Eichelmann, H.; Gais, H.-J. Tetrahe-
(126) Yuan, Y. Q.; Guo, S. R. Synlett 2011, 2750. dron: Asymmetry 1995, 6, 643. (h) Gavrilov, K. N.; Bondarev, O.
(127) Gund, S. H.; Shelkar, R. S.; Nagarkar, J. M. RSC Adv. 2015, 5, G.; Tsarev, V. N.; Shiryaev, A. A.; Lyubimov, S. E.; Kucherenko, A.
62926. S.; Davankov, V. A. Russ. Chem. Bull. 2003, 52, 122. (i) Wolfe, J. A.;
(128) Zhang, K.; Xu, X. H.; Qing, F. L. J. Org. Chem. 2015, 80, 7658. Hitchcock, S. R. Tetrahedron: Asymmetry 2010, 21, 2690. (j) Gais,
(129) (a) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M. Org. Lett. H.-J.; Eichelmann, H.; Spalthoff, N.; Gerhards, F.; Frank, M.;
2002, 4, 4719. (b) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. Raabe, G. Tetrahedron: Asymmetry 1998, 9, 235. (k) Tsarev, V. N.;
M. Synlett 2003, 361. (c) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Konkin, S. I.; Shyryaev, A. A.; Davankov, V. A.; Gavrilov, K. N. Tet-
Parisi, L. M.; Bernini, R. J. Org. Chem. 2004, 69, 5608. rahedron: Asymmetry 2005, 16, 1737.
(130) Reeves, D. C.; Rodriguez, S.; Lee, H.; Haddad, N.; Krishnamurthy, (145) Trost, B. M.; Organ, M. G.; O’Doherty, G. A. J. Am. Chem. Soc.
D.; Senanayake, C. H. Tetrahedron Lett. 2009, 50, 2870. 1995, 117, 9662.
(131) Tian, H.; Cao, A.; Qiao, L.; Yu, A.; Chang, J.; Wu, Y. Tetrahedron (146) Ueda, M.; Hartwig, J. F. Org. Lett. 2010, 12, 92.
2014, 70, 9107. (147) Jegelka, M.; Plietker, B. Org. Lett. 2009, 11, 3462.
(132) Beaulieu, C.; Guay, D.; Wang, Z.; Evans, D. A. Tetrahedron Lett. (148) Jegelka, M.; Plietker, B. Chem. Eur. J. 2011, 17, 10417.
2004, 45, 3233. (149) (a) Dubbaka, S. R.; Vogel, P. Angew. Chem. Int. Ed. 2005, 44, 7674.
(133) Kir, A.; Sayyed, I. A.; Lo, W. F.; Kaiser, H. M.; Beller, M.; Tse, M. K. (b) Dubbaka, S. R.; Vogel, P. Tetrahedron Lett. 2006, 47, 3345.
Org. Lett. 2007, 9, 3405. (c) Dubbaka, S. R.; Vogel, P. Org. Lett. 2004, 6, 95. (d) Dubbaka, S.
(134) Huang, F.; Batey, R. A. Tetrahedron 2007, 63, 7667. R.; Vogel, P. J. Am. Chem. Soc. 2003, 125, 15292. (e) Volla, C. M.
(135) Kantam, M.; Neelima, B.; Sreedhar, B.; Chakravarti, R. Synlett R.; Dubbaka, S. R.; Vogel, P. Tetrahedron 2009, 65, 504.
2008, 1455. (150) Labadie, S. S. J. Org. Chem. 1989, 54, 2496.
(136) Yang, H.; Li, Y.; Jiang, M.; Wang, J.; Fu, H. Chem. Eur. J. 2011, 17, (151) Bandgar, B. P.; Bettigeri, S. V.; Phopase, J. Org. Lett. 2004, 6,
5652. 2105.
(137) Zhou, P. X.; Ye, Y. Y.; Zhao, L. B.; Hou, J. Y.; Kang, X.; Chen, D. Q.; (152) Hu, F.; Lei, X. ChemCatChem 2015, 7, 1539.
Tang, Q.; Zhang, J. Y.; Huang, Q. X.; Zheng, L.; Ma, J. W.; Xu, P. F.; (153) Fu, Y.; Zhu, W.; Zhao, X.; Hügel, H.; Wu, Z.; Su, Y.; Du, Z.; Huang,
Liang, Y. M. Chem. Eur. J. 2014, 20, 16093. D.; Hu, Y. Org. Biomol. Chem. 2014, 12, 4295.
(138) (a) Tsuji, J. Acc. Chem. Res. 1969, 2, 144. (b) Trost, B. M. Tetrahe- (154) Liu, X.; Chen, X.; Mohr, J. T. Org. Lett. 2015, 17, 3572.
dron 1977, 33, 2615. (c) Trost, B. M.; Van Vranken, D. L. Chem. (155) (a) Yamaguchi, J.; Itami, K.; Yamaguchi, A. D. Angew. Chem. Int.
Rev. 1996, 96, 395. (d) Trost, B. M.; Crawley, M. L. Chem. Rev. Ed. 2012, 51, 8960. (b) Gutekunst, W. R.; Baran, P. S. Chem. Soc.
2003, 103, 2921. Rev. 2011, 40, 1976. (c) Ackermann, L. Chem. Rev. 2011, 111,
(139) (a) Billamboz, M.; Mangin, F.; Drillaud, N.; Chevrin-Villette, C.; 1315. (d) Wencel-Delord, J.; Dröge, T.; Liu, F.; Glorius, F. Chem.
Banaszak-Léonard, E.; Len, C. J. Org. Chem. 2014, 79, 493. Soc. Rev. 2011, 40, 4740. (e) Jazzar, R.; Hitce, J.; Renaudat, A.;
(b) Inomata, K.; Yamamoto, T.; Kotake, H. Chem. Lett. 1981, Sofack-Kreutzer, J.; Baudoin, O. Chem. Eur. J. 2010, 16, 2654.
1357. (c) Felpin, F.-X.; Landais, Y. J. Org. Chem. 2005, 70, 6441. (f) Crabtree, R. H. Chem. Rev. 2010, 110, 575. (g) Bergman, R. G.
(d) Liao, M.-C.; Duan, X.-H.; Liang, Y.-M. Tetrahedron Lett. 2005, Nature 2007, 446, 391. (h) Godula, K.; Sames, D. Science 2006,
46, 3469. (e) Uozumi, Y.; Danjo, H.; Hayashi, T. Tetrahedron Lett. 312, 67.
1997, 38, 3557. (f) Seebach, D.; Devaquet, E.; Ernst, A.; (156) Zhao, X.; Dimitrijevic, E.; Dong, V. M. J. Am. Chem. Soc. 2009,
Hayakawa, M.; Kühnle, F. N. M.; Schweizer, W. B.; Weber, B. 131, 3466.
Helv. Chim. Acta 1995, 78, 1636. (g) Vasen, D.; Salzer, A.; (157) Zhao, X.; Dong, V. M. Angew. Chem. Int. Ed. 2011, 50, 932.
Gerhards, F.; Gais, H.-J.; Bieler, N. H.; Togni, A. Organometallics (158) Xu, Y.; Liu, P.; Li, S. L.; Sun, P. J. Org. Chem. 2015, 80, 1269.
2000, 19, 539. (h) Trost, B. M.; Crawley, M. L.; Lee, C. B. Chem. (159) (a) Zhang, D.; Cui, X.; Zhang, Q.; Wu, Y. J. Org. Chem. 2015, 80,
Eur. J. 2006, 12, 2171. (i) Boldrini, G. P.; Savoia, D.; Tagliavini, E.; 1517. (b) Xia, C.; Wei, Z.; Shen, C.; Xu, J.; Yang, Y.; Su, W.; Zhang,
Trombini, C.; Umani-Ronchi, A. J. Organomet. Chem. 1984, 268, P. RSC Adv. 2015, 5, 52588.
97. (160) Xu, Y. H.; Wang, M.; Lu, P.; Loh, T. P. Tetrahedron 2013, 69, 4403.
(140) (a) Safi, M.; Sinou, D. Tetrahedron Lett. 1991, 32, 2025. (b) Kang, (161) Ge, B.; Wang, D.; Dong, W.; Ma, P.; Li, Y.; Ding, Y. Tetrahedron
S.-K.; Park, D.-C.; Jeon, J.-H.; Rho, H.-S.; Yu, C.-M. Tetrahedron Lett. 2014, 55, 5443.
Lett. 1994, 35, 2357. (162) Wu, Z.; Song, H.; Cui, X.; Pi, C.; Du, W.; Wu, Y. Org. Lett. 2013, 15,
1270.

Syn thesis N.-W. Liu et al. Review

(163) Reddy, V. P.; Qiu, R.; Iwasaki, T.; Kambe, N. Org. Biomol. Chem. (183) (a) Deguin, B.; Roulet, J. M.; Vogel, P. Tetrahedron Lett. 1997, 38,
2015, 13, 6803. 6197. (b) Bouchez, L. C.; Turks, M.; Dubbaka, S. R.; Fonquerne,
(164) Liang, H. W.; Jiang, K.; Ding, W.; Yuan, Y.; Shuai, L.; Chen, Y. C.; F.; Craita, C.; Laclef, S.; Vogel, P. Tetrahedron 2005, 61, 11473.
Wei, Y. Chem. Commun. 2015, 51, 16928. (c) Bouchez, L. C.; Dubbaka, S. R.; Turks, M.; Vogel, P. J. Org.
(165) Saidi, O.; Marafie, J.; Ledger, A. E.; Liu, P. M.; Mahon, M. F.; Chem. 2004, 69, 6413. (d) Exner, C. J.; Laclef, S.; Poli, F.; Turks,
Kociok-Köhn, G.; Whittlesey, M. K.; Frost, C. G. J. Am. Chem. Soc. M.; Vogel, P. J. Org. Chem. 2011, 76, 840. (e) Huang, X. G.; Vogel,
2011, 133, 19298. P. Synthesis 2002, 232.
(166) Liu, J.; Yu, L.; Zhuang, S.; Gui, Q.; Chen, X.; Wang, W.; Tan, Z. (184) (a) Bouchez, L. C.; Vogel, P. Chem. Eur. J. 2005, 11, 4609.
Chem. Commun. 2015, 51, 6418. (b) Turks, M.; Huang, X.; Vogel, P. Chem. Eur. J. 2005, 11, 465.
(167) Rao, W. H.; Shi, B. F. Org. Lett. 2015, 17, 2784. (c) Turks, M.; Fonquerne, F.; Vogel, P. Org. Lett. 2004, 6, 1053.
(168) Liang, S.; Liu, N. W.; Manolikakes, G. Adv. Synth. Catal. 2016, 358, (d) Narkevitch, V.; Vogel, P.; Schenk, K. Helv. Chim. Acta 2002, 85,
159. 1674. (e) Huang, X. G.; Craita, C.; Vogel, P. J. Org. Chem. 2004, 69,

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
(169) Rao, W. H.; Zhan, B. B.; Chen, K.; Ling, P. X.; Zhang, Z. Z.; Shi, B. F. 4272. (f) Craita, C.; Didier, C.; Vogel, P. Chem. Commun. 2007,
Org. Lett. 2015, 17, 3552. 2411.
(170) Tang, X.; Huang, L.; Xu, Y.; Yang, J.; Wu, W.; Jiang, H. Angew. (185) (a) Schlosser, M. Organometallics in Synthesis. Third Manual;
Chem. Int. Ed. 2014, 53, 4205. Wiley: Hoboken, 2013. (b) Knochel, P. Handbook of Functional-
(171) Kamijo, S.; Hirota, M.; Tao, K.; Watanabe, M.; Murafuji, T. Tetra- ized Organometallics. Application and Synthesis; Wiley-VCH:
hedron Lett. 2014, 55, 5551. Weinheim, 2005.
(172) Sun, K.; Chen, X. L.; Li, X.; Qu, L. B.; Bi, W. Z.; Chen, X.; Ma, H. L.; (186) Wu, J. P.; Emeigh, J.; Su, X.-P. Org. Lett. 2005, 7, 1223.
Zhang, S. T.; Han, B. W.; Zhao, Y. F.; Li, C. J. Chem. Commun. 2015, (187) (a) Margraf, N.; Manolikakes, G. J. Org. Chem. 2015, 80, 2582.
51, 12111. (b) Umierski, N.; Manolikakes, G. Org. Lett. 2013, 15, 4972.
(173) (a) Xiao, F.; Chen, H.; Xie, H.; Chen, S.; Yang, L.; Deng, G. J. Org. (188) Shavnya, A.; Coffey, S. B.; Smith, A. C.; Mascitti, V. Org. Lett.
Lett. 2014, 16, 50. (b) Katrun, P.; Mueangkaew, C.; Pohmakotr, 2013, 15, 6226.
M.; Reutrakul, V.; Jaipetch, T.; Soorukram, D.; Kuhakarn, C. (189) Shavnya, A.; Hesp, K. D.; Mascitti, V.; Smith, A. C. Angew. Chem.
J. Org. Chem. 2014, 79, 1778. Int. Ed. 2015, 54, 13571.
(174) Nassoy, A. C. M.; Raubo, P.; Harrity, J. P. Chem. Commun. 2015, (190) Johnson, M. W.; Bagley, S. W.; Mankad, N. P.; Bergman, R. G.;
51, 5914. Mascitti, V.; Toste, F. D. Angew. Chem. Int. Ed. 2014, 53, 4404.
(175) Qiu, J. K.; Hao, W. J.; Wang, D. C.; Wei, P.; Sun, J.; Jiang, B.; Tu, S. J. (191) Woolven, H.; González-Rodríguez, C.; Marco, I.; Thompson, A.
Chem. Commun. 2014, 50, 14782. L.; Willis, M. C. Org. Lett. 2011, 13, 4876.
(176) Xiao, F.; Chen, S.; Chen, Y.; Huang, H.; Deng, G. J. Chem. (192) Deeming, A. S.; Russell, C. J.; Hennessy, A. J.; Willis, M. C. Org.
Commun. 2015, 51, 652. Lett. 2014, 16, 150.
(177) (a) Deeming, A. S.; Emmett, E. J.; Richards-Taylor, C. S.; Willis, M. (193) Rocke, B. N.; Bahnck, K. B.; Herr, M.; Lavergne, S.; Mascitti, V.;
C. Synthesis 2014, 46, 2701. (b) Emmett, E. J.; Willis, M. C. Asian Perreault, C.; Polivkova, J.; Shavnya, A. Org. Lett. 2014, 16, 154.
J. Org. Chem. 2015, 4, 602. (c) Liu, G.; Fan, C.; Wu, J. Org. Biomol. (194) Emmett, E. J.; Hayter, B. R.; Willis, M. C. Angew. Chem. Int. Ed.
Chem. 2015, 13, 1592. (d) Vogel, P.; Turks, M.; Bouchez, L.; 2013, 52, 12679.
Markovic, D.; Varela-Álvarez, A.; Sordo, J. Á. Acc. Chem. Res. (195) Emmett, E. J.; Hayter, B. R.; Willis, M. C. Angew. Chem. Int. Ed.
2007, 40, 931. (e) Floriańczyk, Z.; Raducha, D. Pol. J. Chem. 1995, 2014, 53, 10204.
69, 481. (196) Chen, C. C.; Waser, J. Org. Lett. 2015, 17, 736.
(178) (a) Burke, S. D. In Encyclopedia of Reagents for Organic Synthesis; (197) (a) Nguyen, B.; Emmett, E. J.; Willis, M. C. J. Am. Chem. Soc. 2010,
John Wiley & Sons: Chichester, 2001. (b) Pelzer, G.; Herwig, J.; 132, 16372. (b) Emmett, E. J.; Richards-Taylor, C. S.; Nguyen, B.;
Keim, W.; Goddard, R. Russ. Chem. Bull. 1998, 47, 904. Garcia-Rubia, A.; Hayter, B. R.; Willis, M. C. Org. Biomol. Chem.
(c) Hoffman, R. V. Org. Synth. 1981, 60, 121. (d) Malet-Sanz, L.; 2012, 10, 4007.
Madrzak, J.; Ley, S. V.; Baxendale, I. R. Org. Biomol. Chem. 2010, (198) Richards-Taylor, C. S.; Blakemore, D. C.; Willis, M. C. Chem. Sci.
8, 5324. 2014, 5, 222.
(179) (a) Hoffmann, H. M. R. Angew. Chem. Int. Ed. 1969, 8, 556. (199) Liu, X.; Li, W.; Zheng, D.; Fan, X.; Wu, J. Tetrahedron 2015, 71,
(b) Rogic, M. M.; Masilamani, D. J. Am. Chem. Soc. 1977, 99, 5219. 3359.
(c) Markovic, D.; Varela-Alvarez, A.; Sordo, J. A.; Vogel, P. J. Am. (200) Zheng, D.; An, Y.; Li, Z.; Wu, J. Angew. Chem. Int. Ed. 2014, 53,
Chem. Soc. 2006, 128, 7782. 2451.
(180) Wojcinski, L. M.; Boyer, M. T.; Sen, A. Inorg. Chim. Acta 1998, (201) Fan, W.; Su, J.; Shi, D.; Feng, B. Tetrahedron 2015, 71, 6740.
270, 8. (202) Ovenden, S. P. B.; Capon, R. J. J. Nat. Prod. 1999, 62, 1246.
(181) Bouchez, L.; Vogel, P. Synthesis 2002, 225. (203) Baunach, M.; Ding, L.; Willing, K.; Hertweck, C. Angew. Chem.
(182) Marković, D.; Volla, C. M.; Vogel, P.; Varela-Álvarez, A.; Sordo, J. Int. Ed. 2015, 54, 13279.
A. Chem. Eur. J. 2010, 16, 5969. (204) Wendt, E. C. In The Medical Record; Vol. 33; Shrady, G. F.;
Stedman, T. L., Eds.; W. Wood: New York, 1888, 597.

Sulfonation & Oxidation in Chemistry
No ratings yet
Sulfonation & Oxidation in Chemistry
10 pages
Sulfonyl Imidazoles As Reagents For The Preparation of Sulfonates and Sulfonamides
No ratings yet
Sulfonyl Imidazoles As Reagents For The Preparation of Sulfonates and Sulfonamides
4 pages
Lecture 15
No ratings yet
Lecture 15
18 pages
Sulfonamides: History and Synthesis
No ratings yet
Sulfonamides: History and Synthesis
58 pages
Sulfonation Lec 6
No ratings yet
Sulfonation Lec 6
54 pages
Sulfonation Oxidation
No ratings yet
Sulfonation Oxidation
10 pages
Sulfonation and Sulfation: Group 1
No ratings yet
Sulfonation and Sulfation: Group 1
39 pages
Asia 201601732
No ratings yet
Asia 201601732
7 pages
Sulfonation & Sulfation
No ratings yet
Sulfonation & Sulfation
23 pages
Preparation
No ratings yet
Preparation
2 pages
1 s2.0 S0022286018314236 Main
No ratings yet
1 s2.0 S0022286018314236 Main
8 pages
Research Article
No ratings yet
Research Article
11 pages
Chiral Sulfoxide 10
No ratings yet
Chiral Sulfoxide 10
13 pages
Asymmetric Synthesis Techniques in Organic Chemistry
No ratings yet
Asymmetric Synthesis Techniques in Organic Chemistry
10 pages
Sustainable Sulfonation Mechanisms
No ratings yet
Sustainable Sulfonation Mechanisms
23 pages
Tetrahedron Report Number 282: in LJK
No ratings yet
Tetrahedron Report Number 282: in LJK
34 pages
Formation and Disproportionation of Arene Sulfenic Acids: Sujit Ranjan Acharjee and S K Bhattacharjee
No ratings yet
Formation and Disproportionation of Arene Sulfenic Acids: Sujit Ranjan Acharjee and S K Bhattacharjee
6 pages
Chemical Science: Edge Article
No ratings yet
Chemical Science: Edge Article
12 pages
Metal-Free Alkyne Hydrosulfonylation for Vinyl Sulfones
No ratings yet
Metal-Free Alkyne Hydrosulfonylation for Vinyl Sulfones
6 pages
Sulfonation
No ratings yet
Sulfonation
48 pages
Sulfonation
No ratings yet
Sulfonation
12 pages
Marquis 1966
No ratings yet
Marquis 1966
8 pages
Synthesis of Amino-Functionalized Sulfonimidamides and Their Application in The Enantioselective Henry Reaction
No ratings yet
Synthesis of Amino-Functionalized Sulfonimidamides and Their Application in The Enantioselective Henry Reaction
10 pages
Organosulfurcompounds 0471955124
100% (2)
Organosulfurcompounds 0471955124
245 pages
Synthesis and Uses of Sulfur Trioxide
No ratings yet
Synthesis and Uses of Sulfur Trioxide
5 pages
Overview of Sulfonation Processes
No ratings yet
Overview of Sulfonation Processes
48 pages
XII Chapter 7 P Block Element
No ratings yet
XII Chapter 7 P Block Element
32 pages
P Blockelements 1608
No ratings yet
P Blockelements 1608
51 pages
Benzenesulfonic Acids and Their Derivatives: 1. General Aspects
No ratings yet
Benzenesulfonic Acids and Their Derivatives: 1. General Aspects
39 pages
Chemistry of Oxygen and Sulfur
No ratings yet
Chemistry of Oxygen and Sulfur
57 pages
D H Reid - Organic Compounds of Sulphur, Selenium, and Tellurium Vol 1-Royal Society of Chemistry (1970)
No ratings yet
D H Reid - Organic Compounds of Sulphur, Selenium, and Tellurium Vol 1-Royal Society of Chemistry (1970)
518 pages
Effect of Crosslinking On Conductivity
No ratings yet
Effect of Crosslinking On Conductivity
5 pages
Enamines and Ylides
100% (1)
Enamines and Ylides
18 pages
A Simple Method For The Synthesis of Sulfonic Esters
No ratings yet
A Simple Method For The Synthesis of Sulfonic Esters
17 pages
Oooooooiii
No ratings yet
Oooooooiii
8 pages
Kim Et Al 2012 Novel Solid Phase Parallel Synthesis of N Substituted 2 Aminobenzo D Thiazole Derivatives Via
No ratings yet
Kim Et Al 2012 Novel Solid Phase Parallel Synthesis of N Substituted 2 Aminobenzo D Thiazole Derivatives Via
12 pages
R.J. Cremlyn - Chlorosulfonic Acid - A Versatile Reagent-Royal Society of Chemistry (2002) PDF
100% (4)
R.J. Cremlyn - Chlorosulfonic Acid - A Versatile Reagent-Royal Society of Chemistry (2002) PDF
326 pages
2.sulphur Trioxide-Pyridine Complex - A Versatile Organic Reagent
No ratings yet
2.sulphur Trioxide-Pyridine Complex - A Versatile Organic Reagent
2 pages
ChemElectroChem - 2025 - Michiyuki - Electrochemical Preparation and Transformation of Sulfonium Salts
No ratings yet
ChemElectroChem - 2025 - Michiyuki - Electrochemical Preparation and Transformation of Sulfonium Salts
13 pages
Organosulfur Chemistry Challenges
No ratings yet
Organosulfur Chemistry Challenges
7 pages
Butadiene Sulfone
100% (1)
Butadiene Sulfone
58 pages
Towards More Practical Methods
No ratings yet
Towards More Practical Methods
29 pages
Synthesis of Alkyl-benzene Sulfonate Nanoparticles
No ratings yet
Synthesis of Alkyl-benzene Sulfonate Nanoparticles
11 pages
10.7569 Jnge.2018.692504
No ratings yet
10.7569 Jnge.2018.692504
25 pages
Organic Chemistry: Functional Groups
No ratings yet
Organic Chemistry: Functional Groups
57 pages
Sulfonation and Sulfation
80% (5)
Sulfonation and Sulfation
52 pages
Sulphuric Acid
No ratings yet
Sulphuric Acid
52 pages
Sulphur & Its Compounds
No ratings yet
Sulphur & Its Compounds
94 pages
Sulfur Dioxide: Sources, Effects, and Uses
No ratings yet
Sulfur Dioxide: Sources, Effects, and Uses
17 pages
7 P Block Elements 4
No ratings yet
7 P Block Elements 4
20 pages
Aromatic Sulfonation Process Explained
No ratings yet
Aromatic Sulfonation Process Explained
6 pages
Sulfonamide Derivatives: Synthesis & Activity
No ratings yet
Sulfonamide Derivatives: Synthesis & Activity
4 pages
Sulfonamide Derivatives: Synthesis & Activity
No ratings yet
Sulfonamide Derivatives: Synthesis & Activity
4 pages
Pressure Volume Notes
100% (1)
Pressure Volume Notes
25 pages
Vascular Disorders
No ratings yet
Vascular Disorders
11 pages
Cardiac AP
No ratings yet
Cardiac AP
52 pages
Meditation
100% (1)
Meditation
12 pages
Vedic
No ratings yet
Vedic
17 pages
AP Biology Exam Prep Guide
No ratings yet
AP Biology Exam Prep Guide
11 pages
Acid-Base Solutions Simulation Guide
No ratings yet
Acid-Base Solutions Simulation Guide
3 pages
Calculating Relative Formula Masses
No ratings yet
Calculating Relative Formula Masses
13 pages
Understanding Yellow Pigments in Art
No ratings yet
Understanding Yellow Pigments in Art
44 pages
Recovery Nickel From Pregnant Solution by Precipitation Gases HFM
No ratings yet
Recovery Nickel From Pregnant Solution by Precipitation Gases HFM
19 pages
Ethyl Acetate
No ratings yet
Ethyl Acetate
6 pages
FNC Profile Brief-1
No ratings yet
FNC Profile Brief-1
3 pages
Lab 11qualitative Anion Tests - 2
No ratings yet
Lab 11qualitative Anion Tests - 2
7 pages
CBSE Class 12 Chemistry Answer Key 2024 Set 1 56 4 1
No ratings yet
CBSE Class 12 Chemistry Answer Key 2024 Set 1 56 4 1
6 pages
HPP 2022 ISP Bahan Tambang (Biomassa)
No ratings yet
HPP 2022 ISP Bahan Tambang (Biomassa)
56 pages
Ion Exchange in Hydrometallurgy Overview
No ratings yet
Ion Exchange in Hydrometallurgy Overview
33 pages
Cambridge IGCSE Chemistry (0620) (PDFDrive)
100% (5)
Cambridge IGCSE Chemistry (0620) (PDFDrive)
131 pages
Chemical and Physical Information
No ratings yet
Chemical and Physical Information
9 pages
Organic Chemistry MCQ Practice Set
No ratings yet
Organic Chemistry MCQ Practice Set
2 pages
Chemical Technology Subject Code: CH2001
No ratings yet
Chemical Technology Subject Code: CH2001
11 pages
4.5.4 Test (TST) - Teacher-Scored Unit Test (Test)
No ratings yet
4.5.4 Test (TST) - Teacher-Scored Unit Test (Test)
15 pages
Cement Production Basics
No ratings yet
Cement Production Basics
21 pages
Sample File Cmts Icse Che 2025 2026
No ratings yet
Sample File Cmts Icse Che 2025 2026
7 pages
US9999222
No ratings yet
US9999222
119 pages
Sodium Chlorite: Uses and Properties
No ratings yet
Sodium Chlorite: Uses and Properties
21 pages
NCERT Solutions For Class 8 Science Chapter 4
No ratings yet
NCERT Solutions For Class 8 Science Chapter 4
5 pages
Organic Chemistry Practice Problems
No ratings yet
Organic Chemistry Practice Problems
9 pages
List of Colorants
No ratings yet
List of Colorants
13 pages
12C 24 Carboxylic Acid and Derivatives
No ratings yet
12C 24 Carboxylic Acid and Derivatives
75 pages
Understanding Alcohols: Classification & Reactions
No ratings yet
Understanding Alcohols: Classification & Reactions
34 pages
Cold Drinks Content Analysis Project
No ratings yet
Cold Drinks Content Analysis Project
21 pages
10th Chemistry - Carbon and Its Compounds
No ratings yet
10th Chemistry - Carbon and Its Compounds
2 pages
AS T2 Test 1
No ratings yet
AS T2 Test 1
4 pages
The Copper Cycle For Mzila Ifp
No ratings yet
The Copper Cycle For Mzila Ifp
7 pages
(Weaver & Pollard) - The - Chemistry - of - Clay - Minerals (1973) PDF
100% (1)
(Weaver & Pollard) - The - Chemistry - of - Clay - Minerals (1973) PDF
223 pages
Technical Document Analysis
100% (1)
Technical Document Analysis
3 pages