N-Heterocyclic carbene-catalyzed sulfa-Michael addition of enals

Article abstract of DOI:10.1039/c7cc07269d

An efficient N-heterocyclic carbene (NHC) catalyzed sulfa-Michael addition (SMA) between enals and thiols has been developed. Under the catalysis of 10 mol% stable free carbene IPr and with 20 mol% hexafluoroisopropanol (HFIP) as an additive, enals react with a variety of thiols to afford the SMA adducts in 54-98% yields. In this process, the free carbene preferentially interacts with thiols through hydrogen-bonding and no NHC-catalyzed extended Umpolung transformations were observed.

Full text of DOI:10.1039/c7cc07269d

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Z. Cong, Y. Li, G.
Du, C. Gu, B. Dai and L. He, Chem. Commun., 2017, DOI: 10.1039/C7CC07269D.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Please do not adjust margins
ChemComm
Page 1 of 5
View Article Online
DOI: 10.1039/C7CC07269D
Journal Name
ARTICLE
N-heterocyclic carbene–catalyzed sulfa-Michael addition of enals
Zi-Song Cong, Yang-Guo Li, Guang-Fen Du, Cheng-Zhi Gu, Bin Dai and Lin He*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
realized chiral NHC-catayzed asymmetric carba-, aza- and sulfa-
Michael additions of different Michael acceptors. In those
An efficient N-heterocyclic carbene (NHC) catalyzed sulfa-
Michael addition (SMA) between enals and thiols has been processes, NHC was assumed to act as a strong Brønsted base to
developed. Under the catalysis of 10 mol% stable free
carbene IPr and with 20 mol% hexafluoroisopropanol (HFIP)
as additive, enals react with a variety of thiols to afford the
SMA adducts in 54-98% yields. In this process, the free
carbene preferentially interacts with thiols through
hydrogen-bonding and no NHC-catalyzed extended
Umpolung transformations were observed.
activate different proton-containing nucleophiles through
hydrogen-bonding. Despite great progress made in this research,
there is no NHC-catalyzed Michael addition reaction between enals
and proton-containing nucleophiles has been reported to date.
Typically, NHC undergoes nucleophilic addition with the aldehyde
carbonyl group of an enal to form an extended Breslow
intermediate,11 which is also referred as the homoenolate
equivalent. This homoenolate intermediate can react with a broad
The carbon-sulfur (C-S) bond is recognized as one of the most
ubiquitous component that is widely present in a large number of
7
variety of electrophiles to form different cyclic compounds.
natural
products,
biologically
active
compounds
and
pharmaceuticals.1 The significance of this linkage has attracted
remarkable efforts to develop efficient approaches for the
construction of C-S bond and as a result, transition metal or small
organic molecules catalyzed cross-coupling reaction, sulfenylation,
nucleophilic addition and other reactions have been well
established over the past decades.2 Of these different
methodologies, catalytic sulfa-Michael addition between different
Michael acceptors and sulfide nucleophiles has emerged as a
powerful and straightforward strategy for C-S bond formation
reactions.3 Typical organocatalysts, such as cinchona derived
catalysts,4 (thio)urea catalysts5 and chiral secondary amines6 have
been extensively explored in these conjugate addition reactions. As
an important type of nucleophilic organocatalyst, N-heterocyclic
carbenes (NHCs)7 were also applied in several C-S bond formation
reactions.8 Recently, Coquerel,9a-c Scheidt,9d Zhang9e and our
group9f, 9g demonstrated that the strong basic NHC can efficiently
catalyze carba-, oxo-, aza- and sulfa-Michael additions of α,β-
unsaturated ketones. More interestingly, Huang and co-workers10
proposed a novel non-covalent bonding mode and successfully
Meanwhile, the homoenolate can also undergo redox
esterification12 and redox amidation13 with alcohols and amines,
respectively. Very recently, Huang14 and co-workers successfully
developed a chiral NHC-catalyzed highly enantioselective redox
thioesterification of enals through an interesting proton-shuttling
strategy.
In view of the competitive redox transformations, NHC-
catalyzed Michael addition between enals and proton-containing
nucleophiles is particularly challenging. Recently, we documented
that NHC can catalyze the formal cross coupling reaction between
α-haloenals and thiols to give α-thioenals.15 In that reaction, no
redox transformations were observed. Encouraged by this result,
we decided to explore the direct SMA reaction between enals and
thiols. Herein, we wish to report this interesting result.
Our initial experiment began with the investigation of the
readily available cinnamaldehyde 1a and ethanethiol 2a. To
our great delight, under the catalysis of 10 mol% stable NHC
(1,3-bis(diisopropylphenyl)-imidazole-2-ylidene, IPr),16 the
SMA reaction smoothly proceeded in 1,2-dichloroethane at
ambient temperature to afford the desired adduct 3a in 60%
yield. Surprisingly, no redox thioesterification product was
detected in this process (Table 1, entry 1). Motivated by this
result, several other NHCs were subsequently investigated for
the reaction. As shown in Table 1, 10 mol% NHC generated
from imidazolium salt B1 catalyzed the reaction in very low
efficiency (Table 1, entry 2). Increasing the catalyst loading to
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 5
View Article Online
DOI: 10.1039/C7CC07269D
ARTICLE
Journal Name
20 mol%, moderate yield can be obtained (Table 1, entry 3).
However, NHC generated in situ from ICy·BF4 and ItBu·BF4
showed very low catalytic reactivity toward the reaction (Table
1, entries 4 and 5). Interestingly, NHC generated from the
saturated imidazolium salt SIPr·HCl catalyzed the reaction
efficiently, affording the desired product in 58% yield (Table 1,
entry 6). Owing to the low Brønsted basicity, NHCs derived
from triazolium or thiazolium salts showed no catalytic
reactivity for the addition (Table 1, entries 7-9). The
subsequent evaluation of the reaction media indicated that
the addition can proceed in DCM and chloroform, but with low
efficiency (Table 1, entries 10 and 11). Conducting the reaction
in acetonitrile can afford 3a in 60% yield (Table 1, entry 12).
Using DMSO as the reaction media, 3a can be obtained in 45%
yield. However, the high polarity DMF was proved to be
unsuitable for the reaction (Table 1, entries 13 and 14). Other
general solvents, such as THF, toluene and MTBE, were proved
to be inefficient (Table 1, entries 15-17). Unfortunately,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
A
A
A
A
A
A
A
A
A
A
A
A
A
A
(10 mol %), DCM
12
12
12
12
12
12
12
12
12
12
12
12
31
(10 mol %), CHCl3
26
(10 mol %), CH3CN
60
(10 mol %), DMSO
45
(10 mol %), DMF
< 10
< 10
< 10
< 10
63
(10 mol %), THF
(10mol %), toluene
(10 mol %), MTBE
(20 mol %), DCE
(10 mol %), DCE, HFIP (20 mol %)
(10 mol %), DCE, HFIP (10 mol %)
(10 mol %), DCE, HFIP (50 mol %)
95
23
31
(10 mol %), DCE, HFIP (100 mol %) 12
13
(5 mol %), DCE, HFIP (20 mol %) 24
22
a 1a (0.2 mmol), 2a (0.6 mmol), solvent (2.0 mL). b Isolated yield.
With the optimized reaction conditions in hand (Table 1,
entry 19), we subsequently investigated the scope and
generality of this NHC-catalyzed SMA reaction of enals. As
shown in Scheme 1, primary thiols react with cinnamaldehyde
to produce the SMA adducts in high yield (3a-3c and 3e).
However, when the long-chain primary thiol was used for the
increasing NHC
A to 20 mol% led to no obvious improvement
for the reaction yield (Table 1, entry 18). Recently, in the study
of NHC-catalyzed asymmetric Michael additions of electron
10
deficient olefins, Huang and co-workers
found that the
addition of HFIP can improve both reaction yield and
selectivity. The acidic HFIP was assumed to function as a
proton shuttle to facilitate proton transfer during that process.
Inspired by that finding, we added 20 mol% HFIP to our
reaction and fortunately, the reaction yield can be sharply
improved to 95% (Table 1, entry 19). However, neither
increasing nor decreasing the amount of HFIP can further
improve the reaction yield (Table 1, entries 20-22). On the
other hand, reducing NHC loading to 5 mol% led to dramatic
decreasing of the reaction yield (Table 1, entry 23).
reaction, only moderate yield was obtained
(3d). We
concluded that the SMA reaction is reversible and the product
can undergo 1,2-elimination reaction to regenerate the
starting substrates under basic conditions, and thus, lowered
the reaction yield.17 Pleasingly, when we conducted the
conjugate addition in the weak acidic DCE/pH 6.8 phosphate
aqueous mixture, the reaction yield can be dramatically
improved to 82% (3d). Notably, primary thiols with different
functional groups, such as alkene, ester, and heterocycle, can
react with 1a to afford the desired products in high yield (3f-
3h). More interestingly, when 2-mercaptoethanol was applied
for the reaction, only SMA adduct was isolated in 87% yield
and no oxa-Michael adduct or redox esterification product was
detected (3i). Interestingly, the sterically hindered secondary
thiols can also undergo the conjugate addition smoothly,
Table 1 Screening of reaction conditions a
affording the desired products in high yields (3j and 3
Unfortunately, the bulky tert-butyl mercaptan only produced
trace amount of the desired product 3l). Intriguingly,
k).
(
thiophenol was proved to be a competent reactant for the
conjugate addition, producing the corresponding adduct in
54% yield (3m).
Scheme 1 Evaluation of thiols a
SR
10 mol% NHC A
O
O
+
RSH
20 mol% HFIP
DCE, rt
entry conditions
Time (h) Yield (%)b
1a
2
3
1
2
3
4
5
6
7
8
9
A
(10 mol %), DCE
12
12
12
12
12
12
12
12
12
60
B1, t-BuOK (10 mol %)
,
,
DCE
DCE
14
SCH2Ph
O
S(CH2)nCH3
O
S
B1, t-BuOK (20 mol %)
48
B2, t-BuOK (20 mol %), DCE
B3, t-BuOK (20 mol %), DCE
15
O
12
3a, n = 1, 97%
3f, 88%
3e, 91%
C,
t-BuOK (20 mol %), DCE
58
3b, n = 2, 90%
3c, n = 3, 81%
3d, n = 17, 45% (82%)b
D
, t-BuOK (20 mol %), DCE
< 10
< 10
< 10
E1, t-BuOK (20 mol %), DCE
E2, t-BuOK (20 mol %), DCE
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 3 of 5
View Article Online
DOI: 10.1039/C7CC07269D
Journal Name
ARTICLE
SC2H5
SC2H5
O
SC2H5
O
CH2(CH2)3CH3
O
3ab, 0%
3z, 98%
3aa, 0%
a
Reaction conditions: 1a (0.2 mmol),
2 (0.6 mmol), NHC A (10 mol%), HFIP
(20 mol%), DCE (2.0 mL), rt 12 h. Yields are for the isolated products.
Mercaptoisoborneol reacted with cinnamaldehyde smoothly
to produce 3ac in 85% yield, and after the following reduction
and thiol-exchange reaction,18 giving β-thiol alcohol 5ac in 85%
yield (Scheme 3).
a Reaction conditions: 1a (0.2 mmol),
(20 mol%), DCE (2.0 mL), rt 12 h. Yields are for the isolated products.
Using DCE/pH 6.8 phosphate aqueous mixture as the solvent.
2 (0.6 mmol), NHC A (10 mol%), HFIP
b
Scheme 3 Derivation of the product
OH
1a
A
, NHC (10%mol)
We next explored the generality of enals and the results are
summarized in Scheme 2. Enals with electron-withdrawing
substituents on the phenyl ring afford higher yield than those
with electron-donating groups (3n-3p vs 3q and 3r). In
addition, different positions of the substituents have no
obvious effects on the reaction yield (3s-3v). Notably, both
heterocycle and the bulky anthracene derived enals reacted
well, delivering the corresponding products in 64% and 78%
OH
DCE/pH 6.8 buffer
rt, 12h
S
SH
Ph
O
3ac, 85% yield
NaBH4
EtOH
SH
OH
S
CH3(CH2)17SH
Ph
OH
yield, respectively
(3w and 3x). Interestingly, β-alkyl
BF3 OEt2
5ac
, 85% yield
CH2Cl2,rt
substituted enals underwent the conjugate addition
completely, giving the desired products in excellent yields (3y
and 3z). But unfortunately, neither β, β-disubstituted enal nor
α-substituted enal can undergo the conjugate addition under
standard reaction conditions (3aa and 3ab).
Ph
OH
4ac
Based on the pioneer study of Scheidt,9d Coquerel
and
9a-c
Huang,10 a plausible mechanism was proposed as depicted in
Scheme 4. In this process, NHC acts as a strong Brønsted base
to attack the acidic proton of thiol through hydrogen bonding
Scheme 2 Investigation of enals a
to form a NHC-thioxy species I, which undergoes SMA reaction
with enals to form enolate intermediate II. HFIP interact with
this intermediate through H-bonding and assist proton transfer
to give enol intermediate III, and after tautomerization,
affording the final product.
SC2H5
10 mol% NHC A
+
C2H5SH
R
O
20 mol% HFIP
DCE, rt
R
O
2a
3
1
SC2H5
O
SC2H5
SC2H5
Scheme 4 Proposed mechanism
O
O
Cl
F
Br
3o, 88%
3n, 94%
3p, 80%
SC2H5
SC2H5
SC2H5
Cl
O
O
O
H3C
H3CO
3s, 79%
3q, 70%
3r, 70%
NO2 SC2H5
SC2H5
Cl
SC2H5
O
O
O
OCH3
3u, 90%
3v, 82%
3t, 76%
SC2H5
In summary, we have developed the first NHC-catalyzed
Michael addition between enals and proton-containing
nucleophiles. The free carbene activate thiols through H-
bonding and with HFIP as proton shuttle, leading to the
selective occurrence of SMA reaction. This research focus on
the unique Brønsted base characteristics of NHC and
successfully realized the non-Umpolung reaction of enals via
cooperative catalysis of strong Brønsted base (NHC) and weak
O
C2H5S
SC2H5
O
O
O
3y, 97%
3w, 64%
3x
, 78%
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 5
View Article Online
DOI: 10.1039/C7CC07269D
ARTICLE
Journal Name
Niemeier, A. Henseler, Chem. Rev. 2007, 107, 5606; (b) A. T.
Biju, N. Kuhl, F. Glorius, Acc.Chem. Res. 2011, 44, 1182; (c) J.
Mahatthananchai, J. W. Bode, Chem. Sci. 2012, 3, 192–197.
Brønsted acid (HFIP), which must lead to new research interest
of this versatile organocatalyst. Studies on NHCs-catalyzed
Michael additions between enals and other nucleophiles are
ongoing in our laboratory.
(d) A. Grossmann, D. Enders, Angew. Chem. Int. Ed. 2012, 51
,
314; (e) J. Izquierdo, G. E. Hutson, D. T. Cohen, K. A. Scheidt,
Angew. Chem. Int. Ed. 2012, 51, 11686; (f) N. Hopkinson, C.
Richter, M. Schedler, F. Glorius, Nature. 2014, 510, 485-496;
(g) R. S. Menon, A. T. Biju, V. Nair, Chem. Soc. Rev. 2015, 44
5040; (h) D. M. Flanigan, F. Romanov-Michailidis, N. A. White,
T. Rovis, Chem. Rev. 2015, 115, 9307.
(a) S. S. Sohn, J. W. Bode, Angew. Chem. Int. Ed., 2006, 45,
6021. (b) T. Uno, T. Inokuma, Y. Takemoto, Chem. Commun.
2012, 48, 1901. (c) T. Y. Jian, L. He, C. Tang; S. Ye, Angew.
Chem., Int. Ed. 2011, 50, 9104.; (d) S. Singh, L. D. S. Yadav,
Tetrahedron Lett. 2012, 53, 5136; (e) Z.-Q. Liang, D.-Q. Sun,
S. Ye. Adv. Synth. Catal. 2017, 359, 44; (f) T. Wang, Z.-H. Gao
S. Ye, Adv. Synth. Catal. 2017, 359, 3479; (g) X.-N. Wang, L.-T.
,
Conflicts of interest
There are no conflicts to declare.
8
9
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (No.21662029), the Young Scientists
Foundation of Shihezi University (Nos. RCZX201546,
2015ZRKXJQ05) and the Excellent Young Teachers Plan of
Bingtuan (CZ027203).
Shen, S. Ye, Chem. Commun. 2011, 47, 8388.
(a) T. Boddaert, Y. Coquerel, J. Rodriguez, Adv. Synth. Catal.
2009, 351, 1744–1748. (b) T. Boddaert, Y. Coquerel, J.
Rodriguez, Chem. Eur. J. 2011, 17, 2266−2271 (c) M. Hans, L.
Delaude, J. Rodriguez, Y. Coquerel, J. Org. Chem, 2014, 79
,
2758-2764. (d) E. M. Phillips, M. Riedrich, K. A. Scheidt, J.
Am. Chem. Soc. 2010, 132, 13179. (e) Q. Kang, Y. Zhang, Org.
Biomol. Chem. 2011, 9, 6715. (f) H. Guo, F. Xing, G. F. Du, K.
W. Huang, B. Dai, L. He, J. Org. Chem. 2015, 80, 12606; (g) Y.
Z. Li, Y. Wang, G. F. Du, H. Y. Zhang, H. L. Yang, L. He, Asian J.
Notes and references
1
2
J. R. Fraústo daSilva, R. J. P. Williams, The Biological
Chemistry of the Elements. Oxford University Press: New
York, 2001.
Org. Chem. 2015,
10 (a) J. Chen, S. Meng, L. Wang, H. Tang, Y. Huang, Chem. Sci.
2015, , 4184. (b) P. F. Yuan, S. X. Meng, J. A. Chen, Y. Huang,
Synlett, 2016, 27, 1068; (c) J. Chen, Y. Huang, Nat. Commun.
2014, , 3437; (d) L. Wang, J. Chen, Y. Huang, Angew. Chem.
4, 327.
For reviews, see: (a) T. Kondo, T. A. Mitsudo, Chem. Rev.
2000, 100, 3205. (b) M. Sibiand, S. Manyem, Tetrahedron.
2000, 56, 8033. (c) P. Chauhan, S. Mahajan, D. Enders, Chem.
Rev. 2014, 114, 8807; for selected examples see: (d) J. W.
Sun, G. C. Fu, J. Am. Chem. Soc. 2010, 132, 4568. (e) O.
Takanori, K. Naoya, S. Masakatsu, Angew. Chem. Int. Ed.
2012, 51, 8551. (f) M. Roggen, E. M. Carreira, Angew. Chem.
Int. Ed. 2012, 51, 8652. (g) Y. Xia, L. Lin, F. Chang, X. Fu, X.
Liu, X. Feng, Angew. Chem. Int. Ed. 2015, 54, 13748-13752.
6
5
Int. Ed. 2015, 54, 15414.
11 (a) R. Breslow, J. Am. Chem. Soc. 1958, 80, 3719. (b) C.
Burstein, F. Glorius, Angew. Chem. Int. Ed. 2004, 43, 6205; (c)
S. S. Sohn, E. L. Rosen, J. W. Bode, J. Am. Chem. Soc. 2004,
126, 14370.
12 For selected examples,see: (a) N. T. Reynolds, J. R. D. Alaniz,
T. Rovis, J. Am. Chem. Soc. 2004, 126, 9518. (b) K. Y. K. Chow,
J. W. Bode, J. Am. Chem. Soc. 2004, 126, 8126. (c) A. Chan, K.
(h) S. E. Denmark, H. M. Chi, J. Am. Chem. Soc. 2014, 136
3655; (i) S. E. Denmark, E. Hartmann, D. J. P. Kornfilt, H.
Wang, Nat. Chem. 2014, , 1056.
For an excellent review, see: D. Enders, K. Lüttgen, A. A.
Narine, Synthesis. 2007, , 959 and reference 2c.
For selected examples, see: (a) H. Hiemstra, H. Wynberg, J.
Am. Chem. Soc. 1981, 103, 417. (b) P. McDaid, Y. Chen, L.
Deng, Angew. Chem., Int. Ed. 2002, 41, 338. (c) J. B. Ling, Y.
Su, H. L. Zhu, G. Y. Wang, P. F. Xu, Org. Lett. 2012, 14, 1090.
(d) X. Tian, Y. Liu, P. Melchiorre, Angew. Chem., Int. Ed. 2012,
51, 6439. (e) Z. Rodríguez-Docampo, C. Quigley, S. Tallon, S.
J. Connon, J. Org. Chem. 2012, 77, 2407. (f) Y. M. Cao, F. T.
Zhang, F. F. Shen, R. Wang, Chem. Eur. J. 2013, 19, 9476. (g)
X. Wang, T. Yang, X. Cheng, Q. Shen, Angew. Chem., Int. Ed.
2013, 52, 12860.
,
6
3
4
A. Scheidt, Org. Lett. 2005, 7, 905. (d) J. Mahatthananchai, P.
Zheng, J. W. Bode, Angew. Chem., Int. Ed. 2011, 50, 1673. (e)
J. Mo, X. Chen, Y. Chi, J. Am. Chem. Soc. 2012, 134, 8810. (f)
7
J. Izquierdo, K. A. Scheidt, J. Am. Chem. Soc. 2013, 135
,
10634. (g) M. H. Wang, D. T. Cohen, C. B. Schwamb, R. K.
Mishra, K. A. Scheidt, J. Am. Chem. Soc. 2015, 137, 5891; (h)
M. H. Wang, D. Barsoum, C. B. Schwamb, D. T. Cohen, B. C.
Goess, M. Riedrich, A. Chan, B. E. Maki, R. K. Mishra, K. A.
Scheidt, J. Org. Chem. 2017, 82, 4689.
13 (a) H. U. Vora, T. Rovis, J. Am. Chem. Soc. 2007, 129, 13796.
(b) J. W. Bode, S. S. Sohn, J. Am. Chem. Soc. 2007, 129
,
13798. (c) Y. Kawanaka, E. M. Phillips, K. A. Scheidt, J. Am.
Chem. Soc. 2009, 131, 18028. (d) G. Q. Li, Y. Li, L. X. Dai, S. L.
5
6
7
For selected examples, see: (a) L. Zu, J. Wang, H. Li, H. Xie, W.
Jiang, W. Wang, J. Am. Chem. Soc. 2007, 129, 1036; (b) Y. Liu,
B. Sun, B. Wang, M. Wakem, L. Deng, J. Am. Chem. Soc. 2009,
131, 418. (c) M. Moccia, F. Fini, M. Scagnetti, M. F. A.
Adamo, Angew. Chem., Int. Ed. 2011, 50, 6893. (d) N. K.
Rana, V. K. Singh, Org. Lett. 2011, 13, 6520. (e) Z. Jin, J. Xu, S.
You, Org. Lett. 2007,
David, D. Holte, K. A. Scheidt, Nat. Chem. 2010,
9
, 3519. (e) D. E. A. Raup, B. Cardinal-
2, 5345.
14 J. Chen, P. Yuan, L. Wang, Y. Huang, J. Am. Chem. Soc. 2017,
139, 7045.
15 L. He, H. Guo, Y. Z. Li, G. F. Du, B. Dai, Chem. Commun. 2014,
50, 3719.
16 A. J. Arduengo III, R. Krafczyk, R. Schmutzler, Tetrahedron.,
1999, 55, 14523.
17 See supporting information for details.
18 M. Ozeki, K. Nishide, F. Teraoka and M. Node, Tetrahedron:
Asymmetry 2014, 15, 895.
Yang, B. A. Song, Y. R. Chi, Angew. Chem., Int. Ed. 2013, 47
12354.
,
For selected examples, see: (a) M. Marigo, T. Schulte, J.
Franzén, K. A. Jørgensen, J. Am. Chem. Soc. 2005, 127
15710. (b) W. Wang, H. Li, J. Wang, L. Zu, J. Am. Chem. Soc.
2006, 128 10354. (c) S. Brandau, E. Maerten, K. A.
Jørgensen, J. Am. Chem. Soc. 2006, 128, 14986. (d) H. Li, L.
Zu, H. Xie, J. Wang, W. Jiang, W. Wang, Org. Lett. 2007,
,
,
9,
1833. (e) H. Jiang, D. C. Cruz, Y. Li, V. H. Lauridsen, K. A.
Jørgensen, J. Am. Chem. Soc. 2013, 135, 5200.
For selected reviews of NHC catalysis, see: (a) D. Enders, O.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 5
ChemComm
View Article Online
DOI: 10.1039/C7CC07269D
N-heterocyclic carbene–catalyzed sulfa-Michael addition of enals
SR2
10 mol% NHC
R1
R2SH
+
R1
O
O
20 mol% HFIP
solvent, rt
R1, R2 = aryl, alkyl
26 examples
yield up to 98%
No redox products
iPr
iPr
iPr i
N
N
Pr
NHC