Lewis Base/Br?nsted Acid Co-catalyzed Enantioselective Sulfenylation/Semipinacol Rearrangement of Di- and Trisubstituted Allylic Alcohols

Article abstract of DOI:10.1002/anie.201907115

An enantioselective sulfenylation/semipinacol rearrangement of 1,1-disubstituted and trisubstituted allylic alcohols was accomplished with a chiral Lewis base and a chiral Br?nsted acid as cocatalysts, generating various β-arylthio ketones bearing an all-carbon quaternary center in moderate to excellent yields and excellent enantioselectivities. These chiral arylthio ketone products are common intermediates with many applications, for example, in the design of new chiral catalysts/ligands and the total synthesis of natural products. Computational studies (DFT calculations) were carried out to explain the enantioselectivity and the role of the chiral Br?nsted acid. Additionally, the synthetic utility of this method was exemplified by an enantioselective total synthesis of (?)-herbertene and a one-pot synthesis of a chiral sulfoxide and sulfone.

Full text of DOI:10.1002/anie.201907115

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Lewis Base/Brønsted Acid Co-catalyzed Enantioselective
Sulfenylation/Semipinacol Rearrangement of Di- and Tri-
substituted Allylic Alcohols
Authors: Yu-Yang Xie, Zhi-Min Chen, Hui-Yun Luo, Hui Shao,
Yongqiang Tu, Xiaoguang Bao, Ren-Fei Cao, Shu-Yu Zhang,
and Jin-Miao Tian
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201907115
Angew. Chem. 10.1002/ange.201907115
Link to VoR: http://dx.doi.org/10.1002/anie.201907115
http://dx.doi.org/10.1002/ange.201907115

10.1002/anie.201907115
Angewandte Chemie International Edition
COMMUNICATION
Lewis Base/Brønsted Acid Co-catalyzed Enantioselective
Sulfenylation/Semipinacol Rearrangement of Di- and Tri-
substituted Allylic Alcohols
Yu-Yang Xie,[a] Zhi-Min Chen,*[a] Hui-Yun Luo,[a] Hui Shao,[a] Yong-Qiang Tu,*[a,b] Xiaoguang Bao,*[c]
Ren-Fei Cao,[a] Shu-Yu Zhang,[a] and Jin-Miao Tian[a]
Abstract:
An
enantioselective
sulfenylation/semipinacol
rearrangement of 1,1-disubstituted and tri-substituted allylic alcohols
was accomplished under the co-catalysis of chiral Lewis base/chiral
Brønsted acid, to generate various β-phenylthio ketones bearing an
all-carbon quaternary center in moderate to excellent yields and
excellent enantioselectivities. These chiral phenylthio ketone
products are common intermediates with many applications,
including the design of new chiral catalysts/ligands and the total
synthesis of natural products. Computational studies (DFT
calculations) were carried out to explain the origin of
enantioselectivity and the role of chiral Brønsted acid. Additionally,
the synthetic utility of this methodology was exemplified by an
enantioselective total synthesis of (-)-herbertene and a one-pot
synthesis of a chiral sulfoxide and sulfone.
Chiral organosulfur compounds are not only widely present in
bioactive natural products and medicines,[1] but also play an
important role in asymmetric catalysis as chiral catalysts/ligands,
[2]
as well as in material science (Figure 1).
They are also
versatile synthetic intermediates that are useful for numerous
transformations in synthetic chemistry.[3] Accordingly, the
development of synthetic methods to prepare such organosulfur
compounds has attracted much attention and some
enantioselective methodologies have been developed,[4] mainly
including
sulfur-nucleophile
additions,[5]
2,3-sigmatropic
Scheme 1. Design of a catalytic enantioselective sulfenylation/semipinacol
rearrangement of di- and tri-substituted allyl alcohols.
rearrangements of sulfonium ylides,[6] and sulfenylation
reactions[7]. Among them, catalytic enantioselective sulfenylation
of alkenes provides a direct and indispensable strategy for the
preparation of these compounds. In contrast to the
comprehensive and intensive development of enantioselective
halogenations of alkenes during last decade,[8] there are few
examples of catalytic asymmetric sulfenylations of alkenes and
further development is necessary. Recently, some pioneering
studies were reported by Denmark[9], Shi[10] and others[11]
.
Among them, the Denmark group reported the seminal studies
on enantioselective sulfenylation of olefins, using a chiral Lewis
base and an achiral Brønsted acid as co-catalysts (Scheme 1a).
The Shi group made some noteworthy efforts on the catalytic
asymmetric sulfenylation of alkenes using a chiral Brønsted acid
as a catalyst. Despite these advances, catalytic enantioselective
variants for constructing chiral sulfur-containing compounds are
still limited in terms of reaction types and substrate scope. For
example, because of the difficulty in discriminating between
enantiotopic faces of 1,1-disubstituted and tri-substituted
alkenes, sulfenylations of these two substrates to form
Figure 1. Representative examples of bioactive natural products, medicines
and chiral catalysts containing sulfur group.
[a]
Y.-Y. Xie, Prof. Dr. Z.-M. Chen, H.-Y. Luo, H. Shao, Prof. Dr. Y.-Q.
Tu, R.-F. Cao, S.-Y. Zhang, and J.-M. Tian
School of Chemistry and Chemical Engineering and Shanghai Key
Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao
Tong University
quaternary
pharmaceuticals
stereocenters,
which
are
products,
prevalent
give
in
low
and natural
enantioselectivity and remain synthetically challenging (Scheme
1b).[9a,h] The lack of development in this area inspired us to try
and address these challenges with our sulfenylation/semipinacol
rearrangement reaction.
800 Dongchuan Road, Shanghai 200240 (P. R. China)
E-mail: tuyq@sjtu.edu.cn; chenzhimin221@sjtu.edu.cn
Prof. Dr. Y.-Q. Tu
State Key Laboratory of Applied Organic Chemistry and College of
Chemistry and Chemical Engineering, Lanzhou University
Lanzhou 730000 (P. R. China)
[b]
[c]
The semipinacol rearrangement of allylic alcohols has
become a powerful strategy for the formation of a variety of β-
functionalized carbonyl compounds with an α-quaternary carbon
center.[12] Although numerous catalytic enantioselective variants
have been documented,[13] to the best of our knowledge, no
example of a catalytic asymmetric sulfenylation/semipinacol
rearrangement reaction of allylic alcohols has been reported.[14]
E-mail: tuyq@lzu.edu.cn
Prof. Dr. X. Bao
College of Chemistry Chemical Engineering and Materials Science
Soochow University, 199 Ren-Ai Road Suzhou Industrial Park,
Suzhou Jiangsu 215123 (P. R. China)
E-mail: xgbao@suda.edu.cn
This article is protected by copyright. All rights reserved.

10.1002/anie.201907115
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Optimization of the enantioselective reaction.[a]
Table 2. Scope of 1,1-disubstituted allylic alcohols.[a]
[a] Reaction conditions: compound 3a (0.1 mmol), 2 (0.12 mmol), (R)-Cat. (10
mol%) and acid (10 mol%) in CH2Cl2 (1.0 mL) stirred 24 h under argon. [b]
Isolated yield. [c] Determined by chiral HPLC. [d] (R)-Cat. (5 mol%) and (S)-
CPA (5 mol%) were used as co-catalyst.
Herein, we are pleased to present the development of a
successful catalytic asymmetric sulfenylation/semipinacol
rearrangement reaction of 1,1-disubstituted and tri-substituted
allylic alcohols. This process enables a straightforward and
efficient method to synthesize a wide range of β-phenylthio
ketones containing an all-carbon quaternary center (Scheme 1c).
To realize this reaction, a catalytic system containing a chiral
Lewis base and chiral Brønsted acid is required to activate the
sulfenylating agent for the enantioenriched formation of
thiiranium ion intermediates.
In our initial study, 1,1-disubstituted allylic alcohol 3a was
selected as a model substrate with N-phenylthiosaccharin 2a as
sulfenylating agent, and chiral Lewis base selenide 1a as the
catalyst with CH2Cl2 as the solvent. Disappointingly, the reaction
yielded the product in 15% yield and 9% ee at room temperature
after 24 h (Table 1, entry 1). On the basis of previous work,[9]
and the proposed catalytic cycle, a catalytic amount of MeSO3H
was used as a co-catalyst to promote the reaction; this resulted
in the desired rearrangement product being afforded in 53%
yield with a moderate 69% ee at -5 ºC (entry 2). Using EtSO3H
instead of MeSO3H slightly affected the enantioselectivity (entry
3). Inspired by the above results and combined our prior
successful development of chiral Brønsted acid system for
semipinacol rearrangement,[15] we found chiral BINOL-derived
phosphoric acid (CPA) was necessary for this reaction.
Remarkably, the addition of 10 mol% (S)-CPA notably improved
the enantioselectivity to 85% ee, whereas 10 mol% of (R)-CPA
only gave 74% ee (entries 4-5). This outcome suggested the
absolute configuration of the acid is an important variable. No
further improvement was observed when different Lewis bases
were investigated (entries 6-7). It should be noted that the Lewis
Ar = 2-Me-C6H4. [a] Unless otherwise specified, each example represents the
isolated yield on a 0.1 mmol scale under the standard reaction conditions and
ee values were determined by chiral HPLC. [b] (S)-1a and (R)-CPA were used
as co-catalyst.
base played a key role in improving the reaction activity and
enantioselectivity; without a Lewis base, barely any reactivity
was observed (entry 8). Further optimization of the reaction
conditions was performed by varying the sulfenylating agent. To
our delight, the use of 2b as the sulfenylating agent greatly
increased the enantioselectivity to 94% ee with 73% yield (entry
9). To our delight, increasing the reaction temperature to 0 ºC
afforded the desired product 4a in 80% yield and 94% ee (entry
10). It was found that either the yield or the enantioselectivity
decreased when the amount of Lewis base and acid was
reduced (entry 11). Therefore, the conditions of entry 10 gave
the best results and were selected as the optimal conditions.
With these optimized conditions established, the scope of
this reaction was explored with a variety of 1,1-disubstituted
allylic alcohols and some different sulfenylating agents (Table 2).
In general, the desired β-phenylthio ketones were obtained with
moderate to excellent yields and excellent enantiomeric excess.
In contrast to the model substrate (3a), substituents at the ortho-
position of phenyl group markedly decreased the yield (4b),[16]
while a methyl group at the meta- or para-position increased the
yield and had little effect on the enantioselectivity (4c, 4d). It was
found that electron-withdrawing groups at the para-position led
to a subtle reduction in yield (4f, 4g, 4h). Meanwhile, the use of
an electron-donating allylic alcohol increased the yield while
This article is protected by copyright. All rights reserved.

10.1002/anie.201907115
Angewandte Chemie International Edition
COMMUNICATION
Table 3. Scope of the trisubstituted allylic alcohols.[a]
[a] Unless otherwise specified, each example represents the isolated yield on
0.1 mmol scale under the standard reaction conditions and ee values were
determined by chiral HPLC. DMP = Dess-Martin periodinane, m-CPBA = 3-
Chloroperbenzoic acid.
Scheme 2. Synthetic applications of the products.[a]
Ar = 2-Me-C6H4. [a] Unless otherwise specified, each example represents the
isolated yield on 0.1 mmol scale under the standard reaction conditions and ee
values were determined by chiral HPLC. [b] (S)-1a and (R)-CPA were used as
co-catalyst. [c] Reaction conditions: 5a (6 mmol), 2a (7.2 mmol), (R)-1a (5
mol%) and (S)-CPA (5 mol%) in CH2Cl2 (30 mL) stirred 18 h at -10 oC under
argon.
As mentioned above, sulfenylation of tri-substituted alkenes
is still challenging. Given the importance of chiral spirocyclic
skeletons,[18] we sought to further expand our method to
trisubstituted indene-type allylic alcohols. We first examined the
feasibility of the above hypothesis with 1-(1H-inden-3-
yl)cyclobutan-1-ol 5a as the model substrate. To our delight, the
initial attempt with 10 mol % Lewis basic selenide 1a and (S)-
CPA in the presence of 2b in CH2Cl2 at -10 oC successfully gave
the corresponding product 6a in 93% yield and 95% ee (Table 3).
This reaction was also tested with N-phenylthiosaccharin 2a,
which led to the enantioselectivity slightly increasing to 96% ee
maintaining the high enantioselectivity (4i). Substrates with
multiple substituents on the phenyl moiety were tested in this
reaction and they showed excellent enantioselectivity (4j-m).
Again, the electron-withdrawing substituents produced the lower
yields. In particular, using 3-chloro-4-fluorophenyl allylic alcohol
afforded the corresponding product 4j in 52% yield and 96% ee.
Furthermore, 2-naphthyl substituted substrate 3n was also
tolerated by this reaction and the desired product was obtained
in good yield and excellent ee (4n). It was found that the product
(4o) was also obtained in 86% ee albeit with 27% yield when
unbiased alkene compound 3o was used as a substrate under
the standard reaction conditions. The opposite enantiomer of the
product (ent-4a) can be obtained in 82% yield and 93% ee when
(S)-1a and (R)-CPA were used as co-catalysts. Finally,
sulfenylating agents with different substituents on the phenyl
group were also examined; these compounds were successfully
incorporated and afforded the corresponding products in
moderate yields and good enantioselectivities (4p-r). Notably,
the absolute configuration of the rearrangement product was
assigned by X-ray crystallography analysis of the sulfone
derivative of 4a.[17]
1
with negligible impact on the yield (91%, 6b). And the H-NMR
results for crude product
6b
indicated that
the
diastereoselectivity of the reaction was excellent and another
product was not observed.[19] Accordingly, 2a was selected as
the sulfenylating agent and a broad range of substrates were
evaluated under the reaction conditions. Generally, the desired
β-phenylthio spirocyclic ketones were obtained with good yields
and excellent enantioselectivities.
Figure 2. Proposed catalytically active species 12a.
This article is protected by copyright. All rights reserved.

10.1002/anie.201907115
Angewandte Chemie International Edition
COMMUNICATION
Figure 3. Energy profiles for the enantioselective sulfenylation/semipinacol rearrangement of 1,1-disubstituted allylic alcohol (3a) after the formation of 12a. Bond
distances are given in Å.
First, the derivative of chromene 5c was well tolerated delivering
product 6c in 70% yield and 96% ee. Subsequently, various
substrates containing different substituents at the cyclobutanol
moiety were subjected to the standard reactionconditions to
afford products in good yields with satisfying d.r values and
excellent enantiomeric excess (6d-f).[20] The cyclopropanol
substrate only gave 88% ee at -60 oC (6h). The substituent
effects on the phenyl ring were also carefully investigated (6i-m),
which indicated that electron-rich groups led to a higher
enantioselectivity. It is noteworthy that the substrate containing
two vicinal methoxy groups furnished the product with the
highest, 99% ee (6m). It is frustrating that hardly any reaction
was observed using 3-(1-hydroxycyclobutyl)-1H-inden-7-yl
trifluoromethanesulfonate as an electro-deficient substrate. As
expected, the 2-naphthyl substituted substrate afforded the
product 6n in 90% yield and 97% ee. Finally, unactivated 1-
(cyclopent-1-en-1-yl)cyclobutan-1-ol was also tested in this
catalytic system, affording the desired product 6o in 40% yield
and 78% ee. It was found that opposite enantiomer (ent-6b) can
be obtained in excellent yield and enantioselectivity when (S)-1a
and (R)-CPA were employed. To demonstrate the practicality of
this catalytic system, a gram-scale reaction of substrate 5a (6
mmol, 1.116 g) was conducted using the optimized reaction
conditions and the desired product 6b was readily obtained with
maintained yield and ee. It is worth mentioning that the loading
of catalyst can be decreased to 5 mol %.
herbertane-type sesquiterpenoids, which were isolated from the
liverwort Herberta adunca species and showed efficient anti-lipid
peroxidation and anti-fungal activities.[22] However, total
synthesis of chiral herbertene is difficult. Most of the
enantioselective syntheses either incorporate the chiral
stereocenter in the starting substrate or a catalytic asymmetric
fashion with low optical purity.[23] To highlight the synthetic utility
of this asymmetric transformation, an enantioselective total
synthesis of (-)-herbertene was accomplished. First, C-S bond
cleavage followed by oxidation smoothly gave product 7 in 82%
total yield. Subsequently, compound 7 was subjected to a Wittig
reaction to afford methylene compound 8 in near-quantitative
yield, 8 could then be converted to cyclopropane 9 by a
Simmons-Smith cyclopropanation. Finally, hydrogenation of 9
delivered (-)-herbertene in 80% yield. In addition, a one-pot
synthesis of a chiral sulfoxide was also achieved based on this
enantioselective reaction, affording the product 10 in excellent
yield with acceptable diastereoselectivity and excellent
enantioselectivity. The absolute configuration of the main
product 10a was assigned by X-ray crystallography.[17]
Meanwhile, the enantioenriched sulfone 11 was only obtained
when an excess amount (2.5 equiv.) of m-CPBA was used.
Based on previous work,[9] species 12a would be the most
catalytically active intermediate in this transformation when a
chiral Brønsted acid was added (Figure 2). To gain further
insight into this process, some additional low-temperature 31P-
NMR experiments were conducted.[24] The experimental results
indicated that species 12a is formed after the addition of (S)-
As
shown
in
Scheme
2a,
chiral
(1-
methylcyclopentyl)benzene motifs containing an all-carbon
quaternary center exist in many natural products.[21] For example, CPA to this catalytic system.
This article is protected by copyright. All rights reserved.

10.1002/anie.201907115
Angewandte Chemie International Edition
COMMUNICATION
Next,computational studies[25] were carried out to gain
Drug Innovation Major Project of the Ministry of Science and
Technology of China (2018ZX09711001-005-002)
mechanistic
insights
into
the
enantioselective
sulfenylation/semipinacol rearrangement of 1,1-disubstituted
allylic alcohol 3a. After the formation of 12a, the sulfenyl group
transfer via electrophilic attack to the terminal alkenyl carbon of
3a can occur in a SN2 manner. Two approaching modes of the
sulfenyl group from both Si and Re sides of 3a were considered
and the corresponding transition states were designated as
TS1a and TS1b, respectively. The optimized TS1a is
characterized by a lengthening of the Se...S distance to 2.58 Å
while shortening the S…C distance to 2.35 Å. In addition, a π...π
interaction between the phenyl rings of 3a and the sulfenyl group
was found in TS1a. The presence of (S)-CPA- anion favors the
formation of O—H…O and C—H…O H-bonds with 3a.
Analogous geometrical features are also found in TS1b except
for the orientation of (S)-CPA- anion. When the sulfenyl group of
12a approaches the alkenyl carbon from the Si side of 3a, the
two bulky groups of 1a and (S)-CPA- anion stay away from each
other. However, when the sulfenyl group attacks from the Re
side of 3a, there is steric hindrance between the bulky groups of
(S)-CPA- and 1a. Therefore, the predicted free energy barrier via
TS1a is 3.7 kcal/mol lower than that of TS1b, meaning that the
attack from the Si side of 3a is favored (Figure 3). Subsequently,
a thiiranium intermediate could be yielded and the catalyst 1a is
regenerated. Afterwards, the ring opening of the S-containing
three membered ring and the semipinacol rearrangement via the
1,2-carbon migration, accompanying with the proton transfer
from hydroxyl group of 3a to (S)-CPA- anion, could take place to
produce the desired product (4). The computational results
suggest that the rate-limiting step from 12a to the final product is
the electrophilic attack of the sulfenyl group to 3a. The
enantioselectivity of product is determined by the favorable
attack of sulfenyl group of 12a from the Si side of 3a to minimize
the steric hindrance between the bulky groups of 1a and (S)-
CPA- anion.[26]
In conclusion, we have successfully developed the first
example of an enantioselective sulfenylation/semipinacol
rearrangement of 1,1-disubstituted and tri-substituted allylic
alcohols, using a chiral Lewis base and a chiral Brønsted acid as
co-catalysts. This method provides an efficient, direct and facile
synthetic access to enantiomerically enriched β-phenylthio
ketones. Moreover, a chiral all-carbon quaternary stereocenter
was efficiently constructed; in particular, two adjacent
stereocenters were also smoothly formed using trisubstituted
allylic alcohols. Additionally, a convenient synthesis of the
natural product (-)-herbertene and a one-pot synthesis of chiral
sulfoxide and sulfone demonstrated the synthetic utility of this
methodology. The success of a gram-scale transformation
demonstrates that the enantioselective sulfenylation reaction is
transferable to a preparative scale. These chiral sulfur-ketone
products or their analogs may be useful as chiral auxiliaries or
intermediates in asymmetric catalysis and organic synthesis.
Keywords: Semipinacol Rearrangement • Quaternary Center•
Sulfur Compound • Spirocyclic Skeleton • Co-catalysis
[1]
[2]
(a) A. Nudelman, The Chemistry of Optically Active Sulfur Compounds,
Gordon and Breach, New York, 1984; (b) Sulphur‐Containing Drugs
and Related Organic Compounds, (Ed.: L. A. Damani), Wiley, New
York, 1989; (c) M. R. Prinsep, Stud. Nat. Prod. Chem. 2003, 28, 617-
715; (d) M. Feng, B. Tang, S. H. Liang, X. Jiang, Curr. Top. Med. Chem.
2016, 16, 1200-1216.
(a) H. Butenschön, Chem. Rev. 2000, 100, 1527-1564; (b) V. K.
Aggarwal, C. L. Winn, Acc. Chem. Res. 2004, 37, 611-620; (c) M.
Mellah, A. Voituriez, E. Schulz, Chem. Rev. 2007, 107, 5133-5209; (d)
T. Hashimoto, Y. Kawamata, K. Maruoka, Nat. Chem. 2014, 6, 702-
705; (e) S. Otocka, M. Kwiatkowska, L. Madalińska, P. Kiełbasiński,
Chem. Rev. 2017, 117, 4147-4181; (f) M.-M. Li, Y. Wei, J. Liu, H.-W.
Chen, L.-Q. Lu, W.-J. Xiao, J. Am. Chem. Soc. 2017, 139, 14707-
14713.
[3]
[4]
(a) B. M. Trost, Chem. Rev. 1978, 78, 363-382; (b) B. M. Trost, Acc.
Chem. Res. 1978, 11, 453-461; (c) R. D. Norcross, I. Paterson, Chem.
Rev. 1995, 95, 2041-2114; (d) D. J. Faulkner, Nat. Prod. Rep. 1995, 12,
223-269; (e) A. El-Awa, M. N. Noshi, X. M. du Jourdin, P. L. Fuchs,
Chem. Rev. 2009, 109, 2315-2349.
For selected reviews of constructing chiral organosulfur compounds,
see: (a) W. Adam, R. M. Bargon, Chem. Rev. 2004, 104, 251-262; (b)
W. Liu, X. Zhao, Synthesis 2013, 45, 2051-2069; (c) P. Chauhan, S.
Mahajan, D. Enders, Chem. Rev. 2014, 114, 8807-8864; (d) J.-S. Yu,
H.-M. Huang, P.-G. Ding, X.-S. Hu, F. Zhou, J. Zhou, ACS Catal. 2016,
6, 5319-5344; (e) K. L. Dunbar, D. H. Scharf, A. Litomska, C. Hertweck,
Chem. Rev. 2017, 117, 5521-5577.
[5]
[6]
[7]
For selected examples on sulfur-nucleophile additions, see: (a) H.-H.
Lu, F.-G. Zhang, X.-G. Meng, S.-W. Duan, W.-J. Xiao, Org. Lett. 2009,
11, 3946-3949; (b) S. Shaw, J. D. White, Org. Lett. 2015, 17, 4564-
4567; (c) Z. Wang, F. K. Sheong, H. H. Y. Sung, I. D. Williams, Z. Lin, J.
Sun, J. Am. Chem. Soc. 2015, 137, 5895-5898; (d) D. Qian, L. Wu, Z.
Lin, J. Sun, Nat. Commun. 2017, 8, 567; (e) D. Qian, M. Chen, A. C.
Bissember, J. Sun, Angew. Chem., Int. Ed. 2018, 57, 3763-3766;
Angew. Chem. 2018, 130, 3825-3828.
For selected examples on 2,3-sigmatropic rearrangements of sulfonium
ylides, see: (a) P. C. Cagle, A. M. Arif, J. A. Gladysz, J. Am. Chem. Soc.
1994, 116, 3655-3656; (b) K. J. Hock, R. M. Koenigs, Angew. Chem.,
Int. Ed. 2017, 56, 13566-13568; Angew. Chem. 2017, 129, 13752-
13754; (c) Z. Zhang, Z. Sheng, W. Yu, G. Wu, R. Zhang, W.-D. Chu, Y.
Zhang, J. Wang, Nat. Chem. 2017, 9, 970; (d) X. Lin, Y. Tang, W. Yang,
F. Tan, L. Lin, X. Liu, X. Feng, J. Am. Chem. Soc. 2018, 140, 3299-
3305.
For selected examples on sulfenylation reactions, see: (a) X. Li, C. Liu,
X.-S. Xue, J.-P. Cheng, Org. Lett. 2012, 14, 4374-4377; (b) S.
Shirakawa, T. Tokuda, A. Kasai, K. Maruoka, Org. Lett. 2013, 15, 3350-
3353; (c) Z. Jin, J. Xu, S. Yang, B.-A. Song, Y. R. Chi, Angew. Chem.,
Int. Ed. 2013, 52, 12354-12358; Angew. Chem. 2013, 125, 12580-
12584; (d) L. Cui, Y. e. You, X. Mi, S. Luo, Org. Chem. Front. 2018, 5,
2313-2316.
[8]
[9]
For selected reviews of enantioselective halogenations of alkenes, see:
(a) C. K. Tan, L. Zhou, Y.-Y. Yeung, Synlett 2011, 1335-1339; (b) S. E.
Denmark, W. E. Kuester, M. T. Burk, Angew. Chem., Int. Ed. 2012, 51,
10938-10953; Angew. Chem. 2012, 124, 11098-11113; (c) M. L. Landry,
N. Z. Burns, Acc. Chem. Res. 2018, 51, 1260-1271.
(a) S. E. Denmark, D. J. P. Kornfilt, T. Vogler, J. Am. Chem. Soc. 2011,
133, 15308-15311; (b) S. E. Denmark, A. Jaunet, J. Am. Chem. Soc.
2013, 135, 6419-6422; (c) S. E. Denmark, H. M. Chi, J. Am. Chem. Soc.
2014, 136, 3655-3663; (d) S. E. Denmark, S. Rossi, M. P. Webster, H.
Wang, J. Am. Chem. Soc. 2014, 136, 13016-13028; (e) S. E. Denmark,
Acknowledgements
This work was supported by the NSFC (21702135, 21871178
21871117, 21672145, 21290181, and 21642004), and The
This article is protected by copyright. All rights reserved.

10.1002/anie.201907115
Angewandte Chemie International Edition
COMMUNICATION
H. M. Chi, J. Am. Chem. Soc. 2014, 136, 8915-8918; (f) S. E. Denmark,
E. Hartmann, D. J. P. Kornfilt, H. Wang, Nat. Chem. 2014, 6, 1056; (g)
S. E. Denmark, A. Jaunet, J. Org. Chem. 2014, 79, 140-171; (h) E.
Hartmann, S. E. Denmark, Helv. Chim. Acta 2017, 100, e1700158; (i) S.
E. Denmark, D. J. P. Kornfilt, J. Org. Chem. 2017, 82, 3192-3222; (j) Z.
Tao, K. A. Robb, K. Zhao, S. E. Denmark, J. Am. Chem. Soc. 2018,
140, 3569-3573.
[23] (a) S. Takano, M. Moriya, K. Ogasawara, Tetrahedron Lett. 1992, 33,
329-332; (b) M. Tori, T. Miyake, T. Hamaguchi, M. Sono, Tetrahedron:
Asymmetry 1997, 8, 2731-2738; (c) A. Abad, C. Agulló, A. C. Cuñat, R.
H. Perni, J. Org. Chem. 1999, 64, 1741-1744; (d) A. Nayek, S. Ghosh,
Tetrahedron Lett. 2002, 43, 1313-1315; (e) M. R. Luderer, M. J. Mealy,
W. F. Bailey, J. Org. Chem. 2014, 79, 10722-10726.
[24] For 31P-NMR experiments, please see Supporting Information.
[25] See Supporting Information for computational details.
[10] (a) H. Guan, H. Wang, D. Huang, Y. Shi, Tetrahedron 2012, 68, 2728-
2735; (b) L. Li, Z. Li, D. Huang, H. Wang, Y. Shi, RSC Adv. 2013, 3,
4523-4525.
[26] To further illustrate the steric effect of the (S)-CPA- anion in accounting
-
for the enantioselective sulfenylation of 3a, the MeSO3 anion assisted
[11] (a) V. A. Soloshonok, D. J. Nelson, Beilstein Journal of Organic
Chemistry 2011, 7, 744-758; (b) J.-J. Wang, H. Yang, B.-B. Gou, L.
Zhou, J. Chen, J. Org. Chem. 2018, 83, 4730-4738.
[12] For selected reviews on the semipinacol rearrangement, see: (a) L. E.
Overman, Acc. Chem. Res. 1992, 25, 352-359; (b) B. Wang, Y. Q. Tu,
Acc. Chem. Res. 2011, 44, 1207-1222; (c) L. E. Overman, L. D.
Pennington, J. Org. Chem. 2003, 68, 7143-7157; (d) S.-H. Wang, B.-S.
Li, Y.-Q. Tu, Chem. Commun. 2014, 50, 2393-2408; (e) Z.-M. Chen, X.-
M. Zhang, Y.-Q. Tu, Chem. Soc. Rev. 2015, 44, 5220-5245; (f) H. Wu,
Q. Wang, J. Zhu, Eur. J. Org. Chem. 2019, 1964-1980.
sulfenylation of 3a was also considered computationally. The predicted
free energy barrier for attack from the Si side of 3a via TS1aʹ is only 0.9
kcal/mol lower than the competitive attack mode from the Re side via
TS1bʹ (Figure S1). Computational results suggest that the sulfenylation
-
of 3a using the MeSO3 anion is less enantioselective compared with
the (S)-CPA- anion, which is consistent with the experimental
observation.
[13] For selected examples on the semipinacol rearrangement, see: (a) E.
Zhang, C.-A. Fan, Y.-Q. Tu, F.-M. Zhang, Y.-L. Song, J. Am. Chem.
Soc. 2009, 131, 14626-14627; (b) Z.-M. Chen, Q.-W. Zhang, Z.-H.
Chen, H. Li, Y.-Q. Tu, F.-M. Zhang, J.-M. Tian, J. Am. Chem. Soc. 2011,
133, 8818-8821; (c) Z. Chai, T. J. Rainey, J. Am. Chem. Soc. 2012, 134,
3615-3618; (d) F. Romanov-Michailidis, L. Guénée, A. Alexakis, Angew.
Chem., Int. Ed. 2013, 52, 9266-9270; Angew. Chem. 2013, 125, 9436-
9440; (e) F. Romanov-Michailidis, L. Guénée, A. Alexakis, Org. Lett.
2013, 15, 5890-5893; (f) Y. Qin, S.-L. You, Org. Lett. 2014, 16, 1810-
1813; (g) B.-M. Yang, P.-J. Cai, Y.-Q. Tu, Z.-X. Yu, Z.-M. Chen, S.-H.
Wang, S.-H. Wang, F.-M. Zhang, J. Am. Chem. Soc. 2015, 137, 8344-
8347; (h) F. Romanov-Michailidis, M. Romanova-Michaelides, M.
Pupier, A. Alexakis, Chem. Eur. J. 2015, 21, 5561-5583; (i) D. H.
Lukamto, M. J. Gaunt, J. Am. Chem. Soc. 2017, 139, 9160-9163; (j) H.
Wu, Q. Wang, J. Zhu, Chem. Eur. J. 2017, 23, 13037-13041; (k) H. Wu,
R. Andres, Q. Wang, J. Zhu, Angew. Chem., Int. Ed. 2019, 58, 499-
503; Angew. Chem. 2019, 131, 509-513; (l) G. Li, C. Piemontesi, Q.
Wang, J. Zhu, Angew. Chem., Int. Ed. 2019, 58, 2870-2874; Angew.
Chem. 2019, 131, 2896-2900.
[14] During our preparation of this paper, Denmark group published the
article on 1,2-boronate migration: Z. Tao, K. A. Robb, J. L. Panger, S. E.
Denmark, J. Am. Chem. Soc. 2018, 140, 15621-15625.
[15] Q.-W. Zhang, C.-A. Fan, H.-J. Zhang, Y.-Q. Tu, Y.-M. Zhao, P. Gu, Z.-
M. Chen, Angew. Chem., Int. Ed. 2009, 48, 8572-8574; Angew. Chem.
2009, 121, 8724-8726.
[16] Using 1-(1-(o-tolyl)vinyl)cyclobutan-1-ol as a substrate, hardly could
any reaction be observed.
[17] CCDC 1898822 (13a, the sulfone derivative of 4a) and 1904767 (10a)
contain the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre.
[18] (a) J. Xie, Q. Zhou, Acta Chimica Sinica 2014, 72, 778-797; (b) X. Liu,
H. Zheng, Y. Xia, L. Lin, X. Feng, Acc. Chem. Res. 2017, 50, 2621-
2631; (c) X.-H. Chen, Q. Wei, S.-W. Luo, H. Xiao, L.-Z. Gong, J. Am.
Chem. Soc. 2009, 131, 13819-13825; (d) H. Wu, Y.-P. He, L. Xu, D.-Y.
Zhang, L.-Z. Gong, Angew. Chem., Int. Ed. 2014, 53, 3466-3469;
Angew. Chem. 2014, 126, 3534-3537.
[19] For 1H-NMR results, please see Supporting Information.
[20] The configuration of the product 6d-f was assigned by derivation of 6d.
For details, please see Supporting Information.
[21] (a) M. S. Buchanan, J. D. Connolly, D. S. Rycroft, Phytochemistry 1996,
43, 1245-1248; (b) T. Hashimoto, H. Irita, S. Takaoka, M. Tanaka, Y.
Asakawa, Tetrahedron 2000, 56, 3153-3159.
[22] (a) C. Enzell, H. Erdtman, Tetrahedron 1958, 4, 361-368; (b) Y.
Fukuyama, Y. Asakawa, J. Chem. Soc., Perkin Trans. 1 1991, 2737-
2741.
This article is protected by copyright. All rights reserved.

10.1002/anie.201907115
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 2:
RESEARCH ARTICLE
Yu-Yang Xie, Zhi-Min Chen*, Hui-Yun
Luo, Hui Shao, Yong-Qiang Tu*,
Xiaoguang Bao*, Ren-Fei Cao, Shu-Yu
Zhang, and Jin-Miao Tian
Lewis Base/Brønsted Acid Co-
catalyzed Enantioselective
Sulfenylation/Semipinacol
Rearrangement of Di- and Tri-
substituted Allylic Alcohols
Text for Table of Contents
An enantioselective sulfenylation/semipinacol rearrangement of 1,1-disubstituted and
tri-substituted allylic alcohols was accomplished under the co-catalysis of chiral
Lewis base/chiral Brønsted acid, to generate various β-phenylthio ketones bearing
an all-carbon quaternary center in moderate to excellent yields and excellent
enantioselectivities. Computational studies were carried out to explain the origin of
enantioselectivity and the role of chiral Brønsted acid.
This article is protected by copyright. All rights reserved.