Enantioselective Vinylogous Mannich-Type Reactions to Construct CF3S-Containing Stereocenters Catalysed by Chiral Quaternary Phosphonium Salts

Article abstract of DOI:10.1002/adsc.201901621

A series of benzyl trifluoromethyl sulphides bearing a nitro group were utilized as CF₃S-containing building blocks to construct chiral CF₃S-containing molecules via enantioselective vinylogous Mannich-type reactions. In such reactions, high yields and enantioselectivities were obtained using chiral quaternary phosphonium salts derived from amino acids. Moreover, a chiral cyclic urea bearing the CF₃S moiety was obtained from further transformation of the product. (Figure presented.).

Full text of DOI:10.1002/adsc.201901621

Title: Enantioselective Mannich-type Reactions to Construct CF3S-
containing Stereocenters Catalyzed by Chiral Quaternary
Phosphonium Salts
Authors: Gang Zhao, Lijun Xu, Longhui YU, Jun Liu, Hongyu Wang,
and Changwu Zheng
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: Adv. Synth. Catal. 10.1002/adsc.201901621
Link to VoR: http://dx.doi.org/10.1002/adsc.201901621

10.1002/adsc.201901621
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Enantioselective Vinylogous Mannich-type Reactions to
Construct CF3S-Containing Stereocenters Catalysed by Chiral
Quaternary Phosphonium Salts
Lijun Xu,a,b Longhui Yu,b Jun Liu,b Hongyu Wang,b Changwu Zheng,c Gang Zhaob*
a
Research Center of Resource Recycling Science and Engineering, College of Arts and Sciences
Shanghai Polytechnic University, 2360 Jinhai Road, Shanghai 201209, China
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese
b
Academy of Sciences, 345 Lingling Road, Shanghai 200032, China, E-mail: zhaog@sioc.ac.cn
College of Pharmacy Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
c
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract: A series of benzyl trifluoromethyl sulphides
bearing a nitro group were utilized as CF3S-containing
building blocks to construct chiral CF3S-containing
molecules via enantioselective vinylogous Mannich-type
reactions. In such reactions, high yields and
enantioselectivities were obtained using chiral
quaternary phosphonium salts derived from amino acids.
Moreover, a chiral cyclic urea bearing the CF3S moiety
was obtained from further transformation of the product.
Keywords: trifluoromethylthio-containing building
blocks; a nitro group; enantioselectivities; vinylogous
Mannich-type reactions; chiral quaternary phosphonium
salts
Figure 1. Examples of CF3S-containing bioactive
compounds.
trifluoromethylthiolating reagents via asymmetric
catalysis;[5] 2) the development of readily accessible
CF3S-containing building blocks for constructing
chiral compounds. Until now, these strategies have
emerged as the ideal approaches for the incorporation
of CF3S into small molecules. However, in
comparison to the first direct method, the latter with
higher atom economy has not been as extensively
researched in the past few years. In 2017, Wang et al.
developed an efficient approach for the
enantioselective construction of the chiral C(sp3)–
SCF3 bond via Rh(II)- and Cu(I)-catalysed [2,3]-
sigmatropic rearrangements of sulfonium ylide
(Scheme 1, a).[6] Our group has also reported the
enantioselective Mannich-type reactions using cyano-
substituted benzyl trifluoromethyl sulphides to
construct tetrasubstituted carbon stereocenters via
asymmetric dual-reagent catalysis (Scheme 1, b).[7]
The cyano group was crucial for enhancing the
reactivity of substrate, but its presence resulted in
difficulties with further transformation of the product,
which thereby limited the possible applications of
The introduction of fluorine-containing moieties into
drugs and biological molecules can greatly improve
metabolic stability and other pharmacokinetic
properties.[1] In particular, a trifluoromethylthio group
(CF3S) can significantly improve the transmembrane
permeability and enhance the metabolic stability of
drug candidates due to its high lipophilicity (π = 1.44)
and electron-withdrawing characteristics.[2] Over the
past decades, a great number of biologically active
molecules containing CF3S have been developed as
important pharmacophores and agrochemicals,
including methionine analogues, adenosine analogues,
and cefazaflur (Figure 1).[3] Recently, extensive
efforts have been focused on the direct introduction
of the CF3S group into functionalized molecules,[4]
but few advances have been made in the construction
of CF3S-containing chiral centres. Generally, there
are two different strategies for accomplishing the
above goal: 1) direct trifluoromethylthiolation with
electrophilic
such
method.
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901621
Advanced Synthesis & Catalysis
Moreover, the CF3S-containing building blocks that
were meta-
Table 1 Preliminary research on the activated aryl
sulfanes.[a]
Scheme 1. Enantioselective reactions involved CF3S-
containing nucleophiles.
Yield
dr[c]
ee(%)[c]
Entry
X, 1
3
(%)[b]
N.P.
o-NO2, 1a
o-NO2, 1a
H, 1b
–
–
–
83
–
Hence, the development of other CF3S-containing
building blocks for constructing chiral compounds is
still needed. Moreover, our attention has been drawn
to the asymmetric vinylogous addition reaction for
the formation of stereocenters. Fan et al.,[8] Wang et
al.,[9] and Jørgensen et al.[10] have independently
reported an effective vinylogous Michael reaction of
aryl methyl nucleophiles bearing strongly electron-
withdrawing groups with α, β-unsaturated aldehydes.
Herein, benzyl trifluoromethyl sulphide with an
electron-withdrawing group (1)[11] was evaluated as a
simple and readily available CF3S-containing
building blocks for the asymmetric vinylogous
Mannich-type addition (Scheme 1, c).
1[d]
2
90
83:17
3aa
–
3
N.P.
N.P.
N.P.
N.P.
87
–
4
o-CO2Me, 1c
o-CN,1d
–
–
–
–
5
–
–
6
m-NO2, 1e
p-NO2, 1f
–
–
–
7
57:43
12
3fa
[a] The reactions were performed with 1 (0.1 mmol), 2a (0.2
mmol), 4a (10 mol%) in the presence of Cs2CO3 (0.2 mmol) in
toluene (1.0 mL) and stirred at room temperature and the product
3 was obtained as mixtures of diastereoisomers.
[b] Isolated yields of 3.
[c] The dr and ee values were determined by chiral HPLC
analysis; ee values of the major diastereoisomers.
Initially, the vinylogous Mannich-type reaction
using 2-nitrobenzyl trifluoromethyl sulphide (1a)
with the N-Boc imine (2a) was examined via
asymmetric dual-reagent catalysis (Table 1, entry 1).
However, no product was observed under the
previous conditions. In view of the excellent
properties of quaternary phosphonium salts derived
from amino acids in the asymmetric synthesis,[12]
utilizing such salts might improve the above
enantioselective reactions. The corresponding product
3 could be obtained with 90% yield as a mixture of
[d] The condition of the asymmetric dual-reagent catalysis was
shown in the supporting information.
and para-substituted with nitro groups (1e, 1f) were
then investigated under the same conditions (Table 1,
entry 6–7). Only the para-substituted substrate was
suitable for the reaction but with low
enantioselectivity. No reaction proceeded when the
meta-substituted benzyl trifluoromethyl sulphide was
used in the reaction. Therefore, the electronic
properties of the nitro group and its ortho-position on
the ring could enhance the acidity of the benzyl
protons[13] and thereby trigger the desired
transformation via vinylogous Mannich-type addition.
Furthermore, various protecting groups of the imine
were also tested, including p-toluenesulfonyl (Ts) and
benzyloxycarbonyl (Cbz), but the corresponding
yields and enantioselectivities did not improve with
such protecting groups.
diastereoisomers
and
83%
ee
of
major
diastereoisomers when the reaction was carried out
using catalyst 4a and Cs2CO3 (Table 1, entry 2). After
the synthesis of the diastereoisomers, control
experiments were also performed to elucidate the
vital role of the nitro group. For example, the reaction
with BnSCF3 without the nitro group (1b) could not
proceed under the catalytic system. Additionally,
other electron-withdrawing groups such as the ester
(1c) and cyano groups (1d) were also tested, but no
reactions were catalysed by 4a (Table 1, entry 3–5).
To further improve the enantioselectivity of the
reaction, various catalysts, inorganic bases, and
solvents were investigated. As shown in Table 2, no
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901621
Advanced Synthesis & Catalysis
desired products were observed when NaOAc,
Na2CO3, or K2CO3 were used as the base (Table 2,
Table 2. Optimization of chiral catalysts as well as other conditions.[a]
Entry
Cat.
Sol.
Base
T (oC)
Yield (%)[b]
dr[c]
ee (%)[c]
1
2
4a
4a
4a
4a
4a
4a
4b
4c
4d
4e
4f
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCM
NaOAc
Na2CO3
K2CO3
rt.
rt.
rt.
rt.
rt
0
N.P.
N.P.
N.P.
90
–
–
–
–
3
–
–
4
Cs2CO3
KOH
83:17
61:39
86:14
28:72
75:25
33:67
71:39
64:36
90:10
72:28
79:21
71:29
88:12
66:34
53:47
90:10
83
29
90
4
5
91
6
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
89
7
0
89
8
0
88
67
17
-16
6
9
0
90
10
11
12
13
14
15
16
17
18
19
0
81
0
77
4g
4h
4i
0
88
92
11
8
0
91
0
90
4g
4g
4g
4g
4g
0
89
30
78
7
Et2O
0
68
THF
MeCN
Mesitylene
0
61
0
86
Rac.
91
0
91
[a] Unless otherwise noted, the reactions were performed with 1a (0.1 mmol), 2a (0.2 mmol), the chiral chiral quaternary
phosphonium salts 4 (10 mol%) in the presence of base (0.2 mmol) in solvent (1.0 mL) and stirred for 48 h and the product
3aa was obtained as mixtures of diastereoisomers.
[b] Isolated yields of 3aa; N.P. : no products.
[c] The dr and ee values were determined by chiral HPLC analysis; ee values of the major diastereoisomers.
entries 1–4). The reaction with the strong base KOH
produced the desired product with good yield but
decreased stereoselectivity (Table 2, entry 5). We
or urea (4f) led to inferior results (Table 2, entries 10
and 11). Further investigations determined that the
different benzyl groups of the phosphonium centre
were also crucial to the enantioselectivity (Table 2,
entries 12–14). Catalyst 4g, which contained the nitro
group on the meta-position, performed the best under
the same reaction conditions with 88% total isolated
yield and 92% ee of the major diastereoisomers
(Table 2, entry 12). We also investigated the effect of
various solvents on the Mannich-type reactions, but
no improvement in enantioselectivity was observed
(entries 15–19).
found
that
both
diastereoselectivity
and
enantioselectivity of the corresponding products
could be greatly increased by decreasing the reaction
temperature to 0 °C, albeit with extended reaction
time (Table 2, entry 6). Next, a series of chiral
bifunctional quaternary phosphonium salts were
synthesized and evaluated as catalysts. Among the
different catalysts screened, the chiral skeleton
derived from L-phenylalanine performed best in terms
of enantioselectivity and diastereoselectivity (Table 2,
entry 6 versus entries 7–9). Moreover, the amide
group of bifunctional chiral phosphine catalysts
seemed to be crucial for enantiocontrol in the reaction.
Replacement of this amide moiety with thiourea (4e)
With these optimized reaction conditions, we then
turned our attention towards exploring the generality
of the method with various N-Boc imines (2). As
summarized in Table 3, different substituted chiral
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901621
Advanced Synthesis & Catalysis
CF3S-containing amines were obtained in moderate
mostly over 90% ee of the major diastereoisomers
to excellent yields of two diastereoisomers (69–93%),
and
Table 3. Scope of the Mannich-type reaction catalyzed by quaternary phosphonium catalysis.[a]
[a] Unless otherwise noted, the reactions were performed with 1a (0.1 mmol), 2 (0.2 mmol), chiral catalyst 4g (10 mol%)
o
in the presence of Cs2CO3(0.2 mmol) in toluene (1.0 mL) at 0 C for 48 h; The product 3 was obtained as mixtures of
diastereoisomers; Isolated yields of 3; The dr and ee values were determined by chiral HPLC analysis; ee values of the major
diastereoisomers.
[b] The dr value was determined by
1
H NMR of the product; No ee value of the minor diastereoisomers.
moderate levels of diastereoselectivity, including
alkyl (3ab, 3ad–3ai), alkoxyl (3ac) and halide (3aj–
3al) groups, at different positions on the phenyl group
of imines. Generally, substrates with an electron-
donating group produced higher yields and ee values
of major diastereoisomers compared with those of
other substrates bearing halide groups (3ab versus
3aj, 3ak). Particularly, the aryl imine bearing
dimethyl groups on the phenyl reacted efficiently to
produce 3ai in 93% yield and 98% ee of major
diastereoisomers. While the other aryl imine
possessing a CF3 group produced the chiral amine
3am in 89% yield and 94% ee of major
diastereoisomers, which was probably due to steric
effects. Additionally, polycyclic and heteroaryl
aromatic imines were viable under the reaction
conditions, with corresponding products (3an–3aq)
in good yields (80–90%) and high enantioselectivities
of major diastereoisomers (82–93% ee).
Next, the influence of different substituents on the
CF3S-containing nucleophiles (1) on the vinylogous
Mannich-type reaction was further evaluated. As
presented in Table 4, halide pronucleophiles
produced the desired products in 92–94% yields (5a–
5c) and 92–96% ee of major diastereoisomers.
Additionally, the reaction proceeded smoothly with
the C2F5 substituted sulphide to produce the product
5d in 91% yield and 95% ee of major
diastereoisomers. The CF3CF2S group has been
proven to be an important moiety in several
agrochemical and pharmaceutical compounds,[14] and
a few methods for the preparation of analogous
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901621
Advanced Synthesis & Catalysis
CF3CF2S-containing compounds have been described
in literature. [15]
To demonstrate the modifiability of the products,
compound 3ab (96% ee of major diastereoisomers)
was subjected to the removal of the Boc group,
Table 4. Substrate scope of the CF3S-containing building blocks.[a]
[a] Unless otherwise noted, the reactions were performed with 1 (0.1 mmol), 2a (0.2 mmol), chiral catelyst 4g (10 mol%)
o
in the presence of Cs2CO3 (0.20 mmol) in toluene (1.0 mL) at 0 C for 48 h; The product 5 was obtained as mixtures of
diastereoisomers; Isolated yields of 5; The dr and ee values were determined by chiral HPLC analysis; ee values of the major
diastereoisomers.
[b] The dr value was determined by 1 H NMR of the product.
followed by treatment with 3,5-dibromobenzoic acid
to produce the chiral amide 6 in 65% yield and 86%
ee over two steps (Scheme 2, a). The absolute
configuration of the chiral amide 6 was confirmed by
X-ray crystallographic analysis, from which the
absolute structure of the major diastereoisomers was
deduced to be (1R, 2R). Additionally, compound 3aa
was converted to the chiral cyclic urea 7 in 53% yield
while preserving the high enantioselectivity (Scheme
2, b). Notably, the seven-membered heterocyclic 1,3-
benzodiazepin-2-one skeletons have constituted a
core structural unit of many bioactive compounds,[16]
such as compound 8, which have been used as
calcitonin gene-related peptide (CGRP) receptor
antagonists for the treatment of migraines.[17]
Scheme 2. Representative transformation
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901621
Advanced Synthesis & Catalysis
Based on our previous works,[12a–12d] the mechanism
of this catalyst system was considered to form a
possible transition state as illustrated below. We
proposed that the amide moiety of catalyst 4g might
activate the N-Boc imine via H-bonding interactions,
while the phosphonium centre might direct the
nucleophile through static electronic interactions. The
nitronate anion derived from 1a was from the Si face
of the
Figure 2. Possible transition state.
Sailing Program (C81YF19S001). We are grateful for the
financial support from the Gaoyuan Discipline of Shanghai–
Environmental Science and Engineering (Resource Recycling
Science and Engineering).
imine to avoid steric repulsion between the phenyl
groups of the imine and the catalyst (Figure 2).
In summary, we have developed asymmetric vinylogous
Mannich-type reactions to develop CF3S-containing
stereocenters via quaternary phosphonium catalysts. The
nitro group in the substrate could be essential for the
progress of the reaction due to its electronic properties and
ortho-position on the ring. Additionally, the product can be
References
[1] a) K. Mꢀller, C. Faeh, F. Diederich, Science 2007, 317,
1881–1886; b) D. O'Hagan, J. Fluorine Chem. 2010,
131, 1071–1081; Chem. Soc. Rev. 2008, 37, 308; c) P.
Jeschke, ChemBioChem 2004, 5, 570–589; d) Y. Zhou,
J. Wang, Z.-N. Gu, S.-N. Wang, W. Zhu, J. L. Aceꢁ, V.
A. Soloshonok, K. Izawa, H. Liu, Chem. Rev. 2016, 116,
422–518; e) N. Tsomaia, Eur. J. Med. Chem. 2015, 94,
459-470; f） C. Isanbor, D. O'Hagan, J. Fluorine Chem.
2006, 127, 303–319; g) S. Preshlock, M. Tredwell, V.
Gouverneur, Chem. Rev. 2016, 116, 719–766.
further
functionalized
to
give
a
chiral
tetrahydrobenzodiazepin-2-one, which is a potentially
useful drug development candidate, in high efficiency
while maintaining high enantioselectivity. Moreover,
further investigation of the mechanism and synthetic
applications of this transformation are underway in our lab.
Experimental Section
[2] a) A. Leo, C. Hansch, D. Elkins, Chem. Rev. 1971, 71,
525–616; b) C. Hansch, A. Leo, R. W. Taft, Chem. Rev.
1991, 91, 165–195; c) J. Chen, B. R. Dixon, J. Dumas,
D. Brittelli, Tetrahedron Lett. 1999, 40, 9195–9199.
[3] X.-H. Xu, K. Matsuzaki, N. Shibata, Chem. Rev. 2015,
115, 731–764.
A mixture of the CF3S-containing building blocks 1 (0.1
mmol), imine 2 (0.2 mmol) and catalyst 4g (10 mol%) in
toluene (1.0 mL) were cooled to 0 C before Cs2CO3 (0.2
mmol) was introduced. The reaction was stirred for 48 h
and completed according to TLC analysis. The crude
mixture were warmed to the room temperature and
quenched by water (3.0 mL). The aqueous phase was
extracted with EtOAc (3 × 5.0 mL), and the combined
organic layers were dried over anhydrous Na2SO4 and
concentrated in vacuo. The residue was purified by flash

[4] a) G. Teverovskiy, D. S. Surry, S. L. Buchwald, Angew.
Chem. Int. Ed. 2011, 50, 7312–7314; Angew. Chem.
2011, 123, 7450–7452; b) W.-T. Xu, J.-Y. Ma, X.‐A.
Yuan, J. Dai, J. Xie, C.-J. Zhu, Chem. Commun., 2019,
55, 9479–9482; c) M. Hu, C. Ni, J. Hu, J. Am. Chem.
Soc. 2012, 134, 15257–15260; d); S. Dix, M. Jakob, M.
N. Hopkinson, Chem. Eur. J. 2019, 25, 7635–7639; e)
P. Saravanan, P. Anbarasan, Chem. Commun. 2019, 55,
4639–4642; f) C. Zhang, D. A. Vicic, J. Am. Chem. Soc.
2012, 134, 183–185; g) L.-Q. Jiang, Q. Yan, R.-K.
Wang, T.-Q. Ding, W.-B. Yi, W. Zhang, Chem. Eur. J.
2018, 24, 18749–18756; h) W.-T. Xu, J.-Y. Ma, X.‐A.
Yuan, J. Dai, J. Xie, C.-J. Zhu, Angew. Chem. Int. Ed.
2018, 57, 10357–10361; Angew. Chem. 2018, 130,
10514–10518; i) L. Liu, X. Xu, Z. Chen, F.-L. Qing,
Angew. Chem. Int. Ed. 2015, 54, 897–900; Angew.
Chem. 2015, 127, 911–914; j) J. Maury, G. Force, B.
Darses, D. Lebœuf, Adv. Synth. Catal. 2018, 360,
2752–2756; k) N. Fuentes, W. Kong, L. Fernández-
column
chromatography
(silica
gel:
petroleum
ether/AcOEt = 10 : 1) to afford the products 3 or 5.
X-Ray Crystallographic Data of 6
CCDC-1526782 (6) contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
This work was sponsored by the National Natural Science
Foundation of China (Nos. 21272247, 21572247, 21871282), the
Chinese Academy of Sciences (XDB 20020100) and Shanghai
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901621
Advanced Synthesis & Catalysis
Sánchez, E. Merino, C. Nevado J. Am. Chem. Soc.
D.-D. Cao, W.-G. Cao, G. Zhao, Tetrahedron 2017, 73,
2349–2358.
2015, 137, 964–973; l) H. Chachignon, E. V.
Kondrashov, D. Cahard, Adv. Synth. Catal. 2018, 360,
965–971; m) X.-L. He, S. Majumder, J. Wu, C.-D. Jin,
S.-R. Guo, Z.-P. Guo, M.-H. Yang, Org. Chem. Front.,
2019, 6, 2435–2440; n) S. Pan, Y. G. Huang, X.-H. Xu,
F.-L. Qing, Org. Lett. 2017, 19, 4624–4627; o) S. Pan,
H. Li, Y. G. Huang, X.-H. Xu, F.-L. Qing, Org. Lett.
2017, 19, 3247–3250; p) S.-B. Zhang, X.-H. Xu, F.-L.
Qing, J. Fluorine Chem. 2019, 227, 109367; q) X.-W.
Xia, B.-C. Chen, X.-J. Zeng, B. Xu, Adv. Synth. Catal.
2018, 360, 4429–4434; r) C. Chen, Y. Xie, L. Chu, R.-
W. Wang, X. Zhang, F. L. Qing, Angew. Chem. Int. Ed.
2012, 51, 2492–2495; Angew. Chem. 2012, 124, 2542–
2545; s) G. Danoun, B. Bayarmagna, M. F. Grünberg,
L. J. Goossen, Chem. Sci. 2014, 5, 1312–1316; t) B.
Bayarmagna,; C. Matheis, E. Risto, L. J. Goossen, Adv.
Synth. Catal. 2014, 356, 2343–2348; u) F. A. Baert, J.
Colomb, T. Billard, Angew. Chem. Int. Ed. 2012, 51,
10382–10385; Angew. Chem. 2012, 124, 10528–
10531; v) S. Alazet, L. Zimmer, T. Billard, Angew.
Chem. Int. Ed. 2013, 52, 10814–10817; Angew. Chem.
2013, 125, 11014–11017; w) I. Saidalimu, T. Yoshioka,
Y.-M. Liang, E. Tokunaga, N. Shibata, Chem.
Commun., 2018, 54, 8761–8764; x) C. Xu, B. Ma, Q.-L.
Shen, Angew. Chem. Int. Ed. 2014, 53, 9316–9320;
Angew. Chem. 2014, 126, 9470–9474; y) X. Shao, X.
Wang, T. Yang, L. Lu, Q. Shen, Angew. Chem. Int. Ed.
2013, 52, 3457–3460; Angew. Chem. 2013, 125, 3541–
3544; z) Y. Yang, N. Shibata, J. Am. Chem. Soc. 2013,
135, 8782–8785.
[8] Y. Zhang, B.-W. Wei, H. Lin, W.-R. Cui, X.-Q. Zeng,
X.-L. Fan, Adv. Synth. Catal. 2015, 357, 1299–1304.
[9] T.-F. Li, J. Zhu, D.-Y. Wu, X.-M. Li, S.-N. Wang, H.
Li, J. Li, W. Wang, Chem. Eur. J. 2013, 19, 9147–9150.
[10] L. Dell’Amico, X. Companyó, T. Naicker, T. M.
Bräuer, K. A. Jørgensen, Eur. J. Org. Chem. 2013,
5262–5265.
[11] a) M. Jiang, F.-X. Zhu, H.-Y. Xiang, X. Xu, L.-F.
Deng, C.-H. Yang, Org. Biomo. Chem. 2015, 13, 6935–
6939; b) T. Billard, B. R. Langlois, Tetrahedron Lett.
1996, 37, 6865–6868; c) B. R. Langlois,T. Billard, J. C.
Mulatier, C. Yezeguelian, J. Fluorine Chem. 2007, 128,
851–856; d) C. Chen, X.-H. Xu, B. Yang, F.-L. Qing,
Org. Lett. 2014, 16, 3372–3375; e) D.-D. Kong, Z.
Jiang, S.-G. Xin, Z.-S. Bai, Y.-F. Yuan, Z.-Q. Weng,
Tetrahedron 2013, 69, 6046–6050.
[12] a) D.-D. Cao, J.-X. Zhang, H.-Y. Wang, G. Zhao,
Chem. Eur. J. 2015, 21, 9998–10002; b) D.-D. Cao, G.-
S.Fang, J.-X. Zhang, H.-Y. Wang, C.-W. Zheng, G.
Zhao, J. Org. Chem. 2016, 81, 9973–9982; c) J.-X.
Zhang, D.-D. Cao, H.-Y. Wang, C.-W. Zheng, G. Zhao,
Y.-J. Shang, J. Org. Chem. 2016, 81, 10558–10568; d)
R.-M. Pan, J.-X. Zhang, C.-W. Zheng, H.-Y. Wang, D.-
D. Cao, W.-G. Cao, G. Zhao, Tetrahedron 2017, 73,
2349–2358; e) D.-D. Cao, Z. Chai, J.-X. Zhang, Z.-Q.
Ye, H. Xiao, H.-Y. Wang, J.-H. Chen, X.-Y. Wu, G.
Zhao, Chem. Commun. 2013, 49, 5972–-5974; f) J.-K.
Pan, J.-H. Wu, H.-K. Zhang, X.-Y. Ren, J.-P. Tan, L.-X.
Zhu, H.-S. Zhang, C.-H. Jiang, T.-L. Wang, Angew.
Chem. Int. Ed. 2019, 58, 7425–7430; g) Li.-X. Zhu, X.-
Y. Ren, Z.-X. Liao, J.-K. Pan, C.-H. Jiang, T.-L. Wang,
Org. Lett. 2019, 21, 8667–8672; h) J.-P. Tan, P.-Y. Yu,
J.-H. Wu, Y. Chen, J.-K. Pan, C.-H. Jiang, X.-Y. Ren,
H.-S. Zhang, T.-L. Wang, Org. Lett. 2019, 21, 7298–
7302; i) E. Yamamoto, K. Wakafuji, Y. Mori, G.
Teshima, Y. Hidani, M. Tokunaga, 2019, 21, 4030–
4034.
[13] a) M. B. Cid, S. Duce, S. Morales, E. Rodrigo, J. L.
Ruano, Org. Lett. 2010, 12, 3586–3589; b) J.-H. Do, S.
Kim, Tetrahedron Let. 2011, 52, 2353–2355; c) S. Seo,
S. Kim Tetrahedron Let. 2012, 53, 2809–2812; d) J.-J.
Yao, X.-H. Liu, P. He, Y. Zhu, X.-J. Lian, L. Lin, X.-M.
Feng, Chem. Eur. J. 2013, 19, 16424–16430.
[14] D. C. Gary, C. S. Thomas, L. M. Casandra, A. D.
David, B. Kristy, V. B. Annette, H. D. William, P. C.
Denise, S. N. Jaime, H. Ricky, G. S. Jack,
WO2009102736, 2009.
[15] a) J.-X. Xiang, X.-H. Xu, F.-L. Qing, J. Fluorine
Chem. 2017, 203, 110–114; b) B. Exner, B.
Bayarmagnai, C. Matheis, Lukas J. Goossen, J.
Fluorine Chem. 2017, 198, 89–93; c) J.-J. Ma, Q.-R.
Liu, G.-P. Lu, W.-B. Yi, J. Fluorine Chem. 2017, 193,
113–117; d) C. Pooput, W. R. Dolbier, M. Médebielle, J.
Org. Chem. 2006, 71, 3564–3568.
[5] a) S.-S. Li, J.-B. Wang, Acta Chim. Sinica 2018, 76,
913–924; b) T. Bootwicha, X. Liu, R. Pluta, I.
Atodiresei, M. Rueping, Angew. Chem. Int. Ed. 2013,
52, 12856–12859; Angew. Chem. 2013, 125, 13093–
13097; c) X.Q. Wang, T. Yang, X. Cheng, Q. Shen,
Angew. Chem. Int. Ed. 2013, 52, 12860–12864; Angew.
Chem. 2013, 125, 13098–13102; d) X.-L. Zhu, J.-H. Xu,
D.-J. Cheng, L.-J. Zhao, X.-Y. Liu, B. Tan, Org. Lett.
2014, 16, 2192–2195; e) X. Liu, R. An, X. Zhang, J.
Luo, X.-D. Zhao, Angew. Chem. Int. Ed. 2016, 55,
5846–5850; Angew. Chem. 2016, 128, 5940–5944; f) X.
Liu, Y.-Y. Liang, J.-Y. Ji, J. Luo, X.-D. Zhao, J. Am.
Chem. Soc. 2018, 140, 4782–4786; g) J. Luo, Q.-X. Cao,
X.-H. Cao, X.-D. Zhao, Nat. Commun. 2018, 9, 527; h)
T. Qin,Q.-B. Jiang, J.-Y. Ji, J. Luo, X.-D. Zhao, Org.
Biomol. Chem., 2019, 17, 1763–1766; i) J. Luo, Y.-N
Liu, X.-D. Zhao, Org. Lett. 2017, 19, 3434–3437; j) M.-
Y. Jin, J.-C. Li, R.-K. Huang, Y.-X. Zhou, L.-W. Chung,
J. Wang, Chem. Commun., 2018, 54, 4581–4584; k) H.
Zhang, X.-B. Leng, X.-L, Wan, Q.-L. Shen, Org. Chem.
Front. 2017, 4, 1051–1057.
[6] Z.-K. Zhang, Z. Sheng, W.-Z. Yu, G.-J. Wu, R. Zhang,
W.-D. Chu, Y. Zhang, J.-B. Wang, Nature Chem. 2017,
9, 970–976.
[7] a) L.-J. Xu, H.-Y. Wang, C.-W. Zheng, G. Zhao, Adv.
Synth. Catal. 2017, 359, 2942–2948; b) H.-Y. Wang, K. [16] a) J. D. Rodgers, A. J. Cocuzza, D. M. Bilder,
Zhang, C.-W. Zheng, Z. Chai, G. Zhao, Angew. Chem.
Int. Ed. 2015, 54, 1775–1779; c) Y.-P. Lou, C.-W.
Zheng, G. Zhao, Z. Li, Org. Lett. 2015, 17, 688–691; d)
d) R.-M. Pan, J.-X. Zhang, C.-W. Zheng, H.-Y. Wang,
WO0000479A1, 2000; US6204262B1, 2001; b) T. Miki,
M. Kori, A. Fujishima, H. Mabuchi, R. Tozawa, M.
Nakamura, Y. Sugiyama, H. Yukimasa, Bioorg. Med.
Chem. 2002, 10, 385; c) M. Bayssat, G. Ferrand, J. C.
Depin, US4554273A, 1985.
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901621
Advanced Synthesis & Catalysis
[17] a) J. Schnaubelt, E. Stehle, Krueger, T. WO
2007074130A2, 2007; b) P. L. Nichols, J. Skidmore, R.
W. Ward, D. M. Wilson, WO2009000819A1, 2008; c)
C. Dengiz, S. Özcan, E. Şahin, M. Balci, Synthesis 2010,
8, 1365–1370.
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901621
Advanced Synthesis & Catalysis
COMMUNICATION
Enantioselective Vinylogous Mannich-type
Reactions to Construct CF3S-Containing
Stereocenters Catalysed by Chiral Quaternary
Phosphonium Salts
Adv. Synth. Catal. Year, Volume, Page – Page
Lijun Xu,a,b Longhui Yu,b Jun Liu,b Hongyu
Wang,b Changwu Zheng,c Gang Zhaob*
9
This article is protected by copyright. All rights reserved.