Chiral Zinc(II)-Catalyzed Enantioselective Tandem α-Alkenyl Addition/Proton Shift Reaction of Silyl Enol Ethers with Ketimines

Article abstract of DOI:10.1002/anie.201810961

A new catalytic asymmetric tandem α-alkenyl addition/proton shift reaction of silyl enol ethers with ketimines was serendipitously discovered in the presence of chiral N,N′-dioxide/Zn^II complexes. The proton shift preferentially proceeded inste

Full text of DOI:10.1002/anie.201810961

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Accepted Article
Title: Chiral ZnII Complex Catalyzed Enantioselective Tandem α-
Alkenyl Addition/Proton Shift Reaction of Silyl Enol Ethers with
Ketimines
Authors: Tengfei Kang, Weidi Cao, Liuzhen Hou, Qiong Tang, Sijia
Zou, Xiaohua Liu, and Xiaoming Feng
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Angewandte Chemie International Edition
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COMMUNICATION
II
Chiral Zn Complex Catalyzed Enantioselective Tandem -Alkenyl
Addition/Proton Shift Reaction of Silyl Enol Ethers with Ketimines
Tengfei Kang, Weidi Cao, Liuzhen Hou, Qiong Tang, Sijia Zou, Xiaohua Liu and Xiaoming Feng*
Dedication ((optional))
Abstract:
A
new catalytic asymmetric tandem -alkenyl
ethers with high efficiency.
addition/proton shift reaction of silyl enol ethers with ketimines was
II
serendipitously discovered in the presence of chiral N,N'-dioxide/Zn
complexes. Proton shift preferentially occurred than silyl shift after -
alkenyl addition of silyl enol ether to ketimine. A wide range of -
amino silyl enol ethers were achieved in high yields with good to
excellent ee values. Control experiments suggested that the
Mukaiyama-Mannich reaction and tandem -alkenyl addition/proton
shift reaction were competitive reactions in the current catalytic
system. Meanwhile, the obtained -amino silyl enol ethers could be
easily transformed into -fluoroamines containing two vicinal
tetrasubstituted carbon centers.
Silyl enol ethers are isolable and versatile intermediates
serving as convenient carbonyl equivalent donors in organic
synthesis due to their high reactivity and operability, which have
[
1]
enabled broad synthetic utilization. In our previous studies on
silyl enol ethers, several types of reactions were realized by
using chiral Lewis acid catalysts, including [2+2] cycloaddition
Scheme 1. Two pathways of the reaction of cyclopentanone-derived silyl enol
ether 1 with isatin-derived ketimine 2a.
[
2]
between alkynones and cyclic silyl enol ethers,
[4+2]
cycloaddition of silyloxyvinylindoles with ,-unsaturated -
After the preliminary investigation between silyl enol ether
[
3]
[4]
ketoesters and so on. To further expand the application of
silyl enol ethers, we explored a reaction of silyl enol ethers with
imines which anticipated Mukaiyama−Mannich reaction to afford
1
a and ketimine 2a (see Table S1−S3 in the SI for more details),
we found that the reaction proceeded smoothly in CH Cl at
5 C with L -RaPr -Zn(OTf) as the catalyst and 3a was
2
2
3
2
2
2
[
5-7]
the corresponding -amino carbonyl compounds.
The
obtained in 86% yield and 92% ee (Table 1, entry 1). Decreasing
the steric hindrance of the amide moiety improved the
enantioselectivity, however, sharply decreased yield of 3a and
increased yield of byproduct 4a were observed (entry 3 vs
entries 1 and 2). Changing the reaction temperature to 40 C in
reaction of cyclopentanone-derived silyl enol ether 1a and isatin-
derived ketimine 2a underwent -alkenyl addition of silyl enol
ether to C=N double bonds of imine in the presence of the chiral
N,N-dioxide-metal complex, forming a zwitterionic intermediate
[5b,8]
A, subsequent silyl group shift
from oxygen atom to nitrogen
CH
a within 3 hours, giving the same yield and ee value of 3a
entry 4 vs entry 2). To our delight, the yield of 3a could be
2 2
ClCH Cl, the substrate 2a was completely transformed into
atom and rapid desilylation afforded the Mukaiyama−Mannich
product 4a (Scheme 1, path a). Actually, to our surprise, a
mixture of -amino ketone and -amino silyl enol ether (3a) was
serendipitously observed. We conceived that proton shift of the
intermediate A took place to give the unexpected product 3a
3
(
increased to 85% without loss of the enantioselectivity (95% ee)
by employing isopropanol as the additive (entry 5). Decreasing
the steric hindrance of silyl group from TBS to TES and TMS,
increased yields of Mukaiyama-Mannich byproduct 4a were
obtained (entries 5-7). It may because the large repulsion
between TBS and Boc group of the amine make the proton shift
favored to give the product 3a.
(Scheme 1, path b).
The unexpected skeletal reorganization triggered our
interest. To the best of our knowledge, the α-alkenyl addition of
silyl enol ether to imine followed by proton shift has not been
[
9]
reported previously. Herein, we wish to describe a chiral N,N-
II
[10]
dioxide/Zn complex
catalyzed enantioselective tandem α-
alkenyl addition/proton shift process between silyl enol ethers
and ketimines to give the desired enantiopure -amino silyl enol
[
a]
T. F. Kang, Dr. W. D. Cao, L. Z. Hou, Q. Tang, S. J. Zou, Prof. Dr. X.
H. Liu, Prof. Dr. X. M. Feng
Key Laboratory of Green Chemistry & Technology, Ministry of
Education, College of Chemistry, Sichuan University, Chengdu
Figure 1. Ligands used in this study.
610064 (China)
E-mail: xmfeng@scu.edu.cn
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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COMMUNICATION
Table 1. Optimization of the reaction conditions.
[
b]
[c]
[
a]
t
h]
Yield [%]
3/4a
Ee [%]
Entry
ligand
Si
additive
[
3
1
2
3
L
2
-RaPr
-RaEt
-RaMe
2
TBS
TBS
TBS
TBS
TBS
TES
TMS
─
─
7
7
7
3
3
9
5
86/13
68/27
44/52
68/31
85/14
76/22
0/90
92
95
95
95
95
95
-
L
2
2
L
2
2
─
[
d]
4
L
L
L
L
2
-RaEt
-RaEt
-RaEt
-RaEt
2
─
[
[
[
d][e]
d][e]
d][e]
5
6
7
2
2
2
2
i-PrOH
i-PrOH
i-PrOH
2
2
[
a] Unless otherwise noted, the reactions were carried out with 2a (0.10 mmol),
a (1.5 equiv), metal salt (5 mol%), ligand (5 mol%), solvent (0.1 M) and 4 Å
MS (50 mg). MS = molecular sieve. [b] Isolated yields. [c] Determined by
HPLC on a chiral stationary phase. [d] CH ClCH Cl (0.6 mL) was used at
0 °C instead of CH Cl . [e] i-PrOH (1.0 equiv) was added.
1
2
2
4
2
2
[
a]
Scheme 3. Substrate scope of silyl enol ethers . [a] Unless otherwise noted,
With the optimized conditions established (Table 1, entry 5),
a series of isatin-derived ketimines 2 were probed to react with
a, giving the corresponding proton shift products 3a‒3f in high
yields with excellent ee values (Scheme 2, 8390% yields, 94
5% ee). Other isatin-derived ketimines with different protecting
groups of the nitrogen atom, such as -Cbz and -CO Et, gave a
all reactions were performed with L
3
-PiMe
2
/Zn(OTf)
2
, 1a (0.15 mmol), 2a (0.10
ClCH Cl (0.6 mL) at
2
-PiMe was used as ligand. [d] 1
mmol), 4 Å MS (50 mg) and i-PrOH (1.0 equiv) in CH
2
2
1
4
0 C. [b] L
2
-PiEt
2
was used as ligand. [c] L
2
1
(0.20 mmol). [e] D.r. was determined by HPLC or H NMR analysis. [f] Isolated
9
yield of major diastereoisomer.
2
little decreased yields and enantioselectivities which was likely
Subsequently, we turned our attention to broadening the
substrate scope of the silyl enol ethers (Scheme 3). Four-, six-
and seven-membered cyclic silyl enol ethers were tolerated in
this reaction and afforded the desired products 3g-3i in 21−71%
yields with 87−93% ee. 1-Indanone-derived substrates could be
smoothly transformed into the corresponding products 3j-3m in
good yields (6890%) with excellent ee values (9093%). -
Substituted cyclic silyl enol ethers were also tested in the current
catalytic system. The silyl enol ethers bearing -methyl, benzyl,
and chloro-alkyl underwent the reaction smoothly, delivering
attributed to the decreased steric hindrance compared with the
t
2
Boc group. In addition, the low reactivities of aryl and -SO
Bu
protected ketimines could not give the target products (see
Table S3 in the SI for details). The absolute configuration of
product 3a was determined to be S by X-ray crystallography
[
11]
analysis. A gram-scale reaction between 1a (6 mmol) and 2a
[
12]
(4 mmol) provided 3a in 86% yield with 95% ee.
3
n−3p in 61−77% yields, 8:1−>19:1 d.r. and 94−97% ee. Based
on the experimental results (see Table S5 in the SI for more
details), a kinetic resolution process of -substituted cyclic silyl
enol ethers was proposed to explain the observed
diastereoselectivities. The absolute configuration of the product
3
n was determined to be S,R by X-ray crystallography
[
11]
analysis.
We next explored the tandem -alkenyl addition/proton shift
[
13]
reaction between pyrazolinone-derived ketimines
and silyl
enol ethers (Scheme 4). Under the optimized conditions (see
Table S6 in the SI for detailed screening of the reaction
conditions), 98% yield with 93% ee of 6a could be obtained.
Changing the substituent at C3-position of ketimine 5 from
methyl to phenyl, the desired product 6b was obtained in 84%
yield with 92% ee. The absolute configuration of product 6b was
[
a]
Scheme 2. Substrate scope of ketimines . [a] Unless otherwise noted, all
reactions were performed with L -RaEt /Zn(OTf) (1:1, 5 mol%), 1a (0.15
mmol), 2 (0.10 mmol), 4 Å MS (50 mg) and i-PrOH (1.0 equiv) in CH ClCH Cl
0.6 mL) at 40 C. Yields are those of the isolated products. Chiral-phase
HPLC analysis was used to determine ee values. [b] 4.0 mmol scale of 2a.
2
2
2
2
2
(
[11]
determined to be
R by X-ray crystallography analysis.
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COMMUNICATION
Cyclohexanone-derived cyclic silyl enol ether was also explored
in the current catalytic system, providing the corresponding
products 6c in 98% yield with 84% ee. 1-Indanone-derived cyclic
silyl enol ethers reacted with 5a smoothly, delivering 6d in
excellent yield (95%) and ee value (97%). Only 24% yield and
73% ee of 6e was obtained when 1-tetralone-derived silyl enol
ether was utilized. Besides, ,-dimethyl cyclopentanone- and
γ,γ-dimethyl cyclohexanone-derived silyl enol ethers were also
suitable nucleophiles to give the desired products 6f and 6g in
Scheme 5. The fluorination of the -alkenyl addition/proton shift products.
93% yield with 68% ee and 91% yield with 75% ee, respectively.
It was worthy to note that acyclic silyl enol ether could also be
transformed into the corresponding product 6h in 40% yield with
99% ee.
Scheme 4. Substrate scope for silyl enol ethers with pyrazolinone-derived
[
a]
ketimines . [a] Unless otherwise noted, all reactions were performed with L
Ra(OMe) /Zn(NTf , 1 (1.5 equiv), 5 (0.05 mmol) and 4 Å MS (25 mg) in
CH ClCH Cl (0.6 mL) at 40 C. [b] At -20 C. [c] At 0 C. [d] L = L -PiEt . [e] L
-RaMe
2
-
2
2 2
)
2
2
2
2
=
L
2
2
.
Scheme 6. Control experiments and deuterium labeling studies.
To show the synthetic utility of this methodology, the
fluorination of -alkenyl addition/proton shift products was
[
14]
carried out. -Fluoroamine motif
is an important skeleton
[
15]
6
i with >70% D on the nitrogen atom of the formed amine which
revealed that the H of NHBoc come from silyl enol ether indeed
Scheme 6b). In addition, the same H/D ratio (26% D) was
observed in the products 6j and 6i when cross-over
experiment was conducted by treating the mixture of 1h-d and
(Scheme
and 1f severally reacted with 5a in the
-PiEt /Zn(NTf for 10 min and then they were
which is found in numerous of drug candidates. Manipulating
the -amino silyl enol ethers 3a, 3b and 3d with Selectfluor in
acetonitrile at room temperature within 30 min afforded the chiral
(
a

-fluoroamines 7−9 in 80−87% yields, 10:1−>19:1 d.r. with
maintained ee values, which contained two vicinal
1
[
11]
1
6
f under the optimized conditions at 40 °C in CD
c). When 1h-d
2 2
Cl
tetrasubstituted carbon centers (Scheme 5).
1
To gain insight into the mechanism of tandem -alkenyl
addition/proton shift in the current catalytic system, control
experiments were studied. No Mukaiyama-Mannich byproduct
presence of L
2
2
2 2
)
mixed to stir for another 10 min, <20% D of 6j and >50% D of 6i
were observed (Scheme 6d). These results proved that the
proton shift in this reaction underwent an intermolecular process,
and the inference was also in accordance with the experimental
result that the addition of isopropanol could improve the yield of
4
a
was observed when treating 3a under the standard
conditions with or without silica gel for 18 h (Scheme 6a).
Additionally, when a tagged product of 3a-d was mixed with 1a
and 2a under the optimized conditions, only trace amount of
tagged 4a-d was detected (see Scheme S7 in the SI). These
2
3
a (Table 1, entry 5). Isopropanol may act as a medium of
2
transmitting proton from carbon atom to nitrogen atom.
experimental results indicated that the Mukaiyama−Mannich
reaction is a competitive reaction in this system, the possibility of
Mukaiyama−Mannich product comes from 3a is ruled out. To
In summary, we have serendipitously discovered and
developed the first catalytic asymmetric tandem -alkenyl
addition/proton shift reaction of silyl enol ethers with ketimines
make clear the proton shift process, isotopic labeled 1h-d
1
(90%
II
by utilizing chiral N,N-dioxide/Zn complexes as the catalysts,
D) reacted with 5a in dichloromethane-d , affording the product
2
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Angewandte Chemie International Edition
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COMMUNICATION
affording a wide range of -amino silyl enol ethers in up to 98%
yield and 99% ee. The desired products could be easily
transformed into -fluoroamines with high diastereo- and
enantioselectivities under mild conditions. Deuterium labeling
study suggested a key proton shift was involved in this reaction.
Further studies on the mechanism of this reaction are ongoing.
Chem. Int. Ed. 2016, 55, 8970-8974; (g) F. Zhou, H. Yamamoto, Org.
Lett. 2016, 18, 4974-4977.
[
7]
Selected
examples
of
other
organocatalytic
asymmetric
Mukaiyama−Mannich reactions: (a) A. G. Wenzel, E. N. Jacobsen, J.
Am. Chem. Soc. 2002, 124, 12964-12965; (b) A. Hasegawa, Y.
Naganawa, M. Fushimi, K. Ishihara, H. Yamamoto, Org. Lett. 2006, 8,
3175-3178; (c) Q. Wang, M. Leutzsch, M. Gemmeren, B. List, J. Am.
Chem. Soc. 2013, 135, 15334-15337; (d) C. D. Gheewala, B. E. Collins,
T. H. Lambert, Science 2016, 351, 961-965; (e) J.-S. Yu, J. Zhou, Org.
Chem. Front. 2016, 3, 298-303.
Acknowledgements
[
8]
9]
For selected example on silyl group shift from oxygen atom to nitrogen
atom: (a) H. Ishitani, T. Kitazawa, S. Kobayashi, Tetrahedron Lett. 1999,
We appreciate the National Natural Science Foundation of
China (Nos. 21772127 and 21432006) and the Fundamental
Research Funds for the Central Universities (No.
40, 2161-2164; (b) H. Ishitani, M. Ueno, S. Kobayashi, J. Am. Chem.
Soc. 2000, 122, 8180-8186; (c) H. Fujisawa, E. Takahashi, T.
Mukaiyama, Chem. Eur. J. 2006, 12, 5082-5093.
[
[
The α-alkenyl addition/proton shift process of silyl enol ether with fluoral
was previously found. A. Ishii, J. Kojima, K. Mikami, Org. Lett. 1999, 1,
2012017yjsy101) for financial support.
2013-2016.
Keywords: -alkenyl addition • asymmetric catalysis •
deuterium labeling • proton shift • tandem reaction
10] For reviews and selected examples: (a) X. H. Liu, L. L. Lin, X. M. Feng,
Acc. Chem. Res. 2011, 44, 574-587; (b) X. H. Liu, L. L. Lin, X. M. Feng,
Org. Chem. Front. 2014. 1, 298-302; (c) X. H. Liu, H. F. Zheng, Y. Xia,
L. L. Lin, X. M. Feng, Acc. Chem. Res. 2017, 50, 2621-2631; (d) X. H.
Liu, S. X. Dong, L. L. Lin, X. M. Feng, Chin. J. Chem. 2018, 36, 791-
797; (e) Q. Yao, H. Zhang, H. Yu, Q. Xiong, X. H. Liu, X. M. Feng, Org.
Chem. Front. 2017, 4, 2012-2015.
[
1]
(a) M. B. Boxer, B. J. Albert, H. Yamamoto, Aldrichimica Acta 2009, 42,
3-15; (b) L. M. Geary, P. G. Hultin, Tetrahedron: Asymmetry 2009, 20,
131-173; (c) T. Brodmann, M. Lorenz, R. Schäckel, S. Simsek, M.
Kalesse, Synlett 2009, 174-192; (d) J. Matsuo, M. Murakami, Angew.
Chem. 2013,125, 9280-9289; Angew. Chem. Int. Ed. 2013, 52, 9109-
[11] Crystallographic data for 3a, 3n, 6b and 7: CCDC 1857353, 1857355,
1857361 and 1857362 contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre.
9
118; (e) G. L. Beutner, S. E. Denmark, Angew. Chem. 2013, 125,
256-9266; Angew. Chem. Int. Ed. 2013, 52, 2-13; (f) T. Kitanosono, S.
9
Kobayashi, 2013, 355, 3095-3118; (g) S. B. J. Kan, K. K. H. Ng, I.
Paterson, Angew. Chem. 2013, 125, 9267-9279; Angew. Chem. Int. Ed.
[12] In the gram scale reaction, the byproduct 4a was obtained in 13% yield,
6:1 d.r. and 80% ee/61% ee.
2
013, 52, 9097-9108; (h) G. D. Roiban, A. Ilie, M. T. Reetz, Chem. Lett.
014, 43, 2-10.
2
[13] For selected catalytic enantioselective examples on pyrazolinone-
derived ketimines: (a) S. Mahajan, P. Chauhan, U. Kaya, K. Deckers, K.
Rissanen, D. Enders, Chem. Commun. 2017, 53, 6633-6636; (b) P.
Chauhan, S. Mahajan, U. Kaya, A. Peuronen, K. Rissanen, D. Enders,
J. Org. Chem. 2017, 82, 7050-7058; (c) U. Kaya, P. Chauhan, S.
Mahajan, K. Deckers, A. Valkonen, K. Rissanen, D. Enders, Angew.
Chem. 2017, 129, 15560-15564; Angew. Chem. Int. Ed. 2017, 56,
15358-15362; (d) Z. Yang, W. Yang, L. Chen, H. Sun, W. Deng, Adv.
Synth. Catal. 2018, 360, 2049-2054.
[
2]
T. F. Kang, S. L. Ge, L. L. Lin, Y. Lu, X. H. Liu, X. M. Feng, Angew.
Chem. 2016, 128, 5631-5634; Angew. Chem. Int. Ed. 2016, 55, 5541-
5544.
[
[
3]
4]
X. H. Zhao, H. J. Mei, Q. Xiong, K. Fu, L. L. Lin, X. H. Liu, X. M. Feng,
Chem. Commun. 2016, 52, 10692-10695.
(a) S. K. Chen, Z. R. Hou, Y. Zhu, J. Wang, L. L. Lin, X. H. Liu, X. M.
Feng, Chem. Eur. J. 2009, 15, 5884-5887; (b) K. Fu, J. F. Zheng, L. L.
Lin, X. H. Liu, X. M. Feng, Chem. Commun. 2015, 51, 3106-3108; (c) K.
Fu, J. C. Zhang, L. L. Lin, J. Li, X. H. Liu, X. M. Feng, Org. Lett. 2017,
[14] Selected examples on catalytic asymmetric methods accessing to -
fluoroamine building blocks: (a) X. Yang, T. Wu, R. J. Phipps, F. D.
Toste, Chem. Rev. 2015, 115, 826-870; (b) O. O. Fadeyi, C. W.
Lindsley, Org. Lett. 2009, 11, 943-946; (c) C. Appayee, S. E. Brenner-
Moyer, Org. Lett. 2010, 12, 3356-3359. (d) J. Wu, Y. Wang, A. Drljevic,
V. Rauniyar, R. J. Phipps, F. D. Toste, Proc. Natl. Acad. Sci. USA 2013,
110, 13729-13733; (e) H. P. Shunatona, N. Früh, Y. Wang, V. Rauniyar,
F. D. Toste, Angew. Chem. 2013, 125, 7878-7881; Angew. Chem. Int.
Ed. 2013, 52, 7724-7727; (f) J. A. Kalow, A. G. Doyle, Tetrahedron
2013, 69, 5702-5709; (g) X. Liu, J. Zhang, L. Zhao, S. Ma, D. Yang, W.
Yan, R Wang, J. Org. Chem. 2015, 80, 12651-12658; (h) B. M. Trost, T.
Saget, A. Lerchen, C.-I. Hung, Angew. Chem. 2016, 128, 791-794;
Angew. Chem. Int. Ed. 2016, 55, 781-784; (i) B. Li, D.-M. Du, Adv.
Synth. Catal. 2018, 360, 3164-3170.
19, 332-335.
[
5]
Selected examples of asymmetric Mukaiyama−Mannich reactions
catalyzed by chiral Lewis acids: (a) S. Kobayashi, Y. Mori, J. S. Fossey,
M. M. Salter, Chem. Rev. 2011, 111, 2626-2704; (b) H. Ishitani, M.
Ueno, S. Kobayashi, J. Am. Chem. Soc. 1997, 119, 7153-7154; (c) S.
Kobayashi, H. Ishitani, M. Ueno, J. Am. Chem. Soc. 1998, 120, 431-
432; (d) E. Hagiwara, A. Fujii, M. Sodeoka, J. Am. Chem. Soc. 1998.
120, 2474-2475; (e) S. Xue, S. Yu, Y. Deng, W. D. Wulff, Angew. Chem.
2001, 113, 2331-2334; Angew. Chem. Int. Ed. 2001, 40, 2271-2274; (f)
S. Kobayashi, M. Ueno, S. Saito, Y. Mizuki, H. Ishitani, Y. Yamashita,
Proc. Natl. Acad. Sci. USA 2004, 101, 5476-5481; (g) S. Nakamura, H.
Nakashima, H. Sugimoto, H. Sano, M. Hattori, N. Shibata, T. Toru,
Chem. Eur. J. 2008, 14, 2145-2152.
[
6]
Selected examples of asymmetric Mukaiyama−Mannich reactions
catalyzed by phosphoric acids: (a) T. Akiyama, Y. Saitoh, H. Morita, K.
Fuchibe, Adv. Synth. Catal. 2005, 347, 1523-1526; (b) M. Yamanaka, J.
Itoh, K. Fuchibe, T. Akiyama, J. Am. Chem. Soc. 2007,129, 6756-6764;
[15] (a) T. C. Nugent, Chiral Amine Synthesis: Methods, Develepments and
Applications. Wiley-VCH: Weinheim, Germany (2010); (b) T. K. Murray,
K. Whalley, C. S. Robinson, M. A. Ward, E. A. Hicks, D. Lodge, J. L.
Vandergriff, P. Baumbarger, E. Siuda, M. Gates, A. M. Ogden, P.
Skolnick, D. M. Zimmerman, E. S. Nisenbaum, D. Bleakman, M. J.
O’neill, J. Pharmacol. Exp. Ther. 2003, 306, 752-762.
(c) J. Itoh, K. Fuchibe, T. Akiyama, Synthesis 2008, 1319-1322; (d) T.
Akiyama, T. Katoh, K. Mori, K. Kanno, Synlett 2009, 1664-1666; (e) W.
Kashikura, K. Mori, T. Akiyama, Org. Lett. 2011, 13, 1860-1863; (f) F.
Zhou, H. Yamamoto, Angew. Chem. 2016, 128, 9116-9120; Angew.
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Angewandte Chemie International Edition
10.1002/anie.201810961
COMMUNICATION
COMMUNICATION
Tengfei Kang, Weidi Cao, Liuzhen Hou,
Qiong Tang, Sijia Zou, Xiaohua Liu,
Xiaoming Feng*
Page No. – Page No.
II
Chiral Zn Complex Catalyzed
Enantioselective Tandem -Alkenyl
Addition/Proton Shift Reaction of
Silyl Enol Ethers with Ketimines
We have developed an efficient route to the synthesis of optically β-amino silyl enol
ethers via -alkenyl addition/proton shift process of silyl enol ethers to ketimines.
Good to excellent enantioselectivities with a broad substrate scope were achieved
II
catalyzed by chiral N,N'-dioxide/Zn complexes. Deuterium labeling study
suggested a key proton shift process was involved in this reaction. This case
provides an easy access to enantiopure β-fluoroamines with two vicinal
tetrasubstituted carbon centers.
This article is protected by copyright. All rights reserved.