Table 3 Formation and conversion of phosphonium salt 4a
ed. B. M. Trost and I. Fleming, Pergamon Press, Oxford, UK, 1991,
vol. 1, p. 729.
2 For reviews, see: (a) A. Maerckar, Org. React., 1965, 14, 270;
(b) B. E. Maryanoff and A. B. Reitz, Chem. Rev., 1989, 89, 863;
(c) Y. Ju, in Modern Organic Reactions (in Chinese), ed. Y.-F. Hu
and G.-Q. Lin, Chemical Industry Press, Beijing, China, 2008,
vol. 3, p. 413.
3 (a) M. Schlosser and K. F. Christmann, Justus Liebigs Ann.
Chem., 1967, 708, 1; (b) M. Schlosser, H. B. Tuong and
B. Schaub, Tetrahedron Lett., 1985, 26, 311; (c) Q. Wang,
D. Deredas, C. Huynh and M. Schlosser, Chem.–Eur. J., 2003,
9, 570.
Entry
1a
R
Base
4a
4a, dra
3a, Z/Ea
1
2
3
1aa
1aa
1ac
1ag
1ag
Me
Me
4-MeC6H4
2-MeC6H4
2-MeC6H4
n-BuLi
LDA
n-BuLi
n-BuLi
LDA
4aa >99 : 1 >99 : 1
4aa
4ac
90 : 10
84 : 16
90 : 10
84 : 16
4
4ag o1 : 99 o1 : 99
4 (a) B.-L. Yang and S.-K. Tian, Chem. Commun., 2010, 46, 6180;
(b) C.-R. Liu, F.-L. Yang, Y.-Z. Jin, X.-T. Ma, D.-J. Cheng,
N. Li and S.-K. Tian, Org. Lett., 2010, 12, 3832; (c) C.-R.
Liu, M.-B. Li, C.-F. Yang and S.-K. Tian, Chem.–Eur. J.,
2009, 15, 793; (d) C.-R. Liu, M.-B. Li, D.-J. Cheng, C.-F.
Yang and S.-K. Tian, Org. Lett., 2009, 11, 2543; (e) C.-R.
Liu, M.-B. Li, C.-F. Yang and S.-K. Tian, Chem. Commun.,
2008, 1249.
5b
4ag 41 : 59 41 : 59
a
1
b
Determined by H NMR analysis. The reaction of imine 1ag with
phosphonium salt 2a in the presence of LDA afforded alkene 3a as a
41 : 59 mixture of Z/E isomers.
5 (a) D.-N. Liu and S.-K. Tian, Chem.–Eur. J., 2009, 15, 4538;
(b) H.-H. Li, Y.-H. Jin, J.-Q. Wang and S.-K. Tian, Org. Biomol.
Chem., 2009, 7, 3219.
6 D.-J. Dong, H.-H. Li and S.-K. Tian, J. Am. Chem. Soc., 2010,
132, 5018.
7 H. J. Bestmann and F. Seng, Angew. Chem., Int. Ed., 1963,
2, 393.
8 (a) H. J. Bestmann and F. Seng, Tetrahedron, 1965, 21, 1373;
(b) H. J. Bestmann, Angew. Chem., Int. Ed. Engl., 1965, 4, 830.
9 By contrast, under the same reaction conditions the Wittig reaction
of benzaldehyde with n-hexylidenetriphenylphosphorane afforded
alkene 3a as a 90 : 10 mixture of Z/E isomers.
10 We also performed the reaction of PhCH2CH2CHQNMs with
[Me2NCH2CH2PPh3]+BrÀ in the presence of n-BuLi, but did not
obtain the desired allylic amine.
Scheme 2 Proposed mechanism for the tunable stereoselective olefin-
ation of N-sulfonyl imines with nonstabilized phosphonium ylides.
11 About 0.5 mL of the reaction mixture at À78 1C was injected into
an NMR tube and immediately subjected to 31P NMR (162 M)
analysis (at room temperature). When the reaction mixture was
allowed to stand at room temperature, the signal at d 25.0 ppm,
assigned to the betaine intermediate, was found to decrease
and disappear completely in 3 h. The assignment of the betaine
intermediate was substantially supported by 31P NMR analysis of
its HBr salt, phosphonium salt 4aa (Table 3, entry 1), which shows
a signal at d 25.0 ppm. For details, see the ESIw.
12 It is noteworthy that Ph3PO rather than an iminophosphorane was
detected as a byproduct by 31P NMR analysis owing to the rapid
decomposition of the latter by a trace amount of water. The
formation of iminophosphorane as a primary byproduct was
substantially confirmed by the fact that Ph3P18O was generated
after the reaction mixture was worked up with H218O. For details,
see the ESIw.
In summary, we have developed a highly tunable stereoselective
alkene synthesis from readily accessible N-sulfonyl imines and
nonstabilized phosphonium ylides. A broad range of N-sulfonyl
aromatic, heteroaromatic, a,b-unsaturated, and aliphatic imines
react with various nonstabilized phosphonium ylides to afford an
array of both (Z)- and (E)-isomers of 1,2-disubstituted alkenes,
allylic alcohols, and allylic amines in good yields and with greater
than 99 : 1 stereoselectivity. The Z/E selectivity for alkene
synthesis has been demonstrated to originate from the diastereo-
selective addition of nonstabilized phosphonium ylides to
N-sulfonyl imines, wherein the N-sulfonyl groups serve as
powerful handles to finely tune stereoselectivity.
We are grateful for the financial support from the National
Natural Science Foundation of China (20972147 and
20732006), the National Basic Research Program of China
(973 Program 2010CB833300), and the Chinese Academy of
Sciences. We thank Professor Declan G. Gilheany (University
College Dublin) for helpful discussions.
13 Phosphonium salts 4a were obtained in 63–73% yields, and alkene
3a was obtained in 51–89% yields. For details, see the ESIw.
14 For an example on the addition of ester-stabilized phosphonium
ylides to N-Boc imines, see: Y. Zhang, Y.-K. Liu, T.-R. Kang,
Z.-K. Hu and Y.-C. Chen, J. Am. Chem. Soc., 2008, 130,
2456.
15 The dramatic influenceof a base on the stereoselectivity (Table 1)
suggests an effective coordination between lithium cation and an
N-sulfonyl imine.
16 The formation of the betaine intermediate is suggested to
be irreversible by the following experiment. Treatment of
phosphonium salt 4aa (>99 : 1 dr, Table 3, entry 1) successively
with n-BuLi and 4-MeOC6H4CHQNMs at À78 1C to room
temperature led to no formation of alkene Z3b (Table 2, entry 2).
Notes and references
1 For reviews, see: (a) T. Takeda, Modern Carbonyl Olefination, Wiley-
VCH, Weinheim, Germany, 2004; (b) J. M. J. Williams, Preparation
of Alkenes: A Practical Approach, Oxford University Press, Oxford,
UK, 1996; (c) S. E. Kelly, in Comprehensive Organic Synthesis,
c
2160 Chem. Commun., 2011, 47, 2158–2160
This journal is The Royal Society of Chemistry 2011