Published on the web August 21, 2010
1013
Asymmetric Allylation of Aldehydes Catalyzed by Simple Dual Small Organic Molecules:
L-Proline and L-Prolinol
Guo-hong Chen, Ling-yan Liu,* Xiao-ning Wei, Wei-xing Chang, and Jing Li*
The State Key Laboratory Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry,
Nankai University, Tianjin 300071, P. R. China
(Received June 2, 2010; CL-100521; E-mail: lijing@nankai.edu.cn, liulingyan@nankai.edu.cn)
A novel and simple methodology for the asymmetric
allylation of aldehydes was reported. Double small organic
molecules such as L-proline and L-prolinol were first employed
for providing a chiral environment so as to afford chiral
homoallylic alcohols in high yields and moderate enantioselec-
tivities in our protocol.
Table 1. A survey of various chiral promoters
2.0 equiv L-proline
OH
*
1.1 equiv
Chiral promoter
SnBr
3
+
PhCHO
Ph
4ÅMS, CH2Cl2
–78 °C, 10 h
Entry Promoter
Yield/%a ee/%b Config.c
1
2
3
4
5
6
7
8
®
80
80
87
80
83
93
78
80
80
72
80
86
72
83
93
83
95
75
86
20
13
9
10
11
8.5
8.5
8.6
11
10
44
56
53
37
20
11.6
9.5
11
R
R
R
R
R
R
R
R
S
5-Methyl-L-norleucine
L-¢-Homophenylalanine
L-Tyrosine
L-Threonine
L-Arginine
The asymmetric allylation of aldehydes is an important
process to obtain chiral homoallylic alcohols, which are
important building blocks in modern organic synthesis and
widely applied to the synthesis of natural products and
pharmaceuticals. To date, numerous methodologies have already
been developed for the synthesis of chiral homoallylic alcohols.1
Among these approaches, allylsilanes2 and allylstannanes3 are
widely used as allylation reagents for the asymmetric allylation
of aldehydes. In contrast, there are few reports of the asymmetric
allylation of aldehydes using allyltin halide.4 On the other hand,
asymmetric organocatalysis based either on Lewis acid or base
interactions has been recognized as an efficient method for
obtaining chiral compounds with high enantioselectivity. The
application of enantiomerically pure “small” organic molecules
represents a promising alternative catalytic concept in addition
to other frequently used syntheses based on metal containing
catalysts.5 Yanagisawa reported the asymmetric allylation of
aldehydes with tetraallyltin catalyzed by L-aspartic acid in 2004,
but the best enantiomeric-excess value was only 40%.6 In
addition, Tsogoeva et al. published allylation of imine catalyzed
by chiral formamide derivatives with the participation of 2 equiv
of L-proline in 2006.7 Obviously, there was a double-molecule-
chiral catalysis in this reaction. On the basis of these concepts,
and as continuation of our ongoing program on asymmetric
allylation of carbonyl compounds catalyzed by small organic
molecules,4a we herein reported an asymmetric allylation of
aldehydes using triallyltin monobromide catalyzed by double
small organic molecules such as natural L-proline and L-
prolinol, which are widely used owing to availability, stability,
and low cost.
L-Methionine
L-Alanine
9d L-Tyrosine
10d L-Threonine
S
11
12
13
14
15
16
17
18
19
L-Valinol
L-Prolinol
R
R
R
R
R
R
R
R
R
L-Phenylalaninol
L-Methioninol
L-Threoninol
L-Tartaric acid
R-BINOL
S-BINOL
Cinchonidine
8.4
aIsolated yield. bChiral GC (£-cyclodextrin column). cThe
absolute configuration of the product was determined by
comparison of the optical rotation with the literatures. Using
d
D-proline as another promoter.
adding additional natural amino acids than that of no additive,
although all reactions proceed smoothly and afford the corre-
sponding homoallylic alcohol in high or excellent yields
(Table 1, Entries 2-8). It was surmised to be caused by these
two promoters’ chiral mismatch. Thus, D-proline was chosen to
combine with other L-amino acids as co-promoters in the
asymmetric allylation under the same conditions. However, the
same ee value was obtained when D-proline was used instead of
L-proline (Table 1, Entries 9, 10, and 18). The mismatch of the
two promoters can be excluded. In order to get higher ee values,
we turned our attention to amino alcohols directly derived from
natural amino acids. The enantioselectivity was actually increas-
ed as expectated (Table 1, Entries 11-15) and L-prolinol
rendered the best catalytic activity in enantioselectivity with
56% ee. In addition, we also investigated other chiral promoters,
such as L-tartaric acid, R-BINOL, and cinchonidine. As a result,
very high yields could be produced but with lower enantiose-
lectivity (Table 1, Entries 16-19).
At the beginning, various natural amino acids which are
commercially available and their derivatives were examined. A
mixture of benzaldehyde and L-proline (2 equiv) was stirred in
dichloromethane at room temperature in the presence of active
4 ¡ molecular sieves (MS). After that, triallyltin bromide was
added followed by another chiral promoter (1.1 equiv) at
¹78 °C. The product was obtained by aqueous work-up and
column chromatography after stirring at room temperature for
10 h. The results are shown in Table 1. It was found that this
reaction could give high yield up to 80% and 20% ee in the
absence of additional chiral promoter (Table 1, Entry 1).
Unfortunately, lower enantioselectivities were obtained when
Chem. Lett. 2010, 39, 1013-1015
© 2010 The Chemical Society of Japan
Chen, Guo-Hong
