Chiral phosphoric acid catalyzed enantioselective allylation of aldehydes with allyltrichlorosilane

Article abstract of DOI:10.1002/cjoc.201180244

Easily accessible chiral phosphoric acid 1b has been applied as efficient organocatalyst for the asymmetric allylation of aldehydes with allyltrichlorosilane. In the presence of 20 mol% of 1b, the allylation of a broad range of aldehydes proceeded smoothl

Full text of DOI:10.1002/cjoc.201180244

FULL PAPER
Chiral Phosphoric Acid Catalyzed Enantioselective Allylation
of Aldehydes with Allyltrichlorosilane
Cheng, Kea,b(程柯)
Fan, Tiantiana(范甜甜)
Sun, Jian*,a(孙健)
a Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu,
Sichuan 610041, China
b Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, China
Easily accessible chiral phosphoric acid 1b has been applied as efficient organocatalyst for the asymmetric al-
lylation of aldehydes with allyltrichlorosilane. In the presence of 20 mol% of 1b, the allylation of a broad range of
aldehydes proceeded smoothly to give the corresponding homoallylic alcohol with up to 87% ee and 97% yield.
Keywords phosphoric acid, allylation, aldehydes, allyltrichlorosilane
Introduction
R
R
O
P
The asymmetric allylation of aldehydes is one of the
most straightforward methods for the preparation of
stereogenic homoallylic alcohols.1 Activation of allyl
trichlorosilane by a catalytic amount of chiral Lewis
base has been shown to be an efficient asymmetric ally-
lation method. In 1994, the first example of this trans-
formation was reported by Denmark using chiral phos-
phoramide derivatives as the Lewis base catalyst.2 Since
then, several different types of chiral Lewis base cata-
lysts have been developed, including phosphora-
mides,3-5 formamides,6-8 N-oxides,9-12 and sulfoxides.13
Herein, we report that chiral BINOL-derived phosphoric
acids, a new type of organocatalysts that have recently
emerged as excellent promoters for a number of enanti-
oselective transformations,14 could also effectively
catalyze the asymmetric allylation of aldehydes.
O
P
O
O
OH
OH
O
O
R
R
(R)-1a, R = H
(R)-1f, R = H
(R)-1g, R = CH3
(R)-1h, R = Br
(R)-1b, R = CH3
(R)-1c, R = Br
(R)-1d, R = Ph
(R)-1e, R = I
Figure 1 Structure of the catalysts.
Table 1 Enantioselective allylation of benzaldehyde 2a with
allyltrichlorosilane catalyzed by 1a
OH
20 mol% Catalyst 1
+
PhCHO
SiCl3
(2.0 equiv.)
Toluene, -20 oC
Ph
(R)-3a
2a
Yieldb/%
eec,d/%
Results and discussion
Entry
Cat.
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
76
93
45
87
77
Initial attempts to evaluate easily available chiral
phosphoric acid 1a as catalyst for the enantioselective
allylation of benzaldehyde 2a with allyltrichorosilane in
toluene at －20 ℃ gave moderate results (76% yield
and 45% ee). We then prepared a series of chiral
(R)-BINOL-phosphoric acid derivatives (Figure 1) and
tested their efficacies in the allylation of 2a with allyl-
trichlorosilane. As shown in Table 1, catalyst 1b bearing
3,3'-dimethyl substitutents exhibited the best reactivity
and enantioselectivity, affording 93% yield and 87% ee,
whereas 1d with 3,3'-diphenyl substituents had almost
no detectable reactivity (Entry 4). Catalysts 1f—1h with
a partial hydrogenated binaphthyl backbone exhibited
substantially lower reactivity and enantioselectivity than
their counterparts 1a—1c (Entries 6—8). Catalyst 1b
65
N.R.
36
67
32
69
35
66
1g
1h
44
25
a Unless specified otherwise, reactions were carried out with 2.0
equiv. of allyltrichlorosilane on a 0.1 mmol scale for 48 h. b Iso-
c
lated yield based on benzaldehyde. Determined by HPLC.
d Product 3a was R configured in all cases, as revealed by com-
parison of the optical rotation with literature data.2
*
E-mail: sunjian@cib.ac.cn; Tel.: 0086-028-85211220; Fax: 0086-028-85222753
Received March 12, 2011; revised and accepted April 15, 2011.
Project supported by the National Natural Science Foundation of China (Nos. 20732006 and 20972152).
Chin. J. Chem. 2011, 29, 1669— 1671
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Cheng, Fan & Sun
FULL PAPER
exhibiting the best overall efficacy was then selected for
further studies.
Table 3 Enantioselective allylation of various benzaldehydes 2
with allyltrichlorosilane catalyzed by 1ba
To optimize the reaction conditions, different sol-
vents were examined for the 1b-catalyzed allylation of
2a. When toluene was replaced with either dichloro-
methane, chloroform or dichloroethane, a dramatic de-
crease was observed in both reactivity and enantioselec-
tivity (Table 2, Entries 2—4). Although tetrachlorocar-
bon (CCl4) as solvent can also afford good enantioselec-
tivity, only 30% yield was obtained in 48 h (Entry 5).
Lowering the reaction temperature from －20 to －40
℃ had slightly beneficial effects on enantioselectivity,
but caused unacceptable loss of reactivity (Entry 6).
OH
20 mol% Catalyst 1b
+
RCHO
SiCl3
R
Toluene, -20 oC
(2.0 equiv.)
(R)-3a
2
Entry
R
Yieldb/%
eec/%
1
2
2a C6H5
93
96
96
98
72
84
95
84
74
68
95
98
75
88
87
82
78
83
62
72
68
65
59
63
79
84
62
43
2b 4-FC6H4
3
2c 4-BrC6H4
2d 4-CH3C6H4
2e 4-CH3OC6H4
2f 4-NO3C6H4
2g 4-CNC6H4
2h 3-CH3C6H4
2i 3-ClC6H4
2j 3-CF3C6H4
2k 2-ClC6H4
2l 2-BrC6H4
2m 2-Naphthyl
2n Ph(CH2)2
4
5
6
Table 2 Enantioselective allylation of benzaldehyde 2a with
allyltrichlorosilane catalyzed by 1b under different conditions
7
8
OH
20 mol% Catalyst 1b
9
PhCHO
+
SiCl3
Solvent, -20 oC
Ph
10
11
12
13
14
2a
(2.0 equiv.)
(R)-3a
Entry
T/℃
Solvent
Yieldb/%
eec/%
1
2
3
4
5
6
－20
－20
－20
－20
－20
－40
Toluene
CH2Cl2
93
76
52
78
30
34
87
49
48
23
83
88
a Unless specified otherwise, reactions were carried out with 2.0
equiv. of allyltrichlorosilane on a 0.1 mmol scale for 48 h. b Iso-
lated yield based on aldehyde. c Determined by HPLC.
CHCl3
ClCH2CH2Cl
CCl4
Toluene
for the present reaction system, the chiral methylphos-
phate 1i was also tested as catalyst and was found to
have no activity towards the model allylation of ben-
zaldehyde 2a, suggesting that the acidic functionality is
crucial for the catalysis. Thus, we proposed a plausible
bicyclic transition structure 4 featuring a hexavalent
silicon species and a hydrogen bond between the phos-
phoric acid and the aldehyde.
a Unless specified otherwise, reactions were carried out with 2.0
equiv. of allyltrichlorosilane on a 0.1 mmol scale for 48 h. b Iso-
lated yield based on benzaldehyde. c Determined by HPLC.
After having established the optimal reaction condi-
tions, we set out to examine the substrate spectrum of
the present catalyst system. In the presence of 20 mol%
1b, various aldehydes were checked (Table 3).15 Gener-
ally, the aromatic aldehydes with different electronic
natures all underwent smooth asymmetic allylations to
furnish the desired homoallylic alcohol products in good
to excellent yields with moderate to good enantioselec-
tivities. Benzaldehyde 2a gave the highest enantioselec-
tivity (87% ee, Entry 1). The aliphatic aldehyde 2n
could also be allylated to afford the desired product 3n
in good yield, albeit with moderate enantioselectivity
(Entry 14).
Conclusion
In summary, chiral phosphoric acid 1b has been ap-
plied as an efficient organocatalyst for the enantioselec-
tive allylation of aldehydes. This easily prepared cata-
lyst promoted the allylation of a broad range of alde-
hydes in high yield (up to 98%) and good enantioselec-
tivities (up to 87%). The detailed mechanism and the
further application of the present system are under ac-
tive investigation.
To gain some insights into the possible mechanism
Ar
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Chin. J. Chem. 2011, 29, 1669— 1671

Chiral Phosphoric Acid Catalyzed Enantioselective Allylation of Aldehydes
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