use of chiral Lewis base to promote the allylation of
electrophilic imines presents the advantages of higher stabil-
ity to aerobic conditions, the ability to be anchored on a solid
support, and less environmental impact than their metal-based
catalytic processes.8 Following the pioneering work of
Kobayashi,5 we and others have recently shown that chiral
sulfoxides are excellent organocatalysts in the allylation of
aldehyde and hydrazones with trichloroallyl silane.4 Accord-
ingly, excellent enantioselectivities were obtained in the
allylation of benzoyl hydrazones by using simple sulfoxides,
though up to 3 equiv of the organocatalysts was necessary.
Since the exact mechanism of the reaction is still missing,
the only manner to enhance the enantioselectivity and to
reduce the catalyst loading relies on the empirical modifica-
tion of the promoter. Nevertheless, Denmark’s group has
recently reported that the allylation of aldehydes using
phosphoramides as organocatalysts takes place by activation
of the allylsilane by two phosphoramide molecules.9 On the
basis of these findings, in the present study we report our
results on the allylation of benzoyl hydrazone 1 with
trichloroallyl silane 2, using enantiomerically pure methyl-
ene- and ethylene-bridged C2-symmetric bissulfoxides as
chiral promoters (Figure 1, Table 1).
Table 1. Enantioselective Allylation of 1 with Use of
Sulfoxides 4-63
[L*] reaction yield
entrya ligand equiv
(M)
time (h)
(%)b
(R)-3:(S)-3c
1
2
3
4
4
4
4
4
3.0
2.0
2.0
1.0
0.46
0.46
0.16
0.46
0.5
18
18
95
60
59
60
96:4
97:3
91:7
88:12
18
5
6
7
5
5
5
3.0
1.0
1.5
0.46
0.2
0.08
18
18
18
30
10
60
65:35
61:39
58:42
8
9
10
11
12
6
6
6
6
6
1.5
1.0
0.5
0.5
0.5
0.46
0.46
0.46
0.15
0.05
0.25
1.5
18
18
18
81
60
52
45
45
91:9
92:8
80:20
72:28
59:41
a Reactions were conducted in the presence of 0.5 equiv of 2-methyl-
2-butene to suppress ligand racemization. b Isolated yield. c Enantiomeric
excesses were determined by chiral HPLC analysis, using Daicel chiralpack
AD-column.
of lithiomethyl p-tolyl sulfoxide, following a method devel-
oped some 30 years ago by Mislow.11 As already observed
by Kobayashi and by us the concentration of the ligand in
the reaction is very important, the use of 2 equiv of 4 in a
0.46 M solution being the best concentration for a good
enantioselectivity. Any change in this concentration led to a
drop of the enantioselectivity (Table 1, entries 2 and 3).
Significantly, using the methylene-bridged bissulfoxide 5 in
these optimal conditions afforded the desired product 3, in
only 30% yield and 30% ee. Using fewer equivalents of the
ligands leads to a lower ee, while the dilution of the solution
afforded a mostly racemic allylated product.
On the other hand, the use of enantiomerically pure
ethylene-bridged bissulfoxide 6 afforded the allylated product
in excellent yield and excellent enantioselectivity (Table 1,
entry 8). The enantioselectivity is maintained when only 1
mol equiv of 6 is used (Table 1, entry 9). Significantly, the
allylated product 3 is still obtained with an interesting 60%
ee, when only 0.5 mol equiv of the ligand is used.
Nevertheless, upon diluting the reaction mixture, the enan-
tioselectivity drops to 48% ee at 0.15 M and to 18% ee when
the reaction is conducted at 0.05 M concentration.
Figure 1. Structure of C2-symmetric bissulfoxides used as chiral
promoters in allylation of benzoyl hydrazone.
Among the best sulfoxides found so far for the enantio-
selective allylation of benzoylhydrazones with allyl trichlo-
rosilane was the Andersen-Solladie´ reagent (R)-methyl
p-tolyl sulfoxide, which afforded the allylated product with
up to 97% ee and 98% yield.5 So, as a first comparative
study we conducted the allylation of hydrazone 1 with
trichloroallylsilane 2 using sulfoxide 4, together with (R,R)-
bis-(p-tolylsulfinyl)methane 5 and (R,R)-bis-(p-tolylsulfinyl)-
ethane 6. Bissulfoxide 5 was obtained by condensation of
lithiomethyl p-tolyl sulfoxide with (SS)-menthyl p-toluene-
sulfinate, as pioneered by Kuneida.10 On the other hand,
bissulfoxide 6 was obtained by Cu(I)-catalyzed dimerization
(7) (a) Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002,
35, 984. (b) Zhou, P.; Chen, B. C.; Davis, F. A. Tetrahedron 2004, 60,
8003.
(8) Kobayashi, S.; Sugiura, M.; Ogawa, C. AdV. Synth. Catal. 2004, 346,
1023.
(9) (a) Denmark, S. E.; Fu, J. J. Am. Chem Soc. 2000, 122, 12021. (b)
Denmark, S. E.; Fu, J. J. Am. Chem Soc. 2001, 123, 9488.
(10) (a) Kuneida, N.; Kinoshi, M.; Nokami, J. Chem. Lett. 1977, 289.
(b) Solladie´, G.; Colobert, F.; Ruiz, P.; Hamdouchi, C.; Carren˜o, C.; Garc´ıa-
Ruano, J. L. Tetrahedron Lett. 1991, 32, 3695. (c) Khiar, N.; Ferna´ndez,
I.; Alcudia, F. Tetrahedron Lett. 1993, 34, 123.
To evaluate the effect of the substituents at the sulfinyl
sulfur on the enantioselectivity of the process, various aryl
and alkyl ethylene-bridged C2-symmetric bissulfoxides were
(11) Mayarnoff, C. A.; Mayarnoff, B. E.; Tang, G.; Mislow, K. J. Am.
Chem. Soc. 1973, 95, 5839.
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Org. Lett., Vol. 9, No. 11, 2007