Communications
[
a]
Table 2: Asymmetric 1,4-addition of 1 in the presence of ATPH analogues.
[
b]
[c]
[d]
Entry
1
Organolithium
MeLi
Al reagent
Product
R
Yield [%]
de [%]
Abs. config.
5
3g
Me
99
94
S
2
3
allyl-Li
allyl-Li
4
5
3h
3h
97
99
93
95
S
S
4
5
methallyl-Li
prenyl-Li
5
4
3i
92
99
(6.0:1)
99
(5.5:1)
99
(8.5:1)
97
–
–
3b
a: 98;
g: 97
a: 99;
g: 99
a: 99;
g: 98
[
[
[
e]
e]
e]
3
c
6
7
prenyl-Li
prenyl-Li
5
6
3b
–
–
3
c
3b
3
c
8
5
3j
99
99
–
[a] Unless otherwise specified, the reaction was performed with ATPH (1.1 equiv), the chiral ester (1.0 equiv), THF (100 vol%), and RM (1.5 or
2
.0 equiv) in toluene.[b] Yield of isolated, purified alcohols derived by reduction of crude 3. [c] Diastereomeric excess was determined by chiral HPLC
analysis of the corresponding alcohols. [d] Absolute configurations were determined by comparison to literature values. See the Supporting
Information. [e] a-Adduct 3b:g-adduct 3c.
[
13]
20
1
compound: [a]D = À1.28 (c = 1.02, CHCl , for 94% ee); H NMR
3
Although the reactions gave virtually complete yields and
diastereoselectivities for several organolithium reagents, we
found that MeLi and allylic reagents were less suitable. For
example, attempts to use MeLi and allyllithium resulted in
lower diastereoselectivities (86% and 78% de, respectively).
The present strategy facilitates the rational molecular design
ofATPH. Several ATPH analogues were synthesized based
on the X-ray structure and used for the asymmetric 1,4-
addition (Table 2). We observed considerable increase not
only in diastereoselectivities for 3b,g–j (entries 1–8) but also
in the a-selectivity in the reaction with prenyllithium
(
300 MHz, CDCl ): d = 7.50 (m, 5H), 3.50 (m, 2H), 2.67 (m, 1H,),
3
1
6
.83 (m, 2H), 1.61 (m, 2H), 1.22 (m, 4H), 0.83 ppm (t, 3H, J =
.9 Hz). HPLC analysis (OD-H, 1.0 mLmin flow rate, hexane/2-
À1
propanol 40:1 as eluent): t = 12.8 (minor) and t = 15.4 min (major;
S, determined by comparing the value in ref.[13b]). After converting
to the corresponding acid: [a] = + 6.42 (c = 1.04, CHCl ).
R
R
2
D
0
3
Experimental procedures, spectroscopic, and analytical data for
all new compounds, and the X-ray data for the ATPH complex 2
(PDF) are included in the Supporting Information.
Received: September 8, 2003 [Z52809]
(
entries 5–7). The effectiveness of these ATPH analogues in
Keywords: aluminum · asymmetric synthesis · chiral auxiliaries ·
Michael addition · molecular recognition
.
remote stereocontrol, such as asymmetric 1,6-addition, is now
being investigated in our laboratory.
[
1] a) J. Leonard, E. Díez-Barra, S. Merino, Eur. J. Org. Chem. 1998,
2051; b) M. Kanai, Y. Nakagawa, K. Tomioka, Synth. Org. Chem.
Jpn. 1996, 54, 474; c) B. E. Rossiter, N. M. Swingle, Chem. Rev.
1992, 92, 771.
Experimental Section
The following procedure for the reaction of (1R,2S)-2-phenylcyclo-
hexyl cinnamate and n-butyllithium is representative. To a solution of
ATPH (0.33 mmol) in toluene (3.0 mL) was added (1R,2S)-2-phenyl-
cyclohexyl cinnamate (1) (91.9 mg, 0.30 mmol) in toluene (0.5 mL) at
room temperature under Ar. After the mixture had been stirred for
[2] a) B. L. Feringa, Acc. Chem. Res. 2000, 33, 346; b) K. Tomioka,
Y. Nagaoka in Comprehensive Asymmetric Catalysts, Vol. III
(Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer,
Berlin, 1999, p. 1105; c) D. A. Evans, T. Rovis, J. S. Johnson,
Pure Appl. Chem. 1999, 71, 1407; d) Y. Takaya, M. Ogasawara, T.
Hayashi, M. Sakai, N. Miyaura, J. Am. Chem. Soc. 1998, 120,
5579; e) T. Hayashi, T. Senda, Y. Takaya, M. Ogasawara, J. Am.
Chem. Soc. 1999, 121, 11591; f) T. Hayashi, T. Senda, M.
Ogasawara, J. Am. Chem. Soc. 2000, 122, 10726; g) S. J.
Degrado, H. Mizutani, A. H. Hoveyda, J. Am. Chem. Soc.
2002, 124, 13362; h) A. W. Hird, A. H. Hoveyda, Angew. Chem.
2003, 115, 1314; Angew. Chem. Int. Ed. 2003, 42, 1276.
5
min, it was cooled to À788C. THF (3.0 mL) was added dropwise,
and the reaction mixture was stirred for 1 h. To the mixture was added
nBuLi (1.55m, 290 mL, 0.45 mmol) dropwise at the same temperature.
The reaction mixture was stirred for 1 h and quenched with aqueous
hydrogen chloride (1.0m, 5 mL). The organic layer was extracted with
ether, dried over Na SO , and concentrated. The residue was
2
4
dissolved in THF (9.0 mL) and reduced with LiAlH (92%, 63 mg,
4
1
.5 mmol) under Ar at 08C, and stirred for 1 h at room temperature.
The reaction mixture was quenched by a dropwise addition ofMeOH
and neutralized with a 1.0m aqueous HCl. The organic layer was
extracted with ether, dried over Na SO , and concentrated. The
[3] G. Roos, Compendium of Chiral AuxiliaryApplications , Aca-
demic Press, San Diego, 2002.
2
4
residue was purified by column chromatography on silica gel (ether/
hexane 1:3 to 1:2 as the eluent) to give 3-phenylheptanol (99% yield,
[4] For preliminary communication and related work for the present
article, see: a) S. Saito, M. Shiozawa, T. Nagahara, M. Nakadai,
H. Yamamoto, J. Am. Chem. Soc. 2000, 122, 7847; b) S. Saito, M.
9
7% de) as the reduced 1,4-adduct. (S)-3-Phenylheptan-1-ol, known
9
96
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2004, 43, 994 –994