Chemistry Letters 2002
161
Table 2. Catalytic enantioselective rearrangement of epoxidesa
of chiral lithium amide 1b.
Financial supports from the Fujisawa Foundation and the
Japan Securities Scholarship Foundation, and gift of
a
(2S,3aS,7aS)-octahydroindole-2-carboxylic acid from Kawaken
Fine Chemicals Co., Ltd. are gratefully acknowledged. The
authors thank Prof. Masao Tomoi (Yokohama National Uni-
versity) for valuable discussions.
Dedicated to Prof. Teruaki Mukaiyama on the occasion of his
75th birthday.
References and Notes
1
K. Koga, J. Synth. Org. Chem., Jpn., 48, 463(1990); P. J. Coxand N.
S. Simpkins, Tetrahedron: Asymmetry, 2, 1 (1991); K. Koga, Pure
Appl. Chem., 66, 1487(1994); K. Koga and M. Shindo, J. Synth.
Org. Chem., Jpn., 53, 1021 (1995); N. S. Simpkins, Pure Appl.
Chem., 68, 691 (1996); D. M. Hodgson, A. R. Gibbs, and G. P. Lee,
Tetrahedron, 52, 14361 (1996); P. O’Brien, J. Chem. Soc., Perkin
Trans. 1, 1998, 1439.
2
3
M. Asami, J. Synth. Org. Chem., Jpn., 54, 188 (1996); M. Asami, M.
Ogawa, and S. Inoue, Tetrahedron Lett., 40, 1563 (1999); M.
Asami, S. Sato, K. Honda, and S. Inoue, Heterocycles, 52, 1029
(2000)
a) M. Asami, T. Ishizaki, and S. Inoue, Tetrahedron: Asymmetry, 5,
793 (1994). b) M. Asami, T. Suga, K. Honda, and S. Inoue,
Tetrahedron Lett., 38, 6425 (1997). c) M. J. Sodergren, S. K.
¨
Bertilsson, and P. G. Andersson, J. Am. Chem. Soc., 122, 6610
(2000).
4
For example, J. M. Maud, in ‘‘Solid Supports and Catalysts in
Organic Synthesis,’’ ed. by K. Smith, Ellis Horwood Limited, West
Sussex (1992), Chap. 6, p 171; S. J. Shuttleworth, S. M. Allin, and
P. K. Sharma, Synthesis, 1997, 1217; B. Clapham, T. S. Reger, and
K. D. Janda, Tetrahedron, 57, 4637(2001).
Then, we applied the new system to a chiral lithium amide 1b,
prepared from (2S,3aS,7aSÞ-2-(pyrrolidin-1-ylmethyl)octahy-
droindole, which showed much higher selectivity than 1a in the
reaction.3b (S)-2-Cyclohexenol was obtained in good yield with
very high ee (94% ee) by using 0.2 equiv of 1b and 1.8 equiv of 2d
(Table 2, Entry 1). Although the ee of the product was decreased
slightly as the amount of 1b was reduced (Table 2, Entries 2, 3),
the alcohol as high as 92% ee was obtained in high yield by
decreasing the amount of 2d to 1.45 equiv (Table 2, Entry 4). It is
of interest that the selectivity of the reaction was enhanced using
0.05 equiv of 1b and 1.45 equiv of 2d (92% ee) as compared with
thatusing stoichiometric amount(1.5 equiv)of 1b (89%ee) bythe
reaction at rt.3b As the good result was obtained for cyclohexene
oxide, the reaction was applied to cycloheptene oxide, cis-4-
octene oxide, and cis-5-decene oxide using 0.05 equiv of 1b and
1.45 equiv of 2d. High selectivity was achieved in every case and
the corresponding (S)-alcohols were obtained in high enantio-
selectivities (>92% ee) (Table 2, Entries 6–8). It should be noted
that the selectivity of the reaction with cis-4-octene oxide
(Table 2, Entry 7) was significantly improved compared with that
obtained using 0.2 equiv of 1b with 1.8 equiv of LDA (85%, 83%
ee).3b
5
6
Recently, an aldol reaction by the use of polymer-bound lithium
amides was reported: M. Majewski, A. Ulaczyk, and F. Wang,
Tetrahedron Lett., 40, 8755 (1999).
M. Tomoi, Y. Akada, and H. Kakiuchi, Makromol. Chem., Rapid
Commun., 3, 537(1982). Polymer-bound N-isopropyl-p-vinyl-
benzylamine: Anal. Calcd for (C8H8)0:78Á(C12H17N)0:2
(C10H10 0:02: C, 89.30; H, 8.34; N, 2.36%. Found: C, 88.90; H,
8.58; N, 2.52%. Polymer-bound N-cyclohexyl-p-vinylbenzyl-
amine: Anal. Calcd for (C8H8)0:78Á(C15H21N)0:2Á(C10H10 0:02: C,
89.34; H, 8.45; N, 2.21%. Found: C, 89.25; H, 8.22; N, 2.16%.
Á
)
)
7Typical experimental procedure (Table 2, Entry 1) is as follows; To
the mixture of polymer-bound N-cyclohexyl-p-vinylbenzylamine
(1.17g) and (2 S,3aS,7aSÞ-2-(pyrrolidin-1-ylmethyl)octahydroin-
dole (42 mg, 0.20 mmol) in THF (9 mL) was added a hexane
solution of butyllithium (1.24 mL, 2.0 mmol) at rt and stirred for
0.5 h. Cyclohexene oxide (98 mg, 1.0 mmol) in THF (1 mL) was
added to the mixture and stirring was continued for 12 h at rt. After
quenching with saturated aqueous NH4Cl, the resin was removed by
filtration and washed well with CH2Cl2. The organic layer was
washed with 1 M HCl and brine, successively, and dried over anhyd
Na2SO4. After removal of the solvent at atmospheric pressure, the
resulting crude product was benzoylated with benzoyl chloride,
pyridine, and a catalytic amount of 4-N; N-dimethylamino-
pyridine. After the addition of excess N; N-dimethyl-1,3-propan-
diamine, water was added to the mixture. The organic layer was
washed with 1 M HCl and brine, successively, and dried over anhyd
Na2SO4. The organic layer was concentrated in vacuo and the crude
product was purified by preparative TLC, followed by bulb-to-bulb
distillation (120 ꢁC/0.65 mmHg) to give (S)-2-cyclohexenyl benzo-
In conclusion, we have prepared polymer-bound lithium
amide 2c,d and shown the intriguing effect of 2c,d as a superior
reagent to regenerate chiral lithium amide in situ in the catalytic
enantioselective deprotonation of meso-epoxides, and chiral
allylic alcohols were obtained in up to 95% ee using 0.05 equiv
20
ate (180 mg, 89%, ½ꢀꢂD ꢃ210:2 ꢁ (c 1.00, CHCl3)). The ee was
determined to be 94% by HPLC analysis using Opti-pak TA.