LETTER
Enantioselective Strecker Reaction Promoted by Chiral N-Oxides
1553
(6) For preparation of rac-1, see: Fujii, M.; Honda, A. J.
Heterocyclic Chem. 1992, 29, 931.
(7) For preparation of racemic 2–4, see: Thummel, R. P.;
Lefoulon, F. J. Org. Chem. 1985, 50, 666.
electronic density on the aryl ring of aldehyde subunit of
imine increased, enantioselectivity decreased (Table 2,
entries 4, 5). On the contrary, electron-deficient substrates
benefitted the reinforcement of enantiomeric excess
(Table 2, entries 6–9). It is worth noting that 3-nitro deriv-
ative afforded the corresponding product with 73% enan-
tiomeric excess17 (Table 2, entry 9) while Lipton et al
could only obtain essentially racemic products which they
thought was owe to racemizaton of the -amino nitrile.2a
(8) For the resolution of rac-1, see: Supporting Information of
ref.5a.
(9) For the resolution of rac-2, see: Nakajima, M.; Sasaki, Y.;
Shiro, M.; Hashimoto, S. Tetrahedron: Asymmetry 1997, 8,
341.
(10) Preparation of (+)-S-3,3’-trimethylene-2,2’-biquinoline
N,N’-dioxide ((+)-S-3)and (–)-3,3’-tetramethylene-2,2’-
biquinoline N,N’-dioxide ((–)-4):
In summary, chiral N-oxide R-2 has, thus, been demon-
strated to efficiently promote the asymmetric cyanation of
aldimines. The yields are good, but enantioselectivities
are still modest. To improve enantioselectivity, modifica-
tion of the promoter structure can be rationally based and
study on the mechanism of the reaction is underway.
To a solution of dibenzoyl-L-tartaric acid (L-DBTA) (47 mg,
0.13 mmol) in EtOH (0.28 mL) was added the solution of
racemic 3 (81 mg, 0.25 mmol) in CH2Cl2(5.6 mL). The
resulting clear solution was allowed to stand for 30 min at r.t.
to afford yellow prisms. Washing the solution of the yellow
prisms in CH2Cl2 (10mL), a sat. soln of NaHCO3 (3 10
mL), then evaporating organic layer gave optically pure (+)-
3 (> 99% ee) as a yellow solid (31 mg, 38%); mp 163–165
°C; [ ]D20 = +1263(c 0.24, CHCl3); 1H NMR: (ppm)2.38 (m,
2 H), 2.61 (m, 2 H), 3.21 (m, 2 H), 7.85–7.99 (m, 4 H), 8.20
(d, 2 H, J = 8.1), 8.42 (s, 2 H), 8.84 (d, 2 H, J = 8.1);
IR(nujol): 1342, 1319, 1246, 1216 cm–1; ee was determined
by chiral HPLC assay (Daicel Chiralcel OJ, n-hexane/
iPrOH = 65/35, 1.0 mL/min, UV: 254nm).
Acknowledgement
This research was assisted financially by grants from the National
Natural Science Foundation of China (No. 20072037).
References and Notes
(–)-4 was obtained with dibenzoyl-D-tartaric acid (D-
DBTA) according to a similar procedure to preparation of
(+)-3 as yellow solid with 97% ee; mp 205–207 °C; [ ]D
(1) For examples of asymmetric Strecker reaction catalyzed by
chiral Lewis acid, see: (a) Sigman, M. S.; Jacobsen, E. N. J.
Am. Chem. Soc. 1998, 120, 5315. (b) Ishitani, H.;
20
= –1247 (c = 0.22, CHCl3); 1H NMR: (ppm) 1.65 (m, 2 H),
2.17–2.40 (m, 4 H), 2.98–3.10 (m, 2 H), 7.67–7.74 (m, 6 H),
7.89 (d, 2 H, J = 7.8), 8.79 (d, 2 H, J = 8.4); IR(nujol): 1337,
1222, 1213 cm–1; ee was determined by chiral HPLC assay
(Daicel Chiralcel OJ, n-hexane/iPrOH = 65/35, 1.0 mL/min,
UV: 254nm).
Komiyama, S.; Kobayashi, S. Angew. Chem. Int. Ed. Eng.
1998, 37, 3186. (c) Krueger, C. A.; Kuntz, K. W.; Dzierba,
C. D.; Wirschun, W. G.; Gleason, J. D.; Snapper, M. L.;
Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 4284.
(d) Ishitani, H.; Komiyama, S.; Hasegawa, Y.; Kobayashi, S.
J. Am. Chem. Soc. 2000, 122, 762. (e) Porter, J. R.;
Wirschun, W. G.; Kuntz, K. W.; Snapper, M. L.; Hoveyda,
A. H. J. Am. Chem. Soc. 2000, 122, 2657. (f) Takamura,
M.; Hamashima, Y.; Usuda, H.; Kanai, M.; Shibasaki, M.
Angew. Chem. Int. Ed. 2000, 39, 1650. (g) Byrne, J. J.;
Chavarot, M.; Chavant, P.-Y.; Vallee, Y. Tetrahedron Lett.
2000, 41, 873. (h) Nogami, H.; Matsunaga, S.; Kanai, M.;
Shibasaki, M. Tetrahedron Lett. 2001, 42, 279.
(11) Full Crystallographic data will be deposited at the
Cambridge Crystallographic Data Centre.
(12) Preparation of (R)-5,5’,6,6’,7,7’,8,8’-octahydro-3,3’-
dimethyl-2,2’-biquinoline N,N’-dioxide (R-5): (R)-3,3’-
dimethyl-2,2’-biquinoline N,N’-dioxide (R-2) (100 mg, 0.32
mmol) was dissolved in CF3COOH (2ml), PtO2 (12 mg ) was
added, the solution was connected to the hydrogenator and
the air was removed, 50 psi pressure was applied and the
mixture was hydrogenated for 2 h. After usual work-up, of
R-5 (96 mg, 94% yield) was obtained as a colorless solid; mp
190–192 °C; [ ]D20 = +41.3(c = 0.54, CHCl3); 1H NMR
(CDCl3, 300 MHz): (ppm)1.76–1.92 (m, 8 H), 2.07 (s, 6 H),
2.79 (t, 4 H, J = 6.0), 2.83–3.09 (AA’BB’, 4 H), 6.99 (s, 2
H); 13C NMR (CDCl3, 75.5 MHz): (ppm)17.5, 21.6, 21.8,
24.4, 28.5, 128.1, 132.5, 135.7, 139.9, 146.5; IR(nujol):
cm–1 1310, 1289; ESI-HRMS: [M + H]+, 325.1909 (calcd for
C20H25N2O2, 325.1915).
(13) With 1 equiv of HCN in the absence of chiral N-oxide, the
reaction gave trace product after 24 h; but with 2 equiv of
HCN in the same condition, the product was obtained in 39%
yield after 30 h.
(14) (a) Wang, B.; Feng, X.; Cui, X.; Liu, H.; Jiang, Y. Chem.
Commun. 2000, 1605. (b) Chan, A. S. C.; Zhang, F.-Y.; Yip,
C.-W. J. Am. Chem. Soc. 1997, 119, 4080.
(2) For asymmetric Strecker reactions catalyzed by chiral
molecule, see: (a) Iyer, M. S.; Gigstad, K. M.; Namdev, N.
D.; Lipton, M. J. Am. Chem. Soc. 1996, 118, 4910.
(b) Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998,
120, 4901. (c) Corey, E. J.; Grogan, M. J. Org. Lett. 1999, 1,
157. (d) Vachal, P.; Jacobsen, E. N. Org. Lett. 2000, 2, 867.
(e) Sigman, M. S.; Vachal, P.; Jacobsen, E. N. Angew. Chem.
Int. Ed. 2000, 39, 1279.
(3) (a) Karayannis, N. M.; Pytlewski, L. L.; Mikulski, C. M.
Coord. Chem. Rev. 1973, 11, 93. (b) Dyker, G.; Holzer, B.;
Henkel, G. Tetrahedron: Asymmetry 1999, 10, 3297.
(4) (a) O’Neil, I. A.; Turner, C. D.; Kalindjian, S. B. Synlett
1997, 777. (b) Miura, K.; Katsuki, T. Synlett 1999, 783.
(c) Dyker, G.; Holzer, B.; Henkel, G. Tetrahedron:
Asymmetry 1999, 10, 3297. (d) Derdau, V.; Laschat, S.;
Hupe, E.; Konig, W. A.; Dix, I.; Jones, P. G. Eur. J. Inorg.
Chem. 1999, 1001. (e) Saito, M.; Nakajima, M.; Hashimoto,
S. Chem. Commun. 2000, 1851.
(15) A general experimental procedure is given: After a mixture
of R-2 (31.6 mg, 0.1 mmol) and imine (0.1 mmol) was kept
in vacuo for 0.5 h and CH2Cl2 (0.5 mL) was added. The
resulting solution was cooled to 0 °C and TMSCN (26.7 L,
0.2 mmol) was added. The reaction was stopped by
evaporating the solvent directly and the crude residue was
purified by chromatography (SiO2, Et2O–hexanes) to afford
(5) (a) Diana, M. B.; Marchetti, M.; Melloni, G. Tetrahedron:
Asymmetry 1995, 6, 1175. (b) Nakajima, M.; Saito, M.;
Shiro, M.; Hashimoto, S. J. Am. Chem. Soc. 1998, 120,
6419. (c) Nakajima, M.; Saito, M.; Hashimoto, S. Chem.
Pharm. Bull. 2000, 48, 306. (d) Tao, B.; Lo, M. M.-C.; Fu,
G. C. J. Am. Chem. Soc. 2001, 123, 353.
Synlett 2001, No. 10, 1551–1554 ISSN 0936-5214 © Thieme Stuttgart · New York