348
(2)
In conclusion, we have shown that the enantio-enriched α-aminoalkyl cyanocuprate generated from
Pearson’s doubly chiral α-amino alkyllithium undergoes asymmetric Michael addition reactions with
overall retention of configuration at the carbanionic stereocenter. Of particular interest is the finding that
the reaction of the chiral higher-order cuprate with 2-cyclohexenone afforded the 1,4-adduct as a single
stereoisomer. Thus, the present type of asymmetric reaction provides an efficient method for asymmetric
synthesis of γ-amino carbonyl compounds. Further investigation to expand the scope of this approach is
in progress.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education,
Science, Sports and Culture, Japan, and by the Research for the Future Program, administered by the
Japan Society of the Promotion of Science.
References
1. For reviews, see: (a) Krause, N.; Gerold, A. Angew. Chem., Int. Ed. Engl. 1997, 36, 186–204. (b) Rossiter, B. E.; Swingle, N.
M. Chem. Rev. 1992, 92, 771–806. (c) Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis; Pergamon Press:
Oxford, 1992.
2. (a) Linderman, R. J.; Griedel, B. D. J. Org. Chem. 1991, 56, 5491–5493. (b) Linderman, R. J.; Griedel, B. D. J. Org. Chem.
1990, 55, 5428–5430.
3. To our knowledge, only a few examples of racemic α-amino alkylcyanocuprate are reported: (a) Dieter, R. K.; Sadanandan,
E. V. J. Org. Chem. 1997, 62, 3798–3799. (b) Dieter, R. K.; Alexander, C. W. Synlett 1993, 407–409. (c) Dieter, R. K.;
Alexander, C. W. Tetrahedron Lett. 1992, 33, 5693–5696.
4. Schöllkopf et al. have reported the asymmetric conjugate addition reaction of chiral bislactim–ether cuprates: Schöllkopf,
U.; Pettig, D.; Schulze, E.; Klinge, M.; Egert, E.; Benecke, B.; Noltemeyer, M. Angew. Chem., Int. Ed. Engl. 1988, 27,
1194–1195.
5. Beak et al. have reported the asymmetric conjugate addition reactions of enantio-enriched N-Boc anilino benzylic and allylic
organolithium species: Park, Y. S.; Weisenburger, G. A.; Beak, P. J. Am. Chem. Soc. 1997, 119, 10537–10538.
6. (a) Gawley, R. E.; Zhang, Q. J. Org. Chem. 1995, 60, 5763–5769. (b) Burchat, A. F.; Chong, J. M.; Park, S. B. Tetrahedron
Lett. 1993, 34, 51–54. (c) Chong, J. M.; Park, S. B. J. Org. Chem. 1992, 57, 2220–2222. (d) Gawley, R. E.; Rein, K. In
Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol 1, pp. 459–485. (e)
Gawley, R. E.; Rein, K. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon Press: Oxford,
1991; Vol 3, pp. 65–83.
7. (a) Pearson, W. H.; Lindbeck, A. C.; Kampf, J. W. J. Am. Chem. Soc. 1993, 115, 2622–2636. (b) Pearson, W. H.; Lindbeck,
A. C. J. Am. Chem. Soc. 1991, 113, 8546–8548.
8. Recently, we have reported the synthetic utility of the chiral α-amino organolithiums (B) in the context of asymmetric
synthesis of α-amino ketones and β-amino alcohols: Tomoyasu, T.; Tomooka, K.; Nakai, T. Synlett 1998, 1147–1149.
9. The presence of TMSCl is essential for this reaction. In the absence of TMSCl, only a destannylated product was obtained.
For a TMSCl effect on the conjugate addition, see: Bertz, S. H.; Miao, G.; Rossiter, B. E.; Snyder, J. P. J. Am. Chem. Soc.
1995, 117, 11023–11024, and references cited therein.
10. All the compounds were characterized by 1H and 13C NMR. Data for selected products are as follows. Compound 5a: 1H
NMR (CDCl3, 300 MHz) δ 0.84 (t, J=7.4 Hz, 3H), 1.23–1.45 (m, 2H), 1.79–1.90 (m, 1H), 2.02–2.15 (m, 1H), 2.38 (ddd,