A practical one-pot synthesis of trans-4,5-disubstituted 2-pyrrolidinones and the related pyrrolidines

Tetrahedron Letters

Volumn 38, Issue 29, 1997, Pages 5091-5094

  Yee, Nathan K ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 PYRROLIDONE DERIVATIVE; PYRROLIDINE DERIVATIVE;

ARTICLE; DIASTEREOISOMER; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0030835387     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)01134-9     Document Type: Article

References (19)

1. Recent review on pyrrolidinone/pyrrolidine synthesis: see Harrison, T. Contemporary Organic Synthesis, 1996, 209.
2. (a) Elliott, R. L.; Kopecka, H.; Lin, N-H.; He, Y.; Garvey, D. S. Synthesis, 1995, 772.
3. (b) Strubbe, J.; Linz, R. US Patent 3956314, 5/11/76.
4. (c) Lin, N-H.; Carrera, G. M. Jr.; Anderson, D. J. J. Med. Chem. 1994, 37, 3542.
5. (d) Shih, N-Y.; Lupo, A. T. Jr.; Aslanian, R.; Orlando, S.; Piwinski, J. J.; Green, M. J.; Ganguly, A. K.; Clark, M. A.; Tozzi, S.; Kreutner, W.; Hey, J. A. J. Med. Chem. 1995, 38, 1593.
6. Pal, K.; Behnke, M.; Adams, J. US Patent 5594008, 1/14/97.
7. Roth, G. P.; Emmanuel, M.; Tong, L. Tetrahedron Asymmetry, 1997, 8, 185.
8. Dehmlow, E. V.; Dehmlow, S. S. Phase Transfer Catalysis, 3rd Ed., 1993, VCH Publishers, Inc., New York, NY.
9. For phase transfer catalysis reactions of benzylidenebenzylamine with cinnnamic acid derivatives. see: Potapov, V. M.; Gracheva, R. A.; Sivova, N. A. Zh. Org. Khim. 1989, 25, 1876.
10. For stereoselective Michael additions of metal enolates of α-amino ester. see: (a) Tatsukawa, A.; Dan, M.; Ohbatake, M.; Kawatake, K.; Fukata, T.; Wada, E.; Kanemasa, S.; Kakei, S. J. Org. Chem. 1993, 58, 4221.
11. (b) Kanemasa, S.; Uchida, O.; Wada, E. J. Org. Chem. 1990, 55, 4411.
12. 2: C, 71.62; H, 6.01; N, 10.44. Found: C, 71.51; H, 5.97; N, 10.42.
13. 3,400 MHz) δ 8.53 (d, J = 4.2 Hz, 1H), 7.74 (br. s, 1H), 7.59 (br. d, J = 8.4 Hz, 1H), 7.50 - 7.20 (m, 7H), 7.14 (br. s, 1H), 7.03 (d, J = 8.6 Hz, 2H), 6.82 - 6.69 (m, 1H), 6.70 (d, J = 8.7 Hz, 2H), 6.52 (br. s, 2H), 4.73 (br. s, 1H), 4.05 (dt, J = 5.1 and 5.1 Hz, 1H), 3.95 - 3.83 (m, 2H), 3.75 (s, 3H), 3.02, 2.78 (AMX, J = 15.6, 10.9, and 4.7 Hz, 2H), 1.03 (t, J = 7.2 Hz, 3H).
14. It was observed the syn-6 cyclized at a faster rate than the corresponding anti-6 under the given conditions, and hence the trans:cis ratio (93:7) of 7 was higher than the syn:anti ratio (88:12) of 5.
15. Pal, K.; Behnke, M.; Tong, L. Tetrahedron Lett. 1993, 34, 6205.
16. Brown, H. C.; Choi, Y. M.; Narasimhan, S. J. Org. Chem. 1982, 47, 3153.
17. 13C NMR spectroscopy.
18. 2O (from Aldrich) was used as base, A 37% deuterium incorporation was observed at the C-4 methine position of the Michael adduct 5;
19. 2O, toluene, rt, 14 h), no deuterium incorporation was observed at the C-4 methine position of 5.