Synthesis of Homochiral α-Substituted Alanine Derivatives by Diastereocontrolled Alkylation of (5R)-5-Phenyl-3-methyl-3,4-dehydromorpholinones

Synlett

Volumn 1996, Issue 11, 1996, Pages 1051-1053

  Harwood, L M ^a   Vines, K J ^a   Drew, M G B ^a  

^a UNIVERSITY OF READING   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0012963845     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-1996-5682     Document Type: Article

References (19)

1. Cooper, N.; Cox, G. C.; Ager, D.; Garro-Helion, F.; Harwood, L. M. Tetrahedron Asym., 1996, 7, 2563.
2. Cox, G. C.; Harwood, L. M. Tetrahedron Asym., 1994, 5, 1669.
3. For a recent synthesis of α-substituted alanines and leading references, see: Berkowitz, D. B.; Smith, M.B. J.Org. Chem., 1995, 60, 1233.
4. All of the following use n-BuOH to effect simultaneous ester and imine formation: a) Berkowitz, D. B.; Schweizer, W. B. Tetrahedron, 1992, 48, 1715. b) Jiao, X.-Y.; Chen, W.-Y.; Hu, B.-F. Synth. Comm., 1992, 22, 1179. c) Himmelsbach, R. J.; Barone, A. D.; Kleyer, D. L.; Koch, T. H. J. Org. Chem., 1983, 48, 2989.
5. All of the following use n-BuOH to effect simultaneous ester and imine formation: a) Berkowitz, D. B.; Schweizer, W. B. Tetrahedron, 1992, 48, 1715. b) Jiao, X.-Y.; Chen, W.-Y.; Hu, B.-F. Synth. Comm., 1992, 22, 1179. c) Himmelsbach, R. J.; Barone, A. D.; Kleyer, D. L.; Koch, T. H. J. Org. Chem., 1983, 48, 2989.
6. All of the following use n-BuOH to effect simultaneous ester and imine formation: a) Berkowitz, D. B.; Schweizer, W. B. Tetrahedron, 1992, 48, 1715. b) Jiao, X.-Y.; Chen, W.-Y.; Hu, B.-F. Synth. Comm., 1992, 22, 1179. c) Himmelsbach, R. J.; Barone, A. D.; Kleyer, D. L.; Koch, T. H. J. Org. Chem., 1983, 48, 2989.
7. Agami has previously reported the exclusive formation of an oxazoline related to 2 from the reaction of ethyl glyoxylate and phenyl glycinol in refluxing toluene: Agami, C.; Couty, F.; Mathieu, H. Tetrahedron Lett., 1996, 37, 4001. It is proposed that preferred attack of the imine electrophilic centre can be explained by the HSAB theory: Agami, C.; Couty, F.; Prince, B.; Venier, O. Tetrahedron. Lett., 1993, 34, 7061.
8. Agami has previously reported the exclusive formation of an oxazoline related to 2 from the reaction of ethyl glyoxylate and phenyl glycinol in refluxing toluene: Agami, C.; Couty, F.; Mathieu, H. Tetrahedron Lett., 1996, 37, 4001. It is proposed that preferred attack of the imine electrophilic centre can be explained by the HSAB theory: Agami, C.; Couty, F.; Prince, B.; Venier, O. Tetrahedron. Lett., 1993, 34, 7061.
9. +.
10. Non-commercial α-ketoesters were prepared following the procedure of: Kanakarajan, K.; Haider, K.; Czarnik, A. W. Synthesis, 1988, 566.
11. 3) 7.77 (2 H, d, J 6.5 Hz), 7.51-7.32 (3 H, m), 5.41 (1 H, dd, J 16, 1 Hz), 5.31 (1 H, dd, J 16, 2.5 Hz), 4.36 (1 H, t, J 7 Hz), 2.08 (1 H, sept, J 6.5 Hz), 1.95-1.78 (2 H, m), 1.02 (6 H, dd, J 6.5, 4 Hz).
12. We observed complex product mixtures resulting from alkylation of the ester. Others have observed similar results: (a) Fiaud, J.; Kagan, H. B. Tetrahedron Lett., 1970, 1813; b) Shafer, C. M.; Molinski, T. F. J. Org. Chem., 1996, 61, 2044-2050. Alkylation of electron deficient imines with Grignard reagents has been reported: Burger, K.; Sewald, N. Synthesis, 1990, 115.
13. We observed complex product mixtures resulting from alkylation of the ester. Others have observed similar results: (a) Fiaud, J.; Kagan, H. B. Tetrahedron Lett., 1970, 1813; b) Shafer, C. M.; Molinski, T. F. J. Org. Chem., 1996, 61, 2044-2050. Alkylation of electron deficient imines with Grignard reagents has been reported: Burger, K.; Sewald, N. Synthesis, 1990, 115.
14. We observed complex product mixtures resulting from alkylation of the ester. Others have observed similar results: (a) Fiaud, J.; Kagan, H. B. Tetrahedron Lett., 1970, 1813; b) Shafer, C. M.; Molinski, T. F. J. Org. Chem., 1996, 61, 2044-2050. Alkylation of electron deficient imines with Grignard reagents has been reported: Burger, K.; Sewald, N. Synthesis, 1990, 115.
15. +, 190, 104.
16. -3, F(000) = 472. 1970 independent reflections were collected on a Marresearch Image Plate and 1490 reflections with I > 2s(I) were used in the analysis. The structure was solved by direct methods and refined by full-matrix least squares (non-hydrogen atoms anisotropic and hydrogen atoms isotropic in calculated positions) and refined using Shelxl[3]. Final R = 7.07. Crystal data have been deposited at the Cambridge Crystallographic Data Centre.
17. 3OD) 7.18-7.04 (5 H, m), 2.62 (1 H, ddd, J 13.5, 12.5, 4.5 Hz), 2.50 (1 H, ddd, J 13.5, 12.5, 4.5 Hz), 2.05 (1 H, ddd, J 13.5, 12.5, 4.5 Hz), 1.82 (1 H, ddd, J 13.5, 12.5, 4.5 Hz), 1.4 (3 H, s).
18. Schöllkopf, U.; Lonsky, R. Synthesis, 1983, 675.
19. Seebach, D.; Fadel, A. Helv. Chim. Acta, 1985, 68, 1243.