Synthesis of enantiomerically pure cis-2,4-disubstituted piperidines: Extension of chiral homoenolate alkylations toward the preparation of nitrogen heterocycles

Tetrahedron Letters

Volumn 40, Issue 51, 1999, Pages 8965-8968

  Dwyer, Michael P ^a   Lamar, Jason E ^a   Meyers, A I ^a  

^a Veterinary Dentistry and Oral Surgery   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LACTAM DERIVATIVE; METHYL IODIDE; PIPERIDINE DERIVATIVE;

ALKYLATION; ARTICLE; CHIRALITY; ENANTIOMER; HYDROLYSIS; PARTIAL DRUG SYNTHESIS; REDUCTION; STEREOCHEMISTRY;

EID: 0033579607     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01784-0     Document Type: Article

References (28)

1. Elbein, A. D.; Molyneux, R. In Alkaloids; Chemical and Biological Perspectives; Pelletier, S. W., Ed.; John Wiley & Sons: New York, 1987; Vol. 57, p. 1.
2. For recent reviews for the preparation of piperidines, see: (a) Bailey, P. D.; Millwood, P. A.; Smith, P. D. Chem. Commun. 1998, 633.
3. (b) Nadin, A. J. Chem. Soc., Perkin Trans. 1 1998, 3493.
4. (a) Munchhof, M. J.; Meyers, A. I. J. Org. Chem. 1995, 60, 7084.
5. (b) Munchhof, M. J.; Meyers, A. I. J. Org. Chem. 1995, 60, 7086.
6. (c) Munchhof, M. J.; Meyers, A. I. J. Am. Chem. Soc. 1995, 117, 5399.
7. (a) Schwarz, J. B.; Devine, P. N.; Meyers, A. I. Tetrahedron 1997, 53, 8795.
8. (b) Schwarz, J. B.; Meyers, A. I. J. Org. Chem. 1998, 63, 1732.
9. (c) Schwarz, J. B.; Meyers, A. I. J. Org. Chem. 1998, 63, 1732.
10. (a) Matsumura, Y.; Yoshimoto, Y; Horikawa, C.; Maki, T.; Watanabe, M. Tetrahedron Lett. 1996, 37, 5715.
11. (b) Comins, D. L.; Killpac, M. O. J. Am. Chem. Soc. 1992, 114, 10972.
12. (c) Eynde, J.-J. V.; D'Orazio, P.; Mayence, A.; Maguestiau, A. Tetrahedron 1992, 48, 1263.
13. For related bicyclic lactam systems, see: (a) Amat, M.; Llor, N.; Hidalgo, J.; Hernandez, A.; Bosch, J. Tetrahedron: Asymmetry 1996, 7, 977.
14. (b) Amat, M.; Llor, N.; Hidalgo, J.; Bosch, J. Tetrahedron: Asymmetry 1996, 7, 1591.
15. (c) Billon-Souquet, F.; Martens, T.; Royer, J. Tetrahedron Lett. 1999, 40, 3731.
16. Devine, P. N.; Meyers, A. I. J. Am. Chem. Soc. 1994, 116, 2633.
17. Meerwein, H. Org. Syn., Coll. Vol. V. John Wiley & Sons: New York, p. 1080.
18. The use of 98% CuI has been found to be essential for good conversion to the desired α-cyanoenamine. It has been postulated that a Cu(II) salt present in trace amounts, is catalyzing this reaction although iodine has been shown to be essential; see Ref. 4a.
19. Oppolzer, W.; Petrizilka, M. Helv. Chim. Acta 1978, 61, 2755.
20. 3) confirmed the absolute configuration as shown in Scheme 1. This assignment is consistent with observations that have been made in related systems; see Ref. 4a.
21. (a) Meyers, A. I.; Snyder, L. J. Org. Chem. 1992, 57, 3814.
22. (b) Burgess, L. E.; Meyers, A. I. J. Org. Chem. 1992, 57, 1656.
23. (c) Meyers, A. I.; Burgess, L. E. J. Org. Chem. 1991, 56, 2294.
24. During the preparation of 2-substituted piperidines, Munchhoff and Meyers noted the use of these reactions conditions to afford an oxazolidine intermediate; see Ref. 3a.
25. Eliel, E. L.; Kandansamy, D.; Yen, C.-Y.; Hargrave, D. D. J. Am. Chem. Soc. 1980, 102, 3698.
26. Piperidine 8a was converted to the free base for comparison with the literature values.
27. Waldmann reported the first synthesis of piperidine hydrochloride salt 8a in optically pure form, however, it was characterized as an inseparable mixture of diastereomers at C4. The reported NMR data for the major diastereomer (absolute configuration unknown) is in excellent agreement with the values observed in this work suggesting a cis-2,4- dimethyl relationship for the major diastereomer. For the complete account, see: Waldmann, H. Liebigs Ann. Chem. 1989, 231.
28. Meyers, A. I.; Fray, A. H. Bull. Soc. Chim. Fr. 1997, 134, 283.