Efficient and Expeditious Protocols for the Synthesis of Racemic and Enantiomerically Pure Endocyclic Enecarbamates from N-Acyl Lactams and N-Acyl Pyrrolidines

Denilson F. Oliveira; Paulo C. M. L. Miranda; Carlos R. D. Correia

doi:10.1021/jo9903297

Efficient and Expeditious Protocols for the Synthesis of Racemic and Enantiomerically Pure Endocyclic Enecarbamates from N-Acyl Lactams and N-Acyl Pyrrolidines

J Org Chem. 1999 Sep 3;64(18):6646-6652. doi: 10.1021/jo9903297.

Authors

Denilson F. Oliveira¹, Paulo C. M. L. Miranda, Carlos R. D. Correia

Affiliation

¹ Instituto de Química, Universidade Estadual de Campinas, P.O. Box 6154, Campinas, 13083-970 São Paulo, Brazil.

PMID: 11674667
DOI: 10.1021/jo9903297

Abstract

A mild, practical, and straightforward protocol for the construction of endocyclic enecarbamates starting from N-acyl lactams and N-acyl pyrrolidines is presented. Lactams were reduced to the corresponding alpha-hydroxycarbamates in good to excellent yields using DIBAL-H, SuperHydride, or NaBH(4) followed by beta-elimination (dehydration) promoted by trifluoroacetic anhydride in the presence of hindered nitrogenated bases such as 2,6-lutidine, diisopropylethylamine, or triethylamine. Small variations of this protocol permitted the preparation of several endocyclic enecarbamates (12 examples) in good to excellent overall yields (56-96%). The protocol was demonstrated to be applicable to several ring sizes, compatible with different protecting groups, and to be mild enough to prevent racemization of racemization-prone stereocenters. The efficacy of the procedure in the preparation of enantiomerically pure endocyclic enecarbamates was also demonstrated and compared to the commonly used Shono's protocol, which in our hands led to partial racemization of the endocyclic enecarbamate 18c.