The influence of benzylic protection and allylic substituents on the CuCl-TMEDA catalyzed rearrangement of N-allyl-N-benzyl-2,2-dihaloamides to gamma-lactams. Application to the stereoselective synthesis of pilolactam.

A number of N-benzylic protecting groups and allylic substituents have been investigated for the rearrangement, promoted by CuCl-TMEDA, of N-allyl-2,2-dihaloamides to 3,4-disubstituted gamma-lactams. An appreciable chiral induction was observed at the C-4 site when alpha-phenylethylamine was used as a chiral protecting group, while an unexpected Diels-Alder reaction occurred when using a 2-furyl-methyl protection. This rearrangement has been applied to the synthesis of pilolactam, a drug with muscarinic activity. (C) 1999 Elsevier Science Ltd. All rights reserved.