Functionalization of N-[(Silyl)methyl]-beta-lactam Carbanions with Carbon Electrophiles

Abstract

Latent acidity of alpha-alkyl-alpha-amino-N-[(silyl)methyl]-beta-lactams enabled a concise entry to lithium nonenolate N-methyl-azetidinone carbanions lithiated alpha' to the beta-lactam nitrogen, owing to the stabilizing "alpha-effect" of one or two trimethylsilyl groups. (n)BuLi/TMEDA and (t)BuLi/TMEDA were the bases of choice for complete deprotonation of di- and monosilylated beta-lactams, respectively. Trapping of the resulting carbanions with alkyl halides provided the corresponding N-[(alpha'-silyl)-alkyl]-beta-lactams, while carbon dioxide and related electrophiles such as benzyl chloroformates or isocyanates, afforded the corresponding silicon-free N-carboxymethyl-, N-benzyloxycarbonylmethyl-, and N-amidomethyl-beta-lactams in a single synthetic step. Likely structures of these unprecedented lithiated N-[(silyl)methyl]-beta-lactams were studied by MO calculations (B3LYP/6-31G**), and the origin of their relative stability was briefly discussed.