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

摘要

Latent acidity of α-alkyl-α-amino-N-[(silyl)methyl]-β-lactams enabled a concise entry to lithium nonenolate N-methyl-azetidinone carbanions lithiated α′ to the β-lactam nitrogen, owing to the stabilizing "α-effect" of one or two trimethylsilyl groups. ~nBuLi/TMEDA and ~tBuLi/TMEDA were the bases of choice for complete deprotonation of di- and monosilylated β-lactams, respectively. Trapping of the resulting carbanions with alkyl halides provided the corresponding N-[(α′-silyl)-alkyl]-β-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-β-lactams in a single synthetic step. Likely structures of these unprecedented lithiated N-[(silyl)methyl]-β-lactams were studied by MO calculations (B3LYP/6-31G~*), and the origin of their relative stability was briefly discussed.