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Updated: Aug 6, 2026

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Functionalization of N-[(silyl)methyl]-beta-lactam carbanions with carbon electrophiles
Claudio Palomo1, Jesus M Aizpurua, Ana Benito
1Departamento de Química Organica-I, Facultad de Química, Universidad del País Vasco, Apdo 1072, 20080 San Sebastian, Spain. qoppanic@sc.ehu.es
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.
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