Functionalization of N-[(silyl)methyl]-beta-lactam carbanions with carbon electrophiles.
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.
Palomo
Claudio
C
Departamento de Química Organica-I, Facultad de Química, Universidad del País Vasco, Apdo 1072, 20080 San Sebastian, Spain. qoppanic@sc.ehu.es
Aizpurua
Jesus M
JM
Benito
Ana
A
Cuerdo
Lourdes
L
Fratila
Raluca M
RM
Miranda
José I
JI
Linden
Anthony
A
D000478:Alkylation; D000586:Amination; D002244:Carbon / Q000737:chemistry*; D002245:Carbon Dioxide / Q000737:chemistry; D018360:Crystallography, X-Ray; D018020:Lithium Compounds / Q000737:chemistry; D008745:Methylation; D008958:Models, Molecular; D015394:Molecular Structure; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry*
D018020:Lithium Compounds; D047090:beta-Lactams; D002245:Carbon Dioxide; D002244:Carbon