Aziridines in Heteroannulation. Synthesis of 1,4-Benzodiazepines

Significance

Reported here is a one-pot synthesis of 1,4-benzodiazepine derivatives C by treatment of 1-arylaziridine-2-carboxylate B with (2-bromomethyl)trifluoroacetamides A in the presence of base (Et₃N). The reaction proceeds through N-benzylation and highly regioselective ring opening of aziridine by the bromide ion (intermediate of type D), which upon intramolecular N-alkylation leads to the 1,4-benzodiazepine products. In the prototype case, intermediates D and E (10:1 ratio) were isolated (in the absence of base) and subjected to further intramolecular cyclization using different bases. Interestingly, NaOH and DABCO as bases afforded F as the only product, while K₂CO₃ and Cs₂CO₃ gave mixtures of C and F (1:2 and 3:1 ratios, respectively). The best yields of benzodiazepine products C were observed using Et₃N as base. The yields are moderate to good for a one-pot reaction although the scope of the reaction was not well explored.