Synthesis of 1-Azabicyclo[1.1.0]butane and Its Application to Synthesis of New Antibiotics

Abstract

The efficient large-scale synthesis of 1-azabicyclo[1.1.0]butane (ABB) by treatment of 2,3-dibromopropylamine hydrobromide with n-BuLi was successfully established by our research group. In the consecutive cyclization of 2,3-dibromopropylamine with n-BuLi, a possible reaction mechanism generating initially 2-bromomethylaziridine and then ABB has been revealed by utilizing some model experiments, in which an intramolecular S_N2-type N–C bond formation involving the Br...Li coordination must be plausible. ABB has been exploited for expeditious syntheses of a number of useful azetidine derivatives. Several compounds of them have been employed for the syntheses of a new oral 1β-methylcarbapenem antibiotic L-084 and new quinolone antibiotics.

Scheme 1