Semipinacol Rearrangement of Cis-Fused β-Lactam Diols into Keto-Bridged Bicyclic Lactams

The 6-azabicyclo[3.2.1]octane ring system, prevalent in a range of biologically active molecules, is prepared through a novel semipinacol rearrangement utilizing a cyclic phosphorane or sulfite intermediate. The rearrangement proceeds with exclusive N-acyl group migration of a beta-lactam ring and results In carbonyl functionality at the 7-and bridging 8-position of the bicycle. Precursor ring-fused beta-lactam diols are prepared through a sequence of 4-exo trig carbamoyl radical cyclization, regloselective dithiocarbamate group elimination, and dihydroxylation.