ASYMMETRIC RADICAL CYCLIZATION LEADING TO BETA-LACTAMS - STEREOSELECTIVE SYNTHESIS OF CHIRAL KEY INTERMEDIATES FOR CARBAPENEM ANTIBIOTICS PS-5 AND THIENAMYCIN

A stereoselective synthesis of beta-lactams by 4-exo-trig radical cycl izations of N-[2,2-bis(phenylthio)ethenyl]-alpha-bromo amides bearing a chiral inductor on the nitrogen atom has been examined. Bromide 8, u pon treatment with Bu(3)SnH in the presence of AIBN in boiling benzene , gave a mixture of (4S)-2-azetidinone 12a and its (4R)-isomer 12b in a ratio of 71:29 and 69% combined yield. Similar treatment of alpha-br omobutanamide 11 with Bu(3)SnH afforded trans-(4S)-2-azetidinone 17a a s the major product along with its (4R)-isomer 17b (70:30, 77% combine d yield). Compound 17a was converted into 24, a chiral key intermediat e in the synthesis of (+)-PS-5 (25). The cyclization of bromide 28 bea ring an additional stereogenic center [(S)-oxygen functionality] at th e side chain proceeded with much higher (4S)-stereoselectivity to give azetidinone 29a as the major product together with its (4R)-isomer 29 b in a ratio of 78:22 and 40% combined yield. Compound 29a was convert ed. via an inversion of the oxygen functionality, into 37, a chiral ke y intermediate in the synthesis of (+)-thienamycin (38). A possible ex planation for the observed diastereoselectivity in radical cyclization s is presented.