Synthesis of a key intermediate to 1β-methylcarbapenem antibiotics via iodoamidation

Abstract

A stereoselective synthesis of the key intermediate 8 of 1β-methylcarbapenem antibiotics was accomplished. The key features of the scheme include the stereoselective iodoamidation of Z-olefinic allylic alcohol 76 and the regioselective ring opening of aziridine 80c with cyanide. Z-olefinic allylic alcohol 76 was prepared by Wittig reaction of phosphonium salt 74 and aldehyde 71, then transformed into the desired cis-aziridine 80c by stereoselective iodoamidation, acidic hydrolysis and cyclization in sequence. Aziridine 80c was ring-opened with moderate regioselectivity by cyanide in 70% yield employing the freshly generated LiCN-HMPA reagent. Formation of b-lactam 96 from amide 95 was unexpectedly accomplished by its treatment with di-t-butyl dicarbonate. The prepared b-lactam 96 was detosylated at low temperature, then the primary hydroxy group was unmasked. Azitidinone alcohol 33 was converted into the desired product 8 by oxidation with PDC.