A new method for the synthesis of p-lactams by tributyltin hydride (Bu3SnH)-mediated radical cyclizations of N-ethenyl-a-bromo amides bearing sulfur-substituent(s) a t the terminus of the N-vinylic bond is described. N-[2-(Phenylthio)ethenyll-a-bromoacetamide (1 11, upon treatment with BuaSnH in the presence of azobis(isobutyronitri1e) (AIBN) in boiling toluene, underwent radical cyclization in a 4-exo-trig manner to give p-lactam 13, but in low yield (22%), whereas N-[2,2-bis-(pheny1thio)ethenyll congener 23 cyclized with a high degree of effeciency to give p-lactam 25 and a partially desulfurized lactam 13 in 70% combined yield. The effectiveness of the 4-exo cyclization of 23 can be explained in terms of the high stability of the intermediate of radical 19b. Similar treatment of a-bromobutanamide 24 with Bu3SnH afforded, in 58% yield, p-lactam 26, which was transformed, via aldehyde 31, into the key intermediate 35 for the synthesis of (~0 P s -5 (36). 1,2-Asymmetric induction in radical cyclizations leading to P-lactams was then examined. Cyclization of (2S,3R)-3-acetoxy-2-bromo-N-[2-(phenylthio)ethenyllbutanamide (38) proceeded with no diastereoselectivity to give p-lactams 40a and 40b in approximately equal amounts. However, 2,2-bis-(phenylthio) congener 39 provided (3R,4R)-2-azetidinone 41a and its (3S,4S)-isomer 41b in a ratio of ca. 2:l. Similarly, (2R,3S)-butanamide 47 afforded 48a as a major product. Saponification of 48a followed by partial desulfurization of 49 gave alcohol 50, which was then subjected to Mitsunobu inversion to d o r d 52. This compound was converted into the key intermediate 56 for the synthesis of (+)-thienamycin (58). Reversibility of the radical cyclization leading to the p-lactams is discussed.

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