Chem. Pharm. Bull. 53(8) 995—1002 (2005)

ways for carbon–carbon bond formation in organic synthesis. In particular, radical-mediated cyclization has been developed as a potential method for preparing various types of cyclic compounds via intramolecular carbon–carbon bond-forming processes. We have recently developed a new efficient carbon–carbon bond-forming reaction based on sulfanyl, stannyl and alkyl radical addition-cyclization (Chart 1). These radical reactions proceed via formation of a carbon-centered radical species A generated by the addition of a radical (Z · ) to a multiple bond (C A) in substrate 1 and subsequent intramolecular addition of the resulting carbon-centered radical A to a multiple bond (C B). The cyclized products 2 are highly functionalized compounds and thus are regarded as a useful key intermediate for further target molecules. The synthetic potentiality was demonstrated by the synthesis of anantine, oxo-parabenzlactone, a-kainic acid, cispentacin, and the A-ring fragment of 1a ,25-dihydroxyvitamin D3, balanol, deoxynojirimycin, martinelline and other functionalized lactones, lactams, and sultams. During the course of our previous investigations, we employed an isolated double bond, a ,b-unsaturated amide, oxime ether, hydrazone, nitrone, and the related imino groups as a radical acceptor and sulfur, carbon, tin, and silicon radical as a radical in the first step (1→A) of the addition reaction, respectively. However, it is not clarified what atom of the radical is the most suitable for the first step (1→A) in radical addition-cyclization and which double bond the newly formed radical A attacks in the second step (A→2). Therefore, we undertook a systematic study on radical addition–cyclization of substrates having three different radical acceptors such as acrylamide, isolated olefin, and oxime ether using sulfanyl and carbon radicals as the first-step radical (Chart 2). We report here for the first time that both sulfanyl and carbon radicals attack first the a ,b-unsaturated amide but the resulting radical exhibits different behavior. Treatment of 3 with either a sulfanyl radical or a carbon radical gave the lactam 4 or 5 as a respective major product. Additionally, a calculation study and rational explanation based on the result are also described.