INTRAMOLECULAR RING-OPENING OF EPOXIDES BY BIS-ACTIVATED CARBANIONS - THE INFLUENCE OF RING SIZE ON REACTIVITY AND SELECTIVITY

A quantitative study on the effect of ring size in the intramolecular ring opening of epoxides by carbanions is described. Two series of substrates were examined: alpha,alpha-bis-sulfonyl omega-epoxides 1 and alpha-cyano-alpha-sulfonyl omega-epoxides 2; in each series the carbanion is tethered to the epoxide by a chain of variable length from one to four methylene groups. The nucleophile can attack either electrophilic position of the oxirane ring, or both; exo ring opening of cyano sulfonyl epoxides 2 is followed by a second cyclization leading eventually to bicyclic, fused gamma-lactones. Both series of epoxides show the same trend of reactivity as a function of ring size, in the formation of three- to seven-membered rings, with reactivity maxima corresponding to the formation of cyclopropane and cyclopentane derivatives. Unlike S(N)2 ring closure of omega-halogeno carbanions, cyclization to a five-membered ring is the fastest process in this case. The ratio k3/k5 between formation of three- and five-membered rings drops from over 100, in the S(N)2 cyclization of omega-iodo bis-sulfones, to less than 0.5, in the cyclization of omega-epoxy bis-sulfones 1. The difference is discussed in terms of trajectory of approach of the carbanion to the nucleophilic center. Cyclization of cyano sulfonyl epoxide 2a, in which the nucleophilic center and the epoxide are spaced by a single methylene group, is diastereoselective and leads to a bicyclic product with a cis fusion between the gamma-lactone and the cyclopropane ring.