Powerful solvent effect of water in radical reaction: Triethylborane-induced atom-transfer radical cyclization in water

Triethylborane-induced atom-transfer radical cyclization of iodo acetals an d iodoacetates in water is described. Radical cyclization of iodo acetal pr oceeded smoothly both in aqueous methanol and in water. Atom-transfer radic al cyclization of allyl iodoacetate (3a) is much more efficient in water th an in benzene or hexane. For instance, treatment of 3a with triethylborane in benzene or hexane at room temperature did not yield the desired lactone. In contrast, 3a cyclized much more smoothly in water and yielded the corre sponding gamma -lactone in high yield. The remarkable solvent effect of wat er was observed in this reaction, although the medium effect is believed to be small in radical reactions. Powerful solvent effects also operate in th e preparation of medium- and large-ring lactones. Water as a reaction solve nt strikingly promoted the cyclization reaction of large-membered rings. St irring a solution of 3,6-dioxa-8-nonenyl iodoacetate in water in the presen ce of triethylborane at 25 degreesC for 10 h provided a 12-membered ring pr oduct, 4-iodo-6,9-dioxa-11-undecanolide, in 84% yield. On the other hand, r eaction in benzene afforded the lactone in only 22% yield. Ab initio calcul ations were conducted to reveal the origin of the solvent effect of water i n the cyclization of allyl iodoacetate. Calculations with the SCRF/CPCM opt ion indicate that the large dielectric constant of water lowers the barrier not only to rotation from the Z-rotamer to the E-rotamer that can cyclize but also to cyclization constructing the gamma -lactone framework. Moreover , the high cohesive energy density of water also effects acceleration of th e cyclization because water forces a decrease in the volume of the reactant .