US EPA

1171539 

Journal Article 

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

Yorimitsu, H; Nakamura, T; Shinokubo, H; Oshima, K; Omoto, K; Fujimoto, H 

2000 

Yes 

Journal of the American Chemical Society
ISSN: 0002-7863
EISSN: 1520-5126 

AMER CHEMICAL SOC 

WASHINGTON 

122 

45 

11041-11047 

English 

10.1021/ja0014281 

WOS:000165337800001 

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0041909866&partnerID=40&md5=d7c10aec670b57f6b1a3dd83c44072b9
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Triethylborane-induced atom-transfer radical cyclization of iodo acetals and iodoacetates in water is described. Radical cyclization of iodo acetal proceeded smoothly both in aqueous methanol and in water. Atom-transfer radical cyclization of allyl iodoacetate (3a) is much more efficient in water than 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 corresponding γ-lactone in high yield. The remarkable solvent effect of water was observed in this reaction, although the medium effect is believed to be small in radical reactions. Powerful solvent effects also operate in the preparation of medium-and large-ring lactones. Water as a reaction solvent strikingly promoted the cyclization reaction of large-membered rings. Stirring a solution of 3,6-dioxa-8-nonenyl iodoacetate in water in the presence of triethylborane at 25 °C for 10 h provided a 12-membered ring product, 4-iodo-6,9-dioxa-11-undecanolide, in 84% yield. On the other hand, reaction in benzene afforded the lactone in only 22% yield. Ab initio calculations were conducted to reveal the origin of the solvent effect of water in the cyclization of allyl iodoacetate. Calculations with the SCRF/CPCM option 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 γ-lactone framework. Moreover, the high cohesive energy density of water also effects acceleration of the cyclization because water forces a decrease in the volume of the reactant.