Intromolecular reductive cyclization of alkynes and carbonyl compounds promoted by samarium(Ⅱ)iodide

Abstract

Intramolecular ketone (or aldehyde)-alkyne coupling reactions promoted by samarium(II) iodide have been investigated. Intramolecalar reductive cyclitations of carbonyl groups and alkynes promoted by samarium(II) iodide in the presence of HMPA and t-BuOH were successfully performed to provide functionalized carbocycles. The effect of the substituents(H, TMS, Ph, $CO_2R$) at the terminal site of alkyne on the cyclization was examined. Unexpectedly unactivated alkynes were cyclized to give five-membered rings albeit in low yields. In the case of trimethylsilyl substituted alkynes, cyclization proceeded only with methyl 5-trimethylsilyl-4-pentynyl ketone and this observation agrees with the reported results. The cyclization proceeded in reasonable yields with phenyl and ethoxycarbonyl substituted alkynes supporting this expectaion. Ketones always provided slightly better yields than aldehydes, and gave rise to E stereoisomers in all cases. Cyclizations to form six-membered rings were also successful in the reaction of activated alkynes in contrast to the cases with unactivated alkynes. This coupling reaction was successfully expanded to prepare the cyclized products(heterocycles) which contained heteroatoms such as oxygen or nitrogen. In this case, the reductive cyclization of alkoxycarbonyl substituted alkynes and carbonyl compounds proceeded in reasonable yields. Even though numerous synthetic methods have existed, the construction of quaternary carbon center still remains a challenging task to synthetic chemist. Methods for the construction of quaternary carbon center through radical intermediates have been investigated. The intramolecular reductive coupling between carbonyl groups(aldehydes or ketones) and activated tri-substituted alkenes(containing ethoxycarbonyl or cyano group) coupling reactions promoted by samarium(II) iodide has been investigated. This coupling can be utilized to generate a quaternary carbon center. The reductive coupling reactions produc...