Cyclization Reactions of Nucleoside Anomeric Radical with Olefin Tethered on Base: Factors That Induce Anomeric Stereochemistry

Abstract

Nucleoside anomeric radicals were formed through 1,5-translocation of vinyl radicals generated from the 2,2-dibromovinyl group tethered at the uracil 6-position (1, 2, and 4) by tin radical. The anomeric radicals attacked the resulting C-6 vinyl group in a 5-endo-trig manner to afford anomeric spiro nucleosides (11−13, 21, 23, and 24) with the 6,1‘-etheno bridge as the major cyclized products. The anomeric stereochemistry of the cyclization was found to be affected by the 2‘-substituent. To consider the structure of the intermediate anomeric radical, the reaction using α-6-(2,2-dibromovinyl)-2‘-deoxyuridine 9 was investigated. The same anomeric β/α-stereoselectivity as the counterpart of 2 showed that the nucleoside anomeric radical would have nearly a planar structure and the C1‘−N1 bond rotation in the radical is much faster than cyclization. The origin of the minor spiro nucleosides (14−20, 22, and 25−28) with the 6,1‘-ethano bridge has also been investigated and appeared to be (E)-6-(2-bromovinyl)urid...