Cyclization reactions of nucleoside anomeric radical with olefin tethered on base: Factors that induce anomeric stereochemistry

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 maj or cyclized products. The anomeric stereochemistry of the cyclization was f ound to be affected by the 2'-substituent. To consider the structure of the intermediate anomeric radical, the reaction using alpha-6-(2,2-dibromoviny l)-2'-deoxyuridine 9 was investigated. The same anomeric beta/alpha-stereos electivity as the counterpart of 2 showed that the nucleoside anomeric radi cal would have nearly a planar structure and the C1'-N1. bond rotation in t he radical is much faster than cyclization. The origin of the minor spiro n ucleosides (14-20, 22, and 25-28) with the 6,1'-ethano bridge has also been investigated and appeared to be (E)-6-(2-bromovinyl)uridine 7E, a reduced form of 1a, but not (Z)-6-(2-bromovinyl)uridine 7Z, which gave a novel type of unstable compound with 6-exomethylene structure 29 through a different reaction pathway. 6-Chloro-8-(2,2-dibromovinyl)purine nucleoside 10 was nex t studied, and not only 1,5- but also 1,6-translocated products were isolat ed.