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)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 next studied, and not only 1,5- but also 1,6-translocated products were isolated.