SYNTHESIS OF 5-S-SUBSTITUTED 2'-DEOXYURIDINES . STUDY OF FACTORS INFLUENCING STEREOSELECTIVITY OF SILYL MODIFICATION OF HILBERT-JOHNSON REACTION

Coupling of bis-O-(trimethylsilyl)-S-substituted 5-mercaptouracils (3b–f) with 2-deoxy-3,5-di-O-(p-chlorobenzoyl)-α-D-ribofuranosyl chloride (4) under various reaction conditions allowed stereoselective synthesis of the β and α anomers of the corresponding fully protected 2′-deoxyribonucleosides. The anomeric configuration of the nucleosidic products was found to be dependent on the presence or absence of trimethylsilyl chloride during the condensation; reaction conditions allowing rapid removal of the trimethylsilyl chloride formed lead to the β anomer as the only isolatable nucleosidic product, while continued presence of the trimethylsilyl chloride in the reaction mixture favors formation of the a anomer. The halogenose 4, on standing in benzene solution, was found to undergo changes in optical rotation, with eventual degradation to p-chlorobenzoic acid, furfuryl-pchlorobenzoate, and a disaccharide, 14. This process is prevented in the presence of trimethylsilyl chloride. The coupling reactions with the silylpyrimidines, leading to either β or α nucleosidic products, are viewed as proceeding uniformly via an Sn2 mechanism, with inversion of configuration at the anomeric carbon of the α or β halogenose. The free nucleosides were obtained by sodium methoxide catalyzed deacylation. The mercapto nucleosides are rapidly oxidized to the corresponding disulfides, which exhibit very high optical rotation and Cotton effects. © 1969, American Chemical Society. All rights reserved.