Allylic Substitution of 3‘,4‘-Unsaturated Nucleosides: Organosilicon-Based Stereoselective Access to 4‘-C-Branched 2‘,3‘-Didehydro-2‘,3‘-dideoxyribonucleosides

Abstract

Reactions of organosilicon reagents (such as allyltrimethylsilane, silyl enol ethers, cyanotrimethylsilane) with 3‘,4‘-unsaturated nucleosides (of uracil, N4-acetylcytosine, and hypoxanthine) having an allyl ester structure were investigated in the presence of a Lewis acid in CH2Cl2. In the cases of uracil and N4-acetylcytosine derivatives, SnCl4 appeared to be suitable, whereas the use of EtAlCl2 was necessary for the hypoxanthine derivatives. The main pathway of these reactions was found to be α-face-selective SN2‘ allylic substitution, irrespective of the configuration of 2‘-O-acyl leaving group. As a result, a new stereoselective operation for C−C bonds formation leading to 4‘-carbon-substituted 2‘,3‘-didehydro-2‘,3‘-dideoxyribonucleosides has been disclosed for the first time. Stereochemistry of these 4‘-C-branched products can be assigned on the basis of 1H NMR spectroscopy in terms of the anisotropic shift of H-5 of the pyrimidine base (or H-8 of the hypoxanthine), which is caused by the 5‘-O-(tert-butyldiphenylsilyl) protecting group.