Allylic substitution of 3',4'-unsaturated nucleosides: Organosilicon-based stereoselective access to 4'-C-branched 2',3'-didehydro-2',3'-dideoxyribonucleos

• Published in: Journal of organic chemistry Vol. 61; no. 3; pp. 851 - 858
• Main Authors: Haraguchi, K, Tanaka, H, Itoh, Y, Yamaguchi, K, Miyasaka, T
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 09.02.1996
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ALCOHOLS; OXOLANE; REAGENTS; URACIL NUCLEOSIDES; ELIMINATION; RIBONUCLEOSIDES; OXETANE; CLEAVAGE; VERSATILE SYNTHONS; EFFICIENT
• ISSN: 0022-3263
• DOI: 10.1021/jo9516190

Reactions of organosilicon reagents (such as allyltrimethylsilane, silyl enol ethers, cyanotrimethylsilane) with 3',4'-unsaturated nucleosides (of uracil, N-4-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 N-4-acetylcytosine derivatives, SnCl4 appeared to be suitable, whereas the use of EtAlCl(2) was necessary for the hypoxanthine derivatives. The main pathway of these reactions was found to be a-face-selective S(N)2' allylic substitution, irrespective of the configuration of 2'-0-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 H-1 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'-0-(tert-butyldiphenylsilyl) protecting group.