First evident generation of purin-2-yllithium: Lithiation of an 8-silyl-protected 6-chloropurine riboside as a key step for the synthesis of 2-carbon-substituted adenosines

Lithiation at the 2-position of purine ring has been accomplished for the first time by using 6-chloro-9-(2,3-O-isopropylidene-5-O-trityl-beta-D-ribofuranosyl)-8-(triisopropylsilyl)purine (7) as a substrate and LTMP as a lithiating agent. The 8-triisopropylsilyl group in 7 did not undergo anionic migration and, thus, allowed the ready generation of the C2-lithiated species by preventing deprotonation at the 8-position. The electron-withdrawing B-chlorine atom plays an essential role to this C2-lithiation. Reactions of the lithiated species with electrophiles gave the 8-substituted products (Me, Et, i-Pr, CH(OH)C6H11, C(OH)Me-2, CHO, CO2Me, and I) mostly in good yields. Ammonolysis of the 6-chlorine atom of these products (heating at 110 degrees C in a sealed tube with NH3/MeOH) effected simultaneous desilylation at the 8-position to give the corresponding adenosine analogues. The whole sequence provides a new and highly general method for the synthesis of 2-substituted adenosines.