Solvent Effect Observed in Nucleophilic Substitution of 4′-(Benzoyloxy)cordycepin with AlMe₃: Stereochemical Evidence for S_Ni Mechanism

Nucleophilic substitution between the 4′-benzoyloxy derivative of cordycepin (3′-deoxyadenosine) and AlMe₃ proceeds mostly with retention of configuration at the 4′-position: the 4′-benzoyloxy substrate having the β-d-configuration (8a) gave the 4′-methylated β-d-nucleoside (9a) with a high diastereomeric excess, while the substrate 8b having the opposite 4′-configuration gave the corresponding α-l-isomer (9b) with a comparatively lower stereoselectivity. The S_Ni mechanism is proposed for this reaction (from 8 to 9). The polarity of the solvent has a significant influence on the stereoselectivity, especially for the formation of 9b.