Silylative N-hydroxyalkylation of amide compounds: application to the synthesis of acyclic alditol-based nucleoside analogues

Abstract

A rare silylative hydroxyalkylation of amide compounds with chiral aldehydes has been developed utilizing a Lewis acid–Lewis base promoter system consisting of an equimolecular mixture of tert-butyldimethylsilyl trifluoromethanesulfonate and N-diisopropylethylamine. This approach culminated in the synthesis of several enantiopure acyclic nucleoside representatives comprising thymidine analogues 6 , 7 , 9 , 10 , 12 and 13 , uridine analogues 15 and 16 , and 6-chloropurine derivatives 18 and 19 .