Diastereoselective Synthesis of N-Secondary Alkyl 2-Alkoxymethylpyrrolidines via Sequential Addition Reactions of Organolithium and -Magnesium Reagents to N-Thioformyl 2-Alkoxymethylpyrrolidines

Highly efficient sequential addition reactions of organolithium and -magnesium reagents to N-thioformyl 2-methoxymethylpyrrolidine have been described. Various combinations of these reagents gives successful results. A highly efficient and diastereoselective addition reaction is also described. Use of the opposite combinations of substituents on organolithium and -magnesium reagents leads to the selective formation of the opposite diastereomers. The reaction was extended to N-thioformyl 2-siloxymethypyrrolidine and 2-methoxymethylpiperidine, and these showed similar efficiency and selectivity.