Diastereoselective synthesis of α-substituted propargylamines via dicobalt complex methodology

Abstract

Diastereoselective chromium carbene photochemistry afforded a cyclobutanone which was elaborated to a disubstituted butenolide bearing 4'-(benzyloxy)methyl and 4'-ethoxy groups. This template was converted to a 2',3 '-dideoxy-thymidine nucleoside analog. Dicobalt hexacarbonyl complexes of propargyl N,OTMS-acetals were prepared, and the scope of their reactivity was studied. In the presence of TiCl4 a mixture of CO2(CO)6-complex diastereomers was equilibrated to one, indicating a cationic intermediate. An equilibration/alkylation sequence allowed the preparation of propargylamides with high diastereocontrol. The absence of the cluster led to alkylation with decreased diastereoselectivity.