Sequential KOtBu/FeCl3-catalyzed reductive phosphonylation of tertiary amides for the synthesis of α-amino phosphonates and phosphines

Abstract

A simple, mild and efficient sequential KO^tBu/FeCl₃-catalyzed reductive phosphonylation of tertiary amides is herein described. This process first involved the KO^tBu-catalyzed selective semi-reduction of tertiary amides to hemiaminal intermediates by TMDS (1,1,3,3-tetramethyldisiloxane) and then the FeCl₃-catalyzed nucleophilic addition of the hemiaminal intermediates to phosphonates, which allowed the straightforward synthesis of α-amino phosphonates in moderate to good yields. This method applied well to amides and lactams that bear no strong acidic α-hydrogens, and various functional groups, including methoxy, methylthio, cyano, halogen, and heterocycles, could be tolerated.