Sequential KO t Bu/FeCl 3 -catalyzed reductive phosphonylation of tertiary amides for the synthesis of α-amino phosphonates and phosphines.

A simple, mild and efficient sequential KO t Bu/FeCl 3 -catalyzed reductive phosphonylation of tertiary amides is herein described. This process first involved the KO t Bu-catalyzed selective semi-reduction of tertiary amides to hemiaminal intermediates by TMDS (1,1,3,3-tetramethyldisiloxane) and then the FeCl 3 -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.