One-pot silyl imidate formation-N-alkylation reactions of amides with propargyl propionates

The combination of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and i-Pr2NEt promotes the N-alkylation of primary and secondary amides with propargyl propionates. The amide substrates are believed to undergo conversion to nucleophilic silyl imidates in the presence of TMSOTf and the amine base, conditions which also promote propargyl cation formation in the same flask through the loss of trimethylsilyl propionate, leading to Npropargylation of the amide. A range of amides and propargyl propionates react efficiently in this reliable onepot process with yields ranging from 19 to 99%.

Automated summary

The combination of TMSOTf and i-Pr2NEt promotes the N-alkylation of primary and secondary amides with propargyl propionates. The amide substrates are converted to nucleophilic silyl imidates, which undergo N-propargylation through propargyl cation formation. This one-pot process can efficiently react a range of amides and propargyl propionates with yields ranging from 19% to 99%.