N-Silylenamines as Reactive Intermediates: Hydroamination for the Modular Synthesis of Selectively Substituted Pyridines

A modular and selective synthesis of mono-, di-, tri-, tetra-, and pentasubstituted pyridines is reported. Hydroamination of alkynes with N-silylamine using a bis(amidate)-bis(amido)titanium(IV) precatalyst furnishes the regioselective formation of N-silylenamines. Addition of alpha,beta-unsaturated carbonyls to the crude mixtures followed by oxidation affords 47 examples of pyridines in yields of up to 96%. This synthetic route allows for the synthesis of diverse pyridines containing variable substitution patterns, including pharmaceutically relevant 2,4,5-trisubstituted pyridines, using this one-pot protocol.