Regio- and enantioselective amination of acyclic branched α-alkynyl ketones: asymmetric construction of N-containing quaternary stereocenters

The direct regio- and enantioselective amination of acyclic branched alpha-alkynyl ketones with azodicarboxylates has been developed through chiral phosphoric acid catalysis, which generates alpha-hydrazido-alpha-alkynyl ketone products with high enantioselectivity. Control experiments indicate that the alpha-alkynyl group in the ketone substrate is critical for both the reactivity and stereoselectivity of the reaction. Facile derivatizations of the functional group-abundant chiral product further highlight the value of this approach in the asymmetric synthesis of alpha-tertiary amines and N-containing heterocycles.

Automated summary

The direct regio- and enantioselective amination of acyclic branched alpha-alkynyl ketones with azodicarboxylates has been achieved through chiral phosphoric acid catalysis, yielding alpha-hydrazido-alpha-alkynyl ketone products with high enantioselectivity. Control experiments showed the importance of the alkynyl group in the ketone substrate for both reactivity and stereoselectivity, and facile derivatizations of the chiral product highlight the value of this approach in asymmetric synthesis of alpha-tertiary amines and N-containing heterocycles.