Synthesis of α-tertiary primary amines and 1,2-amino alcohols from vinyl azides by light induced denitrogenative alkylarylation/dialkylation

Sterically congested α-tertiary primary amines are ubiquitous substructures in pharmaceutical and agrochemical agents yet are challenging to access. Herein, a straightforward photoredox-catalyzed access to structurally diverse α,α,α-trisubstituted primary amines from denitrogenative alkylarylation or dialkylation of vinyl azides with NHPI esters and cyanoarenes or aryl aldehydes has been developed. The use of vinyl azides as a precursor of primary amines was enabled by the dual role of Hantzsch ester to form electron donor-acceptor (EDA) complexes and to serve as a sacrificial reductant. This strategy provides a modular synthesis of α-tertiary primary amines, including unprotected 1,2-amino alcohols, from simple materials with excellent functional group tolerance. The synthetic applicability of this method was demonstrated by streamlined access to 2,2-disubstituted tetrahydroquinolines. Preliminary investigations support two parallel reductive photocatalytic cycles allowing for the denitrogenative alkylarylation or dialkylation of vinyl azides via decarboxylative radical addition followed by hetero-radical cross-coupling between α-amino radicals and aryl anion radicals or ketyl anion radicals.