Synthesis of Unprotected α-Tertiary Amines and 1,2-Amino Alcohols from Vinyl Azides by Light Induced Denitrogenative Alkylarylation/ Dialkylation

Sterically congested & alpha;-tertiary primary amines are ubiquitous substructures in pharmaceutical and agrochemical agents yet are challenging to access. Herein, straightforward photoredox-catalyzed access to structurally diverse & alpha;,& alpha;,& alpha;-trisubstituted primary amines from denitrogenative alkylarylation or dialkylation of vinyl azides with N-hydroxyphthalimide (NHPI) esters and cyanoarenes or aryl aldehydes has been developed. The use of vinyl azide as a precursor to a primary amine was enabled by the dual role of the Hantzsch ester to form an electron donor-acceptor complex and serve as a sacrificial reductant. This strategy provides a modular synthesis of & alpha;-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 photo catalytic cycles allowing for the denitrogenative alkylarylation or dialkylation of vinyl azides via decarboxylative radical addition followed by heteroradical cross-coupling between & alpha;-amino radicals and aryl anion radicals or ketyl anion radicals.