Palladium-Catalyzed [3+2+1]/[4+2] Heteroannulation of Allylamines with CO and 1,4-Enynes Leading to 1,7,8,8a-Tetrahydroisoquinolin-3(2H)-ones

Abstract

Aminocarbonylative heteroannulation of unsaturated hydrocarbons with amines and CO has become a key transformation in organic synthesis to build N-heterocycles. In this report, a new palladium-catalyzed aminocarbonylative [3+2+1]/[4+2] heteroannulation of allylamines with CO and 4-en-1-yn-3-yl acetates for the synthesis of 1,7,8,8a-tetrahydroisoquinolin-3(2H)-ones has been developed. The method enables the construction of two new six-membered rings in a single reaction step leading to the formation of the isoquinolinone scaffolds, featuring excellent selectivity, good functional group compatibility and broad substrate scope. A possible mechanism involving Pd-catalyzed isomerization to form the allenyl-Pd intermediate, aminocarbonylation and cycloaddition was proposed.