Ruthenium-catalyzed oxidative coupling of primary amines with internal alkynes through C-H bond activation: scope and mechanistic studies

Abstract

The oxidative coupling of primary amines with internal alkynes catalyzed by Ru complexes is presented as a general atom-economy methodology with a broad scope of applications in the synthesis of N-heterocycles. Reactions proceed through regioselective C-H bond activation in 15 minutes under microwave irradiation or in 24 hours with conventional heating. The synthesis of 2,3,5-substituted pyridines, benzo[h]isoquinolines, benzo[g]isoquinolines, 8,9-dihydro-benzo[de]quinoline, 5,6,7,8-tetrahydroisoquinolines, pyrido[3,4g]isoquinolines, and pyrido[4,3g]isoquinolines is achievable depending on the starting primary amine used. DFT calculations on a benzylamine substrate support a reaction mechanism that consists of acetate-assisted C-H bond activation, migratory-insertion, and C[BOND]N bond formation steps that involve 28–30 kcal mol−1. The computational study is extended to additional substrates, namely, 1-naphthylmethyl-, 2-methylallyl-, and 2-thiophenemethylamines.