C(sp3)–H dehydrogenation and C(sp2)–H alkoxy carbonylation of inactivated cyclic amines towards functionalized N-heterocycles

Abstract

A novel and efficient synthesis of tetrahydropyridine (THP)-, dihydropyrrole (DHP)-, or tetrahydroazepine (THA)-3-carboxylates via cascade reactions of inactivated cyclic amines with CO and alcohols is presented. To our knowledge, this should be the first example in which functionalized N-heterocycles were prepared directly from Pd-catalyzed C(sp³)–H dehydrogenation and C(sp²)–H carbonylation of saturated cyclic amines. Moreover, the DHP-3-carboxylates thus obtained could readily undergo an oxidative aromatization to give pyrrole-3-carboxylates by using O₂ as a green oxidant. Notable features of the methods developed herein include simple substrates, high efficiency and excellent atom-economy, mild reaction conditions, and broad substrate scope.