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

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(sp(3))-H dehydrogenation and C(sp(2))-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 O-2 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.