Rh-Catalyzed Chemodivergent [3+3] Annulations of Diazoenals and α-Aminoketones: Direct Synthesis of Functionalized 1,2-Dihydropyridines and Fused 1,4-Oxazines

Abstract

Novel rhodium-catalyzed [3+3] annulations of diazoenals and α-amino ketones has been disclosed here. The reactivity of diazoenals has been switched from carbenoid to vinylogous NH-insertion by altering acyclic to cyclic α-amino ketones. In this direction, we report an efficient strategy to synthesize 1,2-dihydropyridines (DHPs) and fused 1,4-oxazines. Mechanistic investigation revealed that the formyl group is necessary for carbenoid [3+3] annulation and the cyclohexyl group is the dictating factor for vinylogous NH- insertion. The synthetic utility of 1,2-dihydropyridines was demonstrated by synthesizing piperidine, pyrido[1,2-a]indole, and 2-pyridone scaffolds. Further, structural diversification of fused 1,4-oxazines resulted in the short synthesis of hexahydroquinolin-2(1H)-ones, hexahydro quinolines and tetrahydroquinolinones via ring opening rearrangement and a new oxidative deformylation, respectively.

Keywords: NH-insertion; annulation; carbenoids; diazoenals; heterocycles.