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‐aminoketones. 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.

Triple Nucleophilic Head-to-Tail Cascade Polycyclization of Diazodienals via Combination Catalysis: Direct Access to Cyclopentane Fused Aza-Polycycles with Six-Contiguous Stereocenters

“…Initial investigations by us and others revealed that (2 E )-diazoenals (n = 1) are versatile substrates for metal catalysis and combinations catalysis. − Rh-enalcarbenoid reacts with a variety of π- and heteroatom nucleophiles resulting in the (4 + 2), ,,, (4 + 1), (1 + 1 + 3), (3 + 3), and (3 + 2) annulations, olefination, and enal-transfer reactions. Notably, the reaction of diazoenal and N -aryl propargylamine under combination catalysis gave enal-functionalized 1,4-oxazines via cascade Rh-carbenoid NH-insertion and remote 6- exo-dig heterocyclization enabled by synergistic Au­(I) and dienamine catalysis (Figure D) …”