Catalytic synthesis of 1H-2-benzoxocins; Cobalt(III)-carbene radical approach to 8-membered heterocyclic enol ethers

Abstract

The metallo-radical activation of ortho-allylcarbonyl-aryl N-arylsulfonylhydrazones with the paramagnetic cobalt(II) porphyrin catalyst [Co^II(TPP)] (TPP = tetraphenylporphyrin) provides an efficient and powerful method for the synthesis of novel 8-membered heterocyclic enol ethers. The synthetic protocol is versatile, practical and enables the synthesis of a wide range of unique 1H-2-benzoxocins in high yields. The catalytic cyclization reactions proceed with excellent chemoselectivities, have a high functional group tolerance, and provide several opportunities for the synthesis of new bioactive compounds. The reactions are shown to proceed via cobalt(III)-carbene radical intermediates, which are in-volved in intramolecular hydrogen transfer (HAT) from the allylic position to the carbene radical, followed by a near barrierless radical rebound step in the coordination sphere of cobalt. The proposed mechanism is supported by experi-mental observations, density functional theory (DFT) calculations and spin trapping experiments.