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 involved 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 experimental observations, density functional theory (DFT) calculations and spin trapping experiments.

The synthesis of seven- and eight-membered rings by radical strategies

“…Based on these previous results and in view of their continuing interest in Co II , the authors provided an efficient tool for the synthesis of 1H-2-benzoxocins (Scheme 13). 33 The authors modified the terminal allyl position to carbonyl, which was the key for obtaining such compounds. Meanwhile, Cs 2 CO 3 was used instead of organic base, which is more environmentally friendly.…”