Regio- and Atroposelective Ring-Opening of 1H-Benzo[4,5]oxazolopyridinones

Abstract

The development of new methods for regio- and stereoselective activation of C−O bonds in ethers holds significant promise for synthetic chemistry, offering advantages in terms of environmental sustainability and economic efficiency. Moreover, the C−N atropisomers represent a fascinating and crucial chiral system, extensively found in natural products, pharmaceutical leads, and the frameworks of advanced materials. In this work, we have introduced a nickel-catalyzed regio- and enantioselective carbon-oxygen arylation reaction for atroposelective synthesis of N-arylisoquinoline-1,3(2H,4H)-diones. The high regioselectivity of C−O cleavage benefits from the high stability of the in situ formed (amido)ethenolate via oxidative addition. Additionally, the self-activation of the aryl C−O bond facilitates the reaction under mild conditions, leading to outstanding enantioselectivities. The diverse post-functionalizations of the axially chiral isoquinoline-1,3(2H,4H)-diones further highlighted the utility of this protocol in preparing valuable C−N atropisomers, including the chiral phosphine ligands.