Metallaphotoredox-Mediated Decarboxylative Cross-Coupling of α-Oxy Morpholine Carboxylic Acids and (Hetero)Aryl Halides

A decarboxylative C(sp(2))-C(sp(3)) cross-couplingreaction of alpha-oxy carboxylic acids using dual nickel/photoredoxcatalysis has been developed for the synthesis of complex morpholinesand other saturated heterocycles, affording direct entry to scaffoldsof interest in drug discovery. This chemistry can be applied to thecoupling of an array of (hetero)aryl halides and alpha-heteroatomacids, providing C(sp(2))-C(sp(3))-coupledproducts in modest to excellent yields and enabling access to intermediatesthat can be further derivatized to multivector architectures.

Automated summary

A decarboxylative C(sp(2))-C(sp(3)) cross-coupling reaction using dual nickel/photoredox catalysis enables the synthesis of complex morpholines and other saturated heterocycles, providing access to drug discovery scaffolds. This methodology allows coupling of various (hetero)aryl halides and alpha-heteroatom acids to afford C(sp(2))-C(sp(3)) coupled products in modest to excellent yields, allowing for further derivatization to multivector architectures.