Strained rings are increasingly important for the design of biologically active molecules due to their increased metabolic stability and their ability to orient substituents into favorable geometries. Despite their importance, methodologies to decorate strained rings have been underdeveloped. The most abundant source of strained carbocycles and heterocycles is the corresponding carboxylic acid, making methods that employ this substrate pool attractive. Coupling these carboxylic acids with abundant aryl halides would allow for rapid access to a diverse suite of molecules, and the prevalence of strained ring tertiary carboxylic acids would make this a useful method for the formation of all carbon quaternary centers. We have recently developed a nickel-catalyzed cross-electrophile approach that couples a variety of strained ring N-hydroxyphthalimide esters, derived from the carboxylic acid in one step or in situ, with various aryl and heteroaryl halides under reductive conditions. The key to success is the discovery of a new ligand, t-buBpyCamCN, that avoids problematic side reactions. This method enables the incorporation of 3-membered rings, 4-membered rings, and bicyclic fragments onto (hetero)arenes derived from aryl iodides and activated aryl bromides, allowing for easy access to strained ring analogues of diarylmethanes.

Nickel-catalyzed reductive decarboxylative arylation of strained ring N-hydroxyphthalimide esters

ACS Fall 2021

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