Homogeneous Reductant Facilitated Cross-Electrophile Coupling of Aryl Bromides with NHP Esters

Alkyl-substituted N-hydroxyphthalimide (NHP) esters are valuable alternatives to alkyl halides in Ni-catalyzed cross-electrophile coupling reactions because they are typically more stable, can generate alkyl radicals under reductive conditions, and are readily prepared from carboxylic acids. However, the range of aryl halides that can be coupled with NHP esters in XEC has so far been largely limited to aryl iodides. Here, we describe a general method for coupling NHP esters bearing 1°, 2°, and strained ring 3° alkyl groups with aryl bromides. This method is compatible with a broad range of substrates, including drug-like aryl bromides, and operates effectively in various non-amide based solvents. The use of a homogeneous organic reductant is crucial for achieving high yields, as it enables precise control over alkyl radical generation from the NHP ester.