We report a Cu-catalyzed C−N cross-coupling of (hetero)aryl chlorides with a broad range of nitrogen nucleophiles. Nucleophiles include primary, secondary, and α-branched amines; amides; hydrazines; ammonia surrogates; NH-heterocycles; and base-sensitive substrates such as aminomethyl-functionalized azoles. Aryl and heteroaryl halides, including pyridyl and pyrimidyl chlorides, are competent reaction partners. Key reactivity trends of azole methanamines as a function of its azole identity and isomer were elucidated in a head-to-head comparison of heterogeneous and homogeneous C−N cross-coupling conditions using 42 different nucleophiles in a parallel library synthesis. The modular nature of the investigated ligands enabled a systematic structure−activity relationship study to elucidate key design principles, as well as steric and electronic effects on catalysis.
Mcgrath et al. (Thu,) studied this question.