Probing the effect of donor-fragment substitution in Mor-DalPhos on palladium-catalyzed C–N and C–C cross-coupling reactivity

Abstract

The competitive catalytic screening of 18 known and newly prepared Mor-DalPhos ligand variants in the palladium-catalyzed cross-coupling of chlorobenzene with aniline, octylamine, morpholine, indole, ammonia, or acetone is presented, including ligands derived from the new secondary phosphine HP(Me2Ad)2 (Me2Ad = 3,5-dimethyladamantyl). Although triarylphosphine ancillary ligand variants performed poorly in these test reactions, ligands featuring either PAd2 or P(Me2Ad)2 donors (Ad = 1-adamantyl) gave rise to superior catalytic performance. Multiple Mor-DalPhos variants proved effective in cross-couplings involving aniline, octylamine, or morpholine; conversely, only a smaller subset of ligands proved useful in related cross-couplings of indole, ammonia, or acetone. In the case of the N-arylation of indole, a Mor-DalPhos ligand variant featuring ortho-disposed PAd2 and dimethylmorpholino donor fragments (L13) proved superior to all other ligands surveyed, including the parent ligand Mor-DalPhos (L5). Conversely, L5 was found to be superior to all other ligands in the palladium-catalyzed monoarylation of ammonia. Ligand L6 (i.e., the P(Me2Ad)2 variant of L5) proved superior to all other ligands in the monoarylation of acetone and, with the exception of indole N-arylation, was the most broadly useful of the Mor-DalPhos ligands surveyed herein.