New Phosphine-Functionalized NHC Ligands: Discovery of an Effective Catalyst for the Room-Temperature Amination of Aryl Chlorides with Primary and Secondary Amines

We
report convenient and high-yielding syntheses of new phosphine-functionalized
dihydroimidazolium salts and demonstrate their utility as ligand precursors
for Buchwald–Hartwig amination. Several examples of the general
formula [1-Mes-3-{2-(PR2)­phenyl}­imidazolidin-2-ylium]­[BF4] have been prepared, where phosphines of varying steric and
electronic properties (R = Ph (9), Cy (10), 1-Ad (11)) are tethered by an o-phenylene
group. The synthesis was not adaptable to N-aryl
groups other than mesityl, giving unexpected phosphonium salt species
instead. The synthesis was adapted to flexible benzyl-linked variants
of the formula [1-Ar-3-{2-(PCy2)­benzyl}­imidazolidin-2-ylium]­[BF4], which allowed more steric variation of the dihydroimidazolium N-aryl group (Ar = Mes (21), Dipp (22)). A preliminary study of these hybrid NHC/P ligands in Buchwald–Hartwig
amination catalysis (in situ precatalyst formation) revealed 11 to be the most active of the series. Premixing the isolated
free NHC ligand 1-Mes-3-{2-(PAd2)­phenyl}­imidazolidin-2-ylidene
(23) with [Pd­(cinnamyl)­Cl]2 provided a highly
active precatalyst that performed well at room temperature and 1 mol
% catalyst loading. The system was shown to have an unprecedented
ability to arylate both primary alkylamines (monoarylation) and secondary
dialkylamines with aryl chlorides at room temperature. Electron-rich
and -poor aryl and heteroaryl halides, as well as those featuring ortho substitution, were well tolerated, while substrates
featuring both primary and secondary amine groups were selectively
arylated at the NH2 position. Furthermore, a preliminary
examination of performance in ammonia arylation and acetone α-arylation
showed promising results, giving good conversion and high selectivity
for monoarylation in both cases.