A Highly Versatile Catalyst System for the Cross-Coupling of Aryl Chlorides and Amines

The syntheses of 2-(di-tert-butylphosphino)-N,N-dimethylaniline (L1, 71%) and 2-(di-1-adamatylphosphino)-N,N-dimethylaniline (L2, 74%), and their application in Buchwald-Hartwig amination, are reported. In combination with [Pd(allyl)Cl](2) or [Pd-(cinnamyl)Cl](2) these structurally simple and air-stable P,N ligands enable the cross-coupling of aryl and heteroaryl chlorides, including those bearing as substituents enolizable ketones, ethers, esters, carboxylic acids, phenols, alcohols, olefins, amides, and halogens, to a diverse range of amine and related substrates that includes primary alkyl- and arylamines, cyclic and acyclic secondary amines, N-H amines, hydrazones, lithium amide, and ammonia. In many cases, the reactions can be performed at low catalyst loadings (0.5-0.02 mol% Pd) with excellent functional group tolerance and chemoselectivity. Examples Of cross-coupling reactions involving 1,4-bromochlorobenzene and iodobenzene are also reported. Under similar conditions. inferior catalytic performance was achieved when using Pd(OAc)(2), PdCl2 [PdCl2(cod)] (cod = 1,5-cyclooctadiene), [PdCl2(MeCN)(2)], or [Pd-2(dba)(3)] (dba = dibenzylideneacetone) in combination with L1 or L2, or by use of [Pd(ally])Cl](2) or [Pd(cinnamyl)Cl](2), with variants of L1 and L2 bearing less basic or less sterically demanding substituents on phosphorus or lacking an ortho-dimethylamino fragment. Given Current limitations associated with established ligand classes with regard to maintaining high activity across the diverse possible range of C-N Coupling applications, L1 and L2 represent unusually versatile ligand systems for the Of aryl chlorides and cross-coupling amines.