A highly versatile catalyst system for the cross-coupling of aryl chlorides and Amines

Article abstract of DOI:10.1002/chem.200902316

The syntheses of 2-(di-tertbutylphosphino)-N,N-dimethylaniline (L1, 71%) and 2-(di-1-adamantylphosphino)-N,N-dimethylaniline (L2, 74%), and their application in BuchwaldHartwig 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 imines, 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), [PdCl ₂(MeCN)₂], or [Pd₂(dba)₃] (dba = dibenzylideneacetone) in combination with L1 or L2, or by use of [Pd(allyl)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 ortto-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 cross-coupling of aryl chlorides and amines