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

• Published in: Chemistry : a European journal 2010-02, Vol.16 (6), p.1983-1991
• Main Authors: Lundgren, Rylan J., Sappong-Kumankumah, Antonia, Stradiotto, Mark
• Format: Article
• Language: English
• Subjects: Amides; amination; Amines; anilines; Aromatic compounds; Catalysts; Chemistry; Chlorides; Cross coupling; homogeneous catalysis; Ligands; Palladium; phosphanes
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200902316

The syntheses of 2‐(di‐tert‐butylphosphino)‐N,N‐dimethylaniline (L1, 71 %) and 2‐(di‐1‐adamantylphosphino)‐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 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), [PdCl2(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 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 cross‐coupling of aryl chlorides and amines. New amination catalysts: A highly active and widely applicable catalyst system for the cross‐coupling of aryl chlorides to amines has been developed by employing the structurally simple and robust ligands L1 and L2 (see graphic). Suitable amine partners include primary and secondary aryl and alkyl amines, imines, hydrazones, lithium amide, and ammonia, with typical catalyst loadings of 1–0.02 mol % Pd.