Flexible, N-sulfonyl-substituted aliphatic amine ligands in palladium-catalyzed Suzuki–Miyaura C C coupling: Influence of substituents bulkiness and co-ligand size

Abstract Widespread use of commercially available palladium precatalysts is limited by high costs and their synthetic challenges. In this report, series of synthetically affordable, phosphine-free ligands were examined as supports for palladium active centers. 2-(2-Aminoethylamino)ethanol, diethylenetriamine and tris(2-aminoethyl)amine were condensed with sulfonyl chloride reagents in order to obtain flexible, aliphatic amine derivatives with varied steric bulk at the chain ends (ligands 1-Me and 1-tol  = RSO 2 NH CH 2 CH 2 N(SO 2 R) CH 2 CH 2 Cl; ligands 2-ipr and 2-iprNH  = RSO 2 NH CH 2 CH 2 NY CH 2 CH 2 O SO 2 R where Y is H or R; ligands 3-Me , 3-tol and 3-ipr  = RSO 2 N(CH 2 CH 2 NH SO 2 R) 2 ; 3-iprNH  = HN(CH 2 CH 2 NH SO 2 R) 2 ; ligands 4-tol and 4-ipr  = N(CH 2 CH 2 NH SO 2 R) 3 ; R = methyl, tolyl or triiso-propyl). Despite the flexibility of the alkyl fragments in these ligands, placement of sterically demanding groups at amine donors enables formation of active species, which supports high turnover frequencies and yields up to 91% within 5 min and at 0.2 mol % palladium loading. Such activity from synthetically simple alkyl ligand frameworks, which are generally not regarded in Pd catalysis, is unprecedented. In situ catalyst generation is favorable for ligands with less than tridentate chelation capacity and presence of poorly chelating secondary NH-amine donor in the central position of the polyamines hinders catalyst performance. However, the preformed tridentate complexes yielded more attractive and living coupling catalyst efficiencies than their corresponding in situ reactions especially when bulkier co-ligand such as pyridine occupies the fourth coordination position (TOF of 5460 h −1 for Pd(4-tol)py and 4800 h −1 for Pd(4-ipr)py ). Therefore, mutual steric demands between the tridentate-chelated steric ligands such as 4-tol and 4-ipr , and bulky co-ligand fragments cooperatively aids the generation of active species from assembled precatalyst.