New Ligands for a General Palladium‐Catalyzed Amination of Aryl and Heteroaryl Chlorides

Abstract

The synthesis and application of monodentate N-substituted heteroarylphosphines is described. In general, the ligands are conveniently prepared by selective metallation at the 2-position of the respective N-substituted heterocycle (pyrrole, indole) by using n-butyllithium/tetramethylethylenediamine (TMEDA) followed by quenching with dialkyl- or diarylchlorophosphines. Of the different ligands prepared, the new dialkyl-2-(N-arylindolyl)phosphines (cataCXium P) perform excellently in the palladium-catalyzed amination of aryl and heteroaryl chlorides. Coupling of both activated and deactivated chloroarenes proceeds under mild conditions (room temperature to 60 degrees C). By using optimized conditions remarkable catalyst productivity (total turnover number, TON, up to 8000) and activity (turnover frequency, TOF=14000 h(-1) at 75% conversion) are observed.

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

“…[85,86] As a result of their ease of synthesis and utility a significant number of this class are now commercially available ( Figure 1) and their large scale synthesis has been investigated by Rhodia Pharma Solutions and Lanxess [87,88] and now at Shasun and Saltigo. The utility of these ligands has resulted in the introduction of structurally related variants by others [89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105] and has spawned innovative alternative synthetic routes by Diels-Alder reaction [96,106] and formal rhodiumcatalyzed [2+2+2] cycloaddition. [107,108] …”

Highly Reactive, General and Long-Lived Catalysts for Palladium-Catalyzed Amination of Heteroaryl and Aryl Chlorides, Bromides, and Iodides: Scope and Structure–Activity Relationships

“…These factors have limited the use of the coupling of amines to produce less expensive intermediates and commodity building blocks. 6,7 (1) Three general classes of reagents react slowly and require high loading of catalyst, even with most of the most recently developed systems: 8 (1) primary alkylamines, [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] which form substantial amounts of product from diarylation in the absence of an ortho substituent on the haloarene reagent or an excess of the primary amines; (2) heteroaryl halides, 11,12,15,17,19,[24][25][26][27][28][29][30][31][32] which are important for medicinal chemistry applications, but have reacted more slowly, with narrower scope, and with higher catalyst loadings than aryl halides; and (3) aryl iodides, which react more slowly and provide lower yields than aryl bromides in couplings with amine nucleophiles, 15,17,[33][34][35][36][37][38][39][40][41][42]…”

LIGAND FREE Pd CATALYZED CYCLIZATION-INFLUENCE OF STERIC HINDRANCE

“…The six allyl-containing benzenesulfonamides (6)(7)(8)(9)(10)(11) were subjected to C-C cross-coupling by applying Pd(II) acetate under basic conditions (using di-isopropylamine) in either 1-methyl-2-pyrrolidinone or toluene as reaction medium. The attempt of cyclization was made without employing triphenylphosphine ligand which is mandatory for Heck cyclization.…”

“…Formation of C-C bond through cleavage of C-H bond via metal-catalyzed reaction has been developed as the most attractive research area for organic, as well as, organometallic chemists in synthesis of homo/heterocyclic compounds [1][2][3][4] . The inestimable significance of these transition metal-catalyzed synthetic transformations has been disclosed by Stille 5 , Negishi 6 , Suzuki-Miyaura 7 , Hiyama 8 and palladiumcatalyzed Heck cross-couplings [9] using organohalides and other surrogates in synthetic chemistry 10,11 . The traditional Heck reaction drives through: i) a suitable amount of homogenous/heterogeneous palladium (0/II) catalyst, ii) a ligand, usually phosphine and iii) a suitable base.…”