Monoligated Palladium Species as Catalysts in Cross‐Coupling Reactions

Abstract

Palladium-mediated cross-coupling reactions are attractive organometallic transformations for the generation of C--C, C--N, C--O, and C--S bonds. Despite being widely employed in small-scale syntheses, cross-coupling reactions have not found important industrial applications because until recently, only reactive aryl bromides and iodides could be used as substrates. These substrates are generally more expensive and less widely available than their chloride counterparts. Over the past few years, new catalytic systems with the ability to activate unreactive and sterically hindered aryl chlorides have been developed. The new catalysts are based on palladium complexes that contain electron-rich and bulky phosphine or carbene ligands. The enhanced reactivity observed with these new systems has been attributed to the formation of unsaturated and reactive [PdL] species which can readily undergo oxidative addition reactions with ArX to yield [Pd(Ar)X(L)].

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

“…[109][110][111][112][113][114][115][116] In the case of the dialkylbiaryl phosphines the catalytically active species is believed to be the monoligated, highly reactive L 1 Pd(0) complex which exists in equilibrium with the L 2 Pd(0) species. [117] The considerable steric bulk and strong electron donor ability of the dialkylbiaryl phosphine ligands presumably serves to encourage the formation of this active species which allows oxidative addition to occur under mild conditions even with unactivated aryl chlorides. It has been shown using reaction calorimetry that the size of the substituents on the lower ring have a significant effect on the rate of aryl halide amination.…”

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 reactions exceeded the maximum turnover numbers for the reactions of primary alkyl amines with aryl iodides by more than an order of magnitude. 35 Hindered, ortho-substituted aryl halides also reacted with primary alkylamines with low catalyst loadings (Table 3, entries [5][6][7][8]24). For example, the reaction of 1-bromo-2-isopropylbenzene with iso-butylamine formed the coupled product in 95% yield in DME after 48 h at 100 °C in the presence of 0.05 mol % catalyst, and the reaction of 2,6-disubstituted aryl bromides and chlorides occurred with octylamine with only 0.05-0.1 mol % catalyst.…”

“…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]…”

Synthesis of an extremely sterically shielding N-heterocyclic carbene ligand

“…1 The main advantages of these ligands are their ability to kinetically stabilize highly reactive low-valent transition metal atoms with low coordination number. 2 A decisive feature of NHC ligands with ortho-substituted aromatic substituents is their steric shielding of the carbene ligand atom and the metal atom. IPr and its saturated derivative SIPr are typical representatives.…”