Cross-coupling reactions without ligands

Mowery and DeShong used the commercially available hypervalent silicate complex TBAT as a phenylating agent for the cross-coupling reaction with allylic esters. They later reported on the use of the same organosilane for the coupling with aryl iodides and triflates and electron-deficient aryl bromides. The reactions were catalyzed by either Pd(dba)2 or [Pd(allyl)Cl]2 without the need of added phosphine ligands. 

Recently, a mechanism for the cross-coupling reaction between phenyl iodide and methylmagnesium iodide, catalyzed by cis- and fra j-[(PEt2Ph)2Pd(Ph)(I)], was proposed (Scheme 11). The toluene produced from cis-ilS) is thought to result via an intramolecular reductive elimination process without predissociation of the phosphine ligand. 

Pd is also a potential contaminant and Nobile and coworkers recently employed a polymer-supported palladium complex (Pd-pol, Figure 5.3.1), obtained by copolymerization of Pd(AAEMA)2 with ethyl methacrylate and ethylenene glycol dimethacrylate (AAEMA is the deprotonated form of 2-(acetoacetoxy)ethyl methacrylate), as a catalyst in Stille cross-coupling reactions [Equation (5.3.14)]. The reaction can be performed in air without any activating ligand and with non-dried solvents. The catalyst can be recycled several times. 

First, coordinatively unsaturated active palladium catalyst, PdL2, is produced via dissociation of the ligands, which then reacts with acyl halide to give the acylpalladium intermediate. Since deinsertion of CO of the acylpalladium derivatives may occur simul-taneously, the next step, transmetallation (so-called metathesis), is the most crucial for the efficiency of the overall reaction. A variety of organometallic compounds, such as boron, aluminum, copper, zinc, mercury, silicon, tin, lead, zirconium, and bismuth, are used as the partner in this coupling reaction without loss of CO. In this section, the important features of the cross-coupling reactions of a variety of organometallic compounds with acyl halides and related electrophiles are discussed. 

A cross-coupling reaction of an o-iodoaniline and an alkyne is a key step in Merck s synthesis of MK-0462, a 5-HTid receptor agonist and potential antimigraine drug (Scheme 11). As a catalyst, simple palladium(ll) acetate, although in relative high concentrations (2 mol %), is used without any ligand. Under these conditions, 80% of the (partially de-O-protected) substituted indole is formed in DMF at 100... 

Pd-catalyzed site-selective cross-coupling reactions demonstrate the influential role of ligands in transition metal catalysis. The reactions described in this review discuss efficient approaches to introduce various substituents at specific halo-substituted posititMis (Ml (hetero)aromatic compounds. The commercial availability of a variety of dihalo-substituted starting materials makes site-selective crosscoupling reactions practical for the rapid production of diverse (hetero)arenes with multiple substituents. In all examples described here, the reactions proceeded successfully only on substrates containing hetero atoms, and this field of chemistry aims to include substrates without hetero atoms in the substrate scope. 

A solvent-free variant used octahedral CU2O nanoparticles with added PPhj ligand, which effectively catalyzed the cross-coupling reactions of various aryl and heteroaryl halides with terminal alkynes [148]. The catalyst was reusable without any observable loss of activity, but worked only at temperatures above 100 °C. Further improvements to this approach involved the elimination of the Hgand and carrying out the reaction in a mixture of DMSO, K2CO3, and catalytic amounts of CU2O nanoparticles [149]. 

Thus, low loadings of palladium without added ligand can be used in cross-coupling reactions such as the Mizoroki-Heck reaction of atyl bromides, but only when the palladium-substrate ratio is kept particularly low, typically from 0.01-0.1 mol%. Quenching of ionic species (into metal colloids) is less likely at lower concentrations due to a lower collision frequency. Pd black formation is a catalytic dead end. At too low a concentration, the reaction will proceed slowly, if at all. - ... 

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