The Mechanisms of Cross Coupling

The reactions of aryl halides with carbon monoxide and either alcohols or amines to form esters or amides occur by two related yet distinct mechanistic pathways. These pathways are related to the mechanism of cross coupling presented in Chapter 19, and the reader might find it helpful to refer to the discussion of mechanisms of cross coupling in that chapter. Scheme 17.29 outlines the pathways for the carbonylation of aryl halides to form esters and amides. 

In the quest for coordinatively unsaturated palladium catalysts, the more radical approach uses ligandless conditions [165, 166] following the work pioneered by Beletskaya [38b, 167]. However, the mechanism of cross-coupling reactions under these conditions is not known [168]. 

It should be emphasized that the results of these kinetic studies do not represent only the TBAF-promoted coupling of alkenylsilanols. Analyzed in the context of the spectroscopic studies and reported observations - which reveal that sile-tanes, silanols, and fluorosilanes, silyl hydrides, and heterocyclic silanes all form related species when mixed with TBAF - the mechanism deduced by the kinetic studies likely represents the mechanism of cross-coupling of all of these species. These mechanistic results are therefore relevant to a significant body of work, encompassing everything from the early fiuorosilane cross-coupling systems to the more recently developed TBAF-promoted coupling of pyridyl-, thienyl-, and benzylsilanes. 

The mechanism of cross-coupling of alkenylsilanolates with 2-iodothiophene has been elucidated by kinetic measurements and involves interesting key intermediates (Scheme 12). After formation of a siloxypalladium(ii)aryl complex 45 by transmetallation with [PdX(Ar)L ], a second silanolate acts as a nucleophilic activator and generates a pentacoordinate siliconate 46, from which transmetallation to Pd occurs. This generates the alkenylpalladium(ii) complex that reductively eliminates the product. ... 

However, solvent viscosity, rather than polarity, has been a useful tool for mechanistic purposes. Although the quantum yield of the ortho-rearranged product of 4-methylphenyl acetate (20) does not change with viscosity of the medium, the formation of 4-methylphenol (22) is highly sensitive to this factor. Thus, its quantum yield is 0.45 in ethanol (1.00 cP) but only 0.02 in Carbowax 600 (109 cP) (Scheme 8 Table 3) [13], This clearly supports the mechanism involving caged radical pairs. A related aspect is the intramolecular nature of the process confirmed by the lack of cross-coupling products in crossover experiments with mixtures of different esters [10]. 

Because of their frequent use, some late transition metal catalyzed carbon-carbon bond forming reactions evolved into name reactions. The most prominent examples are cross-coupling reactions, where distinction is usually made on the basis of the transmetalating agent used. The common mechanism of cross-coupling reactions and its name variants are discussed in Chapter 2.1. 

Apart from (3-hydride elimination, another important pathway by which palladium(II) intermediates can lead to neutral organic fragments is reductive elimination. This forms the basis of the mechanism for cross-coupling reactions between organometallic reagents and an organic halide or triflate. 

In other studies the mechanism of cross-linking in irradiated copolymers of tetrafluoroethylene and perfluoromethylvinylether has been studied by Forsythe e/o/. " This material is rubbery at room temperature, and hence sufficient molecular mobility is available to permit radical-radical recombination reactions. Thus the material undergoes both chain scission and cross-linking. The authors were able to quantify the yields of new products using F MAS NMR at moderate spinning speeds, since the chemical shift anisotropy and homonuclcar dipole-dipole couplings of the fluorine nuclei are partially averaged by rapid molecular motion in the rubbery state. 

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