Reactions with Aryl Halides and Triflates Synthesis of Biaryls

Reactions with Aryl Halides and Triflates Synthesis of Biaryls... 

The direct preparation of arylboronic esters from aryl halides or triflates now allows a one-pot, two-step procedure for the synthesis of unsymmetrical biaryls. The synthesis of biaryls was readily carried out in the same flask when the first coupling of aryl halide with diboron was followed by the next reaction with another halide or triflate [240]. The protocol offered a direct and efficient method for the synthesis of the boronic ester in the solid-phase that hitherto met with little success using classical methodology (Scheme 44). The solid-phase boronate (106, 107) [243] was quantitatively obtained by treating a polymer-bound haloarene with the diboron. The subsequent coupling with haloarenes furnished various biaryls. The robot synthesis or the parallel synthesis on the surface of resin is the topic of further accounts of the research. 

Transition metal-catalyzed cross-coupling is now recognized to be one of the most powerful carbon-carbon bond-formation reactions [1], The palladium-catalyzed coupling of aryl halides or their synthetic equivalents, for example aryl triflates, with arylmetals is very often employed in the synthesis of biaryl molecules, whose skeletons are found in a wide range of important compounds including natural products and organic functional materials [1-3]. 

The synthesis of unsymmetrical biaryls 8 from two monoaryl species involves the coupling of a metallated aromatic molecule 6 with an aryl halide or triflate 4 under the action of palladium(O) catalysis. The reaction involves a catalytic cycle in which palladium(O) inserts into the C-halogen bond via an oxidative addition to generate an arylpalladium(II) species 5 (Scheme 10.18). This undergoes a trans-metallation with the metallated component, producing a biarylpalladi-um(II) complex 7. The biaryl product is formed by reductive elimination. In the process, Pd(0) is regenerated and this can then react with a second molecule of aryl halide. Pd(0) is therefore a catalyst for the reaction. 

The first application of arylstannanes was presented by Stille who demonstrated the transferability of an aryl group from tetraphenyltin [50]. This approach was generalised by the improved preparation of arylstannanes from trialkylstannanes and aryl halides followed by their Pd(0) catalysed coupling with aryl halides [51]. Similarly to aryl halides, aryl triflates also react with arylstannates to give biphenyls [52]. Electron-rich aryl triflates are especially suitable coupling reagents in the synthesis of unsymmetrical biaryls [53]. Symmetrical biaryls can be easily obtained by the reaction of an aryl triflate with 0.5 eg. of hexamethyldistannane. 

Ready availability of arylboronic esters from aryl halides or triflates (Eqs. 13 and 14) now offers a one-pot, two-step procedure for synthesizing unsymmetrical biaryls. The cross-coupling reaction of bis(pinaco-lato)diboron with triflate in dioxane is followed by a subsequent coupling with another triflate in the presence of K3PO4 to furnish an unsymmetrical biaryl from two triflates (Eq. 63). The synthesis from two different... 

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