Palladium-catalyzed cross-coupling of aryl(dimethyl)silanols: Method development and mechanistic analysis

The palladium-catalyzed cross-coupling of aryl(dimethyl)silanols with substituted aryl halides is effectively promoted by cesium carbonate and cesium hydroxide monohydrate. Extensive optimization studies led to the identification of key variables that influence the rate and selectivity of the process including solvent, catalyst, additive, and hydration level. Manipulation of these features provides an effective coupling method of wide scope and generality. Electron rich aryl(dimethyl)silanols under go cross-coupling with aryl iodides and aryl bromides in high yields and high selectivity for the desired cross-coupling products. Alternatively, high yields of cross-coupling products could be obtained with electron poor or ortho-substituted aryl(dimethyl)silanols when activated with cesium hydroxide monohydrate.; The mechanism of the cross-coupling reactions was studied through kinetic analysis employing initial rate analysis. These studies revealed that transmetalation from a arylpalladium(II) silanolate is the turn over limiting event. This observation allowed for the independent synthesis and isolation of a key intermediate for the preparative cross-coupling reaction. The structure and reactivity of the arylpalladium(II) silanolate intermediate was also found to be competent toward productive cross-coupling to provide unsymmetrical biaryl products.