HIGHLY EFFICIENT AND ACCELERATED SUZUKI ARYL COUPLINGS MEDIATED BY PHOSPHINE-FREE PALLADIUM SOURCES

Suzuki aryl cross-couplings employing aryl bromides and aryl iodides proceed under mild conditions (65 degrees C) with high efficiency (substrate-to-catalyst ratios in excess of 500) in the presence of phosphine-free palladium catalysts derived from palladium acetate, Pd-2(dba)(3).C6H6 (dba = dibenzylideneacetone), and [(eta(3)-C3H5)PdCl](2). Phosphine inhibition is shown to play a key role in limiting catalytic efficiency; qualitative comparison studies show that the phosphine-free systems are 1-2 orders of magnitude more active than phosphine-supported catalytic systems. Pd[P(Ph)(3)](4) proved to be the least active of the catalytic species screened. The phosphine-free methodology appears to be generally applicable; cross-couplings of aryl iodides yielding biaryls 6 and 7 proceed without noticeable steric or electronic effects. Cross-couplings employing aryl bromides are insensitive to electronic effects in the synthesis of 6 but are slowed by steric hindrance in the synthesis of 7. Acceleration of cross-coupling is observed in the presence of polar cosolvents and at high pH.