Highly Efficient and Accelerated Suzuki Aryl Couplings Mediated by Phosphine-Free Palladium Sources

Article abstract of DOI:10.1021/jo00096a056

Suzuki aryl cross-couplings employing aryl bromides and aryl iodides proceed under mild conditions (65 deg C) with high efficiency (substrate-to-catalyst ratios in excess of 500) in the presence of phosphine-free palladium catalysts derived from palladium acetate, Pd2(dba)3*C6H6 (dba = dibenzylideneacetone), and <(η³-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.Pd4 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.