Fukuyama Cross-Coupling Approach to Isoprekinamycin: Discovery of the Highly Active and Bench-Stable Palladium Precatalyst POxAP

An efficient and user-friendly palladium­(II) precatalyst, POxAP (post-oxidative-addition precatalyst), was identified for use in Fukuyama cross-coupling reactions. Suitable for storage under air, the POxAP precatalyst allowed reaction between thioesters and organozinc reagents with turnover numbers of ~90000. A series of 23 ketones were obtained with yields ranging from 53 to 99%. As proof of efficacy, an alternative approach was developed for the synthesis of a key precursor of the natural product isoprekinamycin.