Capretta Group

Palladium-Catalyzed Cross-Coupling Chemistry

Pd-catalyzed cross-couplings are powerful, versatile reactions used routinely by synthetic chemists for C-C and C-heteroatom bond formation. The 2010 Nobel Prize in Chemistry awarded to Heck, Negishi and Suzuki is a testament to the utility and widespread application of these reactions. Key to the success of Pd-catalyzed cross-couplings is the choice of ligand used in the reaction. The Capretta group has developed reliable catalytic systems for organopalladium cross-coupling reactions utilizing ligands based on the phospha-adamantane (PA) skeleton.

We have demonstrated that our PA ligands compete well with others currently used for these reactions but are stable at elevated temperatures, resistant to oxidation and easily derivatized in a single step at the phosphorous allowing for tunable, “tailored” ligands. The chemistry developed has allowed for the creation of a toolkit of structurally diverse PA ligands, each with unique steric and electronic properties, that can be screened to identify the ligand best suited for a particular Pd cross-coupling reaction. Their performance has been outstanding. These ligands allow a variety of Suzuki, Sonogashira, ketone arylation and amination reactions to proceed at room temperature in a few hours, even with less-reactive substrates.

In addition, the PA / Pd-catalytic systems are ideal platforms for library generation as they allow for convergent strategies in high yields; their efficacy allows for low catalyst loadings; and they are easy to use as they do not require any special handling. Furthermore, many of the popular ligands described in the literature are problematic when coupling substrates containing heteroatoms (especially nitrogen) as these compounds often poison the catalytic systems.