Rapid catalyst identification for the synthesis of the pyrimidinone core of HIV integrase inhibitors.

Microscale multiparallel chemistry platform technologiesenable modern synthetic chemists to rapidly apply knownpotential solutions for a given synthetic transformation tonew, high-complexity synthetic problems. This paradigm istypically most successful for solving problems where a richhistory of relevant literature precedents and a thoroughmechanistic understanding of the target reaction alreadyexist. For example, a Suzuki reaction platform employing anarray of known effective phosphine ligands, reaction solvents,and inorganic bases can be screened to uncover optimalsubstrate-specific reaction conditions with a high probabilityof success. However, many synthetic problems arise for whichrationally designedplatformsarenot available,andcannot bedesigned owing to a lack of precedent or understanding.Nevertheless, microscale high-throughput experimentation(HTE) tools can be used to maximize the opportunity toserendipitously improve reaction performance, and severalrecent, high-profile reports have highlighted some initialprogress in this area.