Hydroformylation and carbonylation processes: new trends in the synthesis of pharmaceuticals

Abstract

The synthesis of complex organic molecules by catalytic transformations has made a significant impact on the development of new routes to a variety of pharmaceutical intermediates and optically active drugs. Carbonylation and hydroformylation reactions using metal complex catalysts are particularly attractive in this context as they provide clean, atom-efficient routes for the synthesis of molecules with carboxylic acid, aldehyde and amide functional groups to replace stoichiometric, multi-step routes using toxic and hazardous reagents. This review presents an update of recent research demonstrating the novel features of catalytic carbonylation and hydroformylation reactions and the current state of their development. Besides the expanding applications of carbonylation reactions, their unique features, such as high regioselectivity, high enantioselectivity (using appropriate chiral ligands) and their combination with other reactions to facilitate tandem (one-pot) synthesis, are highly promising. Clearly, the future direction is toward the synthesis of enantiomerically pure drug molecules and intermediates by asymmetric catalysis if the challenges of catalyst-product separation and the development of chiral ligands at a lower cost can be met.