Catalyzing the Synthesis

Researchers develop various catalytic approaches for improving yield, purity, stereoselectivity, and process conditions.
Nov 01, 2011

IMage: Jason Reed / GETTY
Catalysts play an important role in chemical reactions, but they are particularly important in producing fine chemicals or pharmaceutical compounds to meet desired yields, purity, and stereoselectivity. Elucidating how a catalyst may work in a specific synthesis is not only valuable for a given project, but it contributes to an overall understanding of process chemistry. Some recent advances involve asymmetric synthesis and approaches for improved enantioselectivity, oxidation catalysis, and the development of boron-based ligands.

Improving enantioselectivity

Patricia Van Arnum
Researchers at the University of Amsterdam recently reported on an approach for identifying and developing catalysts to synthesize products with high enantioselectivity, a method of utility for making pharmaceutical compounds. The researchers reported on the development of an achiral bisphosphine rhodium complex, which contained a binding site for recognizing chiral anion "guests" or cofactors. Upon binding the small-molecule cofactors, the rhodium complex becomes chiral and can then be used in asymmetric catalysis. The researchers screened a library of cofactors and discovered the optimal cofactors, which led to the identification and development of hydrogenation catalysts that formed products with enantiomeric excess as high as 99%. The researchers also conducted a competition experiment to determine the optimal cofactor among a mixture of 12 cofactors. The optimal cofactor was one that binds strongest to the rhodium complex (i.e., the catalyst) and through the catalyst produced the product with greatest optical purity. The competition experiment provided the basis for creating an efficient way to screen a library of cofactors with other metal–ligand systems (1, 2). The University of Amsterdam chemists have patented the strategy and plan to develop it alongside their other high-throughput ligand-screening strategies through a spin-off company, InCatT.

Raising the bar in catalytic hydrogenation

Formulation development forum: translational pharmaceutics (FIGURE 1 IS COURTESY OF THE AUTHOR)
Researchers at the University of Alberta recently developed a new ruthenium-aminophosphine catalyst with very high turnover. The catalyst system was used for the hydrogenation of a variety of acyclic and cyclic amides to the corresponding alcohols and amines. They reported catalytic activity with turnover as high as 7200. Specifically, the researchers reported that the reaction between 2 equivalents of Ph2P(CH2)2NH2 and cis-[Ru(CH3CN)2 (η3-C3H5) (cod)]BF4 (cod = 1,5-cyclooctadiene) formed a highly active catalyst precursor for the selective hydrogenation of amides. The reaction proceeded with good atom economy, yield, and turnover under moderate reaction conditions (3). The researchers are working to further optimize the catalyst system, according to a Sept. 28, 2011, University of Alberta press release.