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.
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.