Chiral Nucleophiles in Catalysis

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

Professor Edwin Vedejs in the Department of Chemistry at the University of Michigan is supported by the Organic and Macromolecular Chemistry Program for his development of methods to synthesize chiral molecules with high enantioselectivities using chiral phosphabicyclooctane (PBO) catalysts. One of the applications which will be studied is parallel kinetic resolution (PKR) using a polymer-bound PBO catalyst with a lipase catalyst to give two quasi-enantiomeric products, which can be converted into the two enantiomeric compounds. The synthesis of PBO catalysts with improved stability and selectivity will also be pursued. Many organic compounds exist as mixtures of equal amounts of mirror images, related to each other in much the same way a right hand is related to a left hand. These "right-handed" and "left-handed" components are referred to as enantiomers. Many natural products and pharmacologically active substances exist in one enantiomeric form. With the support of the Organic and Macromolecular Chemistry Program, Professor Vedejs is developing new phosphorus-containing catalysts which are used to react selectively with either the "right-handed" or "left-handed" enantiomer of certain organic compounds. In a process called parallel kinetic resolution, one catalyst reacts selectively with the "right-handed" component of a compound A to convert it into a product B and another catalyst reacts selectively with the "left-handed" enantiomer to produce a product C. Compounds B and C are then separated and transformed back to A, thus leading to an efficient separation of the two enantiomers of A. The ability to prepare enantiomerically pure versions of drugs is important for the pharmaceutical industry and would represent a potentially useful application of this methodology.