The design of reagents to control the stereochemistry of organic reactions is an area of growing importance in organic chemistry. Stereochemistry is the study of stereoisomers -- compounds that have the same atomic connectivity but differ in their 3-dimensional orientation in space. Objects that have a non-superimposable mirror image (such as your hands) possess the property of chirality. The configuration of organic molecules has a profound impact on their behavior in chiral environments such as the human body; mirror image molecules are seen as different species and possess different chemical properties. For example, the compounds that provide the flavors of spearmint and caraway are mirror image molecules, which are perceived differently by the taste receptors on the human tongue. Pharmaceutical companies have become increasingly interested in the selective synthesis of one mirror image (enantiomer) of a drug. In most cases, one stereoisomer is active while the other, at best, is just a spectator or, at worst, causes serious complications that compromise the efficacy of the drug.
Our research focuses on the development of a catalytic asymmetric cyclopropanation system utilizing chiral transition metal Schiff base complexes and diazo compounds. The cyclopropane functionality occurs in commercial insecticides as well as many natural products of biological importance and can be converted into other organic functional groups. We have developed a cyclopropanation system in which the active catalytic species is formed in situ from chiral Schiff-base ligands and copper(I) catalyst precursors. This system is active for the cyclopropanation of styrene with high yields and moderate enantioselectivities of up to 56% ee (4:3 = 78:22 ratio) with anti:syn diastereoselectivities ((3+4):(1+2)) on the order of 2:1. In some cases, we have observed an increase in enantioselectivity by lowering the reaction temperature, although this increase is accompanied by a decrease in yield. In order to further improve the stereoselectivities, we have investigated the use of several diazo compounds with differing steric requirements. One of these species results in formation of the cyclopropanation products with very high diastereoselectivities (up to 20:1). We have also developed a novel cyclopropanation system in which the copper catalyst precursor is replaced with a ruthenium complex that, to our knowledge, has never been previously reported as a cyclopropanation catalyst precursor. This system has given enantiomeric excesses up to 80% (90:10 ratio of enantiomers) for the cyclopropanation of styrene.