Using stereocartography for predicting efficacy of stereoinduction by chiral catalysts.

A computational method called stereocartography is used to examine regions around chiral catalysts that are most stereoinducing during Diels-Alder reactions. Geometries and atomic charges of catalysts are first generated quantum mechanically. The transition state of the reaction being catalyzed is then computed quantum mechanically and those enantiomeric transition states are used as probes to determine where around the catalyst stereoinduction is optimal. A description of how to treat catalysts with multiple conformations is given. In this article seven catalysts containing a variety of ligand motifs and metals were evaluated. The hypothesis that the region of maximum stereoinduction must be spatially coincident with the site of chemistry for a catalyst to be efficient is upheld.

Stereocartography: a computational mapping technique that can locate regions of maximum stereoinduction around chiral catalysts.

A hypothesis concerning asymmetric induction by chiral catalysts is posited, tested, and found to be valid. The hypothesis states that chiral catalysts that are efficient at inducing asymmetry will have their region of maximum stereoinduction spatially congruent with the site of chemistry but inefficient catalysts will not. A simple mapping strategy (stereocartography) is used to assess where the region of maximum stereoinduction is located around a given catalyst. The protocol compares interaction energies between mirror image probes at each point in space around the catalyst being considered. The probes are models of the actual transition states of the reaction being catalyzed by a particular catalyst. The hypothesis was tested on three Diels-Alder reactions. Seventeen of the eighteen catalysts conform to the hypothesis. The idea of using this as a catalyst design tool is presented.