46857-AC4
Gas Phase Studies of Stereoselective Binding to Models of Reactive Intermediates in Metal/Salen Catalyzed Epoxidations
During the first year of the grant, progress has been made on several aspects of the project including work focused on the binding of chiral alcohols and epoxides to the Jacobsen catalyst. In addition, we have nearly completed an additional study aimed at determining the relative binding strengths of various ligands to the Jacobsen catalysts.
Chiral Alcohols
We extended and refined our preliminary work on the binding of chiral alcohols to a set of derivatives of the Jacobsen catalyst. These studies led to three important findings: (1) the size of the alcohol is important and stereoselectivity in binding is not seen in simple alcohols such as 2-butanol, but is present in 1-phenylethanol, reaching a maximum preference of 1.58 (S/R); (2) as in solution, the gas phase data indicate that the R,R enantiomer of the catalyst prefers the S enantiomer of 1-phenylethanol; and (3) variations in the structure of the catalyst leads to gas-phase binding trends that mirror results from condensed-phase studies of epoxidations. This work led to a publication in Organic Letters.
Chiral Epoxides
The next target of our studies was binding to chiral epoxides. These represent models for the products of the Jacobsen-catalyzed epoxidations. Overall the level of stereoselectivity is reduced in the epoxides. Preferences from 1.1 to 1.2 are observed and unlike the alcohols, small chiral epoxides (i.e., trans-1,2-dimethyloxirane) and large chiral epoxides (i.e., phenyloxirane and trans-1-methyl-2-phenyloxirane) give about the same result. These data suggest that the geometries of the epoxides place the chiral centers far from the asymmetric environment created by the catalyst. Again, there is some variation based on the structure of the catalyst, but it is not much more significant than the expected uncertainties of the experiment. A small study using chromium rather manganese in the catalyst led to the same conclusion. This is consistent with mechanistic models that suggest an early transition state for the chirality-fixing step of Jacobsen epoxidations. We have decided not to pursue further studies with the epoxides.
Other Ligands
Results from the first two studies indicated that it would be useful to have a general measure of the ligand binding of various functional groups to the Jacobsen catalyst, particularly because the final aspect of the project is assessing the role of addition ligands on the binding selectivity of the catalysts. To this end, we have completed a series of equilibrium experiments in which we compare binding of two potential ligands (achiral). By doing pair-wise comparisons, a scale of ligand affinities can be created. To date, the scale contains 11 species spanning a binding range of 4.5 kcal/mol. The list contains ethers, ketones, alcohols, and amines. Steric effects are significant and THF binds nearly 4 kcal/mol stronger than diethyl ether. We are now extending the scale to stronger binders such as sulfoxides.
Studies Underway/Planned
In the last year of the grant, we plan to finish the work on the binding scale of ligands to the Jacobsen catalyst. This work will be followed up in two ways. First, based on the results, we plan to look at stereoselectivity in binding to stronger, chiral ligands. At this point, the most likely and practical targets are amines. Second, we will investigate the stereochemical preferences of the Jacobsen catalyst when it carries an effectively non-labile ligand (here the target metal complex will be hexacoordinate). In this work, we may need to turn to chromium species because they have a higher affinity for ligands and a greater tendency to become hexacoordinate in the gas-phase.
Participation
As of August, three PhD students and three undergraduates participated in studies related to the project. At this time, two new undergraduates have joined the project. The work also was presented in June at the American Society for Mass Spectrometry in Denver meeting and travel funds were used for that purpose.
