45452-B1
Asymmetric Heterogeneous Catalytic Hydrogenations
Based on our earlier findings we have made further progress on the asymmetric hydrogenation of isophorone on proline-modified Pd catalysts.
It is interesting to see the renewed interest in this reaction since our group began to study this system in 2003 (with the support of an earlier PFR grant). Several groups have joined the search for a more accurate mechanism. The PI’s group made a breakthrough in clarifying the mechanism of the reaction, by discovering that the secondary kinetic resolution is the major source of the enantioselection in the hydrogenation. We have attributed this phenomenon to the special catalysts we have used in the reactions. Another group, however, published contradictory results, stating that the enantioselection is merely the result of a homogeneous reaction between proline and the reactant.
This prompted us to carry out further investigations in this direction, and provide unquestionable experimental results to either support or rule out the homogeneous enantioselection mechanism.
Our recent paper entitled “Nature of Proline-Induced Enantiodifferentiation in Asymmetric Pd Catalyzed Hydrogenations: Is the Catalyst Really Indifferent?” (Mhadgut, M. Török, Dasgupta, B. Török, Catal Letters, 2008, 123, 156-163.) summarizes our findings. Without going into technical details our major finding have provided further experimental evidence to support the heterogeneous enantiodifferentiation model in the proline modified Pd catalyzed C=C double bond hydrogenation of a,b-unsaturated ketones that we proposed earlier. Using the enantioselective hydrogenation of isophorone as a test reaction we have shown that several experimental factors, such as modifier structure, and chemical nature of the catalyst support affect the outcome of the hydrogenations. Our results pointed out that the secondary kinetic resolution was a major reason for obtaining high enantioselectivities on most catalysts. The data also indicated that in the case of effective modifier-catalyst interaction the heterogeneous enantiodifferentiation model is primarily responsible for the high enantioselectivities. We have also proposed a new unified enantioselection model by integrating our results into the currently existing incoherent mechanistic schemes.
Interestingly, several other reports have been published by independent groups providing further experimental support for the heterogeneous enantioselection model proposed by us.
We have also gained substantial amount of data in a diastereoselctive hydrogenation project that is aimed at providing an environmentally benign method for the synthesis of chiral trifluoromethylated amines. This project was delayed by the lack of trifluoromethylated ketones, and we had to make substantial effort to synthesize our starting materials. Several compounds have been synthesized and the subsequent reactions with chiral a-methylbenzylamines have been carried out. We are currently in the phase of carrying out the diastereoselective hydrogenation and hydrogenolysis reactions. Several compounds provided excellent enantiomeric excesses (up to 95% ee), which suggest that the project is near its finish. We expect these results to be published in the next year.
I feel that the generous support from ACS-PRF made a significant positive impact on my career. It helped me, a relatively young researcher, to be able to contribute solving an important problem in heterogeneous asymmetric catalysis. We were able to make a breakthrough in the target reaction, which was already studied in the past 20 years. Obviously the positive impact can be seen not just on the PI, but also on the career of several undergraduate students who have participated in the project. One student (a minority, female student) already graduated and went on to obtain her PhD in Chemistry. Others are still working in the PI’s lab and their graduation is forthcoming in this and the next academic year. It is my sincere hope that after graduation these students will also enter either graduate school, or research oriented careers.
