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This report outlines our achievements in the field of asymmetric catalysis with support of a new faculty undergraduate start-up grant, and discusses the impact of the research on the field of study, the career of the principal investigator, and the research training and careers of the undergraduate students who carried out the work.  In particular, as reported last year, an unexpected result opened up a new line of research in asymmetric homogeneous Lewis acid catalysis that has captured the interest of the P.I. and the P.I.’s student researchers.  This work has led to two scholarly publications, and to the solidification of a fruitful ongoing area of study for the P.I.  In the last year, this work has featured prominently in the P.I. receiving promotion to Associate Professor with tenure, and obtaining a new research grant from the National Science Foundation’s Research in Undergraduate Institutions (RUI) Program.  Alongside the goal of preparing heterogeneous asymmetric titanium Lewis acid catalysts, we began a study soluble, chiral titanium alkoxides as homogeneous catalysts, in order to make comparisons between the heterogeneous and homogeneous systems.  When a student researcher investigating the methylation of benzaldehyde with dimethyl zinc catalyzed by resolved titanium(IV) sec-butoxide discovered an unexpected result, a new line of research began to take hold in our laboratory.  In an interesting example of a "matched pair" asymmetric activation phenomena that allows us to achieve higher enantiomeric excess than previously reported in the literature for this catalysis, we observed that resolved R- or S- titanium sec-butoxide, combined with resolved BINOL (BINOL = 1,1'-bi-2-naphthol) of the opposite configuration designation, yields a dichiral matched pair that mediates the addition of dimethyl zinc to benzaldehyde with higher enantioselectivity than resolved BINOL with achiral Ti(OⁱPr)₄ or the mismatched dichiral pair.

The impact of this research on the field of catalysis is beginning to take shape.  Whereas the titanium mediated reduction of arylaldehydes with diethyl zinc to transfer an ethyl group is well studied, the transfer of a methyl group with dimethyl zinc has yet to be fully addressed.  While we have achieved the best results yet in this system, there is more room for improvement.  We have investigated other ligand systems besides BINOL, such as tetrahydrosalen (tetrahydrosalen = N,N '-bis(o-hydroxybenzyl)-trans-1,2-diaminocyclohexane) and several chiral bis(phosphine oxide) ligands, in combination with resolved titanium sec-butoxide as asymmetric Lewis acid catalysts.  For example, the reaction of racemic or resolved (R,R)-tetrahydrosalen, LH₂, (LH₂ = N,N’-bis(3,5-dichloro-2-hydroxybenzyl)-trans-1,2-diamino-cyclohexane) with resolved Ti(O^R-2Bu)₄ or Ti(O^S-2Bu)₄ yielded a series of 4 compounds which have been characterized by NMR and X-ray crystallography.  Analysis by X-ray crystallography revealed the co-crystallization of two C₂-symmetric products from racemic LH₂, whereas a perfect chiral induction of the ligand to the metal occurred when resolved (R,R)-LH₂ ­was used, resulting in only a Δ fac-fac wrapping mode of the tetradentate ligand about the titanium center. Ab initio electronic structure calculations (DFT) are in agreement that the lowest energy isomers are those that are experimentally observed.  Catalysis screenings show that Ti(O^S-2Bu)₄, in conjunction with (R,R)-LH₂, forms a matched pair that catalyzes the addition of dimethyl zinc to benzaldehyde with higher enantioselectivity than that observed for resolved (R,R)-LH₂ with Ti(O^R-2Bu)₄ or achiral Ti(OⁱPr)₄.  Although the results are not as promising as in the BINOL system, we have found an interesting results with the tetrahydrosalen system; increasing the temperature of the catalysis results in slightly increased enantiomeric excess, although transfer hydrogenation producing benzyl alcohol becomes competitive under certain conditions. 

The results obtained while the PRF new faculty undergraduate start-up grant was active have; i) seeded the scholarship, and therefore career development, of the P.I. in a new area of investigation that featured prominently in a successful review for promotion to Associate Professor, ii) provided research training for several undergraduate students with novel, publishable research, and iii) allowed for the dissemination of the interesting new results at conferences and in publications.  Two former undergraduate students are the lead authors on a publication in 2008 that describes their work on the synthesis of the chiral alkoxides and the catalysis screening with BINOL; both students are now in graduate school in chemistry.  One of these students, along with another former student and a current student were the lead authors of the publication on the tetrahydrosalen work in 2009.  Several other students have also worked on aspects of this project.  All of these students participated in presenting their work at least once at local, regional and/or national meetings of the American Chemical Society.  In addition, this work was selected for presentation by the P.I. at the competitive national Science Foundation Inorganic Chemistry Workshop during the summer of 2009.

In summary, we report that the PRF funded work described here has led to publishable fundamental research in the field of asymmetric catalysis that have positively impacted the scholarship and careers of the P.I. and students who have worked on the project.