Zhaohua Dai, PhD , Pace University
We proposed to develop chiral-TPA derivatives based catalytic systems that can transform aliphatic C-H bonds into chiral alcohols with high enantioselectivity using the environmentally friendly oxidant H2O2. To arrange the pyridyl arms of TPA into propeller-like chiral configuration in FeII complexes and put the reactive intermediate FeV=O in a chiral bias, we proposed that a methylene proton in TPA was to be substituted with a methyl group to chiral podands; in second generation catalysts, a rigidified piperidine ring was to be incorporated by connecting the two chiral arms; further rigidified ligands could incorporate a second ring, resulting in chiral quinuclidine structures. The original design is shown in Figure 1.
Figure 1. Original design of catalytic alkane hydroxylation using rigidified chiral-TPA scaffolds.
The P.I. and his undergraduate and grauduate research assistants have successfully obtained many of the proposed chiral podand, pipredine and quinuclidine ligands. During the previous reporting period, we synthesized some of the original proposed podand, piperidine and quinuclidine TPA ligands, which are shown as the left 3 structures in Figure 2. During this reporting period, the other enantiomer of each of these 3 compounds was obtained by Pace undergraduates Nick Wenyao Zhang, Layanne Valdez, and Pace graduate student (MS candidate) Patrick Carney with the help from Pace undergraduates Daisy Brito and Maykel Khilla, Pace graduate students (MS candidates) Raquele Laury-Lee and Tahsee Washington, NYU undergraduate Jennifer Lee, and Midwood High School student Kirill Grinberg. Theses lignads are fully characterized. The absolute configuration obtained matched what was expected from asymmetric synthesis and the e.e. was determined by chiral HPLC to be >99%. More ligands (the right 3 structures in Figure 2), both chiral and achiral were made during this reporting period.
Figure 2. Structures of the synthesized TPA ligands.
B. Attempt to obtain Fe(II) complexes of the above lignads
We did obtained X-ray quality crystal for Fe(II) complexes of some non-chiral TPA ligands (the right two lignad in Figure 2). LCMS showed the synthesized chiral ligands can form complexes with Fe(II). However, no single crystals of the any complexes between Fe(II) and enantiomerically pure chiral ligand were obtained through recrystallization. From the experience of our collaborators, we learned that single crystals of Fe(II) complexes might be able to be obtained using racemic ligands instead, which we will try. At the same time, we have been simply using the non-crystalline form of the Fe(II) complexes of these chiral ligands for catalysis studies.
C. Catalysis and future work
The catalytic properties of the metal complexes of the synthesized ligands have been investigated during this reporting period. We are able to reproduce Lawrence Que's result by oxidizing cyclohexane into 1-cyclohexanol with hydrogen peroxide catalyzed by the Fe(II)-TPA complex. We were able to oxidize branched alkanes into alcohols (characterized by GCMS) using the Fe(II)-complexes of the synthesized chiral TPA derivatives. We tried to establish the enantiomeric excel (e.e.) of the product using a valine-based chiral GC column. However, this column seems to be unable to separate the enantiomers of the resulted alcohol. After consulting Christina White's paper, we obtained b-cyclodextrin based chiral GC columns to establish the e.e. Such investigation is under way. For this reason, we are asking a one-year no-cost extension of this award.
I had been trying to stimulate students' interest in chemistry through research projects in contemporary issues as described in this proposal. However, due to the high cost of living in New York City, it was hard to recruit Pace undergraduates who are from financially distressed families in the City and who are not from the Tri-state region in the summer. With this grant and other grants, several students are convinced of the scientific rigor of my research and my research assistants get some stipend in the summer. Since then, quite a number of students joined my group, which helps me develop a stable, sustainable and more diverse research work force, advancing the research program at Pace and my own career in academia. Together with my excellence in teaching, service and research, especially research supported by external grants like this grant, I was granted tenure this September.
Successful completion of the different stages of the project gives my students a strong sense of achievement, leading to careers in the discipline of chemistry. Fifteen students, including several members from groups under-represented in the discipline of chemistry, have worked on my research projects and they do pursue careers in chemistry. Michael Isaacman, Stacy-Ann Collins (female, African-American), Steven Lopez (Hispanic) and Cho Tan (female) are in Ph.D programs in chemistry and biochemistry. Amanda Mickley went to graduate school for biochemistry. Patrick Carney, Raquele Laury-Lee (female, African American), Tashee Washington (female, African-American) and Christine Toledo (female, Filipino-American) is getting a Master's degree in forensic chemistry. Jenifer Lee (female) was a psychology major and she decided to pursue career in natural science fields. This September, she is entering medical school. Maykel Khilla, Layanne Valdez (female, Hispanis) and Wenyao Nick Zhang expressed their wishes to pursue graduate degrees in chemistry related fields. Many of our forensic science graduates go on to work as forensic chemists. Kirill Grinberg, a Midwood High School student who worked in my lab on this and other projects, is going to be biochemistry major at Hunter College, CUNY this September.