Sheryl L. Wiskur
|Title:||Associate Professor / Organic
Catalysis / Organometallic / Supramolecular
|Department of Chemistry and Biochemistry|
Office: GSRC 431
Lab: GSRC 436, 803-777-9377
Lab 2: GSRC 437
Sheryl Wiskur Group Website
B.S., 1997, Arizona State University
Ph.D., 2003, University of Texas – Austin
Honors and Awards
USC AI Faculty Partner of the Year, 2014; Division of Organic Chemistry Young Academic Award, 2014; Breakthrough Rising Star USC, 2013; SC EPSCoR Diversity Award, 2012; NSF CAREER Award, 2011-2016.
Synthetic methodology, organocatalysis, physical organic, bioorganic, sensors.
My research interests lie within the area of synthetic organic methodology. We are focused on developing facile methods to efficiently resolve and isolate medicinally important enantiopure compounds. Most recently we have been focused on kinetic resolutions toward accomplishing this goal, and exploring the mechanism of the methodology we have developed.
Optically active intermediates are of increasing importance in the pharmaceutical and agrochemical industries as the number of active chiral compounds in their pipelines grow. Chiral alcohols and amines are of particular importance in the development of many products for these industries. While there are ways to form these compounds asymmetrically, industry has still found kinetic resolutions to be a very efficient and economical way to obtain enantiomerically pure compounds. A kinetic resolution is a separation of enantiomers by selectively reacting one enantiomer over the other in an asymmetric reaction. This works when one of the enantiomers reacts faster than the other (kS > kR). Kinetic resolutions are evaluated by selectivity factors, which is a ratio of the rate of the fast reacting enantiomer over the rate of the slow reacting enantiomer (Figure 1). One of the advantages of a kinetic resolution over an asymmetric reaction is that the enantiomeric excess of the starting material is continuously increasing as the reaction progresses. This allows for the recovery of highly enriched material, even when the resolution only has moderate selectivity.
We have developed new strategies for the separation of alcohols. Our approach towards this employs a silyl group to asymmetrically derivatize one enantiomer over another. We have employed this to resolve cyclic secondary alcohols such as chromanol (Figure 1) and α-hydroxy lactones and lactams (Figure 2). These compounds are all important starting materials in the synthesis of biologically active compounds.
In order to further improve our reaction, an understanding of the mechanism is crucial. We have employed different physical organic techniques in order to gain some understanding of the mechanism, including a linear free energy relationship study and a kinetic study. The ultimate goal is to determine how all the pieces come together to asymmetrically silylate one enantiomer, yet not silylate the other one. This information will help us continue to expand our methodology to include other substrates and other classes of compounds.
Wang, L.; Zhang, T.; Redden, B. K.; Sheppard, C. I.; Clark, R. W.; Smith, M. D.; Wiskur, S. L. “Understanding Internal Chirality Induction of Triarylsilyl Ethers Formed from Enantiopure Alcohols” J. Org. Chem. 2016, 81, 8187-8193. DOI: 10.1021/acs.joc.6b01137.
Wang, L.; Akhani, R. K.; Wiskur, S. L. "Diastereoselective and Enantioselective Silylation
of 2-Aryl Cyclohexanols." Org. Lett. 2015, 17, 2408 - 2411.
Akhani, R. K.; Clark, R. W.; Yuan, L.; Wang, L.; Tang, C.; Wiskur, S. L. "Polystyrene-Supported
Triphenylsilyl Chloride for the Silylation-Based Kinetic Resolution of Secondary Alcohols." ChemCatChem 2015, 7, 1527 - 1530.
Akhani, R. K.; Moore, M. I.; Pribyl, J. G.; Wiskur, S. L. "Linear Free-Energy Relationship and Rate Study on a Silylation-Based Kinetic Resolution: Mechanistic Insights." J. Org. Chem. 2014, 79, 2384 - 2396. DOI: 10.1021/jo402569h.
Clark, R. W.; Deaton, T. M.; Zhang, Y.; Moore, M. I.; Wiskur, S. L. "Silylation-Based Kinetic Resolution of α-Hydroxy Lactones and Lactams." Org. Lett. 2013, 15, 6132 - 6135. DOI: 10.1021/ol402982w.