Paul G. Williard

Professor of ChemistryChair, Department of Chemistry

Research Area

Contact Info

GeoChem 441401-863-3589EmailResearchers@Brown ProfileWilliard Lab Webpage

Research Statement

My research projects are grouped into three distinct areas. 

The first of these focuses on obtaining structural and mechanistic information for reactive intermediates such as enolate anions and amide bases. Hence I have discovered and published an extensive sequence of crystal structures of aggregates that are formed upon mixing enolizable substrates with amide bases. A sequence of aggregated 15-20 structures depicting different possible stages of an aldol reaction can be found on my web page. 

Most recently, I have begun to utilize diffusion oriented NMR (DOSY or DO-NMR) to correlate the solid state crystal structure determined by x-ray diffraction analyses with the corresponding solution state species. We are also developing the DOSY NMR methodology to allow us to determine molecular weights of these species in solution. This is extremely exciting because it allows us to determine the solvation state of the aggregates in solution directly by NMR. This is the only convenient way to obtain such information at the subambient temperatures where these species are typically utilized. 

The second main area of research focuses on developing asymmetric synthetic reaction methods based upon the structural and mechanistic information accumulated in my group. Most recently, we are looking at several template aggregates that have cropped up with a wide range of structure variation but which maintain the same general 2:1 chiral co-factor to reactive nucleophile stoichiometry. Also, we have recently begun to expand this project by preparing small polymeric versions of these chiral templates. Initial results of this study are available. 

Finally, I have maintained an involvement in several purely drug development projects with different collaborators at the affiliated Brown University Hospitals, the Rhode Island Nuclear Science Center, and the RI Cancer Council. These projects involve synthesis of and discovery of new drugs for cancer chemotherapy. The currently active project involves synthesis of gadolinium containing porphyrin derivatives and both in vitro and in vivo screening of these as neutron capture agents. 

Areas of Interest

  • X-ray diffraction analysis
  • organolithium compounds
  • NMR
  • organometallics
  • organic synthesis

Education

  • 1976 - Ph.D.: Columbia University
  • 1974 - M.A. Columbia University
  • 1972 - B.S./M.S.: Bucknell University

Selected Publications

  • Berton, M.; Mello, R.; Williard, P. G.; Gonzalez-Nunez, M. E., Reactivity of Lithium beta-Ketocarboxylates: The Role of Lithium Salts. J Am Chem Soc 2017, 139 (48), 17414-17420.
  • Bradley, D.; Levin, E.; Rodriguez, C.; Williard, P. G.; Stanton, A.; Aaron, M., Equilibrium studies of canola oil transesterification using a sodium glyceroxide catalyst prepared from a biodiesel waste stream. Fuel Processing Technology 2016, 146, 70-75.
  • Fujiu, M.; Negishi, K.; Guang, J.; Williard, P. G.; Kuroki, S.; Mikami, K., Chemo-, regio-, and stereo-selective perfluoroalkylations by a Grignard complex with zirconocene. Dalton T 2015, 44 (45), 19464-19468.
  • Guang, J.; Hopson, R.; Williard, P. G., Diffusion Coefficient-Formula Weight (D-FW) Analysis of H-2 Diffusion-Ordered NMR Spectroscopy (DOSY). J Org Chem 2015, 80 (18), 9102-9107.
  • Guang, J.; Hopson, R.; Williard, P. G.; Fujiu, M.; Negishi, K.; Mikami, K., Perfluoroalkyl Grignard Reagents: NMR Study of 1-Heptafluoropropylmagnesium Chloride in Solution. J Org Chem 2016, 81 (14), 5922-5928.
  • Guang, J.; Liu, Q.; Hopson, R.; Kagan, G.; Li, W. B.; Monroe, T. B.; Williard, P. G., Conformational Polymorphism of Lithium Pinacolone Enolate. J Am Chem Soc 2016, 138 (46), 15177-15188.
  • Guang, J.; Liu, Q. P.; Hopson, R.; Williard, P. G., Lithium Pinacolone Enolate Solvated by Hexamethylphosphoramide. J Am Chem Soc 2015, 137 (23), 7347-7356.
  • Kreye, M.; Freytag, M.; Jones, P. G.; Williard, P. G.; Bernskoetter, W. H.; Walter, M. D., Homolytic H-2 cleavage by a mercury-bridged Ni(I) pincer complex {(PNP)Ni}(2){mu-Hg}. Chem Commun 2015, 51 (14), 2946-2949.
  • Nayyab, S.; O'Connor, M.; Brewster, J.; Gravier, J.; Jamieson, M.; Magno, E.; Miller, R. D.; Phelan, D.; Roohani, K.; Williard, P.; Basu, A.; Reid, C. W., Diamide Inhibitors of the Bacillus subtilis N-Acetylglucosaminidase LytG That Exhibit Antibacterial Activity. Acs Infect Dis 2017, 3 (6), 421-427.
  • Tai, O.; Hopson, R.; Williard, P. G., Aggregation and Solvation of n-Butyllithium. Organic Letters 2017, 19 (15), 3966-3969.
  • Tai, O.; Hopson, R.; Williard, P. G., Ligand Binding Constants to Lithium Hexamethyldisilazide Determined by Diffusion-Ordered NMR Spectroscopy. J Org Chem 2017, 82 (12), 6223-6231.
  • Zhang, Q. F.; Williard, P. G.; Wang, L. S., Polymorphism of Phosphine-Protected Gold Nanoclusters: Synthesis and Characterization of a New 22-Gold-Atom Cluster. Small 2016, 12 (18), 2518-2525.
  • Zhang, Y. Y.; MacIntosh, A. D.; Wong, J. L.; Bielinski, E. A.; Williard, P. G.; Mercado, B. Q.; Hazari, N.; Bernskoetter, W. H., Iron catalyzed CO2 hydrogenation to formate enhanced by Lewis acid co-catalysts. Chem Sci 2015, 6 (7), 4291-4299.
  • Zhang, Y. Y.; Williard, P. G.; Bernskoetter, W. H., Synthesis and Characterization of Pincer-Molybdenum Precatalysts for CO2 Hydrogenation. Organometallics 2016, 35 (6), 860-865.