Physical-organic chemistry: stereoelectronic effects; hydrogen bonding; isotope effects; ionic solvation; naked anions; malonic anhydrides
Awards and Academic Honors
American Chemical Society James Flack Norris Award in Physical Organic Chemistry
Murray Goodman Endowed Chair
Andrew Streitwieser Lecturer, UCBerkeley
Wawzonek Memorial Lecturer, University of Iowa
Visiting Professor, Gothenburg Univrsity
Phi Beta Kappa lecturer, UCSD
UCSD Chancellor's Associates' Faculty Excellence Award for teaching
UCSD Academic Senate Distinguished Teaching Award
Danish Research Academy Visiting Professor
NATO Visiting Professor, University of Padua
Fellow, Amer. Assn. Adv. Science
NIH Special Research Fellow, Gothenburg University
Alfred P. Sloan Fellow
NSF Postdoctoral Fellow, University of California, Berkeley
Our research in physical-organic chemistry is concerned with molecular structure, mechanisms of organic reactions, and effects of structure on reactivity. Areas of current activity include NMR studies of hydrogen-bond symmetry, of isotope effects, of stereochemical effects on reactivity, of the anomeric effect, and of steric hindrance.
Is a hydrogen bond symmetric or asymmetric? The NMR method of isotopic perturbation can answer this for monoanions of 18O-labeled dicarboxylic acids and for various NHN species. The former had always been considered as having a symmetric intramolecular hydrogen bond. Nevertheless, the observed 13C spectra show that all of these exist as a pair of tautomers in solution.
Cationic groups were thought to prefer the equatorial position on a sugar molecule. We reinvestigated this so-called reverse anomeric effect by measuring axial/equatorial ratios of various glucosylamines and glycosylimidazoles. The conformational changes that occur upon N-protonation can be accounted for on the basis of steric effects and an enhancement of the normal anomeric effect. Substituted glucosylanilines fine-tune the localization of positive charge, which increases the steric hindrance to ionic solvation but enhances the anomeric effect to an even greater extent.
A highly accurate (±0.002 pH units!) NMR titration method, applicable to a mixture of closely related molecules, has been developed. We use this method to measure isotope effects on basicity and steric hindrance to ionic solvation. For amines we have demonstrated that the increased basicity on deuteration is of stereoelectronic origin. In contrast, computations and experimental evidence show that the well-known reduction of one-bond NMR coupling constants is not due to lone-pair delocalization, even though this had been the accepted interpretation for forty years.
We have discovered a remarkable new reaction, the addition of nucleophiles to a p-benzyne biradical. As evidence, we showed that the enediyne cyclodeca-1,5-diyn-3-ene, in the presence of lithium halide and a weak acid, can be converted to a good yield of 1-halotetrahydronaphthalene. The reaction is simply first-order in enediyne, and independent of the concentrations of acid and halide. These kinetics are consistent with rate-limiting cyclization to a p-benzyne biradical that rapidly adds halide, to form an aryl anion, which is then protonated. The reaction thus involves nucleophilic addition of halide, which is novel and quite different from the usual radical reactivity of a p-benzyne biradical.
Primary Research Area
Research in my lab has provided a small number of graduate students with an excellent opportunity to develop problem-solving skills while learning new relationships between molecular structure and reactivity.
In my lab, I have mentored numerous undergraduate, graduate and postdoctoral scholars from diverse backgrounds. I have also taken advantage of our proximity to Mexico to present seminars at the Instituto Tecnológico de Tijuana and to participate in congresses of the Mexican Chemical Society.
- C. L. Perrin "Whither Physical Organic Chemistry? Wither? Or Wider?", Isr. J. Chem.DOI: 10.1002/ijch.201500027, 2016, Vol. 56, Issue 56, 46-52
- Perrin, C. L., Chang, K. L. "The Complete Mechanism of an Aldol Condensation.", J Org Chem, 2016,
- Charles L. Perrin "Comment on ‘‘The role of electrostatic induction in secondary isotope effects on acidity’’ (by E. A. Halevi, New J. Chem., 2014, 38, 3840)", New J. Chem, 2015, Vol. 39, 1517-1521
- Charles L. Perrin "Half a century of research, teaching, service", J. Phys. Org. Chem., 2015, Vol. 28, 203-209
- Perrin, C. L., Burke, K. D. "Can a Secondary Isotope Effect Be Larger than a Primary?", J. Phys. Chem. A, 2015, Vol. 119, 5009-5018
- A. E. Carpenter, A. J. McNeece, B. R. Barnett, A. L. Estrada, C. C. Mokhtarzadeh, C. E. Moore, A. L. Rheingold, C. L. Perrin, J. S. Figueroa "Direct Observation of beta-Chloride Elimination from an Isolable beta-Chloroalkyl Complex of Square-Planar Nickel", J. Am. Chem. Soc, 2014, Vol. 136, 15481-15484
- Perrin, C. L., Burke, K. D. "Variable-Temperature Study of Hydrogen-Bond Symmetry in Cyclohexene-1,2-dicarboxylate Monoanion in Chloroform-d", J. Am. Chem. Soc., 2014, Vol. 136, 4355-4362
- Perrin, C. L., Reyes-Rodriguez, G. J. "Selectivity and Isotope Effects in Hydronation of a Naked Aryl Anion", J. Am. Chem. Soc., 2014, Vol. 136, 15263-15269
- Charles L. Perrin "Relation between Errors in Enthalpy and Entropy", J. Phys. Org. Chem., 2013, Vol. 26, 269-270
- Perrin, C. L., Reyes-Rodriguez, G. J. "Reactivity of Nucleophiles toward a p-Benzyne Derived from an Enediyne", J. Phys. Org. Chem., 2013, Vol. 26, 206-210
- Perrin CL, Flach A, Manalo MN, "Decomposition of malonic anhydrides.", J Am Chem Soc, 2012, Vol. 134, Issue 23, 9698-707
- Perrin CL, Karri P, Moore C, Rheingold AL, "Hydrogen-bond symmetry in difluoromaleate monoanion.", J Am Chem Soc, 2012, Vol. 134, Issue 18, 7766-72
- Perrin, C. L.; Zhao, C. "Intramolecular Kinetic Isotope Effect in Hydride Transfer from Dihydroacridine to a Quinolinium Ion. Rejection of a Proposed Two-Step Mechanism with a Kinetically Significant Intermediate", Org. Biomol. Chem., (2008), 6, 3349-3353.
- Perrin, C. L.; Dong, Y. "Secondary Deuterium Isotope Effects on Acidity of Carboxylic Acids and Phenols", J. Am. Chem. Soc. (2007), 129, 4490-4497.
- Perrin, C. L.; Rodgers, B. L.; O'Connor, J. M. "Nucleophilic Addition to a p-Benzyne Derived from an Enediyne: A New Mechanism for Halide Incorporation into Biomolecules" J. Am. Chem. Soc. (2007), 129, 4795-4799.
- Perrin, C. L.; Ohta, B. K.; Kuperman, J.; Liberman, J.; Erdélyi, M. "Stereochemistry of beta-Deuterium Isotope Effects on Amine Basicity", J. Am. Chem. Soc. (2005), 127, 9641-9647.
- Perrin, C. L., "Is There Stereoelectronic Control in Formation and Cleavage of Tetrahedral Intermediates?", Acc. Chem. Res. (2002), 35, 28-34.
- Perrin, C. L. "Are Short, Low-Barrier Hydrogen Bonds Unusually Strong?" Acc. Chem. Res., 2010, 43, 1550.
- Perrin, C. L.; Flach, A. "No Contribution of an Inductive Effect to Secondary Deuterium Isotope Effects on Acidity" Angew. Chem. 2011, 50,7674.
- Perrin, C. L.; Karri, P. "Position-Specific Secondary Deuterium Isotope Effects on Basicity of Pyridine" J. Am. Chem. Soc., 2010, 132, 12145.
- Perrin, C. L.; Lau, J. S.; Kim, Y.-J.; Karri, P.; Moore, C.; Rheingold,A. L. "Asymmetry of the 'Strongest' OHO Hydrogen-Bond, in the Monoanion of (±)-a,a'-Di-tert-butylsuccinate", J. Am. Chem. Soc., 2009, 131, 13548; 2010, 132, 2099