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Literature Background
    The papers below describe the development of isotope analyses within the Singleton group and the their application in basic research to the elucidation of organic, organometallic, and bioorganic reaction mechanisms.

Singleton and A. A. Thomas, J. Am. Chem. Soc.1995, 117, 9357-8. (For commentaries see Chemical and Engineering News, September 18, 1995, and Lucero, M. J.; Houk, K. N. Chemtracts–Org. Chem.1996, 9, 72.)

"Synchronous or Asynchronous? An "Experimental" Transition State from a Direct Comparison of Experimental and Theoretical Kinetic Isotope Effects for a Diels-Alder Reaction," B. R. Beno, K. N. Houk, and D. A. Singleton, J. Am. Chem. Soc.1996, 118, 9984-5.

"The Experimental Geometry of the Epoxidation Transition State," D. A. Singleton,S. R. Merrigan, J. Liu, and K. N. Houk, J. Am. Chem. Soc.1997, 119, 3385-6.

"13C Kinetic Isotope Effects for the Addition of Lithium Dibutylcuprate to Cyclohexenone. Reductive Elimination is Rate-Determining," D. E. Frantz, D. A. Singleton,and J. P. Snyder, J. Am. Chem. Soc., 1997, 119, 3383-4.

"Experimental and Theoretical Kinetic Isotope Effects for Asymmetric Dihydroxylation. Evidence Supporting a Rate-Limiting "(3 + 2)" Cycloaddition," A. J. DelMonte, J. Haller, K. N. Houk, K. B. Sharpless, D. A. Singleton, T. Straßner, and A. A. Thomas, J. Am. Chem. Soc.1997, 119, 9907-9908.

"Deuterium Kinetic Isotope Effects and the Mechanism of the Bacterial Luciferase Reaction," W. A. Francisco, H. M. Abu-Soud, A. J. DelMonte, D. A. Singleton, T. O. Baldwin and F. M. Raushel, Biochemistry1998, 37, 2596.

"Experimental Proof of the Non-Least Motion Cycloadditions of Dichlorocarbene to Alkenes: Kinetic Isotope Effects and Quantum Mechanical Transition States," A. E. Keeting, S. R. Merrigan, D. A. Singleton, and K. N. Houk, J. Am. Chem. Soc.1999, 121, 3933-38.

"Stereochemical Labeling at Natural Abundance. Stereochemistry, Isotope Effects, and Mechanism of the Diels-Alder Reaction of Hexachlorocyclopentadiene with Ethyl Vinyl Ether," D. A. Singleton,* S. R. Merrigan, and A. A. Thomas, Tetrahedron Lett.1999, 40, 639-642.

"Separation of the Primary and Secondary Kinetic Isotope Effects at a Reactive Center Using Starting Material Reactivities. Application to the FeCl3-Catalyzed Oxidation of C-H Bonds with tert-Butyl Hydroperoxide," S. R. Merrigan, V. N. Le Gloahec, J. A. Smith, D. H. R. Barton, and D. A. Singleton, Tetrahedron Lett.1999, 40, 3847-50.

"Isotope Effects for Lewis Acid-Catalyzed Diels-Alder Reactions. The Experimental Transition State," D. A. Singleton, S. R. Merrigan, B. R. Beno, and K. N. Houk, Tetrahedron Lett.1999, 40, 5817-21.

"13C and 2H Kinetic Isotope Effects and the Mechanism of Bromination of 1-Pentene under Synthetic Conditions," S. R. Merrigan and D. A. Singleton, Org. Lett.1999, 1, 327-330.

"Evidence for a Concerted Mechanism in a Palladium Trimethylenemethane Cycloaddition," D. A. Singleton and B. E. Schulmeier, J. Am. Chem. Soc.1999, 121, 9313-9317.

"Simultaneous Determination of Intermolecular and Intramolecular 13C and 2H Kinetic Isotope Effects at Natural Abundance,"D. A. Singleton and M. J. Szymanski, J. Am. Chem. Soc.1999, 121, 9455-9456.

"Reinvestigation of the Isotope Effects for the Claisen and Aromatic Claisen Rearrangements. The Nature of the Claisen Transition States"M. P. Meyer, A. J. DelMonte, and D. A. Singleton, J. Am. Chem. Soc.1999, 121, 10865-10874.

"Isotope Effects and the Experimental Transition State for a Prototypical Thermal Ene Reaction," D. A. Singleton and C. Hang, Tetrahedron Lett.1999, 40, 8939-8942.

"Isotope Effects and the Mechanism of Triazolinedione Ene Reactions. Aziridinium Imides are Innocent Bystanders," D. A. Singleton and C. Hang, J. Am. Chem. Soc.1999, 121, 11885-11893.

"13C and 2H Kinetic Isotope Effects and the Mechanism of Lewis acid-Catalyzed Ene Reactions of Formaldehyde," D. A. Singleton and C. Hang, J. Org. Chem.2000, 65, 895-899.

"13C Kinetic Isotope Effects and the Mechanism of the Uncatalyzed Decarboxylation of Orotic Acid," D. A. Singleton, S. R. Merrigan, B. J. Kim, P. Beak, L. M. Phillips, and J. K. Lee, J. Am. Chem. Soc.2000, 122, 3296-3300.

"Isotope Effects and the Mechanism of Chlorotrimethylsilane-Mediated Addition of Cuprates to Enones," D. E. Frantz and D. A. Singleton, J. Am. Chem. Soc.2000, 122, 3288-3295.

“Isotope Effects and the Mechanism of Allylic Hydroxylation of Alkenes with Selenium Dioxide,” D. A. Singleton and C. Hang, J. Org. Chem.2000, 65, 7554-7560.

“Resolution of Conflicting Mechanistic Observations in Ester Aminolysis. A Warning on the Qualitative Prediction of Isotope Effects for Reactive Intermediates,” D. A. Singleton and S. R. Merrigan, J. Am. Chem. Soc.2000, 122, 11035-6.

“Isotope effects and the distinction between synchronous, asynchronous, and stepwise Diels-Alder reactions,” D. A. Singleton, B. E. Schulmeier, C. Hang, A. A. Thomas, S.-W. Leung, and S. R. Merrigan, Tetrahedron2001, 57, 5149-5160.

“The Minimum Energy Structure of Hydridotris(pyrazolyl)borato Iridium(V) Tetrahydride Is Not a C3v Capped Octahedron,” C. E. Webster, D. A. Singleton, M. J. Szymanski, M. B. Hall, C. Zhao, G. Jia, and Z. Lin, J. Am. Chem. Soc.2001, 123, 9822-9829.

“Mechanism and Origin of Stereoselectivity in Lewis Acid-Catalyzed [2 + 2] Cycloadditions of Ketenes with Aldehydes,” D. A. Singleton, Y. Wang, H. W. Yang, and D. Romo, Angew. Chem. Internat. Ed.2002, 41, 1572-1575.

"Isotope Effects and the Mechanism of an Electron-Transfer-Catalyzed Diels-Alder Reaction," Saettel, N. J.; Wiest, O.; Singleton, D. A.; Meyer, M. P. J. Am. Chem. Soc.2002, 124, 11552-11559.

"Mechanism of Ene Reactions of Singlet Oxygen. A Two-Step No-Intermediate Mechanism," D. A. Singleton, C. Hang, M. J. Szymanski, M. P. Meyer, A. G. Leach, K. T. Kuwata, J. S. Chen, A. Greer, C. S. Foote, and K. N. Houk, J. Am. Chem. Soc.2003, 125, 1319-1328.

"A New Form of Kinetic Isotope Effect. Dynamic Effects on Isotopic Selectivity and Regioselectivity," D. A. Singleton, C. Hang, M. J. Szymanski, and E. E. Greenwald, J. Am. Chem. Soc.2003, 125, 1176-1177.

"Isotope Effects and the Nature of Selectivity in Rhodium-Catalyzed Cyclopropanations," D. T. Nowlan III, T. M. Gregg, H. M. L. Davies, and D. A. Singleton, J. Am. Chem. Soc.2003, 125, 15902-15911.

"Isotope Effects and the Mechanism of Atom Transfer Radical Polymerization," D. A. Singleton,D. T. Nowlan III, N. Jahed, and K. Matyjaszewski, Macromolecules2003, 36, 8609-8616.

"Isotope Effects and the Nature of Stereo- and Regioselectivity in Hydroaminations of Vinylarenes Catalyzed by Palladium(II)- diphosphine Complexes." L. K. Vo and D. A. Singleton, Org. Lett.2004, 6, 2469-2472.

“Isotope Effects and the Mechanism of Fragmentation of Epoxy Imino-1,3,4-oxadiazolines.” D. A. Singleton and Z. Wang, Tetrahedron Lett.2005, 46, 819-822.

"Isotope Effects and the Mechanism of Palladium-Catalyzed Allylic Alkylations," C. F. Christian and D. A. Singleton, Tetrahedron Lett.2005, 46, 1631-1634.

"Isotope Effects, Dynamics, and the Mechanism of Solvolysis of Aryldiazonium Cations in Water," B. R. Ussing and D. A. Singleton, J. Am. Chem. Soc.2005, 127, 2888-2899.

"The Normal Range for Secondary Swain-Schaad Exponents Without Tunneling or Kinetic Complexity," J. Hirschi and D. A. Singleton, J. Am. Chem. Soc.2005, 127, 3294-3295.

"Isotope Effects and the Mechanism of Deoxygenation of Epoxides with Dichlorocarbene," D. A. Singleton and Z. Wang, Tetrahedron Lett.2005, 46, 2033-2036.

"Isotope Effects and the Nature of Enantioselectivity in the Shi Epoxidation. The Importance of Asynchronicity," D. A. Singleton and Z. Wang, J. Am. Chem. Soc.2005, 127, 6679-6685.

"Mechanism and Origin of Enantioselectivity in the Rh2(OAc)(DPTI)3-Catalyzed Cyclopropenation of Alkynes," D. T. Nowlan III and D. A. Singleton, J. Am. Chem. Soc.2005, 127, 6190-6191.

"'Concerted' Transition State, Stepwise Mechanism. Dynamics Effects in C2-C6 Enyne Allene Cyclizations," T. Bekele, M. A. Lipton, D. A. Singleton and C. F. Christian, J. Am. Chem. Soc.2005, 127, 9216-9223.

"Dynamic Effects on the Periselectivity, Rate, Isotope Effects, and Mechanism of Cycloadditions of Ketenes with Cyclopentadiene," B. R. Ussing and D. A. Singleton, J. Am. Chem. Soc.2006, 128, 7594-7607.
"Isotope Effects and the Mechanism of Epoxidation of Cyclohexenone wth tert-Butyl Hydroperoxide," C. F. Christian, T. Takeya, M. J. Szymanski, and D. A. Singleton, J. Org. Chem.2007, ASAP