# overview
The central focus of the Singleton research group is the study of organic, organometallic, and bioorganic reaction mechanisms, and the key tool that we use in these studies is the determination o kinetic isotope effects (KIEs). In the mid-1990's, we developed a method for the high precision combinatorial determination of small KIEs at natural abundance by NMR. Its direct applicability to complex unlabeled reactants makes this methodology 1-2 orders of magnitude faster than studies requiring labeling. At the same time, it is much more versatile - our technique can look at a great number of reactions that would have been impractical or impossible to study by labeling or mass spectral methods, and the choice of reactants can be readily changed in response to each new experimental result. The simultaneous determination of a complete set of 13C, 2H, and 17O isotope effects possible with our methodology provides a much greater level of information than available from conventional methods. In addition, substantial evidence has accumulated supporting the reliable accuracy of our results.

# keywords[]
3407 Theoretical And Computational Chemistry

# keywords[]
3407 Theoretical And Computational Chemistry

# keywords[]
3407 Theoretical And Computational Chemistry

# keywords[]
3407 Theoretical And Computational Chemistry

# keywords[]
3407 Theoretical And Computational Chemistry

# keywords[]
3407 Theoretical And Computational Chemistry

# keywords[]
3407 Theoretical And Computational Chemistry

# educationAndTraining[].organization.label
University of Minnesota - (Minneapolis, Minnesota, United States)

# educationAndTraining[].organization.label
Case Western Reserve University - (Cleveland, Ohio, United States)

# awardsAndHonors[].label
Association of Former Students University-Level Distinguished Achievement Award, The

# awardsAndHonors[].label
Association of Former Students College-Level Teaching Distinguished Achievement Award, The

# awardsAndHonors[].label
Association of Former Students College-Level Teaching Distinguished Achievement Award, The

# publications[].label
TRAPPING OF AN ACYCLIC TRIMETHYLENEMETHANE WITH ELECTRON RICH OLEFINS

# publications[].label
ORGN 295-Failure of the transition state paradigm in common organic reactions

# publications[].label
Synchronous or asynchronous? An ''experimental'' transition state from a direct comparison of experimental and theoretical kinetic isotope effects for a Diels-Alder reaction

# publications[].label
Ir-Catalyzed ortho-Borylation of Phenols Directed by Substrate–Ligand Electrostatic Interactions: A Combined Experimental/in Silico Strategy for Optimizing Weak Interactions

# publications[].label
C-13 kinetic isotope effects and the mechanism of the uncatalyzed decarboxylation of orotic acid

# publications[].label
ACROLEIN ACETALS AS ALLYL CATION PRECURSORS IN THE IONIC DIELS-ALDER REACTION

# publications[].label
2-TRIMETHYLSILYLVINYLBORANES - HIGHLY REACTIVE AND SELECTIVE DIELS-ALDER EQUIVALENTS OF 2-TRIMETHYLSILYLVINYL ALCOHOL AND ACETYLENE

# publications[].label
A new form of kinetic isotope effect. Dynamic effects on isotopic selectivity and regioselectivity.

# publications[].label
Enantioselective synthesis without discrete optically active additives

# publications[].label
Computational and experimental isotope effects of an electron transfer catalyzed cycloaddition.

# publications[].label
Stepwise Diels-Alder reactions of alkynyldichloroboranes via a novel alkynylboration of dienes

# publications[].label
Isotope effects for Lewis acid catalyzed Diels-Alder reactions. The experimental transition state

# publications[].label
"Concerted" transition state, stepwise mechanism. Dynamics effects in C2-C6 enyne allene cyclizations.

# publications[].label
The normal range for secondary Swain-Schaad exponents without tunneling or kinetic complexity.

# publications[].label
Failure and Redemption of Statistical and Nonstatistical Rate Theories in the Hydroboration of Alkenes

# publications[].label
EXTENDED STEREOCONTROL IN SILYL GROUP-TRANSFER CYCLIZATIONS - CONTROL OF 4 CONTIGUOUS CHIRAL CENTERS

# publications[].label
DISTINCTION BETWEEN AMINIUM CATION RADICAL AND PROTIC ACID-CATALYZED DIELS-ALDER REACTIONS

# publications[].label
Exo-selective Diels-Alder reactions of vinylazepines. Origin of divergent stereoselectivity in Diels-Alder reactions of vinylazepines, vinylpiperideines, and vinylcycloalkenes.

# publications[].label
Dynamics and the failure of transition state theory in alkene hydroboration.

# publications[].label
Carbometalations of simple alkenes with allyldibromoborane.

# publications[].label
EXPLORATION OF THE SUPERDEGENERACY APPROACH TO THE SYNTHESIS OF HIGH-SPIN ORGANIC-MOLECULES AS MODELS FOR PI-ORGANIC FERROMAGNETS

# publications[].label
Phenomenon of optical self-purification of chiral non-racemic compounds.

# publications[].label
Reactions of Alkynyldihaloboranes with 1,3-Dienes. 1,4-Alkynylborations and Stepwise Diels-Alder Reactions.

# publications[].label
Comment on "Activation of methane to CH3 +: A selective industrial route to methanesulfonic acid".

# publications[].publisher
American Association for the Advancement of Science (AAAS)

# publications[].label
VINYLBORANES ARE OMNIPHILIC DIENOPHILES - SOME UNUSUAL AND USEFUL PROPERTIES OF VINYLBORANES IN DIELS-ALDER REACTIONS

# publications[].label
Bond Memory in Dynamically Determined Stereoselectivity

# publications[].label
Isotope effects and the distinction between synchronous, asynchronous, and stepwise Diels-Alder reactions

# publications[].label
Reaction of tropone with dienes: [6+4] vs. [8+2] cycloaddition

# publications[].label
13C and (2)H kinetic isotope effects and the mechanism of Lewis acid-catalyzed ene reactions of formaldehyde.

# publications[].label
Reinvestigation of the isotope effects for the Claisen and aromatic Claisen rearrangements: The nature of the Claisen transition states

# publications[].label
Allylboration of alkenes with allyldihaloboranes

# publications[].label
INTRAMOLECULAR DIELS-ALDER REACTIONS OF VINYLBORANES - A HIGHLY STEREOSELECTIVE 2-STEP DECALIN SYNTHESIS

# publications[].label
INTRAMOLECULAR CYCLIZATIONS OF ALLYL AND HOMOALLYL CATIONS - THE FORMATION OF MEDIUM-SIZED RINGS VIA CATIONIC PROCESSES

# publications[].label
13C and 2H kinetic isotope effects and the mechanism of bromination of 1-pentene under synthetic conditions

# publications[].label
Isotope effects and dynamics in the decarboxylation of b-ketoacids: Lifetime and the nature of acid catalysis

# publications[].label
A [4 + 3] TRANSITION-STATE FOR A [4 + 2] CYCLOADDITION - A NEW SECONDARY ORBITAL INTERACTION IN DIELS-ALDER REACTIONS

# publications[].label
Competition between reaction and intramolecular energy redistribution in solution: observation and nature of nonstatistical dynamics in the ozonolysis of vinyl ethers.

# publications[].label
INSITU FORMATION OF VINYLBORANES FOR USE IN DIELS-ALDER REACTIONS - AN EASY ONE-POT DIELS-ALDER SYNTHESIS OF CYCLOHEXENOLS

# publications[].label
13C and 2H kinetic isotope effects and the mechanism of bromination of 1-pentene under synthetic conditions.

# publications[].label
Isotope effects and the mechanism of atom transfer radical polymerization

# publications[].label
Dynamic effects in electrophilic aromatic substitution

# publications[].label
Controlling Selectivity by Controlling the Path of Trajectories.

# publications[].label
Controlling Selectivity by Controlling Energy Partitioning in a Thermal Reaction in Solution.

# publications[].label
Diels-Alder reactions between cyclopentadiene and trans-B-nitrostyrene derivatives: Exploring the free energy landscapes

# publications[].label
HIGH-PRECISION SIMULTANEOUS DETERMINATION OF MULTIPLE SMALL KINETIC ISOTOPE EFFECTS AT NATURAL-ABUNDANCE

# publications[].label
Control elements in dynamically determined selectivity on a bifurcating surface.

# publications[].label
HIGH REACTIVITY, REGIOSELECTIVITY, AND ENDOSTEREOSELECTIVITY OF VINYLBORANES IN DIELS-ALDER REACTIONS

# publications[].label
A [4+3] TRANSITION-STATE FOR A [4+2] CYCLOADDITION - THE IMPORTANCE OF [4+3] INTERACTIONS IN THE END O-STEREOSELECTIVITY OF DIELS-ALDER REACTIONS

# publications[].label
AN UNPRECEDENTED ELECTRONIC PREFERENCE FOR THE META PRODUCT IN DIELS-ALDER REACTIONS OF ETHYNYLDIALKYLBORANES - [(TRIMETHYLSILYL)ETHYNYL]-9-BBN AS A REACTIVE AND VERSATILE DIENOPHILE

# publications[].label
Newtonian kinetic isotope effects. Observation, prediction, and origin of heavy-atom dynamic isotope effects.

# publications[].label
Experimental proof of the non-least-motion cycloadditions of dichlorocarbene to alkenes: Kinetic isotope effects and quantum mechanical transition states

# publications[].label
Experimental and theoretical kinetic isotope effects for asymmetric dihydroxylation. Evidence supporting a rate-limiting ''(3+2)'' cycloaddition

# publications[].label
Isotope effects and the mechanism of chlorotrimethylsilane-mediated addition of cuprates to enones

# publications[].label
Mechanistic Studies of Formal Thioboration Reactions of Alkynes.

# publications[].label
In situ formation of alkenyl- and alkynylboranes for Diels-Alder reactions by boron-silicon exchange with alkenyl- and alkynylsilanes

# publications[].label
Isotope effects and the mechanism of epoxidation of cyclohexenone with tert-butyl hydroperoxide.

# publications[].label
Determination and prediction of heavy-atom dynamic isotope effects.

# publications[].label
A few molecules can control the enantiomeric outcome. Evidence supporting absolute asymmetric synthesis using the Soai asymmetric autocatalysis.

# publications[].label
Stereochemical labeling at natural abundance! Stereochemistry, isotope effects, and mechanism of the Diels-Alder reaction of hexachlorocyclopentadiene with ethyl vinyl ether

# publications[].label
Mechanism and origin of stereoselectivity in Lewis acid catalyzed [2 + 2] cycloadditions of ketenes with aldehydes

# publications[].label
Isotope effects for the aminolysis of ethyl formate with n-butylamine in ethanol. A surprising preassociation mechanism.

# publications[].label
Isotope effects and the nature of selectivity in rhodium-catalyzed cyclopropanations.

# publications[].label
METHYLENECYCLOPROPANECARBOXYLATES AND METHYLENECYCLOPROPANEDICARBOXYLATES, EFFICIENT REAGENTS FOR THE [3 + 2] METHYLENECYCLOPENTANE ANNULATION OF UNACTIVATED AND ELECTRON-RICH ALKENES

# publications[].label
Diels-Alder reaction involving an unusual dienophile: Computational and mechanistic study

# publications[].label
Isotope effects and the nature of enantioselectivity in the shi epoxidation. The importance of asynchronicity.

# publications[].label
Isotope effects and the experimental transition state for a prototypical thermal ene reaction

# publications[].label
Dynamically Complex [6+4] and [4+2] Cycloadditions in the Biosynthesis of Spinosyn A.

# publications[].label
Solvation Dynamics and the Nature of Reaction Barriers and Ion-Pair Intermediates in Carbocation Reactions

# publications[].label
Enantioselective synthesis without discrete optically active additives.

# publications[].label
Racing carbon atoms. Atomic motion reaction coordinates and structural effects on Newtonian kinetic isotope effects.

# publications[].label
Mechanism and origin of enantioselectivity in the Rh2(OAc)(DPTI)3-catalyzed cyclopropenation of alkynes.

# publications[].label
CONTROL OF REGIOSPECIFICITY IN IONIC DIELS-ALDER REACTIONS - THE USE OF ALLYLIC ALCOHOLS AND ALLYLIC ETHERS AS PRECURSORS OF DIENOPHILIC ALLYL CATIONS

# publications[].label
Isotope effects and the mechanism of palladium-catalyzed allylic alkylation

# publications[].label
Isotope effects and the mechanism of triazolinedione ene reactions. Aziridinium imides are innocent bystanders

# publications[].label
Isotope effects and the mechanism of deoxygenation of epoxides with dichlorocarbene

# publications[].label
Isotope effects and the nature of stereo- and regioselectivity in hydroaminations of vinylarenes catalyzed by palladium(ii)-diphosphine complexes.

# publications[].label
DIRECT FREE-RADICAL SUBSTITUTIONS ON ALLYL AND VINYL HALIDES USING ALKYL-HALIDES HEXABUTYLDITIN

# publications[].label
Origin of common competition between "allowed" [2,3]- and "forbidden" [1,2]- sigmatropic rearrangements: A mechanistic investigation

# publications[].label
Deuterium kinetic isotope effects and the mechanism of the bacterial luciferase reaction.

# publications[].label
Isotope effects, dynamic matching, and solvent dynamics in a Wittig reaction. Betaines as bypassed intermediates.

# publications[].label
Entropic intermediates and hidden rate-limiting steps in seemingly concerted cycloadditions. Observation, prediction, and origin of an isotope effect on recrossing.

# publications[].label
Mechanism and origin of stereoselectivity in Lewis acid catalyzed [2 + 2] cycloadditions of ketenes with aldehydes.

# publications[].label
PROTON CATALYZED INTRAMOLECULAR DIELS-ALDER REACTIONS - A CURIOUS PARALLEL BETWEEN PROTIC ACID AND AMINIUM CATION RADICAL PROMOTED REACTIONS

# publications[].label
Hydroboration of alkenes with BH3: A ' hot ' reaction at room temperature in solution

# publications[].label
Electronic effects in iridium C–H borylations : insights from unencumbered substrates and variation of boryl ligand substituents

# publications[].label
Outer-sphere direction in iridium C-H borylation.

# publications[].label
Evidence for a concerted mechanism in a palladium trimethylenemethane cycloaddition

# publications[].label
Longitudinal development of occlusion in African-American children.

# publications[].label
Concert along the Edge: Dynamics and the Nature of the Border between General and Specific Acid-Base Catalysis

# publications[].label
Recrossing and dynamic matching effects on selectivity in a Diels-Alder reaction.

# publications[].label
Nonlinear effects in kinetic resolutions

# publications[].label
Reaction removal of polychlorinated biphenyls from transformer oil: treatment of contaminated oil with poly(ethylene glycol)/potassium hydroxide.

# publications[].label
Simultaneous determination of intermolecular and intramolecular C-13 and H-2 kinetic isotope effects at natural abundance

# publications[].label
TUNING OF VINYLBORANE DIENOPHILICITY - OPTIMIZATION OF REACTIVITY, REGIOSELECTIVITY, ENDOSTEREOSELECTIVITY, AND REAGENT STABILITY

# publications[].label
Mechanism of Ene Reactions of Singlet Oxygen. A Two-Step No-Intermediate Mechanism

# publications[].label
ACID-CATALYZED INTRAMOLECULAR DIELS-ALDER REACTIONS - THE CYCLOADDITION OF ALLYL CATIONS TO 1,3-DIENES

# publications[].label
C-13 kinetic isotope effects for the addition of lithium dibutylcuprate to cyclohexenone. Reductive elimination is rate-determining

# publications[].label
Dynamics and a unified understanding of competitive [2,3]- and [1,2]-sigmatropic rearrangements based on a study of ammonium ylides.

# publications[].label
Isotope-induced desymmetrization can mimic isotopic perturbation of equilibria. On the symmetry of bromonium ions and hydrogen bonds.

# publications[].label
Insights into the facility of "forbidden" [1,2]-sigmatropic rearrangements

# publications[].label
Experimental Evidence for Heavy-Atom Tunneling in the Ring-Opening of Cyclopropylcarbinyl Radical from Intramolecular 12C/13C Kinetic Isotope Effects

# publications[].label
Resolution of conflicting mechanistic observations in ester aminolysis. A warning on the qualitative prediction of isotope effects for reactive intermediates

# publications[].label
Cycloalkenylboranes as Highly Reactive and Selective Diels-Alder Dienophiles. A Simple Synthesis of Bridgehead Bicyclic Alcohols.

# publications[].label
Isotopic effects and the mechanism of triazolinedione ene reactions: Aziridinium imides are innocent bystanders.

# publications[].label
Dynamic effects in ordinary organic reactions in solution.

# publications[].label
Kinetic isotope effect and ab inito investigation of the hydroboration reaction.

# publications[].label
A CONJUNCTIVE DIQUINANE SYNTHESIS USING A FREE-RADICAL CATALYZED INTRAMOLECULAR [3+2] METHYLENECYCLOPENTANE ANNULATION

# publications[].label
Temperature dependence of dynamic isotope effects.

# publications[].label
Isotope effects, dynamics, and the mechanism of solvolysis of aryldiazonium cations in water.

# publications[].label
Dynamic origin of the stereoselectivity of a nucleophilic substitution reaction.

# publications[].label
Kinetic and mechanistic studies of the [6+4] cycloaddition of tropone and cyclopentadiene

# publications[].label
Isotope effect, mechanism, and origin of catalysis in the decarboxylation of mandelylthiamin.

# publications[].label
On the importance of formyl C-H-F "hydrogen bonds" in asymmetric catalysis. The nature of the C-H-F interaction.

# publications[].label
CATALYTIC STEREOCONTROL OF A RADICAL CYCLIZATION

# publications[].label
Cycloalkenylboranes are highly reactive and regioselective Diels-Alder dienophiles. A simple synthesis of bridgehead bicycloalkanols

# publications[].label
Isotope effects and the mechanism of fragmentation of epoxy imino-1,3,4-oxadiazolines

# publications[].label
SYNCHRONICITY IN DIELS-ALDER REACTIONS REVISITED - HIGHLY ASYNCHRONOUS TRANSITION-STATES FOR SYMMETRICAL DIELS-ALDER REACTIONS

# publications[].label
13C and 170 kinetic isotope effects for the addition of lithium dibutylcuprate to cyclohexenone in the presence of chlorotrimethylsilane.

# publications[].label
Insights into the mechanism of flavoprotein-catalyzed amine oxidation from nitrogen isotope effects on the reaction of N-methyltryptophan oxidase.

# publications[].label
Dynamics and the Regiochemistry of Nitration of Toluene.

# publications[].label
Dynamic effects on the periselectivity, rate, isotope effects, and mechanism of cycloadditions of ketenes with cyclopentadiene.

# publications[].label
Isotope effects and heavy-atom tunneling in the Roush allylboration of aldehydes.

# publications[].label
PROPARGYL CATIONS - POWERFUL AMBIENT-TEMPERATURE DIENOPHILES IN THE DIELS-ALDER REACTION

# publications[].label
Stereochemical labeling at natural abundance. Stereochemistry, isotope effects, and mechanism of the Diels-Alder reaction of hexachlorocyclopentadiene with ethyl vinyl ether

# publications[].label
Minimum energy structure of hydridotris(pyrazolyl)borato iridium(V) tetrahydride is not a C(3upsilon) capped octahedron.

# publications[].label
Isotope effects and the mechanism of allylic hydroxylation of alkenes with selenium dioxide.

# publications[].label
Catalysis by temporary covalent activation. A novel catalysis of unactivated Diels-Alder reactions

# publications[].label
Isotope effects and the mechanism of an electron-transfer-catalyzed Diels-Alder reaction.

# publications[].label
Comment on "Activation of methane to CH3+: A selective industrial route to methanesulfonic acid"

# publications[].label
DESTRUCTION REMOVAL OF POLYCHLORINATED-BIPHENYLS FROM NON-POLAR MEDIA - REACTION OF PCB WITH POLY(ETHYLENE GLYCOL) KOH

# publications[].label
Labelling and determination of the energy in reactive intermediates in solution enabled by energy-dependent reaction selectivity.

# publications[].label
Reinvestigation of the heavy-atom isotope effects for the claisen and aromatic claisen rearrangements. The nature of the claisen transition states.

# publications[].label
A case study of the mechanism of alcohol-mediated Morita Baylis-Hillman reactions. The importance of experimental observations.

# publications[].label
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

# publications[].label
Experimental geometry of the epoxidation transition state

# publications[].label
DIELS-ALDER REACTIONS OF 2-ALKENYLBORANES AND CIS-1-ALKENYLBORANES - ANOMALOUS SELECTIVITY THAT ALLOWS A CHOICE OF REGIOCHEMISTRY

# publications[].label
Transition-state geometry measurements from (13)c isotope effects. The experimental transition state for the epoxidation of alkenes with oxaziridines.

# researcherOn[].label
New Concepts In Organic Selectivity and Mechanisms

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of General Medical Science

# researcherOn[].label
New Concepts In Organic Selectivity and Mechanisms

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# streetAddress
Texas A&M University; Chemistry Department; 3255 TAMU

# etdChairOf[].label
Andujar-De Sanctis, Ivonne (2014-10). Unusual Intramolecular Kinetic Isotope Effects: Selectivity beyond Transition State Theory's Jurisdiction. Doctoral Dissertation.

# etdChairOf[].label
Quijano, Larisa Mae Mangaliman 1984- (2012-10). Observation and Nature of Non-statistical Dynamic Effects in Ordinary Organic Reactions. Doctoral Dissertation.

# etdChairOf[].label
Thomas, Jacqueline Besinaiz (2009-05). Mechanistic Investigations into the Origin of Selectivity in Organic Reactions. Doctoral Dissertation.

# etdChairOf[].label
Oyola, Yatsandra (2012-02). The Dynamic Effect in the Hydroboration of Alkenes. Doctoral Dissertation.

# etdChairOf[].label
Plata, Robert Erik (2013-05). Experimental Observations in the Morita Baylis-Hillman Reaction in Methanol. Doctoral Dissertation.

# etdChairOf[].label
Nowlan, Daniel Thomas (2005-08). Mechanisms of transition-metal catalyzed additions to olefins. Doctoral Dissertation.

# etdChairOf[].label
Bogle, Xavier Sheldon (2012-02). Dynamic Effects in Nucleophilic Substitution Reactions. Doctoral Dissertation.

# etdChairOf[].label
Ussing, Bryson Richard (2007-04). Systematic examination of dynamically driven organic reactions via kinetic isotope effects. Doctoral Dissertation.

# etdChairOf[].label
Evans, Anthony Steven (2004-11). Mechanism of the Heck reaction: nature of oxidative addition and alkene insertion. Master's Thesis.

# etdChairOf[].label
Ruiz, N. Rebecca (2009-05). Non-eyring temperature dependence of dynamic isotope effects. Master's Thesis.

# etdChairOf[].label
Collins, Sean Christopher (2011-10). Mechanistic Investigation into the Sommelet-Hauser Rearrangement of an Allyl Ammonium Ylide Through Determination of 13C KIEs. Master's Thesis.

# etdChairOf[].label
Christian, Chad F. (2009-05). The experimental and theoretical determination of combinatorial kinetic isotope effects for mechanistic analysis. Doctoral Dissertation.

# etdChairOf[].label
Wagner, Joshua G. (2010-01). Intramolecular Isotope Effects for the Study of Reactions with MassTransfer Limitations. Master's Thesis.

# etdChairOf[].label
Biswas, Bibaswan (2015-08). Mechanistic Investigation of Rearrangement of Ammonium Ylides. Doctoral Dissertation.

# etdChairOf[].label
Wang, Zhihong (2007-04). Kinetic isotope effects, dynamic effects, and mechanistic studies of organic reactions. Doctoral Dissertation.

# etdChairOf[].label
Vetticatt, Mathew J. (2011-02). Aldol Reactions - Isotope Effects, Mechanism and Dynamic Effects. Doctoral Dissertation.

# etdChairOf[].label
James, Ollie (2012-02). Recrossing and Heavy-atom Tunneling in Common Organic Reactions. Doctoral Dissertation.

# etdChairOf[].label
Hirschi, Jennifer Sue (2009-05). Application of kinetic isotope effects and theoretical calculations to interesting reaction mechanisms. Doctoral Dissertation.

# etdChairOf[].label
Chen, Zhuo (2013-12). Isotope Effects, Dynamic Effects and Mechanisms of [2+2] Cycloadditions. Doctoral Dissertation.

# etdChairOf[].label
Kelly, Kelmara K. (2010-07). Novel Isotope Effects and Organic Reaction Mechanisms. Doctoral Dissertation.