The conventional framework for understanding reactivity and selectivity in organic reactions fails for reactions influenced by dynamic effects. It is proposed to investigate the role of dynamic effects in some of the most common and important reactions in chemistry. Our work with dynamic effects in sigmatropic rearrangements has recently led to a successful strategy for the control of selectivity in these reactions. We plan to extend this strategy to cover a broad array of reactions and develop catalytically enantioselective sigmatropic rearrangements. Another new emphasis in our research is the role of solvent dynamics in reactions. Following up on recent results with the Wittig reaction and arene nitration, we will develop an understanding of how solvent dynamics affects experimental observations in a series of polar reactions. Alkoxy radical cleavage reactions give us a rare opportunity to vary on a near continuum barriers, structure, and excess energy to examine the rules that govern the onset and degree of dynamic effects. Alkoxy radicals are important to broad areas of chemistry, and we aim to understand how dynamics affects their reactions. Following on our prior work with hydroboration and ozonolysis, we aim to examine the reactions induced by the generation of extremely ?hot? intermediates or products in ordinary reactions. The health-relatedness of this work derives from its impact on both strategies to control reaction selectivity and the understanding of reactions important in the synthesis of medicinally important substances and reactions important in biological pathways.

Public Health Relevance

The synthesis of pharmaceuticals and the manipulation of biological pathways depend on the rational design and control of chemical reactions, which in turn depend on the understanding of chemical reactions. Our research is providing fundamental news ways to understand reactions and is demonstrating how this knowledge can be applied to the development and control of new reactions.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Synthetic and Biological Chemistry A Study Section (SBCA)
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Lees, Robert G
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Texas A&M University
Schools of Arts and Sciences
College Station
United States
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Kurouchi, Hiroaki; Singleton, Daniel A (2018) Labelling and determination of the energy in reactive intermediates in solution enabled by energy-dependent reaction selectivity. Nat Chem 10:237-241
Bailey, Johnathan O; Singleton, Daniel A (2017) Failure and Redemption of Statistical and Nonstatistical Rate Theories in the Hydroboration of Alkenes. J Am Chem Soc 139:15710-15723
Issaian, Adena; Faizi, Darius J; Bailey, Johnathan O et al. (2017) Mechanistic Studies of Formal Thioboration Reactions of Alkynes. J Org Chem 82:8165-8178
Aziz, Hannah R; Singleton, Daniel A (2017) Concert along the Edge: Dynamics and the Nature of the Border between General and Specific Acid-Base Catalysis. J Am Chem Soc 139:5965-5972
Patel, Ashay; Chen, Zhuo; Yang, Zhongyue et al. (2016) Dynamically Complex [6+4] and [4+2] Cycloadditions in the Biosynthesis of Spinosyn A. J Am Chem Soc 138:3631-4
Nieves-Quinones, Yexenia; Singleton, Daniel A (2016) Dynamics and the Regiochemistry of Nitration of Toluene. J Am Chem Soc 138:15167-15176
Kurouchi, Hiroaki; Andujar-De Sanctis, Ivonne L; Singleton, Daniel A (2016) Controlling Selectivity by Controlling Energy Partitioning in a Thermal Reaction in Solution. J Am Chem Soc 138:14534-14537
Biswas, Bibaswan; Singleton, Daniel A (2015) Controlling Selectivity by Controlling the Path of Trajectories. J Am Chem Soc 137:14244-7
Plata, R Erik; Singleton, Daniel A (2015) A case study of the mechanism of alcohol-mediated Morita Baylis-Hillman reactions. The importance of experimental observations. J Am Chem Soc 137:3811-26
Andujar-De Sanctis, Ivonne L; Singleton, Daniel A (2012) Racing carbon atoms. Atomic motion reaction coordinates and structural effects on Newtonian kinetic isotope effects. Org Lett 14:5238-41

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