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. In hydroboration, initially published results have called into question all of the standard ideas used to explain selectivity in these reaction;the proposed studies would use isotope effects and selectivity studies to determine the breadth of importance of dynamic effects in these reactions, and would explore ways to improve selectivity based on the its understanding as a dynamic phenomenon. In [2,3]-sigmatropic rearrangements, initial results suggest that dynamics can provide a unified explanation for competing [2,3] and [1,2] rearrangements, and the proposed mechanistic studies would a broad reinterpretation of these reactions. In Diels-Alder reactions and the [2 + 2] cycloadditions of ketenes, recent studies have found that the Newtonian ideas of inertia and mass-dependent acceleration can be the real deciding factor in selectivity. The proposed studies would examine ways to recognize these effects and how broadly they affect reactions. In ozonolysis, initial results have found that the intermediate primary ozonide is unique "hot" in only part of the molecule, and the planned studies would examine how structural effects on energy motion through molecules affects product ratios. Finally, experimental results have implicated that a dynamic effect, previously considered only for triatomic reactions, broadly facilitates the general acid-base catalyzed reactions of organic and enzymatic chemistry. Experiments are proposed to define in particular examples the role of the effect in catalysis. The health-relatedness of this work derives from its impact on the understanding of reactions important in the synthesis of medicinally important substances and reactions important in biological pathways.
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 that should aid in their invention, development, and regulation.
|Biswas, Bibaswan; Singleton, Daniel A (2015) Controlling Selectivity by Controlling the Path of Trajectories. J Am Chem Soc 137:14244-7|
|Bogle, Xavier S; Singleton, Daniel A (2012) Dynamic origin of the stereoselectivity of a nucleophilic substitution reaction. Org Lett 14:2528-31|
|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|
|Quijano, Larisa Mae M; Singleton, Daniel A (2011) Competition between reaction and intramolecular energy redistribution in solution: observation and nature of nonstatistical dynamics in the ozonolysis of vinyl ethers. J Am Chem Soc 133:13824-7|
|Bogle, Xavier S; Singleton, Daniel A (2011) Isotope-induced desymmetrization can mimic isotopic perturbation of equilibria. On the symmetry of bromonium ions and hydrogen bonds. J Am Chem Soc 133:17172-5|
|Gonzalez-James, Ollie M; Singleton, Daniel A (2010) Isotope effect, mechanism, and origin of catalysis in the decarboxylation of mandelylthiamin. J Am Chem Soc 132:6896-7|
|Gonzalez-James, Ollie M; Zhang, Xue; Datta, Ayan et al. (2010) Experimental evidence for heavy-atom tunneling in the ring-opening of cyclopropylcarbinyl radical from intramolecular 12C/13C kinetic isotope effects. J Am Chem Soc 132:12548-9|
|Vanchura 2nd, Britt A; Preshlock, Sean M; Roosen, Philipp C et al. (2010) Electronic effects in iridium C-H borylations: insights from unencumbered substrates and variation of boryl ligand substituents. Chem Commun (Camb) 46:7724-6|
|Hirschi, Jennifer S; Takeya, Tetsuya; Hang, Chao et al. (2009) Transition-state geometry measurements from (13)c isotope effects. The experimental transition state for the epoxidation of alkenes with oxaziridines. J Am Chem Soc 131:2397-403|
|Oyola, Yatsandra; Singleton, Daniel A (2009) Dynamics and the failure of transition state theory in alkene hydroboration. J Am Chem Soc 131:3130-1|
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