Theoretical Studies of Organocatalysis and Stereoselective Organic Reactions.

摘要

This dissertation describes the results of quantum mechanical investigations of a variety of organic reactions. All of the projects stemmed from collaborations with synthetic organic chemists, where experimental and computational tools were combined to understand interesting reaction mechanisms and stereoselectivities.;Chapters 1 and 2 rationalize torquoselectivities observed in cheletropic extrusion and cyclobutene ring-opening reactions, respectively. To our knowledge, an explanation for the torquoselectivity of cheletropic extrusion reactions at an achiral nitrogen center had not been reported prior to our studies (chapter 1). Chapter 2 describes the experimental results of what appeared to be a violation of principles of electrocyclic reactions. Our computations show why an unexpected "inward" rotation of donors in the ring-opening reaction of 3-substituted cyclobutenes was observed.;Chapters 3 and 4 explore the reactions of enamines derived from pyrrolidine and piperidine. Pyrrolidine was used to catalyze a (2,3)-Wittig rearrangement via an enamine intermediate, a reaction that normally requires a strong base. Competing mechanisms were explored and a rationalization for the diastereoselectivity was given (chapter 3). In chapter 4, the conformations of 2,2-dimethyl-6-substituted piperidine enamines were explored. The transition states for alkylation by allyl bromide and ethyl iodide were analyzed theoretically.;In chapter 5, we explore a highly diastereoselective (>20:1) hydride reduction of a planar oxacarbenium. Traditional models of stereoselective nucleophilic addition to oxacarbeniums have been based on anchimeric assistance or preferred ground state conformations. However, neither of these models were applicable to our system under study. Computational modeling of the transition states led to an explanation for the high stereoselectivity observed.;The theme of organocatalysis is revisited in chapter 6, where fluorine was found to have an effect on the reactivity and stereoselectivity of chiral bicyclic triazolium-catalyzed Stetter reactions. Our calculations show that while fluorine does influence catalyst ground state conformations, the preferred conformation of the catalyst in the transition state is the same, regardless of the catalyst used. The varying reactivity of the different catalysts is attributed to differing electrostatic interactions between the catalyst and nitroalkene in the transition state.;Chapters 7 and 8 describe the mechanism and nature of intermediates in the alpha-arylation of aldehydes via SOMO intermediates. A quantum mechanical description of the radical cation enamines involved in a number of reactions developed by MacMillan had not been previously reported. An explanation for the selectivity of the cyclization step is given (chapter 7). This investigation launched a study to explain the relative stabilities of 1-, 2-, and 3-substituted cyclohexadienyl and pentadienyl radicals (chapter 8).;Finally, a characterization of 1,3-dicyclohexyloxyallyl using UB3LYP, CASSCF, and MRMP2 is given in chapter 9. UV-Vis and IR spectra were calculated and compared with experiment. The singlet-triplet gap was predicted, and the barrier for ring closure to the cyclopropanone was calculated.