Computational Investigation of Asymmetric Allylic Alkylation Reactions

描述（由申请人提供）：本提案概述了一个计划，以显著提高当前对支链选择性不对称烯丙基烷基化反应的理解。这类反应在药物的不对称合成中已被证明是有用的。然而，挑战仍然存在，限制了这些反应在某些类型的底物上的应用，特别是在大规模上。在提出的研究中，量子化学方法将用于更全面地了解这些反应中决定选择性的因素。具体来说，钼和铱催化的烯丙基烷基化反应的机理将被计算研究，以确定对映选择性和区域选择性的空间和电子来源。预测模型将被开发，可以应用于其他催化剂和底物的反应。最后，新的催化剂将通过计算设计，预计将提供更高的选择性和效率。这项研究将显著提高我们的

DESCRIPTION (provided by applicant): This proposal outlines a plan to significantly improve current understanding of branched-selective asymmetric allylic alkylation reactions. This class of reactions has demonstrated utility in the asymmetric synthesis of pharmaceuticals. Challenges remain, however, that limit the application of these reactions to certain classes of substrates, particularly on a large scale. In the proposed study, quantum chemical methods will be used to gain a more complete understanding of the factors that dictate selectivity in these reactions. Specifically, the mechanisms of molybdenum- and iridium-catalyzed allylic alkylation reactions will be studied computationally to ascertain the steric and electronic origins of enantioselectivit and regioselectivity. Predictive models will be developed that can be applied to reactions of other catalysts and substrates. Finally, new catalysts will be designed computationally that are predicted to provide enhanced selectivity and efficiency. This study will significantly improve our understanding of this class of reactions and lead to further applications in the synthesis of biologically active compounds.