Computational Investigation of Asymmetric Allylic Alkylation Reactions

描述（由申请人提供）：该提案概述了一项计划，以显着提高目前的理解支链选择性不对称烯丙基烷基化反应。这类反应在药物的不对称合成中已被证明是有用的。然而，仍然存在的挑战限制了这些反应应用于某些类别的底物，特别是大规模的应用。在拟议的研究中，量子化学方法将用于更全面地了解决定这些反应选择性的因素。具体而言，钼和铱催化的烯丙基烷基化反应的机制将进行计算研究，以确定立体和电子的对映选择性和区域选择性的起源。预测模型将被开发，可应用于其他催化剂和底物的反应。最后，将通过计算设计新的催化剂，预测这些催化剂将提供更高的选择性和效率。这项研究将大大提高我们的 这类反应的理解，并导致在生物活性化合物的合成中的进一步应用。

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.