Computational Investigation of Asymmetric Allylic Alkylation Reactions

不对称烯丙基烷基化反应的计算研究

• 批准号: 8525952
• 负责人: Buck Taylor
• 金额: $ 4.71万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8525952
• 关键词: Air; Alkylation; Antibiotics; Area; Biological Factors; Chemicals; Complex; Development; Electronics; Evaluation; Goals; HIV; Investigation; Iridium; Lead; Malignant Neoplasms; Metals; Methods; Modeling; Molybdenum; Mono-S; Outcome; Palladium; Pharmaceutical Preparations; Pharmacologic Substance; Public Health; Reaction; Staging; Theoretical Studies; base; catalyst; chemical reaction; design; drug candidate; functional group; improved; insight; meetings; predictive modeling; public health relevance; quantum; tool; Air; Alkylation; Antibiotics; Area; Biological Factors; Chemicals; Complex; Development; Electronics; Evaluation; Goals; HIV; Investigation; Iridium; Lead; Malignant Neoplasms; Metals; Methods; Modeling; Molybdenum; Mono-S; Outcome; Palladium; Pharmaceutical Preparations; Pharmacologic Substance; Public Health; Reaction; Staging; Theoretical Studies; base; catalyst; chemical reaction; design; drug candidate; functional group; improved; insight; meetings; predictive modeling; public health relevance; quantum; tool

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.

描述（由申请人提供）：该提案概述了一项计划，旨在显着提高对分支选择性非对称烯丙基烷基化反应的当前理解。这类反应已证明了药物不对称合成的实用性。但是，仍然存在挑战，这将这些反应的应用限制在某些类别的基材上，尤其是在大规模上。在拟议的研究中，将使用量子化学方法来更完整地了解决定这些反应中选择性的因素。具体而言，将根据计算进行钼和催化的烯丙基烷基化反应的机理，以确定对映选择性和区域选择性的空间和电子起源。将开发可用于其他催化剂和底物的反应的预测模型。最后，将在计算上设计新的催化剂，这些催化剂预计将提供增强的选择性和效率。这项研究将大大改善我们的 了解这类反应并导致在生物活性化合物合成中进一步应用。