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: 8824953
• 负责人: Buck Taylor
• 金额: $ 2.32万
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8824953
• 关键词: Air; Alkylation; Antibiotics; Area; Biological Factors; Chemicals; Complex; Development; Electronics; Evaluation; Goals; HIV; Health; 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; 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)：本提案概述了一项计划，以显著提高目前对分支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显示出很好的实用性。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，特别是大规模的应用。在这项拟议的研究中，将使用量子化学方法来更全面地了解决定这些反应中选择性的因素。具体地说，将通过计算研究钼和铱催化的烯丙基烷基化反应的机理，以确定对映体选择性和区域选择性的空间和电子来源。将开发可应用于其他催化剂和底物的反应的预测模型。最后，将通过计算设计新的催化剂，预计这些催化剂将提供更高的选择性和效率。这项研究将显著改善我们的 了解这类反应，有助于进一步应用于生物活性化合物的合成。

项目成果

Non-Directed Allylic C-H Acetoxylation in the Presence of Lewis Basic Heterocycles.

• DOI: 10.1039/c3sc53414f
• 发表时间: 2014-06-01
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Malik HA;Taylor BL;Kerrigan JR;Grob JE;Houk KN;Du Bois J;Hamann LG;Patterson AW
• 通讯作者: Patterson AW

Mechanistic analysis of an asymmetric palladium-catalyzed conjugate addition of arylboronic acids to β-substituted cyclic enones.

• DOI: 10.1039/c4sc03337j
• 发表时间: 2015-03
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Boeser CL;Holder JC;Taylor BL;Houk KN;Stoltz BM;Zare RN
• 通讯作者: Zare RN