Enantioselective Synthesis by Chiral Anion Phase Transfer Catalysis

手性阴离子相转移催化对映选择性合成

• 批准号: 8725697
• 负责人: F. Dean Toste
• 金额: $ 28.3万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8725697
• 关键词: Air; Alkenes; Amines; Anions; Biological Factors; Carbon; Catalysis; Charge; Chemicals; Development; Event; FDA approved; Fluorides; Fluorine; Goals; Hydrogen Bonding; Individual; Liquid substance; Mediating; Medicine; Methods; Pharmaceutical Chemistry; Pharmaceutical Preparations; Phase; Phenols; Preparation; Process; Reaction; Reagent; Research; Research Personnel; Role; Solid; Structure; Therapeutic; Therapeutic Agents; Variant; analog; base; catalyst; diene; drug candidate; enantiomer; inorganic phosphate; pi bond; programs; propadiene; public health relevance; tool

DESCRIPTION (provided by applicant): The major goal of this research program is to develop catalytic enantioselective transformations based on the concept of chiral anion phase transfer catalysis that will be broadly applicable to the preparation of therapeutically relevant organic molecules. Towards this end, several new enantioselective reactions of carbon-carbon pi-bonds are proposed, with a major emphasis placed on the development of enantioselective sp3-C-F bond construction. We will develop reactions that involve activation of pi-bonds as electrophiles towards heteroatom and carbon-based nucleophiles, by coordination phosphate-derived chiral anions in the presence of cationic electrophiles. We will also demonstrate that this reactivity manifold is applicable to other reaction classes, such as direct enantioselective fluorination reactions and fluorinated dearomatization. These methods will be exploited in the enantioselective construction of fluorinated building blocks, heterocycles and natural product analogs. Thus, we anticipate that the proposed air and moisture tolerant transformations will provide synthetic chemists and biomedical researchers with additional tools for single enantiomer synthesis.

描述（由申请人提供）：本研究计划的主要目标是开发基于手性阴离子相转移催化概念的催化对映选择性转化，该催化对映选择性转化将广泛适用于制备治疗相关的有机分子。为此，提出了几种新的碳-碳π键的对映选择性反应，重点放在对映选择性sp3-C-F键的构建上。我们将开发的反应，涉及活化的π-键作为亲电试剂对杂原子和碳基亲核试剂，通过协调磷酸衍生的手性阴离子在阳离子亲电试剂的存在下。我们还将证明，这种反应性歧管是适用于其他反应类，如直接对映选择性的异构化反应和氟化脱芳烃。这些方法将被利用在氟化的建筑块，杂环和天然产物类似物的对映选择性的建设。因此，我们预计，拟议的耐空气和水分的转换将提供合成化学家和生物医学研究人员与单一对映体合成的额外工具。