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: 8579783
• 负责人: F. Dean Toste
• 金额: $ 28.35万
• 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/8579783
• 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）：该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，该转化将广泛应用于治疗相关有机分子的制备。为此，提出了几种新的碳-碳π键对映选择性反应，重点放在对映选择性sp3-C-F键结构的开发上。我们将开发涉及通过在阳离子亲电子试剂存在下配位磷酸盐衍生的手性阴离子来激活π键作为亲电子试剂对杂原子和碳基亲核试剂的反应。我们还将证明这种反应流形适用于其他反应类别，例如直接对映选择性氟化反应和氟化脱芳构化反应。这些方法将用于氟化结构单元、杂环化合物和天然产物类似物的对映选择性构建。因此，我们预计所提出的耐空气和耐湿转化将为合成化学家和生物医学研究人员提供用于单一对映体合成的额外工具。