Asymmetric Reactions with Dual-Functional Organocatalysis

双功能有机催化的不对称反应

• 批准号: 8588335
• 负责人: LI DENG
• 金额: $ 33.97万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8588335
• 关键词: Acids; Aldehydes; Biological; Biological Factors; Biomedical Research; Biomimetics; Carbon; Catalysis; Cinchona Alkaloids; Development; Drug Formulations; Esters; Foundations; Funding; Goals; Hydrogen Peroxide; Individual; Methods; Nitrogen; Oxygen; Play; Process; Property; Protons; Public Health; Reaction; Research; Research Personnel; Role; Structure; Sulfhydryl Compounds; Sulfones; Therapeutic; Therapeutic Agents; Validation; Work; analog; base; carbonyl compound; catalyst; chiral molecule; cost effective; deprotonation; design; interest; nitroalkene; peroxidation; programs; protonation; public health relevance; small molecule; tool

DESCRIPTION (provided by applicant): During the last two funding cycles our research program has made significant progress in the development of asymmetric base catalysis, as well as acid-base and iminium-base bifunctional catalysis by organic catalysts as broadly applicable concepts for the development of asymmetric reactions. In our previous studies the catalysts afford activity, enantioselectivity and diastereoselectivity through their involvement in a single transition state of stereochemical consequences. Our proposed studies focus on the invention and development of new reaction cascades. Building on preliminary results revealing the ability of cinchona alkaloids to serve as efficient chiral proton donors, the development of asymmetric dual-functional cooperative organocatalysis becomes a common theme underlying our proposed studies. In this mode of catalysis the organic catalysts act as a bifunctional catalyst to promote two different individual steps in the reaction cascades by activating and orienting the two participating reactants or intermediates. The specific aims are: 1) Development of enantioselective and diastereoselective conjugate addition-protonation reactions of ???-disubstituted nitroalkenes for asymmetric synthesis of chiral amino compounds. 2) Development of biomimetic proton transfer catalysis for enantioselective isomerizations of ???-unsaturated carbonyl to chiral ???-unsaturated carbonyl compounds via tandem deprotonation-protonation reactions. 3) Development of asymmetric peroxidations via enantioselective and chemo-controlled conjugate addition-protonation reactions with hydroperoxides. By establishing a broad range of synthetically important asymmetric transformations that currently represent unmet challenges for existing catalysts, our studies will provide unique entries into and achieve efficient asymmetric syntheses of chiral molecules of biological and therapeutic interest that are either inaccessible or difficult to prepare in a concise and useful manner by existing synthetic methods.

描述（由申请人提供）：在过去的两个资助周期中，我们的研究项目在不对称碱催化以及有机催化剂的酸碱和亚胺碱双功能催化的开发方面取得了重大进展，作为不对称反应开发的广泛适用的概念。在我们之前的研究中，催化剂通过参与立体化学结果的单一过渡态来提供活性、对映选择性和非对映选择性。我们提出的研究重点是新反应级联的发明和开发。基于揭示金鸡纳生物碱作为有效手性质子供体能力的初步结果，不对称双功能协同有机催化的发展成为我们提出的研究的共同主题。在这种催化模式中，有机催化剂充当双功能催化剂，通过活化和定向两种参与的反应物或中间体来促进级联反应中的两个不同的单独步骤。具体目标是： 1) 开发α-二取代硝基烯烃的对映选择性和非对映选择性共轭加成-质子化反应，用于手性氨基化合物的不对称合成。 2）开发仿生质子转移催化，通过串联去质子化-质子化反应，将α-不饱和羰基对映选择性异构化为手性α-不饱和羰基化合物。 3）通过对映选择性和化学控制的与氢过氧化物的共轭加成-质子化反应开发不对称过氧化反应。通过建立广泛的合成上重要的不对称转化（这些转化目前对现有催化剂来说是未解决的挑战），我们的研究将为具有生物和治疗意义的手性分子提供独特的进入并实现有效的不对称合成，而这些手性分子是无法通过现有的合成方法以简洁和有用的方式制备的。