Metal-Catalyzed Nucleophilic Substitution Reactions of Alkyl Electrophiles

金属催化烷基亲电试剂的亲核取代反应

• 批准号: 10406704
• 负责人: GREGORY C FU
• 金额: $ 66.09万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406704
• 关键词: Address; Area; Biochemistry; Bioinorganic Chemistry; Biology; Biomedical Research; Carbohydrates; Carbon; Catalysis; Chemicals; Communities; Complex; Copper; Coupling; DNA; Development; Discipline; Family; Goals; Handedness; Investigation; Life; Metals; Methods; Nickel; Nitrogen; Organic Chemistry; Organic Synthesis; Oxygen; Pathway interactions; Peptides; Pharmaceutical Chemistry; Process; RNA; Reaction; Research; Time; Transition Elements; Vertebral column; enantiomer; insight; interest; nucleophilic substitution; programs; success

PROJECT SUMMARY / ABSTRACT The discovery of powerful new methods for the synthesis of organic compounds can be enabling for biomedical research, e.g., by providing more ready access to known families of target molecules or access for the first time to new classes of molecules. Catalytic and enantioselective methods for carbon–carbon, carbon– nitrogen, and carbon–oxygen formation are of particular interest, due to issues including sustainability, the potentially divergent bioactivity of the two enantiomers of a compound, and the predominance of such bonds in the backbone of organic molecules, respectively. The substitution reaction of an alkyl electrophile by a nucleophile is a particularly straightforward approach to the assembly of organic molecules. Classical pathways for substitution, such as the SN1 and the SN2 reactions, are limited in scope with respect to both the electrophile and the nucleophile. Furthermore, these pathways almost never provide access to highly enantioenriched products from readily available racemic starting materials. Through the use of transition-metal catalysis, wherein the electrophile is converted into an organic radical, it is possible to begin to address both of the key challenges in nucleophilic substitution reactions of alkyl electrophiles–broader scope and control of enantioselectivity. For example, chiral nickel and copper complexes can catalyze the enantioconvergent coupling of a number of racemic secondary and tertiary alkyl electrophiles with a variety of nucleophiles. To date, only a small fraction of the conceivable permutations of electrophilic and nucleophilic partners for metal-catalyzed substitution reactions of alkyl electrophiles have been explored, and still fewer such processes have been rendered enantioselective. The goal of this research program is to address the many unsolved challenges in this area. Efforts will focus on the development of mild and versatile methods to couple families of electrophiles and nucleophiles that have not previously been shown to be suitable reaction partners in aliphatic substitution reactions, including highly hindered substrates, while controlling stereoselectivity at the same time (at up to two stereocenters), including with racemic electrophiles and nucleophiles that lack directing groups. Success in this endeavor will substantially facilitate the synthesis of enantioenriched molecules. Mechanistic studies will be pursued in order to provide insight into the pathways by which the new metal- catalyzed substitution reactions proceed. The mechanistic investigations will facilitate reaction development, as well as enhance the community’s understanding of fundamental chemical reactivity.

项目摘要 /摘要 发现有机综合综合的有力新方法可以实现 生物医学研究，例如，通过为靶标分子的已知家庭提供更多的访问或访问权限的访问 首次进入新的分子。 由于可持续性，包括可持续性， 综合的两个对映异构体的潜在发散生物活性 在有机分子的主链中，尊敬者。 通过亲核试剂将烷基亲电的变异反应是A 有机分子的组装方法。 SN2反应在相对于亲电体和亲核试剂的范围受到限制。 这些途径几乎永远无法从容易获得的外星人 起始材料。 通过使用过渡金属催化，是否将电力转化为有机自由基 可以开始解决烷基亲核化的两个关键挑战 电泳 - 范围的范围和对映选择性的控制。 复合物可以催化许多外星二级和第三级烷基的对映体耦合 带有多种亲核试剂的电力。 迄今 已经探索了烷基EL电力物的金属催化取代，此类过程仍然更少 已将对映选择性的目标呈现。 这一领域的挑战将重点放在夫妇的温和和多才多艺的方法上 仇恨以前不适合正确性的亲电器和细胞核的 脂肪族替代反应，包括高度阻碍的底物，同时控制您的立体选择性 同一时间（最多两个立体中心），包括缺乏的外星电力和亲核器 指导群体。 分子。 与新金属的途径进行机械研究 催化的替代反应过程。 以及增强社区对基本化学反应性的理解。