Catalytic and Stereoselective C-C Bond Forming Reaction

催化和立体选择性 C-C 键形成反应

• 批准号: 6744826
• 负责人: AMIR H HOVEYDA
• 金额: $ 24.74万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6744826
• 关键词: aflatoxins; alkenes; alkyl group; alkylation; antidepressants; antineoplastics; antispasmodic agents; catalyst; chemical addition; chemical bond; chemical synthesis; drug design /synthesis /production; organometallic compounds; stereochemistry; zirconium

DESCRIPTION: (Applicant's Description) Efficient and selective preparation of organic molecules is critical to the synthesis of therapeutics. Thus development of catalytic and stereoselective addition of alkylmetals to olefins stands as an important objective. Catalytic olefin alkylation offers a practical and inexpensive route for synthesis of C-C bonds; these reactions require readily available substrates and alkylmetals. A catalytic enatioselective version would be most useful especially if it were to afford molecules that are readily amenable to further functionalization. Similar to carbomagnesation, the reactions proposed herein are Zr-catalyzed, but they proceed by an entirely different mechanism and will be significantly more general. In catalytic carbometalations reported to-date, the alkyl group of the alkyl metal is typically incorporated within the final product; here it is the alkyl moiety of an electrophilic reagent that is transferred to the product . Thus, the new Zr-catalyzed reactions are unusual: there is efficient reaction between the alkene substrate and the electrophile, but there is little or no reaction between the alkylmetal and the electrophile. The following specific objectives will be pursued: I. Development of regio- and stereoselective Zr-catalyzed alkylation and carbometalation of olefins with alkyl electrophiles. Mechanistic evidence from our previous studies will be used to develop unique methods for catalytic regio- and diastereoselective synthesis of C-C bonds. These transformations offer a new approach to C-C bond formation, where readily available olefinic substrates, alkylmetals and electrophiles can be used. II. Development of diastereoselective intramolecular Zr-catalyzed electrophilic alkylations and carbometalations. The intramolecular version of the Zr-catalyzed alkylation should allow for an unprecedented and efficient synthesis of various carbo- and heterocycles with high regio- and diastereoselectivity. III.Development of Zr-catalyzed enantioselective electrophilic alkylations and carbometalations. We will develop a catalytic and asymmetric alkylation and carbometalation of olefins with various electrophiles. These transformations offer unique and selective routes to the enantioselective synthesis of easily functionalizable molecules. The utility of the new methods will be demonstrated by synthesis of anticancer LY300502, antispastic baclofen, anti-fungal aflatoxin B2, antidepressant gemfexine and anti-leukemic helianane.

描述：（申请人的描述）有效的选择性准备 有机分子对于疗法的合成至关重要。因此 催化和立体选择性烷基金属烷基金属烷基金属的添加 立场是一个重要的目标。催化烯烃烷基化提供 合成C-C键的实用且廉价的途径；这些反应 需要随时可用的底物和烷基计算。催化 EnatioSelective版本最有用，特别是如果它负担得起 很容易适合进一步功能化的分子。 与碳磁化类似，本文提出的反应是ZR催化的， 但是它们以一种完全不同的机制进行，将大大 更一般。在催化碳含量时，报道了烷基 通常将烷基金属掺入最终产品中；在这里 是转移到该烷基的烷基部分 产品 。因此，新的ZR催化反应是不寻常的：有效 烯烃基材和电力箱之间的反应，但是很少 或烷基金属和电力液之间没有反应。下列 将实现具体目标： I.区域和立体选择ZR催化的烷基化和 烯烃用烷基电子的碳测量法。机械证据 我们以前的研究将用于开发催化的独特方法 C-C键的区域和非对映选择性合成。这些转变 为C-C债券形成提供了新的方法，可以随时使用烯烃 可以使用底物，烷基金属和电力。 ii。非对映射内分子ZR催化的亲电的开发 烷基化和碳测量法。分子内版本的 ZR催化的烷基化应允许前所未有的 与高区域和高区域和杂环合成 对映选择性。 III。ZR催化的对映选择性的亲电烷基化和 碳测量值。我们将开发催化和不对称的烷基化和 用各种电力的烯烃碳测量法。这些转变 轻松地为对映选择性合成提供独特的选择性路线 可官能化的分子。新方法的实用性将被证明 通过抗癌LY300502的合成，反毒性baclofen，抗真菌 黄曲霉毒素B2，抗抑郁剂吉非乙氨酸和抗白血病的helianane。