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）高效且选择性地制备 有机分子对于治疗药物的合成至关重要。因此 烷基金属催化和立体选择性加成到烯烃的发展 被视为一个重要目标。催化烯烃烷基化提供了 实用且廉价的 C-C 键合成路线；这些反应 需要现成的底物和烷基金属。具有催化作用 对映选择性版本将是最有用的，特别是如果它能够负担得起 易于进一步功能化的分子。 与碳镁化类似，本文提出的反应是 Zr 催化的， 但它们通过完全不同的机制进行，并且将显着 更一般。在迄今为止报道的催化碳金属化中，烷基 烷基金属通常掺入最终产品中；在这里 是转移到亲电试剂的烷基部分 产品 。因此，新的 Zr 催化反应是不寻常的：有高效的 烯烃底物和亲电子试剂之间发生反应，但反应很少 或者烷基金属和亲电子试剂之间没有反应。下列 将追求的具体目标： I. 区域选择性和立体选择性 Zr 催化烷基化反应的发展 烯烃与烷基亲电子试剂的碳金属化。机械证据来自 我们之前的研究将用于开发独特的催化方法 C-C 键的区域选择性和非对映选择性合成。这些转变 提供了一种形成 C-C 键的新方法，其中容易获得烯烃 可以使用底物、烷基金属和亲电子试剂。 二.非对映选择性分子内Zr催化亲电试剂的开发 烷基化和碳金属化。分子内版本 Zr 催化的烷基化反应应能实现前所未有的高效反应 合成各种具有高区域性和杂环性的碳环和杂环 非对映选择性。 III. Zr催化对映选择性亲电烷基化反应的研究进展 碳金属化。我们将开发催化和不对称烷基化 烯烃与各种亲电子试剂的碳金属化。这些转变 提供独特且选择性的路线来轻松地对映选择性合成 可功能化的分子。新方法的实用性将得到证明 合成抗癌LY300502、解痉巴氯芬、抗真菌 黄曲霉毒素 B2、抗抑郁药吉非辛和抗白血病药物 helianane。