Catalytic Synthesis of alpha-Branched Carbonyl Compounds

α-支化羰基化合物的催化合成

基本信息

批准号：
7655539
负责人：
Joseph M Ready
金额：
$ 24.85万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2012-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Synthetic organic molecules are the most effective tools to modulate biological systems dynamically. Small molecules find use as therapeutic agents and as reagents for biochemical studies. Our long-term goal is to develop new chemical reactions and apply them in the synthesis of natural products and small molecule libraries. The synthesis of compounds containing multiple substituents adjacent to a carbonyl compound remains an important but unsolved problem. We hypothesize that these a-branched carbonyl compounds will arise from a new catalytic substitution reaction. Specifically, a halogen adjacent to a carbonyl may be replaced by an alkyl group from an organometallic reagent. The use of an optically active catalyst may render this process enantioselective. This application describes our 4 related objectives: 1. Develop a catalytic cross-coupling of a-halo carbonyl compounds with organometallic reagents. Using copper catalysts, we will prepare a-branched carbonyl compounds from a wide variety of chlorinated substrates and organometallic reagents. 2. Determine the mechanism by which organometallic reagents react with a-halo carbonyl compounds. We will evaluate reaction kinetics and the structure of reactive intermediates. 3. Develop an enantioselective synthesis of a-branched carbonyl compounds. Most applications in medicine require single-enantiomer compounds. Accordingly, we seek to prepare optically active a-branched carbonyl compounds. 4. Develop an asymmetric catalytic chlorination of carbonyl compounds. Optically active carbonyl compounds are valuable chiral building blocks. They will find use in the copper-catalyzed cross-coupling reaction and a variety of other substitution reactions. These studies will uncover fundamental principles of chemical reactivity and lead to enantioselective syntheses of valuable chiral building blocks. Access to these compounds, in turn, will facilitate drug discovery and production.

描述（由申请人提供）：合成有机分子是动态调节生物系统的最有效工具。小分子发现用作治疗剂和生化研究的试剂。我们的长期目标是开发新的化学反应，并将其应用于天然产物和小分子库的合成中。含有羰基化合物相邻的多种取代基的化合物的合成仍然是一个重要但未解决的问题。我们假设这些A支柱的羰基化合物将来自新的催化取代反应。具体而言，与有机金属试剂的烷基相邻的卤素可以取代。使用光活性催化剂可能会引起此过程对映选择性。该应用描述了我们的4个相关目标：1。开发与有机金属试剂的A-Halo羰基化合物的催化交叉偶联。使用铜催化剂，我们将从各种氯化底物和有机金属试剂中制备A细分的羰基化合物。 2。确定有机金属试剂与A-HALO羰基化合物反应的机制。我们将评估反应动力学和反应性中间体的结构。 3。开发A分支羰基化合物的对映选择性合成。医学中的大多数应用都需要单位异构体化合物。因此，我们试图准备光学活跃的A支线羰基化合物。 4。开发羰基化合物的不对称催化氯化。光活性羰基化合物是有价值的手性构件。他们会发现在铜催化的交叉偶联反应和各种其他替代反应中的用途。这些研究将揭示化学反应性的基本原理，并导致对照式的对照组合的对照组成的构成。反过来，使用这些化合物将有助于毒品发现和生产。