Oxidative carbon-carbon bond formation: a synergy of enamine and Pd(II) catalysis

氧化碳-碳键形成：烯胺和 Pd(II) 催化的协同作用

• 批准号: 7220380
• 负责人: Aubry K Miller
• 金额: $ 4.48万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-14 至 2007-12-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7220380
• 关键词: Aerobic; Alkenes; Amines; Area; Attention; Benign; Binding; Carbon; Catalysis; Chemicals; Chemistry; Communities; Condition; Coupled; Coupling; Development; Drug Industry; Facility Construction Funding Category; Goals; Health; Hydrolysis; Ions; Life; Ligands; Mediating; Molecular; Natural regeneration; Object Attachment; Organic Chemicals; Oxidants; Oxygen; Palladium; Phase; Physical condensation; Process; Reaction; Research; Role; Scheme; Source; Structure; Today; Variant; Water; carbonyl group; catalyst; chemical reaction; concept; design; novel; oxidation

DESCRIPTION (provided by applicant): Selective oxidation of organic chemicals is one of the most critical challenges facing the chemical and pharmaceutical industries today. Over the past 10 years, many groups have endeavored to couple known and novel oxidation processes to the world's most abundant oxidant, molecular oxygen. One challenging area of research in this field is the palladium(ll) mediated oxidative coupling of carbon nucleophiles with unactivated olefins. Concurrent with aerobic oxidation research, organocatalysis, particularly iminium/enamine catalysis, has garnered significant attention from the synthetic community and has proven to be extremely effective at catalyzing reactions with high levels of enantiocontrol under very mild conditions. The proposed study involves a synergy of these two concepts: to successfully merge enamine catalysis with Pd(ll) chemistry to catalyze the oxidative coupling of relatively weak a-carbonyl nucleophiles with unactivated olefins under aerobic conditions. The ultimate goal of this proposal entails probing the mechanism of the reaction and rendering it catalytic in both amine and palladium while being capable of inducing high levels of enantioselectivity. The proposed reaction proceeds via condensation of a secondary amine with a molecule containing an alkene tethered carbonyl to generate an enamine. Electrophilic activation of the tethered alkene by a palladium(ll) source leads to carbon-carbon bond formation. Hydrolysis of the resulting iminium ion with concomitant p-hydride elimination of the palladium affords the oxidatively coupled product. The newly generated Pd(0) can be reoxidized by O2 to Pd(ll) which can re-enter the catalytic cycle. It is expected that use of chiral, enantioenriched secondary amines will enable high enantiocontrol. Chiral secondary amines that have the dual role of palladium ligand will also be investigated for their potential in asymmetric reactions. The design of efficient and benign oxidative chemical transformations is critical for the development of an environmentally sustainable worldwide economy, and therefore, the health of all living things. In this application, we propose the design of a powerful yet mild chemical reaction that uses molecular oxygen as the sole oxidant and generates water as the only byproduct.

描述（由申请人提供）：有机化学物质的选择性氧化是当今化学和制药行业面临的最关键挑战之一。在过去的10年中，许多群体都努力培养已知和新颖的氧化过程与世界上最丰富的氧化剂分子氧。该领域的研究领域一个具有挑战性的领域是钯（LL）介导的碳亲核试剂与未激活的烯烃的氧化偶联。同时，有氧氧化研究，有机刻刻分析，尤其是亚胺/魔力催化，引起了合成群落的极大关注，事实证明，在非常轻微的条件下，具有高水平的对映体控制的反应非常有效。拟议的研究涉及这两个概念的协同作用：成功地将Onamine催化与PD（LL）化学合并，以催化在有氧条件下与未激活的烯烃相对弱的A-羧基亲核试剂的氧化偶联。该提案的最终目标是探测反应机制并在胺和钯中催化其催化性，同时能够诱导高水平的对映选择性。提出的反应是通过将二级胺与含有烯烃束缚羰基的分子缩合来进行的。通过钯（LL）源对拴系烯烃的亲电激活导致碳碳键的形成。所得的亚米族离子的水解和伴有p-氢化物消除钯的水解可提供氧化耦合的产物。新生成的PD（0）可以用O2重新氧化为PD（LL），从而可以重新进入催化循环。预计使用手性对映的二级胺将使高映体控制能力。还将研究具有钯配体双重作用的手性继发胺在不对称反应中的潜力。高效和良性氧化化学转化的设计对于全球环境可持续的经济的发展至关重要，因此是所有生物的健康。在此应用中，我们提出了一种强大而温和的化学反应的设计，该反应使用分子氧作为唯一的氧化剂，并产生水作为唯一的副产品。