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）：有机化学品的选择性氧化是当今化学和制药行业面临的最严峻的挑战之一。在过去的十年中，许多研究小组致力于将已知的和新颖的氧化过程与世界上最丰富的氧化剂分子氧结合起来。该领域的一个具有挑战性的研究领域是钯(II)介导的碳亲核试剂与未活化的烯烃的氧化偶联。与有氧氧化研究同时，有机催化，特别是亚胺/烯胺催化，已引起合成界的极大关注，并已被证明在非常温和的条件下在高水平对映体控制的催化反应方面极其有效。拟议的研究涉及这两个概念的协同作用：成功地将烯胺催化与 Pd(II) 化学结合起来，在有氧条件下催化相对较弱的 α-羰基亲核试剂与未活化的烯烃的氧化偶联。该提案的最终目标是探索反应机理并使其在胺和钯中具有催化作用，同时能够诱导高水平的对映选择性。所提出的反应通过仲胺与含有烯烃束缚羰基的分子缩合来进行，生成烯胺。钯(II)源对束缚烯烃的亲电活化导致碳-碳键的形成。所得亚胺离子的水解以及伴随的钯的对位氢化物消除提供了氧化偶联产物。新生成的Pd(0)可以被O2再氧化为Pd(II)，Pd(II)可以重新进入催化循环。预计使用手性、对映体富集的仲胺将能够实现高对映体控制。具有钯配体双重作用的手性仲胺也将研究其在不对称反应中的潜力。高效且良性的氧化化学转化的设计对于环境可持续的全球经济的发展至关重要，因此对于所有生物的健康也至关重要。在此应用中，我们建议设计一种强大而温和的化学反应，使用分子氧作为唯一的氧化剂并产生水作为唯一的副产物。