Pd-Catalyzed Olefin Functionalization Reactions for Organic Synthesis

Pd 催化的有机合成烯烃官能化反应

• 批准号: 7916141
• 负责人: MATTHEW S SIGMAN
• 金额: $ 23.49万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7916141
• 关键词: Academia; Address; Aerobic; Alcohols; Alder plant; Alkenes; Benign; Catalysis; Chemistry; Complex; Coupled; Coupling; Development; Diels Alder reaction; Environmental Impact; Goals; Hydrogen; Hydrogen Peroxide; Industry; Ketones; Kinetics; Lead; Ligands; Metals; Methodology; Methods; Mission; Molecular; Organic Chemistry; Organic Synthesis; Oxidants; Oxygen; Palladium; Peroxides; Phenols; Process; Reaction; Reagent; Research; Resolution; Salts; Structure; Styrenes; Techniques; Variant; catalyst; dehydrogenation; design; functional group; improved; novel; oxidation; programs; quinone methide

DESCRIPTION (provided by applicant): Oxidation reactions are essential for both functional group manipulation and heteroatom introduction in the synthesis of biologically relevant compounds. Newly discovered and significantly improved oxidative processes can have a direct impact on the efficiency of and approaches to the execution of targeted synthesis. Therefore, the development of selective, practical oxidation reactions is a continuing challenge facing chemists in both academia and industry. A key consideration is selection of the stoichiometric oxidant where versatility, expense, and environmental impact need to be addressed. An attractive approach to this issue is the use of metal-catalyzed oxidations coupled to a practical terminal oxidant such as molecular oxygen or hydrogen peroxide. Therefore, a central goal of oxidation catalysis, and of this program, is the discovery and development of highly active, robust catalysts compatible with practical oxidants. Palladium(II) salts with oxidatively stable ligands have been selected as catalysts primarily due to their ability to effectively use molecular oxygen as a terminal oxidant. The use of ligands allows for high reaction selectivity, including enantioselectivity, and for the design of well-defined Pd-complexes capable of high turnover numbers. Importantly, Pd-catalyzed reactions have revolutionized synthesis through the development of cross-coupling reactions, forming a vast array of C-C, C-N, C-S, and C-O bonds. Therefore, a fundamental goal of the proposed research is to integrate Pd-catalyzed oxidation reactions with cross-coupling processes. The current proposal is directed toward the development of new Pd-catalyzed olefin functionalization reactions via oxidation chemistry. Specifically, we will (1) study and develop our recently discovered Pd-catalyzed aerobic dialkoxylation reactions of styrenes containing a phenol, including expansion to tandem intramolecular addition of nucleophiles/Diels-Alder processes, (2) investigate the scope and mechanism of a recently discovered ligand-modulated direct oxygen coupled Wacker oxidation and develop kinetic resolution and dynamic kinetic resolution of olefins yielding enantiomerically enriched substrates and products, and (3) develop olefin functionalization reactions wherein Pd-catalyzed cross-coupling reactions utilizing organometallic reagents are paired with aerobic alcohol oxidation. The proposed research described herein will be approached using method discovery and development, facilitated by elucidation of mechanistic details using physical organic chemistry techniques. The goal of the proposed research is to develop new metal catalyzed olefin oxidation chemistry employing simple substrates and practical terminal oxidants (O2 and simple peroxides) to create diverse bond constructions in a stereocontrolled manner. Advances in the proposed methodology will directly impact the biomedical mission by providing efficient access to novel derivatives of biologically active core structures.

描述（由申请人提供）：在合成生物学相关化合物的合成中，氧化反应对于功能组操作和杂原子引入至关重要。新发现并显着改善的氧化过程可以直接影响靶向合成的执行效率和方法。因此，在学术界和行业中，选择性，实用的氧化反应的发展是化学家面临的持续挑战。一个关键的考虑因素是选择化学计量氧化剂，其中需要解决多功能性，费用和环境影响。解决这个问题的一种有吸引力的方法是使用金属催化的氧化，结合了实用的末端氧化剂，例如分子氧或过氧化氢。因此，氧化催化和该程序的一个核心目标是发现和开发与实际氧化剂兼容的高度活跃，可靠的催化剂。钯（II）具有氧化稳定配体的盐已被选为催化剂，这主要是由于它们有效使用分子氧作为末端氧化剂的能力。配体的使用允许高反应选择性，包​​括对映选择性，以及设计出明确的PD复合物，能够具有较高的周转数量。重要的是，PD催化的反应通过发展交叉偶联反应，形成了一系列C-C，C-N，C-S和C-O键，彻底改变了综合。因此，提出的研究的基本目标是将PD催化的氧化反应与交叉偶联过程相结合。当前的建议是针对通过氧化化学的新PD催化烯烃官能化反应的发展。具体而言，我们将（1）研究和开发我们最近发现的含有苯酚的苯乙烯的PD催化的有氧二烷基化反应，包括扩展与分子内添加成核菌/DIELS-ALDER过程的分子内添加，（2）研究了最近发现的近来发现的直接和机制的直接氧化和机制，并建立了氧化氧化物氧化剂和机制。烯烃的分辨率产生了对映体富集的底物和产物的分辨率，以及（3）开发烯烃官能化反应，其中使用有氧醇氧化配对使用有机金属试剂的PD催化的交叉偶联反应。本文所述的拟议研究将使用方法发现和开发进行，这是通过使用物理有机化学技术阐明机械细节的促进的。拟议的研究的目的是开发新的金属催化的烯烃氧化化学，采用简单的底物和实用的终末氧化剂（O2和简单的过氧化物），以立体控制的方式创建了多种键结构。拟议方法论的进步将通过有效访问生物活性核心结构的新衍生物来直接影响生物医学任务。