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）：氧化反应对于生物学相关化合物的合成中的官能团操作和杂原子引入都是必不可少的。新发现和显着改进的氧化过程可以对靶向合成的效率和执行方法产生直接影响。因此，开发选择性、实用的氧化反应是学术界和工业界化学家面临的持续挑战。一个关键的考虑因素是化学计量氧化剂的选择，其中需要解决多功能性、费用和环境影响。解决这个问题的一个有吸引力的方法是使用金属催化的氧化与实用的末端氧化剂（例如分子氧或过氧化氢）偶联。因此，氧化催化以及该计划的中心目标是发现和开发与实际氧化剂相容的高活性、稳健的催化剂。具有氧化稳定配体的钯(II)盐被选为催化剂，主要是因为它们能够有效地利用分子氧作为末端氧化剂。配体的使用可以实现高反应选择性，包​​括对映选择性，并可以设计出具有高周转数的明确定义的钯配合物。重要的是，Pd 催化反应通过交叉偶联反应的发展，形成大量的 C-C、C-N、C-S 和 C-O 键，彻底改变了合成。因此，本研究的一个基本目标是将钯催化的氧化反应与交叉偶联过程结合起来。目前的提案旨在通过氧化化学开发新的钯催化烯烃官能化反应。具体来说，我们将（1）研究和开发我们最近发现的含苯酚的苯乙烯的钯催化有氧二烷氧基化反应，包括扩展到亲核试剂/狄尔斯-阿尔德过程的串联分子内加成，（2）研究最近发现的配体调节的直接氧偶联瓦克氧化的范围和机制，并开发动力学分辨率和动态动力学 烯烃的拆分，产生对映体富集的底物和产物，以及(3)开发烯烃官能化反应，其中利用有机金属试剂的Pd催化的交叉偶联反应与需氧醇氧化配对。本文描述的拟议研究将通过方法发现和开发来进行，并通过使用物理有机化学技术阐明机械细节来促进。拟议研究的目标是开发新的金属催化烯烃氧化化学，采用简单的底物和实用的末端氧化剂（O2和简单的过氧化物）以立体控制的方式创建不同的键结构。所提出的方法的进步将通过提供有效获取生物活性核心结构的新型衍生物来直接影响生物医学使命。