Hydrocarbon Oxidation Methods for Synthesis

烃氧化合成方法

• 批准号: 7143520
• 负责人: Maria White
• 金额: $ 29.45万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-26 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7143520
• 关键词: allyl compound; antiinfective agents; catalyst; chemical group; chemical structure function; chemical synthesis; cyclization; dimethylsulfoxide; hexoses; hydrocarbons; lactones; method development; nitrogen compounds; organometallic compounds; oxidation; small molecule; stereochemistry

DESCRIPTION (provided by applicant): The primary focus of this proposal is the discovery and development of highly selective, catalytic allylic C-H functionalization reactions that can be broadly applied to synthesis. Using these reactions to develop strategies for effecting highly efficient syntheses of molecules with valuable properties is one of our ultimate objectives. Another key objective is the mechanistic study of such systems in order to elucidate new fundamental principles of catalyst design and chemical reactivity. We have recently discovered a new class of sulfoxide-based palladium allylic C-H oxidation catalysts that provide access to either linear (E)-allylic acetates or branched allylic acetates from a wide variety of terminal olefin substrates. The distinctive features of these allylic C-H oxidation systems is that they require no heteroatom directing functional group on the substrate to achieve high reactivity and regioselectivity and are extraordinarily functional group tolerant. This revised grant application details our plans to fully optimize, based upon preliminary findings, these two reactions for use in fine chemical synthesis. Towards this goal, we have new preliminary data that: 1. identifies conditions to effect catalytic enantioselective branched allylic oxidation, 2. supports the claim that the allylic C-H macrolactonization method we propose to develop will have broad scope, 3. suggests that other nucleophiles will be competent for allylic C-H functionalization. On the basis of these results, we propose the following: 1. detailed mechanistic studies to determine the nature of reactive intermediates in the two allylic oxidation systems and the effects of sulfoxide and BQ on their formation and reactivity; 2. development of the branched allylic oxidation reaction into an enantioselective process and macrolactonization method for widespread use in synthesis, 3. optimization and use of the linear allylic oxidation reaction to effect a highly streamlined route to the hexoses, 4. exploration of the Pd/sulfoxide reaction manifolds for effecting a broad range of allylic C-H functionalization reactions. The discovery and development of mild and selective C-H functionalization methods, like the ones described in this proposal, stands to impact significantly on both the rate and expense in which new drugs are discovered and manufactured.

描述（由申请人提供）：该提案的主要重点是发现和开发可广泛应用于合成的高选择性催化烯丙基 C-H 官能化反应。利用这些反应来制定策略，实现具有有价值特性的分子的高效合成是我们的最终目标之一。另一个关键目标是对此类系统进行机理研究，以阐明催化剂设计和化学反应性的新基本原理。 我们最近发现了一类新型亚砜基钯烯丙型 C-H 氧化催化剂，可以从各种末端烯烃底物中获得直链 (E)-烯丙型乙酸酯或支链烯丙型乙酸酯。这些烯丙型C-H氧化系统的显着特征是它们不需要底物上的杂原子导向官能团即可实现高反应性和区域选择性，并且具有出色的官能团耐受性。这份修订后的拨款申请详细介绍了我们根据初步发现全面优化这两个用于精细化学合成的反应的计划。为了实现这一目标，我们获得了新的初步数据：1.确定了实现催化对映选择性支化烯丙基氧化的条件，2.支持了我们建议开发的烯丙基C-H大内酯化方法将具有广泛范围的主张，3.表明其他亲核试剂将能够进行烯丙基C-H官能化。基于这些结果，我们提出以下建议：1.详细的机理研究，以确定两个烯丙基氧化体系中反应中间体的性质以及亚砜和BQ对其形成和反应性的影响； 2. 将支链烯丙基氧化反应发展为广泛用于合成的对映选择性过程和大内酯化方法， 3. 优化和使用线性烯丙基氧化反应以实现高度简化的己糖路线， 4. 探索 Pd/亚砜反应歧管以实现广泛的烯丙基 C-H 官能化反应。温和且选择性的 C-H 功能化方法（如本提案中描述的方法）的发现和开发将对新药的发现和制造的速度和费用产生重大影响。