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）：本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。利用这些反应来开发策略，以实现具有有价值的性质的分子的高效合成是我们的最终目标之一。另一个关键目标是这些系统的机理研究，以阐明催化剂设计和化学反应性的新的基本原理。 我们最近发现了一类新的亚砜基钯烯丙基C-H氧化催化剂，其提供了从各种末端烯烃底物获得直链（E）-烯丙基乙酸酯或支链烯丙基乙酸酯的途径。这些烯丙基C-H氧化体系的显著特征是它们不需要在底物上的杂原子导向官能团来实现高反应性和区域选择性，并且是非常耐受官能团的。这个修订后的拨款申请详细说明了我们的计划，以充分优化，基于初步的研究结果，这两个反应用于精细化学品合成。为了实现这一目标，我们有新的初步数据：1。确定了实现催化对映选择性支化烯丙基氧化的条件，2.支持的索赔，烯丙基C-H大环内酯化方法，我们建议开发将具有广泛的范围，3。表明其他亲核试剂将胜任烯丙基C-H官能化。基于这些结果，我们提出了以下几点建议：1.详细的机理研究，以确定在两个烯丙基氧化系统中的反应中间体的性质和亚砜和BQ对它们的形成和反应性的影响; 2.将支化烯丙基氧化反应发展为一种对映选择性的方法，并将大环内酯化方法广泛应用于合成中，3.优化和使用线性烯丙基氧化反应以实现高度流线化的己糖路线，4.探索Pd/亚砜反应歧管用于实现宽范围的烯丙基C-H官能化反应。温和的和选择性的C-H官能化方法的发现和开发，如本提案中所述的那些，将对新药发现和制造的速度和费用产生重大影响。