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(申请人提供)：本建议的主要焦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高效合成具有有价值的分子的策略是我们的最终目标之一。另一个关键目标是对这类体系进行机理研究，以阐明催化剂设计和化学反应的新基本原理。 我们最近发现了一类新的基于亚砜的钯-烯丙基C-H氧化催化剂，它可以从各种各样的末端烯烃底物中获得直链(E)-烯丙基乙酸酯或支链烯丙基乙酸酯。这些烯丙基C-H氧化体系的显著特点是，它们不需要底物上的杂原子直接官能团来获得高的反应性和区域选择性，并且具有非凡的官能团容忍性。这份修订后的拨款申请详细说明了我们的计划，即根据初步发现，充分优化这两个反应，以用于精细化学合成。为了实现这一目标，我们有了新的初步数据：1.确定了影响催化不对称支烯丙基氧化的条件；2.支持我们建议开发的烯丙基C-H大内酯化方法将具有广阔的应用范围；3.表明其他亲核试剂将有能力进行烯丙基C-H官能化。在这些结果的基础上，我们提出了如下建议：1.详细的机理研究以确定两个烯丙基氧化体系中活性中间体的性质以及亚砜和BQ对其形成和反应活性的影响；2.支化的烯丙基氧化反应发展为一种广泛应用于合成的对映选择性过程和大的内酯化方法；3.优化和使用线性烯丙基氧化反应以实现高效的己糖路线；4.探索Pd/亚砜反应流形以实现广泛的烯丙基C-H官能化反应。温和和选择性的C-H功能化方法的发现和发展，如本提案中描述的方法，将对新药的发现和制造的速度和成本产生重大影响。