Synergistic Catalysis for Chemical Synthesis

化学合成协同催化

• 批准号: 8821308
• 负责人: David W MacMillan
• 金额: $ 9.07万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8821308
• 关键词: Address; Aldehydes; Architecture; Binding; Biological Factors; Boranes; Catalysis; Chemicals; Collection; Complex; Copper; Coupling; Development; Event; Grant; Laboratories; Methods; Methylation; Organic Chemistry; Organic Synthesis; Phase; Process; Protocols documentation; Reaction; Research; Research Proposals; Route; Salts; Series; Solutions; System; Tryptamines; adduct; base; catalyst; chemical synthesis; design; improved; novel; programs; single bond

DESCRIPTION (provided by applicant): This research proposal seeks to invent and develop broad new asymmetric catalytic strategies, which will provide enantioselective access to a range of privileged functional motifs not readily available through current approaches. Each of the methods to be pursued in this grant addresses a prominent and long-standing challenge in synthetic organic chemistry. A main focus of this proposal is the invention of new asymmetric methods based on the powerful multicatalytic strategy of "synergistic catalysis." This concept envisions the productive merger of two simultaneous catalytic cycles, which operate in concert to separately activate each reactant, culminating in a single bond- forming event. Because of its enormous potential to enable the development of previously inconceivable chemical transformations, and to dramatically improve the selectivity of existing reactions, we anticipate that asymmetric synergistic catalysis will emerge as a transformative synthetic paradigm. The research to be pursued in Aim I of this grant is directed toward the development of new synergistic methods based on the merger of organocatalysis and copper catalysis. Aims II and III of this proposal outline the development and application of a novel asymmetric catalytic activation mode, recently identified in our laboratory, that utilizes ligated copper catalysis with iodonium salts, to effect the asymmetric functionalization of nucleophilic substrates. Specifically Aim I envisions the development, through the synergistic merger of organocatalysis and copper catalysis, of a collection of powerful new asymmetric methods, namely: -arylation of aldehydes; -vinylation of aldehydes using either vinyl iodonium salts or vinyl borane coupling partners; -methylation of aldehydes; and -arylation of aldehydes. Aim II outlines the development, through application of a novel ligated copper catalysis platform, of a series of new asymmetric transformations by which to achieve: -arylation of carbonyls; -vinylation of carbonyls; and dearomatizing arylation of tryptamine and tryptophol substrates, to deliver pyrroloindoline and furanoindoline motifs. Finally, in Aim III of this proposal, we will demonstrate the ability of our newly developed asymmetric dearomatizing arylation protocol to facilitate the construction of complex target systems, through a convergent asymmetric synthesis of the 3- arrylpyrroloindoline natural product, naseseazine A.

描述(申请人提供)：这项研究提案寻求发明和开发广泛的新的不对称催化策略，这将提供对映体选择性访问一系列特权功能基序，这些功能基序是当前方法难以获得的。在这笔赠款中，每一种方法都解决了合成有机化学中一个突出的和长期存在的挑战。这项提议的一个主要焦点是发明新的不对称方法，该方法基于“协同催化”这一强大的多催化策略。这一概念设想了两个同时进行的催化循环的有效合并，这两个循环协同工作，分别激活每个反应物，最终形成一个单一的键形成事件。由于不对称协同催化具有发展以前难以想象的化学转化和显著提高现有反应的选择性的巨大潜力，我们预计不对称协同催化将成为一种变革性的合成范式。这笔赠款的目标I中将进行的研究旨在开发基于有机催化和铜催化的合并的新的协同方法。本提案的目标II和III概述了我们实验室最近发现的一种新的不对称催化活化模式的开发和应用，该模式利用连接的铜催化 碘盐，以实现亲核底物的不对称官能化。具体来说，我设想通过有机催化和铜催化的协同合并，开发一系列强大的新的不对称方法，即：-醛的芳基化；-使用乙烯基碘盐或乙烯基硼烷偶联对的醛的乙烯基化；-醛的甲基化；以及-醛的芳基化。目的II概述了通过应用一种新型的结合铜催化平台来实现一系列新的不对称转化的发展：-羰基的芳基化；-羰基的乙烯基化；以及色胺和色醇底物的脱芳构化芳基化，以产生吡咯吲哚和呋喃吲哚基元。最后，在这项提案的目标三中，我们将展示我们的 新开发的不对称脱芳构化芳基化方案，通过3-芳基吡咯吲哚天然产物Naseseazine A的收敛不对称合成，促进了复杂目标体系的构建。