Synergistic Catalysis for Chemical Synthesis

化学合成协同催化

• 批准号: 8411656
• 负责人: David W MacMillan
• 金额: $ 29.66万
• 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/8411656
• 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. PUBLIC HEALTH RELEVANCE: The objective of this research is to establish a new catalytic strategy for chemical synthesis whereby natural products, bioactive compounds and medicinal agents can be generated in a highly accelerated fashion from cheap, inexpensive and readily available starting materials.

描述（由申请人提供）：本研究建议旨在发明和制定广泛的新不对称催化策略，该策略将为对敌方的启示访问一系列特权功能主题，而不是通过当前方法不容易获得。本赠款中要采用的每种方法都涉及合成有机化学中的一个突出且长期存在的挑战。该提案的主要重点是基于强大的“协同催化”的多催化策略的新不对称方法的发明。该概念设想了两个同时催化循环的生产合并，它们共同起作用，可分别激活每个反应物，最终在单个键形成事件中达到顶点。由于它具有巨大的潜力，能够发展以前不可思议的化学转化，并显着提高现有反应的选择性，因此我们预计不对称的协同催化将成为一种变革性的合成范式。这项赠款的目标是针对基于器官分析和铜催化的合并的新协同方法的开发。该提案的目标II和III概述了最近在我们的实验室中确定的新型不对称催化激活模式的开发和应用，该模式利用了粘结的铜催化 碘盐，以实现亲核底物的不对称官能化。特别是目的，我通过组织分析和铜催化的协同合并设想了一系列强大的新不对称方法的收集： - 醛的赎回； - 使用乙烯基碘盐或乙烯基硼烷耦合伴侣对醛的乙烯化； - 醛的甲基化；和 - 醛的赎回。 AIM II概述了通过应用新型连接的铜催化平台的开发，该平台通过一系列新的不对称转换来实现： - 碳化化； - 羰基的乙烯化；并芳香化色素和色氨酸底物的芳基化，以递送吡罗洛琳和呋喃糖苷基序。最后，在本提案的目标三，我们将证明我们的能力 新开发的不对称亲爱的芳基化方案，通过3-芳基吡罗洛林天然产物奈瑟·奈酶A的收敛不对称合成来促进复杂靶系统的构建。 公共卫生相关性：这项研究的目的是建立一种新的化学合成催化策略，从而可以通过高度廉价，廉价且易于使用的起始物质以高速加速的方式生成天然产品，生物活性化合物和药用剂。