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（由申请人提供）：本研究计划旨在发明和开发广泛的新型不对称催化策略，该策略将提供对映选择性途径，以获得一系列通过当前方法不易获得的特权功能基序。每一种方法都是为了解决合成有机化学中一个突出的和长期存在的挑战。该提案的一个主要焦点是基于强大的多催化策略“协同催化”发明新的不对称方法。这一概念设想了两个同时发生的催化循环的有效合并，它们协同作用，分别激活每种反应物，最终形成单一的键形成事件。由于其巨大的潜力，使以前难以想象的化学转化的发展，并大大提高现有反应的选择性，我们预计，不对称协同催化将出现作为一个变革性的合成范式。本基金第一期的研究方向是在有机催化和铜催化结合的基础上开发新的协同方法。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型不对称催化激活模式的发展和应用，该模式利用连接铜催化与