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）：本研究提案旨在发明和开发广泛的新的不对称催化策略，这将提供对映选择性地获得一系列特权功能基序，这些功能基序通过目前的方法不易获得。每一种方法将在此补助金追求解决一个突出的和长期存在的挑战，在合成有机化学。该提案的一个主要焦点是基于“协同催化”的强大多催化策略的新的不对称方法的发明。“这一概念设想了两个同时发生的催化循环的生产性合并，这两个催化循环协同工作，分别激活每个反应物，最终形成一个单一的键形成事件。由于其巨大的潜力，使以前无法想象的化学转化的发展，并显着提高现有反应的选择性，我们预计，不对称协同催化将成为一个变革性的合成范式。该研究将在本基金的目标I中进行，旨在开发基于有机催化和铜催化合并的新协同方法。本提案的目标II和III概述了我们实验室最近确定的一种新型不对称催化活化模式的开发和应用，该模式利用配位铜催化， 碘鎓盐，以实现亲核底物的不对称官能化。具体目标我设想的发展，通过有机催化和铜催化的协同合并，收集强大的新的不对称方法，即：-芳基化的醛; -乙烯基化的醛使用乙烯基碘鎓盐或乙烯基硼烷偶联伙伴; -甲基化的醛;和-芳基化的醛。目的II概述了发展，通过应用一种新的连接铜催化平台，一系列新的不对称转化，通过它来实现：-羰基的芳基化; -羰基的乙烯化;和脱芳芳基化色胺和乙醇底物，提供吡咯并吲哚啉和呋喃并吲哚啉图案。最后，在本提案的目标III中，我们将展示我们的能力， 新开发的不对称脱芳构化芳基化方案，通过3-芳基吡咯并吲哚啉天然产物nasesezine A的收敛不对称合成，促进复杂目标系统的构建。