Synergistic Catalysis for Chemical Synthesis

化学合成协同催化

基本信息

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
项目类别：
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

项目摘要

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）：本研究计划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通过当前方法不易获得的特权功能基序。本次资助所采用的每种方法都解决了合成有机化学中一个突出且长期存在的挑战。该提案的主要焦点是基于“协同催化”强大的多催化策略发明新的不对称方法。这一概念设想了两个同时催化循环的有效合并，它们协同作用以分别激活每种反应物，最终形成单一的成键事件。由于其巨大的潜力能够发展以前难以想象的化学转化，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作为一种变革性的合成范式出现。本次资助的目标一将进行的研究旨在开发基于有机催化和铜催化合并的新协同方法。该提案的目标 II 和 III 概述了我们实验室最近确定的新型不对称催化活化模式的开发和应用，该模式利用连接铜催化碘鎓盐，以实现亲核底物的不对称官能化。具体而言，目标 I 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不对称方法，即：醛的芳基化； -使用乙烯基碘鎓盐或乙烯基硼烷偶联配对物进行醛的乙烯基化； -醛的甲基化；和醛的-芳基化。目标 II 概述了通过应用新型连接铜催化平台开发一系列新的不对称转化，从而实现： -羰基的芳基化； -羰基的乙烯基化；色胺和色酚底物的脱芳构化，以提供吡咯并吲哚啉和呋喃吲哚啉基序。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 naseseazine A 的收敛不对称合成，促进复杂目标系统的构建。公共健康相关性：本研究的目的是建立一种新的化学合成催化策略，利用廉价、廉价且易于获得的起始原料，以高度加速的方式生成天然产物、生物活性化合物和药剂。