Inter- und intramolecular, phosphoric acid-catalyzed reactions of in situ-generated ortho-quinone methides and ortho-quinone methide imines towards the enantioselective synthesis of benzoannulated oxygen and nitrogen heterocycles

原位生成的邻醌甲基化物和邻醌甲基化物亚胺的分子间和分子内磷酸催化反应，用于对映选择性合成苯环氧和氮杂环

基本信息

批准号：
268823980
负责人：
Professor Dr. Christoph Schneider
金额：
--
依托单位：
Institut für Organische Chemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2015
资助国家：
德国
起止时间：
2014-12-31 至 2021-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/268823980?language=en
关键词：
Inter und intramolecular phosphoric acid

项目摘要

Ortho-quinone methides are shortlived, highly reactive alkylidene cyclohexadienones, which are generated in situ and are converted into phenols via conjugate addition and cycloaddition reactions under rearomatization. In the first funding period we have been able to show for a broad range of reactions that phosphoric acid-bound, chiral ortho-quinone methides can be easily generated from ortho-hydroxyl benzyl alcohols and treated with enolrich and related nucleophiles to furnish benzoannulated oxygen heterocycles with excellent enantioselectivity through bifunctional activation.In the next funding period we intend to exploit the full potential not only of the ortho-quinone methides but also of the corresponding ortho-quinone methide imines. We intend to develop these reactions into broadly applicable processes for the flexible and highly stereoselective synthesis of benzoannulated oxygen and nitrogen heterocycles. In that respect two main subtopics are planned which go far beyond the previous work conceptually: First, the development of a cooperative-synergistic catalysis strategy, which allows for the combination of phosphoric acid catalysis with amine catalysis in reactions of ortho-quinone methides. Such a strategy shall enable transformations not feasible under monocatalytic conditions and the use of catalytically generated enamines and dienamines. Densely functionalized and highly substituted chromans are to be synthesized in a highly enantioselective manner in reactions with ortho-quinone methides.Second, we intend to study intramolecular, enantioselective cycloadditions of ortho-quinone methide imines in order to access alkaloid-like structures such as benzoannulated indolizidines and quinolizidines. Such a strategy is currently without precedence in an enantioselective fashion and would constitute a significant conceptual advance of the synthetic potential of ortho-quinone methide imines. In preliminary work we have been able to achieve a proof of principle and intend now to develop this strategy into a powerful general method. Furthermore, we intend to study intramolecular conjugate additions of various p-nucleophiles and heteronucleophiles toward ortho-quinone methide imines in order to access polysubstituted and highly functionalized tetrahydroquinolines, benzoazepines, and benzodiazepines.

邻醌甲基化物是短寿命、高反应性的亚烷基环己二酮，其原位生成，并在重芳构化下通过共轭加成和环加成反应转化为苯酚。在第一个资助期间，我们已经能够证明磷酸结合的手性邻醌甲基化物可以很容易地从邻羟基苯甲醇生成，并用富烯醇和相关亲核试剂处理，以提供苯并环化的氧杂环。通过双功能激活具有优异的对映选择性。在下一个资助期内，我们打算不仅充分利用邻醌甲基化物的潜力，而且还开发相应的邻醌甲基亚胺。我们打算将这些反应发展成广泛适用的工艺，用于灵活且高度立体选择性地合成苯并环氧和氮杂环。在这方面，计划的两个主要子主题在概念上远远超出了以前的工作：首先，开发协同催化策略，该策略允许在邻醌甲基化物的反应中将磷酸催化与胺催化相结合。这种策略应能够实现在单催化条件下不可行的转化以及使用催化生成的烯胺和二烯胺。稠密功能化和高度取代的苯并二氢吡喃将以高度对映选择性的方式与邻醌甲基化物反应合成。其次，我们打算研究邻醌甲基化物亚胺的分子内、对映选择性环加成反应，以获得类生物碱结构，例如苯并环化结构。吲哚里西啶和喹里西啶。这种策略目前在对映选择性方式中尚无先例，并且将构成邻醌甲基亚胺合成潜力的重大概念进步。在前期工作中，我们已经能够实现原理证明，现在打算将该策略发展成为一种强大的通用方法。此外，我们打算研究各种对亲核试剂和异亲核试剂对邻醌甲基亚胺的分子内共轭加成，以获得多取代和高度官能化的四氢喹啉、苯并氮杂卓和苯二氮卓类药物。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cooperative Photoinduced/Brønsted Acid Catalyzed Cycloaddition of Transient Thioaldehydes and ortho-Quinone Methides toward a Synthesis of Benzo[e][1,3]oxathiines.

光诱导/布朗斯台德酸催化瞬时硫醛和邻醌甲基化物的环加成反应合成苯并[e][1,3]氧噻啶

DOI：
10.1021/acs.orglett.1c00588
发表时间：
2021
期刊：
Organic letters
影响因子：
5.2
作者：
F. Sachse;C. Schneider
通讯作者：
C. Schneider

Unravelling the configuration of transient ortho-quinone methides by combining microfluidics with gas phase vibrational spectroscopy.

将微流体与气相振动光谱相结合，揭示瞬态邻醌方法的结构

DOI：
10.1039/c9cp06435d
发表时间：
2020
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
0
作者：
M. Mayer;M. Pahl;M. Spanka;M. Grellmann;M. Sickert;C. Schneider;K. Asmis;D. Belder
通讯作者：
D. Belder

Phosphoric Acid Catalyzed Aldehyde Addition to in Situ Generated o-Quinone Methides: An Enantio- and Diastereoselective Entry toward cis-3,4-Diaryl Dihydrocoumarins.