Photoredox Catalysis in Organic Chemistry

有机化学中的光氧化还原催化

• 批准号: 9277495
• 负责人: David W MacMillan
• 金额: $ 30.42万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9277495
• 关键词: 3-hydroxybutanal; Address; Aldehydes; Alkenes; Alkylation; Amination; Amines; Amino Acids; Architecture; Area; Carbon; Catalysis; Complex; Coupling; Decarboxylation; Development; Diamines; Disclosure; Electrons; Formaldehyde; Funding; Generations; Grant; Health; Homo; Human; Hydrogen Bonding; Imines; In Situ; Industrialization; Iridium; Ketones; Light; Mediating; Methane; Methods; Organic Chemistry; Organic Synthesis; Oxidants; Pharmacologic Substance; Production; Protocols documentation; Reaction; Reducing Agents; Reporting; Research; Research Proposals; Route; Ruthenium; Seminal; Series; Societies; Sulfhydryl Compounds; Variant; Visible Radiation; adduct; base; catalyst; chemical reaction; novel; programs; public health relevance; scaffold; unnatural amino acids

DESCRIPTION (provided by applicant): Over the past five years, visible light-mediated photoredox catalysis has emerged as a versatile new activation platform in organic synthesis. Ruthenium or iridium-based polypyridyl photoredox catalysts absorb light in the visible range to generate stable, long-lived excited states that may act as either single-electron oxidants or reductants. Due to their unique reactivity profile, photoredox catalysts have the capacity to enable challenging bond constructions that are not accessible under standard approaches. In a seminal 2008 disclosure, our lab described the asymmetric α-alkylation of aldehydes via the synergistic merger of photoredox catalysis and chiral amine organocatalysis; this powerful dual-catalysis strategy features the simultaneous generation of catalytic quantities of both reactive intermediates. Subsequent reports, from our group and others, have further established the remarkable complexity-building capabilities of photoredox catalysis, particularly when merged with organocatalysis. In this research proposal, we outline new directions for our photoredox-based research program. Each of the four aims proposed herein envisions a novel reactivity platform featuring a transient, photoredox-generated active species that may be productively harnessed for the synthesis of a menu of high-value functional motifs. In Aim 1, we propose to develop direct, one-carbon expanded variants of the Mannich, Michael, and aldol reactions via a novel 5π-electron intermediate species that is transiently generated from ketone or aldehyde precursors through synergistic organocatalysis and photoredox catalysis. Aim 2 leverages an α-amino radical species - generated in situ via photoredox catalysis - en route to valuable amine-containing scaffolds, including vicinal diamines and allylic amines. Aim 3 envisions the direct arylation of labile allylic and benzylic C-H bonds through synergistic thiol-based organocatalysis and photoredox catalysis, as a means by which to gain rapid access to diaryl methanes and vinyl-aryl methanes. Finally, in Aim 4, we propose to accomplish the photoredox-catalyzed decarboxylative functionalization of α-amino acids en route to valuable benzylic amine and alkyl amine motifs. In a key expansion of this project, we will explore opportunities for the development of an asymmetric variant for the synthesis of γ-amino aldehydes via merged photoredox and chiral amine-based organocatalysis.

描述(申请人提供)：在过去的五年里，可见光介导的光氧化还原催化已成为有机合成中一种用途广泛的新的活化平台。基于Ru或Ir的聚吡啶光氧化还原催化剂在可见光范围内吸收光，产生稳定的、长寿命的激发态，这些激发态既可以作为单电子氧化剂，也可以作为还原剂。由于其独特的反应活性，光氧化还原催化剂能够实现具有挑战性的键结构，而这些键结构在标准方法下是无法实现的。在2008年的一项开创性的披露中，我们的实验室通过光氧化还原催化和手性胺有机催化的协同合并描述了醛的不对称α-烷基化反应；这一强大的双催化策略的特点是同时生成两种活性中间体的催化量。来自我们小组和其他人的后续报告进一步证实了光氧化还原催化，特别是当与有机催化合并时，具有显著的复杂性构建能力。在这项研究提案中，我们为我们的基于光氧化还原的研究计划勾勒出新的方向。本文提出的四个目标中的每一个都设想了一个新颖的反应平台，其特征是瞬时的、光氧化还原生成的活性物种，可以有效地利用这些活性物种来合成一系列高价值的功能基序。在目标1中，我们建议开发一种新的5π电子中间体，通过协同有机催化和光氧化还原催化从酮或醛的前体瞬时生成的新的5电子中间体，开发曼尼奇、迈克尔和羟醛反应的直接、单碳扩展变体。AIM 2利用α-氨基自由基物种-通过光氧化还原催化原位生成-在路线上有价值的含胺支架，包括邻二胺和烯丙胺。目的3设想不稳定的烯丙基和苄基C-H键通过协同的硫醇有机催化和光氧化还原催化直接芳基化，作为一种快速获得二芳基甲烷和乙烯基芳基甲烷的方法。最后，在目标4中，我们建议完成光氧化还原催化的脱羧基功能化。 α--在通往有价值的苄基胺和烷基胺的途中的氨基酸。在这个项目的一个关键扩展中，我们将探索开发一种不对称变体的机会，通过合并的光氧化还原和手性胺有机催化合成γ-氨基醛。