Photoredox Catalysis in Organic Chemistry

描述（由申请人提供）：在过去的五年中，可见光介导的光氧化还原催化已经成为有机合成中多功能的新激活平台。钌或铱基聚吡啶基光氧化还原催化剂吸收可见光范围内的光，产生稳定、长寿命的激发态，可以作为单电子氧化剂或还原剂。由于其独特的反应性，光氧化还原催化剂具有在标准方法下无法实现的具有挑战性的键结构的能力。在2008年的一项开创性披露中，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；这种强大的双催化策略的特点是同时产生两种反应中间体的催化量。随后的报告，从我们的小组和其他人，进一步确立了光氧化还原催化的显着的复杂性建设能力，特别是当与有机催化合并。在这个研究计划中，我们概述了我们基于照片的研究计划的新方向。本文提出的四个目标中的每一个都设想了一种新的反应性平台，该平台具有瞬时的、光氧化还原产生的活性物质，可以有效地用于合成一系列高价值功能基序。在Aim 1中，我们建议通过一种新的5π电子中间体，通过协同有机催化和光氧化还原催化，由酮或醛前体瞬时生成，开发Mannich， Michael和aldol反应的直接单碳扩展变体。Aim 2利用α-氨基自由基-通过光氧化还原催化原位生成-在有价值的含胺支架，包括邻胺和烯丙胺。目标3设想通过协同巯基有机催化和光氧化还原催化直接芳化不稳定的烯丙基和苯基C-H键，作为快速获得二芳基甲烷和乙烯基芳基甲烷的一种手段。最后，在Aim 4中，我们建议完成光氧化还原催化的脱羧功能化

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.