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的多功能新活化平台。钌或铱基聚吡啶光氧化还原催化剂吸收可见光范围内的光，以产生稳定、长寿命的激发态，其可以充当单电子氧化剂或还原剂。由于其独特的反应性特征，光氧化还原催化剂能够实现在标准方法下无法实现的具有挑战性的键结构。在2008年的一项开创性的公开中，我们的实验室描述了通过光氧化还原催化和手性胺有机催化的协同合并实现醛的不对称α-烷基化;这种强大的双催化策略的特点是同时产生催化量的两种活性中间体。随后的报告，从我们的小组和其他人，进一步建立了显着的复杂性建设能力的光氧化还原催化，特别是当合并与有机催化。在这项研究计划中，我们概述了我们基于光氧化还原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，其特征在于瞬时的光氧化还原生成的活性物质，其可以有效地用于合成高价值功能基序的菜单。在目标1中，我们提出通过一种新型的5π电子中间体物种开发直接的一碳扩展的Mannich，Michael和aldol反应变体，该中间体物种通过协同有机催化和光氧化还原催化从酮或醛前体瞬时产生。目标2利用α-氨基自由基物种-通过光氧化还原催化原位产生-在路线上有价值的含胺支架，包括邻二胺和烯丙基胺。目标3设想通过协同的基于硫醇的有机催化和光氧化还原催化，将不稳定的烯丙基和苄基C-H键直接芳基化，作为快速获得二芳基甲烷和乙烯基-芳基甲烷的手段。最后，在目标4中，我们提出完成光氧化还原催化的脱羧官能化， α-氨基酸在有价值的苄基胺和烷基胺基序的途中。在该项目的一个关键扩展中，我们将探索通过合并的光氧化还原和手性胺基有机催化合成γ-氨基醛的不对称变体的开发机会。

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.