Nathan A. Romero

In this review, we highlight the use of organic photoredox catalysts in a myriad of synthetic transformations with a range of applications. This overview is arranged by catalyst class where the photophysics and electrochemical characteristics of each is discussed to underscore the differences and advantages to each type of single electron redox agent. We highlight both net reductive and oxidative as well as redox neutral transformations that can be accomplished using purely organic photoredox-active catalysts. An overview of the basic photophysics and electron transfer theory is presented in order to provide a comprehensive guide for employing this class of catalysts in photoredox manifolds.

Over the past several decades, organometallic cross-coupling chemistry has developed into one of the most reliable approaches to assemble complex aromatic compounds from preoxidized starting materials. More recently, transition metal-catalyzed carbon-hydrogen activation has circumvented the need for preoxidized starting materials, but this approach is limited by a lack of practical amination protocols. Here, we present a blueprint for aromatic carbon-hydrogen functionalization via photoredox catalysis and describe the utility of this strategy for arene amination. An organic photoredox-based catalyst system, consisting of an acridinium photooxidant and a nitroxyl radical, promotes site-selective amination of a variety of simple and complex aromatics with heteroaromatic azoles of interest in pharmaceutical research. We also describe the atom-economical use of ammonia to form anilines, without the need for prefunctionalization of the aromatic component.

Herein, we report half-peak potentials for over 180 organic substrates obtained via cyclic voltammetry. These values are of great use in assessing the thermodynamics of an electron-transfer process. In addition, we disclose a simple computational method to determine redox potentials of organic substrates.

We describe our efforts to understand the key mechanistic aspects of the previously reported alkene hydrofunctionalization reactions using 9-mesityl-10-methylacridinium (Mes-Acr(+)) as a photoredox catalyst. Importantly, we are able to detect alkene cation radical intermediates, and confirm that phenylthiyl radical is capable of oxidizing the persistent acridinyl radical in a fast process that unites the catalytic activity of the photoredox and hydrogen atom transfer (HAT) manifolds. Additionally, we present evidence that diphenyl disulfide ((PhS)2) operates on a common catalytic cycle with thiophenol (PhSH) by way of photolytic cleaveage of the disulfide bond. Transition structure analysis of the HAT step using DFT reveals that the activation barrier for H atom donation from PhSH is significantly lower than 2-phenylmalononitrile (PMN) due to structural reorganization. In the early stages of the reaction, Mes-Acr(+) is observed to engage in off-cycle adduct formation, presumably as buildup of PhS(-) becomes significant. The kinetic differences between PhSH and (PhS)2 as HAT catalysts indicate that the proton transfer step may have significant rate limiting influence.

A new Au(III)-catalyzed tandem amination-hydration reaction has been discovered, leading to the formation of α-(N-2-pyridonyl)ketones and heterocyclic analogues in good to excellent yields (14 examples, 48-90%). This reaction demonstrates the unusual use of a heterocyclic sp(2) nitrogen nucleophile in a gold-catalyzed 6-endo-dig cyclization. The tandem process allows rapid access to α-(N-2-pyridonyl)ketones, making them a convenient building block for the synthesis of more complex N-alkyl pyridone targets.