Visible-light photocatalysis has evolved over the last decade into a widely used method in organic synthesis. Photocatalytic variants have been reported for many important transformations, such as cross-coupling reactions, α-amino functionalizations, cycloadditions, ATRA reactions, or fluorinations. To help chemists select photocatalytic methods for their synthesis, we compare in this Review classical and photocatalytic procedures for selected classes of reactions and highlight their advantages and limitations. In many cases, the photocatalytic reactions proceed under milder reaction conditions, typically at room temperature, and stoichiometric reagents are replaced by simple oxidants or reductants, such as air, oxygen, or amines. Does visible-light photocatalysis make a difference in organic synthesis? The prospect of shuttling electrons back and forth to substrates and intermediates or to selectively transfer energy through a visible-light-absorbing photocatalyst holds the promise to improve current procedures in radical chemistry and to open up new avenues by accessing reactive species hitherto unknown, especially by merging photocatalysis with organo- or metal catalysis.

Visible-Light Photocatalysis: Does It Make a Difference in Organic Synthesis?

The targeted choice of specific photocatalysts has been shown to play a critical role for the successful realization of challenging photoredox catalytic transformations. Herein, we demonstrate the successful implementation of a rational design strategy for a series of deliberate structural manipulations of cyanoarene-based, purely organic donor–acceptor photocatalysts, using 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) as a starting point. Systematic modifications of both the donor substituents as well as the acceptors’ molecular core allowed us to identify strongly oxidizing as well as strongly reducing catalysts (e.g., for an unprecedented detriflation of unactivated naphthol triflate), which additionally offer remarkably balanced redox potentials with predictable trends. Especially halogen arene core substitutions are instrumental for our targeted alterations of the catalysts’ redox properties. Based on their preeminent electrochemical and photophysical characteristics, all novel, purely...

A Toolbox Approach To Construct Broadly Applicable Metal-Free Catalysts for Photoredox Chemistry: Deliberate Tuning of Redox Potentials and Importance of Halogens in Donor–Acceptor Cyanoarenes

Photokatalyse mit sichtbarem Licht: Welche Bedeutung hat sie für die organische Synthese?

The first highly enantioselective catalytic protocol for the reductive coupling of ketones and hydrazones is reported. These reactions proceed through neutral ketyl radical intermediates generated via a concerted proton-coupled electron transfer (PCET) event jointly mediated by a chiral phosphoric acid catalyst and the photoredox catalyst Ir(ppy)2(dtbpy)PF6. Remarkably, these neutral ketyl radicals appear to remain H-bonded to the chiral conjugate base of the Brønsted acid during the course of a subsequent C-C bond-forming step, furnishing syn 1,2-amino alcohol derivatives with excellent levels of diastereo- and enantioselectivity. This work provides the first demonstration of the feasibility and potential benefits of concerted PCET activation in asymmetric catalysis.

Enantioselective photoredox catalysis enabled by proton-coupled electron transfer

Metal-Catalyzed Direct Difluoromethylation Reactions

Advances in Photocatalysis: A Microreview of Visible Light Mediated Ruthenium and Iridium Catalyzed Organic Transformations

Solubility of Iridium and Ruthenium Organometallic Photoredox Catalysts

While accessible via UV-irradiation of cis-cyclohexene, trans-cyclohexene has thus far been an investigation driven by curiosity, and due primarily to its short lifespan, has until recently not been employed for productive synthesis. Herein, we present straightforward conditions that provide access to a class of trans-arylcyclohexenes and demonstrate their utility in the formation of oxabicyclic ethers, which are otherwise inaccessible from the corresponding cis-cyclohexene. A key challenge to utilizing the incredible ca. 52 kcal/mol strain energy of trans-cyclohexene to drive synthesis was overcoming its short lifetime. Herein, we show that preorganization via hydrogen bonding between the substrate and the reaction partner prior to isomerization is a viable strategy to overcome the inherently short lifetime of trans-cyclohexene.

Visible Light Mediated Generation of trans-Arylcyclohexenes and Their Utilization in the Synthesis of Cyclic Bridged Ethers.

Functionalized per- and polyfluoroarenes are important building blocks, with many industrially and medicinally important molecules containing them. Nucleophilic aromatic substitution can be employed as a quick and straightforward way to synthesize these building blocks. While many methods to derivatize fluoroarenes exist that use heteroatom centered nucleophiles, there are fewer methods that use carbon centered nucleophiles, and of those many are poorly defined. This work presents the SNAr reaction of nucleophiles generated from nitroalkanes with a variety of fluorinated arenes. Given that the products are versatile, accessing polyfluorinated arene building blocks in substantial scale is important. This method is highly regioselective, and produces good to moderate yields on a large scale, sans chromatography, and thus fulfills this need. In addition, the regioselectivity of the addition was probed using both DFT calculations and experimentally via halogen exchange.

Selective and Scalable Perfluoroarylation of Nitroalkanes.

Within the framework of discovery chemistry, polyfluorination remains a synthetic challenge despite its ability to provide useful characteristics, such as a reduction in the number of hydrogen bond donors and metabolic stability Coupling a reversal of this methodology with photocatalysis has been demonstrated to allow the rapid synthesis of previously difficult or impossible targets by starting with fluorines everywhere and selectively removing or functionalizing them Herein, we demonstrate a novel method to synthesize 1,4-cyclohexadienes through a dearomative photocatalytic C-C coupling reaction This allows for access to materials that are orthogonal to the selectivity of the Birch reaction and are more functional-group-tolerant The reaction also allows the efficient synthesis of polyfluorinated cannabinoids While the yields are modest, the access to the new chemical space provided by the reaction is unprecedented by any means The trifluorinated analog of THC, 1-deoxy-1,2,4-trifluoro-THC, is synthesized, demonstrating the importance of discovery chemistry and the ability to explore otherwise unknown structure-activity relationships

Jon I. Day

Papers

Advances in Photocatalysis: A Microreview of Visible Light Mediated Ruthenium and Iridium Catalyzed Organic Transformations

Solubility of Iridium and Ruthenium Organometallic Photoredox Catalysts

Visible Light Mediated Generation of trans-Arylcyclohexenes and Their Utilization in the Synthesis of Cyclic Bridged Ethers.

Selective and Scalable Perfluoroarylation of Nitroalkanes.

Defluorodearomatization: A Photocatalytic Birch-Like Reduction That Enables C-C Bond Formation and Provides Access to Unnatural Cannabinoids.