Liang-Qiu Lu

Highly Efficient Aerobic Oxidative Hydroxylation of Arylboronic Acids: Photoredox Catalysis Using Visible Light

The development of green and sustainable methods for effective synthesis of fine chemicals is an important goal in our society. During the last decade, visible-light photoredox catalysis has shown great promise as a method to advance these goals. As a result of its high natural abundance, benign environmental impact, cleanliness, and sustainability, photocatalysis using visible light is a reliable and powerful tool. In this context, there are several examples of its usefulness, including asymmetric alkylation of aldehydes, [2+2] cycloaddition of enones, [3+2] cycloaddition of aryl cyclopropyl ketones, reductive dehalogenation, radical addition to unsaturated bonds, and coupling reactions. 9] Despite these advances, oxidative reactions initiated by visible light are largely unexplored. In 2003, Zen et al. reported a visible-light photocatalytic reaction for the oxidation of sulfides into sulfoxides. Later, Zhao et al. oxidized alcohols to aldehydes using visible light and dye-sensitized TiO2. [11] Recently, the groups of Blechert and Wang developed a metal-free photooxidative system to achieve the oxidation of amines and alcohols, and Jiao et al. described the use of a Ru polypyridine complex and 4-methoxypyridine to promote the conversion of a-aryl halogen derivatives into a-aryl carbonyl compounds. The molecular oxygen in air has been widely used as a green oxidant in synthesis. Consequently, the development of visible-light photooxidative reactions using air as the oxidant is highly desirable. We recently developed a visiblelight-induced oxidation/[3+2] cycloaddition/oxidative aromatization sequence for dihydroisoquinoline esters and electrondeficient alkenes or alkynes to construct pyrrolo[2,1-a] isoquinolines. 16] In this sequence, a superoxide radical anion, which was generated from molecular oxygen, plays a key role throughout the process. Based on the investigation of the mechanism, we envisioned that this kind of highly active species might have Lewis basicity and therefore react with the appropriate acidic components. We report herein the realization of this strategy for the direct aerobic oxidative hydroxylation of arylboronic acids to aryl alcohols using visible-light irradiation and air as the source of the terminal oxidant. In this reaction, we envisioned that the superoxide radical anion generated from the photoredox cycle could react with arylboronic acids because of its Lewis acidity, which arises from the vacant p orbital on the boron atom, followed by a series of rearrangements to provide aryl alcohols (Scheme 1).

Visible‐Light‐Induced Formal [3+2] Cycloaddition for Pyrrole Synthesis under Metal‐Free Conditions

A photocatalytic formal [3+2] cycloaddition of 2H-azirines with alkynes has been achieved under irradiation by visible light in the presence of organic dye photocatalysts. This transformation provides efficient access to highly functionalized pyrroles in good yields and has been applied to the synthesis of drug analogues. A primary trial of photocascade catalysis merging energy transfer and redox neutral reactions was shown to be successful.

Exploration of Visible-Light Photocatalysis in Heterocycle Synthesis and Functionalization: Reaction Design and Beyond

Visible-light photocatalysis has recently received increasing attention from chemists because of its wide application in organic synthesis and its significance for sustainable chemistry. This catalytic strategy enables the generation of various reactive species, frequently without stoichiometric activation reagents under mild reaction conditions. Manipulation of these reactive intermediates can result in numerous synthetically useful bond formations in a controllable manner. In this Account, we describe our recent advances in the rational design and strategic application of photocatalysis in the synthesis of various synthetically and biologically important heterocycles. Our main research efforts toward this goal can be classified into four categories: formal cycloaddition and cyclization reactions, radical-mediated olefin functionalization/cyclization cascades, photocatalytic generation and cyclization of N-centered radicals, and photocatalytic functionalization of heterocycles by visible-light-induced dual catalysis. Inspired by the wide application of tertiary amines as reductive additives in photoredox catalysis, we exploited a series of readily accessible or rationally designed tertiary amines with reactive sites in a range of photocatalytic formal cycloaddition and cyclization reactions, providing efficient access to diverse nitrogen heterocycles. Employing various photogenerated radical species, we further developed a series of radical-mediated olefin functionalization/cyclization cascade reactions to successfully assemble various five- and six-membered heterocycles. We have also achieved for the first time the direct catalytic conversion of recalcitrant N-H bonds into neutral N-centered radicals through a visible-light-photocatalytic oxidative deprotonation electron transfer. Using this generic strategy, we have devised several types of radical cyclizations of unsaturated hydrazones, leading to the construction of diversely functionalized pyrazoline and pyridazine derivatives in good yields and selectivity. Moreover, we have demonstrated that this photocatalysis can serve as a mild and highly selective tool for direct functionalization of heterocycles because of its powerful capability to controllably generate diverse reactive intermediates under mild reaction conditions. Guided by the fundamental principles of photocatalysis and the redox properties of the photocatalysts, we successfully developed an array of dual-catalyst systems by combining the photocatalysts with palladium, nickel, or amine, enabling efficient and selective coupling reactions. An intriguing phototandem catalytic system using a single photocatalyst was also identified for the development of cascade reactions. Notably, some of the newly developed methodologies have also been successfully utilized for late-stage modification of biologically active natural compounds and complex molecules and as key steps for formal synthesis of natural products. This Account presents a panoramic view and the logic of our recent contributions to the design, development, and application of photocatalytic systems and reactions that provide not only methods for the efficient synthesis of heterocycles but also useful insights into the exploration of new photochemical reactions.

Visible light-induced intramolecular cyclization reactions of diamines: a new strategy to construct tetrahydroimidazoles

A new and efficient synthesis of highly substituted tetrahydroimidazole derivatives by means of visible light-induced intramolecular cyclization reactions has been described. This photoredox catalytic reaction exhibited high diastereoselectivity and afforded the desired products in good yields.

Redox‐Neutral α‐Allylation of Amines by Combining Palladium Catalysis and Visible‐Light Photoredox Catalysis

An unprecedented α-allylation of amines was achieved by combining palladium catalysis and visible-light photoredox catalysis. In this dual catalysis process, the catalytic generation of allyl radical from the corresponding π-allylpalladium intermediate was achieved without additional metal reducing reagents (redox-neutral). Various allylation products of amines were obtained in high yields through radical cross-coupling under mild reaction conditions. Moreover, the transformation was applied to the formal synthesis of 8-oxoprotoberberine derivatives which show potential anticancer properties.

Highly Chemoselective Metal-Free Reduction of Phosphine Oxides to Phosphines

Unprecedented chemoselective reductions of phosphine oxides to phosphines proceed smoothly in the presence of catalytic amounts of specific Brønsted acids. By utilizing inexpensive silanes, e.g., PMHS or (EtO)(2)MeSiH, other reducible functional groups such as ketones, aldehydes, olefins, nitriles, and esters are well-tolerated under optimized conditions.

Decarboxylative Alkynylation and Carbonylative Alkynylation of Carboxylic Acids Enabled by Visible-Light Photoredox Catalysis†

Visible-light-induced photocatalytic decarboxylative alkynylations of carboxylic acids have been developed for the first time. The reaction features extremely mild conditions, broad substrate scope, and avoids additional oxidants. Importantly, a decarboxylative carbonylative alkynylation has also been carried out in the presence of carbon monoxide (CO) under photocatalytic conditions, which affords valuable ynones in high yields at room temperature.

A New Entry to Cascade Organocatalysis : Reactions of Stable Sulfur Ylides and Nitroolefins Sequentially Catalyzed by Thiourea and DMAP

A novel cascade organocatalysis that allows efficient and rapid access to diverse and structurally complex oxazolidin-2-ones from simple starting materials and catalysts has been developed. A possible mechanism of this reaction has been proposed based on D- and 13C-labeling experiments.

Metal-Free, room-temperature, radical alkoxycarbonylation of aryldiazonium salts through visible-light photoredox catalysis.

The first radical alkoxycarboxylation of aryldiazonium salts using CO gas through visible-light-induced photoredox catalysis (16 W blue LEDs) has been developed. This reaction is entirely metal-free, is carried out at room temperature with a low loading of an organic dye as a photocatalyst (0.5 mol %), and provides a wide range of arylcarboxylic acid esters in high yields. Importantly, this photocatalytic system can be successfully extended to other carboxylation reactions.

Room Temperature CP Bond Formation Enabled by Merging Nickel Catalysis and Visible‐Light‐Induced Photoredox Catalysis

A novel and efficient C-P bond formation reaction of diarylphosphine oxides with aryl iodides was achieved by combining nickel catalysis and visible-light-induced photoredox catalysis. This dual-catalytic reaction showed a broad substrate scope, excellent functional group tolerance, and afforded the corresponding products in good to excellent yields. Compared with the previously reported use of photoredox/nickel dual catalysis in the construction of C-C bonds, the methodology described herein was observed to be the first to allow for C-heteroatom bond formation.