Atroposelective Brønsted Acid-Catalyzed Photocyclization to Access Chiral -Aryl Quinolones with Low Rotational Barriers.

Herein, a novel route to atropisomeric -aryl quinolones with low rotational barriers is demonstrated, leveraging a dual photochemical/organocatalytic approach to the required ring closure in up to 94% yield and up to >99% ee. The use of a continuous flow system allows for impurity suppression and enables rapid scale-up to a decagram scale.

Direct C-H Radiocyanation of Arenes via Organic Photoredox Catalysis.

Innovative labeling methods to incorporate the short-lived positron emitter carbon-11(C) into bioactive molecules are attractive for positron emission tomography (PET) tracer discovery. Herein, we report a direct C-H radiocyanation method that incorporates [C]cyanide (CN) to a series of functional electron-rich arenes via photoredox catalysis. This photoredox-mediated radiocyanation can proceed in an aerobic environment and is not moisture sensitive, which allows for ease of reaction setup and for scalable synthesis of C-aryl nitriles from readily available precursors.

Homobenzylic Oxygenation Enabled by Dual Organic Photoredox and Cobalt Catalysis.

Activation of aliphatic C(sp)-H bonds in the presence of more activated benzylic C(sp)-H bonds is often a nontrivial, if not impossible task. Herein we show that leveraging the reactivity of benzylic C(sp)-H bonds to achieve reactivity at the homobenzylic position can be accomplished using dual organic photoredox/cobalt catalysis. Through a two-part catalytic system, alkyl arenes undergo dehydrogenation followed by an anti-Markovnikov Wacker-type oxidation to grant benzyl ketone products.

Site-Selective C-H Alkylation of Piperazine Substrates via Organic Photoredox Catalysis.

Piperazine-containing compounds serve as one of the most important classes of compounds throughout all fields of chemistry. Alas, current synthetic methods have fallen short of providing a general method for the synthesis of highly decorated piperazine fragments. Herein, we present a site-selective approach to the C-H functionalization of existing piperazine compounds using photoredox catalysis.

Generation and Alkylation of α-Carbamyl Radicals via Organic Photoredox Catalysis.

Strategies for the direct C-H functionalization of amines are valuable as these compounds comprise a number of pharmaceuticals, agrochemicals and natural products. This work describes a novel method for the C-H functionalization of carbamate-protected secondary amines via α-carbamyl radicals generated using photoredox catalysis. The use of the highly oxidizing, organic acridinium photoredox catalyst allows for direct oxidation of carbamate-protected amines with high redox potentials to give the corresponding carbamyl cation radical.

Predictive Model for Site-Selective Aryl and Heteroaryl C-H Functionalization via Organic Photoredox Catalysis.

Direct C-H functionalization of aromatic compounds is a useful synthetic strategy that has garnered much attention because of its application to pharmaceuticals, agrochemicals, and late-stage functionalization reactions on complex molecules. On the basis of previous methods disclosed by our lab, we sought to develop a predictive model for site selectivity and extend this aryl functionalization chemistry to a selected set of heteroaromatic systems commonly used in the pharmaceutical industry. Using electron density calculations, we were able to predict the site selectivity of direct C-H functionalization in a number of heterocycles and identify general trends observed across heterocycle classes.

Direct C-H Cyanation of Arenes via Organic Photoredox Catalysis.

Methods for the direct C-H functionalization of aromatic compounds are in demand for a variety of applications, including the synthesis of agrochemicals, pharmaceuticals, and materials. Herein, we disclose the construction of aromatic nitriles via direct C-H functionalization using an acridinium photoredox catalyst and trimethylsilyl cyanide under an aerobic atmosphere. The reaction proceeds at room temperature under mild conditions and has proven to be compatible with a variety of electron-donating and -withdrawing groups, halogens, and nitrogen- and oxygen-containing heterocycles, as well as aromatic-containing pharmaceutical agents.

Analogues of fenarimol are potent inhibitors of Trypanosoma cruzi and are efficacious in a murine model of Chagas disease.

We report the discovery of nontoxic fungicide fenarimol (1) as an inhibitor of Trypanosoma cruzi ( T. cruzi ), the causative agent of Chagas disease, and the results of structure-activity investigations leading to potent analogues with low nM IC(50)s in a T. cruzi whole cell in vitro assay.