Switchable Decarboxylation by Energy- or Electron-Transfer Photocatalysis.

Kolbe dimerization and Hofer-Moest reactions are well-investigated carboxylic acid transformations, wherein new carbon-carbon and carbon-heteroatom bonds are constructed via electrochemical decarboxylation. These transformations can be switched by choosing an electrode that allows control of the reactive intermediate, such as carbon radical or carbocation. However, the requirement of a high current density diminishes the functional group compatibility with these electrochemical reactions. Here, we demonstrate the photocatalytic decarboxylative transformation of activated carboxylic acids in a switchable and functional group-compatible manner. We discovered that switching between Kolbe-type or Hofer-Moest-type reactions can be accomplished with suitable photocatalysts by controlling the reaction pathways: energy transfer (EnT) and single-electron transfer (SET). The EnT pathway promoted by an organo-photocatalyst yielded 1,2-diarylethane from arylacetic acids, whereas the ruthenium photoredox catalyst allows the construction of an ester scaffold with two arylmethyl moieties via the SET pathway. The resulting radical intermediates were coupled to olefins to realize multicomponent reactions. Consequently, four different products were selectively obtained from a simple carboxylic acid. This discovery offers new opportunities for selectively synthesizing multiple products via switchable reactions using identical substrates with minimal cost and effort.

C-H Acyloxylation of Polycyclic Aromatic Hydrocarbons.

The C-H acyloxylation of polycyclic aromatic hydrocarbons (PAHs) is described. This reaction constructs aryl acyloxylate scaffolds from PAHs with equimolar hypervalent iodine compounds under mild reaction conditions. Interestingly, the blue light irradiation accelerated this transformation. Additionally, the synthesis of structurally new symmetric and unsymmetric diaroyloxylated fluoranthenes was accomplished with a ruthenium photoredox catalyst.

Photoredox-Catalyzed Benzylic Esterification via Radical-Polar Crossover.

Photoredox-catalyzed C-O bond formation reactions are reported. The decarboxylative esterification reaction allows the conversion of a variety of arylacetic acids into the corresponding benzyl carboxylates. Furthermore, the use of (diacetoxyiodo)benzene allows the conversion of the benzylic C-H bond through hydrogen atom transfer. The reactions were applied to the divergent transformation of pharmaceuticals via decarboxylative or C-H esterification reactions.

Late-Stage Functionalization of Arylacetic Acids by Photoredox-Catalyzed Decarboxylative Carbon-Heteroatom Bond Formation.

The rapid transformation of pharmaceuticals and agrochemicals enables access to unexplored chemical space and thus has accelerated the discovery of novel bioactive molecules. Because arylacetic acids are regarded as key structures in bioactive compounds, new transformations of these structures could contribute to drug/agrochemical discovery and chemical biology. This work reports carbon-nitrogen and carbon-oxygen bond formation through the photoredox-catalyzed decarboxylation of arylacetic acids. The reaction shows good functional group compatibility without pre-activation of the nitrogen- or oxygen-based coupling partners. Under similar reaction conditions, carbon-chlorine bond formation was also feasible. This efficient derivatization of arylacetic acids makes it possible to synthesize pharmaceutical analogues and bioconjugates of pharmaceuticals and natural products.

Photoredox-Catalyzed Decarboxylative Oxidation of Arylacetic Acids.

A photoredox-catalyzed decarboxylative oxidation of arylacetic acids, which are privileged scaffolds in pharmaceuticals, is reported herein. The established method is operationally simple and a variety of substrates are applicable, providing rapid access to dehomologated bioisosteres of common pharmaceuticals.