Cathode Material Determines Product Selectivity for Electrochemical C-H Functionalization of Biaryl Ketoximes.

The synthesis of polycyclic N-heteroaromatic compounds and their corresponding N-oxides has been developed through electrochemical C-H functionalization of biaryl ketoximes. The oxime substrates undergo dehydrogenative cyclization when a Pt cathode is used, resulting in unprecedented access to a wide range of N-heteroaromatic N-oxides. The products of the electrosynthesis are switched to the deoxygenated N-heteroaromatics by employing a Pb cathode through sequential anode-promoted dehydrogenative cyclization and cathodic cleavage of the N-O bond in the initially formed N-oxide.

Reagent-Free C-H/N-H Cross-Coupling: Regioselective Synthesis of N-Heteroaromatics from Biaryl Aldehydes and NH3.

An unprecedented synthesis of N-heteroaromatics from biaryl aldehydes and NH3 through reagent-free C-H/N-H cross-coupling has been developed. The electrosynthesis uses NH3 as an inexpensive and atom-economic nitrogen donor, requires no oxidizing agents, and allows efficient and regioselective access to a wide range of phenanthridines and structurally related polycyclic N-heteroaromatic products.

Amidinyl Radical Formation through Anodic N-H Bond Cleavage and Its Application in Aromatic C-H Bond Functionalization.

We report herein an atom-economical and sustainable approach to access amidinyl radical intermediates through the anodic cleavage of N-H bonds. The resulting nitrogen-centered radicals undergo cyclizations with (hetero)arenes, followed by rearomatization, to afford functionalized tetracyclic benzimidazoles in a highly straightforward and efficient manner. This metal- and reagent-free C-H/N-H cross-coupling reaction exhibits a broad substrate scope and proceeds with high chemoselectivity.

Electrochemical C-H/N-H Functionalization for the Synthesis of Highly Functionalized (Aza)indoles.

Indoles and azaindoles are among the most important heterocycles because of their prevalence in nature and their broad utility in pharmaceutical industry. Reported herein is an unprecedented noble-metal- and oxidant-free electrochemical method for the coupling of (hetero)arylamines with tethered alkynes to synthesize highly functionalized indoles, as well as the more challenging azaindoles.

Electrochemical Synthesis of Benzimidazoles via Dehydrogenative Cyclization of Amidines.

The development of efficient and sustainable methodologies for the synthesis of N-heterocycles is a constant focus of organic synthesis. Herein an electrochemical method is reported for the synthesis of benzimidazoles through dehydrogenative cyclization of easily available N-aryl amidines. The reactions were conducted under simple constant current conditions in an undivided cell without need for catalysts, chemical oxidants, or additives, and produced H2 as the only theoretical byproduct.

Site-selective electrooxidation of methylarenes to aromatic acetals.

Aldehyde is one of most synthetically versatile functional groups and can participate in numerous chemical transformations. While a variety of simple aromatic aldehydes are commercially available, those with a more complex substitution pattern are often difficult to obtain. Benzylic oxygenation of methylarenes is a highly attractive method for aldehyde synthesis as the starting materials are easy to obtain and handle. However, regioselective oxidation of functionalized methylarenes, especially those that contain heterocyclic moieties, to aromatic aldehydes remains a significant challenge. Here we show an efficient electrochemical method that achieves site-selective electrooxidation of methyl benzoheterocycles to aromatic acetals without using chemical oxidants or transition-metal catalysts. The acetals can be converted to the corresponding aldehydes through hydrolysis in one-pot or in a separate step. The synthetic utility of our method is highlighted by its application to the efficient preparation of the antihypertensive drug telmisartan.