Dicarbofunctionalization of unactivated alkenes via organo-photoredox catalysis in water: access to cyanoalkylated fused quinazolinones.

A visible light-induced C-C bond cleavage/addition/cyclization cascade of oxime esters and unactivated alkenes has been developed using water as the solvent. This green protocol offers an easy access to medicinally valuable cyanoalkylated quinazolinones. Mild reaction conditions, functional group tolerance and late-stage functionalization of complex molecules are the important features of this transformation.

Ferrocene catalyzed carbohydroxylation of alkenes using H2O and cycloketone oxime esters.

A cyanoalkyl-hydroxylation reaction of aryl alkenes has been successfully devised, employing ferrocene as a catalyst for the addition of a cycloketone oxime ester and H2O across the double bond of the alkene. This environmentally friendly approach employs a solvent mixture consisting of water and demonstrates redox neutrality, along with exceptional regio- and chemoselectivity, leading to the formation of diverse distal hydroxy-nitrile compounds. Moreover, this research presents noteworthy contributions in terms of late-stage functionalization of complex molecules and offers valuable insights into the mechanistic aspects of the reaction.

Organophotoredox-catalyzed cyanoalkylation of 1,4-quinones.

A visible-light-induced metal-free cyanoalkylation of 1,4-quinones under mild and redox-neutral conditions is described. This reaction proceeds at room temperature without the need of extra base or additive and is suitable for a variety of 1,4-quinones and differently substituted cyclobutanone oxime esters. Further transformation of cyano functionality to tetrazole and amine has also been demonstrated to showcase the advantage of this method to prepare drug-like molecules.

Divergent cyanoalkylation/cyanoalkylsulfonylation of enamides under organophotoredox catalytic conditions.

An organophotoredox-catalyzed divergent cyanoalkylation/cyanoalkylsulfonylation of enamides in a highly regio- and stereoselective manner has been reported. In this mild and efficient protocol, cyclobutanone oxime esters serve as a cyanoalkylating source and inexpensive K2S2O5 serves as an SO2 surrogate. Broad substrate scope, compatibility of various sensitive functional groups and further functional group transformation are the highlights of this method.

Visible-light-driven metal-free aerobic synthesis of highly diastereoselective phosphinoylpyrroloindoles.

A visible-light-driven metal-free phosphorus radical mediated construction of 2-phosphinoyl-3H-pyrrolo[1,2,a]indoles is described. This mild tandem phosphinoylation/cyclization protocol utilizes air as a green oxidant and proceeds in a short span of time at room temperature with high functional group tolerance, and excellent chemo- and diastereoselectivity.

Esterification by Redox Dehydration Using Diselenides as Catalytic Organooxidants.

Ortho-functionalized aryl diselenides are catalytic (5.0 mol %) oxidants for the construction of esters from carboxylic acids and alcohols in the presence of stoichiometric triethyl phosphite and dioxygen in air as the terminal redox reagents (redox dehydration conditions). The reaction proceeds through the intermediacy of the anhydride and requires the presence of 10% DMAP to drive the esterification.

"Pruning of biomolecules and natural products (PBNP)": an innovative paradigm in drug discovery.

The source or inspiration of many marketed drugs can be traced back to natural product research. However, the chemical structure of natural products covers a wide spectrum from very simple to complex. With more complex structures it is often desirable to simplify the molecule whilst retaining the desired biological activity. This approach seeks to identify the structural unit or pharmacophore responsible for the desired activity. Such pharmacophores have been the start point for a wide range of lead generation and optimisation programmes using techniques such as Biology Oriented Synthesis, Diversity Oriented Synthesis, Diverted Total Synthesis, and Fragment Based Drug Discovery. This review discusses the literature precedence of simplification strategies in four areas of natural product research: proteins, polysaccharides, nucleic acids, and compounds isolated from natural product extracts, and their impact on identifying therapeutic products.

Ferrocene catalyzed redox-neutral difunctionalization of alkenes using cycloketone oxime esters: access to distal imido-nitriles.

A novel ferrocene-catalyzed cyanoalkyl-imidation of aryl alkenes utilizing cycloketone oxime esters in MeCN under redox-neutral conditions is described. In this three-component reaction, the cycloketone oxime ester is employed as a bifunctional reagent, enabling easy access to diverse distal imido-nitriles with 100% atomic utilization. Preliminary mechanistic studies suggest that the ferrocene-ferrocenium catalytic cycle is responsible for the deconstructive functionalization of cycloketone oxime esters.

Intermolecular trifluoromethyl-alkenylation of alkenes enabled by metal-free photoredox catalysis.

A three-component and redox-neutral trifluoromethylative alkenylation of unactivated alkenes with ß-nitrostyrenes has been developed under visible-light. This metal-free protocol utilizes the easy to handle Langlois reagent (CF3SO2Na) as the CF3 source and is suitable for various unactivated alkenes and ß-nitrostyrenes, affording a series of trifluoromethylated aromatic alkenes under mild conditions in good to excellent yields.

Aerobic, Diselenide-Catalyzed Redox Dehydration: Amides and Peptides.

At 2.5 mol % loadings using reaction temperatures between 30-55 °C, ortho-functionalized diaryl diselenides are highly effective organocatalytic oxidants for aerobic redox dehydrative amidic and peptidic bond formation using triethyl phosphite as a simple terminal reductant. This simple-to-perform organocatalytic reaction relies on the ability of selenols to react directly with dioxygen in air without recourse to metal catalysts. It represents an important step toward the development of a general, economical, and benign catalytic redox dehydration protocol.