Aromatic compounds serve as key feedstocks in the chemical industry, typically undergoing functionalization or full reduction. However, partial reduction via dearomative sequences remains underexplored despite its potential to rapidly generate complex three-dimensional scaffolds and the existing dearomative strategies often require metal-mediated multistep processes or suffer from limited applicability. Herein, a photocatalytic radical cascade approach enabling dearomative difunctionalization through selective spirocyclization/imination of nonactivated arenes is reported. The method employs bifunctional oxime esters and carbonates to introduce multiple functional groups in a single step, forming spirocyclic motifs and iminyl functionalities via N–O bond cleavage, hydrogen-atom transfer, radical addition, spirocyclization, and radical-radical cross-coupling. The reaction constructs up to four bonds (C−O, C−C, C−N) from simple starting materials. Its broad applicability is demonstrated on various substrates, including pharmaceuticals, and it is compatible with scale-up under flow conditions, offering a streamlined approach to synthesizing highly decorated three-dimensional frameworks.

Herein, a straightforward synthetic approach for the construction of phenanthridin-6(5H)-one skeletons is disclosed. The developed protocol relies on palladium catalysis, providing controlled access to a range of functionalized phenanthridin-6(5H)-ones in 59-88% yields. Furthermore, plausible reaction pathways are proposed based on mechanistic experiments.

Alcohols and their derivatives are ubiquitous and versatile motifs in organic synthesis. Deoxygenative transformations of these compounds are often challenging due to the thermodynamic penalty associated with the cleavage of the C−O bond. However, electrochemically driven redox events have been shown to facilitate the C−O bond cleavage in alcohols and their derivatives either through direct electron transfer or through the use of electron transfer mediators and electroactive catalysts. Herein, a comprehensive overview of preparative electrochemically mediated protocols for C−O bond activation and functionalization is detailed, including direct and indirect electrosynthetic methods, as well as photoelectrochemical strategies.

Establishing chemodivergent synthetic strategies remains a daunting task in the realm of free-radical reaction manifolds. In the December issue of Chem, Glorius and co-workers resolve this challenge for selective difunctionalization of aliphatic alkenes. In the disclosed light-promoted radical relay process, switchable trifluoromethylation/alkylation or trifluoromethylation/sulfonylation of alkenes is achieved.

The Wittig reaction is a valuable and powerful tool in organic synthesis, providing a convenient route from aldehydes and ketones to alkenes. Herein, a novel copper-assisted Wittig-type olefination of aldehydes with p-toluenesulfonylmethyl isocyanide (TosMIC) is disclosed, providing a direct and operationally simple approach to (E)-vinyl sulfones under mild conditions, compatible with a multitude of common functional groups. Experimental and computational investigations imply that the reaction proceeds through an intriguing electronically-controlled (3 + 2)/retro-(3 + 2) cycloaddition pathway.

Photoredox catalysis has recently emerged as a powerful synthetic platform for accessing complex chemical structures through non-traditional bond disconnection strategies that proceed through free-radical intermediates. Such synthetic strategies have been used for a range of organic transformations; however, in carbohydrate chemistry they have primarily been applied to the generation of oxocarbenium ion intermediates in the ubiquitous glycosylation reaction. In this Review, we present more intricate light-induced synthetic strategies to modify native carbohydrates through homolytic C–H and C–C bond cleavage. These strategies allow access to glycans and glycoconjugates with profoundly altered carbohydrate skeletons, which are challenging to obtain through conventional synthetic means. Carbohydrate derivatives with such structural motifs represent a broad class of natural products integral to numerous biochemical processes and can be found in active pharmaceutical substances. Here we present progress made in C–H and C–C bond activation of carbohydrates through photoredox catalysis, focusing on the operational mechanisms and the scope of the described methodologies. [Figure not available: see fulltext.]. 

Photo-mediated radical dearomatization involving 5-exo-trig cyclizations has proven to be an important route to accessing spirocyclic compounds, whereas 6-exo-trig spirocyclization has been much less explored. In this work, a dearomative annulation cascade is realized through photoredox-mediated C-O bond activation of aromatic carboxylic acids to produce two kinds of spirocyclic frameworks. Mechanistically, the acyl radical is formed through oxidation of triphenylphosphine and subsequent C-O bond cleavage, followed by a 6-exo-trig cyclization/SET/protonation sequence to generate the spiro-chromanone products in an intramolecular manner. Furthermore, the protocol was extended to more challenging intermolecular tandem sequences consisting of C-O bond cleavage, radical addition to an alkene substrate, and 5-exo-trig cyclization to yield complex spirocyclic lactams. Photo-mediated radical dearomatization involving 5-exo-trig cyclizations has proven to be an important route to accessing spirocyclic compounds, whereas 6-exo-trig spirocyclization has been much less explored. Here, a dearomative annulation cascade is realized through a photoredox-mediated C-O bond activation of aromatic carboxylic acids to produce two kinds of spirocyclic frameworks, whereby the spirocyclizations are triggered by acyl radical formation from benzoic acids leading to spiro-chromanones via a direct intramolecular 6-exo-trig cyclization or spirocyclic lactams via an intermolecular addition/5-exo-trig cyclization cascade.

Recently, development of general synthetic routes to unnatural α-amino acids has gained significant momentum, driven by the high demand for such building blocks in fundamental research within molecular and structural biology, as well as for development of new pharmaceuticals. Herein, we highlight the recent progress in employing photoredox-mediated synthetic methods for accessing unnatural α-amino acids with a focus on various decarboxylative radical-based strategies. 

Electrochemical water splitting constitutes one of the most promising strategies for converting water into hydrogen-based fuels, and this technology is predicted to play a key role in the transition towards a carbon-neutral energy economy. To enable the design of cost-effective electrolysis cells based on this technology, new and more efficient anodes with augmented water splitting activity and stability will be required. Herein, we report an active molecular Ru-based catalyst for electrochemically-driven water oxidation (overpotential of ∼395 mV at pH 7 phosphate buffer) and two simple methods for preparing anodes by attaching this catalyst onto glassy carbon through multi-walled carbon nanotubes to improve stability as well as reactivity. The anodes modified with the molecular catalyst were characterized by a broad toolbox of microscopy and spectroscopy techniques, and interestingly no RuO2 formation was detected during electrocatalysis over 4 h. These results demonstrate that the herein presented strategy can be used to prepare anodes that rival the performance of state-of-the-art metal oxide anodes. 

The first total synthesis of vanilloloside, calleryanin, and a series of naturally occurring omega-esters of vanilloloside was realized through direct glycosylation of vanillin-based aglycones or late-stage derivatization of vanilloloside. All aglycones and their fragments were synthesized from vanillin as the sole aromatic precursor. Subsequently, these intermediates were used to construct various vanillin-derived glucoside omega-esters using a mild acidic deacetylation as the key synthetic step, providing the final products in the total yields of 10-50% and general purity of >95%. Additionally, the first operationally simple and sustainable synthesis of litseafoloside B was realized on large scale, avoiding the use of toxic solvents and reagents, providing an attractive alternative to isolation of this and other similar compounds from plant sources.