Marnix van der Kolk

A new cross-coupling of trifluoromethyl arenes has been realized via multiphoton photoredox catalysis. A series of valuable α,α-difluorobenzylic compounds can be generated while the the addition of D₂O leads to highly deuterated derivatives.

Abstract

A new cross-coupling of trifluoromethyl arenes has been realized via multiphoton photoredox catalysis. Trifluoromethyl arenes were demonstrated to undergo selective mono-defluorinative alkylation under mild reaction conditions providing access to a series of valuable α,α-difluorobenzylic compounds. The reaction shows broad substrate scope and general functional group tolerance. In addition to the electron-deficient trifluoromethyl arenes that are easily reduced to the corresponding radical anion, more challenging electron-rich substrates were also successfully applied. Steady-State Stern-Volmer quenching studies indicated that the trifluoromethyl arenes were reduced by the multiphoton excited Ir-based photocatalyst.

Nature, Published online: 29 March 2024; doi:10.1038/d41586-024-00902-2

The evidence is equivocal on whether screen time is to blame for rising levels of teen depression and anxiety — and rising hysteria could distract us from tackling the real causes.

Nature Chemistry, Published online: 28 March 2024; doi:10.1038/s41557-024-01470-8

Lack of standardization, transparency and interaction creates information gaps in scientific publications. Through strategies such as voluntary information management, standardization of reaction set-ups, and smart screening approaches, this Perspective gives guidelines on how to improve data management in publications reporting chemical reactions, focusing on reproducibility, standardization and evaluation of synthetic transformations.

Photoinduced Generation of Aryl Radical and Applications: Generation of aryl radicals under photosensitized, photoinitiated, and direct or indirect photoredox-catalyzed conditions are reviewed. The utilization of aryl radicals in various reactions is demonstrated with examples.

Abstract

Photoinduced aryl radical generation is a powerful strategy in organic synthesis that facilitates the formation of diverse carbon-carbon and carbon-heteroatom bonds. The synthetic applications of photoinduced aryl radical formation in the synthesis of complex organic compounds, including natural products, physiologically significant molecules, and functional materials, have received immense attention. An overview of current developments in photoinduced aryl radical production methods and their uses in organic synthesis is given in this article. A generalized idea of how to choose the reagents and approach for the generation of aryl radicals is described, along with photoinduced techniques and associated mechanistic insights. Overall, this article offers a critical assessment of the mechanistic results as well as the selection of reaction parameters for specific reagents in the context of radical cascades, cross-coupling reactions, aryl radical functionalization, and selective C−H functionalization of aryl substrates.

This study describes an accessible approach to various solvent-free transition metal-catalyzed C–H and C–X functionalizations. Conditions from eight different Rh-, Ru-, Ir- and Pd-based mechanochemical reactions are adapted to proceed with generally high efficiency by substituting automated ball milling with pestle and mortar grinding and subsequent heating. This is a low-cost, operationally simple method that requires no specialized equipment and offers similar sustainability benefits. The reaction scope encompasses 10 heterocycle types, many pendant functional groups and is demonstrated on the late-stage modification of a variety of bioactive compounds.

Nature Synthesis, Published online: 28 March 2024; doi:10.1038/s44160-024-00507-7

Methods for enzymatic C–F bond formation are rare. Now an enzymatic method for enantioselective C(sp3)–F bond formation is reported, through reprogramming non-haem iron enzyme (S)-2-hydroxypropylphosphonate epoxidase. Mechanistic studies reveal that the process proceeds through an iron-mediated radical fluorine transfer process.

Alcohols are abundant and attractive feedstock molecules for organic synthesis. Many methods for their functionalization require them to first be converted into a more activated derivative, while recent years have seen a vast increase in the number of complexity-building transformations that directly harness unprotected alcohols. This review discusses how transition metal catalysis can be used towards this goal. These transformations are broadly classified into three categories. Etherifications, characterized by derivatization of the O–H bond, represent classical reactivity that has been modernized to include mild reactions conditions, diverse reaction partners, and high selectivities. Deoxygenative functionalizations, representing derivatization of the C–O bond, enable the alcohol to act as a leaving group towards the formation of new C–C bonds. Lastly, chain functionalization reactions are described, wherein the alcohol group acts as a mediator in formal C–H functionalization reactions of the alkyl backbone. Each of these three classes of transformation will be discussed in context of intermolecular alkylation, arylation, and related reactions, illustrating how catalysis can enable alcohols to be directly harnessed for organic synthesis.