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Inspired by the ubiquitous prevalence of 3‐hydroxyoxindoles in natural products and pharmaceuticals, we herein disclose a direct and practical transition‐metal‐free asymmetric hydroxylation using commercially available Davis enantiopure oxaziridines as efficient oxidants, expeditiously affording an array of medicinally active 3‐functionalized 3‐hydroxy‐2‐oxindoles bearing quaternary stereocenters. The protocol features cheap reactants, ease of operation, scalability, and good functional‐group tolerance and efficient formal synthesis of natural products. [ABSTRACT FROM AUTHOR]

A new route to the macrolactone antibiotic berkeleylactone A was developed. As a key step, a ring‐closing alkyne metathesis (RCAM) of an ester substrate featuring 1‐propynyl termini was used. The carboxylic part of the substrate was easily assembled using alkyne chemistry, like carboxylation of a diyne followed by isomerization of the ynoate section to a dienoate and dihydroxylation of the 4,5‐double bond. The synthesis of the alcohol part of the ester started with opening of (R)‐propylene oxide with an acetylide and was followed by two triple bond migrations. After successful RCAM which formed the C8−C9 bond, the triple bond was selectively hydrogenated to the corresponding alkene before the 4,5‐diol was oxidized to the 5‐hydroxy‐4‐oxo derivative. At this stage, the thioether was formed and the 8,9‐double bond reduced. We also prepared the 8,9‐didehydro analog of berkeleylactone A. However, it turned out that its antimicrobial activity was slightly reduced. [ABSTRACT FROM AUTHOR]

We have developed a straightforward methodology for converting arylboronic acids into phenols using NaOH‐mediated air oxidation. This reaction offers several advantages, including simple operation, excellent tolerance towards various functional groups, and scalability. The transmetalation of the resulting borate ester with NaOH occurs readily, enabling convenient derivatization of the borate ester into aryl ethers and esters using alkyl and acyl halides. [ABSTRACT FROM AUTHOR]

Peroxodicarbonate represents a green and largely underexplored oxidizer generated electrochemically from aqueous carbonate solutions. Through state‐of‐the‐art electrolyzer technology, highly concentrated solutions have now become accessible. These were successfully employed as green oxidizer in deborolative hydroxylations. A plethora of phenols and alcohols have thus been synthesized in up to 99 % from organoboron compounds using only green and non‐toxic solvents. This transformation was successfully scaled‐up to multi‐gram batch sizes. [ABSTRACT FROM AUTHOR]

Concomitant selective dehydroxylation during the transformation of flavones into pyrazoles with hydrazine is determined by the A‐ring substitution pattern and propensity to keto enol tautomerization. The obtained pyrazoles show varied tyrosinase inhibition properties, including one nanomolar inhibitor. [ABSTRACT FROM AUTHOR]

Electrochemical hydroxylation of arenes by trifluoroacetic acid provides a straightforward access to aryl oxygen compounds under the mild and environmental benign reaction conditions. Harmful and pollutant stoichiometric amounts of oxidation reagents and the use of metal‐catalysts can be avoided. Herein, we present a novel method for the synthesis of hydroxylated products from electron‐rich arenes that was achieved by the implementation of a continuous‐flow setup. The continuous nature of the process allowed to fine‐tune the reactions conditions in order to prevent the decomposition of the sensitive products expanding the reaction scope beyond electron‐poor and neutral arenes that were previously reported in the batch processes. Thus, synthetically valuable hydroxylated arenes were obtained in good yields with the residence time just over a minute. In order to demonstrate the reliability and the efficiency of the electrochemical flow setup, a scale up experiment was also performed. [ABSTRACT FROM AUTHOR]

Scaling up biocatalytic reactions involving cytochrome P450 monooxygenases (P450s) is challenging due to their instability, low substrate loading, co‐factor, and oxygen requirements as well as the dependency on a reductase partner, which limits their integration into synthetic chemistry. Recently, a biocatalytic study investigated frequently used bacterial P450s to produce bioactive stilbenoids, extending the repertoire of sustainable synthetic strategies with remarkable success. This article explores the complementary application of less common eukaryotic P450s as a viable alternative for generating the same compounds when employed as a Pichia pastoris‐based whole‐cell biocatalyst. In a direct comparison to their bacterial equivalents, the recently discovered P450s CYP5035S7 and CYP5035S9 from the white‐rot fungus Polyporus arcularius are shown to be competitively efficient at synthesising stilbenoids at preparative‐scale. [ABSTRACT FROM AUTHOR]

A convenient one‐pot synthesis of quinoxaline‐2,3‐dione has been achieved by C−H hydroxylation of quinoxalin‐2(1H)‐one using TBN (tert‐butyl nitrite) as a promoter of the reaction in DMSO. First radical‐mediated nitration using TBN at C‐3 of quinoxalin‐2(1H)‐one and followed by hydroxylation with water via ipso‐substitution led to the quinoxaline‐2,3‐dione. [ABSTRACT FROM AUTHOR]

Members of the GE81112 family are interesting candidates for the development of antibiotics. The configuration of the OH group on the pipecolic acid moiety plays a pivotal role in antibiotic activity. To investigate the stereoselectivity of the corresponding hydroxylase GetF, involved in the biosynthetic pathway, we synthesized the two deuterium‐labeled pipecolic acid diastereomers in a highly stereoselective fashion via chelate‐enolate Claisen rearrangement. The stereochemical outcome of the enzymatic hydroxylation step could easily be determined by analysis of mass differences between the products. [ABSTRACT FROM AUTHOR]

The first total synthesis of racemic chebulic acid is reported, which is the aglycon of several antioxidant ingredients of the fruit of the Terminalia chebula tree. The route started with the straightforward preparation of an indanone‐based β‐oxoester from a benzaldehyde derivative (84 % over the first five steps). The side chain of the target compound was then introduced by conjugated addition of a cuprate reagent derived from dimethyl succinate, which was followed by the first key step of the synthesis: a cerium‐catalyzed α‐hydroxylation of an β‐oxoester. The second key step was the cyanide‐catalyzed ring transformation of the cyclic α‐hydroxy‐β‐oxoester to a δ‐lactone. Finally, chebulic acid was obtained after six‐fold demethylation of three methyl ester moieties and three phenolic ether functions. The overall synthetic route consists of nine consecutive steps and was accomplished in 15 % overall yield. [ABSTRACT FROM AUTHOR]

An unprecedented external oxidant‐free electrochemical protocol for 1, 3‐oxohydroxylation of donor‐acceptor cyclopropane is disclosed. The strategy encompasses the activation of the labile π‐electron cloud of the aryl ring to cleave the strained Csp3−Csp3 bond of cyclopropane to afford the β‐hydroxy ketones via insertion of molecular oxygen. More significantly, based on the detailed mechanistic investigations and cyclic voltammetry experiments, a plausible mechanism is proposed. [ABSTRACT FROM AUTHOR]

In this article, we describe simple one‐pot syntheses of 2H‐1,3‐benzoxazines from ketones utilizing an imino‐pyridine directing group (R1R2‐C=N−CH2‐Pyr), which promotes a Cu‐directed sp2 hydroxylation using H2O2 as oxidant and followed by an oxidative intramolecular C−O bond formation upon addition of NEt3. This synthetic protocol is utilized in the gram scale synthesis of the 2H‐1,3‐benzoxazine derived from benzophenone. Mechanistic studies reveal that the cyclization occurs via deprotonation of the benzylic position of the directing group to produce a 2‐azallyl anion intermediate, which is oxidized to the corresponding 2‐azaallyl radical before the C−O bond formation event. Understanding of the cyclization mechanism also allowed us to develop reaction conditions that utilize catalytic amounts of Cu. [ABSTRACT FROM AUTHOR]

Visible‐light‐driven organic reactions are environmentally friendly green chemical transformations among which photosynthetic oxidative hydroxylation of arylboronic acids to phenols has attracted increasing research interest during the very recent years. Given the efficiency and reusability of heterogeneous catalysts, COF‐JLU25, an electron‐rich COF‐based photocatalyst constructed by integrating electron‐donating blocks 1,3,6,8‐tetrakis(4‐aminophenyl)pyrene (PyTA) and 4‐[4‐(4‐formylmethyl)‐2,5‐dimethoxyphenyl] benzaldehyde (TpDA), was selected as a photocatalyst for the oxidative hydroxylation of arylboronic acids. In our studies, COF‐JLU25 demonstrated excellent photocatalytic activity with high efficiency, robust reusability, and low catalyst loading, showcasing an application potential of previously underexplored COF‐based photocatalyst composed solely of electron‐rich units. [ABSTRACT FROM AUTHOR]

A V2O5@TiO2 catalyzed green and efficient protocol for the hydroxylation of boronic acid into phenol has been developed utilizing environmentally benign oxidant hydrogen peroxide. A wide range of electron‐donating and the electron‐withdrawing group‐containing (hetero)aryl boronic acids were transformed into their corresponding phenol. The methodology was also applied successfully to transform various natural and bioactive molecules like tocopherol, amino acids, cinchonidine, vasicinone, menthol, and pharmaceuticals such as ciprofloxacin, ibuprofen, and paracetamol. The other feature of the methodology includes gram‐scale synthetic applicability, recyclability, and short reaction time. [ABSTRACT FROM AUTHOR]

Keywords: Aromatic substitution; Electrolysis; Flow chemistry; Hydroxylation EN Aromatic substitution Electrolysis Flow chemistry Hydroxylation 1 1 1 05/27/22 20220525 NES 220525 B The Front Cover b demonstrates that electrochemistry in continuous flow is so convenient and reliable that even kids could do it. Electrochemical hydroxylation of sensitive electron-rich arenes was achieved by the implementation of a flow setup. Aromatic substitution, Electrolysis, Flow chemistry, Hydroxylation. [Extracted from the article]

Antioxidant, Chebulic acid, Hydroxylation, Lactones, Natural product, Ring-transformation Keywords: Antioxidant; Chebulic acid; Hydroxylation; Lactones; Natural product; Ring-transformation EN Antioxidant Chebulic acid Hydroxylation Lactones Natural product Ring-transformation 1 1 1 02/21/22 20220211 NES 220211 B The Front Cover b shows a branch and some fruits of Terminalia chebula, a tropical tree. Chebulic acid (the formula in the magnifying glass) is the aglycon of several antioxidant ingredients of the fruit. [Extracted from the article]