1,4-Benzoxazin-3-ones are important structural motifs in naturalp roducts and bioactive compounds. Usually,t he synthesis of benzoxazinones requires transitionmetal catalystsa nd pre-functionalized substrates such as aryl halides. However,t he anodicC ÀHa mination of phenoxy acetates offers av ery efficient and sustainable access to these heterocycles. The presented electrochemical protocol can be appliedt oabroad scope of alkylated substrates. Even tert-butyl moieties or halogens ubstituents are compatible with this versatile method.The 1,4-benzoxazin-3-ones caffold has been recognized as an important heterocyclic motif in natural products as well as in pharmaceutically active compounds. [1] Naturally occurring benzoxazin-3-ones, like 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA, 1)a nd 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA, 2)w ere found in gramineousp lants like maize, wheat, rye, and rice ( Figure 1). [2, 3] Biosynthesis of DIMBOA (2)i s accomplished by the hydroxylation of indole derivatives using P450 monooxogenase. Intermediates of this reactionp athway can also be found in tryptophan biosynthesis. [4] Alternatively, benzoxazinones 3 and 4 are interesting compounds for pharmaceutical applications.T he former is an inhibitor of bacterial histidinep rotein kinase, [5] whereas the latter is ap otential agent for the treatment of anxiety and depression symptoms (Figure 1). [6,7] Common synthetic strategies to construct benzoxazin-3-ones employ ortho-substituted nitrophenols or halophenols as startingm aterials. [2, 8] Recently,E lKaïme tal. reported at hreecomponent reaction to access the benzoxazinone scaffold throughaPasserini-Smilesr earrangement, followed by hydrogenationand in situ cyclization. [9] Moreover,Liu and co-workers developed ac opper(I)-catalyzed one-pot synthesis of benzoxazinones. [6] In this approach, ortho-halophenols react with achloroacetamides in the presence of am etal promoter.H owever,adisadvantage of such approaches is the need for transition-metal catalysts as well as pre-functionalized substrates, for example, aryl halogenides or nitroaromatic compounds.I np articular,n itroaromatic starting materials are sometimes difficult to obtain selectively because nitration usually leads to regioisomericmixtures. [10] Purification of such mixturesoften is atedious process. Recently,Y oshida and co-workers reported in as eries of accountsapowerful and selectivee lectrochemical CÀNb ond-formation reactions, [11][12][13] including an ovel method for the synthesis of benzoxazoles 7 (Scheme 1). [14] The phenolic substrates for the electrochemical synthesis of oxazoles 7 were initially modified with ap yrimidine moiety. This promotesa ni ntramolecular electrochemical CÀNc oupling reaction.T he anodic amination proceeds via positivelyc harged Zinckei ntermediates 6 and 9,w hich prevent furthera nodic degradation, thus increasing the selectivity.T he corresponding amino moieties can be liberated in al ater step at non-electrolytic conditions.

Dedicated to Laura Ošeka, who was born during the preparation of the manuscript for this article and helped to write it.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.

The efficientp roduction of many medicinally or synthetically importants tarting materials suffers from wasteful or toxic precursors for the synthesis. In particular,the aromatic non-protected primary amine functionr epresents a versatile synthetic precursor,b ut its synthesis typicallyr equires toxic oxidizing agentsa nd transition metal catalysts. The twofold electrochemical aminationo fa ctivated benzene derivatives via Zincke intermediates provides an alternative sustainable strategy for the formation of new CÀNb onds of high synthetic value. As ap roof of concept, we use our approacht og enerate ab enzoxazinone scaffold that gained attentiona sastarting structurea gainst castrate-resistant prostate cancer.F urther improvement of the structure led to significantly increased cancer cell line toxicity.T hus, exploiting environmentally benign electrooxidation, we presentanew versatile and powerful method basedo nd irect CÀHa ctivation that is applicablef or example the production of medicinally relevant compounds.

The Front Cover 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. Our goal is to motivate organic chemists, who tend to be quite conservative, to apply the modern techniques in their everyday research and explore new reaction pathways. Cover artwork by Alina Andreyenka. More information can be found in the Research Article by M. Ošeka et al.

In recent years, the “Escape-from-Flatland” trend has prompted the synthetic community to develop a set of cross-coupling strategies to introduce sp3-carbon-based fragments in organic compounds. This study presents a novel nickel-catalyzed electrochemical methodology for reductive cross-electrophile coupling. The method enables C(sp2)–C(sp3) linkages using inexpensive amine-derived radical precursors and aryl iodides. The use of electrochemistry as a power source reduces waste and avoids chemical reductants, making this approach a more sustainable alternative to traditional cross-coupling methods.