On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• molecules of substrate together. In addition, the high enantiopurity was ascribed to a chiral environment that presents three elements of asymmetry. Other examples of vanadium-mediated oxidative homocouplings of phenolic substrates include regioselective and asymmetric homocoupling of phenols and 2

• -hydroxycarbazoles [103][104]. Notably, Kozlowsky and co-workers were the first who reported a method for the vanadium-based asymmetric coupling of phenols and 2-hydroxycarbazoles [105] that allowed the synthesis of a wide range of chiral biphenols and bicarbazoles. The use of a vanadium complex with less electron

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• product was also compatible with the reaction conditions. Alkylated phenols 61 were obtained after protonation/isomerization of the generated enolate intermediate (Scheme 24B). In 2018, the same authors continued to explore the synthetic opportunities offered by the enolate generated in MHAT radical

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• highly oxidizing conditions, dehydrogenation of the resulting cyclohexadienol would give 11.The electron-rich 4-hydroxy[2.2]metaparacyclophane (9) participates in ortho selective nitration to give 5. Nitric acid has previously been used to oxidize phenols to cyclohexadienones [69][70], and a plausible

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• scaffold [4]. The Guareschi–Lustgarten reaction is at the basis of the pharmacopoeia assay of thymol (3) [5], and investigation on the color associated with the reaction eventually led to the discovery of the Reimer–Tiemann formylation of phenols [6]. Conversely, the third Guareschi eponymic reaction, the

• Guareschi the discovery of the color reaction of phenols with alkali and chloroform, a reaction he reported in front of the prestigious audience of the Deutsche Chemische Gesellschaft (German Chemical Society) at the annual meeting in 1872 [20][21]. The relevance of novel color reactions for the audience

• is therefore natural that Schiff considered the discovery of Guareschi worth presenting at such an important meeting. What is surprising is that Schiff did not claim any role in the discovery by Guareschi that when phenols are heated with chloroform and solid KOH, a color reaction develops, with a

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• initial studies showed the formation of significant amounts of protodeborylation products, small amounts of boronic acid homocoupling products, and the corresponding phenols as boronic acid oxidation products. To optimise the yields, the amount of the boronic acid was increased to 3 equiv, which was added

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• phenols [14], our results suggest that sequential phenoxide ion attacks on intermediate carbenes (Scheme 7) was indeed the mechanism responsible for the production of compounds 4, 11 and 12. The bis(aryloxy)fluoromethane moiety had proven robust with respect to radical, brominative conditions as well as

• applications. Conclusion We have synthesized the trace impurity 1, using a novel and operationally simple procedure for the construction of acyclic bis(aryloxy)fluoromethanes and extended the transformation to two representative electron-poor phenols. We were able to provide preliminary answers to the

• previously unaddressed question of how heterodihalocarbenes would react with phenols capable of undergoing Reimer–Tiemann formylation. Retrosynthesis of compound 1. Reported bis(aryloxy)fluoromethane syntheses. Reagents and conditions: (a) Cl2FCH, NaOH, 1,4-dioxane/water, 70 °C, 20 min, 90% (+3% (C6F5)3CH

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• effects of phenol, a variety of phenols, including electron-donor and electron-withdrawing groups, were been converted into corresponding 2-iodovinyl phenyl ethers in moderate to excellent yield with high regio- and stereoselectivities. According to the analysis of the mechanism (Scheme 60), a molecule of

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• . Finally, we turned out attention to transition metal-catalyzed formation of phenols from aryl halides [5]. After another round of screening, we successfully applied palladium-catalyzed conditions discovered by the Buchwald group [6], using KOH as the nucleophile and X-Phos as the ligand, to afford 7 in 83

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• demonstrated the synthesis of aryl fluoroalkyl ethers as shown in Scheme 1 [32][33][34]. For example, the reactions of phenols with “gem-difluorocarbene precursors (route (a))” or “bromodifluoroalkyl compounds (route (b))” have been typically used to obtain a variety of aryl gem-difluoromethyl ethers

• corresponding products in comparably high yields (Table 2, entries 7–9). Also, 1-naphthol (1k) was compatible with the reaction conditions giving the product 2k in a good yield of 85% (Table 2, entry 10). As shown in entries 11–13 (Table 2), o-iodophenol (1l) and the alkenyl-substituted phenols 1m and 1n, all

• carbon atom is a reasonable process to forward the reaction with the generation of carbanion 6. Finally, the protonation of 6 by 1 or other acidic compounds, such as water molecules present in the reaction medium, would provide 2. Conclusion We exploited the reaction of various phenols with halothane to

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• Truce–Smiles rearrangement in aryl sulfonamides and aryl phenylsulfonates [44][45][46] or the [3,3]-sigmatropic rearrangement of sulfonium salts arising from the reaction of aryl sulfoxides and phenols [47]. To overcome this problem, the use of a metal catalyst (mainly Ni) was mandatory as reported for

• metal-free eco-sustainable conditions we reinvestigated the photochemistry of di- and triaryl phosphates III and IV (Scheme 1e), compounds that can be easily achieved from the corresponding phenols [62][63]. Results and Discussion At the onset of our investigation, we tested a triaryl phosphate such as

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• [48]. Although, for the nucleophilic substitution reaction with phenol derivatives, they have tried several reaction conditions including the amount of acid as well as phenols. After several experimentations, they found that 30 equivalents of phenol and 1 equivalent of TfOH at 0 °C provided the best

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• merging C–H activation with photoredox catalysis to allow in situ reoxidation of the metal catalyst. In 2015, a procedure combining ruthenium C–H activation of phenols derivatives bearing a pyridine moiety as DG and photoredox catalysis was disclosed (Figure 9) [75]. This ortho-olefination was performed

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• the relatively stable di-tert-butyliminoxyl radical was studied as a reagent in oxidative transformations of various substrates, such as unsaturated hydrocarbons, phenols, amines, and organometallic compounds. A breakthrough in the synthetic use of iminoxyl radicals has occurred in recent years when

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• could be circumvented through ligand modification. Phenol oxidation is ubiquitous in biological systems as demonstrated by the involvement of the copper enzymes tyrosinases (type III) in the melanogenesis process. The regioselectivity and reactivity of the oxidation of phenols are strongly dependent on

• phenols, ketones and 1,3-dienes (Scheme 6) [27]. C–C bond formation Complexes of radical and redox-active ligands with transition metals are known to be able to promote radical reactions through single-electron transfer (SET) processes [28]. Expanding on the research area pioneered by Wieghardt and

• use of copper(I) complexes bearing redox-active guanidine ligands 12 for catalytic aerobic homo- and cross-coupling of phenols with dioxygen as oxidation source (Scheme 9). This strategy allowed access to nonsymmetrical biphenols and the best results were obtained with dinuclear complex 13

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• reaction was excellent as bromides, phenols, thioethers, esters, boronic esters, and heterocycles, including pyridine and quinolines, were well tolerated. The authors carried out mechanistic studies and demonstrated the H-bonding ability of their catalyst by NMR studies. The following mechanism was

Synthesis and circularly polarized luminescence properties of BINOL-derived bisbenzofuro[2,3-b:3’,2’-e]pyridines (BBZFPys)

• Ryo Takishima,
• Yuji Nishii,
• Tomoaki Hinoue,
• Yoshitane Imai and
• Masahiro Miura

Beilstein J. Org. Chem. 2020, 16, 325–336, doi:10.3762/bjoc.16.32

• using cesium carbonate as base in DMF at 40 °C [42], giving both the enantiomers of 2 in optically pure forms. The remaining fluorine substituents were subsequently replaced by a series of phenols including unsubstituted phenol, p-tert-butylphenol, and m-tert-butylphenol to produce the corresponding

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• heteroaromatic species. More recently, the same group reported the synthesis of 2-trifluoromethylselenylated benzofused heterocycles (Scheme 7) [24]. This tandem process consisted in a first Pd-catalyzed cyclization of 2-(2,2-dibromovinyl)phenols/-thiophenols/-anilines, leading to the corresponding 2-brominated

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• -worker’s results [86], in 2015, Rueping and co-workers reported reoxidation reactions via visible photoredox catalysis [87]. In their study, they used photoredox catalyst 9 along with a Ru catalyst for ortho C–H functionalization of phenol derivatives, viz, ortho-(2-pyridyl)phenols (Pyr, Scheme 2

• catalysts was also reported, and this approach allowed for easy and fast transformations to take place. Herein, we cover all the reported strategies for aryl para C–H bond functionalizations by means of photoredox catalysis. Aryl C–H hydroxylation: synthesis of substituted phenols The synthesis of phenol

• formation of carbazoles from biaryl derivatives. Mechanism for the synthesis of phenol derivatives with photoredox catalyst 8. Possible mechanism for the generation of phenols with the aid of photoredox catalyst 5. Proposed mechanism for the synthesis of monobrominated compounds. Mechanism for the synthesis

Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses

• Anne-Marie Caminade,
• Artem Zibarov,
• Eduardo Cueto Diaz,
• Aurélien Hameau,
• Maxime Klausen,
• Kathleen Moineau-Chane Ching,
• Jean-Pierre Majoral,
• Jean-Baptiste Verlhac,
• Olivier Mongin and
• Mireille Blanchard-Desce

Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221

• -hydroxybenzaldehyde. TPA fluorophores on the surface of dendrimers The easiest way to modify the P(S)Cl2 terminal functions of the phosphorhydrazone dendrimers consists in using phenols [36], and all the TPA fluorophores on the surface of dendrimers were linked in this way. The very first example of phosphorhydrazone

• functionalized by two phenols was reacted with two equivalents of N3P3Cl6, to afford a core from which 10 branches emanate, instead of 6 as in the previous cases. The growing of the branches was carried out as outlined in Scheme 1, and diethylethylene diamine was grafted in the last step, to ensure the

• water-soluble dumbbell-like dendrimers retains a similar TPA response as that of the model monomer in ethanol, as shown by σ2 values of 104 GM for G1, 119 for G2, and 127 for G3, in water [56]. The same type of synthetic method was applied to another TPA fluorophore functionalized by two phenols, but

Attempted synthesis of a meta-metalated calix[4]arene

• Christopher D. Jurisch and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2019, 15, 1996–2002, doi:10.3762/bjoc.15.195

• subject of extensive study since the mid-twentieth century [1]. Obtained from the base-catalyzed condensation of para-alkylated phenols and formaldehyde, calix[4]arenes have cyclic bowl-like structures which provide various sites for controlled chemical modifications. The versatility of calix[4]arenes has

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• coupling reactions and as potential covalent probes in protein profiling [14][25][26][27][28]. Phenols (or alcohols) and amines as the most common nucleophiles have been found to react with different S(VI) connectors (SO2F2, CH2=CH-SO2F, SOF4 etc.) to provide diversified sulfonyl fluoride derivatives. The

• reactions of phenols (or alcohols) with SO2F2 [29] or the fluorosulfuryl imidazolium salt were developed for mild and effective formation of the corresponding fluorosulfates to act as biological probes in chemical proteomics studies (Scheme 1, (1)) [1][30]. On the other hand, the reactions of aliphatic or

An azobenzene container showing a definite folding – synthesis and structural investigation

• Abdulselam Adam,
• Saber Mehrparvar and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2019, 15, 1534–1544, doi:10.3762/bjoc.15.156

• far, a series of receptors based on these macrocycles were synthesized. They have been designed for the selective recognition of sulfate ions [4][5][6], di- and triphosphate ions [7], for sensing of pyrophosphate ions in aqueous solutions [8], as receptors for phenols [9], α-chiral primary