1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• easily carried out from the products of β-NQS 8 reactions with substituted amines and phenols (Figure 4). The objective of these transformations is to search for new compounds that present new physicochemical and biological properties. For the first time, Campos and co-workers [90] performed the

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• -rich phenols, as well as those bearing halogen substituents, were suitable substrates under these reaction conditions. In Lei’s report, the reaction shuts down in the presence of TEMPO and in the absence of DDQ; thus, the formation of a phenoxy radical was proposed. In 2018, Zhong and co-workers

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• -yl)imino)methyl)phenols 3, was easily synthesized with yields of up to 91% from the reactions involving a series of 2-(R-substituted) 6-amino-4-(trifluoromethyl)quinolines 1 and 4(5)-R1-substituted salicylaldehydes 2 – in which alkyl/aryl/heteroaryl for 2-R-substituents are Me, Ph, 4-MeC6H4, 4-FC6H4

• (Scheme 1). Results and Discussion Chemistry The synthetic routes and structures for the synthesis of (E)-2-(((2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl)quinolin-6-yl)imino)methyl)phenols 3 are collected in Scheme 2 and Scheme 3. First, a series of six 6-amino-2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl

• reaction (TLC) and cooling the mixture to room temperature, the solid was filtered under reduced pressure. The crude compounds 3 were purified by recrystallization from ethanol to provide the desired (E)-2-(((4-(trifluoromethyl)quinolin-6-yl)imino)methyl) phenols 3 in 20–91% yield. Spectral data (E)-2-(((2

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• -yl)methanols 87 as electrophile and 2-naphthols 88 or phenols 90 as nucleophile (Scheme 29) [45]. The (3-alkynylindol-2-yl)methanol 87 is expected to convert to the allene-iminium intermediate I-24 by accepting a proton from CPA 14. Then, the CPA anion activates the nucleophilic addition between 2

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• , also as protective group for phenolic residues. After ring closure, the ethoxycarbonyl-protected phenols are deprotected simultaneously with the further processing of the carbamate group, either following route A (lithium alanate reduction) to give N-methylated phenolic products, or following route B

• , the ethoxycarbonyl group can as well be utilized for the protection of phenolic groups, which frequently occur in 1-benzyltetrahydroisoquinoline alkaloids. After successful ring closure, the ethoxycarbonyl-protected phenols are deprotected simultaneously with the further processing of the carbamate

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• groups for phenols) and was further utilized in the first total synthesis of the natural product nobilone. Keywords: cross-dehydrogenative coupling; cyclization; fluorenones; nobilone; total synthesis; Introduction Fluorenones are an important class of aromatic natural products, and since the

• ) TFA, DCM, rt, 6 h, 76–98%; e) TBHPaq, 1,2-DCE, 100 °C, 18 h (yields in parentheses). Substrate scope for the oxidative cyclization of 2-(aminomethyl)biphenyls with main focus on protected phenols. Conditions: a) Pd(PPh3)4 (5 mol %), Na2CO3, DMF/H2O, 18 h, 100 °C, 76–99%; b) LAH, AlCl3, THF, 18 h, rt

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• the copper-catalyzed oxidative coupling of alkynes, nucleophiles (e.g., phenols 25 and 28; amines 24, 27, 29, and 32; 2-hydrazinylpyridine 26; alkyne 33; and alcohol 30), and oxidants (benzoquinone or O2). Based on the literature and mechanistic experiments [72][73], the reaction is initiated by the

• )–O cross-coupling using oxime esters and phenols 76 (Scheme 30). In 2020, Loh and co-workers [104] reported the copper-catalyzed highly site-selective alkylation of heteroarene N-oxides in the presence of hypervalent iodineIII carboxylates. As an alkylating agent, the hypervalent iodineIII

• and heteroarenes. Benzylic or α-amino C–H functionalization. α-Amino C–H functionalization of aromatic amines. C–H functionalization of aromatic amines. α-Amino-C–H and alkyl C–H functionalization reactions. Other copper-photocatalyzed reactions. Cross-coupling of oxime esters with phenols or amines

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• with HgCl2 (0.5 equiv) in presence of N-bromosuccinimide (NBS) undergoes cyclization yielding stable bromo alkenes 87 (Scheme 28) [80][81]. Atta et al. reported the specific cyclization of ethynyl phenols 88 in presence of HgCl2 at ambient temperature yielding benzofuran derivatives 89. They had

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• active nickel(0) catalyst 5-III. The synthetic utility of the photoredox nickel-catalyzed C‒H arylation was further elaborated to include C‒O electrophiles which could be readily derived from phenols, as disclosed by the Yu group [58]. Hence, they reported an arylation protocol for α-amino- and α-oxy C

• (Scheme 7b). In a subsequent report, Yu and co-workers also realized the arylation of α-amino C(sp3)‒H bonds with aryl tosylates 11 generated in situ from phenols 12 and p-toluenesulfonyl chloride (TsCl) [59][60]. The combination of visible-light-photoredox catalysis, hydrogen-atom-transfer catalysis, and

• . Arylation of α-amino C(sp3)‒H bonds by in situ generated aryl tosylates from phenols. Formylation of aryl chlorides through redox-neutral 2-functionalization of 1,3-dioxolane (13). Photochemical C(sp3)–H arylation via a dual polyoxometalate HAT and nickel catalytic manifold. Photochemical nickel-catalyzed α

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• intramolecular coupling of arynes by aldehydes or phenols [21][22][23][24], and Lewis acid-catalyzed cyclization of salicylaldehydes and cyclohexenones or tetralones [25]. Some other new and prominent synthesis methods of xanthenes are the tandem arylation/Friedel–Crafts reaction of o-hydroxy bisbenzylic

• , antitumor, antioxidant, and anticarcinogenic. Experimental General information The majority of the chemicals used in this work were commercially available from Merck or Aldrich. The starting compounds 1a–l were prepared by Ullmann coupling of 2-fluorobenzaldehyde and substituted phenols. Compounds 2a–l were

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