Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• Cu···Cu distance of ca. 2.3 Å was detected in these complexes. In 2017, Romanov et al. synthesized a series of amido and (phenolato)Cu–NHC complexes from the reaction of (AdL)MCl (M = Cu, Au) with phenols, thiophenols, or aromatic amines in the presence of NaOt-Bu at rt in anhydrous THF (Scheme 30

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• insertion reactions could occur (Scheme 10) [100]. Systematic evaluation of acidic compounds showed that carboxylic acids (pKa ≈ 5; 85–99% yield) and thiophenols (pKa ≈ 7; 50f, 59%) were especially viable, whereas electron-rich phenols (pKa ≈ 10; 50d, <15% yield) were not. Though electron-poor phenols (pKa

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• substituent at the aforesaid position for which a much diminished enantioselectivity (44%) was obtained (Scheme 24) [54]. Pyrophosphoric acids In 2018, Ishihara and co-workers demonstrated a highly para-selective aza-Friedel–Crafts process using phenols and ortho-monosubstituted phenol analogues 104. As

• . Atroposelective aza-Friedel–Crafts reaction. Coupling of 5-aminopyrazole and 3H-indol-3-ones. Pyrophosphoric acid-catalyzed aza-Friedel–Crafts reaction on phenols. Squaramide-assisted aza-Friedel–Crafts reaction. Thiourea-catalyzed aza-Friedel–Crafts reaction. Squaramide-catalyzed reaction between β-naphthols and

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• -cyclodextrin/polysaccharides (blue curves for chitosan, red for locust bean gum, green for xanthan gum) with saponin (yellow curves correspond to cyclodextrin matrices, without polysaccharide). Sorption of phenols (V, vanillin; Ph, phenol; m-c, m-cresol; 4eP, 4-ethylphenol; Eu, eugenol) in β-cyclodextrin

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• insertion of carbenes derived from diazo arylidene succinimides (DAS) into the O–H bond of phenols is described. The initial adducts underwent a thermally promoted Claisen rearrangement followed by DABCO-catalyzed intramolecular 5-exo-trig oxa-Michael addition. Keywords: Claisen rearrangement; diazo

• impetus from the synthetic point of view. Specifically, we wanted to see if Rh(II)-catalyzed insertion of DAS-derived carbenes could be performed into the O–H bond of phenols and if the resulting phenoxy-substituted succinimides 5 could also undergo a Claisen rearrangement. The products of the latter (6

• synthesized as detailed in Scheme 3. The O–H insertion reaction worked well for electron-neutral or electron-rich phenols. The presence of chlorine substituents (such as 4-Cl or 2,4-diCl) in the phenol component drastically diminished the yield and led to the formation of the earlier reported DAS dimer [16

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

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

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• fluorine atoms were prepared in moderate to good yields via the reactions of phenols and 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane) in the presence of KOH. This simple reaction enabled the construction of highly halogenated compounds with the potential for further functionalization. The reaction

• 2b in 70% yield (Table 2, entry 1). The reaction under these conditions tolerated phenyl-substituted phenols and afforded 2c–e in moderate to good yields (Table 2, entries 2–4). Electron-donating substituents, e.g., those in 3f (4-OMe) and 3g (2-t-Bu), did not compromise the reaction performance

• incompatibility with electron-withdrawing substituents can be attributed to lower nucleophilicity of the phenoxide ion and structural instability of the product, which could lead to unexpected reactions of 2h and 2i during the reaction or purification process. Phenols with allyl or vinyl substituents (3j and 3k

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• José G. Hernández Bochum, Medellín, October 2022 ORCID® iDs Lars Borchardt - https://orcid.org/0000-0002-8778-7816 José G. Hernández - https://orcid.org/0000-0001-9064-4456 a) Mechanochemical PEG-400-assisted halogenation of phenols and anilines using NXS. b) Halogenation of azobenzenes with NXS

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• as an enantioselective catalyst for the asymmetric ring opening of terminal epoxides by phenols. A library of α-aryloxy alcohols 3 was thereafter synthesized in good yield and high ee using 2f via the phenolic KR of epichlorohydrin. Keywords: α-aryloxy alcohols; chiral Co–salen; HKR

• ]. Since their discovery, researchers have investigated several Co–salen complexes for the KR of epoxides with phenols as nucleophiles (Figure 1) [18][19]. Kim et al. described a catalytic system of a chiral Co–salen immobilized on meso/macroporous silica monoliths for the ring opening of epoxides [20

• were explored as well. Furthermore, we present the hydrolytic kinetic resolution (HKR) of epichlorohydrin with water using Co–salen complexes 2, and α-aryloxy alcohols were synthesized by the 2f catalytic system through the asymmetric ring opening of epichlorohydrin and phenols. Results and Discussion

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• catalyst-free halogenation of phenols and anilines via liquid-assisted grinding using PEG-400 as the grinding auxiliary. A series of mono-, di-, and tri-halogenated phenols and anilines was synthesized in good to excellent yields within 10–15 min in a chemoselective manner by controlling the stoichiometry

• catalyst-free methods, the use of costly and low boiling hexafluoroisopropanol (HFIP) as solvent offered the para-selective halogenation of activated aromatic systems (Scheme 1c) [44]. It is noteworthy to mention that over-halogenation of activated systems like phenols and anilines, due to the high

• products 2a–r in high to excellent yields upon employing 1.1 equiv of NBS as the brominating agent and PEG-400 (0.2 mL per mmol of phenols) as the LAG agent. As mentioned, PEG-400 allows the formation of a free-flowing liquid mixture and the reactions were mostly completed within 2–15 min of grinding in an

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• performed a detailed investigation on the dearomatizing anionic cyclization of diphenyl-N-alkyl-N-benzylphosphinamides 107, 116, and 119 by treatment with sec-butyllithium and protonation with various alcohols (MeOH, iPrOH, t-BuOH), phenols (PhOH, 2-tert-butyl-4-methylphenol, and 2,6-di(tert-butyl)-4

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• conversion of 8-hydroxyquinoline and 1,3-dihydroxynaphthalene were observed. Xanthurenic acid and 4-methylumbelliferone were only farnesylated in negligible amounts, and no product formation was observed for phenols or catechols (Figure 5). Overall, 8-hydroxyquinoline-2-carboxylic acid (8-HQA) appeared to be

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• with phenols in the presence of Cs2CO3/DMF affords α-phenoxy-α’-hydroxyketones (1:1 adducts) and α,α-diphenoxyketones (1:2 adducts) in up to 92% and 24% yields, respectively. Both products are formed via ring opening of the same intermediates, 1,3-dioxolan-2-ones, generated in situ from

• bromopropargylic alcohols and Cs2CO3. Keywords: acetylenic alcohol; bromoacetylene; 1,3-dioxolan-2-one; phenols; phenoxyketone; Introduction Due to the relative stability, ease of handling and the presence of reactive sites, bromoacetylenes are widely applied in synthetic organic chemistry. They are known to be

• [17]. Also, M2CO3-catalyzed (M = K or Cs) addition of phenols to bromoacetylenes produced bromovinyl phenyl ethers, which were converted into 4H-chromen-4-ones, benzo[b]furans, etc. [18][19][20][21]. The latter reaction attracted our attention and prompted us to explore the interaction of phenols and

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• isolated in its pure form starting from model mixtures containing various aromatics, phenols, alkanes or alkenes in overall purification yields ranging from 53 to 98%. The lower yields are observed for coordinating phenol and catechol (Table 2, entries 3 and 4), probably impacting the crystallization

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• standard reaction, the goodness of fit of the data using the Hammett substituent constants will be decreased. For example, for phenols which have a direct conjugation of a developing anion with an appropriate substituent, adjusted σ values are available for these substituents. The above is presented to

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