Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• ][6][7][8][9]. Therefore, many efficient methods have been developed in the past decades to synthesize different types of phosphoric esters [10][11][12][13][14][15][16][17][18]. Traditional methods for the construction of P−O bonds in phosphoric esters rely on the phosphorylation of alcohols or phenol

Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes

• Mana Kitano,
• Tsuyoshi Saitoh,
• Shigeru Nishiyama,
• Yasuaki Einaga and
• Takashi Yamamoto

Beilstein J. Org. Chem. 2022, 18, 1154–1158, doi:10.3762/bjoc.18.119

• hydroperoxide/dicumyl peroxide/phenol from cumene, acetophenone from ethylbenzene, and others. Generally, molecular oxygen has been utilized in the straightforward oxidation of aromatic alkyls. However, since molecular oxygen is highly stable, activation of the molecular oxygen itself is necessary, which

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• dimers or cross-coupling products, starting from simple monomers [17][18][19]. Nevertheless, our knowledge of enzyme-mediated dimerization is still limited in contrast to the numerous reported dimeric natural products. Phenol coupling in plant polyphenol biosynthesis is one of the earliest documented

• , Supporting Information File 1). Other plant polyketides, such as anthraquinones 19 and 20 and phenylpropanoids 21–24, failed to be dimerized. The reaction mechanism of P450-mediated phenol dimerization is believed to involve oxidative radical–radical coupling, though other mechanisms, such as radical

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• . Interestingly, the generation of phenol was observed (7% yield), probably because 1a could serve as a hydrogen donor due to the low concentration of hydrogen [32]. Conclusion In conclusion, we have developed a system for the electroreduction of enones using a PEM reactor. The reactions proceeded under mild

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

• an improved yield (77%) of the monobromo product 2a, with a reduced amount of 3a (12%), and a nominal recovery of the starting material were observed (Table 1, entry 2). Incomplete consumption of starting phenol 1a was primarily due to over bromination. The LAG in the presence of water afforded

• monobromination under the optimized reaction conditions to validate the effectiveness of our method using an indigenous electrical grinder. The results are summarized in Scheme 3. At the outset, several electron-rich and electron-deficient phenol derivatives were converted to the corresponding monobrominated

• - and p-positions in the case of bromination as well as iodination (product 2b, 2d, 2h, 2k, 2s, 2w, 2ab, 2ag, etc. in Scheme 3). In some cases, the formation of negligible amounts of dihalo derivatives (3–5%) could not be avoided. Only for the attempted monobromination of unsubstituted phenol, the

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• at 110–160 bar to form the O-allyl phenol which was heated in a second reactor to 265 °C where the Claisen rearrangement under near-critical conditions occurred to yield 2-allyl-4,6-difluorophenol (12) in 64% yield. In this example, the two reactors made of steel were heated directly by the external

• Petasis boron-Mannich (PBM) reaction of glyoxalic acid (30a) or salicylic aldehyde (30b), with morpholine (29) and p-methoxyphenylboronic acid (31) furnished α-aminocarboxylic acid 32a and phenol 32b in excellent yield (98% and 93%), again much higher than the yields found for the batch protocol (77% and

• heated flow system [65][66][67][68][69][70][71]. This is exemplified for the tandem synthesis of benzofuran 47 and phenylindole 48 (Scheme 10, case B) starting from phenol 44 and aniline derivative 46, respectively. The latter reaction was carried out in a glass reactor filled with MagSilicaTM [53

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

• carbonate. In the light of the above, it was unclear, in which direction would proceed the reaction of bromopropargylic alcohols and phenols. In the present paper, we report on the results of these studies. Results and Discussion Initially, bromopropargylic alcohol 1a and phenol (2a) were chosen as the

• to the reaction system. It was shown that the reaction of 1a with 2a in aqueous DMF (1 equiv of Cs2CO3, DMF/H2O, 10:1, 50–55 °C) was highly selective to deliver phenoxyhydroxyketone 4a in 78% yield and dihydroxyketone 8a as a side product (Table 1, entry 6). Hence, the addition of phenol to the

• triple bond is a minor direction for the reaction of bromopropargylic alcohols and phenol in the presence of Cs2CO3/DMF, which was completely suppressed by addition of water. When DMF was replaced by DMSO (Table 1, entry 13), the preparative yield of reaction products decreased possibly due to product

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• catalyst for the oxidation of 2-methylnaphthalene (16) with H2O2 [59]. The complex L1-Fe(III) (L1 = (2-((2-(2-((2-((2-hydroxyphenylimino)methyl)phenoxy)methyl)benzyloxy)benzylidene)amino)phenol) showed the best catalytic activity with 58.54% selectivity and 79.11% conversion (Table 1, entry 13) [59

• electrophilic bromination of the corresponding phenol, followed by hydrolysis promoted by H2O2 [66]. Variations in the methods of 2-methylnaphthol (17) oxidation to menadione (10) with H2O2 were made by changing the catalytic systems in order to increase the yield and selectivity. These include the catalysis by

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

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• bond in the staple (cis and trans, respectively). Synthesis of SMC stapled axin CBD peptides. Reaction conditions: (a) Pd2(dba)3, sSPhos, KF, DME/EtOH/H2O 9:9:2, 120 °C, µwave, 30 min; (b) TFA/TIS/H2O 95:2.5:2.5, DTT, phenol, 2 × 2 h. B(OR)2 = B(OH)2, B(pin), pin = pinacolato, t-Bu = tert-butyl, Trt

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

• (sp3)–H compounds. Iron-catalyzed heteroatomic cross dehydrogenative coupling In 2013, Lei and Pappo independently reported an FeCl3-catalyzed oxidative coupling/cyclization cascade of phenol derivatives 86 and alkenes 87 (Scheme 15) [91][92]. Similar trends were reported by both groups namely electron

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• . Šindelář and Lizal [36] also presented the synthesis of hybrid macrocycles containing glycoluril and aromatic units. In 2014, Keinan et al. [37] reported a series of macrocycles, consisting of alternating urea or thiourea and phenol units, namely, multifarenes. Hitherto, multifarenes and their derivatives

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• reactions [35][36][37][38][39], etc. In this context, the electron-rich aryl(phenol)methane isonitrile may be a new active unit, which can be seen from the previous case of p-QMs type reaction [40][41][42][43][44][45][46][47][48][49][50][51] and the above-mentioned properties of isocyanide. Herein, we

• reaction without adding bases, and unexpectedly found Ag salts could catalyze the 1,6-conjugate addition of TosMIC (2a) and p-QM 1a to provide aryl(phenol)methane isonitrile 4a under base-free conditions (Table 1, entries 6–8). When the silver salt was removed from the reaction conditions, the reaction did

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

• , according to Temel and co-workers who studied a similar scaffold, namely, 4-bromo-2-((quinoline-8-yl)methyl)phenol [27], no imine–hemiaminal tautomer peak transition was observed for the Schiff bases 3. In general, there were slightly significant changes in the transitions according to the changes in the

• -Methyl-4-(trifluoromethyl)quinolin-6-yl)imino)methyl)phenol (3aa): Yellow solid, yield 20%; mp 129–132 °C; 1H NMR (400 MHz, CDCl3) δ 12.98 (s, 1H, OH), 8.72 (s, 1H, CH=N), 8.15 (d, J = 8.9 Hz, 1H, H-8), 7.85 (bs, J = 2.1 Hz, 1H, H-5), 7.74 (dd, J = 9.0, 2.3 Hz, 1H, H-7), 7.61 (s, 1H, H-3), 7.48–7.39 (m

• ]+ calcd for C18H14F3N2O, 331.1053; found, 331.1037. (E)-2-(((2-Phenyl-4-(trifluoromethyl)quinolin-6-yl)imino)methyl)phenol (3ba): Yellow solid, yield 90%; mp 183–186 °C; 1H NMR (600 MHz, CDCl3) δ 12.96 (s, 1H, OH), 8.71 (s, 1H, CH=N), 8.27 (d, J = 8.9 Hz, 1H, H-8), 8.20–8.14 (m, 3H, Ph, H-3), 7.87 (bs, 1H

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

• afforded products 46 in moderate to good yields (50–97%), excellent diastereoselectivities (>95:5 dr), and high enantioselectivities (91:9 to 98:2 er, Scheme 15). The control experiments showed that the N–H group in naphthylindoles, the OH group in phenol, and the carboxylate group in azodicarboxylate play

• indole ring of the propargyl alcohol, the yield decreases, which could be due to steric effects. Since the chiral phosphoric acid catalysts can interact with these groups via double hydrogen bonds, control studies have shown that the free OH on naphthol/phenol and the NH groups on the α-indolyl-α

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

• utilization of the ethoxycarbonyl group for phenol protection. The main objective of this concept was, that after successful N-acyl-Pictet–Spengler cyclization two remaining pairs of transformations might be performed in one single transformation each: route A comprises reduction with lithium alanate, and

• should lead to an N-methyl group and to reductive cleavage of the carbonate-protected phenol(s); route B is based on treatment with an alkyllithium compound [26], which should remove all ethoxycarbonyl groups and provide N-nor analogues of the products obtained in route A (Figure 3). The required

• control) gave the desired racemic N-ethoxycarbonyl-1-benzyltetrahydroisoquinolines 5a–h with intact ethoxycarbonyl protection of the phenolic groups (Table 2). Simultaneous phenol deprotection and reduction of the carbamate group (route A) to an N-methyl group was accomplished by lithium alanate reduction

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

• reaction to give the hydroxyfluorenone 10t (Scheme 6) was unsuccessful, suggesting that here TBHP chemoselectively reacts with the phenolic group to generate non-identifiable products. In order to provide an access to phenolic fluorenones as well, some commonly used phenol protecting groups were tested

• -radical reagents [62]. An extremely poor yield was further obtained with methylenedioxy substrate 15p. Our application of this new protocol to the first total synthesis of the natural product nobilone (1d) is depicted in Scheme 7. The commercially available phenol 16 was TBS-protected to give compound 17

• Suzuki cross-coupling reactions, followed by reduction or reductive amination. The oxidative cyclization conditions are compatible with many functional groups on the aromatic rings (methoxy, chloro, cyano, nitro, and phenol protecting groups like TBS and SEM – but not benzyl and methylenedioxy

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

• frameworks from various tosylanilinoallyl acetals. 4H-Chromene derivatives were also synthesized starting from phenol derivatives (Scheme 38). Cyclization involving alkynes (-C≡C-) Marson et al. had developed the synthesis of substituted furans 133a–c promoted by catalytic use of Hg(II) salt through

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• with O-phenylhydroxylamine as reagent were not successful and only resulted in the formation of the benzonitriles 16a, 16c and 16e. Presumably, the oximes were formed but were unstable and the facile elimination of phenol took place to liberate the benzonitriles. Finally, the use of this methodology

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

• synthesized the novel unactivated alkenes 4a–l containing three aryl groups as the starting materials. The synthesis of 4a is demonstrated in Scheme 1. First, 2-phenoxybenzaldehyde (1a) was synthesized by coupling reaction of phenol with commercial 2-fluorobenzaldehyde. This reaction was carried out with very

• Büchi Melting Point B-540 apparatus. Scope of substrates for intramolecular FCA by activation of 4a–l and their isolated yields. aConditions: 4a–l (0.1 mmol) and TFA (10 mol %) in dry CH2Cl2 (1 mL) were stirred at room temperature for 1–24 hours. bYield of isolated product. Synthesis of 4a: (i) phenol

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• . SMAHOs bearing classical ester groups could be obtained in moderate yields (iPr: 51%; Bn: 53%; allyl: 52%) and the use of less nucleophilic alcohols such as t-BuOH, 2,2,2-trifluoroethanol, (−)-menthol, and phenol led to decreased yields (37%, 34%, 28%, and 17%, respectively). More functionalized alcohols

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

• biologically active molecules (22 and 23) (Scheme 9A) [92]. Interestingly, the same conditions could be used for benzene hydroxylation to obtain phenol but were ineffective with benzene rings bearing either electron-donating or electron-withdrawing substituents. Notably, the catalyst could be reused five times

• reaction suggested it goes through a radical pathway. Similar to the oxidation of alkanes to give alcohols and carbonyl compounds, vanadium complexes have been reported to mediate the hydroxylation of arenes, including the obtaining of phenol from benzene. However, most mechanistic studies provided

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• -4j < unsubstituted 4a < 3,5-diCl 4t < 2,6-diCl 4r < pentachloro 4v, in good agreement with the decreasing order of the pKa values of the pyridines. For example, in order to fluorinate phenol, triMe 5-4j needed heating at 100 °C in a haloalkane solvent for 24 h, whereas pentachloro 5-4v required only

• aromatics such as phenol, cresol, and naphthalene were fluorinated in chloroform at 22 °C (Scheme 18). The N-F imide reagent 7-1a fluorinated the sodium salt of diethyl 1-methylmalonate at −10 °C to give the corresponding fluoro product in high yield (96%). Later (1991 and 1992), the same laboratory

• shown in Scheme 40, the 18-2 pyridinium series proved to be effective fluorinating agents for a wide range of substrates. Moreover, an extremely high ortho-selectivity was observed in the fluorination of phenol. This could be attributed to a hydrogen-bonding interaction between the sulfonate anion and

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• -triazole-based phenol or alcohol coordinates to the Pd center to form complex 158. Then, the electrophilic palladation of the 1,2,3-triazole ring occurs to achieve Pd(II) intermediate 159. Isocyanide migrates to 159 to obtain the seven‐ or eight‐membered palladium cycle 160. The reductive elimination of

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

• pathway involves electrophilic addition para to the phenol to form the ipso-substituted nitro 12 compound. Subsequent rearrangement of the nitro species 12 to the nitrito dienone 13, by homolysis and recombination of the radical pair, is followed by hydrolysis to furnish alcohol 6 [70]. Addition of the