Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• , indoles [30] or phenols [31]. Other arenes (benzene and its substituted derivatives) have not been involved in these reactions. Concerning electron-deficient allenes, bearing electron-withdrawing groups, there is only one example of a trifluoroacetic acid-promoted hydroarylation with indoles [30]. To the

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• with demethylation following subsequently at a slower rate. The experiments on the re-incubation of phenols 7 and 8 failed to lead to any further metabolism, where they appeared to be stable metabolites, certainly for the period (72 h) of the incubation. We were unable to observe a transformation from

• sulfoxide 6 to sulfone 9 in these re-incubation experiments. It may be that there is a barrier to uptake of the phenols into the fungal cells and that they are actively exuded when generated within the cell. As a final experiment sulfone 9, which was not observed as a metabolite, was prepared by mCPBA

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• organic synthesis [48][49][50][51]. Our interest in cyclopropylation reactions led us to explore the use of cyclopropylboronic acid in the O-cyclopropylation of phenols. Unfortunately, efficient conditions could not be identified to perform this seemingly simple extension of the N-cyclopropylation

• reaction. Very recently, Engle and McAlpine disclosed a solution to this problem by developing a highly efficient protocol for the direct O-cyclopropylation of phenols using potassium cyclopropyl trifluoroborate [52]. Surprisingly, and to the best of our knowledge, cyclopropylboronic acid or its various

• -cyclopropylating benzyl mercaptan, an alkylthiol, failed to deliver the desired product. Engle and McAlpine recently reported a very efficient, simple and general protocol for the O-cyclopropylation of phenols using potassium cyclopropyl trifluoroborate (29) that leads to the corresponding aryl cyclopropyl ethers

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• chloride/N,N-dimethylformamide in the presence of a catalytic amount of p-toluenesulfonic acid ended up with only the formation of OPA. Regeneration of phenols from methyl ethers have also been tested by Boovanahalli et al. [26] by using an ionic liquid such as 1-butyl-3-methylimidazolium bromide ([Bmim]Br

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• - and 3,4-dimethoxystyrene in a completely regioselective manner. Thus, oxygenated dihydrostilbenes are obtained that feature the skeleton of scorzodihydrostilbenes – antioxidative agents that were recently isolated from Scorzonera radiata. Selective deprotection liberates the corresponding phenols

• , among them the aglycon of scorzodihydrostilbenes B and D. Keywords: C–H activation; hydroarylation; phenols; regioselectivity; ruthenium; Introduction Among phytochemicals with strong allelopathic effects, various natural products are found that feature the structural motif of dihydrostilbene with

• , 69.56; H, 6.73. General procedure for the synthesis of phenols 9–11 by hydrogenolytic cleavage of benzyl ether protecting groups: An autoclave was equipped with a stirring bar and charged with O-protected dihydrostilbenes 8a,b (0.8 mmol), palladium on charcoal (50 mg) and ethyl acetate (12 mL). The

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• , it shows incompatibility with functional groups such as alkenes, phenols, phenyl ethers, and alcohols, which are readily oxidized. The dibenzylic C–H bonds of fluorene and xanthene were also able to be functionalized. Xanthene (4a) was over-oxidized to the ketone (xanthone, 5a) in 57% yield (Figure 3

Metal-free C–H mercaptalization of benzothiazoles and benzoxazoles using 1,3-propanedithiol as thiol source

• Yan Xiao,
• Bing Jing,
• Xiaoxia Liu,
• Hongyu Xue and
• Yajun Liu

Beilstein J. Org. Chem. 2019, 15, 279–284, doi:10.3762/bjoc.15.24

• benzoxazoles to the corresponding thiols through direct C–H mercaptalization using 1,3-propanedithiol as thiol source. Results and Discussion Previous studies in our group revealed that small aliphatic diols and dithiols are promising reagents for the synthesis of phenols and arylthiols, respectively [23][37

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• oxidative conditions has been developed. The employment of Mn(OAc)3·2H2O or KMnO4 as stoichiometric oxidants allowed the use of a wide range of nucleophiles, such as nitromethane, (aza)indoles, pyrroles, phenols, pyrazole, indazole and diethyl malonate. The formation of the target compounds presumably

• molecules 8–10, in 60%, 53% and 49% yields, respectively. Such well-known π-nucleophiles as phenols could be used for the reaction, though 3-methoxyphenol and 3,5-dimethoxyphenol gave inseparable mixtures of regioisomers 11a and 11b (NMR, LCMS). The reactions with p-isopropyl- and p-tert-butylphenols gave

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• -1-enyl)coumarins 16 were isolated in high overall yields and E-selectivities. Allylation of phenols 16 furnished the RCM precursors 17, which underwent the tandem RCM/allylic oxidation sequence to compounds 15 in fair yields (Table 5). All pyran-2-one-annellated coumarins 15 synthesized in the

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• Geniculosporium sp. [18] and on a series of structurally related phenols, benzaldehydes and anisole derivatives from Hypoxylon invadens [19] that could only be identified with certainty following this approach of extensive compound comparisons. Members of the family Hypoxylaceae are regarded to be extremely rich

• trimethylanisoles with respect to their substitution patterns, and each trimethylphenol consistently elutes slightly later with an increase of the retention index by ca. 30–50 points than the trimethylanisole analogue (Table 2 and Table 3), which is explainable by the significantly higher polarity of the phenols

Synthesis of a tyrosinase inhibitor by consecutive ethenolysis and cross-metathesis of crude cashew nutshell liquid

• Jacqueline Pollini,
• Valentina Bragoni and
• Lukas J. Gooßen

Beilstein J. Org. Chem. 2018, 14, 2737–2744, doi:10.3762/bjoc.14.252

• of the anacardic acid component of CNSL presents several challenges. Since CNSL consists of a mixture of acids, phenols and resorcins with saturated and unsaturated side chains, it seemed to be impossible to derive a single product with a shorter side chain via a cross-metathesis with a short olefin

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• at the betaine intermediate prior to epoxide formation through displacement of THT. This is supported by example 9 which contained a para-methoxy group at the aldehyde component but was isolated as a single diastereomer [28]. Functional groups that are not compatible with this method include phenols

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• oxidative demethylation of 4-(methoxymethyl)phenols via a quinone methide intermediate [28][29]. Based on this precedent and the assumption that DHNO oxidizes the C2–C3 bond, Koetter and Schultz [27] proposed the mechanism shown in Scheme 5 for DHNO. However, members of the p-cresol methylhydroxylase

Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives

• Jiao-Na Han,
• Cong Du,
• Xinju Zhu,
• Zheng-Long Wang,
• Yue Zhu,
• Zhao-Yang Chu,
• Jun-Long Niu and
• Mao-Ping Song

Beilstein J. Org. Chem. 2018, 14, 2090–2097, doi:10.3762/bjoc.14.183

• rapidly in recent years. By contrast, alkoxylation or phenoxylation confronts great challenges because alkanols or phenols are easily converted into the corresponding aldehydes, ketones, or carboxylic acids [7][23][24][25]. Recently, Gooßen [26][27], Sanford [28], Song, [29][30] and others [31][32][33][34

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• the 1,6-enynes from the corresponding 2-halogenated phenols, benzenethiols or anilines, via a simple substitution–elimination–Sonogashira synthetic sequence. In addition, the group has synthesised trifluoromethylated modified versions of certain drugs (Figure 13). Variations on the classical

Functionalization of graphene: does the organic chemistry matter?

• Artur Kasprzak,
• Agnieszka Zuchowska and
• Magdalena Poplawska

Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177

• phenolic compounds [58][59][60][61]. Water should therefore be considered a solvent that facilitates the adsorption of phenols on a graphene-family material during a reaction. This side process, which is visualized in Figure 7, step e, can also influence the reaction rate of the desired radical process

Preparation and X-ray structure of 2-iodoxybenzenesulfonic acid (IBS) – a powerful hypervalent iodine(V) oxidant

• Irina A. Mironova,
• Pavel S. Postnikov,
• Rosa Y. Yusubova,
• Akira Yoshimura,
• Thomas Wirth,
• Viktor V. Zhdankin,
• Victor N. Nemykin and
• Mekhman S. Yusubov

Beilstein J. Org. Chem. 2018, 14, 1854–1858, doi:10.3762/bjoc.14.159

• of phenols to 1,2-quinones [15], the cyclization and cross-coupling reactions [16], and the site-selective hydroxylative dearomatization of 2-substituted phenols to either 1,2-benzoquinols or their cyclodimers [17]. The first preparation and isolation of IBS (1) was attempted in 2006 using two

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• the overlap of the 5p orbital of iodine atom with the orbitals of two ligands (Figure 1) [9]. The chemistry of hypervalent iodine(III) reagents is now a well-established area in organic chemistry. They are efficient oxidants in many synthetic transformations, such as oxidation of alcohols and phenols

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• who want to know the chemistry involved during the dearomatization of phenols and to find the relevant literature available until 2008. In this review article, various approaches for the synthesis of spirocyclic scaffolds using hypervalent iodine reagents are covered including stereoselective

• reactions. Hypervalent iodine reagents are mainly popular for their oxidative properties but various iodine(III) reagents have been used as electrophiles. Numerous iodine(III) reagents have been successfully used to achieve diverse spirocyclic scaffolds. Phenols 7 or 11 having an internal nucleophile at

• oxidation of iodoarene using mCPBA as terminal oxidant [76]. In this report, p-substituted phenols 27 were cyclized to the corresponding spirolactones 29 using iodotoluene 33 as precatalyst, mCPBA as oxidant and TFA as an additive. The spirolactones 29 were isolated as reaction products in excellent yields

Heterogeneous acidic catalysts for the tetrahydropyranylation of alcohols and phenols in green ethereal solvents

• Ugo Azzena,
• Massimo Carraro,
• Gloria Modugno,
• Luisa Pisano and
• Luigi Urtis

Beilstein J. Org. Chem. 2018, 14, 1655–1659, doi:10.3762/bjoc.14.141

• employed reactions is a challenge in contemporary organic chemistry. We applied such an approach to the synthesis and further conversion of tetrahydropyranyl ethers, an important class of compounds widely employed in multistep syntheses. Several alcohols and phenols were almost quantitatively converted

• tetrahydropyranylation of alcohols and phenols in cyclopentyl methyl ether (CPME) and 2-methyltetrahydrofuran (2-MeTHF) in the presence of heterogeneous acidic catalysts. Indeed, both CPME [19][20][21][22] and 2-MeTHF [21][22][23][24][25] are characterized by relatively high boiling points, a narrow explosion range

• phenols, including some known fragrances (3g–j and 3l) [4][5][6][7], as illustrated in Scheme 2. Conversions exceeding 95% were achieved under the mild conditions illustrated in Scheme 2 with primary aliphatic and benzylic alcohols 1b–h. A notable exception is the low conversion of 4-bromobenzyl alcohol

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• or secondary alcohols, while the nucleophilic species needs to be acidic [13] with a pKa < 11. Otherwise the azo reagent would compete with the acidic nucleophile and participate in the substitution reaction [14]. Various compounds comply with that condition: carboxylic acids, phenols, hydrazoic acid

• phenols to achieve aryl glycosides Not only anomeric esters, but also glycosides can be obtained through the Mitsunobu reaction. Dehydrative glycosylation approaches with reducing sugars were previously reviewed [43][44]. As phenols are weak acids, they are suitable reaction partners in the Mitsunobu

• photoswitchable azobenzene α-D-mannoside 47 (Scheme 9) [46]. Notably, in this reaction, traces of an anomeric mixture of the respective furanoside 48 were detected. The Mitsunobu synthesis of aryl glycosides was also applied to p-nitrophenol [47], naphthols [48][49], or multifunctional phenols [27][50]. Such

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• , C–C, C–O, or C–N couplings, dearomatization of phenols, rearrangements, to name but a few, have been reported using these compounds thereby reflecting their versatility. A survey of the general structure of polyvalent organoiodine compounds reveals that they are prepared mostly from iodoarene

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• -arylations of phenols using diaryliodonium salts [23][24][25], which are reactive electrophilic arylation reagents [26][27][28]. As diaryliodonium salts can be easily synthesized in a one-pot manner [28], we envisioned that phenoxazines could be obtained in a straightforward and efficient manner from

• sequence, proceeding via arylation of phenols with diaryliodonium salts using our reported methodology [23][24][25]. In reactions with unsymmetrical iodonium salts, this type of O-arylation is known to have an ortho-effect, i.e., chemoselective transfer of the ortho-substituted aryl moiety [29][30]. The

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• temporary generate potentially unstable λ3-iodane derivatives and immediately convert them under the established α-arylation conditions. A PIDA ((diacetoxyiodo)benzene)-mediated ortho-iodination/O-arylation cascade was developed by Panda and co-workers using diversely functionalised phenols 23 (Scheme 14

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• oxylation of ketones reported by Masson et al. α-Fluorination of β-keto esters. Alkynylation of β-ketoesters and amides catalyzed by phase-transfer catalyst. Alkynylation of β-ketoesters and dearomative alkynylation of phenols. Acknowledgements The authors highly acknowledge the financial assistance