Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• . The Mannich reaction with aromatic aldehydes and cyclic amines was performed efficiently on 2-naphthol, by using SiO2-supported copper triflate under solvent-free conditions, without an additional co-catalyst or additive (Scheme 3) [17]. The treatment of stoichiometric amounts of arylaldehydes

• demonstrated high tolerance to functional groups and runs, under mild conditions, with electron-poor diazo derivatives such as 2-diazoacetate, 2-diazoacetonitrile, 2-diazo-1,1,1-trifluoromethane, diazoamide, and diazophosphonate. Condensation of 2-naphthol, aromatic aldehydes and acyclic 1,3-dicarbonyl

• of an ortho-quinone methide intermediate XXXVII formed through nucleophilic attack of the 2-naphthol to the aldehyde followed by reaction with 1,3-dicarbonyl compound coordinated by the copper. The subsequent intramolecular nucleophilic attack of the oxygen to the enol and water elimination resulted

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• the final step of the reaction, ring opening by the C–C bond cleavage yields the desired product 203. The first phosphoric acid C39-catalyzed asymmetric cycloaddition–elimination cascade reaction of 2-naphthol or phenol enamide derivatives 204 with azonaphthalenes 205 was done by Xu et al. in 2021

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• free naphthol group in high yield (91%). We next turned our attention to the synthesis of benzo[j]fluoranthene 28, which is structurally related to 23, but with a free -OH group at a different position (Scheme 4). Our synthetic sequence commenced with the preparation of the known bromonaphthol 29 in

• two steps from 1,8-DHN (19) [57]. Methoxymethyl (MOM) protection of free -OH group of 29 using NaH and MOMCl afforded MOM-protected naphthol 30 in excellent yield (96%) [58][59]. It is worth highlighting the structural differences of naphthalenes 25 and 30, where the halogen (iodine) is on the same

• formal total synthesis of bulgarein (5) [54]. A careful design of the synthetic sequences enabled the syntheses of benzo[j]fluoranthenes 27 and 32 with differentially protected naphthol groups at different positions, which provides potential opportunities for further structural diversification. Examples

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• quinazolinone scaffold. They have obtained new benzochromenopyrimidinones, abbreviated as BCPOs, whose synthesis has been accomplished in two steps. First, a microwave-assisted reaction of ethyl cyanoacetate, selected aromatic aldehydes, and 2-naphthol was performed. The second step was the condensation of the

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• diaryliodonium salts regardless of their differing counter-anions. A range of 2-naphthol substrates, including those bearing alkyl and aryl groups, halogens, trimethylsilyl, and protected hydroxy at positions 6 and 7, exhibited good tolerance. However, the reaction with 1-naphthol did not yield positive results

• homolytic fragmentation in solution, producing tetramethylpiperidinyl radical and the TEMPO radical. The tetramethylpiperidinyl radical interacts with 2-naphthol derivatives 58, leading to the generation of an oxygen-centered radical through hydrogen atom transfer, which resonates with its respective carbon

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• -naphthol by applying a new ligand L14, leading to the rapid construction of differently substituted chiral spirocyclic enones 40a–j with high yields and enantioselectivities (Scheme 41). It is worth noting that when the C4 position of 1-naphthol was occupied, the reaction occurred at the C2 position

• to be the determining step for the enantioselectivity, while the diastereoselectivity is mainly induced by the chiral alkylated naphthol intermediate in the second annulation step (Scheme 46). Xu et al. [80] realized asymmetric [4 + 1] cyclization of yne-allylic esters with pyrazolones. This

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• reagents have been explored for the oxidation of polycyclic aromatic phenols (PAPs). Oxidation of 1-naphthol derivatives by bis(trifluoroacetoxy)iodobenzene (BTI) furnished p-naphthoquinones [16]. Other PAPs follow the same pattern forming p-quinones or o-quinones when the para-position is structurally

• blocked like in 2-naphthol (1a) [17]. Oxidation with iodoxybenzoic acid (IBX) [17] or stabilised IBX (SIBX) [18] form o-quinones selectively, even when the p-quinones are structurally feasible. However, all these methods constitute toxic hazards and/or produce stoichiometric amounts of waste products

• dimers, which indicates a radical intermediate [36]. Swenton and co-workers [37] established evidence for the phenoxonium ion (Scheme 1), and were further able to divert the reaction into forming ortho-oxidation due to steric hindrance (Scheme 2). Cyclic voltammetry studies of the oxidation of 2-naphthol

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Avenida Francisco J. Múgica S/N 58030, Morelia, Michoacán, México 10.3762/bjoc.20.141 Abstract The reaction mechanism for the chlorination and bromination of 2-naphthol with PIDA or PIFA and AlX3 (X = Cl, Br), previously

• reactions, we explored different pathways of the reaction mechanisms for the ortho-halogenation using 2-naphthol as a model substrate (Scheme 2). In such a way, we found a reaction pathway that was energetically favored. Based on our successful procedure for chlorination, we also developed an efficient

• : MeCN) ω-B97XD/(6-311G(d,p),LANL08d)//ω-B97XD/6-31G(d), LANL08d. Chlorination mechanism The reaction mechanism for the chlorination of 2-naphthol using one equivalent of PIFA and two equivalents of aluminum chloride is outlined in Scheme 4. The chlorination mechanism starts when PIFA coordinates the

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• . Keywords: annulation; arylocyclization; 3,4-benzocoumarin; diaryliodonium salts; naphthol; Introduction Diaryliodonium salts as electrophilic reagents have attracted significant attention in the field of organic synthesis owing to their efficiency and selectivity [1][2][3][4][5][6][7]. Particularly, they

• naphthols and substituted phenols. This method represents an efficient approach to access 3,4-benzocoumarin derivatives (Scheme 1c). Results and Discussion To start the study, we used 2-naphthol (1a) and 1.1 equivalents of ortho-methyl formate-substituted diaryliodonium salt 2a as template substrates. The

• variety of 3,4-benzocoumarin derivatives. Our investigations commenced with 2-naphthol (1), and the results are presented in Table 2. Various substituted naphthols with a broad range of substituents on the naphthalene unit were well tolerated in the reaction, affording the corresponding products 3aa–aq in

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• %) using again a large excess of DBU base (7 equiv) also allowed to prepare unsubstituted fluoranthene in 87% yield (Scheme 1c) [22]. The reaction of naphthol with aryl bromides followed by nonaflation and intramolecular C–H activation for the access to fluoranthenes has also been reported [23]. Most of

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• . Conversion of naphthols to naphthylamines is typically achieved through a three-step sequence whereby the naphthol is first O-alkylated with 2-bromo-2-methylpropionamide and this ether undergoes a Smiles rearrangement to the hydroxyamide, which is hydrolyzed to the free naphthylamine [44][45]. It has

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

• -naphthol moiety 193 afforded the highest yield and enantioselectivity. On protecting the hydroxy group in the ligand as methyl ether, the reaction efficiency decreased remarkably. However, on using NHC ligands without oxygen atom, such as analogues of 193, IMes, and SIMes, no conversion occurred. 2.8 C(sp2

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

• 2004. In this methodology, a 1,1’-bi-2-naphthol (BINOL)-derived chiral phosphoric acid P1 was used as the catalytic reagent to couple 2-methoxyfuran (1) and N-Boc-protected aldimines 2 to incorporate an aza-tertiary stereocenter into the 2’ position of the heteroaromatic products 3 (Scheme 1) [24

• various asymmetric chemical transformations. These compounds play a dual role in the catalytic cycle due to their intrinsic Brønsted acidity and the ability to H-bond formation. Organophosphoric acids can perform as both H-bond acceptors and donors. 1,1’-Bi-2-naphthol (BINOL) and 1,1’-spirobiindane-7,7

• reaction proceeding through aza-Friedel–Crafts reaction and lactonization steps. Main focus of this article was to demonstrate a racemic process between α-naphthol or phenol derivatives and in situ-generated N-acetyl ketimine from methyl 2-acetamidoacrylate (18) in the course of preparing 3-NHAc

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• benzaldehyde (51) (Scheme 13a). Related to this work, Feringa´s team realized also the conjugate addition to chromone (53) [44]. The enolate was again trapped with benzaldehyde in an aldol reaction (Scheme 13b). Naphthol derivatives 55 bearing an α,β-unsaturated ester group undergo a copper(I)-catalyzed

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• the bicyclic alkene followed by migratory insertion affords intermediate 12 which undergoes β-oxygen elimination to form 13. Rearrangement of 13 via β-hydride elimination and enolization generates a 1-naphthol species which undergoes intramolecular cyclization with the ester to form the final product

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• first example of Al‒O/B‒H exchange in catalysis was reported by Woodward, in the enantioselective catalytic hydroboration of ketones with HBcat as the terminal reductant (Scheme 23) [103]. A mixture of 1,1′-bi-2-naphthol (BINOL), 1,1'-binaphthalene-2,2'-dithiol (DTBH2), or 2-hydroxy-2'-mercapto-1,1

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

• sorption capabilities of the matrices has been studied with the corresponding 1-naphthol (1-N) isotherms (Figure 6). When comparing the isotherms of 20Pow, 45spLiq and 45spFoam of single component matrices, a better sorption from the saponin matrices for low 1-naphthol concentrations is detected. Thus, β

• simple hydrogel scaffold for the sorption of 1-naphthol. An aqueous sorbate mixture of five phenolic compounds has been also tested to assess the differences in the sorption behaviours of the different matrices. The absorbed amount changes as a function of the cyclodextrin/polysaccharide ratio, and the

• . Phenolphthalein and 1-naphthol (≥99%) were obtained from Merck (Germany). Methods Synthesis procedures: Firstly, citric acid (1.3 g) is dissolved into 100 mL of deionized water (acidic pH is required for chitosan) with 1.5 g of polysaccharide (either xanthan, or locust bean gum, or chitosan) and/or β-cyclodextrin

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• 110016, P. R. China Institute of Drug Research in Medicine Capital of China, Benxi 117000, P. R. China 10.3762/bjoc.18.169 Abstract The formal total synthesis of macarpine was accomplished by the construction of a naphthol intermediate in Ishikawa’s synthetic route with two different synthetic routes

• total synthesis of macarpine [12] is proposed via a Au(I)-catalyzed cycloisomerization reaction. Retrosynthetically, the target molecule macarpine (1) could be disconnected into naphthol 12 (Scheme 3), a key intermediate reported by Ishikawa in the total synthesis of macarpine. This intermediate could

• ) in tetrahydrofuran (THF), resulting in the formation of naphthol 12 [12][13], a key intermediate in the previous total synthesis of macarpine (1) reported by Ishikawa (Scheme 6). To simplify the synthetic procedure, a more straightforward strategy was proposed by using alkynyl ketone 9 [27][28][29

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

• reaction to explore the generality of this method. Initially, we performed the reaction with a small excess of 1-naphthol (3b, 1.05 equiv) relative to halothane (1.0 equiv), and used the same procedure as for Table 1, entry 6. The reaction proceeded smoothly to give 1-fluoro-2-bromo-2-chloroethenyl ether

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• , 2-aminophenols with methyl groups at the 3-, 4-, and 5-positions provided satisfactory yields of the products 8o, 8s, and 8t, respectively. On the other hand, an aminophenol with a methyl group at the 6-position provided the product 8u in a low yield. The reaction of 3-amino-2-naphthol with 2a

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

• bromination of 2'-hydroxyacetophenone (product 2m, Scheme 3). Notably, easily oxidizable groups like –CHO remained unaffected under the reaction conditions (product 2k and 2l, Scheme 3). It is worthy to mention that the bromination on 2-naphthol and coumarin was extremely fast affording >95% yields within

• the usefulness of the current protocol for quick access to these halo derivatives. Encouraged by this, we attempted monochlorination with selected phenols and anilines. The first attempt with 2-naphthol afforded the desired chloro derivative 2ah in high yield within 2 min. However, unlike in the case

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• 1 M HCl without dehydration in refluxing cat. PPTS/toluene (Table 1, entries 2–4 and 7). From 5,6-dimethoxy substrate 1d, phthalide 4d was also formed together with naphthol 3d (Table 1, entry 4). In contrast, phthalides 4e and 4f were the sole products in the reactions of 6-methoxy and 4,5,6

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

• outcome. α-Naphthol (2b) and β-naphthol (2c) reacted with bromopropargylic alcohol 1a in DMF or DMF/H2O to furnish naphthoxyhydroxyketones 4b,c in preparative yields (up to 81%) comparable to those of 4a. The introduction of an electron-withdrawing substituent (p-NO2) at the benzene ring gave a better

• acidic than phenols 2a–c,f–i (pKa values: 9.99 [25][26] phenol (2a), 9.40 [27] α-naphthol (2b), 9.57 [27] β-naphthol (2c), 7.18 [25][26] p-nitrophenol (2d), 7.23 [25][26] o-nitrophenol (2e), 10.28 [25][26] p-cresol (2f), 10.27 [25][26] p-methoxyphenol (2g), 9.36 [25][26] p-bromophenol (2h), 10.19 eugenol

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• (EDGs) led to naphthol compounds 9, while electron-withdrawing groups (EWGs) led to the anticipated ring-opened 1,1,2-trisubstituted naphthalene framework 10 [61]. On the other hand, Edmunds and co-workers described a ring-opening reaction of C1-substituted OBDs 5 with arylboronic acids that was

• to react. Alternative bases (Table 1, entries 7–10) were tested; however, the reaction produced isomerized naphthol derivative 17 rather than the predicted addition product. These results indicate the formation of a phenoxoiridium(I) species assists in the oxidative addition of the C–H bond, as

• enyliridium(III) alkoxide complex which eventually leads to the formation of isomerized 1-naphthol products [61]. Interestingly, the loading of the iridium precatalyst (Table 1, entries 11–13) also had a substantial effect on the isomerization of 13b, with increased loading producing more byproduct. Other

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• milling (Figure 1b and Figure S5 in Supporting Information File 1). Other substrates such as naphthalene and N-Boc-aniline proved unreactive under the milling conditions with NFSI. However, the more activated arene 2-naphthol underwent double fluorination affording 1,1-difluoronaphthalen-2(1H)-one as the