HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• activities. The most direct way of obtaining this nucleus is the Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR) between aminopyridines, aldehydes, and isocyanides under both Lewis and Brønsted acid catalysis. However, several catalysts for this reaction have major drawbacks such as being

• conditions and the employment of relatively complex starting materials [19]. A more efficient way of obtaining this nucleus is through the Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR) between amidines (aminoazoles), aldehydes, and isocyanides under both Lewis and Brønsted acid catalysis [20

• ][21][22]. Multicomponent reactions (MCRs) provide one-pot reactions, simple synthetic procedures, less waste being produced, fewer purification steps, and a high atom economy [23]. The GBB three-component reaction is carried out in the presence of Lewis or Brønsted acid catalysis to increase the

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• tackle catalyst stability by changing the chloride scavenger [23] or adding other coordinating moieties [24][25]. Hartwig et al. have argued that a Brønsted acid generated in situ from metal triflates may be the “real” catalyst promoting some alkene functionalizations [26]. Therefore, the possibility of

• competing Brønsted acid catalysis in gold-catalyzed alkene functionalization remains a consideration [2], and while it is assumed that alkene activations follow the same prototypical mechanisms as allene and alkyne activations, that is (1) π-activation with nucleophilic attack followed by (2

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• . With this mechanistic blueprint as a backdrop, Phipps and co-workers developed an enantioselective Minisci-type addition, under dual photoredox and chiral Brønsted acid catalysis [44] (Scheme 5A). In their proposed mechanism, the activation of the NHPI ester radical precursor was proposed to occur via

• oxidative quenching photocatalytic cycle employing Ir-based photoreductants and a Brønsted acid additive. While the interaction between the RAE 32 and diphenyl phosphoric acid involves hydrogen bonding, in analogy to the Glorius proposal, it is thought that the substrate activation occurs through proton

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• excellent yield and enantioselectivity. Keywords: asymmetric organocatalysis; chiral Brønsted acid; 3,3-difluoroindoline; Hantzsch ester; transfer hydrogenation; Introduction The introduction of fluoro atoms into organic molecules can alter their lipophilicity, solubility, metabolic stability, and

• organocatalysis using chiral phosphoric acids has also been studied (Scheme 1b) [26][27][28]. In 2010, Magnus Rueping and his co-workers developped an enantioselective Brønsted acid-catalyzed transfer hydrogenation of 3H-indoles [29]. In 2020, Song and Yu successfully applied a new chiral Brønsted acid

• mechanism of the CPA-catalyzed transfer hydrogenation reaction was proposed (Figure 2). The activation of 3,3-difluoro-substituted 3H-indole 1 by protonation through the Brønsted acid generates the iminium A. Subsequent hydrogen transfer from the Hantzsch ester gives the chiral amine 2 and pyridinium salt B

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• examples of the hydration reaction of alkynes carried out in ILs. In one case, a dicationic IL, containing sulfuric acid as catalyst, was used as reaction medium to carry out the hydration of different alkynes under mild conditions (40–60 °C, 0.5–1 h) [84]. In a second case, different Brønsted acid ionic

• pseudobenzylic position, as observed in Lewis acid-assisted Brønsted acid (LBA) catalysis [47][48][49][50]. Internal alkynes afforded the corresponding products in good to excellent yields (Table 4, entries 1–3). In particular, the unsymmetrical alkyl(aryl)alkynes 1b and 1c showed a higher reactivity compared to

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• presence of Brønsted acid. In their pioneering research, Tanaka et al. reported the [3 + 2] cycloaddition reactions of trifluoroacetaldehyde hydrazones and glyoxals to give 4-hydroxy-3-trifluoromethylpyrazoles. The resultant pyrazoles containing a free 4-hydroxy group were easily converted to a variety of

• conditions [38] (Scheme 2). Moreover, a chiral Brønsted acid-catalyzed asymmetric 6π electrocyclization of trifluoroacetaldehyde hydrazones for the synthesis of enantiomerically enriched 3-trifluoromethyl-1,4-dihydropyridazines was first developed by Rueping et al. [39]. The strategy involves chiral ion

• pairs and provides a good basis and scope for further extensions and explorations [39] (Scheme 3). Based on the work by Wu et al. and extending their previous work, Rueping and co-workers explored the effects of fluorine in organocatalytic reactions. They developed an asymmetric Brønsted acid–Lewis base

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• and acetic acid (AcOH) as a Brønsted acid, whereas i(a)midation was achieved by using Pd(OAc)2 as catalyst and Cu(OAc)2 as a Lewis acid. A possible mechanism for this chemodivergent C–H activation is depicted in Scheme 16. First, Pd catalyzed the formation of palladacycle I. Oxidative addition of AcOH

• acid organocatalysts were evaluated for sulfenylation on C3, or C2 position of N-heterocycles 115, including indoles, peptides, pyrrole, and 1-methyl-1H-pyrrolo[2,3-b]pyridine. The authors hypothesized a mechanism for the activation of N-sulfanylsuccinimides 1 or 14 by conjugate Lewis base Brønsted

• formation of three-membered cyclic sulfonium ion II followed by ring-opening of sulfonium ion and intramolecular cyclization. The use of a Lewis base/Brønsted acid catalysis system for the sulfenylation of aromatic substrates 4 was reported by Gustafson et al. (Scheme 55) [87]. In the method, catalyst P

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

• pyrroles/indoles 4/9 allowing access to 2,3-dihydroisoxazoles 77/78 bearing an all-substituted stereocenter at the C3 position. A dual catalytic activity of the Brønsted acid catalyst was illustrated by the authors which was initiated with a smooth protonation of the OH group in 76 with a subsequnte

• Brønsted acid to generate (N-acyl)(propargyl)imine 90 as intermediate which added to the deprotonated phosphoric acid to form phosphate ester 91 as the next intermediate through an equilibrium process. Then, 1,2-addition by the C3 position of the heteroarene ring to the acylimine intermediate afforded the

• Brønsted acid catalyst to execute a straightforward aza-Friedel–Crafts reaction between 3-substituted indoles 4 and N-sulfonyl-substituted aldimines 128. The reaction successfully installed an aza-tertiary stereocenter at the C2 position of the heterocyclic ring. A broad substrate scope was investigated by

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• -dialkoxytetrahydrofuran. This reaction was originally discovered by N. Clauson–Kaas and Z. Tyle in 1952 [37] (Scheme 2a). Initially, acetic acid was used as a catalyst in this classic reaction; however, diverse modifications have been reported for this procedure using various Brønsted acid catalysts, metal catalysts, and

• work-up of intermediate H (Scheme 2b). Review Conventional method for the Clauson–Kaas synthesis of N-substituted pyrroles This section describes Clauson–Kaas pyrrole syntheses using traditional methods, such as Brønsted acid or Lewis acid-catalyzed reactions in various organic solvents at higher

• Clauson–Kaas reaction in a successive cyclization/annulation process from commercially available sulfonamides 14 in the presence of trifluomethanesulfonic acid (TfOH) as Brønsted-acid catalyst. This procedure produces only N-substituted products and preserves other positions open for further

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• and co-workers demonstrated for transannular Diels–Alder cycloaddition reactions of symmetrically tethered large systems (10–18-membered rings) [29]. In this context, we have recently reported the transannular enantioselective (3 + 2) cycloaddition of cycloalkenone hydrazones under Brønsted acid

• alkenes under chiral BINOL-derived Brønsted acid catalysis has been studied by Houk and Rueping in 2014 [33]. These authors established the origin of the enantioselectivity and the differences between the catalyzed and uncatalyzed reactions, suggesting that the catalyzed reaction is, actually, a so-called

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• very poor results with dihydrodithiinmethanol, with incomplete conversion to complex mixtures of diverse addition products. However, we found that the reactions of allyl alcohol 90 with indoles become very reliable and quite general when a large excess of a very strong Brønsted acid is used (Scheme 15a

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• , we improved the formation of iodoarenes through a Brønsted acid-mediated Friedel–Crafts reaction followed by an oxidative cyclization to form the desired CDIS 1 (Scheme 1A). This one-pot approach is based on ortho-iodinated benzyl alcohols as starting materials. It allows access to a variety of

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• in oxidative processes for the activation of electrophilic properties of unsaturated substrates or for the activation of hydroperoxide oxidative properties. In Scheme 4A the proposed transition state for the Brønsted acid-catalyzed asymmetric Baeyer–Villiger reaction is shown, in which the

• organocatalyst forms hydrogen bonds with both H2O2 and cyclic ketones [66]. A chiral Brønsted acid was used as chirality source and activator of H2O2 for an asymmetric sulfoxidation reaction [67] (Scheme 4B). It is generally accepted that in asymmetric Brønsted acid catalysis the activation of both the

• ethanol). Brønsted acid catalysis by TsOH was also employed in a selective sulfoxidation employing PhI(OAc)2 as oxidant [69]. In this case another mode of catalysis was proposed, including the covalent bonding of the acid catalyst anion and the oxidant with the formation of PhI(OTs)OH as the catalytically

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• capsule can catalyze the cyclization of (S)-citronellal forming isopulegol. In this study it was exploited the ability of the resorcinarene capsule to work as a Brønsted acid catalyst, and its aptitude to stabilize cationic intermediates and transition states inside the cavity. Velmurugan, Hu and co

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• intramolecular aldol addition of ketones such as 7 (Scheme 2) [5]. Brønsted-acid catalysis leads via a transition state 8 to the aldol 9, while the use of chelating Lewis acids results via 10 in the epimeric aldol 11. This review is a collection of total syntheses of natural products where vicinal keto esters

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

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

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• in the literature. While pondering possible solutions to fill this void, we drew inspiration in our recent success achieving direct Brønsted acid-catalyzed C-arylation of 4-diazo-isoquinoline-1,3-diones 7 [9] which are, in turn, obtainable via the Regitz diazo transfer reaction onto readily available

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• reported, by using a metal catalyst or Brønsted-acid catalysis [79][80][81]. However, the efficient regio- and stereoselective installation of the endoperoxide structure is still challenging, because of the increased reactivity of activated oxygen/peroxides and the high sensitivity of peroxide bridges to

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• and 4). The reaction promoted by acetic acid (4) as purely Brønsted acid led to comparable conversion of the substrate with respect to the use of 16, albeit with much similar product distribution between isopulegol and neoisopulegol, even extending the reaction time up to 72 h at 60 °C (Table 1

• Brønsted acid and the presence of the accessible cavity of the capsule steers product distribution. It is worth to note that the preferred product isopulegol is an important intermediate product in the industrial production of menthol by the Takasago and BASF processes [46][47]. Many catalytic methods for

• of the substrate. The reaction was repeated with 2 as a hydrogen bonding unit and with acetic acid (4) as a comparable Brønsted acid observing in both cases that the formation of 1,1-diphenylethylene was negligible (Figure 2E and F, Table 2, entries 3 and 4). Further control experiments with the

A Se···O bonding catalysis approach to the synthesis of calix[4]pyrroles

• Qingzhe Tong,
• Zhiguo Zhao and
• Yao Wang

Beilstein J. Org. Chem. 2022, 18, 325–330, doi:10.3762/bjoc.18.36

• , several synthetic methods to access these compounds have been reported [54][55]. The classical approaches to synthesis of calix[4]pyrrole derivatives mainly involved a stepwise synthesis and Lewis acid as well as Brønsted acid catalysis [54][55]. Notably, a noncovalent catalysis approach to accessing

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• type of Brønsted acid catalyst that expanded the range of available acidities as well as molecular arrangements in acid-catalyzed reactions. Veselý and co-workers demonstrated that these catalysts are effective in the enantioselective aminalization of aldehydes with anthranilamides [24]. To explore new

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• halogenoketones or ketocarboxylic acids upon action of SnCl2·H2O, TiCl4/Zn, or Fe/CH3COOH can be mentioned [28][29][30]. 1-Aryl-substituted tetrahydropyrrolo[1,2-a]quinazolin-5-ones can be also obtained by a Brønsted acid-catalyzed annulation of arylcyclopropane aldehydes and N′-anthranilic hydrazides [31], as

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• hydrazoic acid and the formation of lactam, which often prevails, especially when hydrazoic acid is generated in situ by the action of Brønsted acid on sodium azide [25]. The use of trimethylsilyl azide (TMSN3) instead of hydrazoic acid for many transformations has gained attention since TMSN3 is less

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• , ring strain, or α-carbonyl group), α-iminols are typically less stable than their α-amino ketone products. In the presence of a Brønsted acid, protonation of the amine product can be used to drive the rearrangement to completion. Thus, favorable yields and stereoselectivities can be realized by first

• equivalent of aniline in the presence of a Brønsted acid undergoes a multistep rearrangement to form the indole group as part of the target tryptamine 110 (Figure 20). The one-pot conversions occurred successfully over a wide range of monosubstituted anilines, including various para-alkyl groups (65–72

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• stereogenic carbon center with good enantioselectivity (ee up to 80%) and excellent yields (up to 97%). Keywords: aminalization; Brønsted acid; organocatalysis; PCCP; pentacarboxycyclopentadiene; Introduction Nitrogen-containing heterocyclic compounds are commonly occurring in nature and constitute the core

• chiral Brønsted acids. In the scope of Brønsted acid catalysis, chiral phosphoric acids (CPA) are dominating as potent catalysts in various asymmetric transformations [19][20][21][22][23], although the synthesis of these catalysts is expensive and laborious [24]. One of the most frequent examples of CPAs

• chiral phosphoric acids, PCCPs offer less laborious and inexpensive preparation protocols [31][32], which makes them an interesting alternative for chiral Brønsted acid-catalyzed transformations [30][31][32][33][34][35]. Results and Discussion Herein, we describe our findings regarding the aminalization