Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• macrocycles. The formation of (29b)2-Hg was reversible – its reaction with [2.2.2]cryptand resulted in the removal of mercury(II) and the contraction to 29b. Recently, Sessler and co-workers synthesised a new macrocycle 36 exploiting a pyridine-bridged dipyrroledialdehyde 35 (Scheme 10) [131]. The compound

• also demonstrated the crowned fused expanded porphyrinoids incorporating a pyridine moiety [135]. Macrocycles 45 were obtained in 5–10% yield from the condensation of 38 with the corresponding pyridine-based dipyrromethane analogue. Compound 45 exhibited a unique structural arrangement, with the

• pyridine ring and two thiophenes inverted and fused with two pyrrole nitrogen atoms. The macrocycles exhibited facile oxidations, indicating their electron-rich nature, and demonstrated selective sensing of Cu2+ ions. Conclusion and Outlook The construction of new macrocycles has been a driving force for

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• residue was added a solution of ʟ-cysteine methyl ester hydrochloride (2 mg) in pyridine (200 μL), and the mixture was stirred at 65 °C for 1 h. Then, a solution of o-tolyl isothiocyanate (2.2 μL) in pyridine (200 μL) was added and the resulting mixture was stirred at 65 °C for 1 h. The final mixture was

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

• 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

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

• short times and required low catalyst loadings and a single product was obtained in each case. Furthermore, the cycloaddition with an internal alkyne could also be achieved using these catalysts. Interestingly, the catalysts were found effective in the cycloaddition of 2-(prop-1-yn-1-yl)pyridine with

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• challenging, and to the best of our knowledge, only Kawase's group [26] reported the preparation of such compounds starting from α-hydroxy acids or α-amino acids in the presence of trifluoroacetic anhydride and pyridine with very limited substrate scope (Scheme 1c). Therefore, the development of a more

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• oleyl chain. Accordingly, the primary alcohol was protected with p-methoxydiphenylmethyl (MeO-trityl) in pyridine and then, esterified in sn-2 position with benzoyl chloride to produce 9.4. The deprotection of the primary alcohol under acidic conditions gave 9.5. The polar head group was installed by

• protection was not regioselective (a mixture of primary and secondary protected alcohols was formed). The acylation of the secondary alcohol was then achieved with acetic anhydride in the presence of pyridine. Then, the deprotection of the trityl moiety of compound 12.4 by catalytic hydrogenation failed

• pyridine. A stereocontrolled synthesis of 26.4 was reported by Hajdu and Bhatia in 1988. The sequence starts from 27.1 that was prepared from ʟ-glyceric acid (Figure 27) [118]. Then, the free alcohol was converted as an efficient leaving group by reaction with 4-nitrobenzenesulfonyl chloride in the

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• ether α-C–H bond. In the presence of Cu(II), the C(sp2)–C(sp3) coupling of pyridine N-oxides and coumarins with cyclic ethers could be achieved under mild conditions (Scheme 13) [63][64]. These reactions do not all follow the reaction mechanism of the oxidative olefination of simple ethers. The role of

• chemoselective and regioselective CDC between pyridines and ethers, which used Sc(OTf)3 as the catalyst and DTBP as the oxidant (Scheme 36) [101]. This strategy allowed the synthesis of a series of α-substituted pyridine derivatives. The control experiments showed that the mechanism may proceed via a radical

• pathway. Initially, a tert-butoxyl radical is generated by thermal decomposition. Then, the tert-butoxyl radical extracts an α-hydrogen atom from tetrahydrofuran to form tetrahydrofuran radical A. Sc(OTf)3 as a Lewis acid activates pyridine forming the pyridine complex B. Then, radical A adds to the more

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

• pyridine was in fact interacting with the LUMO+1 MO of I-7, corresponding to the σ* orbital oriented along the I–C bond axis [87]. Lüthi et al. quantified the symmetry-adapted perturbation theory (SAPT) interaction energies of halogen bonded acetonitrile complexes of HVI molecules [72], and Huber et al

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• when irradiated with UV light. Keywords: 5-aminopyrazole; azlactone; elimination; fluorescence; one-pot synthesis; pyrazolo[3,4-b]pyridin-6-one; Introduction The pyrazolo[3,4-b]pyridine scaffold is present in many biologically active compounds [1][2][3][4][5][6][7][8][9][10][11][12]. Among them, 4

• formation of the target products with low yields [21]. Therefore, the development of a new effective method for the preparation of 4-arylpyrazolo[3,4-b]pyridin-6-ones is an urgent task. Results and Discussion One of the rational approaches to the synthesis of fused pyridine derivatives is based on the

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• ]pyridines represent an important class of heterocyclic compounds, which skeleton is the key frame of many bioactive and natural compounds. For example, tetrahydrofuro[3,2-c]pyridine A demonstrates excellent in vitro JAK2 inhibitory activity superior to tofacitinib (Figure 1) [1]. Furan B is a potent κ

• relatively selective α2-adrenoceptor antagonist [5]. Despite the simplicity of the tetrahydrofuro[3,2-c]pyridine core, only limited approaches for the synthesis of this subclass of heterocycles using furan derivatives as starting compounds have been described [6][7][8]. The first group of methods is based on

• delight, when 2 equiv of HCl were subsequently added to the solution of imine 3a at 50 °C, the formation of the desired 2-methyl-4-phenyl-4,5,6,7-tetrahydrofuro[3,2-c]pyridine (4a) was observed in 26% yield (Table 1, entry 1). It should be noted that most part of the product 4a was formed as the

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• ]. The well-known Huisgen 1,4-dipoles have a special kind of zwitterionic intermediates and are usually prepared by a nucleophilic addition of pyridine, quinoline, isoquinoline and other aza-arenes to electron-deficient alkynes [4][5][6][7][8]. The reactive Huisgen 1,4-dipoles have been widely employed

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

• , the authors were able to obtain X-ray crystallographic data of the pyridine–catalyst complex which showed two intramolecular H-bonding interactions in the molecular framework of the catalyst where two free OH groups were engaged in interactions with the pyridine. This data clearly indicates the

A fluorescent probe for detection of Hg²⁺ ions constructed by tetramethyl cucurbit[6]uril and 1,2-bis(4-pyridyl)ethene

• Xiaoqian Chen,
• Naqin Yang,
• Yue Ma,
• Xinan Yang and
• Peihua Ma

Beilstein J. Org. Chem. 2023, 19, 864–872, doi:10.3762/bjoc.19.63

• , which provides convenience for studying the host–guest chemistry of TMeQ[6] and constructing fluorescent probes in aqueous solution [37][38]. There is a π–π conjugation effect between the carbon–carbon double bond and the pyridine ring in 1,2-bis(4-pyridyl)ethene (G), which determines its ultraviolet

• absorption [39]. Because the N atom on the pyridine ring of the G molecule has lone-pair electrons, it can form coordination compounds with metal ions. At present, the host–guest fluorescent probes designed by G and Q[n]s have been rarely reported. Therefore, we constructed the host–guest fluorescent probes

• at a wavelength of 350 nm. With the continuous addition of TMeQ[6], the fluorescence intensity of G is continuously enhanced, and the wavelength is redshifted to 391 nm, indicating that TMeQ[6] interacts with the guest molecule G. The TMeQ[6] cavity may limit the rotation of the pyridine ring on the

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• , National Institute of Pharmaceutical Education and Research - Ahmedabad, Gandhinagar, Gujarat, 382355, India 10.3762/bjoc.19.62 Abstract Pyridine is a crucial heterocyclic scaffold that is widely found in organic chemistry, medicines, natural products, and functional materials. In spite of the discovery

• of several methods for the synthesis of functionalized pyridines or their integration into an organic molecule, new methodologies for the direct functionalization of pyridine scaffolds have been developed during the past two decades. In addition, transition-metal-catalyzed C–H functionalization and

• rare earth metal-catalyzed reactions have flourished over the past two decades in the development of functionalized organic molecules of concern. In this review, we discuss recent achievements in the transition-metal and rare earth metal-catalyzed C–H bond functionalization of pyridine and look into

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• 70–95%). The presence of a base and the type of solvent seems to be an important factor for the reaction course. In toluene, ionic liquid or in refluxing ethanol without a base [16][19][20] or in the presence of weakly basic pyridine [17][18][21] (pKa = 5.23 in water, 3.4 in DMSO, 3.3 in DMF, and

• commercially available benzonitriles [39] or by thionation of the corresponding N-substituted amides [40] using pyridine–P4S10 as sulfurization agent. Other chemicals and solvents were purchased from Acros Organics, Sigma-Aldrich, and Fluorochem and were used as received. 1H and 13C (APT) NMR spectra were

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• synthesis of synthetically useful N-arylsulfonylimines from N-(arylsulfonyl)benzylamines using K2S2O8 in the presence of pyridine as a base is reported herein. In addition, a “one-pot” tandem synthesis of pharmaceutically relevant N-heterocycles by the reaction of N-arylsulfonylimines, generated in situ

• using K2S2O8 in the presence of pyridine as a base. The key findings include a) requirement of a mild base for the formation N-arylsulfonylimines, and b) stability of N-arylsulfonylimines, unlike N-arylimines, under the oxidative conditions. Further, to demonstrate the scope and applicability of this

• previous study [14]. Unfortunately, no product formation was observed under these conditions, while substrate 1a remained unreacted (Table 1, entry 1). When the solvent was changed to H2O, a trace quantity of product formation was observed (Table 1, entry 2). To our surprise, when 2 equiv of pyridine were

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• Pd(OAc)2 did not dissolve in toluene even with pyridine. As a substitute for TEMPO, 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) was tried (Table 1, entries 9 and 10) [45]. Although the reactivity was improved compared with the TEMPO catalytic system in Table 1, entries 3–5, the DDQ catalytic system

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• , Zaporizhzhya National University, Zhukovsky str., 66, Zaporizhzhya, 69600, Ukraine 10.3762/bjoc.19.53 Abstract Peptidomimetics with a substituted imidazo[1,2-a]pyridine fragment were synthesized by a tandem of Groebke–Blackburn–Bienaymé and Ugi reactions. The target products contain substituted imidazo[1,2-a

• ]pyridine and peptidomimetic moieties as pharmacophores with four diversity points introduced from readily available starting materials, including scaffold diversity. A small focused compound library of 20 Ugi products was prepared and screened for antibacterial activity. Keywords: Groebke–Blackburn

• –Bienaymé reaction; imidazo[1,2-a]pyridine; isocyanide; multicomponent reaction; peptidomimetic; Ugi reaction; Introduction The use of isocyanide multicomponent reactions (IMCR) to prepare biologically active compounds is one of the most promising tools in modern organic and medicinal chemistry. Therefore

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• triple role as activator of IPs, halide scavenger, and acetylating agent. Results and Discussion Optimization In the quest for the optimal reaction conditions, we started our investigations with 2-phenylimidazo[1,2-a]pyridine (1a) and diethyl bromomalonate (2a) as model substrates. Initially, the

• diverse electronic properties were present in the pyridine ring of the IP moieties (4l–q). With substrates having a methyl substitution at C-7 and C-8 of the pyridine ring, the yields and regioselectivity were still excellent (4l and 4m), but reduced significantly upon introducing a halogen group onto the

• pyridine ring. Except for the 6-bromo-substituted compound (4o), all other substrates having a halogen substituent in the pyridine ring showed reduced yields (4n, and 4p,q). The number of substituents also seemed to negatively affect the yield, as observed for products 4p and 4q, featuring two substituents

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

• (phosphite/phosphine-pyridine amide, phosphine-sulfoxide, phosphoramidite, MINBOL, see Figure 1) and they usually showed excellent diastereoselectivity (dr >20:1). The catalytic systems even with low catalyst loadings tolerated both electron-donating and withdrawing groups on the aromatic substituents

• functional group tolerance with excellent stereoselectivities. In 2016, Ellman and co-workers demonstrated a Rh- or Co-catalyzed highly diastereoselective tandem C–H bond addition/aldol reaction sequence [96][97]. The C–H activation was promoted by pyridine, pyrazole, or imine directing groups, while the

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

• -catalyzed [3 + 2] annulation/ring-opening/dehydration domino reaction of oxabicyclic alkenes 30 with 2-(1-methylhydrazinyl)pyridine (MHP) directed arenes 87 for the synthesis of benzo[b]fluorenones 88 (Scheme 16) [52]. C–H bond functionalization with heterobicyclic alkenes as annulation partners has

• C–H activation as well as its involvement in the dehydration process. This reaction proceeded smoothly with a variety of both EWGs and EDGs on the 2-phenylpyridine. Interestingly, when swapping the pyridine directing group for thiophene or furan, yields were improved although quinolinyl and

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• , up to 91% yield) [119]. 2-Arylpyridine derivatives bearing electron-donating groups, electron-withdrawing groups or halogen at the para- and meta-positions of the aromatic ring were readily functionalized (11a–g, 58–85% yields). Also 2-(2-methoxyphenyl)pyridine (11h) and 2-(2-naphthyl)pyridine (11i

• methyl, methoxy or methylthio groups (17b–d) or by halogen (17e) was achieved (Scheme 8, up to 77% yield). Note that in case of disubstituted 2-(4-ethoxy-3-fluorophenyl)pyridine (17h), the expected product 18h was isolated in 31% yield. Moreover, selective oxidation of the SCF3 residue into the

• derivatives using AgSCF3 (Scheme 11) [124]. This methodology allowed the functionalization of several aromatic compounds bearing a pyridine or a pyrimidine as a directing group (20 examples, up to 65% yield). The reaction proceeded smoothly with substrates bearing an electron-donating group (25b,c), halogen

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• potassium carbonate or methylcopper in pyridine led to compound 116 in only 10% yield. The cleavage of the benzyl ether proved to be complicated, as TFA also opened the lactone at the ester group (Scheme 24) [55]. In an attempt to circumvent these problems, the authors chose to use isovanillin (80) as

• macrocyclization using SO3·pyridine [68] gave the corresponding thioether 151, which was oxidized to the cyclic sulfone 152 using m-CPBA. Extrusion of SO2 by FVP followed by demethylation of the formed macrolide furnished the compound 154 which can be converted in combretastatin D-1 (1) by known methodologies [43

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

• hydroboration of imines [87][92][97], nitriles [92][98][99][100][101], carbodiimides [92][100][102], pyridine [92], and isocyanides [92] with HBpin (Scheme 23). These generally follow a similar proposed catalytic cycle; aluminium-mediated reduction, followed by Al‒N/B‒H exchange with HBpin (Scheme 23). The

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• easier process than the optimization of a new monosubstitution reaction on a native CD [5]. Monotosylation of the primary rim of CDs is the most widely used method to obtain C-6 monofunctionalized CDs. Tosyl chloride (TsCl) reacts with α-, β-, and γ-CD in pyridine to give the C-6-monosubstituted product

• in about 30% yield (for β-CD) [6][7]. The C-6 regioselectivity can be attributed to the inclusion of pyridine into the CD cavity in such a way that it activates only the hydroxy groups on the primary side. Several alternative methods have been developed with the aim of further improving the yield of

• monotosylation or replacing pyridine with a more user-friendly solvent [8]. Regardless of which strategy is used, the complete conversion of the starting material into the monosubstituted product does not occur, and a mixture of overtosylated products and unreacted starting CD is formed. The target