Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• NMR spectra. The solubility issues forced us to investigate also other modification protocols. Thus, macrocycle 11 was subjected to an ozonolysis with subsequent Wittig reaction in a one-pot manner (Scheme 4). Performing the ozonolysis in presence of pyridine led to immediate reduction of the primary

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• -methyltetrahydrofuran following a chemoenzymatic pathway. Whereas, the protection of the primary hydroxy over the lone secondary hydroxy group in the key azido sugar precursor was achieved using bulky tert-butyldiphenylsilyl chloride (TBDPS-Cl) in pyridine in 92% yield following a chemical synthetic pathway. The

• pyridine to afford dimesylated nucleosides 16a,b in 93 and 94% yields, respectively. The reaction of nucleosides 16a,b with NaOH in dioxane/water (1:1) underwent a cascade reaction pathway to form 9a,b in 82 and 84% yields, respectively (Scheme 4). The overall yields for the synthesis of nucleosides 9a,b

• regioselective protection of the primary hydroxy group of diol 17 using TBDPS-Cl in pyridine at room temperature afforded TBDPS-protected furanoside 18, which on acetolysis using AcOH/Ac2O/H2SO4 (100:10:0.1) afforded the anomeric mixture of coupling sugar 19a,b in 80% yield. The Vorbrüggen coupling [29] of

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• HCl(g) in MeOH (Scheme 1). N-Boc protection of cis-amino ester 3 with (Boc)2O in pyridine and 4-(dimethylamino)pyridine (DMAP) gave N-Boc-amino ester 4 (yield 95%). The 1H and 13C NMR spectroscopic data of 4 were in agreement with the proposed structure. Treatment of 4 with OsO4/NMO gave the expected

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• and reported that they were unable to obtain 4-arylamino-1,2-naphthoquinones from β-NQSNa but that these derivatives can be readily prepared from 4-ethoxy-1,2-naphthoquinone. Similarly, Yano and co-workers [72] studied the tautomeric equilibrium of 4-arylamino-1,2-naphthoquinones in DMSO-d6, pyridine

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• desired epoxide 5 in an acceptable 70% yield with excellent stereoselectivity as the sole syn isomer (dr > 95:5). It is worth noting that a small quantity of pyridine was added to prevent unwanted acid-catalyzed epoxide hydrolysis [31]. The stereochemistry of 5 was assigned later after pyrrolidine ring

• %; (c) 12WO3·H3PO4×H2O, H2O2 (35 wt % in H2O), pyridine, ethyl acetate, rt, 48 h, 70%; (d) BF3·OEt2, CH2Cl2, 0 °C, 15 min, 69%; (e) H2 (1 atm), Pd(OH)2/C (5 wt %), MeOH, rt, 2 h, (±)-2, 71%; (f) H2 (1 atm), Pd(OH)2/C (5 wt %), MeOH, rt, 2 h; then formaldehyde (37 wt % in H2O), H2 (1 atm), Pd(OH)2/C (5

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• provided the corresponding carboxylic acid, and further oxidative decarboxylation with lead tetraacetate and pyridine provided oxathiolane 20. Chu and co-workers [41][42] further established a more proficient system for the synthesis of (+)-BCH-189 (1a) from 1,6-thioanhydro-ᴅ-galactose (3d, Scheme 4

• reaction of benzoyl chloride in pyridine to protect the hydroxy group, which results in a high yield. The isopropylidene group was selectively deprotected using 10% HCl, followed by oxidative breakage of the carbon–carbon bond of the resulting diol using sodium periodate. Further reduction of the aldehyde

• afforded the thiol compound 3nb. Further treatment of the thiol 3nb with methyl glyoxylate in dichloromethane solvent along with molecular sieves (4 Å), followed by in situ acetylation using Ac2O, pyridine, and catalytic 4-(N,N-dimethylamino)pyridine (DMAP) provided compound 37. The second route involves

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

• obtained via TBHP-mediated cyclization of 23 and subsequent TBS-deprotection of intermediate 24 with pyridine and HF·pyridine complex [66] in a total yield of 26% over the two steps. The longest linear sequence was 7 steps, with an overall yield of 5%. Finally, the reaction mechanism of the oxidative

• , imidazole, DMF, 50 °C, 18 h; f) LAH, AlCl3, THF, rt, 12 h; g) TBHPaq, DCE, 100 °C, 18 h; h) pyridine, HF·pyridine, EtOAc, rt, 14 h. Proposed mechanism for the oxidative cyclization of amines 2a and 2b to fluorenone (3). Reactivity of different functional groups towards TBHP-mediated cyclization to give

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• compounds with heterocyclic substituents are of high biological and medicinal relevance [34][35]. Therefore, we have decided to evaluate sulfinylurea and thiourea catalysts C1 and C2 also with (E)-2-(2-nitrovinyl)furan (9) and (E)-3-(2-nitrovinyl)pyridine (11) as Michael acceptors. As Michael donor, we

• ). The aliphatic aldehydes propanal (6d) and hexanal (6b) provided medium yields and diastereoselectivity and enantioselectivity. The Michael addition of 3-phenylpropanal (6c) to (E)-3-(2-nitrovinyl)pyridine (11) required long reaction times (120 h) in solution, similar to those for the reaction with (E

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

• acid, reflux, 12 h (74% for 4; 69% for 8); d) SeO2, acetic acid, microwave irradiation, 150 °C, 15 min (74% for 4; 67% for 8); and e) Ac2O, benzene/pyridine, rt, 24 h (74%). Synthesis of 7-oxo intermediate 11 from chenodeoxycholic acid (9). Reagents and conditions: a) EtOAc, pTsOH, reflux, 12 h (66

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

• conversion of 3 into the cyclohexanone product 4 (Figure 2) [4]. The best results were obtained with 2-[4-(S)-tert-butyloxazolin-2-yl]pyridine ((S)-5), which gave >90% yield of (S)-4 in 46% ee. In a similar investigation except with copper(II) as the metal and β-hydroxy-α-diketone 6 as the substrate, the

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• ; Morita–Baylis–Hillman carbonates; Introduction Pyridines are among the most important heterocyclic structural moieties in many biologically active natural products, pharmaceuticals, and agrochemicals [1][2][3]. Therefore, the development of efficient strategies for functionalized pyridine derivatives

• synergistic catalyzed allylic alkylation between electron-deficient 2-ethyl benzoxazoles and MBH carbonates by the combination of a Lewis base and a metal salt [24]. In their studies, although pyridine derivatives were also applicable in the reaction, the presence of a strong electron-withdrawing NO2 group

• the scope of various 2-alkypyridines to react with MBH carbonate 2a under the standard conditions and the results are shown in Scheme 4. Alkyl substituents at the 3 or 5-positions of pyridine were tolerated, giving the desired products in moderate to good yields (4b and 4c, 83% and 71% yield

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• in 2020, an enantioselective C–H annulation of ferrocenylformamides with alkynes was achieved by the Ye group enabled by Ni-Al bimetallic catalysis and a chiral secondary phosphine oxide (SPO) ligand [35]. Hou et al. also reported the asymmetric C−H alkenylation of quinoline- and pyridine-substituted

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• structural motifs to provide the functionalized pyridine and pyrrole derivatives. The functionalization reactions cover iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, alkylation, selenylation, sulfenylation, amidation, esterification, and hydroxylation. We also briefly

• introduce the applications of the products and the reaction mechanisms for the synthesis of corresponding N-heterocycles. Keywords: 1,3-enyne; functionalization; pyridine; pyrrole; tandem annulation; Introduction The pyridine moiety is an important class of six-membered N-heterocycles that is widely found

• in many natural products, pharmaceuticals, and bioactive molecules. For instance, some pyridine derivatives have been used for therapy of HIV, cancer, inflammation, microbial infection and so on [1][2][3][4][5]. In addition, it is also an important synthetic unit, which is frequently used as catalyst

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• analogues of metronidazole Compound 1 reacted with different acid chlorides (6a–e) in the presence of pyridine, a catalytic amount of DMAP and in dry DCM at room temperature. The reaction proceeded smoothly to give the desired metronidazole carboxylate derivatives 7a–e in 86–93% yields [21][22]. The

• compounds 5a–i and 7a–e. Reagents and conditions: (a) TsCl, Et3N, dry DCM, DMAP, 0 °C to room temperature, 5 h, 96%; (b) NaN3, DMF, 70 °C, 3 h, 88%; (c) alkyne derivative (4a–i), CuI, Et3N, CH3CN, room temperature, 3 h, (5a–i) 85–94%. Reagents and conditions: (a) acid chlorides 6a–e, pyridine, dry DCM, DMAP

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• 90 °C. The hydrolysate was extracted with EtOAc and the aqueous layer was neutralized by passing it through an Amberlite IRA-67 column to give the sugar. The sugar obtained from the hydrolysis was dissolved in anhydrous pyridine (0.5 mL) followed by adding of ʟ-cysteine methyl ester hydrochloride

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• -bis(trimethylsilyl)acetamide [34], simultaneous tritylation of N9 and the N2 atoms was achieved using 4,4'-dimethoxytrityl chloride in pyridine. The obtained derivative 4 was amenable to nitrile reduction using diisobutylaluminium hydride (DIBAL-H) in dichloromethane at −78 °C, followed by workup with

• (820 µL, 3.33 mmol) was added dropwise and the reaction mixture was stirred for three hours at room temperature upon which a solution was obtained. Afterwards, the volatile components were removed under reduced pressure and the residue was coevaporated three times with toluene and twice with pyridine

• . The residue was dissolved in pyridine (3.8 mL) and 4,4'-dimethoxytrityl chloride (1.18 g, 3.50 mmol) was added in portions. The solution was stirred for 18 h at 40 °C, subsequently poured into 5% aqueous sodium bicarbonate solution and the suspension was extracted three times with dichloromethane. The

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• )pyrimidine-pyridine (PAPP) group as a pharmacophoric fragment, and these compounds were biologically evaluated. The synthesis of twelve new compounds was performed in three steps and assisted by microwave irradiation in a 1,3-dipolar cycloaddition to obtain 1,2,3-triazole derivatives substituted on carbon C

• in the docking studies. Keywords: chronic myeloid leukemia; 1,3-dipolar cycloaddition; imatinib; (phenylamino)pyrimidine-pyridine; 1,2,3-triazole; Introduction Changes in tyrosine kinase proteins (TKPs), either by mutation or chromosomal translocation, can turn them into potent oncogenes

• 1980s, has led to the identification of the (phenylamino)pyrimidine (PAP) structure [5][6]. The addition of an additional pyridine ring to PAP raised its cellular activity, producing PAPP, which, after some more chemical modifications, culminated in imatinib (IMT) [7]. PAPP has been used to develop new

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• proved to not going via a Minisci-type silyl radical addition [55], as the reaction with pyridine did not afford any product. Bell studied the properties of such molecules which are similar to those used in OLED devices (organic light emitting diodes) in 2017. The molecule 34 was synthesized by base

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• ] cyclotrimerization reactions in the presence of nickel and cobalt catalysts [38]. First, they employed diyne 15 in the reaction with a series of alkynes (16) or nitriles (17) bearing a variety of functional groups including alkyl and alkene chains, hydroxy groups, and benzene and pyridine rings, to achieve the

• corresponding anthraquinones 55 and 57 via a single-step reduction with either zinc/pyridine or zinc/NaOH (Scheme 12). The scope of their work consisted of six examples, and they obtained anthracene derivatives in moderate to good yields (50–87%) [45]. In 2014, Yucel and co-workers synthesized 12 novel

• -free conditions (Scheme 43) [79]. The authors used various heteroaromatic aldehydes and substituted aromatic aldehydes containing electron-donating and electron-withdrawing substituents, to obtain the ortho adducts 188 in variable yields (14–74%). The use of pyridine-3-carbaldehyde and 2,4,5

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

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

• fluorination of pyridine or 2-fluoropyridine in anhydrous hydrogen fluoride [17][18] (Scheme 2). Not surprisingly, 1-1 did not become a popular reagent. In 1967, Banks et al. reported reactions of 1-1 with piperidine and triphenylphosphine, -arsine, and -stibine (Scheme 3, entries 1 and 2) [19]. The former

• -(trimethylsiloxy)pyridine was allowed to react with 5% F2 diluted with N2 in a freon solvent at −78 °C, 1-fluoro-2-pyridone was obtained in 63% yield (Scheme 5). The fluorination efficiency of 3-1 was higher than perfluoro-N-fluoropiperidine (1-1) and the yields of reaction with sodium diethyl malonates improved

• pyridine (10% F2/N2) at low temperature in a freon solvent, could undergo straightforward counteranion replacement with a non-nucleophilic anion. Therefore, exchange with salts such as sodium triflate in acetonitrile generated non-hygroscopic N-fluoropyridinium triflate salts as highly thermally stable

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• multipeptides of varying ring size were successfully obtained with excellent functional group tolerance. In addition, selective N-methylation of the 2-pyridine directing group and successive hydrogenation processes provided an efficient traceless removal of the directing group, affording free-NH tryptophan

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• attention for their inspiring applications in the fields of solar cells [1][2][3], organic devices [4][5][6][7][8], and as chemosensors [9][10]. The acridine core (Figure 1), formed by two benzenes fused to a pyridine ring, is among the most extensively studied heterocyclic aromatic compounds. It has first

• chlorine atom is located at the more reactive electron-poor pyridine moiety of the heterocyclic core structure. In fact, the chlorine position proved to be quite unreactive and all attempts to isolate 2,4,9-tris(phenylethynyl)-5,6,7,8-tetrahydroacridine failed even after using an excess of phenylacetylene

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• ] auxiliaries (Figure 1a). Besides, the cobalt(II)- [31] or nickel(II)-catalyzed [32][33], pyridine oxide (PyO)-directed tandem alkynylation/annulation was realized by Niu and Song et al., which also provided the 3-methyleneisoindolin-1-one scaffolds (Figure 1b). Notably, a sustainable cupraelectro-catalyzed

• unfortunately proven elusive [35]. 2-(1-Methylhydrazinyl)pyridine (MHP) [36] was identified as a powerful removable bidentate directing group, which found widespread application in various cobalt-catalyzed C−H activations [37][38][39][40]. Thus, our group also accomplished a set of electrochemical cobalt

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• ) PPh3, DIAD, TMSN3, MeCN, 80 °C, 48 h. a) BzCl, DMAP, pyridine, CH2Cl2, rt, 24 h, 90%; b) TBSOTf, imidazole, DMAP, DMF, 40 °C, 24 h, 78%; c) Na(s), MeOH, THF, 16 h, 90%; d) DMSO, SO3·pyridine, Et3N, rt, 1 h, 98%; e) H2NOH·HCl, THF, H2O, Na2CO3, 24 h, 80%; f) POCl3, MeCN, 65 °C, 40%; g) TBSOTf, imidazole

• , DMAP, DMF, rt, 24 h, 87%; h) TMSN3, Bu2SnO, toluene, 120 °C, 51%. a) PMBCl, KI, K2CO3, DMF, rt, 53% for 11 and 12; b) BnBr, DMF, Et3N, DCM, rt, 31% for 13 and 14. a) DMSO, SO3·pyridine, Et3N, rt, 1 h, 96%; b) H2NOH·HCl, THF, H2O, Na2CO3, 89%; c) POCl3, MeCN, 65 °C, 59%; d) TMSN3, Bu2SnO, toluene, 120