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

• benzyl ether. Further double bond formation in compound 78 employing triiodoimidazole and PPh3 led to 2 (route A, 32% overall yield from 52). The synthesis of combretastatin D-1 (1) was achieved from the cyclodehydration of compound 77, followed by the hydrogenolysis of the benzyl ether 79 (route B

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• a semipinacol rearrangement leading to 95, followed by subsequent cyclization to natural products guignardone A (96) and C (97). This process involved 1,2-allyl migration and C–O bond formation through a semipinacol rearrangement and a cyclodehydration cascade reaction (Scheme 8). Following the same

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• ]. In the same year, they also realized the synthesis of 2-phenyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxide (55) in 75% yield by heating at 190–200 °C and in 47% yield by DCC condensation of compound 54 – the oxygen analogue of 2-aminobenzyl(phenyl)dithiophosphinic acid 58. The cyclodehydration

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• ]. Various other methods to access this heterocyclic moiety have been reported in the literature, with many focusing on either cyclodehydration or cyclodesulphurisation (Scheme 1) [27]. However, in recent years, there have been a number of oxidative cyclisation protocols reported to access the same 1,3,4

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• antibacterial effects [76]. In this context, Miller and co-workers reported the performance of C2-symmetric chiral phosphoric acids (C2-type) and phosphothreonine-embedded, peptidic phosphoric acids (pThr-type CPAs) to catalyze a wide range of atroposelective cyclodehydration reactions for the synthesis of

• various pyrazolones. Enantioselective and atroposelective synthesis of axially chiral N-arylcarbazoles [73]. Atroposelective cyclodehydration reaction. Atroposelective construction of axially chiral N-arylbenzimidazoles [78]. Proposed reaction mechanism for the atroposelective synthesis of axially chiral

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• /bjoc.17.162 Abstract A facile synthesis of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridine derivatives is reported which is based on POCl3-mediated cyclodehydration followed by double Suzuki–Miyaura cross-coupling. The absorption and fluorescence properties of the obtained products were investigated and

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

• has been reported over the years. The most familiar methods to obtain substituted anthracenes include Friedel–Crafts reactions [17], Elbs reaction [18], aromatic cyclodehydration [19][20], Bradsher-type reactions from diarylmethanes [21][22][23], and, more recently, metal-catalyzed reactions with

• cyclodehydration of substituted 2-arylmethylbenzaldehyde 85a mediated by BF3·OEt2 (Scheme 21) [55]. By using this methodology, they prepared substituted anthracene derivatives 86 in excellent yields (75–93%). Impressively, the authors were able to synthesize these compounds in better yields via a two-step

• procedure involving the cyclization of 2-arylmethylbenzoic acid 85b with triflic acid, followed by a NaBH4-mediated reductive dehydration. Some representative examples included anthracenes 86a–g. For those interested, the cyclodehydration was also extended to 2-(arylmethyl)naphthaldehydes and 2-(arylmethyl

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

• anthranilic acid with 2.2 equivalents of bromine in acetic acid as previously reported [64]. Subsequently, the POCl3-mediated cyclodehydration of 1 and cyclohexanone afforded 2 through an adapted reported procedure (Scheme 1) [65]. Tetrahydroacridine 2 represents a novel synthetic building block for Pd

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• alcohols was shown by Cohen and Kaluszyner [55][56] and by Streitwieser et al. [57]. The cyclodehydration of 9c occurs in polyphosphoric acid to afford fluorene 37 (Scheme 8) [57]. A mechanistic proposal invoking the initial generation of the α-(trifluoromethyl)carbenium ion 10c↔10c’ was mentioned by the

One-pot synthesis of isosorbide from cellulose or lignocellulosic biomass: a challenge?

• Isaline Bonnin,
• Raphaël Mereau,
• Thierry Tassaing and
• Karine De Oliveira Vigier

Beilstein J. Org. Chem. 2020, 16, 1713–1721, doi:10.3762/bjoc.16.143

• phosphoric acid (which is a strong acid) for the conversion of cellulose, an isosorbide yield of 29% is reached indicating that double cyclodehydration is favored under these conditions. On the contrary, the addition of equimolar amounts of boric acid and phosphoric acid decreases the yield of isosorbide and

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• alcohols promoted by trimethylsilyl polyphosphate (PPSE) in solvent-free conditions allowed for the synthesis of several hitherto unreported seven-membered iminothioethers bearing 2-aryl, alkenyl, aralkyl and alkyl substituents. The cyclodehydration reaction is likely to involve an SN2-type displacement

• and affords good to excellent yields of the desired heterocycles in very short reaction times. Keywords: cyclodehydration; medium-size heterocycles; microwaves; PPSE; tetrahydrothiazepines; Introduction Thiazolines (4,5-dihydrothiazoles) are widely studied heterocycles due to their multiple

• reactions in either case. The synthesis of 2-phenyl-4,5,6,7-tetrahydro-1,3-thiazepine by cyclodehydration of N-(4-hydroxybutyl)thiobenzamide was attempted with different condensing agents: PPA (100 °C, 15 h), Burgess (25 °C, 48 h) and PEG-Burgess (80 °C, 2 h) reagents, and under Mitsunobu conditions. In the

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• best of our knowledge, so far only a few methods allow the synthesis of lilolidines arylated at α- [6][7] or β- [8][9][10][11][12][13] positions of the nitrogen atom. In 2014, Chen and Tang et al. reported that NH4PF6 promotes the cyclodehydration of α-aminocarbonyl compounds, leading to the formation

A three-component, Zn(OTf)₂-mediated entry into trisubstituted 2-aminoimidazoles

• Alexei Lukin,
• Anna Bakholdina,
• Anna Kryukova,
• Alexander Sapegin and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103

• the mechanistic prospective, the reaction probably proceeds via Zn(OTf)2-catalyzed alkyne hydroamination followed by cyclodehydration as depicted in Figure 3, in full analogy with the previously proposed mechanism [2][3]. Conclusion In summary, we have successfully employed propargylureas in the

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• acid residue required for the synthesis of key arylquinolines involved in an HIV integrase project. Keywords: cyclodehydration; HIV integrase; isatoic anhydride; masked acyl cyanide; quinoline; Introduction In stark contrast to the prevalence of the quinoline heterocycle in natural products [1

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing electron-withdrawing groups. The sequence involves an initial SNAr displacement, N-acylation and MW-assisted ring closure. Remarkably, the uncatalyzed N-arylation of 2

• -ABA led to the monosubstitution product using equimolar amounts of both reagents. The individual steps were optimized achieving good to excellent overall yields of the desired heterocycles, avoiding additional protection and deprotection steps. A mechanistic interpretation for the cyclodehydration

• primary and secondary amines [98]. On the other hand, it is known that N-unsubstituted amides react with PPSE affording nitriles [99]. In this context, the cyclodehydration of N-monosubstituted amides 3 could in principle involve an initial PPSE-mediated elimination generating a reactive nitrilium ion in

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• the key substrates for aromatic cyclodehydration, also known as the Bradsher reaction [15], which leads to fused, polycyclic aromatic hydrocarbons [16][17][18][19]. This type of reaction found applications in synthesis of organic, optoelectronic materials [20][21][22]. Metal-catalyzed cross-coupling

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

• Kohei Yamada,
• Naoto Kamimura and
• Munetaka Kunishima

Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146

• carboxylic acid 1 and amino acid 2 under conditions improved from [23] (Table 1). A one-pot sequence involving formation of an activated ester from benzoic acid (1a) with DMT-MM, N-benzoylation of alanine (2a), cyclodehydration, and introduction of the triazinyl group was conducted in 1,4-dioxane/H2O to give

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• reported the MW-assisted synthesis of 1,4,5,6-tetrahydropyrimidines and their homologues by cyclodehydration reactions promoted by polyphosphoric acid (PPA) esters PPE and PPSE [58][59][60]. This strategy was successfully applied to the synthesis of 1-aryl-2-imino-1-azacycloalkanes [61], 2-oxazolines, 5,6

• in precursors 5. The cyclodehydration of acetamides 5a–c proceeded under mild reaction conditions (Table 4, entries 1–3), while acetamide 5d required a higher temperature probably due to the steric hindrance produced by the N-isopropyl moiety (Table 4, entry 4). A higher temperature and a longer

• reaction time were necessary in order to achieve cyclodehydration of isobutyramide 5e, and even harsher conditions were required for pivalamide 5f (Table 4, entries 5 and 6). In the case of precursors 5g,h, instead of the expected 1-substituted-2-tert-butyl-1,4-dihydroquinazolines, cyclodehydration led to

Continuous-flow synthesis of highly functionalized imidazo-oxadiazoles facilitated by microfluidic extraction

• Ananda Herath and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2017, 13, 239–246, doi:10.3762/bjoc.13.26

• target oxadiazole is then formed via an intramolecular cyclodehydration (Scheme 1) [27][32][33][34]. For our initial studies on the development of a flow synthesis of 1,2,4-oxadiazoles we focused on the reaction of N-hydroxynicotinimidamide with 3-bromobenzoic acid (Table 1). Screening a variety of

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• ]quinolizinium was synthesized by cyclodehydration route and its optical properties in different media were investigated. The absorption and emission spectra of this compound depend on the pH of the solution. Thus, at higher pH values the deprotonation yields a merocyanine-type dye that exhibits significantly

• , berberine and coptisine, which were also shown to bind to CB[7] [38][39][40] and may thus serve as an appropriate comparison. Results Synthesis Hydroxynaphthoquinolizinium 2 was synthesized by the established cyclodehydration route (Scheme 1) [41][42]. Thus, the quaternization of 2-(1,3-dioxolan-2-yl

Symmetry-based approach to oligostilbenoids: Rapid entry to viniferifuran, shoreaphenol, malibatol A, and diptoindonesin G

• Youngeun Jung,
• Dileep Kumar Singh and
• Ikyon Kim

Beilstein J. Org. Chem. 2016, 12, 2689–2693, doi:10.3762/bjoc.12.266

• diptoindonesin G, a potent cytotoxic and immunosuppressant agent [16][17], by using a highly efficient domino cyclodehydration/intramolecular Friedel–Crafts acylation/regioselective demethylation sequence as a key transformation. Very recently, a dual functional role of diptoindonesin G in modulating α and β

Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

• Jimena E. Díaz,
• María C. Mollo and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2016, 12, 2026–2031, doi:10.3762/bjoc.12.190

• of conventional heating [17]. In previous work, we reported the microwave-assisted synthesis of 5 to 8 membered cyclic amidines by cyclodehydration of N-aryl-N´-acyl-1,n-alkanediamines (n = 2–5) promoted by polyphosphoric acid (PPA) esters PPE and PPSE (Scheme 1, reaction 1) [41][42][43]. In this

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• catalytic role for this metal [33]. However, this role was later demonstrated to be structural rather than catalytic [34]. The Mitchell group showed [35] that the D-protein is actually directly involved in catalysis and uses ATP to activate the backbone amide bond for cyclodehydration, thus explaining the

Synthesis and fluorosolvatochromism of 3-arylnaphtho[1,2-b]quinolizinium derivatives

• Phil M. Pithan,
• David Decker,
• Manlio Sutero Sardo,
• Giampietro Viola and
• Heiko Ihmels

Beilstein J. Org. Chem. 2016, 12, 854–862, doi:10.3762/bjoc.12.84

• -benzylpyridinium derivative 3 and the subsequent cyclodehydration [27] in refluxing HBr (w = 48%) gave the bromonaphtho[1,2-b]quinolizinium 4 in 57% overall yield (Scheme 1). The Suzuki–Miyaura coupling reactions of 3-bromonaphthoquinolizinium derivative 4 with the arylboronic acids 5a–e were performed under

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• was subjected to a Bischler–Napieralski cyclodehydration reaction in presence of POCl3 [27], however under these conditions 2,9-dihydro-β-carboline derivative 7 was obtained as the major product (less than 10% yield) instead of 4-9-dihydro-β-carboline derivative 12 (Scheme 4). Our attempts to improve

• the yield of 7 under Bischler–Napieralski cyclodehydration reaction conditions using POCl3 as the Lewis acid were proved to be futile. This prompted us to test the efficiency of other Lewis acids in this cyclodehydration reaction. The Bischler–Napieralski cyclodehydration reaction was then carried out