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

• quinoid type to study their photophysical properties in solution and in the solid-state, Ooyama and co-workers [106] studied a synthetic route for the preparation of compounds with the tricyclic benzo[c]carbazol-6-one skeleton. The strategy used was through the reaction to β-NQS 18 with a bifunctional

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• different coupling partners, both bi- [142] and tricyclic [143] fused heterocyclic frameworks have been synthesized through iminyl radical cascade cyclization and annulation reactions. Carbooxygenation In 2017, the Bao group reported the first decarboxylative alkyl etherification of alkenes 108 with

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

• nitrogen atom to nitrenium intermediates occurred initially; further stabilization of these species resulted in the formation of hydroxylated lactams [44][45][46][47][48], azaspirocycles [49][50][51][52][53], or tricyclic nitrogen-containing heterocycles [44][53]. Our study commenced with the synthesis of

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

• cyclic lactones [69]. The intramolecular cyclization of the acyl radical A gives the tricyclic radical species C, which then forms fluorenone (3) after abstraction of a hydrogen radical by an additional equivalent of the tert-butoxy radical. Conclusion In summary, we have demonstrated that the metal-free

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• ]. The pyrrolizidine motif has up to now eluded us other than when it forms part of the tricyclic 2,3-dihydro-1H-pyrrolo[1,2-a]indole system [15], as in our route to aziridinomitosenes [16][17]. In the course of our attempts at the syntheses of aryl-bearing indolizidine alkaloids via N-phenacyl

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• with high selectivity using this strategy. In these transformations, two Hg-carbene intermediates were proposed to be involved (Scheme 52). Mercury-catalyzed reactions were also well known for the formation of various complex scaffolds like tricyclic pyrazinones from the corresponding starting

• materials. For example, Zhang et al. showed that refluxing anilide 177 in presence of a catalytic amount of Hg(OAc)2 and 90% formic acid gave the tricyclic heterocyclic scaffold 178 [113]. It involved a two-step process with the rearrangement of the primary cyclization products (Scheme 53). In 2013, Lin et

• -metalation followed by a regioselective mercuri-cyclization reaction (Scheme 60). During the total syntheses of (±)-fastigilin C and (–)-fastigilin C (201), 2 equiv of Hg(TFA)2 were used to synthesize key intermediate tricyclic furan compounds 199, 200, and 203. Hg(TFA)2 helped in the desired ring-formation

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• , enabling the synthesis of a 32mer [272]. The construction of α(1–6)-mannans (up to 10mer) bearing α(1–2)-Man branches was also accomplished using phosphate, N-phenyltrifluoroacetimidate or n-pentenylorthoester donors [273][274]. An approach using a (cationic) ROP method using tricyclic orthoester Man BBs

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

• White’s oxidation method as the final step in the first total synthesis of gracilioether F (75) [157], a natural polyketide with an unusual tricyclic core and five contiguous stereocenters, part of the family of gracilioethers 71–74 (Scheme 26A) extracted from the marine sponge Plakinastrella mamillaris

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• binding is G-clamp (Figure 8), the phenoxazine-derived tricyclic analogue of cytosine [124]. The improvements in affinity provided by the G-clamp are likely a combined effect of superior π-stacking of the rigid and planar aromatic system, electrostatic attraction of the positively charged amine, and

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• converted to fused sultams (Scheme 30) [56]. Anand et al. reported a Cu-catalyzed one-pot method for the preparation of 1,2,3-triazole-fused tricyclic heterocycles 106 via an intramolecular [3 + 2]-annulation. This strategy includes the 1,6-conjugate addition of Me3SiN3 to o-alkynylated p-quinone methides

• functionalized tricyclic triazoles 152–154. It was proved that o‐azidophenols 148 react well with alkynes 149 using CuI in DMF at 120 °C and then, the resulting intermediates react with isocyanides using Pd(OAc)2 and an O2 atmosphere at 120 °C to produce the desired products (Scheme 42). o‐Azidophenols 148 were

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• reaction time (up to 6 d) was required to complete these experiments, and the yield of the isolated products dropped significantly (to 41 and 64%, respectively). In analogy to the tricyclic pyrazole derivative 9a, the expected products 9b–h formed after spontaneous aromatization of the initial [3 + 2

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• veratrole or furan led to the formation of the respective tricyclic 4-aryl-1,2,3,4-tetrahydrophenanthren-2-ols 14ha and 14hb in 73% and 43% yields, respectively. In order to further explore the generality of this cascade Prins/Friedel–Crafts cyclization, the established methodology was also applied to the

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• in 41% yield (Scheme 6c). Furthermore, the tricyclic indoline 14, a structural motif in diverse natural products [4], could be obtained in 60% yield through a reductive cyclization reaction (Scheme 6d). To investigate the mechanism of the cyanomethylarylation of alkenes, a series of control

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• 40% KOH aqueous solution resulted in a skeletal rearrangement of the tricyclic system, which, however, was accompanied by reesterification with methanol and partial hydrolysis of the ester group. As a result, the methyl ester 5a was obtained in 66% yield (Scheme 3). Rearrangement of 1,3-dimethyl- and

• an individual form were found. The methodology proved to be effective for the synthesis of a wide range of target compounds with various substituents in the tricyclic fragment. Investigations of the antiproliferative activity of the synthesized products 4 and 5, as well as possible ways of their

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• carbamate 8 in good yield [27][28][36]. In the next step, the aminohydroxylation was accomplished by potassium osmate(VI) as the catalyst and t-BuOCl in the presence of DIPEA affording oxazolidine-2-one 9 [27]. The reaction was found to be highly stereoselective, giving exclusively the diexo-fused tricyclic

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• duplex where the 2'-oxygen acts as an H-bond acceptor for water, potentially making a favorable contribution to the increased pairing affinity of LNA [161]. Constrained ethyl (cEt) nucleic acids (Figure 7H), which contain a [2.2.1] tricyclic core, have been developed and show improved potency when

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• synthesis of three types of highly functionalized azaheterocyclic scaffolds (dihydropyridazines, tetrahydropyridazines, and partially saturated tricyclic systems) from readily available hydroxypyrrolines and hydrazides are described. The directions of the transformation of a common initial intermediate

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• dipolar cycloaddition to produce tricyclic isoxazolidines [40]. The synthesis started from 5-hexyn-1-ol (4, Scheme 2). The alcohol was treated with dihydropyran followed by alkylation using butyllithium and then, acetal deprotection, providing the alcohol 5 as a key starting compound for the (±)-adaline

• % overall yields. A relevant consideration in Holmes’s synthesis is: the nitrone is the same common intermediate as Gössinger’s [25], which is cyclized to form the tricyclic adducts. While the Gössinger route started from the cyclic 1-hydroxypiperidine, Holmes performed in situ cyclization to prepare the

• tricyclic adduct (+)-23b, a precursor to (−)-adaline (1). This methodology, based on the synthesis of optically active β-sulfinyl nitrones, was proved to be efficient in the synthesis of (+)-euphococcinine (2) in 7 steps from piperidine (17), in an overall yield of 2.1%. Specific rotation for (+)-2 was [α

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• tricyclic compound 25, which led to the synthesis of (±)-hirsutene (14) [22] (Scheme 1A). Refluxing azo compound 22 in acetonitrile generated the proposed biradical intermediate 23 through nitrogen extrusion. This intermediate underwent isomerization to 24 and intramolecular diyl trapping through a [3 + 2

• synthesis of (±)-hirsutene (14) used an alkylidene carbene as source of TMM diyl in the intramolecular [3 + 2] cycloaddition [24] (Scheme 1D). Heating of epoxyaziridinyl imine 32 produced tricyclic compound 36 in 57% yield as a single product. The authors proposed that heating of epoxyaziridinyl imine 32

• generates alkylidene carbene 33. Transformation of 33 to TMM diyl 35 enables an intramolecular [3 + 2] cycloaddition to give the desired tricyclic product 36. Trimethylenemethane (TMM) cycloaddition An intramolecular trimethylenemethane diyl [3 + 2] cycloaddition was reported by Berson [28] and Little [14

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• tricyclic indoles bearing 3,4-fused seven-membered rings, 2‑arylpyridines, aminonaphthalenes and 3-phenylisoquinolines. In addition, this catalyst showed to be recyclable and could be reused several times without significant loss in activity during the course of the reaction process. Keywords: biomass

• activity in organic reactions. Tricyclic indole alkaloids bearing 3,4-fused seven-membered rings have attracted much attention because of their interesting molecular architectures and important biological activities [32][33]. Here the three-component reaction of 4-aminoindole (1a), 4-methylbenzaldehyde (2a

• were shown in Scheme 1. Aldehydes 2 with different functional groups on the benzene ring could react smoothly with compounds 1a and 3a, producing the corresponding 3,4-fused tricyclic indoles 4b–d with yields ranging from 46% to 64%. o-Anisaldehyde, with steric-hindrance effect, also reacted

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• -2,7-diyne reacted chemo- and stereoselectively in a Diels–Alder reaction with N-phenylmaleimide affording the tricyclic products as a mixture of two separable diastereoisomers, the configuration of which was estimated by DFT computations. The reported enediyne metathesis paves the way to the

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• obtained with DeoxoFluor at elevated temperature (Scheme 2). A side-product in this fluorination reaction was the tricyclic compound 12, which presumably formed through an electrophilic aromatic substitution reaction of the activated alcohol intermediate. The inclusion of TMS-morpholine [29] reduced the