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

• total syntheses of many natural products [34]. Despite its wide application in ring formation reactions, only a few review articles on Hg(II)-salt-mediated cyclization reactions are available in the literature [35]. This review describes the intramolecular cyclization of unsaturated compounds in the

• diastereomers 30a,b and 32a,b was obtained, respectively. trans-Isomers were formed as major products over cis-isomers (Scheme 12) [52]. Five- and six-membered N-containing heterocyclic phosphonates were synthesized by intramolecular cyclization of alkenyl α-aminophosphonates in a similar way with the treatment

• cyclization of γ-hydroxyalkene derivative 187 as an intermediate stage to give a mixture of diastereomeric 2,5-disubstituted tetrahydrofurans 188a and 188b (Scheme 58) [119]. Later for the total synthesis of ventiloquinone J (194), a Hg(II)-salt-catalyzed intramolecular cyclization reaction of the ortho-allyl

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• , such as ionic liquid- and transition metal-catalyzed and other metal-free transformations [1]. A strategically diverse route to phenanthridines involves intramolecular cyclization of biaryl oximes, allowing for the formation of a new C–N bond. Such a strategy was explored by Deb and Yoshikai in the Fe

• (III)-catalyzed intramolecular cyclization of O-acetyloximes (Figure 2, reaction 1). However, this transformation was limited to ketoximes and yielded only 6-substituted phenanthridines [7]. Applying photochemical conditions, Rodrıguez and Walton were able to use benzaldehydes utilizing a similar

• intramolecular cyclization of O-acetyloximes to afford phenanthridines. (Figure 2, reaction 2) [8][9]. For these transformations, the reaction is thought to go via the transient iminyl radical [10]. More recently, Yu has reported the use of in situ-derived O-acyl oximes from benzaldehydes that when subjected to

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

• years (2008–2020) and focuses on direct and indirect methods to construct anthracene and anthraquinone frameworks. Keywords: anthracenes; anthraquinones; Friedel–Crafts cyclization; intramolecular cyclization; metal-catalyzed; Introduction Anthracene is an important aromatic hydrocarbon consisting of

• tested, but only the one-step method with sodium borohydride in alkaline medium resulted in 2,3-disubstituted anthracene 74a, the precursor of anthracene target 75, in excellent yield (95%) [50]. Intramolecular cyclization Intramolecular cyclization is a broad category that covers several known

• methodologies for the synthesis of anthracene derivatives. Traditionally, widely used methods include acid-catalyzed Friedel–Crafts intramolecular cyclization and Bradsher-type reactions and their variations [21]. Interestingly, some of the methods already reviewed here could also be included in this category

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• deprotonated by a base, affording an ammonium ylide/enolate. Meanwhile, the Re-face attack is favored after interaction of squaramide portion of the catalyst with coumarin. Then, a Michael addition followed by intramolecular cyclization affords the desired product 75, as shown in Scheme 23. An enantioselective

• intramolecular cyclization [63]. For this transformation, the authors use a squaramide catalyst 90 to perform the enantioselective Michael addition in 1,4-dioxane at room temperature, as shown in Scheme 28a. Moreover, the group tried a reusable immobilised squaramide catalyst 91, which gave the desired product

• -hydroxycoumarins (1) and aromatic imines 63 promoted by cupreine (65). Asymmetric addition of malonic acid half-thioesters 67 to coumarins 66 using the sulphonamide organocatalyst 69. Enantioselective 1,4-addition of azadienes 71 to 3-homoacyl coumarins 70. Michael addition/intramolecular cyclization of 3

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

• activation [37][38][39][40][41]. Hou’s group presented various studies on this theme [42][43], such as a notable work recently published in which they promoted a scandium-catalyzed intramolecular cyclization on benzimidazole substrates, via a C–H activation at the C-2 position (Scheme 2B). In this process, a

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

• via intramolecular cyclization reaction of ketones 31, p-nitrophenyl azide (PNA, 32) and amino esters 33 has been described by Dehaen et al. The products were often obtained in good yield and in all cases with the retention of the configuration of the stereocenter. The reaction was carried out by

• insensitivity to air are advantages of this reaction (Scheme 37) [60]. In 2017, De Borggraeve et al. explained a convenient procedure for the preparation of triazolo[1,5-a]indolones 131 through an intramolecular cyclization via an unprecedented Pd-catalyzed carbonylative C–H functionalization of 1-(2-bromoaryl

• achieved using dehydrogenative intramolecular cyclization of 4-substituted N-benzyltriazoles 163. A phenyl, alkyl, and CO2Me group, respectively, on the triazole scaffold was tolerated under the reaction conditions to form 4-substituted N-benzyltriazoles (Scheme 44). The substituted phenanthro[9,10-d

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• compounds with iron(III) to perform an intramolecular Baeyer–Mills reaction [15][21]. We found that a complete reduction of the nitro group to aniline 7 and oxidation with mCPBA is increasing the yield of the intramolecular cyclization from 39% to 62% (over two steps) for the unsubstituted diazocine 8c as

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• new pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline skeleton was synthesized by free-radical intramolecular cyclization of o-bromophenyl-substituted pyrrolylpyridinium salts using the (TMS)3SiH/AIBN system. The cyclization provides generally good yields of pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline hydrobromides

• °C (Scheme 7). A study of photophysical and electrochemical properties of compounds 3 is in progress and will be published elsewhere. Conclusion A wide range of derivatives with new pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline skeleton was synthesized by free-radical intramolecular cyclization of o

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

• intermediate 6 then would undergo a Prins-type intramolecular cyclization with the olefinic bond to produce a stable benzyl carbocation 7, that may be trapped through a Friedel–Crafts alkylation with an aromatic substrate or through the reaction with an external nucleophile to afford the target product 8

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

• radical A. The subsequent hydrogen abstraction by radical A yields the key alkyl radical B. The addition of radical B or A to the alkene 7a following by an intramolecular cyclization provides the radical intermediates C or E, which are oxidized by the hole of CN-K via SET delivering the product 8a or

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

• combining a nucleophilic addition to N-tert-butanesulfinyl α-chloroimines, and an intramolecular cyclization, the chlorine atom being finally displaced. Chiral N-tert-butanesulfinyl aldimines and ketimines have also been used successfully to form aziridines through aza-Darzens and Corey–Chaykovsky reactions

• using DMF as solvent. After addition, a subsequent intramolecular cyclization involving the resulting amide and the vicinal carbon with bromine atoms took place. By contrary, when the reaction was carried out in THF, the elimination process was suppressed, leading exclusively to enantiomerically pure α

• of anti/syn diastereoisomers. Treatment of compounds 24 with potassium hexamethyldisilazide provided vinylaziridines 22 through an intramolecular cyclization step. This intramolecular nucleophilic substitution is a stereospecific process. In the case of aromatic compounds 24, trans-vinylaziridines

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• intermediate B generated by the addition of aldehyde to enaminone A on intramolecular cyclization furnishes the final product 24 via C. Cyclic isoindole-fused furo[1,4]diazepines 26 were obtained by dehydration of the carbonyl group on the aromatic ring on treatment with an amino group. The authors attributed

• between aldehyde and amidine. The imine G thereby reacts with ethyl cyanoacetate to result in intermediate I, which on intramolecular cyclization leads to D. The remaining pathway pursues same mechanism as the first one (Scheme 27). Later in 2016, Gopalakrishnan and co-workers [74] demonstrated the

• mechanism describes the synthesis by the formation of an intermediate A from the condensation between compounds 33 and 32 in presence of an acid undergoing nucleophilic addition with 93 resulting in intermediate B. This intermediate undergoes an intramolecular cyclization C aided by an acid to give

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• to access aziridines with great structural variability [21]. The reaction of azirines with Grignard and organolithium reagents has been poorly investigated, and only without using green and renewable solvents [22][23]. In turn, 2H-azirines can be smoothly obtained through intramolecular cyclization

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• intramolecular cyclization impossible. Therefore, we attempted the bromofluorination of the easily accessible oxabicycloheptene derivative 18. Unfortunately, the reaction led to a complex mixture, without any halofluorinated product (Scheme 11). As an alternative approach, the N-benzyl imide 19 was investigated

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• 2019499, Scheme 5). The acid 2a reacted with a carbodiimide to form the reactive isourea derivative X which underwent intramolecular cyclization with the formation of furandione 5a which reacted with o-aminothiophenol (1a). Product 3a was formed when the o-aminothiophenol’s SH group attacked the compound

• the suspension of acid 2a with DCC, formation of the white precipitate of dicyclohexylurea was observed, which gave the evidence of intramolecular cyclization to furandione 5a with dicyclohexylurea elimination occurring. The formation of furandione 5a explained well our observations when DMAP was used

• intermediate XI intramolecularly attacked at the amide carbonyl group (Scheme 8). Such a change in the intramolecular cyclization direction, possibly, was due to the electron-withdrawing effect of the chloro-substituent in the o-aminothiophenol moiety, which decreased the nucleophilicity of the SH group

The biomimetic synthesis of balsaminone A and ellagic acid via oxidative dimerization

• Sharna-kay Daley and
• Nadale Downer-Riley

Beilstein J. Org. Chem. 2020, 16, 2026–2031, doi:10.3762/bjoc.16.169

• which undergoes reduction to the dihydroxynaphthalene 8. This is then dimerized by the copper-rich enzyme to quinone arenol 9, which, following intramolecular cyclization, affords balsaminone A (4, Scheme 1). Similarly, the biosynthetic precursor of ellagic acid (5), gallic acid (10), undergoes

• dimerization to the dimeric polyphenolic acid 11, followed by intramolecular cyclization to yield ellagic acid (5, Scheme 2) [20]. Because of the bioactivity of both natural products, there have been previous investigations of the synthesis of balsaminone A (4) [21][22] and ellagic acid (5) [23]. In our

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• of such cases where an aryl radical, formed via the photocatalyzed reduction of diazonium salt 2.1+, added to methyl propiolate. Ensuing cyclization of the resulting vinyl radical 2.2· finally yielded the desired phenanthrene 2.3 [41]. A different approach involves the intramolecular cyclization of α

• ., the 2-thienyl derivative 13.2) afforded vinyl radical 13.5·. The final intramolecular cyclization of 13.5· and re-aromatization smoothly yielded the desired polyheteroaromatic derivative (see the case of 13.6; 84% yield). Interestingly, all the obtained scaffolds bear two heteroatoms in close

• intermediate onto the C–C double bond of 16.1 gave radical 16.2·a upon nitrogen loss, which underwent an intramolecular cyclization and finally afforded the substituted phenanthridine 16.3a in a satisfactory yield (Scheme 16, path a) [81]. The same azide 16.1 underwent trifluoromethyl radical addition to give

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• of amines. The latter then aminolyzed the carbamates 149 to generate ureas 151 and γ-halo-β-hydroxyalkanethiols 150. The intermediates 150 further underwent an intramolecular cyclization to produce the thietane-3-ols 145 in low to good yields [58] (Scheme 30). Paclitaxel (Taxol®) and docetaxel

• (179) is a derivative of aziridine-2-methyl tosylate. After the ring-opening with ammonium tetrathiomolybdate and subsequent intramolecular cyclization, the compound was converted into a bridged thietane 183 in 75% yield. The results indicated that, in the ring-opening step, tetrathiomolybdate

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• rule, a C–O bond is formed in intermolecular reactions, intramolecular cyclization generally occurs with the formation of a five-membered cycle of isoxazoline (C–O bond formation) or nitrone (C–N bond formation). Application of the oxime radicals in organic synthesis: intermolecular reactions Selective

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• variety of substrates, although the methodology required hazardous conditions; i.e., hot benzene [62]. A few years later, similar types of reactions were carried out by Loh and co-workers [63]. In this case, a variety of α,β-unsaturated compounds, that, rather than undergoing intramolecular cyclization

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• addition followed by intramolecular cyclization or vice versa provided compound 12, which was validated by 13C and DEPT NMR studies (Supporting Information File 1 Figures S37and S38). Marred with these observations, compound 11 was treated with aqueous hydroxylamine in the presence of strong base (i.e., 10

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• . Upon electron back transfer to regenerate the [Cu(I)] catalyst, SO2Cl was also incorporated into the product. Finally, an intramolecular cyclization process gave the desired product (Scheme 5). Two years later, Reiser’s group reported another ATRA reaction of perfluoroalkyl iodides with alkenes and

• provide a transient radical, which undergoes an intramolecular cyclization to give the aryl radical anion. A final oxidation/deprotonation sequence delivers the product. In 2018, Reiser and co-workers reported the use of the [Cu(dap)2]Cl catalyst in the oxoazidation of styrene derivatives (Scheme 14) [30

• oxidative quenching. First, the excited [Cu(I)]* species was oxidized in the presence of iodine, furnishing a [Cu(II)] complex. Then, an oxidation of the diarylamine occurred, generating the N-centered radical cation, which undergoes an intramolecular cyclization. A final oxidation of the aryl radical

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• stereoselectivity. It was found that the P-stereogenic β-/γ-mercaptoalkylphosphine oxides underwent intramolecular cyclization to the corresponding bicyclic phosphine oxides with high stereoselectivity and high yield under mild reaction conditions. 1H NMR spectra of compounds 12 and 29. 13C NMR spectra of compounds

Facile regiodivergent synthesis of spiro pyrrole-substituted pseudothiohydantoins and thiohydantoins via reaction of [e]-fused 1H-pyrrole-2,3-diones with thiourea

• Aleksandr I. Kobelev,
• Nikita A. Tretyakov,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Michael Rubin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 2864–2871, doi:10.3762/bjoc.15.280

• further undergone either an intramolecular cyclization by NH attack, forming thiohydantoin ThH (path A), or further dissociation to FPD 1 and thiourea. The latter would subsequently attack FPD 1 with both nucleophilic NH centers, forming thiohydantoin ThH (path B). Conclusion In conclusion, we have

One-pot synthesis of substituted pyrrolo[3,4-b]pyridine-4,5-diones based on the reaction of N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamide with amines

• Valeriya G. Melekhina,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Vitaly S. Mityanov,
• Artem N. Fakhrutdinov,
• Arkady A. Dudinov,
• Vasily A. Migulin,
• Yulia V. Nelyubina,
• Elizaveta K. Melnikova and
• Michail M. Krayushkin

Beilstein J. Org. Chem. 2019, 15, 2840–2846, doi:10.3762/bjoc.15.277

• fragments proceeds first, followed by intramolecular cyclization (Scheme 4B). The structure of the 4-chloro-substituted pyrrolopyrimidinone 1e was proven by single crystal X-ray analysis (Figure 1). Despite the unambiguous dominance of the pyridone-based conformation in the solid state of 1e, two tautomers