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

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• %) efficiently catalyzed the intramolecular cyclization with 65–92% yields (Table 1, entries 3–7). To our delight, the transformation also reached 92% yield by employing 1a at 0.5 mol % (Table 1, entry 4). Compared to literature [60][61][62], catalyst 1a is effective for the tandem cyclization of 2

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• and Research, Pune, Pune 411008, India 10.3762/bjoc.15.234 Abstract The intramolecular cyclization of a C-3-tetrasubstituted furanoid sugar amino acid-derived linear tetrapeptide afforded an oxazolone pseudo-peptide with the formation of an oxazole ring at the C-terminus. A conformational study of

• interaction. However, the role of the neighboring amido groups cannot be ruled out. Moreover, the hydrophobic outer surface of the transporter helps the anion bound complex to permeate efficiently through the lipid bilayer membranes. Conclusion In conclusion, the intramolecular cyclization of linear di- and

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• -catalysed intramolecular tandem stannylation/biaryl coupling protocol gave the attempted pentacyclic products [32]. However, having the biaryls 20a and 20b prepared we intended to develop a new approach to pyrido[4,3,2-mn]acridines by an alternative intramolecular cyclization step. To reach that aim, the

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• intramolecular cyclization of 23. Attempted photochemical cyclization of 25. Representative screening conditions for the biomimetic cascade. Supporting Information Experimental procedures, spectroscopic data and copies of NMR spectra (PDF) as well as crystallographic data of compounds 16 and 17. CIF files for

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• 7c. 1,3-Dipolar cycloaddition of nitrones to alkenes is known to be reversible [13][14]. We recently reported a similar reversibility of the intramolecular cyclization of sterically hindered pent-4-enylnitrone of the 2H-imidazole series [15]. Treatment with Zn in an AcOH/EtOH/EDTA/Na2 mixture was

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• have been reported so far (Scheme 1). Zeni et al. reported the synthesis of imidazoselenoazole using a three-step one-pot reaction of N-alkynylimidazoles with selenium involving the electrophilic intramolecular cyclization of acetylenic compounds (Scheme 1, reaction 1) [6]. Zeni et al. also developed a

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• addition with a subsequent intramolecular cyclization catalyzed by Cu(BDC)MOF. Further, the LC–MS study of the reaction mixture has shown the imine formation to be the major pathway rather than β-nitrostyrene. The reaction involved a two-step reaction mechanism in which aza-Michael adduct 13 was formed in

• mechanisms, i.e., a Chan–Lam coupling and an Ullmann coupling. The Chan–Lam coupling involved a C–N bond formation (intermediate I, 84) which then entered into the Ullmann coupling to undergo intramolecular cyclization to form final product 78 and release Cu(III) to Cu(I) by reductive elimination. In this

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• =)P–CR=C=CMe2, X = Cl, OMe, NR2, or SAr] undergo intramolecular cyclization into the corresponding 1,2-oxaphospholium ions in the Brønsted superacid TfOH. These cations have been thoroughly studied by means of NMR spectroscopy. The hydrolysis of superacidic solutions of these species afforded cyclic

• (Figure 3, Table 2). Despite solvation in the Brønsted superacid TfOH, the P=O group takes part in intramolecular cyclization into oxaphospholium ions (Table 1). These two different types of reaction intermediates, generated from such allenes in Brønsted and Lewis acids, lead to various reaction products

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• excellent yields. The proposed mechanism begins with the formation of the β-aminoketoimine by condensation of the steroid with two molecules of ammonia, followed by the reaction with arylaldehyde and intramolecular cyclization to a dihydropyrimidine skeleton, which suffers oxidation to the aromatic