A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• ], intramolecular cyclisation [36] or a mixture of both [8][37][38][39]. The new ligand system proved to deliver competent catalysis. Conversion was seen in all cases at 1 mol % catalyst loading (Scheme 3). Use of 13 resulted in a slight increase of the anti-Markovnikov hydration product 17 over 18 when compared to

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• methyl ether aromatic substituents were tolerated. Unsymmetrical 10,11-dihydro-5H-dibenzo[b,f]azepine derivatives 71 have been synthesised by ortho-bromination of functionalised dihydrostilbenes 67, followed by intramolecular cyclisation using Buchwald–Hartwig amination (Scheme 14) [54]. The pathway

• final Mizoroki–Heck reaction will be discussed in the following section. The Buchwald group [59] reported a ligand-controlled divergent synthesis involving intramolecular cyclisation, allowing for the formation of several heterocycles, including dibenzo[b,f]azepines 89, in two steps. Screening of

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• diastereoisomer increased. A similar trend was observed when starting from the enantiomerically enriched 3a (Table 2, entry 3). It has been shown that substituted oxindoles can be converted to indolopyrans via intramolecular cyclisation [33]. We also tried synthesizing 4H-pyrans in acidic conditions but no

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• achieved by treating 2-(2-oxo-2-phenylethyl)benzonitriles with amines in the presence of Me3Al. The reaction proceeds via a domino nucleophilic addition with subsequent intramolecular cyclisation. This method provides a wide variety of substituted 1-aminoisoquinolines with good functional group tolerance

• . Furthermore, the synthetic utility of this protocol was demonstrated in the successful synthesis of the antitumor agent CWJ-a-5 in gram scale. Keywords: 1-aminoisoquinolines; CWJ-a-5; intramolecular cyclisation; 2-(2-oxo-2-phenylethyl)benzonitriles; nucleophilic addition; Introduction Heterocyclic compounds

• suitably tailored benzonitriles 3 were cyclized in an intramolecular fashion by installing nuclophilic nitrogen onto the nitrile functionality would generate 1-aminoisoquinolines. Herein we describe our efforts on a Me3Al-mediated nucleophilic addition followed by an intramolecular cyclisation of 2-(2-oxo

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

• moieties, and careful basification resulted in intramolecular cyclisation givnig 5b,c with a yield of 51% and 42%, respectively. Nitrones 5a–c readily react with 4-pentenylmagnesium bromide. Quenching of the reaction mixtures with water under aerobic conditions leads to partial oxidation of resultant N

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• our compound 5. The formation of compound 8 can be explained by the rearrangement of 7 through a hydrogen-shift to form the diazo intermediate 9 which underwent a concerted [2 + 3] intramolecular cyclisation to 3,3-diphenyl-3H-indazole 8 (Scheme 2). The process was facilitated by the presence of a

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• were unable to access 2 (Scheme 7). Instead, the major product isolated in both cases was novel heterocycle 35. It is likely that cleavage of one of the pivaloxymethyl groups, followed by intramolecular cyclisation, results in the formation of 35. Microwave heating of 33 in the presence of DBU also

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• patterns. If the azepinium cation intermediates were stabilised by either α-methyl or β-phenyl substituents, the intramolecular cyclisation with the pyrrole ring proceeded to afford azepinoindoles. If both substituents stabilised the intermediates, N-allyl (n = 1; R1 = R2 = H), N-2-butenyl (n = 1; R1 = H

• detrifluoroacetoxylation of 14 (path b: normal Pummerer reactions) and undergoes intramolecular cyclisation on the pyrrole ring of 19. Aromatisation of dihydropyrrole intermediate 20 leads to the formation of pyrroloazepinic cation 21, which is stabilised by the phenylsulfanyl group at its 3-position. The S-shift reaction

• oxidation proceeded to give the corresponding sulfoxide 5g in high yield. The sequential process, Pummerer reaction of 5g with TFAA, followed by treatment with TBAH to afford the 1,7-sulfur-shifted product 9g as crystals; however, the yield was relatively low. The final ytterbium-catalysed intramolecular

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• absence of any observable intramolecular cyclisation of the unprotected purine nucleoside derivatives typical of solution-phase reactions using such substrates. More variable yields were obtained using potassium selenocyanate which required grinding in the presence of DMF to promote the reaction with

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• additional step of intramolecular cyclisation. An alternative radical chain process was also considered this time, involving notably the reaction of radical 28 with CF3SO2Cl to produce CF3• and intermediate 29. Csp2–CF3 bond-forming reactions Trifluoromethylation of arenes and heteroarenes: The pioneering

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• oxidised to Ag(II) by the persulfate anion; then, CF3SO2– was oxidised to CF3SO2• that generated CF3• by release of SO2. Addition of the CF3 radical to the alkene led to the radical intermediate 50, which underwent intramolecular cyclisation into 51. The sulfate radical anion then oxidised intermediate 51

• with PhI•OAc. Addition of the CF3 radical to the alkene followed by intramolecular cyclisation mediated by PhI•OAc gave the desired oxindole with release of PhI and AcOH (Scheme 28) [49]. For another metal-free trifluoromethylation/cyclisation of N-arylacrylamides by means of a different oxidant, Liu

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• products 22 and 23 [24] (Scheme 3). The proposed mechanism was based on the isolation of the 4-nitrodiaminobenzene imine intermediate which possessed reduced reactivity for intramolecular cyclisation. This type of reaction was exploited in the literature several times for the synthesis of quinoxalin-2(1H

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• alcohols were run in the absence of scCO2 the yields of the corresponding N-alkylated products were lower and more piperidine 2a was observed. These results suggest that the rate of intermolecular alkylation is faster in scCO2, while the rate of intramolecular cyclisation is not significantly affected by

• conditions afforded the desired N-methylpyrrolidine (4) in 95% yield. Extending the alkyl chain using 6-amino-1-hexanol (5), however, favoured methylation over intramolecular cyclisation as only 20% of the cyclised product 6 was observed. The major product was 6-(dimethylamino)-1-methoxyhexane (7, Scheme 2

• dimers were detected and unreacted 16 was the main product observed. The reaction of 15 with CO2 could be supressed using higher temperatures, for example at 380 °C in methanol the intramolecular cyclisation is favoured and N,N’-dimethylpiperazine (10) is obtained as the major product in 68% yield

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

• Olga Eguaogie,
• Patrick F. Conlon,
• Francesco Ravalico,
• Jamie S. T. Sweet,
• Thomas B. Elder,
• Louis P. Conway,
• Marc E. Lennon,
• David R. W. Hodgson and
• Joseph S. Vyle

Beilstein J. Org. Chem. 2017, 13, 87–92, doi:10.3762/bjoc.13.11

• reactions require the use of high-boiling, dipolar aprotic solvents and anionic nucleophiles under anhydrous conditions at elevated temperatures (up to 150 °C). Competing intramolecular cyclisation reactions between both purine and pyrimidine nucleobases and (especially) the 5′-position of the (deoxy

• liquid [13][14][15]. Recently, Jicsinszky et al. described using a planetary ball mill to perform substitution reactions of 6I-O-(p-toluenesulfonyl)-β-cyclodextrin (Ts-β-CD) with azide, halide or thiolate nucleophiles and thereby avoided intramolecular cyclisation (commonly found under solution-phase

• from nucleosides by 4-methoxybenzylthiolate using vibration ball milling (VBM) where competing intramolecular cyclisation reactions are completely avoided. We further demonstrate the application of liquid-assisted grinding to related displacements using potassium selenocyanate. Results and Discussion

Isosorbide and dimethyl carbonate: a green match

• Fabio Aricò and
• Pietro Tundo

Beilstein J. Org. Chem. 2016, 12, 2256–2266, doi:10.3762/bjoc.12.218

• intermediate, as well as the intramolecular cyclisation reaction (BAl2 mechanism). It is also noteworthy that in general alkylation reactions promoted by DMC chemistry are conducted at temperatures above 150 °C [24][25][26][27][28][29][30][31][32][33][34][35], but in this case study the intramolecular

• cyclisation step leading to isosorbide, which is an alkylation reaction (Scheme 2), takes place at the DMC refluxing temperature (90 °C). To explain this result, computational investigations were conducted on a model compound. The collected results demonstrated that the cyclisation reaction leading to the 5

Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

• Bernardas Morkunas,
• Balint Gal,
• Warren R. J. D. Galloway,
• James T. Hodgkinson,
• Brett M. Ibbeson,
• Yaw Sing Tan,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2016, 12, 1428–1433, doi:10.3762/bjoc.12.137

• intramolecular cyclisation of an analogous β-ketoamide in sulphuric acid [27], or pallidum catalysed intramolecular cyclisation of an acetylene derivative under acidic conditions [28]. The 4-alkylquinolin-2(1H)-one molecular scaffold of compound 4 is clearly distinct from that of AHLs; to the best of our

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• compounds gave 17 in 59% yield and the spirocycle 12 in 8% yield. In the case of the dimethyl allyl analogue 22, reversible protonation (HCO3−) of the enamine moiety in 27 (Scheme 7) and subsequent intramolecular cyclisation would realise the bridged heterocycle 22, with this latter reaction promoted by the

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

• Philipp Röse,
• Steffen Emge,
• Jun-ichi Yoshida and
• Gerhard Hilt

Beilstein J. Org. Chem. 2015, 11, 174–183, doi:10.3762/bjoc.11.18

• -dienols were transformed into cyclic phenylselenoethers by intramolecular cyclisation using selenium cations generated by indirect electrolysis. The reaction was carried out by electrolysing a mixture of the 1,4-dienol, diphenyl diselenide and tetraethylammonium bromide in CH3CN at room temperature in an

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

• Haijun Qu,
• Xuejian Li,
• Fan Mo and
• Xufeng Lin

Beilstein J. Org. Chem. 2013, 9, 2846–2851, doi:10.3762/bjoc.9.320

• condensation of imine 5 with substituted acetaldehyde 2. This could then undergo an iodine-catalytic intramolecular cyclisation to afford the final dihydropyrimidinone 4. Based on the observations above, a preliminary investigation on the catalytic asymmetric version was performed. Recently, our group has

Alkyne hydroarylation with Au N-heterocyclic carbene catalysts

• Cristina Tubaro,
• Marco Baron,
• Andrea Biffis and
• Marino Basato

Beilstein J. Org. Chem. 2013, 9, 246–253, doi:10.3762/bjoc.9.29

• the use of gold species as catalysts for alkyne hydroarylation is still quite limited. A substantial number of reports on the intramolecular cyclisation of arenes with tethered alkyne moieties using gold(I) or, to a lesser extent, gold(III) catalysts can be found in the literature [35][36][37][38][39

• -dichloroethane, 25 °C. Hydroarylation of alkynes. Hydroarylation of ethyl propiolate with pentamethylbenzene. Hydroarylation experiment with catalyst VI under neutral conditions. Intramolecular cyclisation through hydroarylation investigated in this work. Hydroarylation of alkynes using gold NHC catalysts

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• thioacetate in toluene proceeds faster at 55 °C (Scheme 4). The synthesis of the unnatural enantiomer of the natural product spirobrassinin has been achieved by substitution at a quaternary centre by a sulfur nucleophile [14]. Intramolecular cyclisation of a dithiocarbamate 13 allows isolation of 14 with

A convenient allylsilane- N-acyliminium route toward indolizidine and quinolizidine alkaloids

• Roland Remuson

Beilstein J. Org. Chem. 2007, 3, No. 32, doi:10.1186/1860-5397-3-32

• alkaloids ideal targets for total synthesis. We have developed a new method to generate bicyclic indolizidine and quinolizidine compounds based on an intramolecular cyclisation of acyliminium ions substituted by an allylsilyl side chain as an internal π-nucleophile (Scheme 1). [6] This reaction has proven

• and the important biological activities of the compound make this alkaloid an ideal target for total synthesis. [9][10][11][12][13][14][15][16] I 1.1 Intramolecular cyclisation We have found that intramolecular cyclisation of an allylsilane on an acyliminium ion constituted an excellent route to

• converted to (-)-lasubine II with LS-selectride in 65% yield. Acylation of (-)-lasubine II with 3,4-dimethoxycinnamic anhydride gave (+)-subcosine II in 60% yield.(Scheme 12) In conclusion, we have described the total synthesis of (-)-lasubine I, (-)-lasubine II and (+)-subcosine II using intramolecular