N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• decrease in the yield of the target compound 6h. The structures of the obtained regioisomers 6g and 6h were confirmed by the NOESY spectra, in which cross-peaks between the protons of the glutarimide ring and the singlet of the proton of the pyrazole cycle are observed. Reactions with benzotriazoles are

• characterized by high regioselectivity. We obtained tetrazol-2-yl glutarimides 6p and 6q in moderate yields. Alternative regioisomers (tetrazol-1-yl glutarimides) were observed only in trace amounts (according to NMR data). It should be noted that in this work the insertion of the diazocarbonyl reagent into the

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• -difluoroalkenes that subsequently undergoes a cycloaddition reaction. Results and Discussion While investigating 1,3-dipolar cycloaddition reactions between organic azides and gem-difluoroalkenes to obtain the 4-fluoro-1,4-disubstituted 1,2,3-triazole regioisomers, we observed an interesting reactivity while

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• whereas heating it in 75% acetic acid solution produced the deprotected compound but migration of the acyl group from the sn-2 to the sn-3 position lead to an inseparable mixture of regioisomers. A selective desilylation of 12.5 was finally achieved with BF3·Et2O producing 12.6 without migration of the

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• preliminary conditions, albeit in low yield (35% yield) and low regioselectivity (1:1) (Table 1, entry 1). No regiocontrol was observed; but remarkably, the regioisomers exhibited distinct retention factors on silica gel, allowing 11 and 12 to be isolated separately in good yield as single trans diastereomers

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• the CD molecule where the monofunctionalization can occur. Consequently, monosubstituted CDs can be mixtures of three regioisomers. The number of known monosubstituted CD derivatives is enormous, since monosubstitution was the almost exclusive reaction for the practical production of selectively

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• promoted by EtAlCl2. Two separable alkene regioisomers 54 and 55 were obtained in 19% and 50% yield, respectively. A metal-catalyzed hydrogen atom transfer (MHAT) allowed 54 to be partially converted to 55 via Shenvi’s isomerization [37]. Selective TBS protection on the bicyclo[3.2.1]octane moiety and

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• -deazahypoxanthine To the best of our knowledge, only one synthesis of 1-deazahypoxanthine has been described so far [29]. Kubo and Hirao started their synthesis from 2,3-diaminopyridine (23) which was converted into benzyl-protected 1-deazaadenine 28 (as a mixture of N7 and N9 regioisomers) in five steps, followed

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• analogous reaction is regioselective and resulted in the formation of two products, i.e., N7- and N9-regioisomers (Scheme 1). In no case, the N1-, N3-, or N6-products were formed, which is comparable to the results reported for the reaction between benzoyl chloride (BzCl) and purine anions [25]. The two

• different regioisomers, 1-N7 and 1-N9, were formed simultaneously in the course of the reaction between adenine anion 1 and FcCOCl in DMF (Scheme 1). According to the 1H NMR spectrum (Figure 1) of a reaction aliquot, the ratio of N9/N7 isomers is 1.5:1, i.e. 60% regioselectivity is reached. The formation of

• , within the group of N7-regioisomers, the calculated %VBur increases with more bulkier groups at the C6-position (as going from 1 to 6), whereas no significant effects are observed in the series of N9-isomers (Table S3 in Supporting Information File 1). These results nicely complement the trend measured

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• anticancer cytotoxic agents. Diverse bioactive compounds based on the privileged 1,4-DHIQ scaffold. Strategy investigated in this work. Preparation of 3(2H)-isoquinolones 11. aObtained as a 10:1 mixture of regioisomers; purified by crystallization. bEmployed in the next step without purification (not

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• rearrangement resulting in the formation of thymol (41) along with its regioisomers 42 and 43. However, using an excess of isopropanol and a relatively low concentration of the organic substrates in scCO2 (5% w/w), thymol (41) is produced in a good yield (72%) and selectivity (92.2%) as shown by GC

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• dichlorinated regioisomers (L5Cl-I and L5Cl-II) (Scheme 1 and Table 1, entry 4). The chlorination of L3 substrate with a primary amine as substituent gave the monochlorinated product L3Cl-I in 46% yield, while the yields of L4Cl-I and L5Cl-I were 85% and 83%, respectively (Table 1, entries 2–4). Although both

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• , entry 16). Notably, no other regioisomers of isoxazole 3a were overserved in any of these reaction conditions. With the optimized reaction conditions for the formation of 3,4,5-trisubstituted isoxazoles 3a (DIPEA, 95% water, 5% methanol, room temperature, Table 1, entry 12) at hands, we explored the

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• -stereocontrolled ring-opening reactions of oxa- and azabicyclic olefins with dialkylzinc reagents catalyzed by a nickel compound (Scheme 1) [60]. The reaction was entirely stereoselective; however, unsymmetrical OBDs 5 produced mixtures of regioisomers 6 and 7. In the same year, Hill and co-workers published a

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• [3,4-d][1,2,3]triazine core with commercially available building blocks, enabling the extension of the protocol to gain other derivatives straightforwardly. Attempts to synthesize 3,7-substituted-4,7-dihydro-3H-pyrazolo[3,4-d][1,2,3]triazines, the regioisomers of the successfully gained 3,6-substituted

•  1, the alkylation protocol did not give a selective conversion in favor of one of the generated isomers. The protocol was not changed or adapted to gain a higher selectivity of one of the isomers, as both regioisomers were used in the subsequent syntheses. For the derivatives 12h and 13c, we were

• viability of HeLa cells, their regioisomers 13a and 13d–h decreased the viability at high micromolar concentrations. A slightly increased cytotoxicity of some derivatives of compound class 12 compared to 13 was observed for 12b and 12c. The amides 9 had no influence on the viability except for derivate 9b

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

• regioisomers. Methoxyfluorenone 10f was afforded in 15% yield and methoxyfluorenone 10d starting from amine 15f in 42% yield. Notably, only 10d was obtained upon cyclization of amine 9d (Scheme 4). Interestingly, the combined yield of the two regioisomers (57%), stemming from one educt exceeds the yields of

• both 10e and 10b starting from amine 15b2. The same trend concerning relative yields between regioisomers can be observed for fluorenones bearing the electron-withdrawing trifluoromethyl group in the same positions (see 10g, 10h, 10i1, and 10i2). This is rather surprising, as electronic effects exerted

AlBr₃-Promoted stereoselective anti-hydroarylation of the acetylene bond in 3-arylpropynenitriles by electron-rich arenes: synthesis of 3,3-diarylpropenenitriles

• Yelizaveta Gorbunova,
• Dmitry S. Ryabukhin and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2663–2667, doi:10.3762/bjoc.17.180

• hydroarylation of nitriles 1. Reactions of nitriles 1a–c with o-xylene led to the formation of regioisomers derived from the electrophilic substitution at different positions of this arene. Thus, nitrile 1a gave two types of regioisomers 2n and 2o. After reactions of nitriles 1b,c with o-xylene, compounds 2l and

• 2m correspondingly were obtained; other regioisomers were not isolated in amounts that were high enough for their identification. This transformation was also tested with another strong Lewis acid, aluminum chloride (AlCl3), for the reaction of nitrile 1a with benzene. However, in this case, mainly

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• % yield), para-alkoxy and para-halogen substituents (45–69%), ortho-methyl (74%), and meta-methyl (80% as a 65:35 mixture of regioisomers). Electron-withdrawing groups (nitro, cyano, and methyl ester) stopped at the ketone intermediate. Interestingly, another tandem sequence that exploits the relief of

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• proton and aromatic protons (see Supporting Information File 1). In the case of the reaction with o-xylene, pairs of E/Z-isomers of two regioisomers, (E/Z)-5b and (E/Z)-5b1, were obtained. We also checked the reaction of oxadiazole 3a with benzene under the action of Lewis acids AlCl3, AlBr3 and acidic

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• precursor, potentially leading to both regioisomers and unwanted side products, complicating purification. As a result, accounts of bis-arylation using radical chemistry are scarce and report very low yields [29][30][31][32]. While transition-metal catalysis is a viable strategy, it is often based on

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• cycloaddition reactions via the copper-catalyzed 1,3-dipolar cycloaddition reaction (CuAAC) of the azides 5 and 9 with suitably functionalized acetylenes 6a–j, using sodium ascorbate and copper sulfate in ACN/H2O 2:1 under microwave irradiation were carried out to obtain the 1,4-regioisomers of the final

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• possibly be utilized for the current investigation with expectations to minimize the formation of regioisomers, dimerized side products and overcome the usage of allylic-OH protected MBH adducts. Metallosalen complexes can be easily prepared and safely handled. The stability of metallosalen complexes

• synthesis of indenes from MBH adducts restricts the formation of regioisomers [10] and hinders the formation of dimerised side products [11]. In addition, the reaction smoothly accesses substituted indenes from MBH adducts at room temperature. In conclusion, the methodology is attractive for its easy

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• synthesis of azulene-bithiophene copolymers 61–65 in which varied ratios of different regioisomers of azulene (1,3- and 4,7-connected) were present (Scheme 13). The synthesis of the key building block 5,5’-bis(trimethylstannyl)-3,3’-didodecyl-2,2’-bithiophene (60) is shown in Scheme 13A. The reaction of the

• bis-stannylated bithiophene 60 with varying ratios of dibromoazulenes 4 and 12 under Stille reaction conditions furnished the azulene-bithiophene copolymers 61–65 in decent yields (Scheme 13B). The final composition of the 1,3- and 4,7-regioisomers of azulene in the polymer chain was determined by 1H

• -diboronate 103 with varying ratios of 1,3-dibromoazulene (4) and 4,7-dibromoazulene (12) under Suzuki reaction conditions (Scheme 20). As stated above in the case of azulene-thiophene polymers 61–65, the final composition of 1,3- and 4,7-regioisomers of azulene in the polymer chain was determined by 1H NMR

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• effect of varying these reaction parameters, using n-pentyl bromide as the prototypical N-alkylating reagent (Table 1). Early investigations revealed that the combination of cesium carbonate (Cs2CO3) in dimethylformamide (DMF) at room temperature (≈ 20 °C) afforded a mixture of N-1 and N-2 regioisomers

• demonstrated a higher preference for N-1 indazole alkylation under conditions B, when compared with conditions A (Table 2, entries 1, 2, 4–7, and 9). Furthermore, C-3 ketone (22) and amide (23 and 24) substituted indazoles also gave the corresponding N-1 regioisomers with a high degree of N-1 regioselectivity

• from the N-2 position to the N-1 atom by the indazole C-3 substituent (vide infra). While the corresponding N-1 and N-2 regioisomers arising from the N-alkylation of C-3 substituted indazoles 12–24 were generally amenable to separation using wet flash column chromatography, the corresponding N-1- and N