A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions

• Vitor A. S. Almodovar and
• Augusto C. Tomé

Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169

• (disubstitution) and non-symmetrical (monosubstitution) DPP derivatives are formed in excellent overall yields. The optical properties of the newly synthesized compounds are also discussed. The new platform may be useful for bioorthogonal chemistry. Keywords: diketopyrrolopyrrole; fluorescent dye; nucleophilic

• functionalized DPP derivatives. As anticipated, it displayed reactivity with thiols and phenols through nucleophilic aromatic substitution at the pentafluorobenzyl groups, yielding both symmetrical (disubstitution) and non-symmetrical (monosubstitution) derivatives in satisfactory yields (Scheme 1). Thiols are

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

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

• ; monosubstitution; reduction; Introduction Cyclodextrins (CDs), as cyclic oligosaccharides, consist of a macrocyclic ring of glucose subunits linked by α-1,4-glycosidic bonds [1]. They are widely used in pharmaceutical, food and chemical industries, as well as in agriculture. It has been known for decades, that CD

• 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

• easier process than the optimization of a new monosubstitution reaction on a native CD [5]. Monotosylation of the primary rim of CDs is the most widely used method to obtain C-6 monofunctionalized CDs. Tosyl chloride (TsCl) reacts with α-, β-, and γ-CD in pyridine to give the C-6-monosubstituted product

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• quenchers (e.g., PhSSPh) to the reaction mixture. When monosubstitution of the aryl group is present, the formed radical cation, the product of the photooxidation of the cinnamyl ether, readily cyclizes to cyclobutene radical cation 217. The latter cleaves the benzylic C–C bond to produce the 1,4-radical

• nucleophile is employed, radical 223 is favored, leading to either monosubstitution or disubstitution with external nucleophiles, depending on the presence of oxidant or reductant in the reaction mixture. Based on this plan, Zhu’s group managed to synthesize a rich number of lignans and congeners, such as

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• -aryloxy alcohols were thereafter synthesized through the KR of epichlorohydrin with different phenols using chiral Co–salen catalyst 2f (Table 3). meta-Substituted methylphenol showed less reactivity and selectivity (Table 3, entry 2), while tert-butyl monosubstitution at the para-position on the phenol

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• modification of native CD skeletons with new functional groups enhances the application of CDs and provides access to new organic chemistry transformations and catalytic systems. Among the approaches used for chemical derivatization of CD skeletons, monosubstitution on the primary rim of CD (Figure 1) is a

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• high selectivity towards the primary rim in monosubstitution of β-CD [22][23]. Our assumption was that targeting the disubstituted product with the same tosylating agent would preserve the side-selectivity and significantly reduce the number of possible regioisomers (6A,6B-, 6A,6C- and 6A,6D-ditosyl-β

Catalysis of linear alkene metathesis by Grubbs-type ruthenium alkylidene complexes containing hemilabile α,α-diphenyl-(monosubstituted-pyridin-2-yl)methanolato ligands

• Tegene T. Tole,
• Johan H. L. Jordaan and
• Hermanus C. M. Vosloo

Beilstein J. Org. Chem. 2019, 15, 194–209, doi:10.3762/bjoc.15.19

• temperatures. The high stability, very good activity, selectivity, TON and TOF of the four precatalysts, at high temperatures, proved that the hemilability of the bidentate hemilabile pyridinyl alcoholato ligand can be influenced by monosubstitution on the pyridinyl moiety. A Ru/1-octene precatalyst

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• , among other fields [2]. Recent studies have improved the properties of CD scaffolds primarily by selective persubstitution and monosubstitution [2][3], thereby broadening their application. However, the synthesis of selectively disubstituted CD derivatives with the same or different functional groups at

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• -ABA led to the monosubstitution product using equimolar amounts of both reagents. The individual steps were optimized achieving good to excellent overall yields of the desired heterocycles, avoiding additional protection and deprotection steps. A mechanistic interpretation for the cyclodehydration

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• -TsOH in aqueous acetonitrile at 75 °C for 4 h afforded the benzotropolone 241. 5.3.2. Reaction of 7-hydroxy-2,3-benzotropone (241): Various monosubstitution products 289–291 of 7-hydroxy-2,3-benzotropone (241) were readily prepared by Nozoe’s group (Figure 12) [174]. The synthesis of bromo-derivative

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• (see Supporting Information File 1 for more details) [37][38][39][40]. The amine 9 was then attached to a squaramide moiety using dimethyl squarate (10) in slight excess to ensure monosubstitution. In this way compound 11 was isolated in 80% yield. We have originally envisaged the transformation from

Synthesis and supramolecular properties of regioisomers of mononaphthylallyl derivatives of γ-cyclodextrin

• Markéta Bláhová,
• Sergey K. Filippov,
• Lubomír Kováčik,
• Jiří Horský,
• Simona Hybelbauerová,
• Zdenka Syrová,
• Tomáš Křížek and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2017, 13, 2509–2520, doi:10.3762/bjoc.13.248

• group at position 2 is the most acidic, and the group at position 3 is most sterically hindered. Therefore, regioselective monosubstitution to positions 2 and 6 can be controlled by the amount and strength of the base used in the reaction, whereas monosubstitution at position 3 can be achieved by

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• formed propargyl group is isomerized to an allene moiety, obviously due to the excess of the strongly basic lithium salt [35]. This unexpected monosubstitution remains unexplained and is not applicable as basis for a general selective synthesis of monoalkynylcamphor derivatives. Alkynes can also be

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• protons unambiguously confirms the monosubstitution pattern (DS = 1) in both cases and was further proven by electrospray ionization mass spectrometry (ESIMS) analysis of the compounds (see Supporting Information File 1). The signals in the aromatic region are well resolved (see Figures S25 and S33

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• exchange required considerably larger halogen/reagent ratios than the solution reactions, sulfur nucleophiles showed a more favourable tendency and the reagent/halogen ratio was either roughly equal or slightly lower than for the monosubstitution. In the solution synthesis [6] of β-CD-per-6-dodecane

• yields that were usually lower that those given by the monosubstitution reactions [22]. The very low aqueous solubility of the CD halides led to the intact starting materials being completely lost during the work-up. The low TU/halogen ratio (entries 2, 7 and 8 in Table 1) gave incomplete reactions

Supramolecular structures based on regioisomers of cinnamyl-α-cyclodextrins – new media for capillary separation techniques

• Gabor Benkovics,
• Ondrej Hodek,
• Martina Havlikova,
• Zuzana Bosakova,
• Pavel Coufal,
• Milo Malanga,
• Eva Fenyvesi,
• Andras Darcsi,
• Szabolcs Beni and
• Jindrich Jindrich

Beilstein J. Org. Chem. 2016, 12, 97–109, doi:10.3762/bjoc.12.11

• compound is unsubstituted at the C6 position, since the characteristic peaks of the two magnetically non-equivalent proton (C6-Ha and C6-Hb), typical for C6 substitution [12] are not detectable in the spectrum. As a consequence the compound is C2- or C3-monosubstituted (the monosubstitution has also been

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• of the product was observed, it was not a clean reaction. The N-methylimidazolium triflate (NMI·Tf) method reported for the monosubstitution of diamidites was found to be effective [53], resulting in relatively clean formation of amidites 10 and 11 (Scheme 3). The initial reaction produced a yellow

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers

• Milo Malanga,
• Mihály Bálint,
• István Puskás,
• Kata Tuza,
• Tamás Sohajda,
• László Jicsinszky,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319

• the case of the β-CD the 60 min reaction was considered to be optimal for the 6-monosubstitution (Figure 1) and the identical conditions were used for the modification of the polymer. In order to set the correct molar ratio between the reagents it is necessary (but not sufficient) to know the Mw of

A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges

• Martin Popr,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2014, 10, 1390–1396, doi:10.3762/bjoc.10.142

• methylation. The majority of the presented reactions are very straightforward with a simple work-up, which avoids the need of chromatographic separation. Thus, these reactions are suitable for the multigram-scale production of monosubstituted cationic CDs. Keywords: cationic; cyclodextrins; monosubstitution

• crystalization from water. So we developed a new chromatography-free method for the purification of the reaction mixture by crystalization. Monosubstitution of β-CD was carried out by the reaction of p-toluenesulfonic anhydride in aqueous NaOH as described previously in literature [17]. The reaction yielded a

Halogenated volatiles from the fungus Geniculosporium and the actinomycete Streptomyces chartreusis

• Tao Wang,
• Patrick Rabe,
• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2767–2777, doi:10.3762/bjoc.9.311

• and 1,2,4-trichloro-3-methoxybenzene by monosubstitution [23], but small amounts of disubstitution products were also formed that were rigorously purified from the mixture by repeated column chromatography. Starting from 1,2,3,5-tetrachlorobenzene (12) the same reaction conditions also provided a

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• ). Even unsubstituted substrate 31 afforded the corresponding product 32 in excellent yield although more forcing conditions were necessary (Scheme 9c). Monosubstitution at carbon C1 or C2 of the chain led to the formation of the product 2,4-cis or 2,5-cis-32 with diastereomeric ratios up to 5.5:1

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• vessel, and consequently they employed a borescope camera to visualise the interior of the reactor. This allowed the authors to make phase measurements by visual inspection, to discover that with n-propanol as the alkylating agent, the best results for monosubstitution were obtained by using either

Structural conditions required for the bridge lithiation and substitution of a basic calix[4]arene

• Conrad Fischer,
• Wilhelm Seichter and
• Edwin Weber

Beilstein J. Org. Chem. 2011, 7, 1602–1608, doi:10.3762/bjoc.7.188

• -bromosuccinimide used, surprisingly only monosubstitution of the chalice is observed by application of the lithiation technique, independent of the amount of n-BuLi. However, twofold substitution on opposite methylene bridges can be achieved by successive application of the latter technique [6]. This may suggest

• potentially accessible for guest inclusion, which is also reflected by a comparatively low packing index (62.9) of the crystal [15]. Conclusion It was shown that the bridge monosubstitution of a basic calix[4]arene via lithiation requires a high conformational flexibility of the calixarene, which is the case

Gold(I)-catalyzed formation of furans by a Claisen-type rearrangement of ynenyl allyl ethers

• Florin M. Istrate and
• Fabien Gagosz

Beilstein J. Org. Chem. 2011, 7, 878–885, doi:10.3762/bjoc.7.100

• corresponding furans 7f, 7g, 7o, 7q and 7s in moderate to quantitative yields (entries 6, 7, 15, 17 and 19). It is also worth noting that an increase in the substitution at the terminus of the allylic moieties of the substrates (monosubstitution in the case of 6b, disubstitution for 6c–s) did not notably