Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• unexpectedly high selectivities, ranging from 87:13 to 98:2 (Scheme 3). The isolated product yields were moderate to good and the products were generally obtained as mixtures of regioisomers. Column chromatography allowed the separation of pure isomers of 2a, 2a’, 3a, 3b, 3d, 3h, 3l, 3m, and 3n. However, no

Mesoionic tetrazolium-5-aminides: Synthesis, molecular and crystal structures, UV–vis spectra, and DFT calculations

• Vladislav A. Budevich,
• Sergei V. Voitekhovich,
• Alexander V. Zuraev,
• Vadim E. Matulis,
• Vitaly E. Matulis,
• Alexander S. Lyakhov,
• Ludmila S. Ivashkevich and
• Oleg A. Ivashkevich

Beilstein J. Org. Chem. 2021, 17, 385–395, doi:10.3762/bjoc.17.34

• -regioisomers (152–156 and 143.4 ppm for 1-methyl-5H-tetrazole) [31]. The de-tert-butylation selectivity observed for compound 11b can be explained by the higher stability of the t-Bu cation versus the Me cation. Crystal structures The mesoionic compounds 8a, 10, 11a, and salt 9 were characterized by single

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• mol−1 for endo-1h and 121.75 kJ mol−1 for exo-1h and were consistent with the predicted ones. Next, the reaction with some other cyclic dienes was investigated. The reaction with the unsymmetrical 1-methoxy-1,3-cyclohexadiene (Scheme 5) led to the formation of a mixture of four products (regioisomers

• and stereoisomers, respectively) 3d in 40% overall yield. Two pairs of regioisomers were partially separated by column chromatography with sufficiently slow elution and analyzed by 1H NMR spectroscopy. The structure assignment was made as depicted in Scheme 5. The structures of two pairs of

• regioisomers were assigned by chemical shifts of the singlet of the methoxy group. The products having the MeO and NO2 groups in the adjacent position have the signal of the methoxy protons shifted to a lower field. The assignment of the exo/endo-isomers was carried out by the position of the benzylic proton

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• –20-fold amount. Furthermore, the aryl radical/cation addition onto the aromatic reactant may lead to a mixture of regioisomers when using non-symmetrical Ar–H. A possible solution is having recourse to an intramolecular free radical ipso substitution reaction where an XSO2 tether is placed between

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• reactions of 2-diazomalonates with aliphatic amines [40][52]. The first approach leads to a mixture of two regioisomers and the second method involves the use of explosive diazo compounds. Therefore, such compounds are better prepared by a recently found method in our laboratory which includes the reaction

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• under argon, they obtained a mixture of the two regioisomers (1,4-DHP/1,2-DHP 32:68), proving further the complexity of this reaction [19]. Therefore, continuing our studies for the development and application of environmentally friendly methodologies for multicomponent reactions [20], we attempted to

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• isomers were characterized via HSQC and HMBC NMR spectroscopy (Figure 1). The 13C and 1H measurements of the two regioisomers show remarkable differences in chemical shifts and multiplicity of the relevant signals, though the merged signal of H2’ and an OH group in one of the spectra (Figure 1A) impedes

• in the presence of AgNO3, yielding a mixture of two regioisomers, although with the 2’-O-TBDMS protected isomer in excess over the 3’-O-TBDMS isomer [31]. Both species can be separated by chromatography; and often it is trusted that the isomer with the higher Rf value is the desired 2’-O-isomer. As

• the traditional method of reacting the 2’-, 3’- unprotected nucleoside and subsequently separating the formed regioisomers, in particular if like here, the desired 2’-O-isomer is the minor product. Moreover, the regiospecific iodination of the C8-position of 3’,5’-O-di-tert-butylsilyl-2’-O-TBDMS

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• leading to the observed regioisomers of the isoprenyl esters. All acids shown were found in form of their isoprenyl esters. (Z)-9-Hexadecenoic acid is obtained from palmitic acid by a Δ9-desaturase (ds). Malonate elongation and reduction (red) leads to (Z)-3-hydroxy-11-octadecenoic acid, an intermediate

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• in the formation of two regioisomers, 4a and 4b (Scheme 3). In this context, the isomers 4a and 4b were separated by column chromatography (see Experimental section), and the structure of both was established by X-ray diffraction. In the 19F NMR spectra of both isomers 4a and 4b, the resonances

• to the formation of two regioisomers, but interestingly, the ratio of the 7-CF2H- and 9-CF2H-isomers varied broadly from 1:2 [22] to 3:2, depending on the reaction conditions and the source of difluorocarbene [11]. Mechanism, regiochemistry, and rotation barriers of the CH(CF3)2 group The mechanism

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• separable regioisomers were obtained in moderate-to-good overall yields (Scheme 19). In similar fashion, trisubstituted sumanene derivatives were also prepared as shown in Scheme 19. The monochlorosumanene 88 was also reported by Amaya and Hirao in three steps from the sumanene (2) using a classic nitration

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• regioselectivity, as the main direction is cyclization through the N1 nitrogen atom with the formation of 3-phosphonylated thiazolo[3,2-a]-7-oxopyrimidines 4a–c and 5-oxo regioisomers 5a–c in a ≈1:0.1–0.3 ratio with yields of 87–91% (Scheme 7). The structure of thiazolopyrimidines 4a–c and 5a–с is difficult to

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• [8][9]. However, these nitration methods are less effective because the yield of the desired product is reduced by the formation of regioisomers. Although the hydroxylation of 3-arylated-1-fluoro-4-nitrobenzene has also been reported as a related strategy, multistep reactions are necessary for

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• stoichiometric amount of Co2(CO)8. Products 59 were obtained in moderate to excellent yields, as single regioisomers, and 59c as a 1:1 mixture of diastereoisomers. The most striking feature was the unexpected regiochemical outcome of this study; the fluorinated moiety occupied the α-position in the final

• used in this study, namely norbornene and ethylene (Scheme 39). Contrary to the results observed with norbonadiene and ethylene, which both furnished a single regioisomer, the use of norbornene afforded mixtures of regioisomers, although the same α-CF3 isomer was favored in all cases. The

• substituents such as dimethylaminium, trifluoromethyl, and acetyl favored the β-regioisomer (71B). The 4-fluorine substituted diarylalkynes had a very weak EWG effect yielding an equimolar mixture of both regioisomers. The experimental results were confirmed by a DFT study of the NBO charges of the α-alkyne

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• crystals from derivative 8a were unsuccessful. It has to be emphasized that theoretically, the formation of four dimer-like regioisomers could be expected from aldehydes 1a–d, each of them as the mixture of two diastereomeric racemates. Although HPLC–MS measurements indeed indicated the presence of

• formation of dimers 5. Rearrangement of aminoaldehydes 1 to regioisomers 2 and formation of dimer-like products 3 and 8. Proposed mechanism of the isomerization of aldehydes 1 via isoindoles 4. Proposed mechanism of the formation of dimer-like products 3a,b. Proposed mechanism for the formation of dimer

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• of water (2 equiv) to the reaction mixture with BTMS (12 equiv, Table 1, entry 5) resulted in the complete conversion of substrate 10 into compounds 15–17 within 24 h. In this case, over 60% of the reaction mixture constituted compound 15, while the regioisomers 16 and 17 were formed in comparable

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• charge at C-4. The existence of 4-hydroxy regioisomers was established by comparison of the 1H NMR spectrum of 8a with the already reported values for the known 5-hydroxyisoxazolidine possessing the same substituents at the N2 and C-3 atom [32]. The main differences between both regioisomers can be

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• % yields). Mixtures of regioisomers were obtained when a m-substituted N,N-dimethylaniline was used. The authors have proposed a reductive quenching pathway mechanism for this protocol (Scheme 8). The use of NiTPP as photoreductant was also exploited in the selenylation and thiolation reactions of anilines

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• to generate 13a and 13b as a mixture of regioisomers in a ratio of 4:1. There was no requirement to separate these isomers at this stage. Subsequent addition of potassium tert-butoxide into a mixture of 13a and 13b in dichloromethane (DCM) resulted in an efficient elimination to generate vinyl

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

• the pure product TOI1 in 55% yield. The isolated compound was thoroughly characterized by spectroscopic techniques. Having successfully establish reaction conditions for the synthesis of TOI1, we then focused our efforts on the generation of regioisomers TOI2 and TOI3-rev, respectively. Initial

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• definition and fails as a real “click” reaction. Although this cyclization reaction requires elevated temperatures and often yields both the 1,4- and 1,5-regioisomers, the Cu or Ru alkyne–azide cycloaddition falls exactly into the above definition [11]. In this respect, the copper-catalyzed cycloaddition

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• protons at 6.65–7.45 ppm. The spectral data obtained for the tetrahydropyrimidines 4 most likely corresponded to the possible regioisomers A and B (Figure 1). Additional NOESY experiments, in particular for compound 4k, showed the presence of cross-peaks between the CH proton at position 5 with the

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• method was evaluated using aldehydes containing different functionalities. For example, the use of vanillin, an aldehyde containing the acidic phenol group as substituent, gave the corresponding product 2o in 93% yield in an 82:18 ratio of regioisomers. In the same way, when aldehydes containing an ester

• in parentheses refers to the mixture of propagyl and allenyl regioisomers determined by GC analysis. Synthesis of potassium allenyltrifluoroborate (4). Propargylation of aldehydes using potassium allenyltrifluoroborate (4). Propargylation of 2-naphthaldehyde with allenylboronic acid pinacol ester (1

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• substrates, a mixture of regioisomers, resulting from α- and β-arylation, was formed (see Supporting Information File 1, Figures S16 and S17, S32 and S33) [21]. In case of the reaction with allyl alcohol, the generated products isomerized in situ to give the saturated aldehydes, compounds 12, 21, and 22, a

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• amounts of carbohydrate-containing molecules. Due to the chemical nature of carbohydrates, with multiple possible linkage positions giving rise to different regioisomers, with two possible anomeric configurations, the chemical synthesis of complex oligosaccharides is difficult and a rather time-consuming

• disaccharides and the yield by integration of the signals corresponding to the anomeric positions or other well-resolved signals. The reaction mixtures were purified by column chromatography in order to obtain the products for characterization, and to confirm the yields of the isolated regioisomers. The

Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

• Zachary Lee,
• Brandon R. Jones,
• Nyochembeng Nkengbeza,
• Michael Phillips,
• Kayla Valentine,
• Alexis Stewart,
• Brandon Sellers,
• Nicholas Shuber and
• Karelle S. Aiken

Beilstein J. Org. Chem. 2019, 15, 2747–2752, doi:10.3762/bjoc.15.265

• , internal alkynes results in a mixture of regioisomers [20][23][24]. Moreover, per Baldwin’s rules, with neighboring group participation, a 5-exo-dig (via 13 and 14) or 6-endo-dig pathway (via 16 and 17), or both, are possible outcomes for such alkynes [25]. The 5-exo-dig route would provide 15, while the 6