KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• Qiao Lin Shiling Zhang Bin Li School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, Guangdong Province, P.R. China 10.3762/bjoc.16.44 Abstract An efficient and simple KOt-Bu-promoted selective ring-opening N-alkylation of 2-methyl-2-oxazoline or 2-(methylthio)-4,5

• important role to promote this ring-opening N-alkylation, but also acts as an oxygen donor. Keywords: N-alkylation; oxazolines; potassium tert-butoxide; ring opening; thiazolidinones; Introduction 2-Oxazolines are important structural units in pharmaceutical applications and efficient ligands in

• TMSN3 as the azide source [10] (Scheme 1a). Coates described a Co2(CO)8-catalyzed ring-opening hydroformylation of oxazolines for the synthesis of β-amidoaldehydes [11] (Scheme 1a). However, the ring-opening N-alkylation of 2-oxazolines to produce 2-aminoethyl acetate derivatives under basic conditions

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

• with a bromoalkyne (Scheme 24) [39]. The catalyst was selected using a combinatorial approach for the selection of the optimal catalyst structure. The product was isolated in an excellent 87% yield. In 2018, Wang, Xu, and co-workers described the reductive decarboxylative alkylation of glycine and

• -phenylglycine ester, and the alkylated products were obtained in good to excellent yields. In addition, various glycine derivatives were also alkylated in good yields. Finally, the authors demonstrated the synthetic interest of their methodology through the alkylation of di- and tripeptides. The authors studied

• amination of NHP esters. Photocatalytic decarboxylative alkynylation using [Cu(I)(dq)(binap)]BF4. Copper-photocatalyzed alkylation of glycine esters. Copper-photocatalyzed borylation of organic halides. aUnder continuous flow conditions. Copper-photocatalyzed α-functionalization of alcohols with glycine

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• values were observed (20–36% ee), whereas no reactivity was observed with α,β-unsaturated amides. Although Pineschi’s conditions were ineffective for amides [49], Harutyunyan and co-workers achieved an important breakthrough by reporting the first enantioselective alkylation of α,β-unsaturated amides [50

Synthesis, liquid crystalline behaviour and structure–property relationships of 1,3-bis(5-substituted-1,3,4-oxadiazol-2-yl)benzenes

• Afef Mabrouki,
• Malek Fouzai,
• Armand Soldera,
• Abdelkader Kriaa and
• Ahmed Hedhli

Beilstein J. Org. Chem. 2020, 16, 149–158, doi:10.3762/bjoc.16.17

• acids in the presence of phosphorus oxychloride according to standard methods [29], oxadiazole derivatives 2 were obtained (Scheme 1). On the other hand, we converted compound 1 into sulfanyloxadiazole derivatives 4 by treatment with carbon disulfide and subsequent alkylation of the obtained

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• -anchored indole-5-carboxylic acid was successful during the homogeneous two-phase alkenylation reaction. Subsequently, during its removal from the support under alkaline conditions, N-alkylation occurred through a Michael addition to the acrylate 2a, followed by the formation of the methyl ester of the 5

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• , so it was sought to minimise their exposure to these conditions during synthesis. In the end, we used two routes to the thioindoxyls: either Friedel–Crafts acylation of α-phenylthioacetic acids (which are easily accessible from thiophenols by alkylation using 2-chloroacetic acid, Figure 1b) or else

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• derivatives of 2 [30]. The library contained 29 compounds grouped into several series: with natural amino acid mutations affecting the amphipathicity (series i), with point mutations that modulate polarity and conformational stability of the β-structural elements (series ii), with backbone N-alkylation and

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• purification (Scheme 2). The equatorial arrangement of the C-glycosyl linkage was supported from the large value of the coupling constant J1,2 (9.5 Hz), indicating a 1,2-trans orientation of the respective protons. The monomethyl phosphonate ester 9 was then subjected to alkylation reactions in order to allow

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• nucleophile 16 affords the 2,3-elimination product 19. To substantiate the reaction mechanism and expand the substrate scope, we synthesized derivatives 21 and 25 through alkylation of 3 with MeI/NaH and BnBr/NaH, respectively, in DMF, following the reported procedures [35], which afforded the trimethylated

Design, synthesis and investigation of water-soluble hemi-indigo photoswitches for bioapplications

• Daria V. Berdnikova

Beilstein J. Org. Chem. 2019, 15, 2822–2829, doi:10.3762/bjoc.15.275

• solubility in aqueous medium and potential RNA-binding properties, the dimethylaminopropyl substituent [19] was introduced to hemi-indigo Z-1c. Two synthetically straightforward approaches of the alkylamino group introduction were considered: (i) N-alkylation of the indoxyl core and (ii) O-alkylation of the

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• acetonitrile, forming the BAPTA precursor 1b. The palladium-catalyzed benzyl cleavage was followed by a double alkylation with 2, reactant 2 being synthesized from 4-(4-nitrophenyl)butanoic acid. The 4-nitrobenzene groups of the pendant arms were subsequently reduced yielding the corresponding anilines (1e). A

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

• and his group developed an electrochemical strategy for the asymmetric alkylation of 2-acylimidazole derivatives 94 with substituted para-methylphenols 95 using Ni(OAc)2 as a Lewis acid catalyst in presence of chiral diamine ligand 96 (Scheme 34) [71]. Based on their detailed mechanistic studies, the

• group further extended the application of the SOMO protocol to the enantioselective α-alkylation of aldehydes [75]. Using modified chiral secondary amine 114, the authors showed that constant current electrolysis of aldehydes 105' with xanthenes 113 in an undivided cell resulted in α-alkylated aldehydes

• synthesized chiral compounds based on phosphorus esters and investigated their effects as chiral auxiliaries in the α-alkylation of secondary amines via anodic oxidation [100]. The constant current methoxylation of N-protected chiral pyrrolidines 173 in an undivided cell resulted in 174 in excellent yield

Synthesis of aryl-substituted thieno[3,2-b]thiophene derivatives and their use for N,S-heterotetracene construction

• Nadezhda S. Demina,
• Nikita A. Kazin,
• Nikolay A. Rasputin,
• Roman A. Irgashev and
• Gennady L. Rusinov

Beilstein J. Org. Chem. 2019, 15, 2678–2683, doi:10.3762/bjoc.15.261

• derivatives 6a–o, substrate and product scopes, and yields. Alkylation of TTI 6d. Supporting Information X-ray crystallographic data. Deposition number CCDC 1944913 for compound 7d contain the crystallographic data for these structures. These data can be obtained free of charge from the Cambridge

Plasma membrane imaging with a fluorescent benzothiadiazole derivative

• Pedro H. P. R. Carvalho,
• Jose R. Correa,
• Karen L. R. Paiva,
• Daniel F. S. Machado,
• Jackson D. Scholten and
• Brenno A. D. Neto

Beilstein J. Org. Chem. 2019, 15, 2644–2654, doi:10.3762/bjoc.15.257

• purification [41]. The new derivative was then synthesized by a direct alkylation reaction which afforded the desired compound BTD-4APTEG in 65% yield after purification (see details in the Experimental section). The structure of BTD-4APTEG bears a lipophilic anchor to improve its affinity towards the lipidic

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• results in the sensing of anions. In fact, strictly speaking this interaction is not a hydrogen bonding interaction seen as there is no X···H–Y unit (X, Y = O, N, F) but these interactions are often referred to as such in the literature. The anion binding can be enhanced by the alkylation of 1,2,3

• macroring. A second strategy is the macrocyclization of an acyclic precursor containing pre-functionalized triazole by other ring closure methods such as Grubbs metathesis [25] and amidation reactions. The macrocyclization is normally followed by N-alkylation (often methylation) leading to the synthesis of

• -triazolium receptors A ferrocene-containing dicationic bis-triazolium macrocycle 4 (see Figure 4) has been designed and synthesized by utilising the intramolecular Eglinton cyclisation of an acyclic bis(triazolylalkyne)ferrocene precursor followed by alkylation. The anion sensing ability was investigated by

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• at either α or β-position has been of particular interest [23]. Just to mention Córdova’s α-oxygenation [11][12][13] or β-alkylation or β-arylation reported by Melchiorre [16] and MacMillan [17][18]) which represents only a tip of an iceberg of photochemical methods for the introduction of

1,2,3,4-Tetrahydro-1,4,5,8-tetraazaanthracene revisited: properties and structural evidence of aromaticity loss

• Arnault Heynderickx,
• Sébastien Nénon,
• Olivier Siri,
• Vladimir Lokshin and
• Vladimir Khodorkovsky

Beilstein J. Org. Chem. 2019, 15, 2059–2068, doi:10.3762/bjoc.15.203

• undergoes alkylation by methyl iodide or propyl iodide in MeCN for 2 days to afford 7a and 7b in 90 and 92% yields, respectively (Scheme 2). The dimethyl derivative 8 can be prepared using a stronger methylating agent such as trimethyloxonium tetrafluoroborate. Comparison of the 1H NMR spectra clearly

• : nitrogen, blue; carbon, grey; iodine, violet. Synthesis of THTTA (3). Protonation, alkylation and acylation of 3. Charge transfer and delocalization within 3 and its diprotonated (6a) and monomethylated (7a) derivatives. Experimental and calculated selected bond lengths (Å). Supporting Information

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• potential was estimated to be approximately +1.0 V (vs SCE) which is sufficient to photocatalyze typical organic reactions. The photoredox catalytic activity in the visible light range was tested by the α-alkylation of 1-octanal as benchmark reaction. Irradiations were performed with LEDs in the visible

• cNDI 2 [48][49]. Hence, the photoredox properties of the new cNDI 2–6 are comparable to those of eosin Y and rhodamine 6G as other organic photoredox catalysts. Photoredox catalysis with NDI 1 and cNDI 6 The α-alkylation of 1-octanal (12) by diethyl 2-bromomalonate (13) yielding product 14 (Scheme 2

• solutions of cNDIs 2–6 in DMF. Photocatalytic α-alkylation of octanal (12): 500 mM 12, 250 mM 13, 50 mM (20 mol %) organocatalyst 15, 500 mM 2,6-lutidine, NDI 1 or cNDI 2–6 as photoredox catalyst in 1.3 mL solvent, stirring, irradiation by LED, see Table 2. Optical and electrochemical properties of NDI 1

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• -catalyzed lactonization, and iii) construction of the epoxides by a newly developed methodology. The synthesis commenced from the alkylation of tetralone 22 with 3-(2-iodoethyl)dihydrofuran-2(3H)-one (23) to give diastereomeric lactones that subsequently reacted with dimethylamine to afford a 1:1 mixture of

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• reaction [14]. Recently, several hydroxyalkylation reactions followed by alkylation of arenes have been reported involving heterocycle-based superelectrophiles: pyridines, thiazoles, quinolines, isoquinolines, pyrazines, pyrazoles, imidazole and furans, bearing a formyl (carbonyl) group [15][16][17][18][19

• (Figure 3) with arenes under the action of Brønsted (super)acids CF3SO3H (TfOH, triflic acid), H2SO4 and strong Lewis acids AlX3 (X = Cl, Br). One would expect the electrophilic activation of carbonyl or 2-hydroxyalkyl groups of these benzimidazoles in hydroxyalkylation and alkylation of arenes. Results

Morphology-tunable and pH-responsive supramolecular self-assemblies based on AB₂-type host–guest-conjugated amphiphilic molecules for controlled drug delivery

• Yang Bai,
• Cai-ping Liu,
• Di Chen,
• Long-hai Zhuo,
• Huai-tian Bu and
• Wei Tian

Beilstein J. Org. Chem. 2019, 15, 1925–1932, doi:10.3762/bjoc.15.188

• been successfully conducted. Subsequently, BM-Alk was synthesized by the alkylation reaction between benzimidazole and propargyl bromide according to the literature [46]. The appearance of the alkynyl absorption peaks at 2127 cm−1 in the FTIR spectrum (Figure S1A-a, Supporting Information File 1) and

Functional panchromatic BODIPY dyes with near-infrared absorption: design, synthesis, characterization and use in dye-sensitized solar cells

• Quentin Huaulmé,
• Cyril Aumaitre,
• Outi Vilhelmiina Kontkanen,
• David Beljonne,
• Alexandra Sutter,
• Gilles Ulrich,
• Renaud Demadrille and
• Nicolas Leclerc

Beilstein J. Org. Chem. 2019, 15, 1758–1768, doi:10.3762/bjoc.15.169

• observed in BOD-TTPA-alk is likely due to the boron center alkylation. Similar effects have been already shown after fluorine substitution of BODIPY [33]. 5. DSSCs fabrication and device performances In order to investigate the photovoltaic performances of the two functional dyes BOD-TTPA-alk and BOD-TTPA

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• aziridine ring opening combined with functionalization of the C2 substituent and optional alkylation or arylation of the nitrogen atom [44]. Following a similar regioselective aziridine opening, a mixture of epimeric amino alcohols (2R/S,1'R)-23 was prepared in two steps from the aziridine alcohol (2R/S,1'R

• )-24 was obtained. On the other hand, alkylation of 2,6-dimethylphenol with the tosylate (2S,1'R)-25 proceeded regioselectively to give (2S,1'R)-26, a precursor to (S)-24. (−)-Cathinone ((S)-27) is an alkaloid acting as a central nervous system stimulant found in leaves of Catha edulis. It was

• -(iodomethyl)oxazolidin-2-one (4R,1'S)-39 via a regioselective opening with iodide and cyclization (Scheme 12) [50]. As expected alkylation of the indole ring with (4R,1'S)-39 occurred at C3 to give (4S,1'S)-40 which was deprotected in two steps (Birch reduction and alkaline hydrolysis) to provide ʟ

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

• easy recovery and reusability [69]. The role of rhodium in synthetic chemistry Rhodium in the form of Wilkinsons catalyst [RhCl(PPh3)3] played a major role in the field of catalysis [70]. Rhodium is capable of catalyzing a number of organic reactions viz., heterocyclic alkylation and arylation with a

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• N-alkylation of a pyridine [19][20][21][22][23][24][25][26][27], isoquinoline [26][27][28][29][30][31][32], or related structures [33][34][35], followed by deprotonation. Such ylides are formally azomethine structures assuming reactivity of the aromatic ring as an iminium ion, although the reaction

• reaction of quinolinium salts bearing electron-withdrawing groups other than ketones, we prepared ester 4 [55] and amide 5 by alkylation of quinoline. Arylidenemalononitriles such as 6a are known to undergo related chemistry [41], so we heated this compound with the quinolinium salts in the presence of