Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• , MG, Brazil 10.3762/bjoc.17.66 Abstract Desulfonylative alkylation of N-tosyl-1,2,3-triazoles under metal-free conditions leading to β-triazolylenones is reported here. The present study encompasses the synthesis of triazoles with a new substitution pattern in a single step from cyclic 1,3-dicarbonyl

• leading to poor N1/N2 selectivity, for instance, in the direct N-alkylation of triazoles [21][22][23]. Despite these challenges, a number of N1- and N2-selective alkylation methods have been developed employing transition metal catalysts which include Au-catalysed desulfonylative coupling N-tosyl-1,2,3

• functionalization of triazoles under metal-free conditions has been reported. These include the Broensted acid-catalysed N2 alkylation [27], organocatalytic N1 alkylation [28][29], N2-arylation using hypervalent iodine (Scheme 1c) [30], N2-alkylation involving radical intermediate [31], pyridine-N-oxide-mediated N1

Synthesis, structural characterization, and optical properties of benzo[f]naphtho[2,3-b]phosphoindoles

• Mio Matsumura,
• Takahiro Teramoto,
• Masato Kawakubo,
• Masatoshi Kawahata,
• Yuki Murata,
• Kentaro Yamaguchi,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2021, 17, 671–677, doi:10.3762/bjoc.17.56

• phosphorus center can be easily chemically modified and converted to phosphole derivatives with different electronic properties by reactions such as oxidation, alkylation, and coordination to a Lewis acid [1][2][3][4][5][6][7][8]. Theoretically, pentacyclic benzonaphthophosphindole contains six structural

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• reported by us [30]. It is known that the alkylation of phthalazinones depends on the reaction conditions and can proceed in two ways involving either the nitrogen or the oxygen atom (lactam–lactim tautomerism). It has been proven that potassium salts of phthalazinones or the bromo derivatives are

• = Me, 85%; 3b R1 = iPr, 84%) were obtained by the direct alkylation of bromophthalazinone 2 with methyl or isopropyl iodide in the presence of K2CO3 in dry acetone as the solvent (conventional heating). In the similar way also the 2-aminoethyl lactams 3c (R1 = CH2CH2NMe2) and 3d (R1 = CH2CH2(morpholin

• In conclusion, we have demonstrated an efficient synthesis of 2-substituted (alkyl, aminoalkyl) 4-aminophthalazinones 5 and 6 via the direct bromination of phthalazin-1(2H)-one (1) with potassium tribromide, followed by the alkylation of 4-bromophthalazinone 2 with methyl iodide, isopropyl iodide or

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• reviewed, including the phosphonylation of hydroxy esters with phosphonochloridates, the condensation of phosphonic monoesters and hydroxy esters, the alkylation of phosphonic monoesters with 1-(alkoxycarbonyl)alkyl halides or sulfonates, multicomponent condensation of amides, aldehydes, and

• phosphonodepsipeptides with C-1-hydroxyalkylphosphonic acids. Keywords: alkylation; mimetic; multicomponent condensation; peptide; phosphonopeptide; phosphonodepsipeptide; phosphonylation; Introduction Both, phosphonopeptides and phosphonodepsipeptides are phosphorus analogues of peptides [1][2][3][4][5]. The

• ) produced the desired product 171 in 62% yield in the reaction. However, aliphatic aldehydes did not work (Scheme 32) [52]. Synthesis of phosphonodepsipeptides via the alkylation of phosphonic monoesters with 1-(alkoxycarbonyl)alkyl halides or sulfonates The alkylation of N-protected 1-aminoalkylphosphonic

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• -halopurines [41]. O-Alkylation of guanosine and inosine with Cu(I)-stabilized carbenes derived form α-diazocarbonyl compounds is also known [42]. Alkylation of 6-oxopurine derivatives under Mitsunobu conditions which usually proceeds with O-regioselectivity are mostly described for guanine derivatives [43][44

• of purine [73][74][75][76] or alkylation of inosine or guanosine derivatives (Ib→II, Scheme 1) [30][36]. In the next step, azide can be introduced either by a second SNAr reaction on the C2-halo derivative or by diazotization/azidation at C2. Then, the Cu(I)-catalyzed azide–alkyne cycloaddition

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• trichloride; dichloroalkenes; Friedel–Crafts alkylation; rearrangement; trifluoroalkanes; Introduction 1,1-Dichloro-1-alkenes are valuable synthetic intermediates and have been employed in Pd-mediated cross couplings of one or both chlorine atoms [1][2][3][4][5][6][7], carbonylation reactions [8], and C–H

• ) equivalents of AlCl3, a further two products were obtained, whose structures were elucidated as the 8,9-dihydrobenzo[7]annulen-9-ones 9 and 10 (Scheme 4). Presumably, these bicyclic compounds arise via an intramolecular Friedel–Crafts alkylation of 6b, promoted by the ortho/para-directing nature of the

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

• -containing alkylation reagents [27]. Very recently, this aminide was found to be a suitable ligand for manganese complexes [28] and used as the agent for the preparation of salts with high energy density [29]. Also, it is worth noting that today only a few examples of mesoionic tetrazole aminide X-ray

• tetrazolium-5-aminide allows to displace halo- and methylsulfonyl groups, whereas 5-aminotetrazoles do not react under analogous conditions. So, we prepared the bistetrazolium salt 9 by the alkylation of aminide 8a with 1,2-dibromoethane (Scheme 2). The obtained salt 9 was subjected to deprotonation to give

• energy of S0→S1 transition increases, and a blue shift is observed in polar media. Conclusion Mesoionic tetrazolium-5-aminides can be easily prepared by the alkylation of readily available 5-aminotetrazole and its N-alkyl derivatives in a t-BuOH/HClO4 system followed by the treatment of the tetrazolium

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• innovative approach (85% yield, for details see [21]). To further exploit the value of this continuous flow approach the possibility of converting selected carbamate products into derivatives of β-amino acids (e.g., 8) was evaluated. Although this may be achieved by a conventional alkylation of the carbamate

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• ethers 41b upon the reaction in a dichloromethane solution of sulfuric acid or triflic acid [60][61]. The authors also reported that indenes 42 could undergo a subsequent Friedel–Crafts alkylation when 41b was reacted in the presence of an external aromatic partner Ar’H in pure triflic acid. Thus, a

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• for esterases [23][38]. The alkylation of 4NTC with homoallylic bromide under basic conditions gave a mixture of mono- and dialkylated 4NTC derivatives, with 10 (38%) predominating because of the preferential formation of the phenolate at the para-position (relative to the nitro group) [39]. Osmium

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• (OEt)3 Next, we switched to pathway B (Scheme 2) and prepared 2,6-diazidopurine derivative 5 from 2,6-dichloropurine (11) via a Mitsunobu alkylation and SNAr reaction with NaN3 (Scheme 5) [22]. 2,6-Bistriazolylpurine derivatives 6a–i were obtained in CuAAC reactions with various alkynes in 35–76% yield

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• evidence [60]. The synthetic route was designed in such a way that intercept both Ryu’s intermediate (+)-69 [50] and Hatakeyama’s intermediate (+)-82b [22] (Scheme 12 and Scheme 13). In this approach, the asymmetric alkylation of 96 with alkyne 95 under Carreira’s conditions [61][62][63] afforded (−)-98 in

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• dipolar cycloaddition to produce tricyclic isoxazolidines [40]. The synthesis started from 5-hexyn-1-ol (4, Scheme 2). The alcohol was treated with dihydropyran followed by alkylation using butyllithium and then, acetal deprotection, providing the alcohol 5 as a key starting compound for the (±)-adaline

Synthesis of tetrafluorinated piperidines from nitrones via a visible-light-promoted annelation reaction

• Vyacheslav I. Supranovich,
• Igor A. Dmitriev and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 3104–3108, doi:10.3762/bjoc.16.260

• likely starts from the addition of the fluorinated radical to the C=N bond followed by a conversion of the nitroxyl radical via hydrogen atom transfer [26][27] providing hydroxylamine 4. At the next stage, the intramolecular N-alkylation occurs leading to an N-oxide. This step of nucleophilic

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• vacuum. For tryptic digestion, the dried sample was reconstituted in 10 µL of reduction–alkylation buffer containing 100 mM Tris buffer, 1% w/v SDC, 10 mM tris(2-carboxyethyl)phosphine (TCEP), and 40 mM chloroacetamide (CAA). Upon mixing for 5 min, the samples were incubated for 5 min at 95 °C and cooled

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• reactivity of the nonalkylated phenolic moieties [45]. The fast reaction afforded the corresponding dinitro derivative 3 within a few minutes with 70% yield. As we found in our previous attempts [43][45], the alkylation of dinitrocalixarenes to form the 1,3-alternate conformation is a synthetic challenge. In

• fact, irrespective of the base or solvent used, the alkylation with appropriate n-propyl or n-hexyl halides always led to the partial cone conformation as the main product. To overcome this problematic step, we used the conditions described by Böhmer et al. [46] for a similar system bearing propyl

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• lipophilic character of the metallocene [11]. However, only a limited number of reports described the application of ultrasonic irradiation for the synthesis of phenothiazine derivatives, and included the N-alkylation of 10H-phenothiazine [12], condensation of phenothiazine carbaldehyde with hydrazino

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• substrate failed (Scheme 7). Next, the alkylated diynols 7b, 7c, and 8b–d were deprotected using standard methodologies affording the products in moderate to good yields (Scheme 8). With the diynols 4a–d in hand, we were able to synthesize a small library of allylated oxaenediynes 2 by the alkylation of the

• and Mo catalysts. Beneficial effect of ethene atmosphere. Enantioselective dienyne metathesis [21]. Diastereoselective endiyne metathesis [31]. Synthesis of hepta-1,6-diyn-4-ol (4a). Protection of hepta-1,6-diyn-4-ol (4a). Alkylation of the protected diynols 7a and 8a. Deprotection of protected

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

• were prepared by the reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (1) with the corresponding substrates, resulting in the selective alkylation of one of the nitrogen atoms of the imidazole ring. The reaction proceeds under mild conditions in a polar solvent, giving the alkylated

• products in 47–78% yield. While for purine and 4- and 5-azabenzimidazole, the reaction led to a mixture of two isomers, the reaction of adenine and the corresponding 2-fluoro derivative was regioselective, resulting in the formation of only one isomer in each case. The alkylation of theophylline led to the

• °C, 1 d), leading (unexpectedly) to the formation of only one isomer (5a and 6a, respectively) in each case (Scheme 4). Another surprising feature of these reactions was the selective alkylation of the nitrogen atoms of the imidazole ring rather than the amino group. This is in sharp contrast to the

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• -imidazol-1-yl)methane (5) was synthesized from imidazole (4) and CH2Br2 following a literature procedure [62][63] with slight modifications. Then, BImNs (N = 4, 10, 12, 14) were synthesized from 5 by mono-alkylation using the corresponding n-alkyl halides in DMF. Finally, PBImNs (N = 4, 10, 12, 14) were

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• quantitative yield [47]. Single crystals of intermediate thienopyrrole 25 were obtained by slow evaporation of a chloroform solution and an X-ray structure analysis was performed. Structural details and packing motifs of the molecule are described in Supporting Information File 1. Alkylation to N-propyl

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• with photoredox catalysis was reported by Nicewicz and MacMillan [1] for the alpha alkylation of aldehydes 1 with various alkyl bromides bearing an electron-withdrawing substituent 2, which while seemingly trivial, was not possible with enamine catalysis alone (Scheme 1). The proposed mechanism

• ketyl radical anion 166•−. The latter intermediate 166•− can then abstract an iodine atom from another molecule of 163 to propagate the chain reaction and generate alkyl iodide 167, which collapses to give the desired enantioenriched alkylation products 168 in moderate yields and excellent

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• ), whereas host 1 and guest 3 would lead to a 75 backbone-atom trefoil (and unknotted macrocycle). Results and Discussion The synthesis of bis-macrocyclic host 1 began by breaking the symmetry of naphthalene-1,5-diol (4) by alkylation of one of the alcohols with 2-azidoethyl mesylate to yield azide 5 in 27

• % yield (Scheme 1). Alkylation of 5 with 1,2-dibromoethane provided key intermediate azido-bromide 6 in 60% yield. This two-step route to 6 is efficient, but the 16% overall yield was lower than desired. An alternate route began by converting diol 4 to bis(2-hydroxyethoxy)naphthalene 7 in 92% yield by

• ascorbic acid to provide a 42% yield of triazole 11. Alkylation of diethyl 2,5-dihydroxyterephthalate (12) with 11 under standard conditions provided low yields (12–18%) of the core diester 13, which contains all the atoms of host 1. The yields for this route were disappointingly low, so it was hoped that

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

• achieve this goal, they commenced with the two-fold Friedel–Crafts alkylation reaction of sumanene (2) with 2,5-dichloro-2,5-dimethylhexane (50) involving AlCl3 to generate compound 51 which on subsequent oxidation provided triketosumanene 52 (Scheme 11). Finally, compound 52 was reacted with ethylene

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• [192], reliable and commercially available [193]. Selectfluor® is synthesized on a multiton p.a. scale in a simple and efficient method (Scheme 3) [193]. The precursor 24 is prepared by alkylation of DABCO (1,4-diazabicyclo[2.2.2]octane) with DCM. A counterion exchange with NaBF4 causes NaCl