Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• cycloaddition reactions and also serves as a precursor for the generation of important functional groups like amines, aldehydes, ketones and carboxylic acids. Even though the nitrile functional group is prevalent in the transformation into different functional groups, the synthetic approaches that incorporate

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• 12 in good yields (75–95%) with up to 99% ee. Several sulfonic acids and carboxylic acids were tested as co-catalysts and trifluoroacetic acid (TFA) was found to give the best results [28]. Here the role of the co-catalyst is to assist in the formation of the iminium intermediate (Table 2) [29]. It

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• ). In 2020, Zhang’s group [77] described the photoinduced copper-catalyzed decarboxylative alkynylation of redox-active esters with terminal alkynes. N-Hydroxy-tetrachlorophthalimide (TCNHPI, 36) derived from carboxylic acids was identified as the ideal radical precursor. Under irradiation, the CuI

• [100] groups reported that NHPI esters (67, 68) have been used as alkyl radical precursors in decarboxylative coupling reactions. These reactions feature a wide substrate scope. Primary, secondary, and tertiary alkyl carboxylic acids exhibit good yield, such as decarboxylative coupling reactions

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• tetrahydroisoquinoline derivatives, 7,12-dihydro-6,12-methanodibenzo[c,f]-azocine-5-carboxylic acids by three component Petasis reaction with the use of aminoacetaldehyde acetals bearing substituted benzyl groups as the amine components followed by Pomeranz–Fritsch double cyclization reaction. By applying this method

• transformed into racemic tetrahydroisoquinoline-1-carboxylic acids [19], simple isoquinoline alkaloids [20], and (+)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid [21]. In this paper we report a straightforward synthesis of new strained tetracyclic tetrahydroisoquinoline derivatives

• , variously substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids, via our modified method based on a combination of the Petasis reaction, in which we used aminoacetaldehyde acetals with substituted N-benzyl groups as the amine component and the Pomeranz–Fritsch double cyclization

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• , or mercuric trifluoroacetate as shown in Scheme 41 [97]. Alkyne carboxylic acids also undergo oxymercuration reactions to form furan- and pyran-like derivatives. When γ-alkyne carboxylic derivative 140 was refluxed with HgO the cyclization took place to give product 141 in almost quantitative yields

• -dihydroquinoline derivatives by Hg(OTf)2 and b) plausible mechanism of formation. Synthesis of Hg(II)-salt-catalyzed heteroaromatic derivatives. Hg(II)-salt-catalyzed synthesis of dihydropyranone derivatives. Hg(II)-salt-catalyzed cyclization of alkynoic acids. Hg(II)-salt-mediated cyclization of alkyne carboxylic

• acids and alcohol to furan, pyran, and spirocyclic derivatives. Hg(II)-salt-mediated cyclization of 1,4-dihydroxy-5-alkyne derivatives. Six-membered morpholine derivative formation by catalytic Hg(II)-salt-induced cyclization. Hg(OTf)2-catalyzed hydroxylative carbocyclization of 1,6-enyne. a) Hg(OTf)2

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• radical and toluene as well as aldehyde; iv) product formation in a nickel catalytic cycle; and v) regeneration of nickel(II) species. Recently, the group of Huo developed a nickel-catalyzed enantioselective acylation of α-amino C(sp3)–H bonds with carboxylic acids under visible light irradiation (Scheme

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• anthracene derivatives 33. The strategy involved a palladium(II)-catalyzed tandem transformation with diphenyl carboxylic acids 31 and acrylates 32 (Scheme 7) [41]. This new methodology involved a carboxyl-directed C–H alkenylation, a carboxyl-directed secondary C–H activation, an intramolecular C–C-bond

• formation, and further decarboxylative aromatization. The authors used several diphenyl carboxylic acids bearing electron-donating and electron-withdrawing groups on the aromatic rings to produce the corresponding substituted anthracenes, such as compounds 33a–f, in good yields [41]. Recently, Kim and co

• employed palladium(II) acetate and visible light under O2 in the reactions between ethyl acrylate (192) and substituted diaryl carboxylic acids 193, to produce anthraquinones 194 in low to moderate yields (30–68%). In a direct comparison with the methodology proposed by Hong for the synthesis of

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties (Scheme 2). Bojanowski and co-workers developed a methodology to synthetize 3,4-dihydrocoumarins 10 through a decarboxylative and dearomatizative cascade reaction [33]. This reaction was carried out using coumarin-3-carboxylic acids 8

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• usually mediated by V(V) and V(IV)-oxo-peroxo complexes, which are produced in situ from vanadium-oxo and dioxo precatalysts in the presence of oxidants, such as H2O2, O2, and tert-butyl hydroperoxide (TBHP) [76][77][78][79][80][81][82]. Inorganic acids and chelating and non-chelating carboxylic acids

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• ′-carboxylic acids 65a–c which in turn were prepared through the (2,2,6,6-tetramethylpiperidin-1-oxyl) (TEMPO) and 1,1-bis(acetoxy)iodobenzene (BAIB)-assisted oxidation of the 5′-hydroxymethylene group in adenosine/uridine by following the methodology developed by Epp and Widlanski [53]. The nucleoside-5

• ′-carboxylic acids 65a–c were reacted with 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) as coupling reagent followed by reaction with phthalazin-1-ylhydrazin hydrochloride in DMF in the presence of diisopropylethylamine (DIPEA) as base to afford the double-headed

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• CN-K-based heterogeneous protocol for the cyanomethylarylation of N-arylallylamines with acetonitrile. Pleasingly, after the systematic evaluation of various NHPI esters, which are easily prepared from readily available carboxylic acids, the yield of the product 3a could be increased to 75% when

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

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

• library of carboxylic acids 72 in the presence of coupling reagents (Scheme 11) [27]. Alternatively, the 1,3-protected glycerol 73 was first converted into various 2,3-protected glycerols 74, which were further transformed to methyl 2-alkoxy-3-hydroxypropanoates 75. Following a similar strategy as above

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

• mass spectrometry and so it was converted to carboxylic acids 14 and 15 by the treatment with silica gel and NaOH, respectively, in order to confirm its identity. A possible mechanism for the formation of 13 from 5n could involve the formation of a terminal carbocation from trichloroalkanone 8n

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

• . Results and Discussion Flow investigations commenced with the development of a continuous Curtius rearrangement process based on previous reports [22][23][24]. Specifically, we targeted utilization of a range of commercially available carboxylic acids 1 (1.0 equiv) in combination with DPPA (2, 0.9 equiv

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• introduction before being biotransformed to new trifluoromethyl-containing metabolites (Figure 15). 19F NMR was also employed to determine the degree of biotransformation of drug-like fluorophenylpyridine carboxylic acids in the same fungus [107]. However, aside from these few examples, the technique is not

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• hydrogenolysis of benzyl ethers (H2, Pd) [72], DIBAL-H reduction of esters to form alcohols [73], oxidative cleavage of vinyl groups to form carboxylic acids (KMnO4) [74], and the conversion of the acids into amines using the Curtius rearrangement (SOCl2, followed by Me3SiN3, thermolysis, and acid hydrolysis of

• O–H and N–H bonds of water, alcohols, carboxylic acids, and amines to form the observed products 121. 1,1-Difluoro-2-siloxy-2-vinylcyclopropane (122) was subjected to a fluoride-catalyzed ring opening to afford 1-fluorovinyl vinyl ketones such as 123. These compounds underwent a Lewis acid-catalyzed

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• , a rare genetic condition [27]. On the other hand, the tetrazole moiety is known to have a bioisosteric relationship to carboxylic acids [28], which also makes them suitable for usage as biologically active compounds. Vasella et al., for example, have previously prepared compounds similar to reported

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• and not as fluorination of acyl fluorides. Thus, the acyl fluoride moiety is commonly sacrificed as a “leaving group” in reactions. On the other hand, the transformation to CF3 derivatives from carboxylic acids are traditionally examined. In 1960, Engelhardt [27] performed the deoxyfluorination of

• carboxylic acids with sulfur tetrafluoride (SF4) at 120 to 150 °C in liquid hydrogen fluoride (HF) (Scheme 1c). Very recently, Mykhailiuk [28][29] improved the method to use SF4 for the deoxofluorination of carboxylic acids with or without HF in the gram scale (Scheme 1c). Although Mykhailiuk’s protocol is

• toxic sulfur tetrafluoride [32] and the explosive (diethylamino)sulfur trifluoride (DAST) [33]. Although the 2010 report by Umemoto provided a method for the deoxyfluorination of a wide variety of substrates, including alcohols, ketones, and even carboxylic acids to the mono-, di-, and trifluoromethyl

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

• corresponding amides 4a–d by treatment with phosphorus decasulfide (Scheme 1). It is worth noting that amides of 1-alkyl-1,2,3-triazole-4-carboxylic acids are poorly represented in the literature and the methods of their preparation require the addition of alkyl azides to acetylene carboxylic esters and

• amidines of azolyl and pyridine carboxylic acids. The most promising aspect for organic synthesis and green chemistry is a solvent-free process which was successfully applied to prepare sulfonyl amidines containing pyridine and isoxazolyl rings and 1-alkyl-1,2,3-triazole-4-N-sulfonylamidino-1,2,3-triazoles

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• , carboxylic acids [16][17][18][19][20], acyl anhydrides [21][22][23], acyl chlorides [24][25][26][27], esters [28], thioamides [29][30][31], dithionates [32][33], or thiocarbamates [34] are employed as electrophilic components, but oxidative cyclocondensations with aldehydes have also been showcased [35][36

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• underlines that building block 5 is an ideal template for the synthesis of molecules with a 2,4- and 3,6-functional group pattern. However, after investigating the metal-binding properties of the synthesized diamines and the carboxylic acids, no conformational changes could be observed. Hence, the compounds

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• described for analytes ranging from inorganic ions over low-molecular-weight neutral and charged organic compounds, such as carboxylic acids, amino acids, and nucleotides, to larger biomolecules such as peptides and proteins [1][2][3][4][5][6][13]. All of these systems have specific areas of application

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• the improvement of the switching efficiency. Thiol (σ = 0.15) and thiolethers (σ ≈ 0.0) are less electron donating than methoxy substituents, however, upon deprotonation, the thiolate (σ = −1.2) should considerably improve coordination and potentially restore switchability in water. Carboxylic acids