UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• ], followed by further functionalization with ethylamine at the carboxylic acid in two steps to obtain the GCP ethyl amide, which has been synthesized before, by a different method [9]. The novel building block for GCI was synthesized in a 4-step synthesis adapted from a previous work [28] and then

• functionalized accordingly, yielding the GCI ethyl amide (for detailed synthesis routes, see Scheme S1 and Scheme S2 in Supporting Information File 1). The functionalization of the binding motifs GCP and GCI were performed since in the presence of the free guanidinium moiety the free carboxylic acid leads to a

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

• commercially available levoglucosan. It was shown that the building block could undergo alkylations under strongly basic conditions. The building block with azido groups could furthermore take part in CuAAC reactions, generating derivatives with ester or carboxylic acid functionalities. In addition, the

• refluxing the compounds in an aqueous solution of NaOH giving access to the carboxylic acid derivatives 16 and 17 (Scheme 3) demonstrating the versatility of the azido groups to be handles for introducing other metal-chelating groups. The simplicity of the synthetic steps and the versatility of the products

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• 13, which only needed to be oxidised to the carboxylic acid 14 then coupled to piperidine in order to deliver the target compound, 2. However, the oxidation of 13 proved to be unexpectedly troublesome. Mild oxidising agents caused incomplete consumption of 13, while vigorous conditions led to the

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

• shown that the spin switching efficiency is strongly dependent on the solvent and on the substituent at the 4-position of the pyridine unit. We now introduced thiol, disulfide, thioethers, nitrile and carboxylic acid groups and investigated their spin switching efficiency. Keywords: azopyridines; Ni(II

• that methoxy substitution (σ = −0.27) improved the spin switching efficiency in organic solvents to >98% in both directions [13]. However, the switching efficiency drops in protic solvents, particularly in water [3][14]. We now synthesized sulfur and carboxylic acid substituted record players aiming at

• or strain might be the reasons for the deviations. We cannot exclude that these groups coordinate directly to the Ni ion. Whereas the thiol (1h) and thiolate (1h−) exhibit disappointingly low switching efficiencies (Δ = 28% and 34%), the carboxylic acid (1j) and the corresponding carboxylate anion

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

• between carboxylic acid/alcohol 76 and enal 77 (Scheme 10a) [46]. Analogously to the mechanism outlined in Scheme 9, it was proposed that formation of excited state iminium ion 66* is used to oxidise 76 to give radical cation 76•+ and alkyl radical 66•. Nucleophilic addition from the carboxylic acid or

• carboxylic acids 155 with alkenes 156. A low yielding benzylation reaction was required for determination of enantioselectivities and a large excess of alkene was required for the reaction. The reaction is proposed to proceed via hydrogen-bonded complex 157, that lowers the triplet energy of the carboxylic

• acid so that a Dexter energy transfer process is possible from the photocatalyst to the substrate to promote 155 into its triplet state, which can then cyclise with 156 to give enantioenriched cycloaddition products 158. The selectivity of this reaction is generally low (6 examples, up to 93:7 er, 67

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

• to the functional group transformation (molecular-surgery-type functionalization) by treating them with NaOH in EtOH/H2O (10:1) under reflux conditions to first convert esters functionality into the corresponding carboxylic acid derivatives. As displayed in Scheme 47, these acid derivatives were then

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• –7.81 (m, 4H, ArH), 7.64–7.58 (m, 4H, ArH), 7.42–7.20 (m, 10H, ArH), 6.90 (br. s, 2H, NH), 4.13–4.03 (m, 10H, CH2), 3.75–3.53 (m, 5H, CH2), 2.84–2.67 (m, 5H, CH2), 1.35 (s, 18H, Boc ), 1.28–1.21 (m, 6H, aliphatic proton). Synthesis of 4: To a solution of pyrrole carboxylic acid (A, 2 equiv), HCTU (2

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

• the respective products. Employing the optimum reaction conditions, Lectka and co-workers fluorinated phenylalanine-containing di- and tripeptides to give the products 70a–f in modest to excellent yield (34–84%, Scheme 29). The carboxylic acid function could be free or protected as an ester without

Synthesis of 6,13-difluoropentacene

• Matthias W. Tripp and
• Ulrich Koert

Beilstein J. Org. Chem. 2020, 16, 2136–2140, doi:10.3762/bjoc.16.181

• subsequent reduction of the anthraquinone gave 1,4-difluoroanthracene. After ortho-lithiation and reaction with phthalic anhydride a carboxylic acid was obtained whose Friedel–Crafts acylation and subsequent reductive removal of the oxygen-functionalities resulted in the formation of the target compound. The

• phthalic anhydride in THF precooled to –100 °C [16]. Using these conditions, the carboxylic acid 12 was isolated in 82% yield. The subsequent Friedel–Crafts acylation proofed to be challenging. Using reagents like PCl5 resulted in a quantitative substitution of the fluorine substituents in the

• two fluorine substituents was investigated. The retrosynthetic analysis for this strategy is shown in Scheme 1. The formation of the C5,5a-bond colored in red could be accomplished by an intramolecular Friedel–Crafts type acylation with the acylium-cation intermediate 6. The corresponding carboxylic

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• . The removal of the silyl protecting group and hydrolysis of the methyl ester afforded the carboxylic acid 108. A subsequently attempted Suzuki–Miyaura coupling of 108 with vinyl boronates was described as “capricious”, and thus the acid was esterified with the tert-butyl donor reagent 109 to afford

• -butyl esters with formic acid gave the carboxylic acid 9, 7, or 5. Additionally, the treatment of the thailanstatin A tert-butyl ester with lithium chloride generated the thailanstatin B tert-butyl ester. Ghosh used a similar cross-metathesis/Suzuki–Miyaura coupling sequence for the preparation of

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• associated with controlling their stereochemical outcome [33][34][35] severely restrict their applicability in medicinal chemistry [36]. The typical Passerini three-component reaction (P-3CR) of a carboxylic acid 1, an aldehyde 2, and an isocyanide 3 being conducted in a polar-aprotic solvent such as THF or

• -component reaction (U-4CR) a carboxylic acid 1, an aldehyde 2, and an isocyanide 3 are complemented by a primary amine 5 that altogether undergo a condensation into a peptide-like adduct 6. These reactions are typically conducted in polar protic solvents such as methanol or water. Several examples of

Three new O-isocrotonyl-3-hydroxybutyric acid congeners produced by a sea anemone-derived marine bacterium of the genus Vibrio

• Dandan Li,
• Enjuro Harunari,
• Tao Zhou,
• Naoya Oku and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1869–1874, doi:10.3762/bjoc.16.154

• showed HMBC correlations to the same carboxy carbon C1 (δC 165.6), revealing an intervening ester linkage. Finally, HMBC correlations from the methylene proton H22 and the oxymethine proton H3 to the other carboxy carbon C1 (δC 175.3) placed a carboxylic acid functionality on the methylene group, which

• chiral center and the carboxylic acid functionality [11]. Thus, the R-configuration was concluded for all four compounds 1–4. The compounds 1–4 are closely related to PHAs, the energy reserve substances for eubacteria and some species of archaea [12]. Both groups of compounds are composed of (R

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• ]. Tetrazole derivatives are a potent class of heterocyclic compounds with a wide range of biological activities owing to their unique structure. They play an important role not only as a bioisostere of the carboxylic acid group but also as flexible ligands which easily adopt to different binding modes [12][13

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• paper, this formal [2 + 2] protocol is extended to the use of trifluoroacetophenones to develop an enantioselective route to β-trifluoromethyl-β-hydroxy carboxylic acid derivatives (Figure 2C). Results and Discussion Optimization Optimization of the NHC-catalyzed formal [2 + 2] cycloaddition using the α

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• recommend exploring the article for further details [95]. Molecules with functional groups such as carboxylic acid present complex surface topologies from bridging and bidentate binding modes [91]. Yoshida and co-workers studied the adsorption of benzene derivatives on TiO2 surfaces by solid-state NMR and

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• are used as the photoredox catalyst to prepare the corresponding primary and secondary alcohols from terminal and internal olefins. The substrate scope is broad, with excellent regioselectivities and yields up to 96% (Scheme 17). Decarboxylation reactions Carboxylic acid often serves as an inexpensive

• generates the active species Mes–Acr–Me*. Then, the single-electron oxidation of the deprotonated carboxylic acid 52 with Mes–Acr–Me* results in the formation of an acyloxyl radical 53. The subsequent rearrangement of the radical 53 gives a carbon-centered radical 54 and carbon dioxide. The phenyl thiyl

• alkanes provided an efficient protocol for the synthesis of alkanes from carboxylic acid substrates previously inaccessible through other methods. The mechanism of this reaction is similar to the previously proposed mechanism in Scheme 19. Isomerization reactions Thiyl radical-mediated isomerizations of C

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• , chloromethyloxirane (142a) was first converted into a thietan-3-ol 145a by treatment with H2S and Ba(OH)2. Compound 145a was further transformed to 3-aminothietane-3-carboxylic acid (146), a modulator of the N-methyl-D-aspartate (NMDA) receptor [57] (Scheme 29). Several thietane-3-ol derivatives 145 were synthesized

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• gases were determined by mass spectrometry. In general, each type of surface group decomposes to a defined product such as CO2 from carboxylic acid or lactones and CO from carbonyl, hydroxide, phenol, ether or quinone groups and thus, information on the amounts of oxygen-containing surface groups are

• components lignin, cellulose and xylan by KOH activation with TPD. The different prepared materials showed no significant difference of the surface functionalities. All TPD spectra show a water peak at about 500 K according to dehydration of carboxylic acid during formation of anhydrides, a CO peak at 900 K

• -containing surface groups on the activated carbon materials. They could observe that gas phase oxidation led to a higher amount of mainly hydroxy and carbonyl groups, whereas liquid phase treatment with nitric acid results in an increase of carboxylic acid groups [110]. Lillo-Ródenas et al. used TPD for the

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• [32]. Recently, photoredox catalysis has emerged as a powerful tool to access C(sp3) radicals, and organic dyes (ODs) have been demonstrated to act as competent photocatalysts for these light-mediated reactions. The main strategies used include decarboxylations from carboxylic acid derivatives (CO2X

• venerable transformations [39][40], allowing the smooth generation of alkyl radicals from carboxylic acid derivatives. One of the main strategies for accessing C(sp3) radicals from carboxylic acids relies on the oxidation of the CO2H group. However, the high oxidation potential of these species makes them

• reported a visible light-promoted photochemical reductive decarboxylation/alkylation of carboxylic acid analogs (Scheme 4) [45]. In this protocol, the carboxylic acids are converted into the corresponding RAE 4.1 by a condensation with N-hydroxyphthalimide. The organic dye eosin Y (OD13, E(PC/PC−) ≈ −1.1 V

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

• direct addition of isocyanide and carboxylic acid. The Ugi products were obtained in 41–89% and 72–96% yields from 1,2,3,4-tetrahydroisoquinoline (Scheme 60) and dibenzylamine (Scheme 61), respectively [102]. Furthermore, Che and co-workers obtained a wide range of Mannich-type products by coupling N

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• based on the reaction of carboxylic acid with N-Boc-protected aliphatic diamine in the presence of activators and then deprotection of the tert‐butoxycarbonyl (Boc) group using trifluoroacetic acid (TFA) [20]. Compared with the mentioned methods, the latter method achieves the higher yield (up to 90

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• biologically active compounds. As an example, we can consider peptide bond formation between an amine and a carboxylic acid. This transformation is a very important reaction in organic synthesis and therefore, many coupling reagents are available on the market [25][26][27][28][29]. Our previous studies have

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

• (Scheme 26). These magnetically retrievable nanoparticles could be recycled five times. Copper(II) was supported by carboxylic acid-rich Fe3O4–pectin (124) to afford copper(II)-supported Fe3O4–pectin, Cu(II)@Fe3O4–pectin (125), as a superparamagnetic nanobiopolymer (Scheme 27) [97]. Briefly, 125 was

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• of radicals with visible light photoredox catalysis. The reductive formation of the carboxymethanide radical could be used for lactone formation with styrene. Benzene was found to be the best solvent for this reaction. However, the reaction is associated with some unsolved problems. The carboxylic

• acid group seems to be advantageous for the activation of monochloroacetic acid, but the apolar solvent in combination with formation of HCl is likely to cause catalyst deactivation/precipitation. This effect is more pronounced if electron-poor styrenes are used. We also found indications that a

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• was obtained by the reaction of ʟ-valinol with in situ-generated indolylacyl chloride. The latter compound was obtained through an oxalic acid-mediated chlorination of carboxylic acid 96 with dimethylformamide as catalyst in dichloromethane. Next, oxazoline derivative 98 was obtained via a

• carbon dioxide and phenyllithium gives the phosphine ferrocene carboxylic acid 152 as the major reagent. Oxidation of the phosphine using hydrogen peroxide generated the phosphine oxide 153. In situ chlorination of the carboxylic acid followed by addition of the chiral amino alcohols gave the phosphoryl