Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• smoothly under the set conditions to form the corresponding phenyl(TMP)iodonium(III) carboxylates 7aa–ad in high yield. Additionally, a range of aliphatic carboxylic acids such as acetic acid (6e), pivalic acid (6f), cyclohexanecarboxylic acid (6g), and aliphatic carboxylic acid with acidic α-proton (6h

• ) was also tolerated under these conditions to produce the corresponding phenyl(TMP)iodonium(III) carboxylates (3ae, 7af–ah) in 63–81% yield without any signs of side reactions. The adenosine receptor antagonist acefylline (6i) was also used as a carboxylic acid to give the corresponding phenyl(TMP

• )iodonium(III) carboxylate 7ai in 86% yield, opening up new avenues for structural modifications of drug candidates to improve their properties and consequently, bioactivities [38][39][40]. The umbelliferone-3-carboxylic acid derivative 6j was also employed to produce the phenyl(TMP)iodonium(III

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• been five natural MMFs isolated and characterized, with all of the MMFs being isolated from Streptomyces coelicolor W75 (Figure 1B). These compounds are 2,3,4-trisubstituted furans, and all five contain a carboxylic acid at the three position and a hydroxymethyl group at the four position. They differ

• the carboxylic acid in the three position, the phenyl group is most likely too electron-donating, as well as potentially being too sterically bulky. Finally, pyrrole 21 was tested and ultimately resulted in an inconclusive amount of conversion. Compound 21 does not ionize well on our LC–MS and thus we

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• synthesis of a set of 12 desired products. These included an ethyl ester and a carboxylic acid, and were all obtained in good yields of up to 99% (Scheme 45). Conclusion We have summarized the importance of carbon monoxide as C1 building block to promote different kinds of transformations to synthesize and

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• Institute, Palackӯ University in Olomouc, Olomouc, Czech Republic 10.3762/bjoc.20.85 Abstract Tetrazole is widely utilized as a bioisostere for carboxylic acid in the field of medicinal chemistry and drug development, enhancing the drug-like characteristics of various molecules. Typically, tetrazoles are

• ready-to-screen drug-like molecules remains a key challenge in the medicinal chemistry field [5][6]. Tetrazole is considered as a privileged scaffold in pharmaceutical and medicinal chemistry, used as a carboxylic acid bioisostere and a cis-amide mimic contributing to improvements in lipophilicity

• 1H-tetrazole as a bioisostere for carboxylic acid has long been recognized for its potential in enhancing drug-like properties [37]. Predominantly, tetrazoles are currently introduced by a late-stage-functionalization approach from their nitrile precursors. This work, however, takes an additional

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• studied due to the easy accessibility of fluoride ions with many methods directly employing the parent carboxylic acid as substrate. These processes avoid an additional pre-functionalisation step and have been reported using a range of deoxyfluorinating reagents including (diethylamino)sulfur trifluoride

• -handle solids that can be readily produced on a multigram scale from relatively inexpensive starting materials. During the optimisation studies for the latter process with carboxylic acid substrates, in addition to the desired (trifluoromethyl)thioester products, small amounts of the corresponding acyl

• carboxyl α-position. Finally, to assess the influence of the reaction on the stereochemical integrity of chiral carboxylic acid substrates, the deoxyfluorination was performed on the enantiopure (S)-isomer of ibuprofen (er = 99:1). Pleasingly, efficient conversion to the corresponding amide (S)-5l was

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• schistosomiasis [22][23][24][25]. The combination of the privileged heterocycles tetrazole and tetrahydroisoquinoline in one molecule generates new molecules which could have biological activities. A standard Ugi four-component reaction (Ugi-4CR) of an aldehyde, amine, isocyanide, and a carboxylic acid produces

• highly diverse peptidic structures A with up to four points of substitution (Scheme 1) [26][27]. By replacing the carboxylic acid with a nucleophilic azide reagent XN3 (generally TMSN3), the Ugi-azide four-component reaction (UA-4CR) of an aldehyde, amine, isocyanide, and azide gives 1,5-disubstituted 1H

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• activity, if not an improvement [1]. Often-used bioisosteres include the tetrazole group for a carboxylic acid [2][3][4][5] and fluorine atoms in place of hydrogens [6][7]. The inclusion of fluorine can alter the polarity of a molecule and can also be used to prevent epimerisation, as seen in

• -workers also reported the modification of these 1,2-BCHs to increase the number of derivatives accessible using this approach (Scheme 3B) [38]. Transformation of the naphthyl ketone moiety of BCH (±)-25d by Baeyer–Villiger oxidation followed by hydrolysis gave carboxylic acid (±)-26. Through Curtius

• reduction. Deprotection of the alcohol followed by two-step oxidation to the carboxylic acid yielded the non-natural β-amino acid (±)-50, which could then be transformed into diamine (±)-51 by Curtius rearrangement. Recently, Mykhailiuk and co-workers also reported the synthesis of 1,2-BCHs using an

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• by the preceding modules (highlighted in purple) [14][16]. Furthermore, the structures of 1 and 2 show a shifted triene portion that is not in conjugation with the carboxylic acid function. NMR studies of off-loaded intermediates with the TE deletion mutant revealed that these double bond shifts are

• ester 5 was coupled with the carboxylic acid (S)-8, derived from ʟ-leucine ((S)-6) via hydroxyacid (S)-7, to yield the amide (S)-9. Deprotection through catalytic hydrogenation to (S)-10, saponification of the acetate ester and Steglich esterification with N-acetylcysteamine gave access to the desired

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• serve as a nutrient source for phytoplankton and other organisms [4]. The distinctive structural feature of these siderophores is the α-hydroxy carboxylic acid (i.e., β-hydroxyaspartate), relevant to a photoreactive functional group [2][4]. In 2016, using the gene encoding a hydroxylase specific to the

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• demonstrated that 1,1,1,4,4,4-hexafluorobut-2-ene reacts with dithietane, sulfur and KF with the formation of the corresponding 1,3-dithiole [16]. Also, a recent patent presents a method for the preparation of 5,6-bis(trifluoromethyl)-1,2,4-triazine-3-carboxylic acid ethyl ester starting from 1,1,1,4,4,4

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• acid ester 9 was hydrolyzed under basic conditions in an ethanol/water mixture. After the reaction, the pH of the mixture was adjusted to 4 with hydrochloric acid, which resulted in the precipitation of the product 10 in excellent yield (95%). Next, carboxylic acid 10 was converted into the

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• . Trialkylboranes can react in a similar way with enones [3] whereas, distinctively, suitable acceptors for the reaction with dialkylzinc reagents also include α,β-unsaturated carboxylic acid derivatives such as α,β-unsaturated (di)esters [4][5], N-enoyloxazolidinones [6][7], N-enoyloxazolidines [8], or

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• carboxylic acid and pivalic anhydride than aryl bromide. The halides provided versatile synthetic handles for further transformations. Substrates bearing thiophene (3k) furan (3j) and other heterocycle (3l,m) moieties were also applicable to this reaction. This protocol allowed for the coupling of not only

• light-induced charge transfer event to give trifluoroethoxyl radical B, followed by a 1,2-hydrogen atom transfer (HAT), producing the stable radical C. For the nickel cycle, it is initiated by oxidative addition of Ni(0) catalyst E to acyl electrophile D formed in situ from carboxylic acid 1 with

• -trifluoroethoxyphthalimide: In the glove box with nitrogen atmosphere, to an 8 mL vial equipped with a magnetic stir bar, NiBr2(dtbbpy) (19.6 mg, 0.04 mmol, 10 mol %), alkyl carboxylic acid 1 (0.4 mmol, 1.0 equiv), N-trifluoroethoxyphthalimide (2, 147.1 mg, 0.6 mmol, 1.5 equiv), Hantzsch ester (152.0 mg, 0.6 mmol, 1.5 equiv

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• acylation of lyso-PAF with a series of functionalized carboxylic acid was reported in a series of articles from the group of Salomon [98][99]. This group aimed to identify natural compounds that could be formed by the oxidation of ether lipids featuring a polyunsaturated acyl chain in sn-2 position. This

• work includes, in addition to the oxidation of such type of polyunsaturated EL incorporated in liposomes [99], the formal synthesis of some oxidized derivatives. As an illustration, lyso-PAF 15.1 (extracted from egg albumin) was acylated using Steglich conditions with ω-unsaturated carboxylic acid to

• produce 15.2a [99] (Figure 15A and B) or with functionalized furane to produce 15.2b. The acylation was also achieved by reaction with cyclic acid anhydride to place in ω-position a carboxylic acid function as exemplified with 15.3a [98]. The acetyl group present in the structure of PAF in position sn-2

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• , Yang et al. [18][19] have developed a catalytic system involving Pd/Ti(OiPr)4 or Pd/carboxylic acid for the direct allylation of anilines with alcohols. The synthesis of N-allylimidazole derivatives 3 has been previously carried out using acyclic MBH adducts bearing good leaving groups, such as bromide

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• the mechanism. In 2015, the Groves group reported their manganese porphin-based catalyst V and related species being capable of participating in decarboxylation reactions (Scheme 4) [42]. The activated Mn(V) species is proposed to perform HAT carboxylic acid O–H bond, directly forming a carboxyl

• beautiful decarboxylative azidation examples, combining iron-mediated photodecarboxylation via LMCT and azide RLT (Scheme 5) [11]. Irradiating a substoichiometric amount of iron(III) nitrate hydrate III in the presence of carboxylic acid, TMS azide, and sodium carbonate allows for direct synthesis of alkyl

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• ≈ 8; 50e, 64–74% yield) were suitable, they were unreactive in the presence of a carboxylic acid (50c). If these insertions proceed via initial protonation of the iodonium ylide to produce 51 (Figure 11), its high acidity (pKa ≈ 0) [131][132] would suggest that only strong acids should undergo this

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• inducing cytotoxicity. In addition, another study demonstrated that a lanostanoid glycoside derivative with a glucosyl ester at the C-21 carboxylic acid group was active in a cytotoxic activity assay, whereas the galactosyl ester counterpart was inactive [36]. Similarly, the carboxylic acid group at C-21

• was shown to be a key player in lanostane triterpenoid cytotoxicity; increased activity was demonstrated either by its esterification with glucose or by its reduction into a hydroxymethylene group unlike its presence as a free carboxylic acid moiety [23]. Thus, our findings provide further insights

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• products, demonstrating a clear preference for addition to alkenes even in the presence of alkyne functionalities. Due to basic conditions of the reductive quenching (RQ) route, the formation of lactone side product 30h could be observed with a carboxylic acid functionality. In the absence of Et3N, the

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• powder, possesses a molecular formula of C16H24O3 (5 degrees of unsaturation) derived from its HRESIMS (m/z 287.1614, calcd 287.1618 [M + Na]+). Comparing the NMR data of 1 with those of 4 indicates that the Δ4,5 double bond migrates to Δ3,4 and the carboxylic acid group becomes a methyl ester derivative

• (Table 3). The difference is that the carboxylic acid at C-4 in 3 undergoes reduction to form a hydroxymethyl group at C-4 in 5. This alteration is supported by the analysis of the HMBC correlations (Figure 2) of H-3/C-4 (δC 128.6), C-14 (δC 63.5) and H-14/C-4, C-5 (δC 141.9). Thus, the planar structure

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• photoredox cycle (Figure 1b). Alternatively, we envisioned a more established approach expecting the direct oxidative photoredox decarboxylation of the carboxylic acid/carboxylate (by SET from the activated photocatalyst) of DMAT to generate the α-aminoalkyl radical that might readily be captured/trapped

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• substituent at C-2 of the phenol moiety. The final carbon atom at 171.9 ppm (C-15) could be attributed to a carboxylic acid function with HMBC correlations from H-13 and H-14, thereby completing the determination of the planar structure of 1. To determine the configuration of 1, we measured its optical

• ) and a proton resonance at δH 3.73 ppm (H-16). Both H-16 and H-14 show HMBC correlations to the carbonyl C-15. It can therefore be concluded that a methyl ester function replaced the carboxylic acid function of compound 1. Measurements of the optical rotation of 2 were not possible due to the low

• 16 Da compared to compound 3, confirming that it is the reduced form of the carboxylic acid. Compound 5 (0.6 mg) was obtained as a brown oil. It possesses a molecular ion at m/z 278.1231 [M + H]+, which suggests a molecular formula of C15H19NO2S (calcd. for C15H20NO3S, 278.1220) and corresponds to

Light-responsive rotaxane-based materials: inducing motion in the solid state

• Adrian Saura-Sanmartin

Beilstein J. Org. Chem. 2023, 19, 873–880, doi:10.3762/bjoc.19.64

• the interlocked arrangement. As an illustrative example, cucurbit[8]uril-based pseudorotaxanes having a pair of styrylpyridinium threads bearing carboxylic acid groups were employed in the preparation of the uranium-organic framework U-CB[8]-MPyVB (Figure 4a) [63]. The solid structure of the MOFs

• shows the styrene-based derivatives coordinated in an antiparallel manner through the carboxylic acid group placed at the end of each thread, thus avoiding the dethreading process. Two identical intertwined scaffolds were formed differing in the photoactivities due to different conformations. In the

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• (δC 43.8), and H-12/C-10, C-11. The presence of a conjugated carboxylic acid was verified by the HMBC correlation of H2-2 to C-1 (δC 177.1). Concerning the geometry of 7, the ROESY correlation (Figure 2 and Figure S32 in Supporting Information File 1) of H-10/H2-12 disclosed that the ∆10,11

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• temperature derived from the heat of reaction accelerated the reaction. The quantitative yield by HPLC was 98.3% and the byproduct carboxylic acid 3a was 1.3%. 3a was easily purged by extraction with a weak base such as NaHCO3. From the above discussion, the throughput was improved to 1.4 kg/day (= 57 g/h