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

• of the desired amide 5a after 16 h at rt, which could be isolated in 80% yield after column chromatography. A survey of carboxylic acids 1 revealed that the one-pot approach is efficient for a variety of substitution profiles (Scheme 2). Aromatic acids bearing methyl substituents at the para-, ortho

• functionalisation chemistry such as coupling reactions (5g, 5m, 5n). Heteroaromatic (5o) and aliphatic carboxylic acids (5j, 5p, 5q) also reacted smoothly under the optimised conditions. As demonstrated by the efficient formation of amide 5q in 84% yield, the process is tolerant of significant steric bulk at the

• 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

(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

• ]. The ability of 1,5-BCHeps to act as bioisosteres of meta-benzenes was also studied by Anderson and co-workers. They reported the comparison of fatty acid amide hydrolase inhibitor URB597 with its 1,5-BCHep isostere 146 (Figure 21) [27]. They found that while replacement of one of the meta-benzenes

• acid motif, formation of the Weinreb amide 181 and Curtius rearrangement (to 182) were all possible. Comparative physicochemical and biological data for selected 1,3-cubanes and meta-benzene was reported by MacMillan and co-workers. They compared lumacaftor, one of the active compounds of the cystic

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• of hydrophilic oligopeptide anchors (oligo-Lys, oligo-Glu, and oligo-Arg) were synthesized. A previously reported Prato reaction adduct of a biscarboxylic acid-substituted C60 derivative was subjected to a solid phase synthesis for amide formation with N-terminal amines of peptides on resin to

• suitable for the coupling to peptides on resin, prepared by solid-phase peptide synthesis (SPPS) [35]. The detailed conditions for the amide-forming reaction were optimized using biscarboxylic acid-substituted C60 derivative 3 and a similar peptide with a primary amine derived from γ-aminobutyric acid

• on resin, a GABA residue was attached to the N-terminus of the peptide in order to provide a less-hindered primary amine, enabling an efficient amide conjugation reaction with biscarboxylic acid-substituted C60 derivative 3. Compound 3 was prepared by Prato reaction of C60 and an N-glycine derivative

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• linkers capable to connect these porphyrins with biomolecules, thus improving their biomedical characteristics and theraputic efficacy for PDT and BNCT due to the combination of different substituents within porphyrin framework. Amide coupling of A3B-type carboranylporphyrin containing an amino

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

• 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

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• TE-catalyzed marcolactonization [69]. The synthesis of linear peptide 34 commenced with the lactone opening of 26 to afford Weinreb amide 27. Following primary alcohol protection and amide reduction, the aldehyde 28 was coupled with iodide 29 to afford 30 via Nozaki–Hiyama–Kishi coupling, which was

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• such as 4d and 4e could be obtained in 84% and 78% yield, respectively. We were pleased to see that the presence of an acetamide did not shut down the reaction, the corresponding product 4f was obtained in 68%. The amide could have competed with the alkynyl-trifluoroborate for the carbocation trapping

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• , amoxapine, an ibrutinib derivative, N-desmethyl sildenafil, silodosin, and lapatinib (4d–k, 35–67%). The late-stage modification of these drug agents and their derivatives in this MCR underlined the synthetic value and high functional group tolerance (e.g., aromatic amine, amide, alcohol, heterocycle). We

• 7 and 8 were produced in high yields through LiAlH4 conditions or nucleophilic addition of methylmagnesium bromide. Moreover, product 4a could be easily transformed to unsaturated ε-amino amide 9 in total 76% yield. Likewise, Weinreb amide 10 was produced and further transformed into ketone 11 in 84

Synthesis of photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophene-3(2Н)-ones with a terminal phenanthroline group

• Vladimir P. Rybalkin,
• Sofiya Yu. Zmeeva,
• Lidiya L. Popova,
• Irina V. Dubonosova,
• Olga Yu. Karlutova,
• Oleg P. Demidov,
• Alexander D. Dubonosov and
• Vladimir A. Bren

Beilstein J. Org. Chem. 2024, 20, 552–560, doi:10.3762/bjoc.20.47

• vibrations of the thiophene and amide carbonyl groups were observed at 1663–1678 and 1705–1713 cm−1, respectively. The 1H NMR spectra contained signals of methine protons (=CH–) in the region 7.92–9.02 ppm, which corresponded to the Z-configuration of the C=C bond. According to data previously obtained [14

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• their solvation sphere occupy part of the cavity and prevent non-coordinating guests from entering the binding cavity. By extending the spacer between the terpy and the arms from a single C–C bond to an amide functional group that also participates in the coordination of the Zn2+, non-coordinating

• luminescence properties of the system could then be regulated by closing/opening but also by the addition of Cl− that could form hydrogen bonding with the amide function of the spacer between the switching and the functional units. The WLA has also been applied to obtain switchable molecular tweezers for

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• groups as measured by rates of Michael addition [52]. This suggests that in fact nitrogen nucleophilicity alone is not the most relevant factor since sulfonamides react much slower in hydroamination. Sulfonamide N–H bonds are significantly more acidic than urea, amide and carbamate N–H bonds (16.1 versus

• ; more basic carbonyls react faster and undergo N–H/D exchange faster in the presence of gold suggesting gold nucleophile interactions drive reactivity. • Rate inhibition is observed at the highest concentrations of urea 1a and amide 1b; the increasing basicity would slow down any acid mediated processes

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains

• Sharmila Neupane,
• Marcelo Rodrigues de Amorim and
• Elizabeth Skellam

Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32

• of several catalytic domains organized into modules. Typically, a module possesses an adenylation (A) domain for selecting and activating amino- or keto acids, a thiolation (T) domain for shuttling intermediates between catalytic domains, and a condensation (C) domain that catalyzes amide or ester

• . The 1H and 13C NMR spectra of 1 revealed the presence of seven amide NH signals between δH 7.43 and 8.44 ppm supported by the amide carbonyl signals at δC 173.1, 172.6, 172.6, 172.1, 172.1, 171.1 and 171.0 ppm (Table 1). An additional NH signal at δH 10.82 ppm and four aromatic signals at δH 7.50

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• 4aa [35] was isolated in 62% yield (Scheme 4). On the basis of the transformation of 3aa to 4aa, a tentative reaction mechanism is proposed. As shown in Scheme 5, the spiropyridazine-benzosultam 3aa was firstly oxidized to intermediate A. Next, an aziridine was formed with the hydrolysis of the amide

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• presence of methyl vinyl ketone (MVK) as a radical acceptor (Table 1). Tetrabutylammonium dibutyl phosphate (phosphate base), which operates as a PCET initiator through hydrogen bond formation with the N–H bond of amide/carbamate [11], was used as an additive. As a result, N-alkylated product 3 was

• current (Figure 2B, blue line). We considered that the inter- and intramolecular chemoselectivities were derived from the pKa of the proton sources. The pre-organization of the amide substrate and phosphate bases is an important process in PCET [13]. Recently, Gschwind et al. published a detailed NMR

• hydroamination reaction compared to the less acidic PhOH (pKa = 9.95 in H2O) because PhSH supplied free protons (H+) and contributed to the persistence of small aggregates composed of the amide and phosphate base [14]. On the other hand, owing to the insufficient dissociation constant between the proton and

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• unchanged, although quinoline and its derivatives are easily aminated under the same conditions [17]. No interaction occurred under the conditions of the Chichibabin reaction in an attempt to aminate compound 5 with sodium amide in N,N-dimethylaniline at 140–155 °C for an hour. Thus, quinoquinoline 5

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• shift was observed, which can be attributed to a weakening of the indigo-type resonance, while the amide resonance remained relatively unaffected (Figure 10). One of the crucial problems accompanying the investigations of photoswitchable molecules are the situations when the photoisomerization product

• the Z-isomer with metal cations. Schematic representation of indigo-type (left) and amide-type (right) resonances in N,N'-acetylindigo (9a). Suggested intermediates for the double bond cleavage for the thermal relaxation of N,N'-diacylindigos: (A) a biradical transient species, (B) a dipolar transient

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• occurs first at the amide position. This approach enabled the successful synthesis of a broad spectrum of dibenzodiazepinone units in a one-pot fashion. The synthetic utility of Laha’s approach was highlighted by preparing the corresponding dibenzodiazepinone which was further reacted with N

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• such as 2d, 2e, and 2f performed well, affording the brominated product 3aa in excellent yields (90–99%). However, transformations of amide 1a to the brominated product 3aa employing unactivated alkyl bromides (2g–i) as reaction partners proceeded with low efficiency (0–53%). Notably, the reactivity of

• aliphatic amide substrates, and proceeds well with activated and unactivated alkyl bromides. Further studies on mechanistic details and the persistent exploration of halogen sources are ongoing in our laboratory. Experimental A 35 mL sealed tube equipped with a stirring bar was charged with 8

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• substructures. Consequently, the macrocycle was tethered to the peptide segment through amide–amide hydrogen bonding, and 44 was obtained with 30% yield. The generation of 44 was accompanied by the formation of the corresponding free thread with 62% yield, resulting from the reaction between the thread

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• amine functionalized substrate, because of competition of the reaction site during the synthesis of substrates. However, an amide-substituted indole furnished a clean product without competition; for example, product 3u was derived from melatonin with an amide functional group, whose reaction to the

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• the amine 2b gave the corresponding amide 2g in 28% yield. The chloro-substituted derivative 2e was synthesized in a Sandmeyer-reaction from 2b in 20% yield. The products 2a–g were identified and fully characterized by NMR spectroscopy (1H, 13C, COSY, HSQC, and HMBC), elemental analyses, and mass

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• donors attached to the alkyl substituent of the phosphonium center (Figure 3). This hypothesis is further supported by the observation of two very different chemical shifts for the two amide protons in the 1H NMR spectrum of 2b in CDCl3 giving resonance at 5.21 and 8.58 ppm. Kinetic studies In the next

• for the conversion of acrylamide, which is probably disturbed when the hydrogen bond donor solvent methanol is interacting with the amide group and/or the hydroxy group. Conclusion The conjugate addition of 2,4-di-tert-butyl-6-(diphenylphosphino)phenol to Michael acceptor molecules allows for a facile

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• equiv amide, 15 mol % CuI, 30 mol % diglyme, 3.00 equiv K2CO3 and 2.00 equiv dibenzo[b,d]iodol-5-ium trifluoromethanesulfonate. Scope of iodanes. aIsolated yields, 200 µmol scale, all reactions carried out in p-xylene, with 1.00 equiv amide 15 mol % CuI, 30 mol % diglyme, 3.00 equiv K2CO3 and 2.00 equiv

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• NHC·CS2 zwitterions relies on the deprotonation of an azolium salt with a strong base, typically potassium tert-butoxide or potassium bis(trimethylsilyl)amide (also known as potassium hexamethyldisilazide, KHMDS) followed by the addition of carbon disulfide either in one pot or after the isolation of the

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• derivatives. In fullerene 8, this is an amide with a short ethylene tether for the tertiary amine (Figure 3). Fullerene 8 catalyzed the formation of the addition product 6 with high selectivity over the decarboxylation product 7 [12]. The experimental product ratio A/D8 was divided by the product ratio A/D9

• control 12, a secondary Bingel amide in 13 caused a drop to A/D13/12 = 1.6. Similarly, low A/D14/12 = 1.5 for an ester in 14 supported that removal of the hydrogen-bond donor in 5 rather than steric constraints account for the decrease in anion–π catalysis. Elongation of the tether in the ester series 14

• –16 was as in the amide series from 8 and thus supported entropic contributions to anion–π catalysis. Steric increase of the secondary amide in 17 impeded anion–π catalysis, presumably because the catalytic π surface next to the ammonium cation became inaccessible for anions paired with the tethered