Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• oxocarbenium 7 and 7’ which exists as a stabilized form including an intramolecular stabilizing interaction between the carbocation and the ester carbonyl group. However, in close agreement with Hess and Baldwin’s values found for the rearrangement of cis-1,3-pentadiene [24], this transition state was high in

• % yields. The success of the reaction with an ester substituent to give 12k is surprising if we compare it with other electron-withdrawing groups like CN or NO2, which failed to give the corresponding cyclization products 12l–n (not shown). Instead, olefin products 13l–n arising from an elimination were

• structure shows one disordered ethyl ester group (backward). Examples of cyclolignan natural products [25][26][27]. The Hock rearrangement: (a) General mechanism (substituents are omitted); (b) Example of previous tandem process; (c) Objective of this work. One-pot conversion of substrate 1 into

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

• tolerated, affording the desired products in excellent yields (92‒99%). These results indicated that the electronic effect of substituents affected the reaction only slightly. Products with substituents with derivatization feasibilities such as halogen (3ga–ia), acetyloxy (3ja), and ester groups (3ka) also

• . The scope of the bromination reaction was further extended with various alkyl bromides. As shown in Scheme 3, a series of activated alkyl bromides containing ester, difluoromethylene, benzyl motifs (2b–f), and unactivated alkyl bromides (2g–i) were evaluated in this reaction. Activated alkyl bromides

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

• adduct leads to the formation of a spiro compound [89][90][91][92][93][94]. Ester-substituted, electron-deficient alkenes have also been employed in [2 + 2] CA–RE reactions involving electron-rich alkynes. Alkenes featuring either one or two ester substitutions exclusively catalyze [2 + 2] CA–RE

• reactions, yielding multicyanated ethenes [95]. Contrarily, alkenes bearing three or four ester substitutions partake in a [4 + 2]-type hetero-Diels–Alder (DA) reaction, yielding a third product, presumably through a [3 + 2] cycloaddition reaction, followed by rearrangement. The [2 + 2] CA–RE reactions

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

• acceptor methyl acrylate reacts much faster in chloroform than acrylonitrile. A likely explanation is the preorganization of the Michael acceptor and donor by hydrogen bonding between the phosphine’s hydroxy group and the carbonyl group of the ester B’. Such a preorganization facilitates the proton

Facile access to pyridinium-based bent aromatic amphiphiles: nonionic surface modification of nanocarbons in water

• Lorenzo Catti,
• Shinji Aoyama and
• Michito Yoshizawa

Beilstein J. Org. Chem. 2024, 20, 32–40, doi:10.3762/bjoc.20.5

• sheets with thicknesses of 10–30 nm and widths of 150–300 nm (Figure 6c,d), indicating solubilization of (g-C3N4)m as 20–60 stacks. The encircled g-C3N4-based host–guest composite was subsequently deposited onto a mixed cellulose ester (MCE) filter (50 nm pore-size) using a simple filtration protocol

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

• possible products. We obtained p-halogenide- and p-pseudohalogenide-substituted compounds 2c–g in good yields of 76–87%. It is noteworthy that the para-chloro-substituted compound 2f is a known fluorophore [5]. The reaction tolerated methoxy- and methyl ester-substitution to give 2h and 2i in 84% and 90

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• dihydrospiro[indoline-3,5'-[1,2]diazepines] 5a–i: A 10 mL reaction tube was charged with α-halogenated acylhydrazone (0.2 mmol), MBH ester of isatin (0.1 mmol), DABCO (0.2 mmol, 0.0224 g), and dichloromethane (4.0 mL) and the mixture was stirred at room temperature for 24 hours. After removing the solvent by

• ] 7a–l: A 10 mL reaction tube was charged with α-halogenated N-tosylhydrazone (0.2 mmol), MBH ester of isatin (0.2 mmol), triethylamine (0.4 mmol, 0.0364 g), and dichloromethane (4.0 mL) and the mixture was stirred at room temperature for three hours. After removing the solvent by rotatory evaporation

• -bromo-N-acylhydrazones were used. Yields refer to isolated compounds. Synthesis of spiro[indoline-3,5'-[1,2]diazepines] 5a–g. Conditions: α-halogenated acylhydrazone (0.2 mmol), MBH ester of isatin (0.1 mmol), DABCO (0.2 mmol), DCM (4.0 mL), rt, 24 h; aα-chloro-N-acylhydrazone was used, for other

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

• 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

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

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• . An EDA complex was formed through non-covalent interaction between the redox ester 10 and n-Bu4NI (Scheme 7). Subsequently, upon the photoexcitation, radical pairs I were generated via a SET process, accompanied by the liberation of CO2 and the phthalimide anion. The recombination of the alkyl

• ], it was proposed that the decarboxylative cascade cyclization reaction proceeded through the formation of a charge-transfer complex (CTC) II involving PPh3, NaI, and NHP ester 3 (Scheme 20). Upon photofragmentation of the CTC complex II, two important intermediates were generated: an alkyl radical A

Quinoxaline derivatives as attractive electron-transporting materials

• Zeeshan Abid,
• Liaqat Ali,
• Sughra Gulzar,
• Faiza Wahad,
• Raja Shahid Ashraf and
• Christian B. Nielsen

Beilstein J. Org. Chem. 2023, 19, 1694–1712, doi:10.3762/bjoc.19.124

• phenyl-C61-butyric acid methyl ester (PCBM) acceptor when used in bulk heterojunction polymer solar cell devices with poly(3-hexylthiophene) (P3HT) as the donor material. This improvement was attributed to the anchoring effect of the bulkier groups present in TQT-C60, which hindered the movement and

• and demonstrated n-type properties due to the electronegative Qx unit [53]. Mikie et al. explored ester-functionalized quinoxalines (QEs) as building units for both p-type and n-type polymers. They synthesized two new π-conjugated polymers, Qx51 and Qx-52, with low-lying HOMO (–5.5 eV) and LUMO (–3.4

A deep-red fluorophore based on naphthothiadiazole as emitter with hybridized local and charge transfer and ambipolar transporting properties for electroluminescent devices

• Suangsiri Arunlimsawat,
• Patteera Funchien,
• Pongsakorn Chasing,
• Atthapon Saenubol,
• Taweesak Sudyoadsuk and
• Vinich Promarak

Beilstein J. Org. Chem. 2023, 19, 1664–1676, doi:10.3762/bjoc.19.122

• -N-carbazole 2 in good yield (87%). Compound 2 was then converted to the boronic ester intermediate 3 in 41% yield over two steps: monobromination at the carbazole unit of 2 with NBS/THF at low temperature giving the unisolated mixed brominated product followed by borylation with bis(pinacolato

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• electrospray ionization HRESIMS analysis, and quantum chemical electronic CD calculations. Furthermore, the absolute configurations of sugar residues were determined by derivatization of the hydrolysates with ʟ-cysteine methyl ester and o-tolyl isothiocyanate followed by HPLC analysis. The anti-inflammatory

• by acid hydrolysis of 1 using the method developed by Tanaka et al. [16], in which the hydrolysates are derivatized with ʟ-cysteine methyl ester and o-tolyl isothiocyanate followed by HPLC analysis. For compound 1, peaks were observed at retention times of 13.96, 20.83, and 22.16 min. The peaks at

• 5.78 (d, J = 7.8 Hz, 1H, H-1′); δC 94.0 (C-1′)] implied that compound 4 was a β-glycosyl ester. The HMBC correlation of H-1′ with a carbonyl carbon [δC 174.7 (C-3)] revealed that esterification occurred at C-3 with a glucopyranose moiety at the anomeric position (Figure 4). A β-1,3-glucosyl linkage

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

• , 1,4-additions of dialkylzinc reagents have been reported with dehydroamino ester derivatives [13][14] and α-bromoacrylates [15], which both involve an SH2 at zinc of tertiary α-alkoxycarbonyl radicals (Scheme 2, top). Here, the key to unlock the reactivity is the presence of a Lewis-basic substituent

• , thereby precluding its synthetic exploitation. Results and Discussion Preparation of α-(aminomethyl)acrylates We commenced our study by preparing a selection of α-(aminomethyl)acrylates with variations of the nitrogen protecting group and the ester substituent. Towards this end, the direct allylation of

• . Importantly, the protocol was found to be similarly applicable with enoates 8b (Table 3, entry 6) and 8c (entry 7) having tert-butyl and benzyl ester groups, which, as the methyl ester unit, are typical in the context of amino acid synthesis. ZnBu2 was also amenable to 1,4-addition (Table 3, entry 8), but not

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

• complex between Hantzsch ester and N-trifluoroethoxyphthalimide was subsequently engaged in a nickel-catalyzed coupling reaction with in situ-activated alkyl carboxylic acids. This convenient protocol does not require photocatalysts and metal reductants, providing a straightforward and efficient access to

• elegant strategies on direct conversion of in situ-activated carboxylic acids for ketone synthesis [27][35][38], we chose dimethyl dicarbonate (DMDC, A1) as the activating reagent. To our delight, the reaction of 1a and 2 in the presence of NiBr2(dtbbpy) (10 mol %), Hantzsch ester (HE) and A1 in DMAc

• -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

• (plasmalogen) is highly sensitive to oxidation and it is reported that this function is even more reactive than unsaturated and polyunsaturated lipid chains [27]. Accordingly, plasmalogens could act as ROS scavenger and thus protect tissues (e.g., brain) from oxidative stress. The replacement of an ester

• mild conditions the benzylation of the alcohol function to yield 7.3. Then, the removing of the tosyl group required a two-step sequence. First, 7.3 reacted with cesium acetate and then the resulting ester was reduced with LiAlH4 to produce 7.4 with control of its stereochemistry. Very recently, a new

• with mCPBA produced the epoxide 13.3. Then, the addition of benzoic acid in the presence of acid catalysis produced an ester that was saponified to yield the diol 13.4. A three-step sequence is applied to produce compound 13.5 that features a secondary alcohol protected with a benzyl group. Then, the

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

• methylene groups at δH 2.65/2.69 (H2-2') and δH 2.69/2.72 (H2-4') to an ester carbonyl (δC 172.4, C-1') and a carboxyl (δC 175.0, C-5'), respectively. In addition, both methylene groups together with a methyl singlet at δH 1.38 (s, H3-6') disclosed key HMBC correlations to a quaternary oxygenated carbon at

• of H-17 and C-21, respectively. By comparing the HRESIMS, 1H and 13C NMR data of compound 1 and those reported for forpinioside A [23][28], it was obviously recognized that compound 1 lacks the ester group at δH 3.62 (OCH3-5'; δC 51.9) on the 3-hydroxy-3-methylglutaroyl substituent. Further

• 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

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

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• heterocyclic system, namely imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines 3 (Scheme 1B). Results and Discussion In a continuation of our studies [22] aimed at the synthesis of functionalized imidazothiazolotriazine derivatives, we attempted to hydrolyze the ester group of imidazothiazolotriazines 1 and to

• ][1,3]thiazino[2,3-c][1,2,4]triazines 3a–i as a result of ester group hydrolysis and thiazolidine ring expansion to the corresponding thiazine (Scheme 3). The potassium salts 3a,b were isolated in 81 and 63% yield, respectively. Compounds 3c–i were used in further transformations without isolation. 1H

• NMR reaction monitoring showed that compound 1d under conditions of excess of KOH in methanol undergoes alkaline hydrolysis along with transesterification of the ester group to give the ring-opened form 6d (Scheme 4), the maximum concentration of which was observed approximately 30 minutes after the

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• excellent purity in all experiments (Figures 2D, 3C, and Figures S8 and S9 in Supporting Information File 1). For these compounds, we explored two different post-AGA procedures: the standard path A based on photocleavage and HPLC purification, and path B involving on resin methanolysis of the ester groups

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

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• for the functionalization of the C3–H bond in indoles 9 in the presence of BINOL-derived chiral phosphoric acid P6 as the catalytic agent. They utilized trifluoromethyl ester-substituted N-unprotected imine 15 as the potential electrophile to install an aza-quaternary stereocenter in the C3 position

• reaction between 2-methoxyfuran (1) and aryl-α-ketimino ester 26 to activate the C2’–H bond in 1. The C1-symmetric catalyst P10 was the optimal catalyst for the second reaction furnishing the products with excellent chemical yields and enantioselectivities. To understand the activities of the catalysts

• aryl moieties. For this purpose, sterically bulky substituents need to be present in the aryl ring attached to the C3 position of the starting indoles. The axial chirality was attributed to ester and phenolic OH groups at the ortho-positions of the aryl ring and an additional phenolic OH functionality

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• ). This reaction has been successfully used for common amines using acetic acid and water, but benzylamines and benzamides show no reaction under aqueous conditions. In the case of amino acid ester hydrochlorides, the reaction to give pyrrole can be carried out without the need for the two-phase

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

• carboxylate anion and/or reduction of the corresponding N-hydroxyphthalimide- (NHPI)-derived redox-active ester, although it destroys their stereochemical information [46][47][48][49][50][51]. In addition, the side-chains of aromatic amino acids (mainly electron-rich tryptophan and tyrosine) can be

• proton transfer from the oxidized indole radical cation [75], generated by SET from the activated photocatalyst. The α-amino radical generated by reductive decarboxylation of a DMAT derivative with a redox-active ester (−1.26 V to −1.37 V vs a saturated calomel electrode) would enable turnover of the

• ]. Regioselective palladium-catalyzed prenylation of 2 with prenylboronic acid pinacol ester and subsequent hydrolysis with LiOH provided the linear prenylated acid 4 in good yield. Coupling acid 4 with N-hydroxyphthalimide using DCC and a catalytic amount of DMAP afforded the key intermediate 5 in 59% yield. With

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

• ) 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

• reactions (e.g., hydrolysis, esterification, oxidation) might be due to the isolation conditions or they could be attributed to unspecific enzymatic biotransformations. For compound 1, no spontaneous conversion to the ester 2 was observed, even after storage in methanol for two months. In contrast, the