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

• 1883 and involves its synthesis from phenylhydrazine and an aldehyde or ketone using an appropriate acid catalyst [8]. In the following years, new processes were developed for the synthesis of indole such as the Castro, Bischler, and Larock synthesis etc. [2][9][10]. Carbonylation reactions represent a

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• -containing electron-withdrawing groups such as methyl ester and ketone did not show much of an effect in the outcome of the reaction, providing compounds 4bd and 4be in high yields and good er. On the other hand, product 4bq was obtained in a higher yield but with a lower er. The p-halogen-containing

(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

• -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

• (±)-30. In a related strategy, Procter and co-workers prepared 1,2-BCHs (±)-33a–e from BCBs 32 via a SmI2-catalysed radical relay alkene insertion (Scheme 3C) [35]. This approach relied on single-electron reduction of the ketone moiety and ring-expansion from the ketyl radical anion. Electron-deficient

• alkenes including acrylates, vinyl sulfones, and acrylamides could all be incorporated and the number of accessible bifunctional 1,2-BCHs was increased further by chemical transformation (Scheme 3D) [35]. Among the reported transformations were reduction of the ketone (to (±)-34), hydrolysis of the

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• 10 and 11 can be oxidized to the same 9-oxospiroviolane (12) in the same 92% isolated yield, hence confirming the structural assignment of 10 and 11. By reacting with 2,4-dinitrophenylhydrazine [34], ketone 12 was further converted to hydrazone derivative 13, which gave a brownish-yellow crystal

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• the exo-face. This process was used to prepare the known compounds 10a–c, and the novel materials 10d–f [9]. Thus, the reaction of o-dibromoxylene with cyrene gave the alcohol 10d in 71% yield over two-steps through the spirocyclic ketone 9d. Alkylation of 2 with methyl iodide gave an inseparable

• mixture of ketone 9e and the O-alkylated enol ether by-product, which was then reduced using NaBH4 to give alcohol 10e with 98:2 selectivity. Similarly, the reaction of 4-methoxybenzyl bromide and 2 gave ketone 9f in 35% yield without chromatography, and when reduced resulted in only a single alcohol

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• that the only difference between compounds 3 and 2 is the position of the hydroxy group [28]. Analyses of the NMR data of compound 4 concluded that it is an analogue of 2. In comparison with 2, compound 4 has a ketone carbonyl signal at δC 219.1 and we finally confirmed its structure by comparing it

• a precursor for derivatives 2–4. The biosynthetic pathway is likely to involve enzymatic modifications at the C-2 and C-3 positions, leading to the formation of diols 2 and 3, with additional oxidation steps producing ketone 4 (Figure 3b). This supports the presence of three P450s in the cav cluster

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

• azido-hydration reaction [18]. The homopropargylic azide was obtained in only 28% yield using phenyl vinyl ketone. Based on reported aza-alkynylation reactions [19][20][21][22][23] and modern azidation methods using radical chemistry [17][24][25][26] three approaches could be envisaged. All of them

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

• 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

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• )/δC 206.9 (C-9) connected C-11 and C-8 through a ketone carbonyl carbon at C-9 and hemiacetal carbon at C-10, revealing the 16-membered macrolide structure of 1. The HMBC, δH 4.27 (H-1’)/δC 85.3 (C-5), revealed that the disaccharide moiety was connected to C-5. Finally, considering the molecular

• compounds 1 and 5 were identical. To reveal the absolute configuration, we recorded the ECD spectrum of 1 (Figure 4) and compared it with those of 2 and 5 reported in previous papers [5][6]. We detected a Cotton effect of negative sign at around 280 nm corresponding to the n–π* transition of a ketone group

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• m/z 341.1862 [M − H]− (calcd for C20H25N2O3, 341.1870). Spectroscopic analysis, including 1H NMR, 13C NMR (Table 1), and DEPT, revealed that compound 1 contains three methyl groups, one of which is oxygenated, four methines, three saturated non-protonated carbons, and two ketone carbonyl carbons (δC

• 335.1719 [M + Na]+ (calcd for C19H24N2O2Na+, 335.1730) and m/z 311.1755 [M − H]− (calcd for C19H23N2O2, 311.1765). Spectroscopic analysis using 1H NMR, 13C NMR, and DEPT (Table 2) indicated that compound 2 comprises two methyl groups, five methines, five saturated non-protonated carbons, and one ketone

• carbonyl carbon (δC 174.6). Its NMR profile is similar to brocaeloid C [24], with the distinction of an added succinimide substructure at N-15, where the ketone carbonyl carbon at C-16 is replaced by a hydroxy carbon. The isoprene group is consistent with that in compound 1. HMBC cross-peaks from H-10 to C

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• formation of NADH, we are assuming the formation of a ketone product. However, further experiments are required to verify this assumption and determine which inositol position is being oxidized. When we tested Hyg17 with myo-inositol and NADP, we found no activity, showing that Hyg17 is NAD+-dependent

• Bacillus subtilis, BsIDH, has an optimal pH between 9.5–10 [12][13]. We also compared product formation between reactions with Hyg17 or BsIDH and myo-inositol using thin-layer chromatography (Supporting Information File 1, Figure S3). We found that both enzymes generated a ketone product with identical

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• enolization of the monofluoro-diketone intermediates. In addition, imines and α-diboryl ketone derivatives can also be transformed to 2,2-difluoroketones using an N–F electrophilic fluorinating reagent [18]. Alternatively, building blocks containing CF2 units such as ethyl bromodifluoroacetate and

• 13C{1H} NMR spectra contained signals supporting the presence of ketone (e.g., δC = 185.6 ppm for 5a) and ester (δC = 161.9 ppm for 5a) functionalities. Difluoroketoester products were found to hydrate readily to give gem-diol derivatives during aqueous work-up [39], thus reducing the efficiency of

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• . The difference between the two mechanistic pathways is the nature of activation of the carbonyl group. Protic acids induce the protonation of the carbonyl group of the aldehyde or ketone, enhancing its electrophilic character. Whereas, Lewis acid catalysts bind to the heteroatom of the carbonyl group

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• mechanism discussed in Scheme 7B. Lastly, radical–radical coupling between 64 and 147, accompanied by elimination of the NHC catalyst, yields ketone product 149. In subsequent studies, this NHC-catalyzed radical relay activation mode has been extended to the alkylation of aliphatic aldehydes [107] and to

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• π-CPCs relies on the extrusion of carbon monoxide (CO) from soluble precursors incorporating bridging ketone fragment(s). In contrast with the thermal activation required in retro-Diels–Alder reactions, photoirradiation of α-diketones triggers a Strating–Zwanenburg decarbonylation leading to the

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

• electrochemical conditions. Experimental General procedure of anodic oxidation Compound 1 (145 mg, 0.2 mmol), Bu4NPF6 (387 mg, 1 mmol), CH2Cl2 (10 mL), phosphate base (90 mg, 0.2 mmol) and methyl vinyl ketone (32.7 μL, 0.4 mmol) were added to a test tube, which was then subjected to a constant electrical current

• in vacuo and the resulting residue was subjected to 1H NMR spectroscopy or column chromatography. A divided-cell experiment was performed using an H-type cell (4G glass filter). Compound 1 (0.2 mmol), Bu4NPF6 (387 mg, 1 mmol), phosphate base (90 mg, 0.2 mmol), CH2Cl2 (10 mL), and methyl vinyl ketone

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• -annelated IF-DTF 12 by removal of the tosyl (Ts) group under alkaline conditions, followed by nucleophilic substitution to incorporate the hexyl chain on the pyrrole. Furthermore, treatment of the IF-DTF ketone 4 with Lawesson’s reagent (using a recently established protocol [20]) yielded the large dimer 13

• as a mixture of E and Z isomers (ca. 4:1). Further functionalization of the IF-DTF ketone 11 was obtained by Ramirez/Corey–Fuchs dibromo-olefination and Knoevenagel condensation to yield vinylic dibromide 14 and diester 15, respectively, as illustrated in Scheme 2. We noted that the dibromo

• in Figure 6, and potentials against ferrocene (Fc/Fc+) (obtained from differential pulse voltammetry, see Supporting Information File 1) are summarized in Table 2. Compounds 11 and 15 showed two irreversible first oxidations at +0.34 V and +0.38 V vs Fc/Fc+, showing that replacing the ketone with the

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

• University of Technology, Stremayrgasse 9, 8010 Graz, Austria 10.3762/bjoc.20.6 Abstract The reactions of 2,4-di-tert-butyl-6-(diphenylphosphino)phenol and various Michael acceptors (acrylonitrile, acrylamide, methyl vinyl ketone, several acrylates, methyl vinyl sulfone) yield the respective phosphonium

• carbanion [13][14]. Also with other Michael acceptors such as methyl vinyl ketone, several acrylates as well as methyl vinyl sulfone the reaction proceeds smoothly under the same reaction conditions (Scheme 1). Conversions of 1 are usually quantitative within 24 h and all phosphonium phenolates can be

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• well-known and useful reaction in organic chemistry, affording carbonyl compounds based on an atom-economical approach. Indeed, the addition of water to the triple bond of a terminal alkyne leads to the formation of the corresponding methyl ketone or aldehyde, in the case of Markovnikov or anti

• diphenylacetylene (1a), affording the corresponding ketones in high yields after 5 h. Otherwise, terminal alkynes generally showed higher reactivity compared to internal ones. For all the studied terminal alkynes, only ketone products (Markovnikov) were obtained, excluding the formation of the anti-Markovnikov ones

• 1f decreased the selectivity with respect to formation of the hydration product 2f, favouring the condensation product 3f (Table 4, entry 6). On the other hand, an ortho methyl group in 1g favoured formation of the ketone 2g, with a good yield, probably due to the steric hindrance of the aldol

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• Ar and CF3 groups can localize the negative charge and also provide steric effects to afford stereoselective cycloaddition products with 3:1 to 6:1 dr. The steric hindrance also prevents products 9 from undergoing a second cycloaddition. The control reactions of methyl ketone or benzaldehydes gave

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

•  1) exhibited signals corresponding to a spiro-carbon at δC 100.6 (C-9) and a ketone carbon at δC 213.3 (C-8). The HMBC correlations of H-10β/C-8, C-9, C-11, C-12; H-11/C-9, C-13; H2-13/C-9; H-16/C-7, C-8; and H3-18/C-11, C-12, C-13 and the connectivity confirmed by DQF-COSY indicated that 3 also

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• well-defined polymer brushes from polymer surfaces [170][171]. Photoinduced processes, including photoATRP and PET-RAFT were used [172][173][174][175]. Poly(aryl ether ketone)s such as poly(ether ether ketone), bearing a diaryl ketone moiety resembling that of benzophenone, can generate biradicals upon

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• 196.1 for a ketone group, 169.2 and 165.6 attributed to oxygenated aromatic carbons, and three other signals at δC 109.4, 106.2, and 16.6 (Figure S6 in Supporting Information File 1). On the other hand, each of the two aromatic methyl signals displayed a set of three cross peaks; the first one at δH

• 2.09 with the carbon signals at δC 165.6, 122.0, and 120.3, and the second one at δH 2.02 with the carbon signals at δC 169.2, 165.6, and 106.2 (Figure 2). These findings clearly indicated the presence of the 1,3-dimethylbenzene moiety linked to a side chain containing an ethyl group and a ketone group

• and 28.8. Hence, these key correlations permitted to assign the attachment of the hemiketal carbon (δC 106.1) to the ketone group and the benzene ring. Based on the above evidence, the structure of 1 was assigned with a trivial name of 5,7-dimethylpseudopithonone (Figure 1). Pseudopithonone was

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• reductive elimination to yield ketone 78. In the acylthiolation cycle, the azaphilic ZnCl2 activated NTSE 1’’’ via N–Zn coordination to facilitate the leaving ability of succinimide. Then, nucleophilic substitution of arylmagnesium bromide 75 to intermediate IV provided thioester 79. In 2022, Gao and co

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• by X-ray analysis (see Supporting Information File 1). Both, hydroxy ketone 1 and the corresponding enone 2, can be converted into the same indanone 3 in comparable yields; see pairs of reactions for 1a and 2a (indanone 3a), 1d and 2d (indanone 3d), 1i and 3i (indanone 3i), and 1n and 3n (indanone 3n

• -rich enones 2o,t,u, bearing electron-donating substituents in the aromatic rings, afford complex mixtures of oligomeric materials. The cyclization of hydroxy ketone 1k into indanone 3k is accompanied by demethylation of one of the methoxy groups (Scheme 6). The positions of hydroxy and methoxy groups

• delocalization of the positive charge from the carbonyl group to the aromatic ring. It should be mentioned that cation Bm was generated by two ways in TfOH: either directly by protonation of enone 2m or from hydroxy ketone 1m. The latter was found to undergo fast dehydration into enone 2m in TfOH at room