A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

•  1b). Alternatively, the oxidation of α-C–H of active methylene ketones generate α-carbon-centered radicals, thus providing another way to obtain thiazoles. Recently, Sun et al. reported a tert-butyl hydroperoxide/azodiisobutyronitrile-mediated synthesis of 2-aminothiazoles from active methylene

• the in situ generation of α-iodocarbonyl ketones from constant current electrolysis (CCE) of ketones in the presence of iodide ions. It is worth noting that we have also reported an electrochemical method for the synthesis of 2-aminothiazoles via the one-pot direct α-C–H functionalization of ketones

• demonstrate the feasibility of our idea, ethyl acetoacetate (1a) and thiourea (2a) were chosen as model substrates for the optimization of reaction conditions. Based on our previous studies on the halide-mediated α-C–H functionalization of carbonyl compounds [32][33][34][35], graphite was chosen as the

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• (Figure S1 in Supporting Information File 1) is characterized by C7–H7···O12i hydrogen bonds resulting in chain formation along the a direction [C7–H7: 0.93 Å, H7···O12: 2.42 Å, C7···O12: 3.325(3) Å, C7–H7···O12: 164˚; symmetry code: (i) 1 + x, y, z]. Neighboring chains connect by C–H···π interactions

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• amination by oxidative C−H bond functionalizations. These methods showed significant improvement with respect to the substrate scope and reaction conditions. However, mostly they are restricted to substrates containing hydrogen [13][14], alkyl [14][15], or (substituted) phenyl moieties [14][16][17] as N

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• investigate their suitability as substrates in the Regitz diazo transfer. We reasoned that if the C–H acidity of the methylene group in 11 would turn out to be insufficient for the Regitz protocol to be directly applied, these substrates could have been additionally activated by trifluoroacetylation

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• can be modified by the presence of a base or by a single electron cathodic reduction of the C–H between nitrogen atoms of the imidazolium ring (Scheme 1), inducing the formation of a N-heterocyclic carbene (NHC) [7][8]. In recent years, NHCs have achieved great success: they have been frequently used

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• method to synthesize 1,2-azaphospholidine 2-oxide derivatives 13. Arylphosphinyl azides generate arylphosphinyl nitrenes under photoirradiation. The phosphinyl nitrenes underwent an intramolecular insertion into the ortho C–H bond of the aryl group accompanied with the Curtius-like rearrangement as well

• [24]. Both monomesityl and dimesitylphosphinyl azides 14 generated 2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 15 in 31% and 20%, respectively, via an intramolecular nitrene C–H insertion, for dimesitylphosphinyl azide (14b), with 51% yield of phosphonamidate 16 as byproduct. Bis(2,4,6

• (Scheme 5) [25]. The metal-free intramolecular oxidative C–H bond amidation of methyl and ethyl 2,6-dimethylphenylphosphonamidates 24, 26, and 28 is an interesting strategy for the synthesis of 1-methoxy/ethoxy-7-methyl-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxide derivatives 25, 27, and 29 in

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• or dialkyl diselenides, followed by C–H selenation with imidazopyridines to form the corresponding compounds. We also reported the one-pot two-step reaction of Se powder with imidazopyridine and triarylbismuthines using the CuI/1,10-phenanthroline catalytic system without bases, which formed similar

• selenides [25]. In this reaction, unlike the former, bis(imidazo[1,2-a]pyridin-3-yl) diselenides are generated through C–H selenation at the 3-position of 2-arylimidazopyridines with Se powder, followed by the cross-coupling reaction between diselenides and triarylbismuthines. These one-pot reactions are

• [1,2-a]pyridin-3-yl) diselenides using a Cu-catalyzed C–H selenation at the 3-position of 2-arylimidazo[1,2-a]pyridines with Se powder [32]. Initially, the reaction of bis(2-phenylimidazo[1,2-a]pyridin-3-yl) diselenide (2a), generated from Se powder and 2-phenylimidazo[1,2-a]pyridine (1a), with

Thiophene/selenophene-based S-shaped double helicenes: regioselective synthesis and structures

• Mengjie Wang,
• Lanping Dang,
• Wan Xu,
• Zhiying Ma,
• Liuliu Shao,
• Guangxia Wang,
• Chunli Li and
• Hua Wang

Beilstein J. Org. Chem. 2022, 18, 809–817, doi:10.3762/bjoc.18.81

• ···C (3.31 Å), S···C (3.45 Å), and C···H (2.90 Å). Each of the two DH-2 molecules (blue and red molecules, Supporting Information File 2, Figure S7) in the unit cell interact with eight adjacent molecules through multiple interactions, such as, C···C (3.40 Å), Se···H (3.09 Å), H···H (2.26 Å), C···H

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• , perfluorohexylation, and perfluorobutylation. Keywords: α-(perfluoroalkylsulfonyl)propiophenones; innate functionalization; late-stage functionalization; light-mediated perfluoroalkylation; perfluoroalkyl sulfinates; Introduction Perfluorinated compounds are a family of molecules containing a backbone where all C–H

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• review, we give an overview of selected methods for the synthesis of odorants in flow, including heterogeneously catalyzed reactions, gas reactions, and photochemical C–H functionalization processes. After a brief introduction on types of odorants, the presented odorant syntheses are ordered according to

• resembling that of hawthorn or a harsh orange-blossom type“. Acetophenone appears in vintage Geoffrey Beene: Grey Flannel at 0.14%, and Shiseido: Zen and Gap: Om at approx. 0.014%. In 2013, Roberge, Kappe, and co-workers investigated the C–H oxidation of ethylbenzene (37) to acetophenone with oxygen as an

• somewhat similar to coumarin is phthalide (50), having a sweet and powdery scent reminiscent of coconut and tonka bean [43]. Phthalide can be considered as a top note type of coumarin. Recently, Noël and co-workers developed a method for the photochemical, decatungstate-catalyzed C–H oxidation of activated

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• highly reactive Fe(IV)=O species and a succinate byproduct. This Fe(IV)=O abstracts a hydrogen atom from an aliphatic C–H bond of the substrate to generate a radical intermediate. When the enzyme catalyzes the hydroxylation reaction, the radical reacts with the Fe(III)-OH species to form a hydroxylated

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• Dajana Barisic Mario Pajic Ivan Halasz Darko Babic Manda Curic Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, Zagreb, Croatia 10.3762/bjoc.18.69 Abstract The direct and selective mechanochemical halogenation of C–H bonds in unsymmetrically substituted azobenzenes

• using N-halosuccinimides as the halogen source under neat grinding or liquid-assisted grinding conditions in a ball mill has been described. Depending on the azobenzene substrate used, halogenation of the C–H bonds occurs in the absence or only in the presence of PdII catalysts. Insight into the

• species, cyclopalladated intermediates, and products (Figure 1). The monitoring results confirmed the crucial role of TsOH and acetonitrile (MeCN) as additives in the catalytic bromination of the C–H bond in L1. The experimental results were supported by quantum-chemical calculations, which showed that

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• Dongming Zhang Bin Lv Pan Gao Xiaodong Jia Yu Yuan College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, P. R. of China 10.3762/bjoc.18.65 Abstract An efficient Cu-catalyzed strategy for the direct C–H amination of arenes in high yields using N-hydroxyphthalimide as

• decades. With the combination of C–H activation, many aminations of aryl compounds have been established [6][7][8][9][10][11][12][13][14][15][16]. However, it is necessary to introduce the directing group into the arene in most successful cases. As a good amino source, phthalimides have been widely

• the direct C–H amination of arenes in good yields using N-hydroxyphthalimides as the amido radical precursor under mild conditions. This reaction has a broad substrate scope and leads to moderate to good yields in most cases. Also, good chemoselectivities were observed with some substrates. It is

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• direct C–H amination is vital to provide many amine derivatives by sustainable methods [36][37]. The dehydrogenative C–N cross-coupling reactions from unreactive N–H and C–H bonds can lead to various nitrogen-containing heterocycles [32][38]. Herein, we disclose the DDQ-mediated oxidative C–N coupling

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• -ray analysis revealed the presence of the expected [N–H···O] hydrogen bonds between the secondary ammonium station and the crown-ether macrocycle, but also additional [C–H···O] hydrogen bonds involving the benzylammonium methylene groups (see Figure 4). Interestingly, the presence of the directional

• -alkylene-linkers, the diastereoselectivity decreases with increasing linker length (79/33/12% de for C3/C6/C12-linkers, respectively). This is in line with an expected localization of the macrocycle around the ester functionality due to weak [C–H···O] interactions from the COOCH2 group to the macrocycle

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• of the reactants contained a Br, F, or CF3 group in the para-position or contained a thiophene ring (compounds 3b,c,h,i,k, and l). We also explored the reactions between phenyl hydroximoyl chlorides 1a–c and β-ketoesters 2g,h or β-ketoamides 2f,i under the optimized reaction conditions (DIPEA, 95

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

• Zhihang Bai,
• Krishnasamy Velmurugan,
• Xueqi Tian,
• Minzan Zuo,
• Kaiya Wang and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• supramolecular assembly with a two-step FRET process by the utilization of a metallacycle-tetraphenylethylene (TPE) donor and eosin Y (EsY) and sulforhodamine (SR101) as first and second acceptors, respectively. The resulting supramolecular energy transfer system was applied to the alkylation of C–H bonds via a

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• , azides, halides and alkenes, oxidation of remote C–H bonds and alkenes, and substitution reactions involving ring-opening cyclization of epoxides, nucleophilic substitution of allylic chlorides, and hydrolysis reactions. The product selectivity is interpreted as the consequence of the space shape and

• , directing groups are introduced to the substrates covalently to achieve site-selective C–H bond activation, which prospered greatly in the past decades [7][8][9]. Template regulation is also introduced to locate reactive centers in a noncovalent way through hydrogen bonding [10][11][12]. Even though

• powerful role of molecular containers to achieve precise transformation of complex molecules. Oxidation C–H bonds are ubiquitously distributed in nearly all of the organic compounds, which makes them predominant candidates for the modification of complex molecules. Without pre-activation, direct

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• indole derivative 31 in 82% yield (Scheme 11) [22]. Being a kinetically very active catalyst, Rh2(OAc)4 favored the formation of the five-membered ring. On the other hand, employment of Pd(OAc)2-catalysis switched the regioselectivity of this C–H insertion reaction. More specifically, under Pd(OAc)2

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• of the alkyl halide and C–H activation can be increased by the presence of active Lewis acid sites on the iron(III) nanoparticles. The scope for this catalytic system can be figured out by the presence of high temperature, high ligand concentration and activated ligands. Chen and co-workers

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• regioselectivity. The mechanism and origins of selectivity in the iridium-catalyzed hydroacylation reaction has been examined at the M06/Def2TZVP level of theory. The catalytic cycle consists of three key steps including oxidative addition into the aldehyde C–H bond, insertion of the olefin into the iridium

• hydride, and C–C bond-forming reductive elimination. Computational results indicate the origin of regioselectivity is involved in the reductive elimination step. Keywords: C–H activation; density functional theory; hydroacylation; iridium catalysis; regioselectivity; Introduction Organic synthesis is

• bonds [6][7][8][9][10][11][12][13]. Hydroacylation reactions, the formal addition of an aldehyde C–H bond across a C–C π-system, has emerged as a powerful, and highly atom-economic approach to synthesize ketones. As such, C–H functionalizations are inherently both environmentally benign and economically

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• are scarce and they have mostly been focused on the fluorinations of enolizable substrates. These considerations led us to explore the behavior of NFSI in fluorinations of activated arenes under ball-milling conditions towards an eventual implementation of mechanochemistry in late-stage C–H

• . To assist the metal-free amidation of the aromatic C–H bond in 5, we repeated the milling experiment at 40 °C using a heat gun to increase the temperature of the milling jar (see Supporting Information File 1, Figure S2) [42], which gave a mixture of 5 and 6 (ratio 85:15). The same experiment at 60

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• . Also, a higher C–H acidity of the proton at the stereogenic centre and possible racemisation can’t be excluded. A heteroaromatic oxindole derivative afforded the product 3j in lower yield and high ee values. 4- and 5-bromo oxindole derivatives (2l and 2k, respectively) were also used as starting

High-speed C–H chlorination of ethylene carbonate using a new photoflow setup

• Takayoshi Kasakado,
• Takahide Fukuyama,
• Tomohiro Nakagawa,
• Shinji Taguchi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2022, 18, 152–158, doi:10.3762/bjoc.18.16

• Research & Development Group, Nankai Chemical Co. Ltd., 1-1-38 Kozaika, Wakayama 641-0007, Japan Department of Applied Chemistry, National Yang Ming Chiao Tung University (NYCU), Hsinchu 30010, Taiwan 10.3762/bjoc.18.16 Abstract We report the high-speed C–H chlorination of ethylene carbonate, which gives

• ethylene carbonate was introduced to the reactor, the residence time was measured to be 15 or 30 s, depending on the slope of the reactor set at 15 or 5°, respectively. Such short time of exposition sufficed the photo C–H chlorination. The partial irradiation of the flow channels also sufficed for the C–H

• of ethylene carbonate such as 61%, the selectivity for monochlorinated ethylene carbonate over dichlorinated ethylene carbonate was 86%. We found that the substrate contamination with water negatively influenced the performance of the C–H chlorination. Keywords: C–H chlorination; chlorine gas