Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• thiols by nucleophilic radicals with the formation of electrophilic thiyl radicals ensured the wide application of thiols in so-called polarity reversal catalysis [118][119][120][121]. In a number of works thiyl radicals were used for hydrogen atom abstraction in the arylation of activated CH-reagents

• . Electrochemical benzylic oxidation mediated by triarylimidazoles. Thiyl radical-catalyzed CH-arylation of allylic substrates by aryl cyanides. Synthesis of redox-active alkyl tetrafluoropyridinyl sulfides by unactivated C–H bond cleavage by tetrafluoropyridinyl thiyl radicals (SPyf). Main intermediates in quinone

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• ][19][20][21]. Among them, triarylbismuth dichlorides (Ar3BiCl2) have been widely used as aryl group donors for the C- and O-arylation of phenol derivatives [22][23][24], N-arylation of pyridin-2-ones [25][26], α-arylation of α,β-unsaturated carbonyls [27][28], and tandem 1,3-bisarylation of

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• -catalyzed hydrophosphinylation [45]. The key heterocyclization of 11 into 12 was accomplished using silver-promoted homolytic aromatic substitution [46], which was superior to our own manganese methodology (43% yield) [36]. Copper-catalyzed arylation [34] of 12 with iodobenzene and 4-nitroiodobenzene gave

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• -catalyzed cross-coupling reactions, such as arylation reactions catalyzed by Pd2(dba)3/CuI, as well as allylation and methylation reactions catalyzed by CuI⋅PPh3. C3-Benzyldimethylsilyl-appended furfurals are thus introduced as versatile platforms, providing a modular access to 3-substituted 2-furyl

• -catalyzed arylation reactions (Scheme 7). Fluoride-promoted arylation reactions of benzyldimethyl(alkenyl)silanes have been reported, and it is established that they proceed through the cleavage of the benzyl moiety from the benzyldimethylsilyl groups, leading to either dimethylsilanols or cyclic siloxanes

• activation by alkoxides did not prove useful, C3–Si bond functionalization is achieved from benzyldimethylsilyl units upon siloxane formation in the presence of TBAF. Protocols for fluoride-promoted Pd/Cu-catalyzed arylation, as well as Cu-catalyzed allylation and methylation, have been developed. Overall

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

• de Caxias do Sul, 95070-560, Caxias do Sul-RS, Brazil 10.3762/bjoc.18.110 Abstract The broad application of 1H-indazoles has prompted the development of several approaches for the synthesis of such compounds, including metal-free, palladium-, or copper-promoted intramolecular N-arylation of in situ

• available and less expensive than brominated analogs. Seeking to cover a lack in the literature, this work reports a convenient protocol for the synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of o-chlorinated arylhydrazones. Therefore, a series of seven N

• ‐substituents, and others suffer from poor regioselectivity for substrates without a directing group [18][19][21][22]. On the other hand, methods based on metal-free [23], palladium- [24][25], and copper-promoted [26][27][28][29][30][31] intramolecular N-arylation of in situ-generated or isolated o

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

• in the literature. While pondering possible solutions to fill this void, we drew inspiration in our recent success achieving direct Brønsted acid-catalyzed C-arylation of 4-diazo-isoquinoline-1,3-diones 7 [9] which are, in turn, obtainable via the Regitz diazo transfer reaction onto readily available

• literature. Lured by the prospects of applying a diazo chemistry route to an expedited synthesis of hitherto undescribed 1,2,4-trisubstituted 1,4-DHIQs 9 from 11, we set off to investigate the obtainability of 10 from 11 by the Regitz [21] diazo transfer and the usage of 10 in acid-promoted direct arylation

• -arylation reaction (Table 1) [13]. The excess of benzene was varied in the range 10 to 60 equiv and the yield of product 9a was found to improve from 63% to 83% which also allowed lowering the excess of triflic acid to 1.5 equiv. Product 9a was in all cases obtained after only 15 min reaction with high

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• , yielding a reduced arylation product 77 [86][87]. Mechanistically, either diazo or carbene intermediates can be proposed, as Barluenga has outlined, and migration of the aryl group leads to an alkylboronic acid, which is hydrolyzed by protodeboronation, yielding the arylation product 77. A two-step flow

• based on steel beads. A continuous two-step flow process over a period of almost two days yielded the arylation product in 88% yield, demonstrating the robustness of the process [87]. The use of water as a green solvent is a greatly increasing field of research. But besides its reduced environmental

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

• studied rhodium complexes as catalysts for the arylation and alkylation of benzo- and naphthoquinones [83]. They synthesized menadione (10) (Scheme 3) by reacting 1,4-naphthoquinone (1) with methylboronic acid in the presence of [Cp*RhCl2]2 as catalyst for 10 h, in 31% isolated yield. Later in 2019, Yang

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• derivatives may be metalated in a Li–halogen exchange reaction [27]. In another versatile approach, arylation and alkenylation reactions of the norbornadiene may be accomplished with a Suzuki–Miyaura coupling reaction. In this case, halogenated norbornadienes react with arylboronic acids or their esters to

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

• and co-workers reported a novel Fe-catalyzed cross-coupling for the arylation of terminal alkynes by using a combination of FeCl3 and N,N’-dimethylethylenediamine (dmeda) in catalytic amount [25]. A sample reaction in the absence of catalyst/ligand was also conducted, which yielded no desired product

• synthesized 2-arylbenzo[b]furans by intramolecular arylation and Sonogashira cross-coupling of o-iodophenol with phenylacetylene/1-substituted-2-trimethylsilylacetylene under iron(III) catalysis in the presence of 5 mol % 1,10-phenanthroline as ligand and Cs2CO3 as base (Scheme 14) [31]. The use of 1,10

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• naphtho[1,2-d]oxazoles from β-NQS. A) Arylation and vinylation of β-NQS catalyzed by Ni(II) salts. B) Transformation of the 1,2-dicarbonyl group in the fused imidazo[4,5-a] heterocycle. Benzo[a]carbazole and benzo[c]carbazoles fused with 1,2-naphthoquinone. Synthesis of 1,2-naphthoquinones having a C=C

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• -switchable azobenzene staple [33][34]. Moreover, it has been shown that Pd-mediated cross-couplings can be successfully employed in the generation of cyclic and conformationally stabilised peptides. The groups of Buchwald, Pentelute, and Ackermann pioneered the development of Pd-mediated arylation chemistry

• 1% in proteins, but is highly conserved in binding sites on protein surfaces mediating PPI [43], it is an attractive target for the development of selective diversifications. C–H activation of the indole C2 position by Pd-catalysis allows both selective arylation [44][45][46][47][48] and formation

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• . Lineu Prestes 1524, 05508-900 São Paulo-SP, Brazil 10.3762/bjoc.17.206 Abstract Microwave-mediated N-arylation of 4-chloroquinazolines in THF/H2O rapidly and efficiently afforded a library of novel 6-halo-2-phenyl-substituted 4-anilinoquinazolines. The methodology was compatible with numerous ortho

• -anilinoquinazoline; anticancer agents; N-arylation; 4-chloroquinazoline; microwave irradiation; Introduction N-Heterocyclic compounds are commonly present in pharmaceuticals, bioactive natural products, agrochemicals, and synthetic drugs [1][2]. Quinazoline, a benzo-fused N-heterocyclic framework (benzo-1,3-diazine

• substituted anilines or N-methylanilines bearing electron-withdrawing or -donating groups at the ortho-, meta-, or para-positions. Results and Discussion We started by synthesizing 6-bromo-4-chloro-2-phenylquinazoline (8a) and 4-chloro-6-iodo-2-phenylquinazoline (8b) as substrates for the N-arylation study

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• Supporting Information File 1, Tables S4 and S5 for details). A plausible mechanism for the aldehyde arylation is presented in Scheme 3 based on previous literature reports [19][26][33][34] and our mechanistic investigation experiments. Upon blue light irradiation, the photocatalyst is excited generating the

• performed in the absence of DABCO (see Supporting Information File 1, Scheme S2 for details). cAldehyde (10 equiv), performed at 40 °C without cooling fan. dAldehyde (10 equiv). Mechanistic investigations of the HAT reaction using DABCO. Proposed mechanism for aldehyde arylation. PC = photocatalyst Ir[dF

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• ]. The group expanded the reaction to include 1,6-dienes 24 leading to 25 via the formation of three C–C bonds through a radical cyclization/arylation cascade, like that reported by Kang et al. (Scheme 3). The authors hypothesized the alkyl halide could react with aryl iron species 27 to form the alkyl

• propagation sites it is terminated, typically through the generation of a new radical species. The Zhu group followed up on this work by disclosing the use of acetonitrile as the radical precursor for the cyanomethylation/arylation of arylacrylamides to access oxindoles [82]. Despite the small scope of

• aliphatic nitriles explored, the reaction further demonstrated the synthetic potential of C(sp3)–H species within CDC methodology. In 2013, the Li group established a carbonyl-arylation of N-arylacrylamides 60 with alkyl and aryl aldehydes 65 (Scheme 11) [83]. Like Li’s report in 2013 (Scheme 10) [80], the

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• ) (Scheme 2). The electronic properties of the substituents on the 2-naphthylamine showed remarkable effects on the chemical yield but had negligible impact on the enantioselectivity [42]. The direct arylation reaction of quinones 6 and 2-naphthols 7 was described by Tan and co-workers in 2015. The

• presence of a chiral phosphoric acid, the azo group has recently been revealed to be a useful moiety that may efficiently activate an aromatic ring for formal nucleophilic aromatic substitution, resulting in the cleavage of the aryl C–H bond and direct arylation of the nucleophile [58]. In 2018, Tan and co

• -workers showed that azo groups enable the organocatalytic asymmetric arylation of indoles. The nucleophilic aromatic substitution between the azobenzene derivative 24 and indoles 25 was carried out in the presence of 2.5 mol % chiral phosphoric acid (CPA 8, Scheme 9a), leading to the intermediate I-4

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• aliphatic alcohols. In 2015, Ackermann’s group [88] disclosed the visible light-induced copper-catalyzed arylation of azoles. In this case, the mechanistic studies revealed that amino acid ligands accelerated the cross-coupling (Scheme 22). In 2020, a visible-light-induced copper-catalyzed arylation of C

• . Aerobic oxidative C(sp)–S coupling reaction. Copper-catalyzed alkylation of carbazoles with alkyl halides. C–N coupling of organic halides with amides and aliphatic amines. Copper-catalyzed C–X (N, S, O) bond formation reactions. Arylation of C(sp2)–H bonds of azoles. C–C cross-coupling of aryl halides

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• (Scheme 1a) [17][18][19][20][21][22]. Early in 2015, the Ackermann group reported the first example of a low-valent Co-catalyzed C–H alkenylation of 2-pyridinylferrocene [23]. In 2017, the Butenschön group reported the ortho-C–H alkylation and arylation of ferrocene derivatives enabled by a combination of

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• structural motifs to provide the functionalized pyridine and pyrrole derivatives. The functionalization reactions cover iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, alkylation, selenylation, sulfenylation, amidation, esterification, and hydroxylation. We also briefly

• functionalizations of pyrrole derivatives, such as iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, and alkylation. The proposed mechanism generally involves two kinds of intramolecular cyclizations: one is 6-endo-dig cyclization to promote the formation of pyridine ring

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• Pieterjan Winant Wim Dehaen Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium 10.3762/bjoc.17.149 Abstract A metal-free protocol for the direct bis-arylation of 2,5-dichlorobenzoquinone with aryldiazonium salts is reported. The reactive

• salts; Green Chemistry; Meerwein arylation; photoredox; Introduction Quinones or quinoid-based structures are ubiquitous in nature [1][2][3]. These versatile structures have shown promising antimalarial [4][5], antibacterial [6], and chemotherapeutic [6][7][8] properties. Their inherent oxidative

• , resulting in a multitude of applications in dyes [11], molecular electronics [12], and oxidants or ligands in organic chemistry [13][14]. This wide range of applications has long fueled an interest in exploring innovative ways of functionalizing quinones. However, arylation of (benzo)quinones has proven to

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• ]. In this review, we highlight the developments in C–H activation enabled by nickel photocatalysis. Review Arylation The arylation of C(sp3)‒H bonds constitutes a potential tool for the rapid diversification of simple organic molecules into valuable scaffolds [48][49][50][51][52]. In 2014, Doyle

• , MacMillan and co-workers demonstrated an inspiring C(sp3)‒H arylation of dimethylaniline (1a) with a variety of aryl halides using the photoredox nickel catalysis [53]. Here, the combination of the iridium photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6 and the commercially available nickel catalyst NiCl2·glyme

• dimethylaniline (1a) and should intercept with the nickel catalytic cycle to result in the desired products 4. In another work by the same laboratory, a strategy for the arylation of α-amino C(sp3)–H bonds in various acyclic and cyclic amine compounds 6 was realized using photoredox-mediated hydrogen atom

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• intramolecular coupling of arynes by aldehydes or phenols [21][22][23][24], and Lewis acid-catalyzed cyclization of salicylaldehydes and cyclohexenones or tetralones [25]. Some other new and prominent synthesis methods of xanthenes are the tandem arylation/Friedel–Crafts reaction of o-hydroxy bisbenzylic

• ]. Therefore, there has been an increase in arylation methods using Friedel–Crafts alkylation (FCA) protocols without transition metals [35][36]. Environmentally friendly methods, in which metal-free catalysts are used, have come to the fore and are gaining importance because there are many disadvantages of

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• direct C–H arylation strategy to obtain the polymers 81 and 83, respectively, in good yields (Scheme 17). Both polymers 81 and 83 were soluble in solvents such as chloroform and chlorobenzene and their Mn and PDI were found to be 22100 and 13500 Da, and 3.68 and 3.26, respectively. Their thermal

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• (denoted as CuO@GO, 0.38 mol %) catalyzed S-arylation (C–S coupling) of 2-iodoindole (92) to synthesize diindol-2-ylsulfide (84) in 75% yield (Scheme 12) [79]. Here 1.5 equivalents of thiourea acted as the sulfur source. Bis(indol-3-yl)sulfides are also present as structural motifs in important organic

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• usually achieved by a nucleophilic substitution of an alkyl halide by the deprotonated malonate [12][13][14][15][16][17][18][19], but other strategies could be envisioned: Cu-catalyzed arylation reactions for aryl-substituted MAHOs [20][21][22][23]; Knoevenagel/reduction sequences for benzyl-substituted