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

• strategy for aldehyde C–H activation. The acyl radicals generated in this step were arylated with aryl bromides through a well stablished nickel cross-coupling methodology, leading to a variety of interesting aryl ketones in good yields. We also performed computational calculations to shine light in the

• through this step were used in a well-stablished nickel-catalyzed cross-coupling reaction [19][27][28][29][30] with aryl bromides as a proof of concept, leading to the synthesis of aryl ketones. We also present computational calculations of the HAT reaction step with the DABCO radical cation as the

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 design of novel domino reactions. Keywords: cascade; catalysis; coupling; earth-abundant; iron; Introduction Over the past couple decades, the use of transition-metal-catalyzed cross-coupling reactions have become a staple within the organic chemist’s arsenal of carbon–carbon and carbon

• first Fe-catalyzed cross-coupling reaction between Grignard reagents and vinyl halides [37]. As of late, the development of Fe-catalyzed cross-coupling methodology and mechanistic rationales have burgeoned [38]. Today, the rate of growth within the field of iron catalysis is much greater than that

• compared to the more studied late TMs [39][40][41][42][43]. Besides the more recognized concept of TM cross-coupling reactions revolving around an organic electrophile bearing a leaving group and an organometallic nucleophile, there is another large area of cross-coupling reactions that have been under

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• [13], as well as Ir-catalyzed intramolecular dehydrative cross-coupling of 2-(pyrrolidine-1-yl)benzamide [14]. Another approach to compounds of type 1 that relies on a cascade formation of the pyrimidine and pyrrole rings have found much wider application (see Scheme 1B). One of its variations

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

• acids are widely used in stereoselective oxidative/cross-coupling of two aryl counterparts, asymmetric control of aromatic ring formation, atroposelective functionalization of biaryl compounds, and so on [17][29][30]. In this context, Akiyama (2004) described that chiral phosphoric acids (CPAs) have

• aryl–aryl cross-coupling using various transition-metal catalysts has rarely been successful for the enantioselective construction of hindered biaryls [39] due to the discord between the temperature tolerance of the rotational axis and the high temperature required for C–H activation and suffered from

• poor chemoselectivity [40]. However, the realization of this redox-neutral aryl–aryl cross-coupling is a formidable challenge. Therefore, the discovery of efficient catalysts and ligands to achieve high stereoselectivity is a fundamental issue in catalytic asymmetric synthesis [14]. In this section, we

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• radical cyclizations [22], Pschorr reactions [23], and diverse cycloaddition protocols [24][25]. Especially transition-metal-catalyzed cross-coupling reactions starting from benzophenones, benzoic acids, dihalogenated benzene building blocks and others have emerged as new approaches in recent years [26

• ][27][28]. Various approaches starting from functionalized biaryls have hereby attracted considerable interest, since the precursors are readily available by established cross-coupling reactions. Beyond transition-metal-catalyzed reactions, acid-mediated cyclizations of biphenylcarboxylic acids and

• Suzuki cross-coupling reactions, followed by reduction or reductive amination. The oxidative cyclization conditions are compatible with many functional groups on the aromatic rings (methoxy, chloro, cyano, nitro, and phenol protecting groups like TBS and SEM – but not benzyl and methylenedioxy

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• 43 Prague 2, Czech Republic 10.3762/bjoc.17.179 Abstract The stereoselective Suzuki–Miyaura cross-coupling of (Z)-β-enamido triflates is demonstrated. Depending on the nature of the ligand in the palladium catalyst, either retention or inversion of the configuration during the synthesis of β,β

• of cytotoxic, antifungal, or antibiotic properties [10][11][12]. Modern stereoselective syntheses leading to highly substituted enamides include cross-coupling of vinyl (pseudo)halides or organoboron compounds [13], hydroamidation of alkynes [14][15][16], ynamide functionalization [17][18][19], or

• were found to undergo cross-coupling reactions with retention of configuration on the double bond and served as valuable starting materials for the synthesis of functionalized β,β-disubstituted enamides (Scheme 1A) [21][23]. In the last decade, only a few reports describing isomerization of the double

Electrocatalytic C(sp³)–H/C(sp)–H cross-coupling in continuous flow through TEMPO/copper relay catalysis

• Bin Guo and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2021, 17, 2650–2656, doi:10.3762/bjoc.17.178

• Bin Guo Hai-Chao Xu Key Laboratory of Chemical Biology of Fujian Province and College of Chemistry and Chemical Engineering, Xiamen University, People’s Republic of China 10.3762/bjoc.17.178 Abstract Electrocatalytic dehydrogenative C(sp3)–H/C(sp)–H cross-coupling of tetrahydroisoquinolines with

• and sustainable access to 2-functionalized tetrahydroisoquinolines. Keywords: continuous flow; copper; catalysis; dehydrogenative cross-coupling; electrochemistry; Introduction The dehydrogenative cross-coupling of two C–H bonds represents an ideal strategy for the construction of C–C bonds [1][2

• ]. In this context, few methods have been developed for the dehydrogenative cross-coupling of tetrahydroisoquinolines with terminal alkynes because of the prevalence of the tetrahydroisoquinoline moiety in natural products and bioactive molecules [3][4][5][6][7][8][9][10]. These methods proceed through

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

• salts or the substitution of thermal heating for LED irradiation resulted in a low yield of the cross-coupling products 22 and 23, indicating the necessity of the copper salt and LED irradiation. Mild conditions, such as Pd-free and high reaction yields at room temperature, make this method a very

• promising, scalable green process that can be used as an alternative to the conventional Sonogashira cross-coupling reactions. In 2018, Lalic and co-workers [66] extended this approach to alkyl halides and reported the photoinduced copper-catalyzed Sonogashira coupling of alkynes and alkyl iodide 21. The

• ester acted as an ideal radical precursor and accepted a single electron from the excited state CuI-acetylide complex. The copper catalyst plays a dual role, namely, as a photoredox catalyst and a cross-coupling catalyst. NHP-type esters inhibited the homodimerization of the alkyl radical and terminal

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• /bjoc.17.162 Abstract A facile synthesis of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridine derivatives is reported which is based on POCl3-mediated cyclodehydration followed by double Suzuki–Miyaura cross-coupling. The absorption and fluorescence properties of the obtained products were investigated and

• their HOMO/LUMO energy levels were estimated by cyclic voltammetry measurements. Besides, density functional theory calculations were carried out for further exploration of their electronic properties. Keywords: catalysis; cross-coupling; cyclization; fluorescence; palladium; Introduction π-Conjugated

• their optoelectronic properties, the search for new candidates is of ongoing interest. Recently, considerable attention has been given to acridines in our laboratory and we developed new synthetic methods for dibenzoacridines and acridones based on Pd-catalyzed cross-coupling reactions [55][56]. More

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• Matthew J. Fleming David M. Hodgson Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom 10.3762/bjoc.17.155 Abstract α-Lithiated terminal epoxides and N-(tert-butylsulfonyl)aziridines undergo eliminative cross-coupling with

• (Scheme 1). The eliminative cross-coupling of carbenoids can provide a way to unsymmetrical alkenes, provided the differential reactivity of the two carbenoids is suitably matched [2]. In the current letter, we report preliminary results on the latter strategy to form alkenes which possess an allylic

• with cross-coupling using the same carbenoid and epoxide 5 (Scheme 5), where the presence of LTMP also proved necessary. A cinnamylamine 23 could be obtained in a tin-free process (Scheme 10), which utilises the increased acidity of a benzylic ether 22. In this case, the presence of LTMP was necessary

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• –Miyaura cross-coupling reaction of a variety of halogenated methoxybenzene-containing compounds with 2-(formylphenyl)boronic acids in generally good yields [15]. As a next step, the biaryl aldehydes 13a–f were converted into their corresponding oximes 14a–f in good yields as a mixture of (E) and (Z

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• recently as precursors in Friedel–Crafts reactions of arenes [30][31] and cross-coupling reactions of arylboronic reagents [32]. However, the direct SN1 reaction of such isatin-derived 3-phosphate-substituted oxindoles by halide ions as nucleophiles has not been developed yet and remains an unsolved

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

• powerful strategy in organic synthesis due to the improved atom-, step- and resource economy in comparison with cross-coupling or classical organic functional group transformations. Despite the significant advances in the metal-catalyzed C‒H activations, recent developments in the field of

• a reliable strategy in modern organic synthesis. Palladium-catalyzed cross-coupling reactions such as Mizoroki–Heck [5][6][7][8], Suzuki–Miyaura [9][10][11], Buchwald–Hartwig [12][13], Negishi [14][15], Migita–Stille [16], Sonogashira [17], among others [18][19][20], significantly changed the design

• of synthetic routes for modern pharmaceuticals [21][22]. Over the past two decades, nickel has emerged as an attractive alternative to palladium due to its relative earth-abundance, less toxicity, and inexpensiveness. Despite the fact that the nickel-catalyzed cross-coupling reactions represent a

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

• -(n-dodecyl)azulene (16) is shown in Scheme 5A. The Sonogashira cross-coupling reaction between 4,7-dibromo-6-(n-dodecyl)azulene (13) and 4,7-diethynyl-6-(n-dodecyl)azulene (16) yielded 4,7-polyazulene 17 linked through ethynyl bridges (Scheme 5B). Similarly, the Yamamoto cross-coupling reaction

• -azulene) units capable of absorbing in the near IR region (1.0 to 2.5 μm). Their synthetic strategy involved employing 1,3-dibromo-[2-(3-dodecylthien-2-yl)]azulene (46) as a key precursor and Suzuki and Stille cross-coupling reactions as polymerization tools. The polymer 50 was synthesized from the 1,3

• In 2009, Xu and co-workers [40] synthesized various examples of azulene-fluorene conjugated polymers by using Suzuki cross-coupling reactions. The first set of polymers, poly[2,7-(9,9-dialkylfluorenyl)-alt-(1’,3’-azulenyl)] 106–109 was prepared by the reaction of 1,3-dibromoazulene (4) with 9,9

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

• indolyl amines through Buchwald–Hartwig cross coupling. Synthesis of 3,3’-bis(indolyl) ethers. C–H silylation of indoles. n-BuLi-mediated syntheses of bis(indol-3-yl)silanes. Acid-catalyzed syntheses of bis(indol-3-yl)silanes and mechanisms. B(C6F5)3 and Al(C6F5)3-catalyzed syntheses of bis(indol-3-yl

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• 3-amino-2-naphthoic acid (97) to a Sandmeyer reaction and obtained 98. Then, a Curtius rearrangement of 98 by using diphenylphosphoryl azide (DPPA) yielded 3-iodonaphthalen-2-amine, that was subjected to a Suzuki cross-coupling with potassium vinyltrifluoroborate resulting in aminostyrene 99. The

• -dibromo-2,5-dimethylbenzene (101), with subsequent Suzuki cross-coupling of compound 102 with potassium vinyltrifluoroborate, removal of the N-Boc protecting group of 103 with trifluoroacetic acid, and borylative cyclization of precursor aminostyrene 104 [58]. Sparr’s research group developed the 1,5

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• -catalyzed cross-coupling reactions of coumarin derivatives [24]. Coumarins are a promising scaffold for design and development of bioactive agents, however it possesses a flat system [25]. One of the attractive benefits of introducing chirality in a drug candidate is that it leads to increased complexity to

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• in a cheaper way leading to an easier access of currently expensive treatments to the general population. Chromium-catalyzed C–H activation Chromium is a relatively abundant transition metal that has been used for oxidative reactions, including cross-coupling and carbon–carbon bond formation

• high importance in the field of Alzheimer’s disease studies [169]. In 2020, Xu and co-workers described an unprecedented dual C–H functionalization of indolin-2-ones and benzofuran-2-ones via an oxidative C(sp3)–H cross-coupling protocol catalyzed by inexpensive FeCl3 and ligand-free conditions (Scheme

• ] and batteries [174]. Due to its accessibility, it is well explored in catalysis for many fields, such as cycloaddition reactions [175], polymerization [176], and C–C cross-coupling methods [177]. Several biologically active compounds have been obtained through cobalt catalysis [178][179][180

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• containing a stretch of four DNA nucleotides in the middle, flanked by the modifications in a ´mixmer´ design, which is important for designing gapmer ASOs [31]. Another well-established method for C-5 pyrimidine modification involves the Sonogashira cross-coupling reaction between an alkyne group and a 5

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• selectivity, which is observed at the more electron-rich and the less sterically hindered position. Manganese-catalyzed late-stage C–H alkynylation Alkynes are invaluable intermediates in organic synthesis and are conventionally prepared via palladium-catalyzed cross-coupling reactions [62]. Moreover, they

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• properties. Herein, starting from readily available anthranilic acid, an efficient synthesis of 2,4-bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridine derivatives was accomplished via a one-pot double Sonogashira cross-coupling method. The UV-visible absorption and emission properties of the synthesized

• molecules have been examined. Additionally, theoretical studies based on density functional theory (DFT/B3LYP/6-31G(d)) were carried out. Keywords: alkynes; catalysis; cross-coupling; heterocycles; palladium; Introduction The development and design of small π-conjugated molecules have attracted increasing

• )-9-chloro-5,6,7,8-tetrahydroacridine derivatives via a double Sonogashira cross-coupling method. The arylethynyl groups expand the π-conjugation of the tetrahydroacridine core. The substituents located at the aryl group influenced the photophysical properties of the prepared molecules. In particular

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• 134 were used as starting material in the Sonogashira and Suzuki reactions. The Sonogashira−Hagihara cross-coupling led to alkynylation at position 5 of the triazole ring in the presence of CuI and Pd(PPh3)4 as catalytic system as well as K3PO4 as base in THF as solvent at 65 °C. However, the Suzuki

• −Miyaura cross-coupling produced a series of 5-aryl-4-ethynyl triazoles 136 in the presence of Pd(PPh3)4 as catalyst and K3PO4 as base in 1,4-dioxane as solvent at 100 °C (Scheme 39) [62]. A paper by Sekar et al. described the synthesis of polycyclic triazoles 142 through a domino alkyne insertion and C–H

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• C, which undergoes an oxidation process to generate carbocation D. A proton abstraction from D then affords the observed product. Cross-coupling reaction between unactivated olefins and alkyl halides under nickel catalysis The use of alkyl halides in transition-metal-catalyzed cross-couplings to

• form new C(sp3)–C(sp3) bonds remains a formidable challenge. The main issues associated with obtaining these cross-coupling products are the tendency of the alkylmetal intermediate generated during the reaction to undergo a β-hydride elimination and the slow rate of the oxidation step [100][101

• ]. Nickel catalysis is a viable alternative for this kind of cross-coupling reactions due to its particular radical mechanism, instead of the common metal-oxidative addition to organohalides [102][103][104]. Examples of the coupling between primary, secondary, and even tertiary alkyl halides with

Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• components, the concept of creating one-component OSCs appeared [54]. Following this strategy, isoindigo was used as platform for the synthesis of compound 35a, combining acceptor (perylene diimide) and donor (polythiophene) fragments in the structure. Both polymers were obtained using the Stille cross

• -coupling reaction (Scheme 19). However, the OSC of such a cell showed an efficiency of only 1%. Using polymeric isoindigo 35b as an acceptor component, a nonfullerene OSC was also obtained, which showed a record efficiency of 12.03% among the composites based on isoindigo described to date [55]. Polymeric

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• makes them promising candidates for applications in photopharmacology. The halogen substituents allow further functionalization via cross-coupling reactions. Keywords: bridged azobenzene; diazocine; photopharmacology; photoswitch; triazocine; visible light switch; water-soluble switch; Introduction