Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• , 3o, 3q, 3s, 3t and 3x) gave a good yield of the corresponding product, respectively. Here also, the halo-substituted aryl ring on 1 can be further used for transition-metal-catalyzed cross coupling reactions, thus providing a very good application. Then the effect of N-protecting groups on the

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• involved in various transformations including homo- and cross-coupling [1][2][3][4][5][6][7], addition [1][8][9], cycloaddition [1][10][11] and other reactions. Of particular synthetic value is the addition to the triple bond of bromoacetylenes to provide vinyl adducts, which can undergo numerous

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

• (HRMS). To assess the suitability of the boronic esters 2a and 2b to be used as building blocks in Suzuki–Miyaura reactions, the Pd-catalyzed cross-coupling reaction of norbornadiene 2a and bromobenzene (4a) was examined under different conditions (Table 1, Scheme 2). First experiments were conducted

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• intermediate spontaneously turns into the carbanion C, thus realizing the imine umpolung and allowing the cross-coupling reaction with the remaining electrophilic ketimine 1. The complete diastereoselectivity would arise from the mutual approach of the two oxindole nuclei from the less hindered side, that is

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• –Spengler-like cyclization processes [12]. Some 4-substituted 3,4-dihydroquinazolines were prepared by copper-catalyzed oxidative cross coupling of hydroxy intermediates with various nucleophiles [13]. Other 3,4-dihydroquinazolines were also obtained efficiently by intramolecular aza-Wittig reactions [14

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

• emphasis given to green strategies. This is the first review on iron- and cobalt-catalyzed Sonogashira coupling reactions which comprehends literature up to 2020. Keywords: C–C bond formation; cobalt; green reaction; iron; nanoparticles; Sonogashira; Introduction The palladium-catalyzed cross-coupling

• exceptional versatility [13][14][15]. Therefore, the low cost first series transition metals such as iron and cobalt show higher significance than other transition metals. Naturally, Sonogashira cross-coupling reactions using cobalt or iron catalysts were reported as more cost-effective alternatives to the

• cross-coupling reactions Homogeneous green protocols Tsai et al. discussed an efficient, simple and environmentally friendly method for the coupling of arylynols 3 with an aryl halide [21]. This strategy discloses a one pot reaction catalyzed by FeCl3 in an aqueous medium associated with the cationic

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

• the art and science of selective molecular engineering [1]. To date, organic synthesis has largely been governed by the interconversion of pre-existing functional groups through the use of more traditional transition-metal-catalyzed cross-coupling reactions [2][3][4][5]. Although these reactions have

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• delivered 3c in 53% yield (Scheme 6). In an alternative approach we tried to synthesize non-benzylated species 1a from methyl indol-2-ylacetate. Iodination at position 3 of the indole backbone in the presence of N-iodosuccinimide [45] followed by Ullmann cross-coupling with o-bromo-nitrobenzene [46] was

• labile CH2 protons. This afforded the iodinated compound 23 in 80% yield. However, Ullmann cross-coupling with o-bromo-nitrobenzene gave only trace amounts of the desired product, which we could not separate by chromatographic methods from the major homo-coupling species 24 of this reaction (Scheme 7

• N-(2-bromophenyl)-2-(1H-indol-2-yl)acetamide. Synthesis of scaffold C and analogues by route (c). Attempted Ullmann cross-coupling of 23 with o-bromo-nitrobenzene. Supporting Information CCDC 2072772−2072777 and 2103781 contain the supplementary crystallographic data for this paper. These data can

Earth-abundant 3d transition metals on the rise in catalysis

• Nikolaos Kaplaneris and
• Lutz Ackermann

Beilstein J. Org. Chem. 2022, 18, 86–88, doi:10.3762/bjoc.18.8

• syntheses, crop protection or medicinal chemistry. Particularly, cross-coupling reactions [1], as well as alkene and alkyne metathesis [2][3], have considerably changed the art of molecular synthesis, with a major impact on neighboring disciplines, such as molecular biology or materials sciences. Despite of

• transformations to form C–C and C–heteroatom bonds, thereby providing a more sustainable future for, among others, drug development in generations to come. Particularly, Nobel prize-winning palladium-catalyzed cross-coupling reactions have been recognized by the practitioners in agrochemical and pharmaceutical

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• oxidative cyanation of aza-Baylis–Hillman adducts. Synthesis of 1° alkyl nitriles using [Ru(bpy)3](PF6)2 as the photocatalyst. Synthesis of 2° and 3° alkyl nitriles using [Ru(bpy)3](PF6)2 as the photocatalyst. Photoredox cross coupling reaction. Synthesis of α-amino nitriles from amines via a one-pot

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

• –Miyaura cross-coupling of bromotryptophan-containing peptides of the catenin-binding domain of axin. Optimisation of the linker length in order to find a compromise between both sufficient linker rigidity and flexibility resulted in a peptide with an increased α-helicity and enhanced binding affinity to

• –Miyaura cross-coupling; Introduction Peptide cyclisation emerged as a popular approach to limit conformational mobility in order to enhance the binding affinity towards a biological target. Moreover, cyclic peptides are more stable against proteolytic digestion and can provide an improved membrane

• ]. Additionally, halotryptophans were incorporated in pentapeptides as building blocks for macrocyclisation by Suzuki–Miyaura cross-coupling (SMC) aiming at the preparation of bicyclic peptides [71]. Recently, intramolecular SMC has been successfully applied to side chain-to-tail cyclisation between

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