A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• of acrylic acids with alkynes was reported by Mei and coworkers [59]. Diverse functional groups on the aryl group connected to the alkyne are compatible with this transformation, and dialkylalkynes can also be effectively reacted. Extensive mechanistic studies have led to the following proposed

• pargyline and ethisterone (Scheme 43). 1.3.8 Au-assisted anodic oxidation. A gold-catalyzed C(sp3)–C(sp) coupling of diverse alkynes and arylhydrazines under mild electrochemical conditions with the dinuclear gold complex, bis(diphenylphosphino)methane digold(I) dichloride (dppm(AuCl)2) as catalyst and n

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• containing alkyne substrates could also give the corresponding gem-difluorinated compounds (in-cell method). The ex-cell electrolysis method was also applicable for gem-difluorination of alkynes. Keywords: carbon–carbon triple bonds; chemical method; electrochemistry; gem-difluorination; Introduction

• the use of HF or its complexes as a reagent. These reactions seem to proceed via the formation of the vinyl fluoride as the intermediate [25][26][27][28]. In the first example, Olah and co-workers reported the reaction of terminal alkynes with HF/pyridine (Olah reagent) (Figure 1, reaction 1) [29][30

• to be a good reagent for the gem-difluorination of alkynes, reported by Hammond and Xu (Figure 1, reaction 3) [37]. HF/DMPU is easy to handle under experimental conditions. In addition, they recently reported the utilization of a combination of KHSO4·13HF and DMPU·12HF under neat conditions for the

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• ] cycloaddition–retroelectrocyclization (CA-RE) between electron-rich alkynes and electron-deficient olefins [8]. The [2 + 2] CA-RE click reactions were employed to produce a variety of functional materials, such as nonlinear optical chromophores [9][10], super acceptors [11][12], ion sensing D–A systems [13

• (PCM) solvent (Figure 4). The reaction initially started with the addition of benzyl azide to one of the internal alkynes of 5. Although the benzyl group is situated on the interior side of DBA, a more energetically unstable transition state (in-ts) is generated. However, the resulting monoadduct (in

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• -carbon alkynoyl building blocks [121][122] could be generated catalytically [123], thereby facilitating reactions under mild reaction conditions and opening novel one-pot pathways for consecutive multicomponent syntheses of pyrazoles. Sonogashira alkynylation of terminal alkynes and (hetero)aroyl

• necessary [73]. Most advantageously, this methodology tolerates many polar functional groups and allows access to pyrazole libraries from simple starting materials (alkynes, acid chlorides, hydrazines) in good to excellent yield. Notably, pyrazoles 102 and 103 demonstrate intense luminescence both in

• and high optical refraction. Functionalized alkynes can alternatively be prepared in situ by a Kumada coupling [133] of aryl iodides and ethynylmagnesium bromide [134]. The Pd catalyst is reused in the subsequent Sonogashira coupling for the synthesis of alkynones in the sense of sequential catalysis

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• nonmetallic reagents as an attractive alternative is less developed. In 2014, Antonchick and Manna firstly reported the synthesis of a series of 3,4-diaryl-substituted isoquinolinone derivatives through oxidative annulation between alkynes and benzamide derivatives using iodobenzene as a catalyst and

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• semihydrogenation of alkynes to form Z-alkenes using a PEM reactor [31]. The Pd/C catalyst was essential for the reaction. They recently found that a PEM reactor with a Rh/C catalyst was effective for the stereoselective reduction of cyclic ketones [40]. Nagaki et al. reported the electrochemical deuteration of

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• ][10][11][12][13][14]. For example, such molecules can be utilized to access free amines [3][13] and undergo Staudinger-type ligations [14]. Furthermore, they can be very efficiently employed for triazole-forming 1,3-dipolar cycloadditions with alkynes (“click-chemistry”) [9][10][11][12]. As a

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• generated by addition reaction of isocyanides to electron-deficient alkynes, which were sequentially trapped by various electrophiles and nucleophiles to give versatile acyclic and heterocyclic compounds [15][16][17][18][19][20][21][22][23][24][25][26]. In recent years, many multicomponent reactions based

• on alkyl isocyanides, electron-deficient alkynes and other reagents have been successfully developed for the synthesis of various carbocyclic and heterocyclic compounds [27][28][29][30][31][32][33][34][35]. The 5,6-unsubstituted 1,4-dihydropyridine is one of special kinds of 1,4-dihydropyridines. It

• -deficient alkynes [59][60][61][62][63]. The in situ generated cyclic intermediate C has a resonance hybrid C’. Then, the further nucleophilic addition of the electron-rich enamino unit to 5-(alkylimino)cyclopenta-1,3-diene intermediate C gave intermediate D. At last, the coupling of the iminium cation with

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• cycloaddition of the gained synthesized azidopyrazoles with different alkynes was to be conducted. The 3-(3,3-diisopropyltriaz-1-en-1-yl)-1H-pyrazole precursors 15a–d were synthesized according to previously reported procedures [3][26][27] via the generation of a diazonium salt from aminopyrazoles 14a–d

• aromatic and aliphatic alkynes 20a–h in a copper-catalyzed azide–alkyne cycloaddition (CuAAC). All attempted reactions could be conducted under standard conditions using copper sulfate and sodium ascorbate in THF/water (depicted in Scheme 3 and Figure 2). For selected derivatives, 21sd and 21vg, crystals

• the alkyne depends on the substitutions on the pyrazole, and no general trend is visible – reactions with electron-poor, electron-rich as well as sterically demanding alkynes give high product yields, depending on the respective pyrazole. The functionalization of the NH-unsubstituted derivative 21jd

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• organic dye Mes–Acr–MeClO4 as photocatalyst (Scheme 5). They demonstrated intermolecular radical cyclization of o-hydroxybenzoic acid derivatives with terminal alkynes to afford flavone derivatives. Here, functionally diverse flavonoids were synthesized in moderate to excellent yield by reacting various

• and provide the desired products with good yield. Cyclopentanol-derived oxalates, some heterocyclic oxalates, and natural-product-derived oxalates were also compatible with this method. In 2018, Chu and co-workers [47] devised an elegant protocol for achieving syn-alkylarylation of terminal alkynes

• photocatalysis. The generated alkyl radicals then undergo the desired addition with alkyne to produce alkenyl radicals that via Ni-catalysed coupling reactions with aryl bromides form trisubstituted alkenes Z-selectively. Internal alkynes are not suitable for this transformation due to the steric reason, but

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• steady state absorption and fluorescence spectroscopy which give insights of the influence of the substitution pattern and of the type of substituents on the optical properties. Keywords: alkynes; catalysis; fluorescence; heterocycles; palladium; Introduction Quinoline is a well-known core structure

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

• vinyl propargylic esters could be employed as five-carbon atom building blocks in [5 + 2] cycloadditions with alkynes or alkenes by carbene intermediates. Starting from those results they envisaged the benzannulation of heteroaryl propargylic esters favored by CO [44]. The process led to the desired

• , the Li’s group and Zeng and Alper developed two different methods for carrying out a direct carbonylation of indoles with alkynes. Li’s group reported the direct Sonogashira carbonylation coupling reaction of indoles and alkynes catalyzed by Pd/CuI in the presence of iodine as oxidant [71]. The

• of indoles/CO/alkynes (alkynylcarboxylates) towards linear α,β-unsaturated ketones [72]. The reactions occurred in the presence of Pd(CH3CN)4(BF4)2/Xantphos as catalyst system under 20.7 bar of CO at 105 °C in THF. After 15 h, each reaction led selectively to the desired products (Scheme 40). More

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• Jun Kikuchi Roi Nakajima Naohiko Yoshikai Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan 10.3762/bjoc.20.79 Abstract A stereoselective N-alkenylation of azoles with alkynes and iodine(III) electrophile is reported. The reaction

• between various azoles and internal alkynes is mediated by benziodoxole triflate as the electrophile in a trans-fashion, affording azole-bearing vinylbenziodoxoles in moderate to good yields. The tolerable azole nuclei include pyrazole, indazole, 1,2,3-triazole, benzotriazole, and tetrazole. The iodanyl

• group in the product can be leveraged as a versatile synthetic handle, allowing for the preparation of hitherto inaccessible types of densely functionalized N-vinylazoles. Keywords: alkynes; azoles; cross-coupling; hypervalent iodine; Introduction N-Functionalized azoles are prevalent in bioactive

(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

• benzenes are by now relatively well established. Cubanes [16][17], alkynes [18], and bicyclo[2.2.2]octanes [19] can all replicate the linear geometry of the para-substituents, but arguably the most well-investigated para-benzene bioisostere is bicyclo[1.1.1]pentane (BCP) [20][21][22][23] (Figure 1). The

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• focusing on hydrochlorination reactions. Firstly, an outstanding overview, including extensive research from the former Soviet Union, was reported in 1982 by Sergeev and co-workers [12]. Secondly, the chapter on “Addition of H-X Reagents to Alkenes and Alkynes” in comprehensive organic synthesis gives a

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

• discovery and development of the synthesis of homopropargylic azides by the azido-alkynylation of alkenes. Initially, a strategy involving SOMOphilic alkynes was adopted, but only resulted in a 29% yield of the desired product. By switching to a radical-polar crossover approach and after optimization, a

• elimination of the organometallic intermediate would lead to the desired product (Scheme 1B, reaction 1). Unfortunately, this approach will not be compatible in the case of azidation since the copper, azides and alkynes present in the mixture are expected to undergo alkyne–azide cycloaddition reactions [28

• ]. Moreover, different azide sources are known to efficiently promote the diazidation of alkenes in the presence of a copper catalyst, often proceeding via a radical mechanism [24][29][30][31]. A second approach would involve SOMOphilic alkynes to trap the radical by a purely open-shell mechanism (Scheme 1B

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• seen with imidazolidines (cf. for IPr TEP[Ir] = 2050.2 cm−1) [34]. A benchmarking exercise was then performed looking at the reactivity of 13 compared against reaction of symmetrical IPrAuCl across a range of known gold-mediated transformations of alkynes featuring intermolecular attack [35

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• Since the seminal 1998 report by Teles et al. on the gold(I)-catalyzed addition of alcohols to alkynes [1], a multitude of gold-catalyzed reactions have been reported. Great successes in mechanistic analysis and synthetic methods have been achieved for allene and alkyne activation, while the activation

• ) protodeauration (Scheme 1), the depth of experimental mechanistic validation achieved for allenes and alkynes have not been reproduced with alkenes. In an important foundational study by Toste, the expected alkylgold intermediate from intramolecular alkene hydroamination was isolated, however, turnover

• solvent and anion effects add complexity to mechanistic interpretation, and the reluctance of alkylgold complexes to undergo protodeauration under similar conditions give us pause [28]. While computational studies support protodeauration, the significantly lower reactivity of alkenes compared to alkynes

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• generation of alkyl radicals [39]. After that, a series of methods for the modification of alkylthianthrenium salts have been developed, including the transition-metal-catalyzed cross-coupling with terminal alkynes [40], sulfonylation with DABCO·(SO2)2 [41][42][43], or alkylation of active alkenes [44][45

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• formation of unsaturated products, often in the form of polyenes or alkynes [28]. The non-standard transition method found here in the acenaphthene–acenaphthylene pair is a previously unknown approach for the synthesis of acenaphthylenes based on tele-elimination (see also below). Changing the nucleophile

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• ) reactions involving diverse electron-rich alkynes and electron-deficient alkenes. In this review, a comprehensive investigation of the recent and noteworthy advancements in the research on push–pull chromophores prepared via the [2 + 2] CA–RE reaction is conducted. In particular, an overview of the

• optoelectronics) [1][2]. The synthesis of push–pull chromophores is often achieved through click-type reactions between electron-rich alkynes and electron-deficient alkenes, which is a reliable and atom-economical method. Diverse chromophores can be obtained via this method, depending upon the choice of alkynes

• have explored the synthesis of various push–pull chromophores, primarily via reactions between alkynes and alkenes. Several comprehensive reviews of nonplanar push–pull chromophores have since enriched the scientific literature [4][5][6]. In 2018, Michinobu and Diederich provided an exemplary overview

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

• a subsequent Glaser–Hay coupling reaction, a RA acceptor unit was introduced to provide a DTF-IF-RA donor–acceptor scaffold with a low-energy charge-transfer absorption and multi-redox behavior. Keywords: alkynes; chromophores; fused-ring systems; heterocycles; redox chemistry; Introduction

• , ethynylbenzene, or 4-ethynylbenzonitrile yielded compounds 19–21, while two-fold Sonogashira coupling with ((2-ethynylphenyl)ethynyl)triisopropylsilane resulted in compound 22. Desilylation of the alkynes of compound 22 with tetrabutylammonium fluoride (TBAF) and subsequent intramolecular Glaser–Hay coupling of

• the terminal alkynes afforded the macrocyclic DTF-IF-RA scaffold 23. Molecular sieves (4 Å) were added to the reaction mixture as this has previously been shown to significantly promote the Glaser–Hay coupling [28]. Compounds 20 and 21 were unfortunately very sensitive compounds that were found to

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

• , UK Department of Chemistry, Sapienza University of Rome, piazzale Aldo Moro, 5, 00185 Rome, Italy 10.3762/bjoc.19.147 Abstract In order to replace the expensive metal/ligand catalysts and classic toxic and volatile solvents, commonly used for the hydration of alkynes, the hydration reaction of

• alkynes was studied in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate (BMIm-BF4) adding boron trifluoride diethyl etherate (BF3·Et2O) as catalyst. Different ionic liquids were used, varying the cation or the anion, in order to identify the best one, in terms of both efficiency and reduced

• costs. The developed method was efficaciously applied to different alkynes, achieving the desired hydration products with good yields. The results obtained using a conventional approach (i.e., adding BF3·Et2O) were compared with those achieved using BF3 electrogenerated in BMIm-BF4, demonstrating the

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• through Sonogashira cross-coupling reactions with alkynes featuring different protecting groups such as TIPS, TES, and TIBS. Scheme 7 illustrates the derivatization process using one of the chosen examples, specifically the TIPS group. Accordingly, the cross-coupling products 33a–c were obtained in yields