Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• substituents. Under the catalysis of IPrAuCl/AgSbF₆, substrates bearing unsubstituted terminal alkynes underwent 7-exo-dig cyclization driven by the strong nucleophilicity of the 3,5-dimethoxyphenyl group, exclusively affording dibenzo[b,d]azepine 54 (Scheme 12, path a). Conversely, substrates with aryl

• -substituted internal alkynes underwent exclusive 8-endo-dig cyclization, efficiently delivering the strained dibenzo[b,d]azocine 56 (Scheme 12, path b). Distinct activation modes governed the selectivity, where regioselective terminal gold coordination triggered 7-exo-dig cyclization in terminal alkynes

• afforded selective access to four indole derivatives through modulation of the alkyne's terminal substituents and nucleophile type (Scheme 14) [21][22]. The gold(I) catalyst activated the unsubstituted terminal alkynes to initiate a 5-exo-dig cyclization, generating a spiro[indoline-3,3'-pyrrolidine

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• benzamides with terminal alkynes, 5-exo-dig aza-cyclization of 2-alkynylbenzamides as well as reductive cascade annulation of o-alkynylbenzamides. Pyrroles and imidazoles were formed efficiently via electrochemical annulation of alkynes with enamides and tandem Michael addition/azidation/cyclization of

• annulation of benzamides and terminal alkynes was established for the synthesis of isoindolones by Ackermann in 2019 (Scheme 8) [207]. After screening the reaction carefully, the optimum conditions were presented as following: a mixture of benzamide 22 (0.25 mmol), alkyne 23 (0.50 mmol), NaOPiv (0.25 mmol

• tandem C–H indolization of 2-alkynylanilines with 3-functionalized indoles. The electrochemical and copper-catalyzed annulation of benzamides and terminal alkynes formed isoindolones in high yields. Isoindolinone could be also afforded via electrochemical 5-exo-dig aza-cyclization of 2-alkynylbenzamides

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• [14]. Interestingly, this also works for terminal alkynes, which are typically known to undergo direct C(sp)–H arylation instead [15][16]. In the context of 1,2-carbofunctionalization, terminal alkynes are more scarcely studied. Among those few examples is a trifluoromethylative thiocyclization

• reaction [17] and a [4 + 2] annulation reaction between o-carboxylic ester-containing diaryl-λ3-iodanes and some terminal alkynes [18]. Looking to expand the possibilities for terminal alkyne carbofunctionalization, we turned our attention to propargylsilanes, which are prone to undergo cationic

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• ) [46]. In 2019, Li, Yang, Van der Eycken and co-workers reported a modification of this strategy relying on thermal activation instead of cationic gold catalysis [47]. The approach worked particularly well with substrates featuring terminal alkynes. Inspired by these developments and taking into

• pyrazolodiazepines 16w and 16x, respectively. Such an outcome is notable, as related carbocyclizations often switch to an exo mode when shifting from internal to terminal alkynes [61][62][63]. To demonstrate the robustness of our methodology, we tested a telescope procedure in which, after the Ugi step, the product

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• readily available starting materials: terminal alkynes, HBdan, polymethylhydrosiloxane (PMHS), and allylic phosphates, through a complex cascade hydroboration and hydroallylation sequence [56]. Shortly after this work, Xiong, Zhu, and co-workers reported a ligand-controlled copper-catalyzed regiodivergent

• asymmetric difunctionalization of terminal alkynes through a cascade process involving initial hydroboration followed by a hydroallylation (Scheme 15) [57]. Employing a catalytic system consisting of (R)-DTBM-Segphos (L4) and CuBr resulted in the exclusive 1,1-difunctionalization of aryl- and alkyl

• -substituted terminal alkynes 42, including the industrially relevant acetylene and propyne. Interestingly, switching to the ligand (S,S)-Ph-BPE (L1) resulted in the asymmetric 1,2-difunctionalization of aryl-substituted terminal alkynes 42. The high levels of regio- and stereoselectivity achieved under mild

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• ) nitrenoid intermediate INT-7. Subsequent nitrene insertion, protodemetalation, and intramolecular cyclization furnish the desired 1,2,4-triazole. 1.3 Three-component formation of N-acyl amidines In 2019, N-acyl amidines were prepared from dioxazolones using a copper catalyst with terminal alkynes and

• terminal alkynes did not result in the desired N-acyl amidine 10l. Based on the substrate scope of acetylenes, the authors noted that the lower acidity of terminal acetylenes led to a diminished formation of the copper acetylide intermediate. Based on several mechanistic experiments and density functional

• were tolerated, while a dioxazolone containing bromobenzene displayed lower reactivity (26c). The enamide 26d, derived from lobatamide, was successfully produced without altering the stereochemistry of the oxime ether. Terminal alkynes with linear alkyl group, protected alcohol, and sulfonamide

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• toxic chemical oxidants and releasing hydrogen gas as the sole byproduct. Various benzamides 1 and terminal arylalkynes 2 bearing electron-rich or electron-withdrawing groups provided the desired products 3 with high chemoselectivities. However, terminal alkynes with alkyl substituents did not yield the

• desired annulation products. Moreover, the same products were generated using alkynyl carboxylic acids instead of terminal alkynes via decarboxylative C–H alkynylation and annulation. Cyclic voltammetry (CV) studies exhibited an oxidative current at 0.95 V vs SCE in the presence of the Cu(II) salt, base

• enantioselective C–H alkynylation of ferrocene carboxamides with terminal alkynes by using Cu/BINOL and an electrocatalytic system (Figure 5) [49]. 8-Aminoquinoline-assisted C–H functionalization provided planar chiral ferrocenes with high yield and enantioselectivity. This reaction can be applied to a wide range

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• ]. Three-component coupling of amines, aldehydes or ketones, and terminal alkynes catalyzed by Cu(OTf)2 is a fruitful tool for the production of α-substituted propargylamines 10 (Scheme 7) [20]. The reaction involves the alkynylation of the corresponding imines formed in situ and provides higher yields

• as a catalyst in three-component processes was also demonstrated in three-component reactions involving alkynes, amines and α,β-unsaturated aldehydes to obtain 1,4-dihydropyridines 20 (Scheme 14) [31]. By using terminal alkynes, 2,6-unsubstituted products were achieved. Concerning the mechanism, it

• the initial formation of imine XII and enamine XIII, reacting each other in a mechanism that involved two Mannich-type reactions (Scheme 15) [32]. Activation of terminal alkynes with Cu(OTf)2 is the key step for the preparation of furoquinoxalines 22 from o-phenylenediamine and ethyl glyoxylate

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• via a radical mechanism and the presence of terminal alkynes was found to be crucial for the smooth progression of the reaction, which suggested that the reaction proceeded through the same copper vinyl allenylidene intermediate (Scheme 23). Yne-allylic substitutions through dearomatization and

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

• 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

• substrate for gem-difluorination to yield the difluorinated compound 2e (Table 2, entries 8 and 9). Interestingly, terminal alkynes bearing –OH and –O– functional groups, such as 1f and 1g, were used for reactions, and the corresponding products 2f and 2g were obtained by both methods (Table 2, entries 10

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

• possible in a pseudo-seven-component reaction starting from 1,4-diiodobenzene. The product 108c showed strong solvatochromism. The synthesis of pyrazoles from terminal alkynes, acyl chlorides, and hydrazines [124][126] can be extended by subsequent halogenation at position 4 with N-halosuccinimide 109 (X

• synthesized 4 halopyrazoles 111 and their Suzuki products 110 fluoresce blue in solution and have quantum yields of 29–72 % (Scheme 40) [137]. The Suzuki coupling can also be used for the functionalization of pyrazoles. For this purpose, p-bromo-substituted terminal alkynes 112, acyl chlorides 114, 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

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

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

• catalysis encompassed various azoles such as pyrazole, indazole, and (benzo)triazole, exhibiting high Z-selectivity. In addition, Cao et al. reported a gold-catalyzed addition of 5-substituted tetrazoles to terminal alkynes [11]. Analogous hydroazolation reactions of alkynes have also been achieved under

• oxazolidinone-substituted ynamide also proved to undergo iodo(III)azolation in a regio- and stereoselective fashion to give the product 4ai in a moderate yield. Note that terminal alkynes such as phenylacetylene also took part in the reaction, albeit in a much-diminished yield (7% by 1H NMR; data not shown

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

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

• 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

• hexafluorophosphate (BMIm-PF6) as co-solvent with methanol and water to allow recycling of a phosphine-based Au(I) complex, as an efficient catalytic system for the hydration of terminal alkynes [87]. Moreover, the interesting properties of ILs have also been exploited to synthesize new solid polymeric catalysts for

• anion. Subsequently, we extended the method to different internal and terminal alkynes. Finally, we studied the reaction in the electrogenerated BF3/BMIm-BF4 system, comparing the results with those obtained with the chemical route (BF3·Et2O). Results and Discussion Optimization of the reaction

• diphenylacetylene (1a), affording the corresponding ketones in high yields after 5 h. Otherwise, terminal alkynes generally showed higher reactivity compared to internal ones. For all the studied terminal alkynes, only ketone products (Markovnikov) were obtained, excluding the formation of the anti-Markovnikov ones

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• with alkynes under click chemistry conditions (Scheme 48) [15]. The products were obtained in high yields (93–99%). Cazin and co-workers systematically investigated the [3 + 2] cycloaddition of a series of six azides with seven terminal alkynes catalyzed by different 1,2,3-triazolylidene–CuCl complexes

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• azide was combined with a subsequent copper-catalyzed (3 + 2) cycloaddition with terminal alkynes. This one-pot process was developed with a simple model alkyne, but then applied to more complex alkynes bearing enantiopure 1,2-oxazinyl substituents. Hence, the precursor compounds 1,2-, 1,3- or 1,4-bis

Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an alkynylation–cyclization–iodination–alkylation sequence

• Nadia Ledermann,
• Alae-Eddine Moubsit and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2023, 19, 1379–1385, doi:10.3762/bjoc.19.99

• generated by a consecutive four-component reaction starting from ortho-haloanilines, terminal alkynes, N-iodosuccinimide, and alkyl halides in yields of 11–69%. Initiated by a copper-free alkynylation, followed by a base-catalyzed cyclizive indole formation, electrophilic iodination, and finally

• to directly employ these standard conditions to the sequence of ortho-haloanilines 1, terminal alkynes 2, N-iodosuccinimide (3), and alkyl halides 4 to screen the scope of the one-pot synthesis of trisubstituted 3-iodoindoles 5 in a consecutive four-component fashion (Scheme 2). The sequence

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• terminal alkynes at room temperature (Scheme 15a) [67]. The ability to tune the reactivity of the trityl ion rationally improves the approach with excellent regio- and diastereoselectivity for the unsymmetric ethers. In 2018, Ye et al. reported a CDC reaction to form C(sp)–C(sp3) coupling products from

• -catalyzed formation of 1,1-bis-indolylmethane derivatives. Alkylation of coumarins and flavonoids. Direct CDC α-arylation of azoles with ethers. CDC of terminal alkynes with C(sp3)–H bonds adjacent to oxygen, sulfur or nitrogen atoms. Alkylation of terminal alkynes. Co-catalyzed functionalization of glycine

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• Heck cross-coupling [69][70]. However, researchers have developed various methods for the transition-metal-catalyzed C(sp2)–H olefination using various types of alkenes as coupling partners [71][72][73]. This part of the review covers reports for the alkenylation of pyridine with terminal alkynes

Synthesis, structure, and properties of switchable cross-conjugated 1,4-diaryl-1,3-butadiynes based on 1,8-bis(dimethylamino)naphthalene

• Semyon V. Tsybulin,
• Ekaterina A. Filatova,
• Alexander F. Pozharskii,
• Valery A. Ozeryanskii and
• Anna V. Gulevskaya

Beilstein J. Org. Chem. 2023, 19, 674–686, doi:10.3762/bjoc.19.49

• recrystallization of the crude product from ethanol. Next, the oxidative dimerization of terminal alkynes 6a–e was carried out in an aerobic medium in the CuI/TMEDA/iPr2NH system at room temperature, which proved to be effective in the synthesis of butadiynes 1–4 [15] (Scheme 3). The desired diarylbutadiynes 5a–e

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• connect a porphyrin with a chromophoric group. Among these, the copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction [1][2] of azides with terminal alkynes is a popular and well established process to link a porphyrin with other moieties via 1,2,3-triazole group [3] (Figure 1). The term “click

• triazoloporphyrins 32a–c and triazole-bridged bisporphyrins 34 in good yields. The “click reaction” of azidoporphyrin 30 with the terminal alkynes 31a–c and 33 in a THF/water (3:1) mixture was investigated by using different catalytic systems. Among these, copper carbene (SIMes)CuBr proved to be a better catalyst