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

• group across alkenes 27. This reaction is applicable not only to a wide range of terminal styrenes but also to internal alkenylarenes, enynes, and allenes, providing enantioenriched products in good yields with high enantioselectivities. This reaction involves Co-catalyzed HAT and Cu-catalyzed

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• provides radical E. tert-Butylperoxy group transfer from Co(III)OO-t-Bu A to E gives the coupling product F, which gives the final three-component product 118 and releases the Co(II) catalyst. A copper(0)- and cobalt(II)-catalyzed difunctionalization of enynes 119 with the sp3 α-carbon of alcohols 120 and

• -peroxyamides 148 with TBHP and formamide derivatives 147 by difunctionalization of 1,3-diene, 1,3-enynes as well as styrenes 146 (Scheme 46) [110]. The iron catalyst is believed to mediate the formation of tert-butoxy and tert-butylperoxy radicals. The former abstracts the hydrogen atom from the formyl C–H

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

• related to yne-allylic substitutions. Review Copper-catalyzed yne-allylic substitutions affording 1,3- and 1,4-enynes In 2022, Fang et al. [62] realized the copper-catalyzed yne-allylic substitution involving stabilized “soft” nucleophiles for the first time. Indoles and pyrroles with various substituents

• were found to be suitable for the reaction, delivering 1,3-enynes with medium to high yields and excellent regioselectivities (Scheme 3, 3a–e, 3n–p). Interestingly, when the 3-position of indole was blocked by a methyl group, the 2-position of indole underwent nucleophilic attack with an E/Z ratio of 2

• drug molecules were all suitable nucleophiles (Scheme 4, 5a–k). When R2 is an H atom, the reactions occur at the γ-position, resulting in the formation of 1,4-enynes (Scheme 4, 6a–d). Acyclic 1,3-dicarbonyls could also react with yne-allylic carbonates 1 at the γ-position because of the possible

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• -naphthylacetylene (5g) provided the corresponding enynes (3b–g) in 43–92% yields (Table 4, entries 1–6). On the contrary, electron-withdrawing substituents such as chloro, trifluoromethyl and nitro groups resulted in low cross-coupling yields (3h–j) (Table 4, entries 7–9). p-Acetyl or p-formylphenylacetylene (5k or

• -coupling between 1 derived from various phenols and 5a. Vinyl ethers 1b–d were converted into enynes 3t–v in 29–35% yields (Table 4, entries 19–21). The reaction using 1e, which bears an amino group on the benzene ring, did not complete despite requiring a long reaction time (Table 4, entry 22). Therefore

• fluoroalkenes could be synthesized by applying other cross-couplings to 2. In addition, enynes 3 could be converted into derivatives, such as fluorine-containing alkynylalcohols [47], allene compounds [48][49][50], and heterocycles [51][52]. However, further experiments are required to expand the abilities of 2

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

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• and γ,σ-unsaturated N-(acyloxy)phthalimides. Proposed mechanism for the decarboxylative [3 + 2]/[4 + 2] annulation. Decarboxylative cascade annulation of alkenes/1,6-enynes with N-hydroxyphthalimide esters. Decarboxylative radical cascade cyclization of N-arylacrylamides. NaI/PPh3-driven

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• reactive allenes (reaction e), which serve as synthetic intermediates for polyfunctionalized enynes [8]. The ring strain of the cyclopropane ring facilitates the cleavage of the C–C bond, and both cation and anion are stabilized by the adjacent phenyl group and ester functions, respectively (reaction f

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

• dehydrated producing 193 which finally undergoes a Prins-type cyclization to afford the final product 185. In 2018, the Fan laboratory reported the Rh-catalyzed asymmetric cyclization/addition domino reaction of 1,6-enynes 194 with oxa/azabenzonorbornadienes 30 (Scheme 34) [82]. Both oxa- and

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• reactivity and complex synthesis. Based on previous work and own initial results, a new stereospecific sequential hydrozirconation/Pd-catalyzed acylation of enynes with acyl chlorides towards conjugated (2E,4E)-dienones is reported. We investigated a number of substrates with different alkyl and aryl

• substituents in the one-pot reaction and showed that regardless of the substitution pattern, the reactions lead to the stereoselective formation (≥95% (2E,4E)) of the respective dienones under mild conditions. It was found that enynes with alkyl chains gave higher yields than the corresponding aryl-substituted

• approach to convert (E)-enynes 25 via hydrozirconation to the corresponding (E)-alkenylzirconocenes 24 and subsequent Pd-catalyzed acylation to conjugated (2E,4E)-dienones 27. Results and Discussion The investigation of the hydrozirconation/acylation sequence required first the synthesis of (E)-enynes 25

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• future synthetic developments [61][62][63][64][65][66][67]. The NaI/PPh3 system has been further broadly applied to the functionalization of alkenes [68][69][70], as well as to decarboxylative C(sp3)–X bond formation [71], cyclization of 1,7-enynes [72][73] and other reactions [74][75][76][77]. Inspired

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• whose geometry, in low-polarity solvents, is controlled by the 1,2,3-alternate conformation of the calix[6]arene skeleton. These catalysts can tune the selectivity of the catalytic cycloisomerization of 1,6-enynes in response to the relative orientation of the coordinated gold(I) atom with respect to

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• polarity solvents, of a novel class of diametric phosphine gold(I) cavitands characterized by a 1,2,3-alternate geometry. Preliminary catalytic studies were performed on a model cycloisomerization of 1,6-enynes as a function of the relative orientation of the bonded gold(I) nuclei with respect to the

• catalytic activity was demonstrated in promoting gold(I)-catalyzed cycloisomerization of 1,6-enynes, with ample scope and high regioselectivity. However, preliminary studies suggested that the catalytic event occurs outside the macrocyclic cavity. In order to get more insights on the role of the cavity to

• in controlling the reactivity of gold(I)-catalyzed transformations by means of supramolecular macrocycles, we choose a cycloisomerization of 1,6-enynes as a model reaction [36]. Substrate 1a was reacted in the presence of monomeric gold(I) catalyst A’(AuCl) (2 mol %), using AgSbF6 as the chloride

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

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

• , Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, 92 Aiguo Road, Nanchang, Jiangxi, 330006, China 10.3762/bjoc.17.163 Abstract Great progress has been made in the tandem annulation of enynes in the past few years. This review only presents the corresponding reactions of 1,3-enyne

• annulation. Recently, there have been several elegant reviews covering the 1,3-enynes chemistry [46][47][48]. For instance, Procter and co-workers reviewed the copper-catalyzed functionalization of enynes [46]. In 2020, the Wang group reviewed the development of 2-activated 1,3-enyne in enantioselective

• synthesis [47]. Further, the Liu group reviewed the synthesis of allenes via transition metal-catalyzed 1,4-functionalizations of unactivated 1,3-enynes [48]. In this review, we will highlight the recent advances in the tandem annulation reactions of 1,3-enyne structural motifs for the construction of

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• hence it leads to the formation of racemic products with moderate yields (Scheme 44). 1,6-Enynes 156 underwent smooth hydroxylative carbocyclization in the presence of catalytic Hg(OTf)2. As an example, 3-methylene five-membered cyclic derivatives 157 were synthesized by Nishizawa et al. via the Hg(OTf

• )2-catalyzed hydroxylative carbocyclization of 1,6-enyne 156 (Scheme 45) [104]. It was observed that from 1,7-enynes, six-membered rings were formed in low to moderate yield while from 1,8-enynes, uncyclized hydrated products were isolated. as major products along with different byproducts. In a Hg

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• alkynylation of cyclopropanes 161 with terminal alkynes that led to the formation of the isomeric fluorinated enynes 164 and 165. Shortly before, a Pd-catalyzed ring-opening sulfonylation of gem-difluorocyclopropanes with the formation of 2-fluoroallylic sulfones 166 has been reported (Scheme 71) [122]. The

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• reactions of substrates containing three or more multiple bonds attracted special attention due to the applications in tandem metathesis processes [9][10] or stereodiscriminating enantioselective ring-closing metathetic reactions [11][12][13]. Apart from metathesis, enynes are also interesting substrates

• RCEYM of enynes leads to products containing a conjugated double bond system, which can undergo a Diels–Alder reaction and further can be employed in the synthesis of biologically active compounds, as for example cacospongiolide B [38], norsalvinorin A [39] or salvinorin A [40]. The substituted

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• the PKR of enynes containing a fluoride moiety. Keywords: alkene; alkyne; enyne; fluorine; Pauson–Khand; Introduction The prevalence of fluorine-containing molecules in drug-discovery programs is nowadays unquestionable [1][2][3]. The presence of fluorine atoms or fluorine-containing units at

• that will be discussed in this review belongs to the fluorinated building blocks category. More specifically, the participation of fluorine-containing olefins and alkynes in the Pauson–Khand cyclization, with a special focus on the intramolecular version using fluorinated enynes, which will be

• of fluorine-containing compounds The utility of the Pauson–Khand reaction in the preparation of polycyclic compounds bearing both nitrogenated and cyclopentenone rings, two ubiquitous domains in drugs and natural products, has been reported in various contributions using 1,n-enynes, particularly 4

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• combined an enyne ring-closing metathesis and an alkene cross-metathesis reaction in a sequential mode, using the appropriate enantiopure enynes and the Hoveyda–Grubbs catalyst in both transformations (Scheme 15). High yields and excellent chemoselectivities toward the diene products were attained in both

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• phenyl rings 294 there was no conversion, highlighting the influence of the alkyl groups on silicon (Scheme 47) [85]. Xu and co-workers have described a simultaneous double silylation on conjugated enynes 297, where either racemic or enantiomerically enriched 1,3-bis(silyl)propenes are formed in good

• , which upon reaction with I-CH2F leads to the borylfluoromethylated product (e.g., 362–365, Scheme 58) [108]. Yin and co-workers described Cu(I)-catalyzed asymmetric additions to challenging trifluoromethyl and perfluoroalkyl ketones 370, starting with 1,3-enynes 369 and a slight excess of B2pin2 in THF

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• coupling) should be over 80%. Under the optimized conditions, the reactivities of alkynes 1 and α-bromocarbonyl compounds 2 were examined (Figure 1). The two-step tandem alkyne transformation produced various 1,3-enynes 3 with concomitant formation of ATRA adducts as side-products. It was very difficult to

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• -mediated reactions of alkynes (Scheme 1, path b). In 2007, Echavarren and co-workers have developed an intramolecular cyclopropanation reaction of 1,6-enynes by silver catalysis, involving probably the generation of a silver-carbene species [15]. Wang and co-workers reported a range of propargylic esters

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• .15.141 Abstract 1,3-Enynes are important building blocks in organic synthesis and also constitute the key motif in various bioactive natural products and functional materials. However, synthetic approaches to stereodefined substituted 1,3-enynes remain a challenge, as they are limited to Wittig and cross

• -coupling reactions. Herein, stereodefined 1,3-enynes, including tetrasubstituted ones, were straightforwardly synthesized from cis or trans-alkynylated oxiranes in good to excellent yields by a one-pot cascade process. The procedure relies on oxirane deprotonation, borylation and a stereospecific

• rearrangement of the so-formed alkynyloxiranyl borates. This stereospecific process overall transfers the cis or trans-stereochemistry of the starting alkynyloxiranes to the resulting 1,3-enynes. Keywords: boron; enyne; lithium; oxirane; rearrangement; Introduction Lithiated oxiranes are useful intermediates

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• alkenes, which required a stoichiometric amount of oxidant. Herein, we wish to review the cobalt-catalyzed hydroarylation of alkynes, alkenes, allenes, enynes, imines, and isocyanates. These reactions usually proceed via either an oxidative addition of Ar–H to a low-valent cobalt to form A1 intermediate

• . Protonation and isomerization generate cobalt complex G4, which is converted into alkenated product 54 by ligand exchange. 4. Hydroarylation of enynes Catalytic cyclization of 1,n-enynes has become as an attractive tool for the preparation of cyclic adducts with a variety of functionalities in a one-pot

• process [92]. As the cyclization of 1,n-enynes with organometallics is well-known, the addition of an inert C–H bond to 1,n-enynes further enhances the economy of cyclization process. Thus, Cheng and co-workers reported a cobalt-catalyzed hydroarylative cyclization of 1,n-enynes with carbonyl compounds 55

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• ways and 20c is a precursor to an API. Another method for benzothiopene construction is seen in Kumar and co-workers’ report describing a dehydrogenative oxytrifluoromethylation cascade reaction of 1,6-enynes, catalysed by phenanthrene-9,10-dione (PQ) (Ered*(cat/cat•−) +1.6 V vs SCE) using visible

• the 1,6-enynes from the corresponding 2-halogenated phenols, benzenethiols or anilines, via a simple substitution–elimination–Sonogashira synthetic sequence. In addition, the group has synthesised trifluoromethylated modified versions of certain drugs (Figure 13). Variations on the classical