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

• compounds 7a–e in 42–62% yields, but also gave higher amounts of products 9a–e (10–30%). Thus, the Pd- and phosphine-free Castro–Stephens coupling was a good enough alternative to synthesize alkynes 7. The structure of the double alkynylation product 9e was confirmed by X-ray diffraction data (see

• 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

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• -alkynylketones 129 in good yields. Conjugate additions with organozirconium reagents The hydrozirconation of alkenes and alkynes generates mild organozirconium compounds that can be used in various transformations. Fletcher and co-workers developed the utilization of organozirconium reagents in Cu-catalyzed

• derivatization is possible through the oxidation of the silyl motif to alcohol or the dehydration of the aldol adduct. Other tandem conjugate addition/enolate-trapping reactions In 2016, Nishiyama and co-workers have studied a three-component coupling reaction of alkynes, enones, and aldehydes via direct

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

• difunctionalization of norbornene derivatives 15 with alkynes (Scheme 3) [35]. It was noted the reaction is amenable to both electron-donating groups (EDGs) and electron-withdrawing groups (EWGs); however, yields were diminished with increasing electron deficiency. Moreover, the use of the bulkier tert

• product 19c, the latter was obtained in a greatly reduced yield, perhaps due to less ring strain providing a thermodynamic driving force. In 2013, Mannathan et al. discussed a Ni-catalyzed intermolecular three-component difunctionalization of oxabicyclic alkenes 1 with organoboronic acids 20 and alkynes

• exo face of 30b, oxidative cyclization can afford the ruthenacycle 101. Unlike previous works studying Ru-catalyzed cyclizations involving bicyclic alkenes and alkynes [56][57][58][59], the reaction preferentially undergoes β-hydride elimination to generate 102 rather than reductive elimination which

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• the standard reactions for catalytic hydrogenations with copper(I)/NHC complexes [4]. In this vein, we tested complex 5 from solid and liquid phase synthesis in the catalytic hydrogenation of esters, carbonyl compounds and in the semihydrogenation of alkynes. In the catalytic hydrogenation of ethyl

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

• 55 as sensitizers for dye-sensitized solar cells (DSSCs). These porphyrin conjugates were synthesized through the click reaction between azidoporphyrin 51 and alkynes 52 or 54. Further, porphyrin 57 bearing a CN and a COOH group was prepared by the treatment of porphyrin 55 with 2-cyanoacetic acid

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• -catalysed hydroboration of alkynes was first reported by Periasamy using N,N-diethylaniline·BH3 as the catalyst and HBcat as the turnover reagent (terminal reductant) [48][49]. This was followed by Hoshi who used dialkylboranes, 9-borabicyclo(3.3.1)nonane (H-B-9-BBN) and dicyclohexylborane (Cy2BH) to

• catalyse the hydroboration of alkynes with HBcat [50]. Hoshi later reported that Cy2BH [51] and in situ generated bis(pentafluorophenyl)borane, Piers’ borane [52], catalysed the hydroboration of alkynes with HBpin, to give alkenyl pinacol boronic esters. Tris(2,4,6-trifluorophenyl)borane [53], tris(3,4,5

• -trifluorophenyl)borane [54], BH3 [55][56][57], and H-B-9-BBN [58] have also been reported as catalysts for the hydroboration of alkynes with HBpin (Scheme 2). Lloyd-Jones et al. investigated the mechanism of this reaction and found transborylation, group 13 exchange between boron atoms, enabled catalytic turnover

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• favoring reactivity with various types of substrates, ranging from halides to carbonyls and alkenes/alkynes. It is comprehensible that this reagent attracted early interest in natural product synthesis and more precisely on medium-sized ring formation. 4.1 SmI2-mediated Barbier-type ring annulation towards

• ester. Finally, this latter was hydrolyzed or reduced to respectively provide albolic acid (178) and ceroplastol II (179). The scope of the reaction was also extended to various products containing the [X-8-5] tricyclic system (Figure 6). Several functionalized terminal alkynes succeeded in the Pauson

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

• ]. Since the early work by Wailes, Schwartz and Buchwald on the Schwartz reagent Cp2Zr(H)Cl and its reactivity towards alkynes, alkenes, and C–X double bonds particularly hydrozirconation has gained much attention [25][26][27][28][29][30]. It has been successfully employed in methodology studies [31][32

• Crombie’s work on dienamides and prepared dienoates 15 by hydrozirconation of terminal alkynes 16 followed by Pd-catalyzed cross coupling with enoates 17 [55][56]. A repetitive approach gave rise to oligoenoates [57]. Hydrozirconations were also combined with carbonylations to install carbonyl groups. For

• example, the sequential hydrozirconation/carbonylation of propargylic ethers 18 reported by Donato [58] yielded α,β-unsaturated lactones 19. Beside the hydrozirconation/acylation sequence of nitriles utilizing acid chlorides published by Majoral/Floreancig [59][60], Cox revealed that terminal alkynes 16

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• of 1,2-difunctionalized arenes with alkynes or carbon monoxide (Scheme 1b, III) [13][14][15][16], have been widely applied for the assembly of isocoumarins over the past decades. Recently, the transition-metal-catalyzed ortho C–H activation/annulation of benzoic acids has emerged as an attractive

• approach towards isocoumarins [17][18]. Pioneering examples relying on the Pd, Ru, and Ir-catalyzed C–H cross coupling of benzoic acids with alkenes and alkynes were realized by the groups of Miura [19], Lee [20], Ackermann [21], Zhang [22], Jiang [23], and Jeganmohan [24] et al. Despite these impressive

• easily available, which have been established as versatile synthetic building blocks for the synthesis of cyclic scaffolds [25]. In 2016, Zhu et al. reported the first example of a Rh-catalyzed C–H functionalization of enaminones with alkynes and α-diazo-β-ketoesters to access naphthalenes [26]. Very

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• pyrrole-fused heterocyclic tricycles [33]. The involvement of Nazarov and in particular aza-Nazarov reactions in the cyclization of alkynes that go through metal carbene intermediates has recently been reviewed by Gao and co-workers [34]. In 2019, we reported a highly effective aza-Nazarov cyclization for

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• ) triazoloquinoxaline complexes as well as a new TIQ rhenium complex were synthesized. As a result, a small 1,2,3-triazoloquinoxaline library was obtained and the method could be expanded towards 4-substituted tetrazoloquinoxalines. The compatibility of various aliphatic and aromatic alkynes towards the reaction was

• , a small library of 1,2,3-triazole-substituted quinoxalines was synthesized applying the method of Chattopadhyay et al. [10] with minor adjustments. Altogether, a series of 21 different aliphatic and aromatic terminal alkynes were reacted with tetrazolo[1,5-a]quinoxaline and Cu(I) triflate as a

• the compatibility of the conversion with a diverse set of alkynes. Reduction of the starting material 11a to quinoxalin-2-amine as a side product was observed in some cases (see Supporting Information File 1 for details). The wide range of tolerated alkynes allows the installation of functional groups

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• cycloaddition reaction of α-diazomethylphosphonates with o-(trimethylsilyl)phenyl triflate in the presence of CsF [13], Cu2+-mediated N−N bond formation from ketimines in the presence of oxygen [14], Pd2+-mediated oxidative benzannulation from pyrazoles and internal alkynes [15], Pd-catalyzed Aza–Nenitzescu

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• ]. For instance, they recently reported a stereoselective reduction of alkynes to Z-alkenes using a PEM reactor. The use of a Pd/C cathode catalyst and the appropriate cathode potential realize the selective synthesis of Z-alkenes [22][23][24]. They also reported the stereoselective hydrogenation of α,β

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• -carboxamides with unprecedented rearrangement of the alkyl group [34] (reaction 4 in Scheme 1). Inspired by these novel reactions and in continuation of our aim to develop domino reactions of electron-deficient alkynes [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50], we have investigated the

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• reaction between terminal alkynes and diimidazopyridinyl diselenides, generated from imidazo[1,2-a]pyridines and Se powder, using 10 mol % of CuI and 1,10-phenanthroline as the catalytic system under aerobic conditions. The C(sp2)–Se and C(sp)–Se bond-formation reaction can be performed in one-pot by using

• inexpensive and easy to handle Se powder as the Se source. The reaction proceeded with terminal alkynes having various substitutions, such as aryl, vinyl, and alkyl groups. The obtained alkynyl imidazopyridinyl selenide was found to undergo nucleophilic substitution reaction on Se atom using organolithium

• with an imidazo[1,2-a]pyridine ring, this study focused on the Cu-catalyzed one-pot C(sp2)–Se and C(sp)–Se bond formation for the synthesis of novel alkynyl imidazopyridinyl selenides using Se powder, 2-arylimidazo[1,2-a]pyridines, and terminal alkynes. Results and Discussion Synthesis of alkynyl

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• the synthesis of chemical reagents with an endoperoxide bridge have been reported [77][78]. The classical method for endoperoxide synthesis is through cycloadditions of dienes and alkenes, using singlet oxygen. Furthermore, cyclizations of hydroperoxides with pendant alkenes or alkynes have also been

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• reactors (Scheme 12, case A). There, it performs a second role by also becoming a source for a copper catalyst, either by being released into solution or by acting as a surface-active species capable of promoting "click" reactions between alkynes and azides [76][77][78][79][80][81]. The process can be

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• the construction of diverse carbocyclic systems [17][18][19][20][21][22][23][24]. In these reactions, the tertiary phosphine firstly adds to electron-deficient alkenes, alkynes, and allenes to give active ionic intermediates. Then, the in situ-generated ionic intermediates further react with various

• respect, we have also developed several domino reactions by employing tertiary phosphine addition to electron-deficient alkynes as key protocol for the construction of diverse polycyclic spirooxindoles [53][54][55][56][57][58][59]. In continuation of our aim to explore elegant domino reactions for spiro

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• treated with copper iodide to obtain the phenanthroline–Cu(I) complex (R)-8. A Glaser-type coupling with the terminal alkynes 9, followed by demetalation, proceeds smoothly in 78% yield. This furnishes the desired chiral rotaxane (R)-10, consisting of a BINOL-based macrocycle and a diyne thread. The CD

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• cycloaddition of alkynes and nitrile oxides performed in organic solvents at elevated temperatures (Figure 1) [11][12][13][14][15][16]. In this method, while 3,5-disubstituted isoxazoles can be accessed from terminal alkynes, 3,4,5-trisubstituted isoxazoles require a high degree of substitution on non-terminal

• alkynes to activate them for a decent yield of the isoxazole products, thus limiting the scope of the substrates in this method. In addition, this method requires high heat and produces very poor regioselectivity of the products [17][18]. The addition of copper catalysts in this route can help the

• reaction proceed at room temperature and improve both the regioselectivity and yields of the isoxazoles. However, these catalysts only work for the reaction with terminal alkynes and only produce 3,5-disubstituted isoxazole products (Figure 1) [19][20]. The synthesis of 3,4,5-trisubstituted isoxazoles from

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• -LED light [111]. Under these conditions, menadione (10) and terminal alkynes 66 underwent a [2 + 2] cycloaddition reaction generating compounds containing cyclobutene rings (67a–c), that are important precursors in natural products syntheses. It is important to note that the choice of the blue-LED

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

• based on Diels–Alder reactions of cyclopentadiene with alkynes [13][14][15][16][17][18][19][20][21][22][23]. However, since this synthetic route requires strongly electrophilic alkynes, its scope is limited to products that contain at least one electron-acceptor group, such as an ester, a nitrile or

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• more reactive alkynes and allylic alcohols. Both the microenvironment of the supramolecular catalyst and the steric profile of the substrate were responsible for the site-selectivity of hydrogenation. This beautiful work of a supramolecular-mediated catalytic site-selective reaction exhibited the

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

• products. Both, asymmetric and symmetric alkynes were synthesized by this one pot method without the use of any organic solvent. For a better yield of the coupled alkyne product, Zn powder was used as a reductant. Lower yields were obtained by the use of ortho-substituted arylynols as the substrate due to

• steric effects. Anilkumar and co-workers reported an iron-catalyzed Sonogashira coupling of aryl iodides with terminal alkynes in the presence of a catalytic system made up of the greenest solvent, water, in the presence of 10 mol % FeCl3·6H2O and 20 mol % 1,10-phenanthroline as ligand under aerobic

• and co-workers reported a novel Fe-catalyzed cross-coupling for the arylation of terminal alkynes by using a combination of FeCl3 and N,N’-dimethylethylenediamine (dmeda) in catalytic amount [25]. A sample reaction in the absence of catalyst/ligand was also conducted, which yielded no desired product

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• approach has been used to synthesise 1,2,3-triazole-linked sialic acid derivatives at C-2 from various non-aromatic alkynes, among which a long hydrophobic chain showed the best inhibitory activity (IC50 = 28 µM) for a bacterial neuraminidase [20]. More recently, a long alkyl chain (benzyl N-butylcarbamate

• (CuAAC, click chemistry), from α-azidosialic acid 1 and commercially available terminal alkynes (Figure 2B), and assessed their inhibitory activity towards TcTS and bacterial neuraminidase. Results and Discussion Synthesis of sialic acid derivatives A small series of anomeric 1,2,3-triazole-linked sialic

• 13C NMR experiment, where the α-anomer is a doublet and the β-anomer is a singlet [28]. The key intermediate 1 was further used in CuAAC reaction [29][30][31][32] with eleven (hetero)aromatic and non-aromatic terminal alkynes readily available in our lab [23]. Although CuAAC is reputedly tolerant of a