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

• offers the unique merit of enabling rapid access to structurally diverse N-functionalized azoles because one versatile method would potentially apply to various azole nuclei. In this context, the N-alkenylation of azoles represents an attractive transformation due to the occurrence of the N-vinylazole

• reaction parameters, the desired three-component N-alkenylation was found to proceed smoothly by reacting 3a with excess amounts of 1 (2 equiv) and 2a (5 equiv) in MeCN (0.2 M) at room temperature, affording the trans-difunctionalized product 4aa as a single regio- and stereoisomer in 77% yield (Table 1

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• -catalyzed decarboxylative functionalizations employing RAEs have been established (Scheme 24). Baran and co-workers have reported arylation protocols (Scheme 24A) using arylzinc reagents [84][85], Grignard reagents [85] and arylboronic acids [86], as well as decarboxylative alkenylation [87] (Scheme 24B

• of RAEs with organozinc reagents under Co-catalysis, effecting diverse arylation, alkenylation, and alkynylation reactions [92]. The second type of reaction is referred to as cross-electrophile coupling and involves the Ni-catalyzed reaction of NHPI esters with aryl- and vinyl halides under reducing

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

• groundbreaking work of Shang and Fu on photocatalytic decarboxylative alkylations in 2019, a wide range of organic transformations, such as alkylation, alkenylation, cyclization, amination, iodination, and monofluoromethylation, have been progressively achieved using a combination of iodide and PPh3. In this

• transformations such as alkenylation, alkylation, cyclization, amination, iodination, and many others. The discovery of these conversions has significantly expanded the scope and versatility of the NaI/PPh3 catalytic system, now making it a powerful tool in synthesis. Alkenylation In 2020, Shang, Fu, and

• colleagues reported on the photocatalytic decarboxylative alkenylation reactions facilitated by cooperative NaI/PPh3 catalysis [9]. These conversions involved the coupling of 1,1-diarylethene/cinnamic acid derivatives (1, 2) with redox-active esters 3 (Scheme 3). Notably, the reactions were driven by blue

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

• carboxylation, C(sp2)–H alkenylation and allylation, C(sp2)–H arylation, C(sp2)–H amidation, and C(sp2)–H thiolation. Preceding the section of applications, a brief description of the structure of NHCs, nature of NHC–metal bond, and methods of preparation of NHC–Cu complexes is provided. Keywords: conjugate

• heterocyclic compounds with CO2 resulting in higher yields than those obtained with the imidazolylidene carbene ligand, IPr (Scheme 70). 2.7 C(sp2)–H Alkenylation and allylation In 2016, Chang and co-worker [93] achieved an NHCs–Cu-catalyzed efficient C(sp2)–H allylation of polyfluoroarenes 183 and

• isomerization-induced alkenylation of electron-rich heteroarenes 187 and 188 utilizing allyl halides as reactants. The same catalyst system was found to effectively promote double-bond migration of the initially formed allylarenes resulting in vinylarene products. This method has been successfully used to

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

• benzothiazole, in which benzothiazole compounds have higher reactivity and regioselectivity than thiazole. In 2014, Lei et al. successfully realized the copper-catalyzed oxidative alkenylation of simple ethers to construct allyl ethers in the presence of di-tert-butyl peroxide and KI (Scheme 10) [60]. The

• tetrahydropyrans. CDC of thiazole with cyclic ethers. Cu(I)-catalyzed oxidative alkenylation of simple ethers. Cross-dehydrogenation coupling of isochroman C(sp3)–H bonds with anisole C(sp2)–H bonds. Pd(OAc)2/Cu(OTf)2-catalyzed arylation of α-C(sp3)–H bonds of ethers. Cu-catalyzed C(sp3)–H/C(sp2)–H activation

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

• , diversely functionalized pyridines have been synthesized via C–H activation under transition-metal and rare earth metal catalysis, including C–H alkylation, alkenylation, arylation, heteroarylation, borylation, etc. Recently, metal-free approaches have also been developed for the C–H functionalization of N

• NHC aryl part with trans-styrene was highly important for the reaction to proceed and for the enantiocontrolled formation of the products. Alkenylation The C–H alkenylation is another important C–C bond-forming reaction. Olefinated organic molecules like vinylarenes play a significant role as key

• 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

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• changing the redox state of the aldehyde function, we have developed a number of directed Ru(0)-catalyzed C3-functionalizations of furfurylimines, such as alkylation [21], arylation [22], alkenylation [23] and acylation [24], as well as an Ir-catalyzed directed C3-silylation (Scheme 1a) [25]. These batch

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

• hydroacylation on alkynyl compound 124 to construct the cyclooctanone unit. Despite several attempts, no cyclization occurred (Scheme 24). 3 Pd-mediated cyclization 3.1 Pd-promoted intramolecular alkenylation of methyl ketone: synthesis of cotylenin A (130) Nakada exploited the usefulness of a Pd-promoted

• intramolecular alkenylation of methyl ketone to forge in the late-stage of the synthesis the eight-membered ring of cotylenin A (130) [63]. To this end, the two cyclopentane units of the tricyclic core of cotylenin A were prepared separately and first assembled by an Utimoto coupling reaction to give after

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• could afford satisfying coupling yields by a suitable variation of the nature of the leaving group. In 2008, Cahiez reported an iron-catalyzed alkenylation of organomagnesium reagents with enol phosphates as electrophiles, instead of alkenyl halides [19]. In this case, when reactive enol phosphates

• synthesis of codling moth sex pheromone 4 using an iron-mediated cross-coupling between an α,ω-difunctionalized Grignard reagent and a dienyl bromide. Iron-catalyzed alkenylation of enol phosphates by Grignard reagents by Cahiez. Selected additives used in iron-mediated cross-coupling procedures and their

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

• derivatives may be metalated in a Li–halogen exchange reaction [27]. In another versatile approach, arylation and alkenylation reactions of the norbornadiene may be accomplished with a Suzuki–Miyaura coupling reaction. In this case, halogenated norbornadienes react with arylboronic acids or their esters to

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• alkenylation product ii, directed by a neighboring histidine residue. Upon exposure to 365-nm light, photocleavage of the caging group (red) was observed, producing the free peptide i. Irradiation longer than 10 minutes were sometimes necessary for maximal yield of photo-deprotected product i [16]. Furthermore

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

• alkylation Under mild conditions, copper salts are able to catalyze olefinic C–H functionalization or allylic alkylation, thus allow introducing alkenyl or allyl groups into organic molecules. Alkenylation and allylation reactions have been extensively investigated under thermal conditions. However, only few

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• (Scheme 1a) [17][18][19][20][21][22]. Early in 2015, the Ackermann group reported the first example of a low-valent Co-catalyzed C–H alkenylation of 2-pyridinylferrocene [23]. In 2017, the Butenschön group reported the ortho-C–H alkylation and arylation of ferrocene derivatives enabled by a combination of

• Fe or Co catalyst and N-containing directing groups, while an excess of Grignard reagents was used [24][25]. Thereafter, they also reported the Cp*Co-catalyzed ortho-C–H alkenylation of ferrocenes with alkynes [26] and the mono- and di-selectivity could be controlled by the fine-tuned directing

• in 2020, an enantioselective C–H annulation of ferrocenylformamides with alkynes was achieved by the Ye group enabled by Ni-Al bimetallic catalysis and a chiral secondary phosphine oxide (SPO) ligand [35]. Hou et al. also reported the asymmetric C−H alkenylation of quinoline- and pyridine-substituted

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

• capture of the thus formed alkyl radical by the nickel catalyst was proposed. Alkenylation Over the past few decades, outstanding progress has been realized in the direct alkenylation transformation of C(sp2)–H bonds [95][96][97][98][99][100][101]. However, the related C(sp3)–H alkenylation is much less

• developed due to lower reactivity, poor regioselectivities and the need of noble metal catalysts [50][102][103][104][105][106]. Recently, Yu and co-workers conveniently achieved the direct alkenylation of α-amino C(sp3)–H bonds of amines 1 with alkenyl tosylates 58. The combination of the Ru(bpy)3Cl2·6H2O

• photocatalyst and NiCl2·glyme as the nickel catalyst enabled this C–H alkenylation protocol using alkenyl C(sp2)–O electrophiles at ambient reaction temperature under blue light irradiation (Scheme 31) [58]. In general, the method displayed broad substrate scope, good functional group tolerance, and excellent

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• anthracene derivatives 33. The strategy involved a palladium(II)-catalyzed tandem transformation with diphenyl carboxylic acids 31 and acrylates 32 (Scheme 7) [41]. This new methodology involved a carboxyl-directed C–H alkenylation, a carboxyl-directed secondary C–H activation, an intramolecular C–C-bond

• ] cyclotrimerization reactions with bis(trimethylsilyl)acetylene (23). [2 + 2 + 2] Alkyne-cyclotrimerization reactions catalyzed by a CoCl2·6H2O/Zn reagent. Pd(II)-catalyzed sp3 C–H alkenylation of diphenyl carboxylic acids with acrylates. Pd(II)-catalyzed sp3 C–H arylation with o-tolualdehydes and aryl iodides

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• ] including its application in C–H activation reactions [181][182][183][184][185]. The synthesis of biologically important compounds using C–H activation techniques has been described by Ackermann and co-workers in 2019 [186]. In this specific work, a cobalt-Cp* catalyzed C–H alkenylation was performed at the

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• 31n, regarded as a potentially viable peptide-based biosensor. Manganese-catalyzed inter- and intramolecular C–H alkenylations Manganese(I)-catalyzed C–H alkenylation of 2-phenylpyridines or N-pyridinylindoles with alkynes is characterized by proximity-induced C–H activation through chelation

• assistance. However, application of this protocol for late-stage functionalization remains challenging [96][97][98][99][100][101][102][103]. In 2021, it was revealed by the Ackermann group that manganese(I) catalysis enabled the bioorthogonal late-stage alkenylation of structurally sophisticated peptides

• [104]. The manganese(I)-catalyzed intermolecular alkenylation of tryptophan-containing peptides 32 was performed under basic conditions, yielding hybrid peptides 34 without racemization, containing a trans-alkene linker bearing biologically active motifs in chemo- and site-selective manners assisted by

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• alkynyl-Prins cyclization, Friedel–Crafts alkenylation, and dehydration/aromatization reaction between 1-aryl-3-hexyne-2,6-diol derivatives and aldehydes, that led to the formation of 1,4-dihydro-2H-benzo[f]isochromenes [16]. The Prins reaction-induced cyclization, inter alia, became a versatile tool for

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

•  27). It is worth noting that EDA complex has been firstly employed for the generation of alkoxy radicals under visible-light irradiation, achieving selective C(sp3)–C(sp3)-bond cleavage and allylation or alkenylation. In 2017, Li and colleagues [57] reported a reaction for the synthesis of

• [32] found a bifunctional group reaction of perfluoroalkylation and β-alkenylation by a perfluoroalkyl radical. Perfluoroalkylation product 93 was synthesized by utilizing (E)-3-methyl-1-phenylhept-1,6-dien-3-ol (92) and perfluorobutyl iodide (28) as substrates and potassium phosphate and DABCO as

Palladium nanoparticles supported on chitin-based nanomaterials as heterogeneous catalysts for the Heck coupling reaction

• Tony Jin,
• Malickah Hicks,
• Davis Kurdyla,
• Sabahudin Hrapovic,
• Edmond Lam and
• Audrey Moores

Beilstein J. Org. Chem. 2020, 16, 2477–2483, doi:10.3762/bjoc.16.201

• ChNC or the ChsNC during catalyst fabrication. The lack of metallic Pd peaks present in XRD is indicative of extreme broadening of the reflections of very small Pd NPs within the packets found. Heck coupling is a prominent reaction for arene alkenylation, as the production of stilbene derivatives is

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• , and 3-furyl residues, respectively, to be introduced at the N1 position of the pyrimidone ring, affording compounds 3u–w. Stimulated by the reported examples of the copper-catalyzed N-alkenylation of heterocycles [40][43][44][45][46][47][48], we extended the reaction scope to β-styrylboronic acid (4

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• A one-pot RCEYM/Diels–Alder reaction sequence was used to generate a new type of structural diversity in steroids, taking benefit of the propargylic alcohol group of 17-ethynyl-17-hydroxysteroids. After an alkenylation of the alcohol present on the commercially available steroids, providing with

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• /bjoc.16.56 Abstract Copper catalysis allows the direct oxygen alkenylation of dialkyl phosphonates with alkenyl(aryl)iodonium salts with selective transfer of the alkenyl group. This novel methodology proceeds with a wide range of phosphonates under mild conditions and gives straightforward access to

• valuable enol phosphonates in very good yields. Keywords: alkenylation; copper; C(sp2)–O bond formation; hypervalent iodine; phosphonates; Introduction Organophosphorus compounds represent an important class of products with a wide range of applications in biology, agriculture and synthetic organic

• (alkenyl)iodonium salts, which are air- and moisture-stable, nontoxic and easy to prepare compounds, have become efficient reagents for mild and selective arylation and alkenylation reactions in organic synthesis [16][17][18]. In particular, the use of these hypervalent iodine reagents in copper catalysis

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• are biologically and medicinally very important compounds, and their syntheses have received considerable attention. Herein, we report the synthesis of 3-alkenylindoles via a regioselective alkenylation of indoles, catalysed by a ruthenium nanocatalyst (RuNC). The reaction tolerates several electron

• on the surface are responsible for the high catalytic efficiency of the Ru nanocatalyst. Keywords: alkenylation; C–H activation; heterogeneous catalysis; nanocatalysis; ruthenium catalysis; Introduction The synthesis of functionalised indole ring systems has received significant attention over the

• purification [17][18]. As an example for the second category, Jiao and co-workers developed an organocatalytic C3–H alkenylation of indoles by the reaction of indoles with α,β-unsaturated aldehydes in presence of morpholin-4-ium trifluoroacetate as a catalyst and a stoichiometric amount of DDQ to achieve