Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• , Turkey King Abdulaziz University, Faculty of Science, Chemistry Department, 21589 Jeddah, Saudi Arabia 10.3762/bjoc.17.164 Abstract The development of long-wavelength photoinduced copper-catalyzed azide–alkyne click (CuAAC) reaction routes is attractive for organic and polymer chemistry. In this study

• [40]. BPNs were tested as NIR photoinitiator for the CuAAC reactions of low molar mass compounds and polymers possessing antagonist azide and alkyne functionalities (Figure 1). The optical absorption spectra of BPNs, copper(I) chloride (CuICl, 0.05 mmol) and copper(II) chloride (CuIICl2, 0.05 mmol

• phenylacetylene (Alk-3) in the presence of copper(II) chloride/ N,N,N’,N’,N’’-pentamethyldiethylenetriamine (CuIICl2/PMDETA) and exfoliated BPNs under the white LED irradiation was performed (Figure 3). The reaction was followed by 1H NMR spectroscopy during the click process. The decrease of the acetylene proton

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

• 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

• . Normally, (E)-2-en-4-yn-1-azides 1 with electron-rich substituent groups favorably give the 5-iodopyridine 3, while for substrates containing electron-poor groups, the 2-acylpyrrole 4 is favored (Scheme 3). Then, the Reddy group developed a copper-catalyzed aminative aza-annulation of enynyl azides with N

• synthesis of selenyl- and sulfenylpyridines has attracted considerable attention. In 2019, the Reddy group reported a copper-catalyzed aza-annulation of enynyl azides 1 for the synthesis of 5-selenyl- and sulfenylpyridine derivatives 18 and 19 (Scheme 7) [51]. Diorganyl dichalcogenides (R1XXR1, X = Se, S

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• materials, dyes, agrochemicals, photostabilizers, and corrosion inhibitors (copper alloys) [6]. Incorporation of the 1H-1,2,3-triazole moiety is well known to impact on the physical, chemical and biological potential properties of organic molecules. Due to this reason, many efforts have been exerted to

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• , aryldiazonium salts have long played an essential role as radical precursors [20]. Their use in CH-arylation reactions of olefins, catalyzed by copper salts, was first published by Meerwein in 1939 [21]. Recently, we published a Meerwein arylation/cyclization sequence to benzofuropyridine derivatives in this

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• developed by Sharpless and collaborators, to the Huisgen cycloaddition (a 1,3-dipolar cycloaddition reaction to obtain this heterocycle) allowed the regiospecific synthesis of the 1,4-disubstituted isomers with good yields in the presence of copper(I) salts [15][16][17]. Since then, medicinal chemists used

• cycloaddition reactions via the copper-catalyzed 1,3-dipolar cycloaddition reaction (CuAAC) of the azides 5 and 9 with suitably functionalized acetylenes 6a–j, using sodium ascorbate and copper sulfate in ACN/H2O 2:1 under microwave irradiation were carried out to obtain the 1,4-regioisomers of the final

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• , iron(III) chloride hexahydrate, trifluoroacetic acid (TFA), N-trifylphosphoramide (NTPA), benzoic acid, diphenyl phosphate (DPP), malonic acid, chloroacetic acid, copper(II) triflate, acetic acid, and p-toluenesulfonic acid (p-TSA) were used as catalysts. TFA gave the best yield of these catalysts with

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• ) and Yang (2016) [82][83]. Both reactions used aerial oxygen as the oxidizing agent for sulfur (Scheme 15). Shibahara utilized 20 mol % copper(I) thiophene-2-carboxylate (CuTC) as the catalyst, where heating N-methylindole (1) with elemental sulfur in DMSO as solvent at 90 °C under aerial oxygen led to

• the desired product 101 in 49% yield [82]. Other copper catalysts such as CuCl or CuBr gave low yields, even when used with 2,2’-bipyridyl as the ligand. First, oxidation of copper(I) takes place, which interacts with elemental sulfur to “activate” it. A nucleophilic attack from N-methylindole (1) to

• the sulfur species 102 takes place to generate copper sulfide complex 103. An oxidative homocoupling gives the bis(indol-3-yl)sulfide 101. Simultaneously, an oxidative homocoupling of the copper sulfide complex can take place to afford disulfide 104, that reacts with N-methylindole again under

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

• monofunctionalized naphthyl substrates. These authors demonstrated that the rhodium-catalyzed oxidative 1:2 coupling reactions of arylboronic acids 7 with alkyne 8 occurred in the presence of a copper–air oxidant, to give the corresponding 1,2,3,4-tetrasubtituted anthracene derivatives 9a and 9b (Scheme 1) [34

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

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• to 1,8-dihydroxynaphthalene (1,8-DHN) (10) by Abr1, a multi-copper reductase. In a last step polymerization of 1,8-DHN monomers is facilitated by the laccase Abr2 [45][149][150][151][152]. Knock out mutants of either ayg1, arp2, or abr2 lead to different coloured conidia while loss of pksP aborts DHN

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• using 0.6 mol % of tetrakis(triphenylphosphine)palladium(0) and 1.2 mol % of copper iodide (Scheme 2, Table 1). The reaction proceeded chemoselectively at the two carbon–bromine bonds giving 2,4-bis(phenylethynyl)-9-chloro-5,6,7,8-tetrahydroacridine (4a). This result was not entirely predictable, as the

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• 1,2,3-triazoles through multicomponent reactions and the relevant mechanistic aspects have been surveyed by Chen, Ren, et al. [27]. The 1,3-dipolar cycloaddition reaction between azides and alkynes is the most efficient pathway for the preparation of disubstituted 1,2,3-triazole derivatives. The copper

• , altogether leading to a moderate to high yield of the products (Scheme 19) [50]. A reasonable mechanism for this cyclization/coupling reaction involves the generation of a 5-copper(I)-substituted triazolide intermediate 62, which coordinates with propargyl carbonate 59. Further insertion of the C–C triple

• bond of an alkyne into the Cu–triazole bond gives 64, which then undergoes syn-β-oxygen elimination to provide the target product. On the other hand, an oxidative addition and reductive elimination sequence can also generate the target product (Scheme 20) [50]. An immobilized copper complex has been

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• Institute for Sustainable Chemistry (WISCh), Georg-August-Universität Göttingen, Tammannstraße 2, 37077 Göttingen, Germany 10.3762/bjoc.17.113 Abstract The efficient copper-mediated oxidative C–H alkynylation of benzhydrazides was accomplished with terminal alkynes. Thus, a heteroaromatic removable N-2

• : benzhydrazides; copper; 3-methyleneisoindolin-1-one; removable directing group; Introduction Inexpensive copper-promoted oxidative C−H activations [1][2][3][4][5][6][7][8][9][10][11] have been recognized as competent tools for the efficient assembly and late-stage functionalization of organic molecules due to

• the natural abundance and versatile reactivity. Early examples of copper-promoted C−H activation of 2-arylpyridines were disclosed by Yu et al. [12] and Chatami et al. [13] independently. Inspired by these studies, various copper-induced C−H functionalizations, such as arylations, alkynylations

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• adjustments from the previous conditions (Scheme 2) [25], such as conducting the reaction at a higher temperature and adding a copper salt to reoxidize possible Pd(0) species produced in the cyclization process [32]. Two compounds containing quaternary centers were synthetized in moderate yields (Scheme 4

• radical initiator and a copper salt as an additive, the reaction between unactivated olefins and alkanes (in large excess, 50 mL/mmol) afforded anti-Markovnikov hydroalkylation products at high temperature (110 °C) (Scheme 37). Two examples of the synthesis of quaternary carbon centers were reported using

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• -ethynylpyrene (40) under copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction conditions to yield the double-headed nucleoside 41 (Scheme 10) [23]. The double-headed nucleoside 41 was phosphitylated and then incorporated into oligonucleotides and was found to form highly stable DNA duplexes and three

• nucleosides were further reacted with propargylated nucleobases through a copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction followed by treatment with methanolic ammonia to give the C-3′-substituted double-headed ribofuranonucleosides 46a–c and 50a–e (Scheme 11) [36]. The double-headed nucleosides

• nucleoside 102 with phenylacetylene in the presence of sodium ascorbate and copper sulfate in a solvent mixture of t-BuOH, water and pyridine, followed by the removal of the tert-butyldimethylsilyl protecting group gave nucleoside 103 (Scheme 22) [14]. Under similar reaction conditions, the treatment of

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• the bromination using Br2/CH2Cl2 and then subsequent alkylation followed by Ullmann-type copper-mediated cross-coupling reaction in overall good yield (Scheme 4). On the other hand, imidazole and benzimidazole containing C3-symmetric truxene-based molecules (14 and 16) have also been assembled from

• the hexaalkylated tribromotruxene 5 by means of Ullmann-type reaction in the presence of copper powder using pristine imidazole (13) and benzimidazole (15), respectively (Scheme 5). Moreover, we have successfully constructed the C3-symmetric oxazole containing truxene derivative 20 along with

• (method A). Method C: Tribromotruxene derivative 5 (400 mg, 0.43 mmol), pyrrole (12, 102.5 mg, 1.50 mmol), K2CO3 (6.5 equiv), and copper power (3.5 equiv) were dissolved in dry DMSO (10 mL) and the reaction mixture was heated at 130 °C under nitrogen atmosphere for 2 days. After completion of the reaction

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• understanding of the process itself [142][143][144]. Benaglia et al. exemplified 3D printing with a copper-catalysed Henry reaction [145]. Benzaldehyde (17) and the homogenous catalyst were mixed with nitroethane and the DIPEA base solution in a 1 mL polylactic acid (PLA) square-channelled microreactor. The

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• on this feature to isolate biguanide as a copper complex. Interestingly, transition metal-biguanide complexes often present vivid colors because of a strong absorption in the visible range. Biguanides have been used in chemistry as versatile starting materials in organic synthesis, catalysts [5

• transesterification of several vegetable oils [5]. Since the first reported copper-biguanide complex, the synthesis of a variety of stable biguanide complexes has been reported with VIV, CrIII, MnIII, MnIV, CoII, CoIII, NiII, CuII, ZnII, PdII, ReV, OsVI [8], etc. Many of these complexes found applications as

• reagent to prepare biguanides dates back to the 1880s at the time of the first historical syntheses. During the decade following the biguanide discovery, three different techniques were investigated: a) the reaction of cyanoguanidine with an aqueous solution of an amine in the presence of copper salts [13

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• -position of an oxazoline or amide is selectively activated using a copper or palladium catalyst. Manganese is one of the most abundant and nontoxic transition metals found in the earth’s crust and its corresponding complexes and salts are useful in synthetic organic reactions [29][30][31][32][33][34][35

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• Meldal have independently developed a copper-catalysed azide–alkyne cycloaddition that accelerated the rate of the reaction and allowed the selective preparation of 1,5-disubstituted 1,2,3-triazoles [16][17][18][19]. As noted above, a wide range of methods are available in the literature for the

• an easy pathway to synthesize such triazolylenones. Inspired by this result, we proceeded to optimize the reaction conditions to further improve the yield. Replacement of rhodium by copper (II) acetate slowed down the reaction with a marginal change in the yield of the product 3a (Table 1, entry 2

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• anticancer drug vatalanib [26][27][28] (Figure 1). On the other hand, aminophthalazinones can be prospective candidates as N- and O-donor ligands to form complexes with biological significant metal ions, such as copper or zinc [29]. Recently, we have demonstrated a strategy for the synthesis of phthalazinone

• -bromobenzoate via palladium-catalyzed isocyanide insertion [32][33] (a method that is limited to tertiary-substituted isocyanides) or 2) the palladium or copper-catalyzed coupling of bromolactams with amines (a method that requires the usually lengthy synthesis of the bromoprecursors) [19][34]. Therefore, the

• 63Cu2+/65Cu2+ ion complex containing two ligands L2. However, a significant amount of unchanged ligand was also visible. For the ion at m/z = 719.5 Da, tandem spectra were recorded. The first fragmentation gave ions at m/z = 329.3 Da (L2 + H+) and 391.4 Da (ligand L2 and copper). The further

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• tetraacetate (Scheme 39) [60][61]. To develop novel bone-targeting prodrugs, a copper-catalyzed carbene insertion of tetraethyl diazomethyldiphosphonate (216) with N-Boc-protected amino acids 214 and 215 provided a simple method to synthesize phosphonodepsipeptides 217 and 218 containing a C-1

• -catalyzed carbene insertion. Synthesis of phosphonodepsipeptides with a C-1-hydroxyalkylphosphonate motif via a copper-catalyzed carbene insertion reaction. Funding The project was supported by the National Natural Science Foundation of China (Nos. 21772010 and 21572017).

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• -Dimethylformamide (DMF) was purified by a solvent-purification system (GlassContour) equipped with columns of activated alumina and supported-copper catalyst (Q-5) before use. 1,1,1,3,3,3-Hexafluoropropan-2-ol (HFIP) was distilled from molecular sieves 4 Å and stored over activated molecular sieves 4 Å. 1,4-Dioxane

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