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

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• ]pyridin-3-yl] diselenide showed an excellent anticancer activity and low cytotoxicity toward noncancer cells, suggesting that this diselenide is a potential lead compound for anticancer therapy. Keywords: anticancer activity; copper catalyst; diselenide; imidazopyridine; selenide; selenium; Introduction

• ). The interconversion of the diselenide 2 and the selenide 3 is also possibility in this reaction, with the expected mechanism shown in Scheme 3. The oxidative addition of the copper catalyst to the diselenide 2 generates the intermediate E, which is then attacked by an imidazopyridine 1 at the 3

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• reactivity of the heteroaromatic alkenyl substrates by Lewis acid activation in combination with readily available and highly reactive Grignard reagents and a copper catalyst bound to a chiral diphosphine ligand. Using this methodology, various chiral heteroaromatic products were obtained with high

• promoted the addition of Grignard reagents to N-Cbz-pyridone and N-Cbz-2,3-dihydropyridone Michael acceptors with high enantioselectivity and yield. It is worth mentioning that in copper-catalysed additions of Grignard reagents to N-Cbz-pyridone, the use of a Lewis acid (BF3·OEt2) together with the copper

• catalyst is essential for achieving a high yield as well as a high regio- and enantioselectivity (up to 99% ee). Although organoaluminium, organozinc, and Grignard reagents were all successfully applied in the ACA of 2,3-dehydro-4-piperidones, an introduction of the vinyl group was not successful until

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• iminosemiquinone redox-active ligand which was oxidized to iminobenzoquinone. The Canary group [30] reported a redox-reconfigurable copper catalyst that exhibits reversal of its helical chirality through redox stimuli (Scheme 8). Combining ʟ-methionine and catalytic urea groups with two different copper salts as

• trifluoromethylation of heteroaromatics with redox-active iminosemiquinone ligands. Reversal of helical chirality upon redox stimuli and enantioselective Michael addition with a redox-reconfigurable copper catalyst. Interaction of guanidine-copper catalyst with oxygen and representative coupling products. a4 mol

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

• reaction. This represents the first example done in a water/THF solvent system at room temperature, giving moderate chemical yields and ees. It has been proposed that the ligand itself acts as an organocatalyst, eliminating the need for a copper catalyst. 1.3 Additions to aldehydes The Oestreich group [42

• later, however, Lipshutz et al. revisited this reaction, showing that it could be performed using only 3 mol % of the copper catalyst, while leading to high chemical yields of the desired silylated product 112 (Scheme 22, left) [53]. In the same year, Hosomi and co-workers reported that the alternative

• achiral copper for similar purposes. In general, the pathway for introducing boron into unsaturated compounds (C–B coupling) mediated by a copper catalyst relies on the reaction of a Cu(I) salt with an alkoxide (M–OR) which then undergoes transmetallation with an organoborane to form, e.g., L-Cu-Bpin (306

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

• copper catalyst on an alkenyl(aryl)iodonium salt [33][34] would generate an alkenyl–copper(III) species which might undergo nucleophilic attack of the Lewis-basic oxygen of a dialkyl phosphonate. The resulting phosphonium-like intermediate would evolve by Arbuzov-type substitution of one of the alkyl

• conversion was achieved and enol phosphonate 3a was isolated in 78% yield with full selectivity towards the monoalkenylation product (Table 1, entry 7). Importantly, no reaction was observed in the absence of copper catalyst (Table 1, entry 8), while the absence of dtbpy led to a minimal conversion (Table 1

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• (Scheme 14). The synthesized copper-catalyst 74 could be reused in up to ten consecutive cycles, and only very little leaching (0.08%) was observed. A novel and reusable, synergistic and dual catalyst Pd–Cu@rGO (78) was designed and synthesized by Naeimi and Ansarian through the decoration of reduced

• , washed with THF and dichloromethane, and dried. Different organic halides (benzyl bromides, benzyl chloride, allyl bromide, aliphatic epoxides, and aromatic epoxides) were treated with sodium azide and phenylacetylene in the presence of a catalytic amount of the copper catalyst 121 in water at 70 °C

• copper catalyst 131 loadings (0.1 mol %) at 30 °C for 24 h (Scheme 28). The heterogeneous catalyst 131 could be recycled eleven times, with only a small decrease in catalytic activity. After that, the yield of the riazole product significantly decreased. A new magnetic catalyst 136 was prepared using a

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• work of Stryker and co-workers on triphenylphosphine-stabilized copper hydride complexes [1][2], copper hydrides have been widely used for conjugate reductions of α,β-unsaturated carbonyl compounds [3]. Especially a chiral copper catalyst combined with a stoichiometric amount of a silane reagent, which

• chiral p-tol-BINAP/copper catalyst established the excellent utility of chiral bisphosphine ligands for this type of reaction [4]. Surprisingly, however, chiral ligands based on N-heterocyclic carbenes (NHCs) [12] have not been applied to the conjugate reduction of α,β-unsaturated carbonyl compounds

• , while an achiral NHC/copper catalyst has successfully been utilized in this reaction [13]. Meanwhile, we devoted our effort to develop novel enantioselective C–C bond formation reactions utilizing chiral phenol–NHC/copper catalyst systems [14][15][16][17][18], in which the phenol group of the NHC ligand

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

• reaction of 3 equivalents of terminal alkyne 1 (aryl substituted alkyne) and an α-bromocarbonyl compound 2 (tertiary alkyl radical precursor) undergoes tandem alkyl radical addition/Sonogashira coupling to produce 1,3-enyne compound 3 possessing a quaternary carbon in the presence of a copper catalyst

• . Moreover, the reaction of α-bromocarbonyl compound 2 and an alkyne 4 possessing a carboxamide moiety undergoes tandem alkyl radical addition/C–H coupling to produce indolinone derivative 5. Keywords: copper catalyst; 1,3-enyne; functionalized quaternary carbon; indolinone; tandem alkyl radical addition

• ][14][15][16]. Recently, we have prepared quaternary carbon centers via radical reactions by using α-bromocarbonyl compounds (a tertiary alkyl source) and olefins or heteroatoms in the presence of a copper catalyst [17][18][19]. During our studies, we found that combinations of alkynes and tertiary

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• )]/[Cu(I)]*/[Cu(II)] species and the reduction of the Zhdankin reagent by the copper catalyst to form an azidyl radical, which then reacted with the olefin. The resulting benzyl radical could then be oxidized, probably by the catalyst in the +II oxidation state, to generate a benzylic carbocation and the

• tetrahydroquinolines and octahydroisoquinolo[2,1-a]pyrrolo[3,4-c]quinolines (Scheme 13) [29]. Importantly, the formation of the key α-amino radical resulted from an oxidation reaction catalyzed by the copper catalyst in the oxidation state +II. Using the [Cu(I)(dap)2]Cl complex as the catalyst and 2 equivalents of TFA

• and co-worker described the synthesis of a new heteroleptic copper complex bearing a substituted bipyridine ligand (Scheme 18) [34]. The novel copper catalyst was fully characterized by X-ray crystallographic analysis, UV–visible absorption and emission as well as cyclic voltammetry. The catalyst [Cu

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• system opens the possibility to synthesize well-defined polymeric materials in a green way due to the photochemical stability, low copper-catalyst concentration and the use of NIR light. Taking advantage of good penetration of NIR light, this approach provides also the opportunity to embed UV absorbing

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• 79. The complex 79 consisting of diols and a chiral copper catalyst Cu–L* easily gets deprotonated by cathodically generated MeO− to afford alkoxide anions 80, which reacts with anodically generated Br+ to form O-brominated intermediates 81. Finally, MeO− removed HBr from 81 to afford products 75/78

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• phase-transfer copper catalyst (Scheme 27). Notably, with 10 mol % of (IPr)CuOTf, full conversion can be accomplished in 10 minutes at 45 °C. Allylic fluorination: In 2013, there is an example of a copper-catalyzed fluorination of internal allylic bromides (Scheme 28). In Liu’s study, this approach was

• the same year, Loh’s group [132] used the same copper catalyst and Togni’s reagent to achieve the trifluoromethylation of enamides in good yields at room temperature (Scheme 72a). Meanwhile, this reaction exhibited excellent stereoselectivity towards the E-isomer. One year later, the same group [133

• , mild reaction conditions (room temperature) and excellent functional group tolerance. In this instance, the copper catalyst may only promote the generation of the tert-butoxyl radical from TBHP. The oxidation of the intermediate A with t-BuOOH produces a carbocation B, followed by an oxidative

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• copper catalyst was not present (Table 1, entry 2). Several bases were screened for the reaction of 1a with Se powder (Table 1, entries 2–8). The use of Cs2CO3 resulted in the highest yield of 2a (99%, Table 1, entry 2). Decreasing the loading of Cs2CO3 from 2 to 1 equivalent significantly reduced the

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• copper catalyst dissolved in ionic liquid to four synthetic cycles. Nanotechnology coupled with heterogeneous catalysis has emerged as an efficient field of catalysis for various organic transformations. Inspired from this Bagdi et al. have reported a nano-copper oxide-mediated three-component A3

• , where the absence of copper did not lead to the product formation (Table 4, entry 1). A double oxidative C–H amination reaction for the synthesis of 2-iodoimidazo[1,2-a]pyridines 137 was reported by Dheer et al. using a copper catalyst (Scheme 47) [129]. The synthesis of this moiety was also reported by

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• (Scheme 4). In this case, copper catalyst and alkynes are also used but, unlike the above method, alkynes 18 are monosubstituted. The third component is an indole or pyrrole derivative 19 and the result of the reaction is a 3,3-disubstituted isoindolinone derivative 20, which contains a newly formed

Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• 2-aminophenol derivative 2a (Table 1, entries 3 and 4). Moreover, a cationic copper catalyst generated from CuCl2 and two equivalents of AgSbF6 was effective to afford 2a in good yield (Table 1, entry 5), even at 30 °C (Table 1, entry 8). The use of a ligand, such as 1,10-phenanthroline (phen) and

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• catalytic benzoyloxy-trifluoromethylation using Togni’s reagent 5 (Scheme 4 and Scheme 5), the 1,2-benzoyloxy-azidation of alkenes can be performed in the presence of a copper catalyst with the azidobenziodoxolone ABX 40. The reaction takes place in dichloromethane using the copper(II) complex Cu(OTf)2 as

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• Shafir, Lledós, and co-workers, who investigated the intrinsic conversion of novel N-heterocyclic aryliodonium salts 1b [35]. Under the influence of base, copper catalyst and N-Me-benzimidazole as a ligand, the heterocyclic aryliodonium salt 1b was converted into the N1-aryl-5-iodoimidazole 18 as the

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• ]. To perform cyclopropanation reactions in polymersomes, the membrane was cross-linked with bisoxazoline (BOX) ligands complexing the copper catalyst. Cyclopropanation reactions were efficiently performed in water, resulting in high yields and enantioselectivities, comparable to those when the reaction

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• fluoroalkylated pyruvates is shown with dimethylzinc as a methylating reagent in the presence of a copper catalyst bearing a chiral phosphine ligand. This is the first catalytic asymmetric methylation to synthesize various α-fluoroalkylated tertiary alcohols with CF3, CF2H, CF2Br, and n-CnF2n+1 (n = 2, 3, 8

• copper. Keywords: asymmetric methylation; chiral phosphine ligand; copper catalyst; dimethylzinc; trifluoropyruvate; Introduction The introduction of fluorine atoms into organic compounds plays an important role in the discovery of lead candidates with unique biological and physicochemical properties

• . Herein, we disclose the catalytic asymmetric methylation of trifluoropyruvate derivatives as electrophiles and dimethylzinc as a methylating nucleophile by a chiral copper catalyst. This method is also applicable to the asymmetric synthesis of various α-fluoroalkylated tertiary alcohols bearing CF2H

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• 49. Finally, oxidation of 49 by Cu(n + 1) and aromatisation afforded the oxindole and regenerated the copper catalyst (Scheme 25). The same indoles bearing a 2,2,2-trifluoroethyl side-chain were also obtained in reactions performed with CF3SO2Na and (NH4)2S2O8 as the oxidant in the presence of a

• concentration, obtained by increasing the amount of copper catalyst, was beneficial to the chemoselectivity. Both styrene derivatives and terminal unactivated alkenes were suitable substrates in this transformation but not internal alkenes [55]. Csp2–CF3 bond-forming reactions Direct trifluoromethylation of

• authors studied the effect of structural variations in the substrate (R1 = aryl, heteroaryl, alkyl; R2 = H, 6-OMe, 2-Me). Aniline amides gave no conversion nor did quinoline having an ester group at the 8 position instead of the 8-amino group. The chitosan-based copper catalyst was efficiently reused in

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• (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 CaH2 and stored over activated 4 Å molecular sieves. Unless otherwise noted, materials were obtained from commercial sources and used directly

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• complete this reaction, which was further corroborated by ex situ analyses. The fact that we were able to monitor milling by method 2c, as opposed to methods 2a and 2b where copper catalyst was directly added to reaction mixture in catalytic quantity of 2–5 mol %, could tentatively be explained by even a

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• reaction with α-bromo ketoximes 1 (Scheme 36). The reaction requires a copper catalyst, which transforms the diazo compound 96 into a metal carbene complex 97. The latter reacts with a nitrosoalkene intermediate NSA (formed from α-bromo ketoxime 1) producing isoxazoline 93 with recovery of the catalyst