Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• and 23 steps) to access grayananes with a cyclopentenone moiety on the A ring. It should be noted that although this is a racemic synthesis, intermediate 37 was also synthesized in enantioenriched form using a chiral copper catalyst for the cyclopropanation and a chiral auxiliary on the ester moiety

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• most crucial restriction in coupling two CD units by propargyl ether is the volatility of the latter compound. Thus, we discovered that performing the reaction at room temperature, prolonging the reaction time, and using an equivalent amount of the copper catalyst resulted in the best yields. Another

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

• reagents and 1,3-dipolar azide–alkyne cycloaddition based on the alkyne moiety. Keywords: alkynyl imidazopyridinyl selenide; copper catalyst; imidazo[1,2-a]pyridine; selenium; tandem reaction; terminal alkyne; Introduction Imidazo[1,2-a]pyridines are important heterocycles that serve as key functional

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

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• (40 mol %) in the presence of P(OEt)3 (6 equiv, triethyl phosphite) under air at 100 °C (Table 1). The yield of the corresponding amide 3a was 78% (Table 1, entry 1). The reaction was completely inhibited in the absence of the copper catalyst or P(OEt)3, and no product was detected (Table 1, entries 2

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• most effectively, further promoting the conversion of the substrate. Other changes in reaction conditions, such as heating at 70 °C, increasing the amount of copper catalyst to 10 mol % and switching the copper salt from CuSO4 to the more soluble Cu(OTf)2, did not improve the yield significantly (Table

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

• chlorosulfonylated products 8 and 9, whereas replacing the copper catalyst by ruthenium-based, iridium-based, and eosin Y catalysts afforded the desired products only in trace amount. Unexpectedly, the corresponding CuII complex, Cu(dap)Cl2, also produced the desired product with good yield. Based on the literature

• ester acted as an ideal radical precursor and accepted a single electron from the excited state CuI-acetylide complex. The copper catalyst plays a dual role, namely, as a photoredox catalyst and a cross-coupling catalyst. NHP-type esters inhibited the homodimerization of the alkyl radical and terminal

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

• %), largely due to the poison of copper catalyst by thioether. Acyclic amines were also tested and the amination products were obtained in low yields (4n, 18%; 4o, 15%). Unfortunately, primary amines and anilines were completely inert. Encouraged by the above results, we further tried to synthesize ferrocene

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

• formed, which trough the CuAAC path generates the C5-cuprate triazole intermediate 115. The oxidative addition of arylboronic acid to the copper center forms the intermediate 116. The reductive elimination occurs to give the corresponding triazole 112 and to reform the copper catalyst for the next run

• complex (ʟ-proline-MCM-41-CuCl) was obtained by the reaction of ʟ-proline-MCM-41 with CuCl in acetone at mild temperature (Scheme 21) [51]. A possible mechanism for this reaction is shown in Scheme 22. Initially, copper(I)-substituted acetylide intermediate 70 is produced via the reaction of copper

• catalyst with the corresponding acetylide by using LiOt-Bu. Further intermolecular [3 + 2]-cycloadditions of azide 67 with intermediate 70 affords a 5-copper(I)-substituted triazolide intermediate 71. The oxidative addition of 1-bromoalkyne 68 forms an alkyne–Cu(III)Br–triazole complex intermediate 72

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

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• ; heterogeneous catalyst; immobilized copper catalyst; lignosulfonate; nitrogen-containing heterocycles; solid acid; Introduction Heterogeneous metal catalysts have been continuously receiving considerable attention in the field of organic synthesis owing to the advantages of easy separation and recycling [1][2

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• binding site to nanoswitch [Cu(68)]+ preventing its action as an organocatalyst (OFF-1), while the copper catalyst [Cu(69)]+ was available to catalyze a click reaction between 4-nitrophenylacetylene (47) and benzyl azide (46) (ON-2). The addition of 1 equiv of phenanthroline 69 to the state SelfSORT-I

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• followed by the addition of CuI through an intermediate 11. This procedure provided a very low yield (7%) of a mixture of 12 (syn) and 13 (anti) products. Therefore, they opted an alternative route which involves the formation of organotin compound 14 followed by trimerization in the presence of copper

• catalyst 15 to yield the trimerized products 12 (syn) and 13 (anti) in respectable yields (Scheme 2). The alkene-bridge exchange of 12 (syn) was accomplished by tandem ring-opening and ring-closing metathesis (ROM–RCM) in the presence of Grubbs’ first generation (G-I) catalyst to generate a C3-symmetric

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