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

• organosilicon [17][18][19][20] and organoboron [21][22][23][24] compounds (i.e., C(sp3)–Si and C(sp3)–B). Nonetheless, considering the extent of their use and their increasing popularity in the pharmaceutical industry, as well as the significant growth in the development of Cu-catalyzed processes applied to

• their syntheses, a review on this subject seems quite timely. Therefore, we will focus on highlights of the past 5–6 years in this area, dividing the document into two sections: C–Si and C–B bond formation. Review Cu-catalyzed C–Si bond formation 1.1 Substitution reactions Alkylsilanes are an

• mechanism(s), a variety of substrates were suitable for this transformation, giving the desired products 42–44 in good chemical yields (Scheme 10) [32]. 1.2 Additions to imines Among the very first studies on Cu-catalyzed additions to imines one can include the work of Moeller and co-workers published in

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

• enantioselectivity. Conclusion A chiral phenol–NHC ligand efficiently promoted the enantioselective conjugate reduction of α,β-unsaturated esters with a hydrosilane. To the best of our knowledge, this is the first demonstration of the applicability of chiral NHC ligands in Cu-catalyzed enantioselective conjugate

Copper-catalyzed remote C–H arylation of polycyclic aromatic hydrocarbons (PAHs)

• Anping Luo,
• Min Zhang,
• Zhangyi Fu,
• Jingbo Lan,
• Di Wu and
• Jingsong You

Beilstein J. Org. Chem. 2020, 16, 530–536, doi:10.3762/bjoc.16.49

• and 4i). Notably, 1-naphthamides with alkenyl (1l) and alkynyl (1m) groups were also suitable substrates for this direct C7−H arylation, affording 4k and 4l in good yields (Scheme 3, 4k and 4l). Furthermore, this Cu-catalyzed direct C−H arylation could tolerate other PAH substrates. The regioselective

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

• methodology can realize a Pd-free catalyst system to prepare complex quaternary carbon atoms. Herein, we report the Cu-catalyzed control of the reactivity of an alkyne (addition and coupling) undergoing tandem tertiary alkylation and alkynylation to produce a 1,3-enyne containing a quaternary carbon center

• radical reaction [36]. Both cases were helpful in our development of the current Cu-catalyzed cascade C–H cyclization system. After careful optimization, we found that CuI, 1,10-Phen, Cy2NMe as a base, and 1,4-dioxane were effective for obtaining the best yields of products 5 (Figure 2). In this

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• 97% ee, Scheme 23) [52]. This methodology was successfully applied to the synthesis of various natural molecules, such as (S)-Florhydral® and (S)-(+)-ar-turmerone or key intermediates in the synthesis of 8-deoxyanisatin and frondosin. Conclusion The enantioselective Cu-catalyzed conjugate addition of

• and productivity, and a wide scope, and on the other hand, to include this highly promising methodology in many synthetic strategies. Competitive side reactions in the Cu ECA of organometallic reagents to α,β-unsaturated aldehydes. Cu-catalyzed ECA of α,β-unsaturated aldehydes with phosphoramidite- (a

• ) and phosphine-based ligands (b). One-pot Cu-catalyzed ECA/organocatalyzed α-substitution of enals. Combination of copper and amino catalysis for enantioselective β-functionalizations of enals. Optimized conditions for the Cu ECAs of R2Zn, RMgBr, and AlMe3 with α,β-unsaturated aldehydes. CuECA of

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• , Viale Morgagni 85, 50134 Florence, Italy 10.3762/bjoc.16.23 Abstract The Cu-catalyzed multicomponent ketone–amine–alkyne (KA2) reaction was combined with a Pauson–Khand cycloaddition to give access of unprecedented constrained spirocyclic pyrrolocyclopentenone derivatives following a DOS couple-pair

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• silyl ether, which are derived from the Pd-catalyzed allylic silylation of 2a and the Cu-catalyzed silylation of 1a and the subsequent [1,2]-Brook rearrangement, respectively. In this coupling reaction, (SIPr)CuCl was a slightly better copper complex than (IPr)CuCl (62%), (SIMes)CuCl (60%) and (IMes

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• detected in imidazolium-type ILs. However, complete conversion of 1a was observed in [TBP][4EtOV], without Et3N, proving that the solvent can act as a base in itself (Table 1, #2) as it was demonstrated for Cu-catalyzed C–N coupling reactions [34]. When, we attempted to couple 1a and 2a in the absence of

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

• transformation is proposed in Scheme 33 below. Notably, Cu acts as both a mediator and an oxidizer in this reaction. In the same year, Daugulis et al. [78] presented a Cu-catalyzed selective fluorination of benzoic acid derivatives and benzylamine derivatives assisted by an aminoquinoline auxiliary. With a CuI

• Cu-catalyzed fluorination of 2-pyridylaryl bromides was achieved by Liu and co-workers [80] through a Cu(I/III) catalytic cycle as well (Scheme 36). This method is based on the aid of an important pyridyl directing group and the final aryl C–F bond is formed after the reductive elimination of ArCu

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

• Ar(aryl)–Se bonds [9][10][11][12][13]. Various metals, such as Pd, Ni, Fe, and Cu have been used to catalyze the reactions of a Se source with aryl donors. Among these, Cu-catalyzed tandem cyclization via a one-step Ullmann-type Se-arylation and Csp2–H selenation are efficient methods for

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

• of biologically active imidazo[1,2-a] pyridine derivatives [108]. Encouraged by the direct synthetic strategies for imidazo[1,2-a]pyridines (IPs), Donthiri et al. have reported an efficient Cu-catalyzed C–H functionalization of pyridines with vinyl azide derivatives [109]. Their use of vinyl azide

Selenophene-containing heterotriacenes by a C–Se coupling/cyclization reaction

• Pierre-Olivier Schwartz,
• Sebastian Förtsch,
• Astrid Vogt,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2019, 15, 1379–1393, doi:10.3762/bjoc.15.138

• starting material, but also ring fusion to selenophene was achieved by Cu-catalyzed C–Se cross-coupling reaction [28]. The detailed geometric structure and the packing behaviour in the solid state of triacenes 2–4 have been elucidated by single crystal X-ray structure analysis and X-ray diffraction on

• reinvestigated the synthesis of DTT 1 by using a Cu-catalyzed C–S cross-coupling reaction with potassium sulfide (K2S) as sulfur source [29]. The best results for this C–S ring-closure reaction were achieved by reacting 3,3’-diiodo-2,2’-bithiophene (5) [30] with the system K2S and copper iodide (CuI) as catalyst

• reagents as aforementioned or DTT 1 with thiourea or thioacetate in a Pd-catalyzed reaction [33] led in both cases to substantially lower yields. For the synthesis of selenolotriacenes (DST) 3 and (DSS) 4 we followed the same strategies and applied the above described Cu-catalyzed C–S and C–Se cross

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• cytotoxicity [9]. However, it is of great importance to obtain all stereoisomers for the study of biological activity. Therefore, the development of methods for the asymmetric synthesis of polyfunctional sulfones is valuable. The most notable of them are Ag- and Cu-catalyzed 1,3-dipolar cycloaddition reactions

• , which allows to obtain chiral cyclic sulfones with high enantioselectivity [10][11][12]. Also non-racemic cyclic sulfones can be obtained by the Diels–Alder reaction, catalyzed by chiral Lewis acids or organocatalysts. Rh- and Cu-catalyzed CH-insertion reactions occurring at moderate or high

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• , BIFOL, Figure 1) [52][54] and it´s derivative, the chiral chlorophosphite ligand 6 (BIFOP-Cl, Figure 1), e.g., in Cu-catalyzed 1,4-additions [53], in Pd-catalyzed alkyl–aryl cross coupling reactions [55][56], as well as for organoaluminum fencholate reagents [57]. Unexpected stability against hydrolysis

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• Negishi coupling with aryl bromide, affording the corresponding sterically congested alkene 17b-Ar in 56% yield after two steps. The Negishi coupling with benzyl chloride and the Cu-catalyzed allylation of allyl bromide also afforded the corresponding products 17b-Bn and 17b-Allyl, respectively, in good

• species B (step a). Finally, transmetalation between B and the arylboronic ester affords the product, along with the aryl-Rh intermediate A (step b) After this contribution, the Cu-catalyzed carboxylation of aryl and alkenylboronic esters was independently reported by the groups of Iwasawa and How [55][56

• ]. Direct C(sp2)–H bond carboxylation As described above, C–H carboxylations with CO2, particularly C(sp2)–H carboxylation reactions, have attracted much research interest. As a consequence, Nolan [57] and Hou [58] independently reported Cu-catalyzed carboxylations using heteroarenes as substrates, which

Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives

• Jiao-Na Han,
• Cong Du,
• Xinju Zhu,
• Zheng-Long Wang,
• Yue Zhu,
• Zhao-Yang Chu,
• Jun-Long Niu and
• Mao-Ping Song

Beilstein J. Org. Chem. 2018, 14, 2090–2097, doi:10.3762/bjoc.14.183

• structural units present in many natural products, functional materials, and pharmaceuticals [1]. Consequently, a variety of strategies have emerged to access them, including Pd-catalyzed and Cu-catalyzed coupling reactions (Buchwald–Harting couplings and Ullmann reactions) [2][3][4]. However, these classic

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• extend and possibly improve the supramolecular binding abilities of CyNSs, mixed cyclodextrin-calixarene co-polymers nanosponges (CyCaNSs) were recently synthesized by exploiting a classical “click-chemistry” approach, namely the CuAAC reaction (Cu-catalyzed azide–alkyne cycloaddition [28][29][30

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• recently, Bolm and co-workers reported a metal-free cyclization of iodo-substituted diaryl ethers with a broad scope (Scheme 1b) [18]. Transition metal-catalyzed cross couplings have also been employed to form the required C–O and C–N bonds, e.g., by Cu-catalyzed cyclization of 2-(2-bromophenoxy)anilines

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• heterocycle formation and the other an IAAC. Unlike some of the reported strategies using Cu-catalyzed IAAC [13][15], we postulated that the intramolecular dipolar cycloaddition would proceed under thermal conditions (metal-free) due to the close proximity of the azide and similar functionalities in the

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• was paid on trifluoroacetates. Trifluoroacetate is readily available and one of the cheapest and most convenient sources of the trifluoromethylation for both industrial and medicinal purposes. In 2011, a practical and ligand-free Cu-catalyzed decarboxylative trifluoromethylation of aryl iodides was

• explored the trifluoromethylation of primary and secondary alkylboronic acids with the Ruppert–Prakash reagent (TMSCF3) (Scheme 17) [32]. These alkylboronic acids were prepared from the corresponding alkyl halides or tosylates by using their previously developed Cu-catalyzed borylation method [33]. Both

• allylic CF3 bonds from olefins. Following examples described the straightforward trifluoromethylation of terminal alkenes via allylic C(sp3)–H bond activation generating allylic trifluoromethylated compounds. In 2011, the group of Fu and Liu [49] described an unprecedented type of a Cu-catalyzed

Ni nanoparticles on RGO as reusable heterogeneous catalyst: effect of Ni particle size and intermediate composite structures in C–S cross-coupling reaction

• Debasish Sengupta,
• Koushik Bhowmik,
• Goutam De and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 1796–1806, doi:10.3762/bjoc.13.174

• reductive elimination. A more detailed study describing Pd- or Cu-catalyzed C–S coupling reactions as compared to Ni-catalyzed reaction has been published [7][53][54]. However, as proposed in previous investigations on the Ni-catalyzed C–S coupling reaction [15][22][23], the catalytic cycle here is likely

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• conditions were feasible for the synthesis of glycosyl azides which are highly useful precursors for N-linked glycans [95] or Cu-catalyzed cycloadditions with alkynes (as shown above) [85]. By using tetrabutylammonium chloride and an amine base the highly reactive chlorinated intermediate forms that can be

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• attached through Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction (couple phase). Noteworthy, herein we utilized the CuAAC reaction as a medium for coupling different building blocks assembled iteratively to generate a 1,2,3-triazole moiety. This 1,2,3-triazole moiety linked as a spacer due to its

Energy down converting organic fluorophore functionalized mesoporous silica hybrids for monolith-coated light emitting diodes

• Markus Börgardts and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 768–778, doi:10.3762/bjoc.13.76

• functionalization can be achieved upon ligating a triethylsiloxy-functionalized azide and a terminal alkynyl-functionalized luminophore by CuAAC (Cu-catalyzed azide–alkyne cycloaddition) [21][22][23]. Commencing from a 2-hydroxy-substituted Nile red 1 or 3-hydroxymethylperylene (2) the alkyne-substituted

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• arylation of aminocholanes has been described for the first time. While this Cu-catalyzed protocol provides high yields in reactions of aminocholanes with iodoarenes, Pd catalysis was found to be preferable for the reactions of aminocholanes with dichloroanthraquinones. UV–vis titration of bis(cholanylamino

• arylaminocholanes and cholane-diaminoanthraquinone derivatives by Pd- and Cu-catalyzed amination. Such compounds not only have cation binding properties, but also might be easily introduced in lipid membranes to form ion channels. Appropriate close location of lipophilic steroid fragments in bis(cholanediamino

• LiAlH4 (Scheme 2) [37]. Cu-catalyzed amination is known to be a very efficient approach for C–N bond formation [38][39]. The availability of the variety of inexpensive ligands for copper(I) is a crucial benefit in comparison to the Pd-catalyzed variant. Primary amines of different structures can readily