Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• derivatives by covalently attaching water-soluble moieties to the fullerene core. Subsequently, Nakamura and co-workers further developed reactions between C60 and organocopper reagents, enabling the sequential addition of functional groups to obtain penta- and decaadducts, which largely enhanced the water

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• screening of various organocopper reagents (prepared from MeLi, EtMgBr, ZnEt2 or AlMe3 and copper halide or thiophene-2-carboxylate (CuTC)) was conducted, to no avail. In most cases, the starting material was recovered without indication that the pyrone ring interacted instead with the reagent. To decrease

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

• radical and the organocopper via SET with hydrogen atom abstraction from CH3CN. Subsequently, the benzyl radical was captured by the organocopper to generate the hydroamination products (Scheme 10). In 2020, the same group [60] reported the copper-catalyzed asymmetric dual carbofunctionalization of

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• organocopper derivative was then oxidized resulting in the formation of the desired products. Note that in 2018 the same group reported the copper-mediated oxidative difluoromethylation of heteroarenes under similar reaction conditions (TMSCF2H, CuCN, 9,10-phenanthrenequinone, t-BuOK in NMP) [46]. Not only

Towards triptycene functionalization and triptycene-linked porphyrin arrays

• Gemma M. Locke,
• Keith J. Flanagan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70

• [34] directly through various Pd-catalyzed or organocopper cross-coupling [35] reactions. However, exploratory studies did not show much promise and this approach was abandoned, as was the functionalization of 9,10-dibromoanthracene with phenyl spacers prior to triptycene formation (see Supporting

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

• yields (Scheme 48). They proposed a mechanism in which LCu(I)–Si coordinates first with the triple bond, which eventually forms a monosilylated diene. The resulting organocopper species then participates in a second catalytic cycle to furnish the disilylated products [86]. 2 Cu-catalyzed carbon–boron

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

• 2-AP to Cu(OTf)2, forming an intermediate 7, that was followed by migratory insertion by haloalkyne (Scheme 4). The organocopper species 8 thus formed would undergo deprotonation/oxidation and finally reductive elimination to give the cyclized product 6 (Scheme 4). Along with the unprecedented

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• attention to their stereoselective oxidation reaction (Scheme 5). Considering electrophilic oxidation processes of organometallic species, molecular oxygen seems to be the most obvious choice due to its abundancy and low cost. Nevertheless, the reaction of molecular oxygen with a organocopper species

• usually proceeds through single-electron transfer to dioxygen, leading to either a loss of stereoselectivity, degradation of the organocopper or to the formation of dimer as major products [71]. Therefore, it was clear that a different approach for the oxidation process was needed. Oxenoid, possessing the

• resulting t-BuOOLi was transferred to the organocopper dropwise at −78 °C via a cannula. The mixture (orange to brown) was stirred at this temperature until disappearance of the cyclopropylcopper species (followed by TLC, eluent hexane/EtOAc 9:1, ca. 30 min). The reaction was then quenched with an aqueous

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• intermediate 15, which undergoes a ring-opening process to form the radical intermediate 16 [52][53]. Then, the radical 16 reacts with copper(II) acetate to produce organocopper intermediate 17. Finally, the intramolecular insertion of C–Cu in compounds 17 to the carbon–carbon double bond takes place to

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• the products 32 were obtained, but most commonly the reactions resulted in a mixture of stereoisomers (Scheme 22). The yield of the reaction was dependent on the kind of substrate and ranged from 14 to 68% [38]. The reaction involving organocopper compounds as carbon nucleophiles (R2CuLi, where R

• nucleophiles and their subsequent intermolecular Wittig reaction with aldehydes or ketones. Intermolecular Wittig reaction with the use of vinylphosphonium bromide and organocopper compounds as carbon nucleophiles. Intermolecular Wittig reaction with the use of ylides generated from vinylphosphonium bromides

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

• erythronolide B, this result indicates that the organocopper compounds undergo conjugate addition to nitrosoalkenes in much more selective manner as compared to organolithium and organomagnesium reagents. Later on, Weinreb and co-workers demonstrated that organocopper reagents smoothly react with α-chlorooximes

Bridgehead vicinal diallylation of norbornene derivatives and extension to propellane derivatives via ring-closing metathesis

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2016, 12, 1877–1883, doi:10.3762/bjoc.12.177

• stereocontrolled manner in a single step is not a trivial exercise. Generally, it was accomplished by radical three-component coupling reactions or Michael-type additions of organocopper reagents starting with conjugated carbonyl compounds [33][34]. But, the resulting alkyl groups are in trans orientation. Our

Copper-catalyzed stereoselective conjugate addition of alkylboranes to alkynoates

• Takamichi Wakamatsu,
• Kazunori Nagao,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2015, 11, 2444–2450, doi:10.3762/bjoc.11.265

• the α-position of the carbonyl group (93% D). The syn selectivity was slightly decreased due to the deuterium isotope effect: Slower D-trap caused isomerization of organocopper intermediates (vide infra). This experimental result indicates that t-BuOH acts as a proton source. A possible mechanism for

Coupling of α,α-difluoro-substituted organozinc reagents with 1-bromoalkynes

• Artem A. Zemtsov,
• Alexander D. Volodin,
• Vitalij V. Levin,
• Marina I. Struchkova and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2015, 11, 2145–2149, doi:10.3762/bjoc.11.231

• reaction tolerates ester groups or TBS-protected hydroxy groups. Aromatic iodide also remains unaffected (Table 2, entry 2). As for the mechanism, we believe that the reaction starts with the zinc/copper exchange resulting in the formation of fluorinated organocopper species 5 (Scheme 2). Compound 5

The facile construction of the phthalazin-1(2H)-one scaffold via copper-mediated C–H(sp²)/C–H(sp) coupling under mild conditions

• Wei Zhu,
• Bao Wang,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 1624–1631, doi:10.3762/bjoc.11.177

• organocopper(II) complex M2, which undergoes Cu(OAc)2-promoted oxidation and intramolecular C–H cupration to deliver chelated organocopper(III) intermediate M4. The corresponding product 3a is formed by the subsequent reductive elimination and intramolecular annulation. Conclusion In conclusion, we have

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• addition reactions where they employed organocopper reagents and chiral phosphorus-based ligands [18]. This breakthrough in the field led to the development of different chiral ligands for asymmetric CA reactions. Another major advancement occurred in 1997 when Feringa’s group developed the first catalytic

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• reaction mixture). Under various reaction conditions, it has been observed that the CuAAC reaction mixtures show a transient yellow colour upon addition of the copper catalyst (precursor) to the substrates’ solution. This colour has been attributed to the formation of polynuclear organocopper species [42

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• ). Almost complete selectivity was achieved when BF3·Et2O (6 equiv) and CuI (0.3 equiv) were used (>99:1 anti/syn). They reasoned that the high selectivity arose from the use of a monodentate Lewis acid and the highly dissociated anion derived from the organocopper species. Recently Lam reported interesting

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• allene synthesis by copper-mediated SN2’-substitution [51] (Table 1, see below). In order to establish suitable reaction conditions, we first examined the synthesis of the butyl-substituted model substrate 6a. Treatment of propargyl tosylate 5a with the organocopper reagent formed in situ from n-BuMgCl

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• ][45][46], organomagnesium (sp2–sp3) [47], or organocopper (sp3–sp3) [48][49] cross-couplings; or (2) bidirectional extension of a central thiophene C4-fragment [50]. Two fundamentally different approaches worth special mention are the synthesis of the iso-C14 acid 3 by direct hydro-isopropylation of

Copper(II)-salt-promoted oxidative ring-opening reactions of bicyclic cyclopropanol derivatives via radical pathways

• Eietsu Hasegawa,
• Minami Tateyama,
• Ryosuke Nagumo,
• Eiji Tayama and
• Hajime Iwamoto

Beilstein J. Org. Chem. 2013, 9, 1397–1406, doi:10.3762/bjoc.9.156

• produces spirocyclic primary alkyl radical 11. Hydrogen-atom abstraction by 11 then leads to formation of spirocyclic ketone product 2, while trapping of 11 by CuOAc followed by β-H elimination (either hydride elimination or deprotonation) [39] of the resulting organocopper intermediate 12 generates the

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

• Yury Minko,
• Morgane Pasco,
• Helena Chechik and
• Ilan Marek

Beilstein J. Org. Chem. 2013, 9, 526–532, doi:10.3762/bjoc.9.57

• : carbometallation; enamides; organocopper; regiochemistry; ynamides; Introduction Due to a strong differentiation of electron density on the two sp-hybridized carbon atoms, N-alkynylamides (ynamides) have become attractive substrates involved in many synthetically useful transformations [1][2][3][4]. The

• -addition of the organocopper reagent on the triple bond [23], the regioselectivity is dependent on the nature of the α-substituent on the alkyne 1. The presence of a donor substituent (XR = OR, NR2, Path B, Scheme 1) leads generally to the β-isomer in which the copper atom adds to the carbon β of the

• the coordination of the organometallic species by the sulfonyl group should control the regioselectivity of the carbometallation reaction in favor of the α-isomer. When 2 was added to an organocopper (easily prepared by the addition of one equivalent of R2MgBr to one equivalent of CuBr in Et2O at −50

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• ] However, the C2-selectivity observed in the presence of Cu(I) salts as cocatalyst, or used alone, was suspected to arise from a proton–metal exchange of the most acidic position leading to an organocopper intermediate suitable for a nucleophilic substitution reaction. Daugulis reported a first

• ]. The resulting C2-carbanion may be in equilibrium with a stabilized carbene intermediate and finally reacts with copper iodide to give the organocopper intermediate. Bellina and Rossi also noted that this last transmetalation step may be complicated by a second, well-known equilibrium of the 2

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

• Bryan Ringstrand,
• Martin Oltmanns,
• Jeffrey A. Batt,
• Aleksandra Jankowiak,
• Richard P. Denicola and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2011, 7, 386–393, doi:10.3762/bjoc.7.49

• efficient and the product is crystalline, which simplifies its purification. Another route to VII involves a two-step sequence of conjugate addition of an organocopper reagent to glutaconate diester [38] followed by reduction (Method 1C, Scheme 1). Yield of diols from this sequence are typically around 70

Recent advances in carbocupration of α-heterosubstituted alkynes

• Ahmad Basheer and
• Ilan Marek

Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77

• species to an alkyne (carbometalation reaction) is an extremely useful reaction for the preparation of polysubstituted stereodefined alkenyl metal derivatives. When the organometallic species involved is an organocopper reagent, the reaction is termed carbocupration. To be synthetically useful, the new

• organocopper 3 must have a reactivity different from that of 1 in order to avoid oligomerization of the carbometalated product 3 (Scheme 1) [1][2][3]. For most carbocupration reactions, a strict syn-addition prevails but the regioselectivity is usually dependent of the substitution pattern of the alkyne [4

• ]. Indeed, the presence of a donor or acceptor groups in close proximity to the acetylenic moiety can influence the regioselectivity of the addition and different isomers could be formed [5][6][7]. The most pronounced effect concerns the intermolecular addition of an organocopper to α-heterosubstituted