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

• Takamichi Wakamatsu Kazunori Nagao Hirohisa Ohmiya Masaya Sawamura Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan 10.3762/bjoc.11.265 Abstract A copper-catalyzed conjugate addition of alkylboron compounds (alkyl-9-BBN, prepared by hydroboration of

• and their compatibility with a multitude of functional groups, organoboron compounds are especially popular organometallic reagents. Recently, Yamamoto and co-workers developed copper-catalyzed conjugate additions of aryl- and allylboron compounds to alkynoates [9][10], but alkylboron compounds have

• not been used for these methods [11]. As related studies we reported earlier the copper-catalyzed conjugate addition of alkylboranes (alkyl-9-BBN) to imidazole-2-yl α,β-unsaturated ketones [12][13][14] and the copper-catalyzed three-component coupling with alkylboranes, alkynoates, and tributyltin

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• Chimie, 8 Rue de l’Ecole Normale, 34296 Montpellier Cedex 5, France 10.3762/bjoc.11.263 Abstract The copper-catalyzed asymmetric conjugate addition (ACA) of nucleophiles onto polyenic Michael acceptors represents an attractive and powerful methodology for the synthesis of relevant chiral molecules, as

• provided dramatic breakthroughs during the last two decades. This review aims to describe the early examples and recent advances in copper-catalyzed asymmetric conjugate additions of organometallic reagents to extended Michael acceptors. First, seminal reports dealing with the reactivity of extended

• co-workers discovered in 2001 the first example of copper-catalyzed enantioselective 1,6-conjugate addition [16]. Using phosphoramidite ligand (S,R,R)-L1 and Cu(OTf)2 as the copper source, diethylzinc was added to dienone 16 with a full 1,6-regioselectivity, and an ee of 35% (Scheme 1). In 2006

Copper-catalyzed arylation of alkyl halides with arylaluminum reagents

• Bijay Shrestha and
• Ramesh Giri

Beilstein J. Org. Chem. 2015, 11, 2400–2407, doi:10.3762/bjoc.11.261

Cu(I)-catalyzed N,N’-diarylation of natural diamines and polyamines with aryl iodides

• Svetlana P. Panchenko,
• Alexei D. Averin,
• Maksim V. Anokhin,
• Olga A. Maloshitskaya and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2015, 11, 2297–2305, doi:10.3762/bjoc.11.250

• iodides in the copper-catalyzed amination of di- and polyamines providing mainly N-monoaryl derivatives [31]. On the basis of our recent investigations, in order to obtain N,N’-diaryl derivatives, we employed the most suitable catalytic systems, CuI/L-proline (L1) and CuI/2-(isobutyryl)cyclohexanone (L2

• )-catalysis conditions is a more challenging task than N,N’-diarylation of diamines because copper-catalyzed amination is less selective than palladium-catalyzed coupling. In view of earlier obtained data we used the CuI/L1/EtCN catalytic system for the diarylation of the triamine 5 (Scheme 5, Table 4). In

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• Kirk W. Shimkin Donald A. Watson Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States 10.3762/bjoc.11.248 Abstract Recently, a number of papers have emerged demonstrating copper-catalyzed alkylation reactions of electron-rich small molecules. The

• the most common and effective [14]. Recently, several groups, including our own, have developed copper-catalyzed alkylation reactions of molecules containing electron-rich π-systems. These reactions all utilize alkyl halides as the alkylating agent, and deliver reactivity that is not observed in the

• non-catalyzed reactions. Mechanistically, it is believed that these reactions all share features of classic ATR reactions, but are distinct as they deliver simple alkylation products. These transformations represent a new paradigm in copper-catalyzed radical reactions. This article will highlight

Copper catalysis in organic synthesis

• Sherry R. Chemler

Beilstein J. Org. Chem. 2015, 11, 2252–2253, doi:10.3762/bjoc.11.244

• also an essential element, responsible for important biological processes. The title of this Thematic Series published in the Beilstein Journal of Organic Chemistry is “Copper catalysis in organic synthesis”. A web of scienceTM topic search of “copper-catalyzed synthesis” indicated over 500 papers had

• . Some of the most highly cited papers of all time on this topic are reviews on conjugate addition, cross-coupling, and [3 + 2] “Click” reaction applied to bioconjugation. The growth in copper-catalyzed organic reactions may be driven by a couple of factors. First, copper chemistry is incredibly diverse

• field of copper-catalysis from 7 countries make up this Thematic Series, “Copper catalysis in organic synthesis”. Contributions include authoritative reviews on the latest developments in copper-catalyzed Click applications, C–N cross-coupling, C–H functionalization, trifluoromethylations, asymmetric

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• copper catalysis is in the C–N bond formation by using carbon sources and nitrogen functional groups such as amides. In this review, the recent progress in the amidation reactions employing copper-catalyzed C–H amidation is summarized. Keywords: amidation; C–H bond; cascade reactions; Copper catalysis

• to be capable of catalyzing the C–H amidation reactions, copper is particularly advantageous because of the low cost, low toxicity and broad tolerance of copper catalysts. Therefore, the present review summarizes the advances on the copper-catalyzed C–H activation-based amidation (including related

• ] reported the copper-catalyzed, tert-butyl hydroperoxide (TBHP)-assisted C–H amidation of tertiary amines 1. By heating at 80 °C, the C–H bond in dimethylaniline underwent direct amidation to provide products 3 in the presence of amides 2. On the other hand, the dephenylation transformation via C–C bond

Molecular-oxygen-promoted Cu-catalyzed oxidative direct amidation of nonactivated carboxylic acids with azoles

• Wen Ding,
• Shaoyu Mai and
• Qiuling Song

Beilstein J. Org. Chem. 2015, 11, 2158–2165, doi:10.3762/bjoc.11.233

• Sciences, Beijing, 100190, P. R. China 10.3762/bjoc.11.233 Abstract A copper-catalyzed oxidative direct formation of amides from nonactivated carboxylic acids and azoles with dioxygen as an activating reagent is reported. The azole amides were produced in good to excellent yields with a broad substrate

• [25][26]. Currently, copper-catalyzed, aerobic, oxidative transformations with dioxygen as the sole oxidant have emerged as a useful and powerful strategy to construct carbon–carbon and carbon–heteroatom bonds [27][28][29]. It is known that Cu(II) superoxide species are usually reported to be formed

• ), inexpensive and readily available pyridine was employed as both the ligand and base in our case. Results and Discussion Our initial exploration commenced with benzoic acid (1) and benzimidazole (2) as the model substrates to investigate the copper-catalyzed oxidative direct amidation reaction (Table 1). The

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

• . Conclusion In summary, a method for the copper-catalyzed coupling of α,α-difluoro-substituted organozinc compounds with 1-bromoalkynes has been developed. The reaction is performed under mild conditions affording gem-difluoro-substituted alkynes in good yields. Reaction of organozinc compounds. Proposed

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• groups in organic synthesis, they are frequently and widely employed in the synthesis of numerous organic products. The generation of a C–X bond, therefore, constitutes an issue of universal interest. Herein, the research advances on the copper-catalyzed and mediated C–X (X = F, Cl, Br, I) bond formation

• catalysis in modern organic synthesis, herein, we would like to highlight the recent progress in the C–H bond halogenation with copper catalysis or mediation. Review Copper-catalyzed/mediated halogenation of the C(sp2)–H bond Halogenation of the arene C(sp2)–H bond In the synthesis of aryl halides employing

• -halosuccinimide, X = Cl or Br). The application of different acids which participated in the in situ formation of acyl hypohalites enabled the selective generation of products 2 and 7 (Scheme 5). Notably, the C–H iodinated product of type 2 was also observed as key intermediate in the copper-catalyzed pyridinyl

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• products [6][7][8][9][10][11][12][13]. Specifically, we reported that N-arylnitrones 3 can be prepared by a Chan–Lam coupling of 1 and 2 and that these compounds undergo a copper-catalyzed rearrangement to α,β-epoxyimines such as 4 [8]. Reduction of these products in the presence of a Lewis acid gave

• ][38], fragment couplings [39][40][41][42], and transition metal-catalyzed C–H bond functionalization of α,β-unsaturated imines and oximes [43][44][45][46][47][48][49][50]. We were inspired by the copper-catalyzed coupling of protected α,β-unsaturated oximes and alkenylboronic acids developed by

• modularity of the Chan–Lam coupling process, and proceeds through a pathway that is distinct from the Liebeskind copper-catalyzed C–N bond coupling and electrocyclization (Scheme 2). Results and Discussion A Chan–Lam coupling between chalcone oxime 6a and cyclohexenylboronic acid (7a) was initially tested

A new approach to ferrocene derived alkenes via copper-catalyzed olefination

• Vasily M. Muzalevskiy,
• Aleksei V. Shastin,
• Alexandra D. Demidovich,
• Namiq G. Shikhaliev,
• Abel M. Magerramov,
• Victor N. Khrustalev,
• Rustem D. Rakhimov,
• Sergey Z. Vatsadze and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2015, 11, 2072–2078, doi:10.3762/bjoc.11.223

• , 28 Vavilov Street, Moscow 119991, Russia 10.3762/bjoc.11.223 Abstract A new approach to ferrocenyl haloalkenes and bis-alkenes was elaborated. The key procedure involves copper catalyzed olefination of N-unsubstituted hydrazones, obtained from ferrocene-containing carbonyl compounds and hydrazine

• –Fuchs reaction) using a 2–4-fold molar excess of triphenylphosphine [27][28][29][30][31]. Results and Discussion Synthesis of halovinylferrocenes A few years ago we discovered a new reaction for a double carbon–carbon bond formation – the reaction of catalytic olefination. It was shown that the copper

• -catalyzed reaction of unsubstituted hydrazones of aromatic (aliphatic) aldehydes and ketones with a wide range of polyhalogenalkanes leads to the corresponding substituted ethylenes with one or two geminal halogen atoms [32][33][34][35][36]. In the present study, we investigated the possibility of using a

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• Ya Lin Tnay Gim Yean Ang Shunsuke Chiba Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore 10.3762/bjoc.11.209 Abstract We report herein studies on copper-catalyzed aerobic radical C–C bond

• iminyl radicals (Scheme 2). However, the instability of N–H ketimines [50] limits their use as starting materials. Recently, we have studied the chemical reactivity of N–H ketimines towards copper-catalyzed aerobic reaction conditions [51][52][53]. In these studies, we employed the nucleophilic addition

• found to undergo copper-catalyzed aerobic aromatic C–H amination (Scheme 3a) [52] or 1,4-aminooxygenation (spirocyclization) (Scheme 3b) [51], affording phenanthridine derivatives and azaspirocyclohexadienones, respectively, depending on the helical sense of the biaryl axis. Herein we report

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• alkaloid aspidophytine published in 2008 [14]. In 2005, Stevens and coworkers reported that treatment of trichloroacetamide-substituted N-sulfonylindole 3 under conditions for copper-catalyzed atom transfer cyclization provided chlorine transfer product 4 with the N-sulfonyl group intact (Scheme 1) [15

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• obtained together with recovered starting material. In order to test the functionalization of the above synthesized aryl iodides through a subsequent transition-metal-catalyzed coupling reaction we subjected three of them to a copper-catalyzed N-arylation reaction. Thus, the iodides 3b, 3d and 4d were

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• stoichiometric amounts of metal. A recent cyclohexanone–amine–silylacetylene coupling forms silyl-protected tetrasubstituted propargylamines in a single copper-catalyzed step. The development of the tandem silyl deprotection–triazole formation reported herein offers rapid access to alpha-tetrasubstituted

• ; copper catalysis; multicomponent reactions; tetrasubstituted carbon; triazole; Introduction 1,2,3-Triazoles demonstrate wide spread application in biological systems and drug development [1][2][3][4][5][6][7][8][9][10][11][12]. Copper-catalyzed azide–alkyne cycloadditions (CuAAC) regioselectively

• Scheme 1 would streamline the synthesis of alpha-tetrasubstituted triazoles 6. In the first step, our solvent-free copper-catalyzed three-component coupling of cyclohexanone (1), amines 2, and alkynes 3 provides high yields of silyl-protected propargylic amines 4 [24][25]. Trimethylsilyl (TMS) acetylene

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• provided acrylate 226, which was subjected to enantioselective copper-catalyzed conjugate addition with a methyl Grignard reagent involving (R)-tol-BINAP ligand to generate ester 227 in good yield and high enantiopurity. This intermediate was then converted to the key metathesis precursor involving a three

• ] have reported the synthesis of a glycotriazolophane 309 (carbohydrate–triazole–cyclophane hybrid) from a sugar amino acid via a copper-catalyzed azide-alkyne cycloaddition sequence. An aminosugar acid was identified as a useful building block to generate cyclophanes. Thus, the treatment of 304 with

Intermolecular addition reactions of N-alkyl-N-chlorosulfonamides to unsaturated compounds

• Gerold Heuger and
• Richard Göttlich

Beilstein J. Org. Chem. 2015, 11, 1226–1234, doi:10.3762/bjoc.11.136

• and polar pathways as competing mechanisms and has developed a nice copper-catalyzed oxidative amidation of alkenes whilst Muñiz [27] in a recent publication proposes a polar sulfonamido-chlorination mechanism of alkenes. Similar, intramolecular and intermolecular additions of N-chlorosulfonamides and

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• attempt to reduce the amount of catalyst, however, only led to a decrease in the conversion (Table 2, entry 10). The copper-catalyzed protocol was quite unsuccessful (Table 2, entry 11). Generally, chloro derivatives (and especially non-activated ones) remain challenging substrates for copper catalysis

Tuning of tetrathiafulvalene properties: versatile synthesis of N-arylated monopyrrolotetrathiafulvalenes via Ullmann-type coupling reactions

• Vladimir A. Azov,
• Diana Janott,
• Dirk Schlüter and
• Matthias Zeller

Beilstein J. Org. Chem. 2015, 11, 860–868, doi:10.3762/bjoc.11.96

• different analytical methods and X-ray crystallography. Experimental Copper-catalyzed N-arylation reaction of monopyrrolo-tetrathiafulvalenes, general procedure. The reaction was performed in a similar manner as described before [22]. A heavy walled Schlenk tube with a wide bore Teflon screw stopcock was

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• combines residue-specific incorporation of unnatural amino acids with chemical oxidative aldehyde formation at the N-terminus of a protein. Our approach relies on the selective introduction of two different functional moieties in a protein by mutually orthogonal copper-catalyzed azide–alkyne cycloaddition

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• described. A modified tyrosine-based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent organocatalysts 4a–c was

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• 12) had marginal impact on the binding suggesting a saturation of binding site occupancy. For the structure with 6 units of maltose on each arm, a KD of 1 μM was measured which is 700-fold more potent (40-fold per sugar) than monovalent maltose. The advent of the copper-catalyzed azide–alkyne

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

• ][3][4]. Alkenyl, alkynyl and aryl organometallic reagents have been used less frequently [78][79][80][81][82][83][84]. Feringa and co-workers reported the first copper-catalyzed ECA reactions of α,β-unsaturated lactams in 2004 [22]. They were able to perform these reactions in high yields and

• enantioselectivity was worse than using diethylzinc. So far, this methodology is limited to using 6-membered lactams. In 2013, Alexakis and co-workers reported the copper-catalyzed enantioselective 1,4-addition of a variety alkyl- and alkenylalanes to N-protected 5,6-dihydropyrrolinones [86]. In their report, they

• enanitoselectivities. So far, only copper-catalyzed ECA reactions of α,β-unsaturated lactams have been discussed. These reactions have also been applied to α,β-unsaturated N-alkenoyloxazolidinones. For instance, Hird and Hoveyda developed the copper-catalyzed asymmetric 1,4-addition of alkylzinc reagents to α,β

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• Sharpless [46] (Scheme 1 and Table 1). The click chemistry process, carried out with equimolar amounts of the respective dipolarophiles, afforded in all the cases the corresponding C-5’-triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides 13 and 14 in good yields (79–89%). According to other copper-catalyzed azide