Copper catalysis in organic synthesis

• Sherry R. Chemler

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

• Sherry R. Chemler Department of Chemistry, Natural Sciences Complex, SUNY Buffalo, Buffalo, NY 14260, USA 10.3762/bjoc.11.244 Keywords: copper catalysis; Copper is a very versatile transition metal that has been used as a building material by human civilizations for over 6000 years. Copper is

• 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

• 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

• Jie-Ping Wan Yanfeng Jing College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, P.R. China 10.3762/bjoc.11.240 Abstract Copper catalysis has been known as a powerful tool for its ubiquitous application in organic synthesis. One of the fundamental utilities of

• 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

• 11, 12 and 13 enabled the final production of the N-alkylamides [43]. Also by means of copper catalysis, Powell et al. [44] reported the synthesis of N-alkylsulfonamides 16 via the C–H amidation of various sp3C–H bonds such as benzylic, allylic and tertiary carbon ones (14) in the presence of primary

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

• application in C–H bond functionalizations in recent years owing to their distinct advantages such as low cost, high stability and flexible forms of presence [29][30][31]. In the area of C–H bond halogenation, the copper catalysis also constitutes a major practical option. To show the power of copper

• 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

• challenging chemical bond for direct activation. Consequently, the examples on copper-catalyzed halogenation of inactive C(sp3)–H bond remained barely explored. In 2010, Ball and Kundu [68] developed a protocol of remote C–H chlorination of alkyl hydroperoxides by means of copper catalysis. As displayed in

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

• of vinyl groups: while for the monoalkene containing molecules no reduction is seen, the divinyl products are reduced in several steps. Keywords: catalytic olefination; copper catalysis; cyclic voltammetry; ferrocene; Introduction The introduction of complex functional fragments into the specified

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

• pyrrole and indole substrates 1 and 2, the unsubstituted azoles were reacted with aryl and heteroaryl iodides under copper catalysis. As far as the derivatives 1a,b, 1d,e and 2a–e are concerned, the reactions were carried out by using 1.5 equiv of the azole, 0.2 equiv of copper, 2 equiv of caesium

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

• ; 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

• for the inclusion of sensitive and hindered substrates, this unprecedented method should be applicable to the robust and less hindered substrates more common in triazole literature. The power of copper catalysis will accelerate further exploration of the therapeutic potential of alpha-tetrasubstituted

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

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• + NH4+, 280.1543; found, 280.1550. For those products as diastereomers, the conversion of keto esters and diastereoselectivities of lactones were determined by GC analyses. Mechanism of reductive aldol–lactonization reaction of maleate with a carbonyl and silane under copper catalysis. Possible copper

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• -(1,2-diarylindol-3-yl)-N-protected-THIQs 1 by employing palladium, copper, and iron-catalyzed methods. Results and Discussion Catalyst price and availability were important considerations for selecting transformations to be used in this project. Whenever possible, iron or copper catalysis was

• immediately. Although a broad range of (hetero)arenes undergo C–H-arylation under copper catalysis, heterocycles possessing acidic N–H bonds react at the nitrogen preferentially [52][53]. Moreover, directing groups such as acetyl (in combination with a hypervalent iodine aryl source) [42], or 2-pyridinyl

• , copper is superior to iron in this particular transformation. Thus, the remaining N-arylindoles 5c–e were reacted under copper catalysis exclusively. Again, the electron-rich thiophen-2-yl-substituted substrate gave 7c in a good yield of 78% (Table 5, entry 3). Also the 4-fluorophenyl precursor 5d

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• chlororhodium complex. The silylgroup was not incorporated in the vinylphosphine product 138a and methanol was added as a proton source for completing the reaction. The adducts 138a were formed with good to high syn-selectivity. Kondoh et al. demonstrated the P–H addition to 1-alkynylphosphines under copper

• catalysis (Table 16) [244]. Besides copper(I) iodide several other copper salts effectuated the reaction albeit in lower yields as did silver(I) iodide, palladium(II) chloride and platinum(II) chloride. Other transition metal catalysts such as gold(I) chloride, nickel(II) chloride and cobalt(II) chloride

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

• Rupankar Paira,
• Tarique Anwar,
• Maitreyee Banerjee,
• Yogesh P. Bharitkar,
• Shyamal Mondal,
• Sandip Kundu,
• Abhijit Hazra,
• Prakas R. Maulik and
• Nirup B. Mondal

Beilstein J. Org. Chem. 2014, 10, 692–700, doi:10.3762/bjoc.10.62

• outcome and forced us to explore new catalytic systems. While searching for this goal, we were attracted by the possible application of copper-catalysis, which has always been an effective tool especially with Diels–Alder reactions [26][27]. Thus, we studied the effect of a number of catalytic systems and

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• coworkers [174] applied the DVCPR in the core structure synthesis of actinophyllic acid (218, see Scheme 25) [175]. Subjection of diazo compound 213 to copper catalysis yielded vinylcyclopropane 214. Deprotonation and silyl ether formation resulted in intermediate cis-divinylcyclopropane 215, which smoothly

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• reported by J. F. Hartwig [45], J. M. Shreeve [46] and further investigated and generalized to both open-chain and cyclic α-fluoroketones by F. L. Qing [47][48]. However, further decarbonylation to the monofluoromethyl group proved difficult. 1.2 Copper catalysis Recently a copper-catalyzed

• Catalytic difluoromethylation The synthesis of difluoromethylated aromatics attracted considerable interest in recent years due to their potential pharmacological and agrochemical activity [42][50][51][52][53][54][55][56]. 2.1 Copper catalysis In contrast to widely used stoichiometric copper-mediated

• regenerates the copper catalyst, thus allowing the catalytic turnover (Figure 1). 2.2 Iron catalysis Similarly to the work of J. Hu and colleagues using copper catalysis, the group of Z.-Q. Liu reported on the decarboxylative difluoromethylation of α,β-unsaturated carboxylic acids. However, the latter used

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• in flow previously as a route to densely functionalized heterocycles using HBr generated in a prior step as the catalyst for the reaction [51]. Copper catalysis has also been used in flow mode for preparing PEG-immobilized dihydropyrimidines [52]. We decided to screen a set of conditions for the

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• , versatile, efficient and economically attractive procedure for the synthesis of sulfur heterocycles and a variety of sulfides with good yields. This one-pot methodology involves a cascade of reactions starting with a C–S bond formation by copper catalysis and followed by consecutive acyl transfers

New efficient ligand for sub-mol % copper-catalyzed C–N cross-coupling reactions running under air

• Per-Fredrik Larsson,
• Peter Astvik and
• Per-Ola Norrby

Beilstein J. Org. Chem. 2012, 8, 1909–1915, doi:10.3762/bjoc.8.221

• Goldberg reactions [8]) the reaction type has had a reputation of being inefficient, requiring high temperature and high catalytic loading (near stoichiometric) [1]. However, the revival of copper catalysis by Buchwald and co-workers [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] and

• the ligand is more effective at solvating the active catalyst. The fact that DMDETA proved to be an effective ligand in sub-mol % copper catalysis further indicates the necessity for the Me–N–ethylene–N–Me motif in the ligand design of these systems. However, in our hands the synthetic procedures for

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

• arylation of heterocycles, including electron-rich azoles with aryl bromides, by using potassium phosphate as a base and phenanthroline as a ligand (Scheme 8) [47]. Over the past few decades, it has also been demonstrated that copper catalysis is not required in order to attain good yield and selectivity in

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• heterocyclization. In recent years, the direct hydroxylation of aryl halides has been developed by several groups by using palladium- or copper-catalyzed protocols. Whereas the reactions under copper catalysis work well for aryl iodides [45][46][47][48], the palladium-catalyzed hydroxylation also takes place with

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• -carboxylate (39) and 2-bromobenzaldehyde O-benzyl oxime (38), and only a moderate yield (53%) using CuI [59]. Targeting the same product, Ma et al. used copper catalysis some years previously. The coupling of 1,4-diiodobenzene (41) and (S)-ethyl 3-amino-6-hydroxyhexanoate (42), and subsequent esterification

Synthesis of new triazole- based trifluoromethyl scaffolds

• Michela Martinelli,
• Thierry Milcent,
• Sandrine Ongeri and
• Benoit Crousse

Beilstein J. Org. Chem. 2008, 4, No. 19, doi:10.3762/bjoc.4.19

• scaffolds. Keywords: copper; catalysis; fluorine; heterocycle; click chemistry; peptidomimetics; Background The 1,2,3-triazole system has widespread uses, and it has been considered as an interesting component in terms of biological activity [1][2][3][4][5]. Although the use of heterocyclic moieties in