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

• phase-transfer copper catalyst (Scheme 27). Notably, with 10 mol % of (IPr)CuOTf, full conversion can be accomplished in 10 minutes at 45 °C. Allylic fluorination: In 2013, there is an example of a copper-catalyzed fluorination of internal allylic bromides (Scheme 28). In Liu’s study, this approach was

• (Scheme 31a) [74]. Che and co-workers [75] achieved a similar α-fluorination of β-ketoesters and N-Boc-oxindoles (Scheme 31b). Compared with Du’s method, Che employed both AgClO4 and chiral iron(III)-salan complexes as the catalyst. In 2016, the group of Nishikata [76] described a copper-catalyzed site

• five and six-membered ring β-ketoesters were converted to the corresponding products in high yields and enantioselectivities (Scheme 56). In 2018, the first example for the copper-catalyzed stereospecific trifluoromethylation of secondary propargyl sulfonates was described by the group of Zhang [116

Attempted synthesis of a meta-metalated calix[4]arene

• Christopher D. Jurisch and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2019, 15, 1996–2002, doi:10.3762/bjoc.15.195

• Ullmann-type coupling to give aryl azide 2, which readily reacted with phenylacetylene in a copper-catalyzed Huisgen 1,3-dipolar cycloaddition to give 1,2,3-triazole 3 (Scheme 1). The formation of the ruthenacycle was then achieved using Albrecht’s method involving regioselective methylation of triazole 3

• our case column chromatography was only used once (to purify the monoazidocalix[4]arene 7), whilst the other procedure needed chromatography at each step. Introduction of the triazole moiety onto the upper rim of the calix[4]arene was then achieved with a copper-catalyzed Huisgen 1,3-dipolar

A metal-free approach for the synthesis of amides/esters with pyridinium salts of phenacyl bromides via oxidative C–C bond cleavage

• Kesari Lakshmi Manasa,
• Yellaiah Tangella,
• Namballa Hari Krishna and
• Mallika Alvala

Beilstein J. Org. Chem. 2019, 15, 1864–1871, doi:10.3762/bjoc.15.182

• new C–N bonds in the presence of transition metal catalysts [25][26][27][28][29][30][31][32][33][34]. Tang and Jiao reported copper catalyzed C–C single bond cleavage and C–N bond formation [35]. However, the transition metal catalysts and additives employed in these transformations are toxic and

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

• been given much attention in various research fields, such as the discovery of lead compounds in medicinal chemistry, or combinatorial chemistry [95][96]. Copper-catalyzed synthetic protocols Ghosh and Mishra [97] have successfully reported the synthesis of imidazo[1,2-a]pyridines in a three-component

• process oxygen (air) acts as oxidant which resulted in the oxidation of Cu(II) to Cu(III) and Cu(I) back to Cu(II) (Scheme 28). A copper-catalyzed oxidative cyclization approach has been used for the synthesis of formyl-substituted imidazo[1,2-a]pyridines 89. The remarkable feature of this method was the

• , perhaps because the α,β-unsaturated double bond affected the iodination. Mohan et al. successfully developed an efficient copper-catalyzed aerobic oxidative amination of C(sp3)–H bonds to synthesize imidazo[1,5-a]pyridine derivatives [122]. The reaction was also applicable to amino acid derivatives, as

Synthesis of 9-O-arylated berberines via copper-catalyzed C_Ar–O coupling reactions

• Qiaoqiao Teng,
• Xinhui Zhu,
• Qianqian Guo,
• Weihua Jiang,
• Jiang Liu and
• Qi Meng

Beilstein J. Org. Chem. 2019, 15, 1575–1580, doi:10.3762/bjoc.15.161

• 9-O-phenylene-bridged berberine dimer (5) was synthesized by copper-catalyzed cross-coupling of tetrahydroberberrubine and aryl iodides, followed by oxidation with I2. Keywords: arylation; berberines; cross-coupling; copper; lipophilicity; structural modification; Introduction Berberine (BBR) is a

• of 5. Conclusion We have presented the synthesis of unprecedented 9-(O)-aryl-substituted BBR through a copper-catalyzed cross coupling of tetrahydroberberrubine with aryl iodides and subsequent oxidation. The substrate scope is generally broad and various aryl groups have been introduced to the BBR

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

• crucial cyclization steps to the stable and soluble fused systems were achieved by copper-catalyzed C–S and C–Se coupling/cyclization reactions. Structures and packing motifs in the solid state were elucidated by single crystal X-ray analysis and XRD powder measurements. Comparison of the optoelectronic

• different scan rates (right). Synthesis of heterotriacenes DTT 1 and DTS 2 via copper-catalyzed cross-coupling reactions. Synthesis of selenolotriacenes DST 3 and DSS 4. Oxidative polymerization of heterotriacenes 1–4 to corresponding conjugated polymers P1–P4. Bond distances, bond angles, and distances D

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• –alkynylation (GA) [48] and an activation–alkynylation (AA) [49] sequence, which both take advantage of a copper-catalyzed alkynylation of the intermediary formed (hetero)arylglyoxyl chloride (Scheme 1). The alkynediones can be subsequently transformed, still in the same reaction vessel, to quinoxalines [48][50

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• -cyclopropylation reactions, a transformation which is similar to the Chan [45], Evans [46], Lam [47] arylation reaction of N–H and O–H containing substrates. These seminal reports greatly contributed to the synthesis of cyclopropylated compounds in addition to expanding the scope of copper-catalyzed reactions in

• agent of thiophenols (Scheme 2g). The publication of copper-catalyzed methods by Feng and Xu to S-arylate thiophenols [53] and by Guy to S-arylate alkyl thiols [54] gave us confidence to proceed ahead with our endeavour for which we herein report our results. Results and Discussion We began by testing

• only viable alternative to bipyridine (Table 1, entry 7), with other ligands commonly used in copper-catalyzed reactions such as proline and 2,2,6,6-tetramethyl-3,5-heptanedione giving yields under 15%. Reducing the number of equivalents of boronic acid 25 and sodium carbonate was found to be well

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• (aryltriazolyl)methyl galactopyranosyls 10a–n in fair to good yields (42–78% yields) via a copper-catalyzed Huisgen cycloaddition [17][32]. The resulting (aryltriazolyl)methyl galactopyranosyls 10a–n were debenzylated using palladium hydroxide on carbon in a 2:1 cyclohexene and ethanol mixture to give 1a–n in

Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

• Ayato Yamada,
• Manabu Abe,
• Yoshinobu Nishimura,
• Shoji Ishizaka,
• Masashi Namba,
• Taku Nakashima,
• Kiyofumi Shimoji and
• Noboru Hattori

Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84

• -iodo-4-nitrobenzene (3) [68]. The TEMPO moiety was introduced at the benzylic position of 5a and 5b using the copper-catalyzed radical reaction in the presence of tert-butyl hydroperoxide (TBHP) to afford 2a and 2b in 38% and 52% yield, respectively [69]. The caged TEMPOs 2a and 2b were thermally

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• to non-methylated CDs was developed. For our purposes of using the derivatives as catalysts for enantioselective reactions, we focused on α- and β-CD skeletons. Our successful approach consisted of attaching these molecules through copper-catalyzed alkyne–azide cycloaddition (CuAAC). First, the

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• -terminal groups of the peptide and their putative target. This method has been used for the macrocyclization of peptides through, for example, copper-catalyzed azide–alkyne cycloadditions [14], ring-closing olefin metathesis [13] or the formation of an aryl–aryl bond between the side chain of two aromatic

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

• , followed by a subsequent trapping of the resulting cyclopropylmetal species with an electrophilic source of oxygen (oxenoid) afforded various tetrasubstituted cyclopropanol derivatives in high diastereo- and enantiomeric ratios. Similarly, the enantioselective copper-catalyzed carbomagnesiation/oxidation

• access to non-racemic unfunctionalized cyclopropanols. Based on the pioneering work of Lautens [62], Nakamura [60], Fox [61], Gevorgyan [51] and Tortosa [84], we anticipated that an enantioselective copper-catalyzed carbometalation reaction [83][85] would be an ideal solution to access the desired

• polysubstituted enantioenriched cyclopropanols. As reported, the copper-catalyzed diastereo- and enantioselective carbomagnesiation reaction of cyclopropenes 6 was easily achieved in the presence of (R,S)-Josiphos (2.2 mol %, Scheme 7). Having in hand, diastereoisomerically pure and enantiomerically enriched

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• derivative PM75 [30]. Finally, the bromoaryl group in PO3 was engaged in a coupling with ethynylbenzene to give PO34. This latter reaction proves that the N-oxide moiety is compatible with palladium/copper-catalyzed reactions [30]. The conversion of the 5-alkoxy substituent into a nonafloxy group (as shown

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• , azides and alkynes can be visualized by the Staudinger ligation [8] or the azide–alkyne cycloaddition, that can be performed either copper-catalyzed [9][10] or strain-promoted [11][12]. Another type of reporter group that has been proven to be a valuable tool are electron-rich or strained alkenes, that

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• synthesis of a novel library of 9-alkyl-2-amino-6-triazolylpurine derivatives. Thus, copper-catalyzed azide–alkyne 1,3-dipolar cycloaddition reaction of compounds 6a–c with different para-substituted phenylacetylenes produced the expected compounds 7a–f, 8a–f and 9 (Scheme 1). The yields of 1,3-dipolar

Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions

• Nicholas L. Reed,
• Madeline I. Herman,
• Vladimir P. Miltchev and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2019, 15, 351–356, doi:10.3762/bjoc.15.30

• dioxygen for this purpose is frequently exploited to effect synthetically useful copper-catalyzed aerobic oxidation reactions [27][28]. However, the use of molecular oxygen as a terminal oxidant presents unique challenges in photoredox chemistry. Triplet dioxygen rapidly quenches the excited state of most

• of Cu(TFA)2 to 10 mol % and assessed the effect of a series of alternate oxidants that have been used in other copper-catalyzed oxidation reactions. Most failed to produce significant quantities of the desired product (Table 1, entries 1–3). As expected, the use of oxygen as a terminal oxidant

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• iron salt) [28][29][30]. Another representative transformation is the copper-catalyzed addition of Grignard reagents to secondary unprotected cyclopropenylcarbinols which proceeds with high levels of chirality transfer to afford alkylidenecyclopropanes possessing a quaternary stereocenter at C2 [31][33

• the past few years to access hetero-substituted and/or functionalized alkylidenecyclopropanes. Review [2,3]-Sigmatropic rearrangements involving cyclopropenylcarbinol derivatives Following their report on the synthesis of chiral alkylidenecyclopropanes by copper-catalyzed addition of Grignard reagents

Metal-free C–H mercaptalization of benzothiazoles and benzoxazoles using 1,3-propanedithiol as thiol source

• Yan Xiao,
• Bing Jing,
• Xiaoxia Liu,
• Hongyu Xue and
• Yajun Liu

Beilstein J. Org. Chem. 2019, 15, 279–284, doi:10.3762/bjoc.15.24

• 2009, the Daugulis group reported that benzoxazole was converted to 2-mercaptobenzoxazoles in the presence of sulfur and potassium tert-butoxide, but only one example was shown [35]. In 2017, the Lei group reported a copper catalyzed C–H mercaptalization strategy using elementary sulfur as thiol source

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

• via a radical pathway, which could take place smoothly under cartalyst- and additive-free conditions. However, the addition of the radical initiator AIBN in this reaction did not accelerate the reaction. Next, Huang’s group proposed the copper-catalyzed ring-opening and cyclization of MCPs 1 with

• . Notably, this finding was the first example for silver-catalyzed regioselective C2-alkylation of heterorarenes with primary alkyl radicals, generated from cyclopropanols through a radical ring-opening process. Lopp’s group also reported an efficient approach for copper-catalyzed ring-opening and

• copper-catalyzed ring-opening and trifluoromethylation or trifluoromethylthiolation of cyclopropanols 91 for the synthesis of β-CF3/SCF3-substituted ketones 113 (Scheme 24) [102]. This strategy was also applied to the synthesis of LY2409021. The LY2409021 was a glucagon receptor antagonist and used in

Copper(I)-catalyzed tandem reaction: synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and alkynes

• Muhammad Israr,
• Changqing Ye,
• Munira Taj Muhammad,
• Yajun Li and
• Hongli Bao

Beilstein J. Org. Chem. 2018, 14, 2916–2922, doi:10.3762/bjoc.14.270

• Academy of Sciences, 155 Yangqiao Road West, Fuzhou, Fujian 350002, P. R. China University of Chinese academy of Science (UCAS), Beijing 100190, P. R. China 10.3762/bjoc.14.270 Abstract A copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction for the synthesis of 1,4-disubstituted 1,2,3-triazoles

• research and synthesis of functionalized compounds that have applications in medicinal chemistry, drug discovery, materials chemistry, and as well as in bioconjugates [2][3][4][5][6][7][8][9][10][11][12]. The copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction [13][14][15][16][17][18][19][20][21

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• numerous organic compounds [24][25][26][27][28]. The amazingly rapid and broad permeation of 1,2,3-triazoles to multidisciplinary areas can majorly be attributed to the occurrence of robust synthetic methods toward this heterocycle. The copper-catalyzed click [3 + 2] cycloaddition of azides and alkynes [29

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• (6) ring threaded onto a water-soluble axle [80]. The rotaxane was synthesized in 23% yield by a template/capping strategy where one stopper is attached using copper-catalyzed azide–alkyne click chemistry after the formation of the precursor pseudorotaxane. Due to the hydrophobic effect, the neutral

• = 6,300 M−1) which is embedded in an axle molecule with two azide residues. The second station, the dihydroxynaphthalene moiety (green), displays a lower association constant of Ka = 5,800 M−1. The pseudorotaxane precursor was end-capped by a double copper-catalyzed azide–alkyne click reaction in CH2Cl2

• in 2008 (Figure 20) [97]. The tripodal [4]rotaxane 22, consisting of a trivalent axle, in which each arm is encircled by a host molecule 3, was synthesized by a copper-catalyzed click protocol in 40% yield. A combination of electrochemical and spectroscopic methods was used to investigate a potential

Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles

• James T. Fletcher,
• Matthew D. Hanson,
• Joseph A. Christensen and
• Eric M. Villa

Beilstein J. Org. Chem. 2018, 14, 2098–2105, doi:10.3762/bjoc.14.184

• recent years [1][2][3][4][5][6][7], enabled by efficient preparation from the Sharpless–Meldal copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction [8][9][10][11]. Click chelators with a variety of N-donor units connected at the 4-triazolyl position have been reported, including pyridine [12][13

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• nitrile is slower compared to the unstabilized 9b. The Stoltz and co-workers reported the preparation of a series of PHOX ligands using Buchwald’s copper-catalyzed C–P bond construction [48][49]. This reaction allows the Ullmann coupling of aryl halides with secondary phosphines to afford tertiary