Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• with molecular oxygen can be used to perform benzylic oxidations [20]. The aerobic copper-catalyzed α-oxygenation of 2-arylthioacetamides was reported by Moghaddam [21]. In this transformation CuCl2 and K2CO3 in DMF were used to produce α-ketoarylthioacetamides. The coupling of 2-arylacetaldehydes with

Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

• Yan Li,
• Xue Zhou,
• Guangfan Zheng and
• Qian Zhang

Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293

• atmosphere at 70 °C for 10.0 h, the desired aminooxygenation product 3a was obtained in 39% yield (Table 1, entry 1). A variety of copper salts such as CuCl, CuBr, CuI, [(CH3CN)4Cu]PF6, CuCN, Cu(acac)2, Cu(OAc)2, CuBr2 and CuCl2 were examined (Table 1, entries 2–10). We found that CuCl2 was the most

• (1.2 mmol, 4.0 equiv), 2 (0.3 mmol, 1.0 equiv), CuCl2 (10 mol %), DCM (2.0 mL), N2, 70 °C, 10.0 h. Isolated yields. Copper-catalyzed radical aminooxygenation reaction of styrenes. The plausible mechanism. Selective reduction of the aminooxygenation product. The optimization of reaction conditionsa

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

• and benzene C–H bonds. Copper-catalyzed C–H amination/amidation of quinoline N-oxides. Copper-catalyzed aldehyde formyl C–H amidation. Copper-catalyzed formamide C–H amidation. Copper-catalyzed sulfonamidation of vinyl C–H bonds. CuCl2-catalyzed amidation/sulfonamidation of alkynyl C–H bonds. Cu(OH)2

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

• . These kinds of reactions were later systematically investigated by Xie and co-workers [42]. By using Cu(OAc)2 as the catalyst and CuCl2 as the chlorine source in DCE, a broad array of 5-chloro-8-acylaminoquinolines 13 were obtained via the selective 5-chlorination of 8-amidoquinolines 12 (Scheme 8

• halogenations. In 2006, Gusevskaya and Menini [47][48] reported a highly selective method for C–H chlorination and bromination of various phenols under aerobic, copper-catalyzed conditions. As displayed in Scheme 11, the reaction of phenols 19 with 2 equiv of LiCl in the prensence of O2 and 12.5 mol % CuCl2 in

• chlorination of 33 was not observed under the corresponding chlorination conditions, probably because the decomposition of CuCl2 into CuCl and Cl2 is much less favorable. The mechanism of the chlorination was not yet clear, but presumably the reaction was initiated by electron transfer from the arenes to the

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

• . This two-step sequence converts commercially available starting materials into alpha-tetrasubstituted amines via three reactions. It is important to note that triazole 6a is formed in 65% overall yield (Scheme 3). The first step simply involves heating 5 mol % CuCl2 with equimolar amounts of three

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

• -workers [96] demonstrated a macrocylization, with an inbuilt conformation control element to form rigid cyclophanes through the Glaser–Hay coupling. In this regard, diynes 59a–c were treated with CuCl2 and TMEDA in the presence of oxygen to afford the cyclized products 61a–c (Scheme 9). Intramolecular

Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole)

• Friederike Danneberg,
• Alice Ghidini,
• Plamena Dogandzhiyski,
• Elisabeth Kalden,
• Roger Strömberg and
• Michael W. Göbel

Beilstein J. Org. Chem. 2015, 11, 493–498, doi:10.3762/bjoc.11.55

• include metal salts like CuCl2 or HgCl2 and carbodiimides such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) or N,N’-diisopropylcarbodiimide (DIC) [17]. Another method developed by Lipton et al. uses Mukaiyama's reagent (2-chloro-1-methylpyridinium iodide) to prepare guanidines in high yields

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• ∙5H2O (Cu2+ used for decarboxylative CuAAC) at 120 °C for 12 h. It failed to undergo the oxidative dehydrogenative coupling reaction and the triazole derivative 3a was isolated in 79–82% yield (Table 1, entries 1–1b). A similar reaction sequence was performed with different copper salts such as CuCl2

Loose-fit polypseudorotaxanes constructed from γ-CDs and PHEMA-PPG-PEG-PPG-PHEMA

• Tao Kong,
• Lin Ye,
• Ai-ying Zhang and
• Zeng-guo Feng

Beilstein J. Org. Chem. 2014, 10, 2461–2469, doi:10.3762/bjoc.10.257

• ) was refluxed with p-toluenesulfonyl chloride and distilled under vacuum. Copper(I) chloride (Cu(I)Cl) was prepared from CuCl2, purified by stirring in hydrochloric acid, washed with methanol and finally dried under vacuum prior to use. CH2Cl2 was stirred with CaH2 and distilled under reduced pressure

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• synthetic construction of substituted tetrahydrofurans. Recently, we have described a novel type of PdCl2/CuCl2-catalysed bicyclisation reaction of α-O-benzyl-protected sugar-derived alkenitols A, that provided 2,5-dioxabicyclo[2.2.1]heptanes B with high 1,4-threo-selectivity (Scheme 1) [22][23]. In this

• bicyclisation of α-O-benzyl-protected polyols bearing a terminal alkene moiety [22]. Thus, the reactions incorporating the PdII–Pd0 catalytic cycle (Scheme 6) were carried out using PdCl2 (0.1 equiv) as a catalyst, CuCl2 (3 equiv) as a reoxidant, NaOAc (3 equiv) as a buffer in AcOH at room temperature (Table 1

• . The further synthetic studies toward ocellenynes are currently underway. Examples of naturally occurring tetrahydrofurans. Structures of C5-alkenitols. Structure of 43. An ORTEP [44] view of crystal and molecular structure of 53. PdCl2/CuCl2-catalysed bicyclisation of unsaturated polyols [22

Synthesis of ethoxy dibenzooxaphosphorin oxides through palladium-catalyzed C(sp²)–H activation/C–O formation

• Seohyun Shin,
• Dongjin Kang,
• Woo Hyung Jeon and
• Phil Ho Lee

Beilstein J. Org. Chem. 2014, 10, 1220–1227, doi:10.3762/bjoc.10.120

• )arylphosphonates by using L-Selectride (Scheme 2). The C–H activation/C–O formation of 2-(phenyl)phenylphosphonic acid monoethyl ester (1a) was examined with a variety of oxidants and bases in the presence of Pd(OAc)2. A multitude of oxidants such as K2S2O8, BQ, benzoyl peroxide, PhI(TFA)2, Cu(OAc)2, CuCl2, CuBr

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• chlorination such as the use of N-chlorosuccinimide or, as reported more recently, CuCl2 produced, in the latter case, 7-6 with full stereocontrol (Scheme 7-iii) as unambiguously determined by X-ray diffraction analysis [31]. The addition of nucleophilic species (amine, alcohol, alkyllithium, etc.) on 7-6 or

The influence of intraannular templates on the liquid crystallinity of shape-persistent macrocycles

• Joscha Vollmeyer,
• Ute Baumeister and
• Sigurd Höger

Beilstein J. Org. Chem. 2014, 10, 910–920, doi:10.3762/bjoc.10.89

• (insoluble) byproducts. However, the unexpected moderate yield in the template-directed synthesis suggests that the material may slowly decompose under the cyclization condition. Since other protocols (e.g., CuCl/CuCl2 in pyridine) did not give reproducible results, we tested whether high-dilution conditions

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

• summarized in Table 1, revealed the supremacy of copper catalysts in this particular reaction over the others; CuCl2 appeared to be the catalyst of choice (Table 1, entries 8–32). In order to explore the effect of ligands, a number of phosphines, bis-oxazocines, pyrazolyl-pyrimidines and phenanthroline

• , entries 21–28). Bis-oxazocines and pyrazolyl-pyrimidines on the other hand showed some promising results (Table 1, entries 29 and 30). However, both in terms of yield and cleaner reaction profile, 1,10-phenanthrolines (L1, L2) were identified as the best partners for CuCl2 (Table 1, entries 31 and 32

• ). Thus, the 1,3-dipolar cycloaddition reaction between 9a (1 equiv) and 4a (1.1 equiv) yielded 94% of 10a within 3 h, when 5 mol % CuCl2 and 5 mol % of either L1 or L2 were employed with DBU as the base in acetonitrile solvent at 65 °C. This was taken as the best conditions to perform the reaction. The

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• lifetimes of gold(III) chloride catalysts in A3-MCRs by the addition of inexpensive and commercially available reagents such as CuCl2 and TEMPO [36]. The proposed rationale seems simple and elegant: the reduction of gold(I) (real active species) to colloidal Au(0) was responsible for the deactivation of the

• catalyst. CuCl2 was able to reoxidize Au(0) to Au(I) which increased the number of turnovers (up to 33 cycles). The Cu(I) was oxidized back to Cu(II) by TEMPO. Also O2 had a role in this cycle, probably as a reoxidizing agent for TEMPO. Another challenge in an A3-coupling strategy is its transformation in

Aminofluorination of 2-alkynylanilines: a Au-catalyzed entry to fluorinated indoles

• Antonio Arcadi,
• Emanuela Pietropaolo,
• Antonello Alvino and
• Véronique Michelet

Beilstein J. Org. Chem. 2014, 10, 449–458, doi:10.3762/bjoc.10.42

• gold catalysts such as gold(III) species presented interesting results for the reaction beside lower yield than gold(I) catalyst (Table 1, entries 14–16 vs entries 9 and 13). Other transition metal catalysts such as PdCl2, PtCl2, CuCl2·2H2O, RuCl3·2H2O, or AgNTf2 were also tested, but did not give the

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• start with the same for the synthesis of dasyclamide (6). As explained in Scheme 5 attempts to get enamide 22 by reductive dehydroxylation of compound (±)-18 using NaBH4/CuCl2·2H2O or Al-NiCl2·2H2O [16][17][18] and reductive deacetoxylation of compound (±)-21 using NaBH4/t-BuOH or LiBEt3H, THF [19][20

• ][21] did not yield fruitful results. These failures pushed us to explore the dehydroxylation or deacetoxylation reaction using a simpler precursor (±)-16. However, attempts to dehydroxylate the Baylis–Hillman adduct (±)-16 with NaBH4/CuCl2·2H2O [17] and Al-NiCl2·2H2O proved unsuccessful hence, we

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

• copper(I) complexes, which are highly active in CuAAC reactions on water or under neat conditions (Scheme 7) [130]. Albeit no single crystals of the copper(I) complex shown in Scheme 7 could be grown, NMR measurements as well as a single crystal X-ray structure of an analogous C186tren-complex with CuCl2

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• of secondary alcohols. The efficiency of the process relied on the stabilization of cationic [Au(III)] species by using a catalytic amount CuCl2 (16 mol %), which prevented gold deactivation via parasitic reductive side reactions [30][31]. Moreover, recent advances in the alkoxylation of olefins

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

• used, (Table 2, entry 1), copper(II) 2-ethylhexanoate, Cu(ehex)2, serves as an effective oxidant in transforming 1b to 3 in a yield that is comparable to the process promoted by Cu(OAc)2 (compare Table 2, entry 2 to entry 3). Noticeable amounts of 2 are also generated in this reaction. When CuCl2 is

• employed to oxidize 1b, only ring-expanded ketones 4 and 14 are produced along with a lesser amount of chloro ketone 15, and competitive formation of 2 and 3 does not occur (Table 2, entry 4). An increase in the amount of CuCl2 causes a slight increase in the conversion of 1b and the total yield of ring

• -expanded products 4 and 14 (compare Table 2, entry 5 to entry 4). Interestingly, CuCl2 (1.1 equiv) could also promote the reaction of silyl ether 1a to produce 4 (23%), 14 (4%) and 15 (3%) at 89% conversion of 1a. Although the origin of 15 is uncertain, one possibility is that it is formed by halogen

Copper-catalyzed aerobic aliphatic C–H oxygenation with hydroperoxides

• Pei Chui Too,
• Ya Lin Tnay and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2013, 9, 1217–1225, doi:10.3762/bjoc.9.138

• -phenanthroline (1,10-phen) accelerated the reaction (Table 1, entries 2 and 3). The reactions with CuCl2 (Table 1, entry 4) as well as CuCl (Table 1, entry 5) resulted in comparable results with that by Cu(OAc)2. Further optimization of the reaction conditions by the solvent screening (Table 1, entries 6–11

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• ][47]. We initiated our efforts by exposing aminal 7 to stoichiometric amounts of CuCl2 in acetonitrile under a nitrogen atmosphere, which led to the formation of 2 in 81% yield (Table 1, entry 1). To improve the efficiency of the process, catalytic conditions were subsequently evaluated. When aminal 7

• was heated under reflux in an oxygen atmosphere and in the presence of 20 mol % of CuCl2, 2 was only observed in trace amounts; deoxyvasicinone (4) and peroxide 8 were also formed as products. Switching the catalyst to Cu(OAc)2 led to a 15% yield of the desired product 2, but the process was still

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

• calcium hydride. Toluene was dried through distillation and stored under nitrogen. DMF was distilled over calcium hydride and stored under nitrogen. CuCl2 (Aldrich, purity of 99.999% metal basis), K3PO4 (98%), and pyrazole (98%) were stored under air- and moisture-free conditions. All other chemicals were

• to a maximum of 25% yield. The kinetic investigation was carried out by varying the concentration of one component and keeping the rest of the components constant under standard reaction conditions; pyrazole (136 mg, 2 mmol, 1 equiv), iodobenzene (334 μL, 1.5 equiv), CuCl2 (40 μL, 0.01 mol %) K3PO4

• (849 mg, 2 equiv), DMDETA (26 mg, 0.2 mmol, 10 mol %) and dodecane (50 μL, 0.22 mmol). Into a microwave vial was added pyrazole (A mmol) and K3PO4 (B mmol). The vial was sealed and a CuCl2 solution (C μL, 5 mM in dry THF) was added. The THF was removed by three cycles of vacuum followed by nitrogen

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• switching reaction solvent and temperature (Scheme 27) [83]. The unforeseen formation of alkenylation/esterification products plausibly arises from a direct intervention of dimethylformamide or dimethylacetamide used as the solvent. The presence of CuCl2 slows the β-hydride-elimination process from the σ