Copper-mediated Reaction Research Articles

Regiospecific synthesis of 2,6-bis-indazol-1-ylpyridines from 2,6-bis-hydrazinopyridine

The synthesis of 2,6-bis-hydrazonopyridines from 2,6-bis-hydrazinopyridine and the conversion of these bis-hydrazones into 2,6-bis-indazol-1-ylpyridines were studied. The conversion of bis-haloarylhydrazones to bis-indazoles was systematically optimized using iron and copper mediated reactions and various bases and ligands. By varying solvent, base, transition metal, and ligand, a novel regiospecific route to the 2,6-bis-indazol-1-ylpyridine class of ligands was developed.

Selectivity in metal ions mediated C–N bond formation reactions of 8‐aminoquinoline derivatives

Cyclisation reactions via C–N bond formation of 2‐bromo‐N‐(quinolin‐8‐yl)propanamide (I) and 2‐bromo‐N‐(quinolin‐8‐yl)acetamide (II) are facilitated by metal salts such as copper (+2), nickel (+2) perchlorate or nitrate and palladium (+2) acetate. Nickel (+2) perchlorate mediated reaction of I and II resulted in C–N bond formation to give corresponding perchlorate salts of three fused six‐membered heterocyclic rings. The copper (+2) mediated reactions are found to be solvent dependent for I, but independent for II. Copper mediated reaction of II gave cyclised product analogous to the one obtained from reaction of II with nickel (+2) perchlorate in methanol or ethanol. But the reaction of I with copper (+2) perchlorate in methanol gave C–N bonded methoxylated cyclised product. This reaction took place in two steps, cyclisation followed by methoxylation. The source of methoxy group is confirmed to be from methanol by deuterium labelling experiments. Whereas similar copper mediated reaction of I in ethanol led to nucleophilic substitution of bromide ion by ethoxide. The structures of the salts of fused heterocyclic compounds were determined and their fluorescence emissions were studied. The large difference in fluorescence emission of compound V formed from copper mediated reaction in ethanol from the compound VI formed from nickel mediated reaction in methanol or ethanol, this feature can be used to distinguish nickel (+2) and copper (+2) ions. The reaction of II with palladium (+2) acetate resulted in the formation of C–N bond to yield the corresponding heterocycle as bromide salt; without anion exchange. Copyright © 2011 John Wiley & Sons, Ltd.

Green Recyclable Supported-Metal Catalyst for Useful Organic Transformations

One of the major challenges confronted by modern chemists is the development of sustainable chemistry to maintain environmental chastity. With this perspective in mind, heterogeneous organometallic chemistry has been intensively investigated in recent times. The advantages offered by the heterogeneous catalysts are ease of separation of product, reusability of the catalyst, improved efficiency, eco-compatibility and economic feasibility. This review focuses on the application of heterogeneous catalysis in different synthetic approaches. The review consists of six units namely, palladium mediated reactions, copper mediated reactions, ruthenium mediated reactions, rhodium mediated reactions, multimetallic catalytic systems and supported catalysts for asymmetric transformations, which cover almost all sorts of latest developments in organic transformations promoted by immobilized transition metal catalysts. The discussion not only involves the illustration of efficiency and reusability but also highlights the scope and limitations associated with the supported catalytic systems from a green chemistry standpoint.

A copper-mediated cyclization reaction of hydrazine with enediynones providing pyrazolo[1,5-a]pyridines

2,7-Disubstituted pyrazolo[1,5-a]pyridines were synthesized in good chemical yields by the reaction of enediynones with hydrazine, followed by addition of copper chloride. This reaction can tolerate many functional groups.

ChemInform Abstract: Methods for Vinyl Ether Synthesis

AbstractReview: ca. 100 refs.

ChemInform Abstract: Copper(I) Salt Mediated Arylation of Phosphinyl-Stabilized Carbanions and Synthetic Application to Heterocyclic Compounds.

The copper-mediated reaction of phosphinyl-stabilized carbanions 2a-c with aryl halides 1a-i in DMF or HMPA produced (arylmethyl)phosphonates 3-11 in good yields. Similar treatment of N-(2-iodophenyl)- and N-(2-iodophenyl)-N-methyl-α-(diethoxyphosphinyl)acetamides (12 and 14) led to 2-[(diethoxyphosphinyl)methyl]benzoxazole (13) and 1-methyl-3-(diethoxyphosphinyl)oxindole (15) in 71 and 85% yields, respectively. 4-(Ethorycarbonyl)-3,4-dihydroisoquinoline N-oxide (33) was synthesized by the reaction of ethyl α-(o-formylphenyl)acrylate (31), derived from 6 and paraformaldehyde, with hydrorylamine. The cycloaddition of 33 to olefins such as dimethyl maleate, methyl acrylate, and styrene was studied

ChemInform Abstract: Diamine Ligands in Copper‐Catalyzed Reactions.

AbstractReview: 229 refs.

Methods for Vinyl Ether Synthesis

Deceptively simple as the structure may appear, there is no singlegeneral method by which to synthesize the vinyl (enol) ether functionality.However, there exists a diverse array of complementary methods bywhich this functionality has been achieved. This review presentsthe scope and limitations of these methods according to reactiontype, specifically via ether modifications, elimination reactions,carbonyl olefinations, alcohol additions and carbon-oxygencoupling reactions. 1 Introduction 2 Modification of Ethers 2.1 Vinyl Ether Substrates 2.2 Allyl Ether Substrates 2.3 Acetylenic Ether Substrates 3 Elimination Reactions 3.1 Halide and Pseudohalide Leaving Groups 3.2 Alkoxide and Silyloxide Leaving Groups 3.3 Selenium Oxidation-Elimination 4 Olefination of Carbonyl Substrates 4.1 Phosphorus Reagents 4.2 Silicon Reagents 4.3 Sulfur Reagents 4.4 Metal Carbene Reagents 5 Addition of Alcohols 5.1 Alkyne Substrates 5.2 Dicarbonyl Substrates 6 Carbon-Oxygen Coupling Reactions 6.1 Palladium-Mediated Reactions 6.2 Copper-Mediated Reactions 7 Conclusion

Trifluoromethylation of Organic Compounds and Related Reactions

This review concentrates on trifluoromethylation and related reactions from the authors’ group. Mainly, our new rhodium complex catalyzed synthesis of trifluoromethyl and other fluorine compounds will be discussed. However, initially we would like to discuss the origins and development of this reaction. Thus, trifluoromethylation of aromatic and aliphatic halides with trifluoromethyl iodide in the presence copper powder will be discussed first, and then the application of this copper-mediated reaction to ethyl bromodifluoroacetate for the synthesis of difluoromethylene compounds will be presented. The investigation of the mechanism of this reaction led us to the Michael addition of the (ethoxycarbonyl)difluoromethyl group to α,β-unsaturated carbonyl compounds. To improve this reaction, we examined the rhodium-catalyzed Michael reaction, and found that the fluorine substituent was introduced surprisingly not to the β-position but to the α-position. This reaction could be used to introduce other fluoroalkyl groups, including­ the trifluoromethyl group, to the α-position of almost all Michael acceptors. Furthermore, this reaction was developed for the introduction of the trifluoromethyl or other fluoroalkyl groups into the α-position of ketones or carboxylic acid derivatives through silyl­ enol ethers or ketene silyl acetals.

Synthesis of Functionalized Aryliron Complexes [CpFe(CO)2Ar] by Copper-Mediated Transmetalation between [CpFe(CO)2I] and Aryltin Reagents

Transmetalation between [CpFe(CO)2I] and aryltin reagents in the presence of copper salts yields the corresponding aryliron complexes [CpFe(CO)2Ar]. The high functional group compatibility of this copper-mediated reaction enables us to obtain [CpFe(CO)2Ar] having an acetyl or formyl group, which cannot be prepared by the previous methods with arylzinc or arylboron reagents under palladium catalysis.

Highly Regiospecific Synthetic Approach to Monobay-Functionalized Perylene Bisimide and Di(perylene bisimide)

Monobay-dichlorinated perylene bisimide and diperylene bisimide have been regiospecifically synthesized from tetrachlorinated perylene bisimide in different copper-mediated reaction conditions, thus opening a new avenue to their monobay-functionalization.

The First Total Synthesis of Kynapcin-24 by Palladium Catalysis

The synthesis of kynapcin-24, which can be isolated from the Korean mushroom Polyozellus multiflex Murr, is achieved in 12% overall yield from commercially available 3,4-dihydroxybenzaldehyde by a route in which the longest linear sequence is only 14 steps. The key transformations in the synthesis are copper-mediated and palladium-catalyzed coupling reactions of the iodide 3-iodo-5,6-diisopropoxy-2-[(tetrahydropyran-2-yloxy)methyl]benzofuran with the corresponding stannane 5,6-diisopropoxy-2-[(tetrahydropyran-2-yloxy)methyl]-3-(tributylstannyl)benzofuran, and a 5-endo-dig iodocyclization of a (hydroxyphenyl)propargyl ether.

First cross-coupling reactions on halogenated 1 H-1,2,4-triazole nucleosides

The halogenated 1 H-1,2,4-triazole glycosides 6– 10 were synthesized by BF 3-activated glycosylation of 3(5)-chloro-1,2,4-triazole ( 2 ), 3,5-dichloro-1,2,4-triazole ( 3 ), 3,5-dibromo-1,2,4-triazole ( 4 ), and 3(5)-bromo-5(3)-chloro-1,2,4-triazole ( 5 ) with 1,2,3,4-tetra- O-pivaloyl-β- d-xylopyranose ( 1 ). The β-anomeric major products 3-chloro-1-(2,3,4-tri- O-pivaloyl-β- d-xylopyranosyl)-1,2,4-triazole ( 6β ), 3,5-dichloro-1-(2,3,4-tri- O-pivaloyl-β- d-xylopyranosyl)-1,2,4-triazole ( 7β ), and 3,5-dibromo-1-(2,3,4-tri- O-pivaloyl-β- d-xylopyranosyl)-1,2,4-triazole ( 8β ) were used as starting materials for transition metal catalyzed C–C-coupling reactions. Arylations of the triazole ring of 7β , and 8β were successful in 5-position with phenylboronic acid, 4-vinylphenylboronic acid, and 4-methoxyphenylboronic acid, respectively, under Suzuki cross-coupling conditions (products 11– 17 ). Moreover, a Cu-catalyzed perfluoroalkylation of 8β is reported with 1-iodo-perfluorohexane yielding 3-perfluorohexyl-1-(2,3,4-tri- O-pivaloyl-β- d-xylopyranosyl)-1,2,4-triazole ( 18 ). Compound 18 was depivaloylated to the trihydroxy derivative 19 . The copper-mediated reaction of 8β with Rupert's reagent gave the bis(3-bromo-1-(2,3,4-tri- O-pivaloyl-β- d-xylopyranosyl)-1,2,4-triazol-5-yl) ( 20 ).

Copper elicits an increase in cytosolic free calcium in cultured tobacco cells

At concentrations greater than 0.1 mM, CuSO 4 provoked a rapid and sustained increase in the cytosolic free Ca 2+ concentration ([Ca 2+] cyt), in tobacco suspension culture cells expressing apoaequorin, a Ca 2+-sensitive photoprotein. The increase was suppressed by treatment with LaCl 3, indicating that the increase is due to an influx of Ca 2+ from the apoplast through plasma membrane Ca 2+ channels. Although stimulation of H 2O 2 production upon the CuSO 4 treatment (0.1 mM) was observed, treatment with catalase did not inhibit the increase in [Ca 2+] cyt, and treatment with H 2O 2 dose-dependently suppressed or delayed the increase. These results suggested that active oxygen species generated through copper-mediated reactions, or copper-mediated oxidative damages to plasma membrane, are not responsible for the increase. Treatment with sulfhydryl reagents, which alkylate or oxidize thiol groups, or acidification of the culture medium suppressed the increase in [Ca 2+] cyt. These results demonstrated that copper causes an influx of Ca 2+ through plasma membrane Ca 2+ channels, and that plasma membrane thiol groups play an important role in activating the Ca 2+ channels.

Stereoselective synthesis of ( Z)-fluoroalkenes directed to peptide isosteres: copper mediated reaction of trialkylaluminum with 4,4-difluoro-5-hydroxyallylic alcohol derivatives

Copper mediated alkyl-transfer reaction of trialkylaluminum (R 3Al) with ( E)-4,4-difluoro-5-hydroxyallylic alcohol derivative smoothly proceeded to give the corresponding 2-alkylated 4-fluoro-5-hydroxyhomoallylic alcohol derivative with completely Z and 2,5- syn selective manner. Regio- and stereoselective conversion of the C5-hydroxyl group of the fluoroolefin thus obtained to amino group could be achieved through one-pot mesylation and azidation reaction.

Efficient copper-mediated reactions of nitrenes derived from sulfonimidamides.

[reaction: see text] Sulfonimidamides lead efficiently to nitrenes and have been converted to sulfimides, sulfoximines, and aziridines in good yields, through a copper-mediated multicomponent reaction. The stereogenic sulfur atom and the trivalent nitrogen atom present in the molecules open the way to asymmetric synthesis, whose first results are presented.

Reactions of Ethyl Bromodifluoroacetate in the Presence of Copper Powder.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Modern Synthetic Methods for Copper‐Mediated C(aryl)—O, C(aryl)—N, and C(aryl)—S Bond Formation

AbstractFor Abstract see ChemInform Abstract in Full Text.

Modern synthetic methods for copper-mediated C(aryl)[bond]O, C(aryl)[bond]N, and C(aryl)[bond]S bond formation.

The copper-mediated C(aryl)[bond]N, C(aryl)[bond]O, and C(aryl)[bond]S bond formation is an important transformation and has been developed to include a wide range of substrates. This Review highlights the recent developments in the copper-mediated (both stoichiometric and catalytic) reactions of aryl boronic acids, aryl halides, iodonium salts, siloxanes, stannanes, plumbanes, bismuthates, and trifluoroborate salts as aryl donors. In particular, the recent introduction of boronic acids as reaction partners in both O- and N-arylation has been a significant discovery and will occupy centre-stage in this review. Clear improvements can be obtained by the correct choice of copper source, base, ligands, and other additives. Mechanistic investigations should provide insight into the catalytically active species, which would aid in the development of milder, more-efficient methods.

Copper‐Mediated Coupling Reaction of Kinetically Stabilized 1‐Methyl‐2‐phosphaethenyllithiums Involving an Isomerization to a 3‐Phospha‐2‐propenyllithium Derivative.

AbstractFor Abstract see ChemInform Abstract in Full Text.