- 15.1 Copper-catalysed Coupling Reactions
- 15.1.1 Ullman-type Couplings
- 15.1.2 Glaser-type Couplings
- 15.1.3 Sonogashira Couplings
- 15.1.4 Coupling with Boronic Acids
- 15.1.5 Enantioselective Allylic Alkylations
- 15.2 Copper-catalysed Addition Reactions
- 15.2.1 Enantioselective Conjugate Additions
- 15.2.2 Azide–Alkyne Cycloadditions
- 15.2.3 Hydroboration and Carboboration
- 15.3 Copper-catalysed Oxidative Reactions under Molecular Oxygen
- 15.3.1 Oxidation of Alcohols and Naphthols
- 15.3.2 Oxidation of Carbonyl Compounds
- 15.3.3 Aromatic C–H Bond Functionalisations
- 15.4 Copper-catalysed Reactions Utilising Carbon Dioxide
- 15.4.1 Carbon–Carbon Bond-forming Reactions with Carbon Dioxide
- 15.4.2 Carbon–Oxygen Bond-forming Reactions with Carbon Dioxide
- 15.4.3 Reduction of Carbon Dioxide to Formates and Carbon Monoxide
- 15.5 Conclusions
Chapter 15: Copper-based Catalysts
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Published:16 Nov 2015
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Special Collection: 2015 ebook collection , ECCC Environmental eBooks 1968-2022 , 2011-2015 physical chemistry subject collectionSeries: Green Chemistry Series
Y. Tsuji and T. Fujihara, in Sustainable Catalysis: With Non-endangered Metals, Part 2, ed. M. North and M. North, The Royal Society of Chemistry, 2015, ch. 15, pp. 1-40.
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Copper is one of the ubiquitous and inexpensive metals. In classical methodology, a stoichiometric amount of copper species has been utilised for organic synthesis. However, the development of copper-catalysed reactions is most important from the viewpoint of sustainability and green chemistry. This chapter summarises valuable homogeneous copper-catalysed reactions such as crosscouplings, oxidation, fixation of carbon dioxide, and others.
15.1 Copper-catalysed Coupling Reactions
Copper complexes realise a wide variety of coupling reactions. Some of them have been known for a long time. However, copper salts are easily aggregated and deactivated, so the efficiency of the reactions was often low. In order to generate an active species realising catalytic reactions, ligands on copper centres play an important role. This chapter starts with two classic coupling reaction, i.e., Ullman-type and Glaser-type coupling reactions, then followed by more recent reactions.
15.1.1 Ullman-type Couplings
Efficient and selective coupling of aryl and vinyl halides with N, O, and C nucleophiles are indispensable and important transformations to construct useful compounds. Over 110 years ago, Ullmann and Goldberg found the synthesis of aryl ethers and aryl amines by C–N and C–O bond-forming reactions in the presence of copper powder or copper salt.1 However, even until the late twenty century, these transformations often required stoichiometric amounts of copper reagent in polar solvents (such as N-methylpyrrolidone, nitrobenzene, and dimethylformamide) at high reaction temperatures (>200 °C). These harsh reaction conditions frequently led to severe limitations in the general use of the reaction due to limited applicable substrates and low product yields.
The situation was dramatically improved by using an appropriate auxiliary ligand for the copper centre.2 These ligands prevent copper aggregation, realising good catalyst solubility and stabilising active catalyst species. It was reported that 1,10-phenanthroline (phen) was a particularly effective ligand in the copper-catalysed reactions of aromatic amines with aryl iodides to afford arylamines in good yields in three hours (Scheme 15.1).3 The reactions can be carried out even in refluxing toluene. Subsequently, a wide variety of chelating ligands (N–N, O–O, and N–O) such as diamines, diols, diketones, and amino alcohols were found to be highly efficient with copper catalysts.2c–f In the presence of a catalytic amount of copper iodide and chelating ligands, aliphatic amines (Scheme 15.2)4a and amides (Scheme 15.3)4b are catalytically arylated with aryl iodides under relatively milder reaction conditions. N-Heterocycles are also alkenylated with alkenyl iodides (Scheme 15.4)4c,d Primary and secondary alkylamines are arylated with aryl halides even at room temperature employing β-diketones5a or 1,1′-bi-2-naphthol5b as a ligand.
Copper-catalysed reaction of an aliphatic amine with an aryl iodide.
Proper choice of chelating ligand is also a key to realise efficient catalytic C–O bond formations. Diaryl ethers are afforded from phenols and aryl iodides in the presence of copper catalysts with N–O and N–N chelating ligands (Scheme 15.5).6a,b When phenols are arylated with aryl bromides bearing directing groups at the ortho position in the presence of copper iodide and N,N-dimethylglycine as a ligand, highly efficient C–O bond formation proceeds even at room temperature (Scheme 15.6).6c
C–O bond-forming reaction of an aryl iodide with a phenol in the presence of copper catalysts.
C–O bond-forming reaction of an aryl iodide with a phenol in the presence of copper catalysts.
Copper-catalysed coupling reaction of a phenol with an aryl bromide.
Ullmann found that aryl halides underwent self-dimerisation (carbon–carbon bond-forming reaction) to afford the corresponding dimer (biaryls) in the presence of a stoichiometric amount of copper powder at high temperature (>200 °C).7a Usually, even with highly activated copper powder or copper(i) salts, the carbon–carbon bond-forming reaction must be carried out at over 100 °C. Thus, this transformation was not so valuable as a synthetic method. However, copper(i) thiophene 2-carboxylate (CuTC) was found to be a highly efficient copper reagent to provide biaryls from aryl iodides and bromides at room temperature (Scheme 15.7).7b
The mechanism of Ullmann-type coupling reactions seems to be complicated. Density-functional calculations on the arylation reactions of methanol and methylamine with iodobenzene have been carried out,8 in which copper(i) complexes bearing β-diketone or 1,10-phenanthroline as a ligand are employed as catalysts. The results suggest that the arylation occurs via single-electron transfer (SET) or iodine atom transfer, depending on the electron-donating abilities of the ligand and nucleophile.
15.1.2 Glaser-type Couplings
In 1869, Glaser found that copper(i) phenylacetylide prepared from phenylacetylene and a copper salt gave the acetylene dimer by air oxidation (Scheme 15.8).9a This reaction system was heterogeneous and the reaction was rather slow. In addition, the potentially explosive copper acetylides had to be isolated before the oxidation. However, copper iodide bearing pyridine as a ligand9b as well as copper(i) chloride having pyridine or TMEDA (N,N,N′,N′-tetramethylethylenediamine) as a ligand9c,d form a homogeneous catalyst system, and copper acetylides generated in situ can be utilised in the oxidation.10a Thus, terminal alkynes are oxidatively dimerised to buta-1,3-diynes with copper(i) under oxygen at room temperature (Scheme 15.9).10b An excess amount of copper(ii) with terminal alkynes also successfully afforded 1,3-diynes (Scheme 15.10).10c The present oxidative coupling reactions are usually the method of choice for the construction of macrocycles containing buta-1,3-diynediyl moieties.10d,e
Copper-mediated Glaser coupling of 1-alkynes bearing carboxyl groups.
Selective crosscoupling of two different terminal alkynes is difficult in the usual Glaser coupling reaction. For these unsymmetrical conjugated diynes, copper(i)-catalysed coupling reaction of 1-halo alkynes with 1-alkynes in pyrrolidine provides the desired products at 20 °C (Scheme 15.11).11a Similarly a variety of unsymmetrical 1,4-biaryl-1,3-butadiyne derivatives are prepared by the crosscoupling reaction of alkynylsilanes with 1-chloroalkynes in the presence of copper(i) chloride as a catalyst in DMF at 80 °C (Scheme 15.12).11b
Copper-catalysed coupling reaction of 1-haloalkynes with 1-alkynes.
Copper-catalysed crosscoupling reaction of alkynylsilanes with 1-chloroalkynes.
Copper-catalysed crosscoupling reaction of alkynylsilanes with 1-chloroalkynes.
15.1.3 Sonogashira Couplings
Sonogashira found the crosscoupling reaction of aryl halides with terminal alkynes in the presence of a palladium complex and copper(i) compound (Scheme 15.13).12 However, palladium complexes are rather expensive, so intensive efforts have been made to realise the Sonogashira reaction only with copper catalysts.13
Palladium-catalysed Sonogashira coupling in the presence of a catalytic amount of copper salts.
Palladium-catalysed Sonogashira coupling in the presence of a catalytic amount of copper salts.
Miura et al. reported the first palladium-free Sonogashira coupling reaction of aryl iodides or vinyl iodides with terminal alkynes in the presence of a copper iodide/triphenylphosphine/potassium carbonate catalyst system (Scheme 15.14).13b o-Iodo-acetanilide derivatives react with 1-alkynes smoothly even at room temperature in the presence of a copper iodide/N-methylpyrrolidine-2-carboxamide catalyst system (Scheme 15.15).13c Various functionalities are tolerated in the catalytic reactions. Alkynylsilanes also react with a various aryl iodides in the presence of copper(i) chloride/triphenylphosphine/potassium benzoate catalyst system, affording unsymmetrical diarylethynes in good to excellent yields (Scheme 15.16).13d
Copper-catalysed Sonogashira coupling of aryl iodides with 1-alkynes.
Copper-catalysed Sonogashira coupling of aryl iodides with 1-alkynes employing N-methylpyrrolidine-2-carboxamide as the additive.
Copper-catalysed Sonogashira coupling of aryl iodides with 1-alkynes employing N-methylpyrrolidine-2-carboxamide as the additive.
Copper-catalysed Sonogashira coupling of aryl iodides with alkynylsilanes.
15.1.4 Coupling with Boronic Acids
Boronic acid derivatives are easily available and useful substrates especially in the palladium-catalysed Suzuki–Miyaura coupling reaction.14 In copper-catalysed reactions, they are also versatile starting materials. Dimerisation of arylboronic acids was first reported with copper acetate as a catalyst under oxygen at 100 °C.15a Later, it was found that CuCl(OH)(phen) complex was much more efficient as a catalyst to afford dimer in high yields at 28 °C (Scheme 15.17).15b
Selective C–H bond arylation of electron-rich arenes with aryl boronic acids proceeds to give biaryls (Scheme 15.18).16a It is noteworthy that the homocoupling of arylboronic acids does not occur. Although the oxygen atmosphere is not required for the coupling, the rate increases significantly under oxygen. Oxidative arylation of terminal alkynes with aryl boronic acids are carried out in the presence of a catalytic amount of copper(i) oxide (10 mol%) at room temperature under air (Scheme 15.19).16b
Oxidative C–H arylation of electron-rich arenes with aryl boronic acids in the presence of a stoichiometric amount of copper salt.
Oxidative C–H arylation of electron-rich arenes with aryl boronic acids in the presence of a stoichiometric amount of copper salt.
Copper-catalysed oxidative arylation of terminal alkynes with aryl boronic acids.
Copper-catalysed oxidative arylation of terminal alkynes with aryl boronic acids.
In Ullman-type coupling, aryl boronic acids are much more efficient coupling partners with amines and phenols as compared with aryl halides. They successfully couple at room temperature in the presence of a copper acetate/triethylamine (or pyridine) catalyst system and the corresponding arylated products were provided in high yields (Scheme 15.20).17a,b Similarly, aryl boronic acids are successfully coupled with structurally and electronically diverse substrates such as amides and sulfonamides to afford the corresponding N-arylated products.17a,c
C–N/C–O bond-forming reactions of aryl boronic acids with amines, amides or phenols.
C–N/C–O bond-forming reactions of aryl boronic acids with amines, amides or phenols.
15.1.5 Enantioselective Allylic Alkylations
Allylic substitutions, especially allylic alkylations, are important carbon–carbon bond-forming reactions. Palladium complexes are known as efficient catalysts in the reactions with soft carbon nucleophiles such as malonate carboanions.18 In contrast, copper catalysts allow the use of hard nucleophiles such as Grignard and organozinc reagents.19 In addition, these reactions usually proceed with high SN2′ fashion. Since the discovery of copper-catalysed asymmetric allylic alkylation of allylic acetate with butylmagnesium reagent (Scheme 15.21),20 the asymmetric alkylations have been developed considerably realising high enantioselectivity.21
Copper-catalysed asymmetric allylic alkylation of allylic acetate with Grignard reagent.
Copper-catalysed asymmetric allylic alkylation of allylic acetate with Grignard reagent.
A bidentate N-heterocyclic carbene (NHC) ligand was found to be efficient for the asymmetric allylic alkylation employing diethylzinc (Scheme 15.22).22 In the reaction, a binuclear silver complex undergoes facile ligand exchange with a copper salt to afford an effective copper catalyst. γ-Selective allylic alkylation is realised with alkylboranes as nucleophiles that are easily prepared by the hydroboration of the corresponding alkenes.23a The enantioselective version of the coupling reaction is established by the reaction of (Z)-allyl chloride with an alkylborane employing a copper catalyst with (R)-DTBM-SEGPHOS as a ligand (Scheme 15.23).23b Aryl, alkenyl, and allylboronates are also utilised as nucleophiles in the copper-catalysed enantioselective allylic funtionalisation.24
Asymmetric allylic alkylation with diethylzinc employing a chiral Cu-NHC catalyst.
Asymmetric allylic alkylation with diethylzinc employing a chiral Cu-NHC catalyst.
Copper-catalysed asymmetric allylic alkylation with alkyl boranes employing a chiral bidentate phosphine.
Copper-catalysed asymmetric allylic alkylation with alkyl boranes employing a chiral bidentate phosphine.
15.2 Copper-catalysed Addition Reactions
Addition reactions are highly atom efficient transformations, since all the atoms of substrates are incorporated in products. Copper catalysts play an important role as sustainable catalysts for addition reactions.
15.2.1 Enantioselective Conjugate Additions
Enantioselective conjugated addition to Michael acceptors is one of the most powerful carbon–carbon bond-forming reactions to synthesise synthons for biological active and natural compounds. As the catalyst, copper21c,25 and rhodium26 are especially efficient: many copper catalysts are employed for the introduction of alkyl moieties, while rhodium catalysts are often used for the addition of aryl and alkenyl groups.
Copper-catalysed enantioselective conjugate addition of Grignard reagents to α,β-unsaturated methyl esters is successfully carried out to provide β-substituted chiral esters in good yields and with excellent enantioselectivities (Scheme 15.24).27a A combination of copper iodide and commercially available chiral (R)-2,2′-bis(di-p-tolyl-phosphino)-1,1′-binaphthyl (Tol-BINAP) is also effective.27b
Copper-catalysed asymmetric conjugated addition of Grignard reagents to α,β-unsaturated methyl esters.
Copper-catalysed asymmetric conjugated addition of Grignard reagents to α,β-unsaturated methyl esters.
Alkylzincs undergo conjugate addition to nitroalkenes in the presence of a catalytic amount of (CuOTf)2·C6H628a or [(MeCN)4Cu]PF628b with a chiral peptide ligand. Optically enriched nitroalkanes bearing all-carbon quaternary carbon stereogenic centres are obtained efficiently (Scheme 15.25).28a Similar catalytic asymmetric conjugated addition of alkylzincs to tetrasubstituted cyclic enones proceeds in the presence of air-stable copper cyanide and a chiral ligand.28c
Asymmetric conjugated addition of alkyl zinc reagents to nitroalkanes employing a chiral copper catalyst.
Asymmetric conjugated addition of alkyl zinc reagents to nitroalkanes employing a chiral copper catalyst.
Organoboranes are much milder nucleophiles, and may be attractive in the conjugate addition reaction due to their good stability and ease of handling. Arylboranes add to alkylidene cyanoacetates enantioselectively in the presence of a catalytic amount of copper(i) bromide and a chiral imidazolium salt as a precursor for the corresponding NHC ligand (Scheme 15.26).28d Furthermore, alkylboranes undergo enantioselective conjugate addition to imidazol-2-yl α,β-unsaturated ketones with copper(i) chloride and NHC ligand.28e
Copper-catalysed asymmetric conjugated addition of aryl boronic esters to alkylidene cyanoacetates.
Copper-catalysed asymmetric conjugated addition of aryl boronic esters to alkylidene cyanoacetates.
15.2.2 Azide–Alkyne Cycloadditions
The copper-catalysed azide–alkyne cycloaddition (CuAAC)29 is known as the “click reaction” that was introduced by Sharpless to describe reactions realising simple procedure, high yield, high selectivity, and wide range of scope.30 The azide-alkyne cycloaddition was thoroughly investigated by Huisgen and coworkers in the 1950s as a 1,3-dipolar cycloaddition reaction.31 Although the 1,3-dipolar cycloaddition reactions between alkynes and organoazides proceeds thermally, it was reported that the rate of the reaction with copper catalysts was increased by a factor of 107 as compared to the thermal process. In addition, the copper-catalysed reactions afford the 1,4-regioisomer selectively. A simplified reaction mechanism is shown in Scheme 15.27. A copper catalyst reacts with terminal alkynes to generate copper acetylide species. Coordination of organoazide to copper followed by cyclisation reaction gives a 1,2,3-triazolato-copper intermediate. Finally, protonation leads 1,2,3-triazole and the copper catalyst regenerates. Detailed mechanistic studies clarified that the reaction mechanism is not so simple; some experiments suggest that dinuclear copper complexes may be involved as reaction intermediates (Scheme 15.28).32
A simplified reaction scheme for copper-catalysed azide–alkyne cycloaddition.
A simplified reaction scheme for copper-catalysed azide–alkyne cycloaddition.
A modified reaction scheme for copper-catalysed azide–alkyne cycloaddition.
A wide range of reaction conditions for copper-catalysed click reactions have been developed.29a Regarding copper catalysts, both copper(i) and copper(ii) salts are acceptable. Since active catalyst species is believed to be a copper(i) state, copper(i) species are generated from copper(ii) salts using suitable reducing agents such as sodium ascorbate. The reaction is catalysed by in situ generated copper(i) species from elemental copper; a small amount of copper wire or turning is added to the reaction mixture, followed by vigorous stirring or shaking. As solvents, aqueous alcohols (methanol, ethanol, and t-butanol), tetrahydrofuran (THF), dimethylformamide (DMF), and dimethyl sulfoxide (DMSO) can be used in the procedures. In general, the copper-catalysed click reactions could proceed without ligand when suitable reaction conditions are adopted. However, copper complexes with various ligands such as triphenylphosphine (Scheme 15.29),33 and NHCs (Scheme 15.30)34 are known as good catalysts in organic solvents. With a heteroleptic bis(NHC) copper complex as a catalyst, the reaction proceeds with 5 ppm catalyst loading (Scheme 15.31).35 A water-soluble bathophenanthroline works as a good ligand for the synthesis of polymers36a and modification of surfaces.36b Tris(benzyltriazolylmethyl)amine (TBTA), which is prepared by the reaction of tripropargylamine with benzyl azide via CuAAC reaction works a good ligand (Scheme 15.32).37
Copper-catalysed azide–alkyne cycloaddition employing a phosphine as the ligand.
Copper-catalysed azide–alkyne cycloaddition employing a phosphine as the ligand.
Copper-catalysed azide–alkyne cycloaddition employing a NHC as the ligand.
Low catalyst loading reaction of copper-catalysed azide–alkyne cycloaddition.
Low catalyst loading reaction of copper-catalysed azide–alkyne cycloaddition.
Copper-catalysed azide–alkyne cycloaddition employing tris(benzyltriazolylmethyl)amine as the ligand.
Copper-catalysed azide–alkyne cycloaddition employing tris(benzyltriazolylmethyl)amine as the ligand.
15.2.3 Hydroboration and Carboboration
Organoboron compounds are useful reagents in carbon–carbon and carbon–heteroatom bond formations.14,26,38 Conventionally, these compounds are prepared by the hydroboration of unsaturated compounds39 or by the reaction of highly reactive organolithium or Grignard reagents with boron electrophiles.14 In place of these classical methodologies, much attention has been paid to develop transition metal-catalysed borylation reactions, in which various organoboron compounds with unique reactivity are prepared with good functional group compatibility. In the reactions, copper compounds show good catalytic activity and bis(pinacolato)diboron (B2(pin)2) is a typical boron source.40 In a catalytic cycle, a borylcopper (Cu–B) species is generated as a key intermediate by the reaction of copper alkoxide with B2(pin)2.41
Stoichiometric amounts of copper(i) chloride, B2(pin)2, and potassium acetate are employed in hydroboration of terminal alkynes (Scheme 15.33).42 Catalytic hydroboration of terminal alkynes with B2(pin)2 is achieved by employing a copper catalyst.43 Products are obtained regioselectively by employing a suitable NHC ligand (Scheme 15.34). A bulky bidentate phosphine ligand is effective for regioselective hydroboration of aryl-substituted internal alkynes44 as well as internal alkynes bearing a propargyl ether, homopropargyl ether, and propargyl amine functionalities (Scheme 15.35).44c
Hydroboration of 1-octyne with B2(pin)2 in the presence of a stoichiometric amount of copper chlorides.
Hydroboration of 1-octyne with B2(pin)2 in the presence of a stoichiometric amount of copper chlorides.
Ligand-controlled regioselective hydroboration of terminal alkynes.
Copper-catalysed regioselective hydroboration of unsymmetrical internal alkynes.
Copper-catalysed regioselective hydroboration of unsymmetrical internal alkynes.
The β-selective hydroboration of styrene derivatives proceeds in the presence of a catalytic amount of (SIMes)CuCl (Scheme 15.36).45 An asymmetric variant is also achieved by using a chiral NHC ligand.45b The hydroboration of unactivated alkenes such as 1-hexene is facilitated by a copper(i) chloride/Xantphos catalytic system, giving a linear product with high regioselectivity (Scheme 15.37).45c Copper-catalysed hydroboration of allenes employing B2(pin)2 is carried out regioselectively.46
Carboboration of carbon–carbon multiple bonds that realises simultaneous carbon–boron and carbon–carbon bond formations is achieved with B2(pin)2 and carbon electrophiles in the presence of a copper catalyst. The reaction of phenylacetylene with methyl iodide and B2(pin)2 in the presence of copper(i) chloride/Xantphos catalyst system gives the corresponding carboboration products (Scheme 15.38).47a The carboboration of internal alkynes with benzyl chloride as an electrophile occurs in the presence of the copper acetate/tricyclohexylphosphine catalyst (Scheme 15.39).47b Copper-catalysed arylboration of internal alkynes occurs employing B2(pin)2 and an aryl iodide.48
Carboboration of alkynes with alkyl halide and B2(pin)2 employing Cu-Xantohos catalyst.
Carboboration of alkynes with alkyl halide and B2(pin)2 employing Cu-Xantohos catalyst.
Carboboration of alkynes with benzyl chloride and B2(pin)2 employing Cu-PCy3 catalyst.
Carboboration of alkynes with benzyl chloride and B2(pin)2 employing Cu-PCy3 catalyst.
Intramolecular alkylboration of silyl-substituted homoallylic mesylates with B2(pin)2 achieves stereospecific synthesis of silyl-substituted cyclobutylboronates (Scheme 15.40).49a Furthermore, the intramolecular alkylboration of silyl-substituted allylic carbonates can proceed enantioselectively.49b Carbonyl compounds can be used as a carbon electrophile enantioselectively in the reaction of allenes with B2(pin)2 in the presence of a suitable chiral copper catalyst (Scheme 15.41).50
Copper-catalysed intramolecular alkylboration of silyl-substituted homoallylic mesylates with B2(pin)2.
Copper-catalysed intramolecular alkylboration of silyl-substituted homoallylic mesylates with B2(pin)2.
Copper-catalysed enantioselective alkylborations of silyl-substituted allylic carbonates with B2(pin)2.
Copper-catalysed enantioselective alkylborations of silyl-substituted allylic carbonates with B2(pin)2.
Copper-catalysed borylative allyl–allyl coupling reaction using allylic phosphates as electrophiles has been reported (Scheme 15.42).51aA copper catalyst bearing ICy as a ligand is most effective for this reaction, and borylative 1,5-diene derivatives are obtained in high yields and with high selectivities. The asymmetric variant of the borylative allyl–allyl coupling reaction is also established employing a chiral NHC ligand (Scheme 15.43).51b This method has been applied to synthesis of various natural products.
Asymmetric borylative allyl–allyl coupling reactions with chiral copper catalysts.
Asymmetric borylative allyl–allyl coupling reactions with chiral copper catalysts.
15.3 Copper-catalysed Oxidative Reactions under Molecular Oxygen
Molecular oxygen is a highly environmentally benign and abundant oxidant. A range of useful oxidative transformations have been developed under an oxygen atmosphere in the presence of a copper catalyst.52 Representative examples are given below.
15.3.1 Oxidation of Alcohols and Naphthols
Benzylic and allylic alcohols are oxidised to the corresponding aldehydes or ketones in the presence of copper(ii) chloride/cesium carbonate as a catalyst under oxygen (Scheme 15.44).53a A catalytically active μ-hydroxyl-bridged trinuclear copper species was isolated and its X-ray crystal structure was determined. A highly efficient oxidation of propargylic alcohols to ynones under air has been carried out in the presence of copper nanoparticles (Cu Nps) with bipyridine as a ligand (Scheme 15.45).53b
Oxidative dimerisation of 2-naphthols to 1,1′-bis-2,2′-naphthol (BINOL) derivatives has been studied extensively. Copper(ii) catalyst under molecular oxygen has shown broad versatility in this transformation. Copper(ii)–Schiff base complexes reveal good catalytic activity in the dimerisation of 2-naphthols with low catalyst loading. This catalyst system is not so effective for substrates bearing electron-withdrawing substituents.53c Cu(OH)Cl(TMEDA) is stable and shows good catalytic activity even for electron-poor naphthols under oxygen or air (Scheme 15.46).53d The copper-catalysed aerobic coupling of 2-naphthols were carried out enantioselectively to provide homochiral biaryl natural compounds.53e,f
15.3.2 Oxidation of Carbonyl Compounds
Aromatic aldehydes are oxidised to the corresponding carboxylic acids in the presence of 150 nm-size copper(ii) oxide under molecular oxygen in good yield (Scheme 15.47).54a Aromatic, heterocyclic, and tertiary aliphatic nitriles are prepared from aldehydes under oxygen with copper powder (2 equivalents, 50 μm) and ammonium chloride (2 equivalents) in pyridine at 60 °C (Scheme 15.48).54b Cycloalkanones are shown to undergo regioselective oxidative cleavage under oxygen in the presence of a catalytic amount (6–7.5 mol%) of hydrated copper nitrate in a mixture of acetic acid and water (Scheme 15.49).54c When the optically active substrate is employed, the corresponding ketoacid is afforded in good yield without loss of enantiopurity.
Oxidation of aldehydes to carboxylic acids in the presence of copper oxide.
Transformation of aldehydes to nitriles employing copper powder and ammonium salts.
Transformation of aldehydes to nitriles employing copper powder and ammonium salts.
Copper-catalysed oxidative cleavage of cycloalkanone with dioxygen.
In the Baeyer–Villiger reaction, ketones are treated with peracids to give carboxylic esters by the insertion of oxygen. A similar reaction of ketones is catalysed by copper(ii) acetate under oxygen in the presence of an added aldehyde that generates a peracid in situ with oxygen (Scheme 15.50).54d The oxidation occurs at the more substituted side of ketone as in the typical Baeyer–Villiger reaction. Chiral copper complexes catalyse the Baeyer–Villiger reaction giving optically active lactones with up to 95% enantiomeric excess.54e
Synthesis of carboxylic ester from ketone employing aldehyde and dioxygen in the presence of copper catalyst.
Synthesis of carboxylic ester from ketone employing aldehyde and dioxygen in the presence of copper catalyst.
15.3.3 Aromatic C–H Bond Functionalisations
The selective oxidative aromatic C–H bond functionalisation for new carbon–carbon bond formation is versatile, and various copper-catalysed or mediated reactions have been developed under molecular oxygen or air.55
For intramolecular reactions, 3,3-disubstituted oxindoles are provided by the oxidative coupling of Ar–H and C–H moieties in the presence of stoichiometric amounts of copper(ii) complex and a base56a,b (Scheme 15.51).56a Similar reactions are carried out catalytically with copper(ii) acetate (5 mol%) under air (Scheme 15.52).56b Indoline-2,3-diones (isatins) are afforded by copper-catalysed intramolecular C–H oxidation/acylation with formyl-N-arylformamides under oxygen (Scheme 15.53).56c
Copper-mediated intramolecular coupling reactions between C(sp2)–H and C(sp3)–H bonds.
Copper-mediated intramolecular coupling reactions between C(sp2)–H and C(sp3)–H bonds.
Copper-catalysed intramolecular oxidative coupling reactions between C(sp2)–H and C(sp3)–H bonds in the presence of dioxygen.
Copper-catalysed intramolecular oxidative coupling reactions between C(sp2)–H and C(sp3)–H bonds in the presence of dioxygen.
Copper-catalysed intramolecular C–H oxidation/acylation with formyl-N-arylformamides.
Copper-catalysed intramolecular C–H oxidation/acylation with formyl-N-arylformamides.
Intermolecular oxidative dimerisation of electron-poor arenes as well as electron-rich and electron-poor heterocycles proceeds in high yields in the presence of a catalytic amount of copper(ii) chloride under oxygen (Scheme 15.54).57a Biazoles are efficiently prepared by oxidative dimerisation of azoles (imidazoles, oxazoles, and thiazoles) with copper(i) chloride (1 mol%) as a catalyst under air (Scheme 15.55).57b
Copper-catalysed intermolecular oxidative dimerisation of arenes.
The direct crosscoupling of unfunctionalised aromatic compounds with terminal alkynes affords the same products as in the Sonogashira coupling reaction and is very attractive. 1,3,4-Oxadiazoles and oxazoles are coupled with terminal alkynes in the presence of a stoichiometric amount of copper(i) chloride at 120 °C under oxygen (Scheme 15.56).58a Here, alkynes must be added over one hour to avoid the homocoupling of alkynes. On the other hand, polyfluoroarenes are also reactive and couple with terminal alkynes with a copper catalyst under oxygen58b,c (Scheme 15.57).58b
Direct C–H alkynylation of oxazoles with terminal alkynes in the presence of a stoichiometric amount of copper salts.
Direct C–H alkynylation of oxazoles with terminal alkynes in the presence of a stoichiometric amount of copper salts.
Copper-catalysed alkynylation of electron-deficient arenes with terminal alkynes.
Copper-catalysed alkynylation of electron-deficient arenes with terminal alkynes.
15.4 Copper-catalysed Reactions Utilising Carbon Dioxide
Transformation of carbon dioxide to valuable chemicals is one of the central challenges for chemists.59 Various transition-metal catalysts have been reported to be highly reliable in the utilisation of carbon dioxide.60,61 Some representative copper-catalysed reaction of carbon dioxide are discussed below.
15.4.1 Carbon–Carbon Bond-forming Reactions with Carbon Dioxide
The catalytic transformation of organic substrates with carbon dioxide via carbon–carbon bond formation is an important synthetic method for various carboxylic acids. It was reported that carboxylation of terminal alkynes with carbon dioxide and alkyl halides proceeded in the presence of a copper catalyst and a bases (Scheme 15.58).62a The reaction proceeds via carboxylation of a copper-alkynyl intermediate generated from a terminal alkyne and copper species Similar copper-catalysed carboxylations of alkynes have been reported and the corresponding esters are obtained in good to high yields.62b–g The copper-catalysed direct C–H carboxylation of heteroaromatic compounds has been reported (Scheme 15.59).63a Benzoxazoles and benzthiozoles that have a relatively acidic C–H bond react with carbon dioxide in the presence of copper catalyst and a suitable base.
Copper-catalysed carboxylation of terminal alkynes with carbon dioxide.
Direct C–H carboxylation of heteroarenes with carbon dioxide employing copper catalysts.
Direct C–H carboxylation of heteroarenes with carbon dioxide employing copper catalysts.
Copper complexes catalyse the carboxylation of organoboron compounds. Aryl and vinylboronates react with carbon dioxide in the presence of copper catalysts and base to give the corresponding carboxylic acids in good to high yield (Scheme 15.60).64a In the reaction, NHC64a and bisoxazoline64b are efficient ligands. Employing a NHC–copper complex, several catalytic intermediates were isolated and characterised by X-ray crystallography.64a Copper complexes also show good catalytic activity in the carboxylation of alkylboranes (Scheme 15.61).65 Since the substrates are easily prepared by the hydroboration of terminal alkenes with 9-borabicyclo[3.3.1]nonane (9-BBN-H), the overall process is represented as a formal hydrocarboxylation of terminal alkenes with carbon dioxide. Allylboronates are also carboxylated in the presence of IPrCuCl as a catalyst.66 Copper-catalysed carboxylation of aryl iodides is reported to provide benzoic acid derivatives (Scheme 15.62).67a In the reaction, diethylzinc is used as a reducing agent. Similar carboxylations of aryl halides are reported with nickel67b or palladium67c catalysts.
Copper-catalysed carboxylation of arylboronates with carbon dioxide.
Copper-catalysed carboxylation of an alkylborane with carbon dioxide.
Copper-catalysed carboxylation of an aryl iodide with carbon dioxide employing diethylzinc.
Copper-catalysed carboxylation of an aryl iodide with carbon dioxide employing diethylzinc.
The first catalytic hydrocarboxylation of alkynes employing carbon dioxide was reported with hydrosilanes as stable and easy-to-handle reducing agents. The reaction gives the corresponding α,β-unsaturated carboxylic acids in good to high yields (Scheme 15.63).68 The fixation of carbon dioxide along with simultaneous introduction of another heteroatom moiety must be useful. The silacarboxylation of alkynes employing silylborane as a silicon source was reported (Scheme 15.64).69a Various internal alkynes are converted to the corresponding silalactones selectively in good to high yields employing tricyclohexylphosphine as a ligand. Silacarboxylation of allenes occurs similarly (Scheme 15.65).69b It is noteworthy that the reaction proceeds in regiodivergent manner. When rac-Me-DuPhos is employed as a ligand in hexane, vinylsilanes are obtained selectively. In contrast, tricyclohexylphosphine selectively provides allylsilanes.69b Furthermore, the copper-catalysed boracarboxylation of alkynes employing bis(pinacolato)diboron as a boron source proceeds effectively, giving the corresponding lithium salt of boralactones (Scheme 15.66).70
Hydrocarboxylation of alkynes employing carbon dioxide and hydrosilanes in the presence of copper–NHC catalysts.
Hydrocarboxylation of alkynes employing carbon dioxide and hydrosilanes in the presence of copper–NHC catalysts.
Copper-catalysed silacarboxylation of alkynes employing carbon dioxide and silylborane.
Copper-catalysed silacarboxylation of alkynes employing carbon dioxide and silylborane.
Ligand-controlled regiodivergent silacarboxylation of allenes employing copper catalysts.
Ligand-controlled regiodivergent silacarboxylation of allenes employing copper catalysts.
Copper-catalysed boracarboxylation of alkynes employing carbon dioxide with B2(pin)2.
Copper-catalysed boracarboxylation of alkynes employing carbon dioxide with B2(pin)2.
15.4.2 Carbon–Oxygen Bond-forming Reactions with Carbon Dioxide
The synthesis of cyclic carbonates is one of the important reactions with regard to fixation of CO2. Copper complexes catalyse the reaction of epoxides with carbon dioxide, giving the corresponding carbonates (Scheme 15.67).71a In the reaction, a binaphthylamine-based salen acts as good ligand. Similar reactions have been carried out employing phthalocyanine and porphyrin as ligands.71b The reaction of a propargyl alcohol with carbon dioxide proceeded effectively in the presence of a copper catalyst in an ionic liquid (Scheme 15.68).72a α, α-Disubstituted propargyl alcohols are converted to the corresponding α-methylene cyclic carbonates in high yields. When a propargyl alcohol is treated with a primary amine under a carbon-dioxide atmosphere, the corresponding cyclic carbamates are obtained (Scheme 15.69).72b
Copper-catalysed reaction of propylene oxide with carbon dioxide.
Copper-catalysed reaction of propargyl alcohols with carbon dioxide in ionic liquids.
Copper-catalysed reaction of propargyl alcohols with carbon dioxide in ionic liquids.
Synthesis of cyclic carbamates from propargyl alcohols and carbon dioxide in the presence of amines.
Synthesis of cyclic carbamates from propargyl alcohols and carbon dioxide in the presence of amines.
15.4.3 Reduction of Carbon Dioxide to Formates and Carbon Monoxide
Copper complexes catalyse the reduction of carbon dioxide to formate employing hydrosilane as a reducing agent (Scheme 15.70).73 In the reaction, bidentate phosphines such as dppbz73a,b and NHC73c are efficient ligands. Carbon dioxide is also converted to formate in the presence of IPrCuOtBu as a catalyst and a hydroborane as a reducing agent.74 A borylcopper complex, IPrCuB(pin), reacts with carbon dioxide to give carbon monoxide and IPrCuOB(pin) (Scheme 15.71).41 The borylcopper complex works as a catalyst for the reduction of carbon dioxide to carbon monoxide employing B2(pin)2 as a reagent. A silylcopper complex, IPrCuSiMe2Ph, also reacts with carbon dioxide, giving carbon monoxide.75 A copper complex bearing a bis(pyridylmethyl)amine based ligand catalysed the reduction of carbon dioxide to oxalate under electrochemical conditions. Surprisingly, the fixation of carbon dioxide proceeded under an air atmosphere (Scheme 15.72).76
Copper-catalysed reduction of carbon dioxide to carbon monoxide.
Electrochemical reduction of carbon dioxide to oxalates with a copper catalyst.
Electrochemical reduction of carbon dioxide to oxalates with a copper catalyst.
15.5 Conclusions
As described in this chapter, homogeneous copper catalysts work well in various organic transformations including carbon–carbon bond-forming reactions, oxidations, reductions, and fixation of carbon dioxide. In some cases, ligands on the copper play important roles in realising high efficiency and excellent regio- and stereoselectivities. Continued efforts on developing copper catalysts will contribute to efficient syntheses of many valuable molecules.