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, 119 (4), 2954-3031

Copper-Promoted Functionalization of Organic Molecules: From Biologically Relevant Cu/O 2 Model Systems to Organometallic Transformations

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Copper-Promoted Functionalization of Organic Molecules: From Biologically Relevant Cu/O 2 Model Systems to Organometallic Transformations

Rachel Trammell et al. Chem Rev.

Abstract

Copper is one of the most abundant and less toxic transition metals. Nature takes advantage of the bioavailability and rich redox chemistry of Cu to carry out oxygenase and oxidase organic transformations using O2 (or H2O2) as oxidant. Inspired by the reactivity of these Cu-dependent metalloenzymes, chemists have developed synthetic protocols to functionalize organic molecules under enviormentally benign conditions. Copper also promotes other transformations usually catalyzed by 4d and 5d transition metals (Pd, Pt, Rh, etc.) such as nitrene insertions or C-C and C-heteroatom coupling reactions. In this review, we summarized the most relevant research in which copper promotes or catalyzes the functionalization of organic molecules, including biological catalysis, bioinspired model systems, and organometallic reactivity. The reaction mechanisms by which these processes take place are discussed in detail.

Conflict of interest statement

Notes

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Scope of this review article.
Figure 2.
Figure 2.
(A) Energetics of the stepwise 4H+/4e reduction of dioxygen to water. (B) Mononuclear, (C) dinuclear, (D) trinuclear and tetranuclear Cu/O2 species formed in the reduction of O2 (and its reduced forms).
Figure 3.
Figure 3.
Galactose oxidase (GAO): active center (i), reaction catalyzed (ii), and proposed catalytic cycle (iii).
Figure 4.
Figure 4.
Galactose oxidase model system.,
Figure 5.
Figure 5.
(A) Dinuclear and (B) mononuclear galactose oxidase model systems.,
Figure 6.
Figure 6.
Copper (and zinc) galactose oxidase model systems.
Figure 7.
Figure 7.
Cu-catalyzed oxidation of alcohols.
Figure 8.
Figure 8.
Cu-catalyzed oxidation of (A and B) primary and (B) secondary alcohols.
Figure 9.
Figure 9.
Synthetic method for the oxidation of alcohols.,
Figure 10.
Figure 10.
Catalytic copper-nitroxyl systems beyond oxidation of alcohols: oxidation of amines to (A) imines and to (B) nitriles; (C) oxidative coupling of alcohols and amines and (D) lactonization of diols.
Figure 11.
Figure 11.
Copper-catalyzed oxidation of amines to imines and nitriles.
Figure 12.
Figure 12.
Biosynthesis of 2,4,5-trihydroxyphenylalanine-quinone (TPQ) and lysine tyrosyl-quinone (LTQ).
Figure 13.
Figure 13.
1H+/1e oxidation of phenols promoted by Cu/O2 species: (A) mechanistic tools to identify possible reaction pathways and research reports in which this methodology has been used to understand the reactivity of Cu/O2 species [(B) mononuclear and (C) dinuclear] toward phenols.
Figure 14.
Figure 14.
Cu-catalyzed aerobic oxidation of phenols.
Figure 15.
Figure 15.
Cu-catalyzed naphthol coupling.,
Figure 16.
Figure 16.
Cu-catalyzed oxidative C–O coupling of phenols and quinones.
Figure 17.
Figure 17.
Cu-promoted synthesis of arylomycin cores.
Figure 18.
Figure 18.
Peptidylglycine α-hydroxylating monooxygenase (PHM): (i) active center, (ii) reaction catalyzed, and (iii) proposed catalyztic cycle. Note: For C2, it was proposed that a radical cation, located over the three ligands bound to the Cu, was formed.
Figure 19.
Figure 19.
(A) Particulate methane monoooxygenase (pMMO) and (B) lytic polysaccharide monooxygenase (LPMO): active centers, reactions catalyzed, (C) histidine brace binding motif, and (D) putative Cu/O2 species responsible of C–H oxidation.
Figure 20.
Figure 20.
Intramolecular C–H hydroxylation promoted by an ESII species.,
Figure 21.
Figure 21.
Intermolecular C–H hydroxylation promoted by an ESII species.
Figure 22.
Figure 22.
Intramolecular N-dealkylaiton oxidation promoted by an EHPII species.
Figure 23.
Figure 23.
Intramolecular C–H hydroxylations (promoted by putative EHPII species) for synthetic purposes.,,
Figure 24.
Figure 24.
Cu-promoted intermolecular oxidations and intramolecular hydroxylation involving ESII, EHPII, and O·II intermediates.
Figure 25.
Figure 25.
Intermolecular 1H+/1e oxidation of C−H bonds by high-valent OHIII complexes.,
Figure 26.
Figure 26.
Thermodynamic analysis of the 1H+/1e reactivity of an ESII,II core.
Figure 27.
Figure 27.
Inter- and intramolecular C–H oxidations performed by an SPII,II species.
Figure 28.
Figure 28.
Inter- and intramolecular C–H oxidations performed by O,OIII,III cores.
Figure 29.
Figure 29.
Intermolecular oxidation of weak C–H bonds by O,OIII,III cores bearing biologically relevant ligands.
Figure 30.
Figure 30.
Generation of O,OIII,III cores bound by Lewis-acids and their reactivity toward weak C–H bonds.
Figure 31.
Figure 31.
Thermodynamic analysis of the 1H+/1e reactivity of an OII,II core.
Figure 32.
Figure 32.
Cu-catalyzed hydroxylation of cyclohexane using H2O2 as oxidant.,
Figure 33.
Figure 33.
Cu-catalyzed peroxidation of strong C–H bonds using H2O2 as oxidant.
Figure 34.
Figure 34.
Cu-catalyzed oxidation of alkanes using H2O2 as oxidant.
Figure 35.
Figure 35.
LPMO-like oxidation of C–H bonds with H2O2.
Figure 36.
Figure 36.
Cu-catalyzed hydroxylation of C–H bonds with H2O2. Note: these oxidations were carried out under excess amounts of substrate (i.e., H2O2 was the limiting reagent), which led to very low product yields.
Figure 37.
Figure 37.
Cu-catalyzed sp3 C–H oxidation of toluene using O2 as oxidant.
Figure 38.
Figure 38.
Cu-catalyzed hydroxylation of strong C–H bonds using O2 and H2O2 as oxidants.
Figure 39.
Figure 39.
Tyrosinase: active center (i), reaction catalyzed (ii) and proposed catalytic cycle (iii).
Figure 40.
Figure 40.
Cu2O2 model systems able to perform tyrosinase-like stoichiometric ortho-hydroxylation of phenolates: types of cores, (i) mechanistic evidence, and (ii) proposed hydroxylation pathways.
Figure 41.
Figure 41.
Catalytic tyrosinase-like reactivity.
Figure 42.
Figure 42.
Catalytic tyrosinase-like reactivity.
Figure 43.
Figure 43.
Cu-catalyzed oxygenation and functionalization of phenols for synthetic purposes.,
Figure 44.
Figure 44.
Intramolecular sp2 C–H hydroxylation involving an EHPII species.
Figure 45.
Figure 45.
Intramolecular sp2 C–H hydroxylation and intermolecular oxidations involving EAPII species.,
Figure 46.
Figure 46.
Intramolecular hydroxylation of sp2 C–H bonds in a mononuclear copper complex using O2 as oxidant.
Figure 47.
Figure 47.
Intramolecular hydroxylation of sp2 C–H bonds in a dinuclear copper complex using O2 as oxidant.
Figure 48.
Figure 48.
Intramolecular hydroxylation of sp2 C–H bonds promoted by O,OIII,III cores.
Figure 49.
Figure 49.
Intramolecular hydroxylation of sp2 C–H bonds promoted by O,OIII,III cores.
Figure 50.
Figure 50.
Intramolecular double hydroxylation of sp2 C–H bonds in a dinuclear copper complex using H2O2 as oxidant.
Figure 51.
Figure 51.
Cu-catalyzed hydroxylation of sp2 C–H bonds using H2O2 as oxidant.,
Figure 52.
Figure 52.
Cu-catalyzed hydroxylation of benzene using H2O2 as oxidant.
Figure 53.
Figure 53.
Nucleophilic reactivity of an ESII complex.
Figure 54.
Figure 54.
Nucleophilic reactivity of EAPII complexes.
Figure 55.
Figure 55.
Electrophilic and acid–base reactivity of a mononuclear Cu/O2 species.
Figure 56.
Figure 56.
Cu-catalyzed sulfoxidations using H2O2 as oxidant.
Figure 57.
Figure 57.
Putative intermediates formed in the reaction between Cu and oxene and nitrene sources.
Figure 58.
Figure 58.
Cu-catalyzed aziridinations.
Figure 59.
Figure 59.
Cu-catalyzed aziridinations and aminations.
Figure 60.
Figure 60.
Cu-catalyzed synthesis of sulfinamides and isothiazoles.
Figure 61.
Figure 61.
Cu-catalyzed intermolecular aminations.
Figure 62.
Figure 62.
Cu-catalyzed amination of C–H bonds using tBuOOtBu as sacrificial oxidant and amines as N-sources.
Figure 63.
Figure 63.
Generation and reactivity of “masked” copper-nitrene species.
Figure 64.
Figure 64.
Generation and reactivity of copper-nitrene species stabilized by Lewis acids.
Figure 65.
Figure 65.
Generation and reactivity of a mononuclear copper-nitrene species.
Figure 66.
Figure 66.
Generation of mononuclear and dinuclear copper- (di)nitrene species.
Figure 67.
Figure 67.
Generation and tyrosinase-like reactivity of a dicopper(II)- arylnitroso complex.
Figure 68.
Figure 68.
Cu-catalyzed C–O coupling reactions between aryl halides and phenols.
Figure 69.
Figure 69.
Cu-catalyzed C–N coupling reactions between aryl iodides and amines.,
Figure 70.
Figure 70.
Tandem copper-catalyzed synthesis of 1,4-benzodiazepines and imidazobenzodiazepines.
Figure 71.
Figure 71.
Mechanistic study on Cu-catalyzed C–O coupling reactions with auxiliary anionic ligands.
Figure 72.
Figure 72.
Mechanistic study on the Cu-catalyzed Hurtley-type reactions.
Figure 73.
Figure 73.
Cu-catalyzed coupling reactions in macrocylic ligands.,
Figure 74.
Figure 74.
Cu-catalyzed aryl halide exchange reactions in macrocylic ligands.
Figure 75.
Figure 75.
Mechanistic study of the Cu-catalyzed Chan–Evans–Lam C–O coupling reaction.,
Figure 76.
Figure 76.
Mechanistic study and synthetic applications of the Cu-catalyzed Chan–Evans–Lam C–N coupling reaction.
Figure 77.
Figure 77.
Stochiometric Cu-promoted trifluoromethylation of arylboronic acids.
Figure 78.
Figure 78.
Mechanism of Cu-catalyzed oxidative aerobic trifluoromethylation.
Figure 79.
Figure 79.
Cu-promoted pentafluoroethylation of acid chlorides.
Figure 80.
Figure 80.
Mechanistic studies of the Cu-promoted intramolecular C– C and C–N coupling reactions using copper complexes bearing redox-active ligands.,
Figure 81.
Figure 81.
Synthesis, characterization, and reactivity of organocopper- (III) spiro species.
Figure 82.
Figure 82.
Synthesis, characterization, and reactivity of organocopper- (III) species.
Figure 83.
Figure 83.
Synthesis, characterization, and reactivity of organocopper- (III) species.
Figure 84.
Figure 84.
Synthesis, characterization, and reactivity of organocopper- (II) and organocopper(III) species.
Figure 85.
Figure 85.
Mechanistic studies of the Cu-catalyzed functionalization of sp2 C–H bonds using a macrocylic ligand as substrate.,
Figure 86.
Figure 86.
Mechanistic study of the Cu-promoted functionalization of sp2 C–H bonds using N-(8-quinolinyl)benzamide as model substrate.
Figure 87.
Figure 87.
Cu-promoted trifluoromethylation of sp2 C–H bonds using directing groups.
Figure 88.
Figure 88.
Cu-catalyzed amidation and imidation of unactivated alkanes using amides and imides as N-sources and tBuOOtBu as oxidant.
Figure 89.
Figure 89.
Cu-catalyzed C–C coupling reaction of benzylic C–H bonds and arylboronic esters using tBuOOtBu as oxidant.
Figure 90.
Figure 90.
Cu-catalyzed enantioselective cyanation of benzylic substrates.
Figure 91.
Figure 91.
Cu-catalyzed allylic aminations.
Figure 92.
Figure 92.
Cu-catalyzed synthesis of allylic alcohols via hydrocabonylative coupling of alkynes with alkyl halides.
Figure 93.
Figure 93.
Cu-catalyzed C–N cross-coupling reaction with light.
Figure 94.
Figure 94.
Cu-catalyzed enantioselective C–N cross-coupling reaction with light.
Figure 95.
Figure 95.
Cu-catalyzed synthesis of carbamate-protected amines using carbamate nucleophiles, unactivated secondary alkyl bromides and light.
Figure 96.
Figure 96.
Cu-catalyzed oxidative coupling of phenols and terminal alkynes to synthesize ketones using light.
Figure 97.
Figure 97.
Cu-promoted intramolecular fluorinations of α-bromoamide substrates.
Figure 98.
Figure 98.
Cu-promoted ortho-functionalization of aryl C–H bonds using pyridyl as directing group.
Figure 99.
Figure 99.
Cu-catalyzed Ritter-type C–H amination of sp3 C–H bonds.
Figure 100.
Figure 100.
Cu-catalyzed bromination of sp3 C–H bonds distal to functional groups.
Figure 101.
Figure 101.
Cu-catalyzed β-functionalization of saturated ketones.
Figure 102.
Figure 102.
Cu-catalyzed etherification of alkanes using tBuOOtBu as oxidant.
Figure 103.
Figure 103.
Cu-catalyzed dehydrogenative carboxylation of unactivated alkanes to form allylic esters using tBuOOtBu as oxidant.
Figure 104.
Figure 104.
Mechanistic studies of the Cu-catalyzed functionalization of N-aryl tetrahydroisoquinolines.
Figure 105.
Figure 105.
Cu-catalyzed remote sp3 C–H chlorination of alkyl hydroperoxides.
Figure 106.
Figure 106.
Cu-promoted synthesis of functionalized epoxides.
Figure 107.
Figure 107.
Cu-catalyzed intramolecluar functionalization of alkenes.
Figure 108.
Figure 108.
Cu-catalyzed ortho-amination of phenols.
Figure 109.
Figure 109.
Cu-catalyzed dehydrogenative borylation of terminal alkynes.
Figure 110.
Figure 110.
Cu-catalyzed C–N coupling reactions using tBuOOtBu as oxidant.
Figure 111.
Figure 111.
Cu-catalyzed sysnthesis of nitriles via C–C cleavage of α- azido carbonyl compounds.
Figure 112.
Figure 112.
Cu-catalyzed synthesis of azaspirocyclohexadienones.
Figure 113.
Figure 113.
Cu-catalyzed spirocyclization of biaryl-N-H-imines.
Figure 114.
Figure 114.
Cu-catalyzed synthesis of dihydrooxazoles.
Figure 115.
Figure 115.
Cu-catalyzed synthesis of α-ketoamides.
Figure 116.
Figure 116.
Cu-catalyzed synthesis of α-ketoamides via oxidative coupling of aryl acetaldehydes and anilines.
Figure 117.
Figure 117.
Cu-mediated the synthesis of primary α-ketoamides.
Figure 118.
Figure 118.
Cu-promoted synthesis of oxazoles.
Figure 119.
Figure 119.
Cu-catalyzed synthesis of 1,4-napthoquinones.
Figure 120.
Figure 120.
Cu-catalyzed C–C cleavage of α-aminocarbonyl substrates.
Figure 121.
Figure 121.
Cu-catalyzed synthesis of formyl-substituted aromatic N-heterocycles.
Figure 122.
Figure 122.
Cu-catalyzed synthesis of 4-carbonyl-quinolines.
Figure 123.
Figure 123.
Cu-catalyzed synthesis of 3-functionalized indoles.
Figure 124.
Figure 124.
Cu-catalyzed synthesis of benzoimidazo[1,2-a]-imidazolone.
Figure 125.
Figure 125.
Cu-catalyzed vinylogous aerobic oxidation of unsaturated compounds.
Figure 126.
Figure 126.
Cu-promoted hydroxylation and amination of sp2 C–H bonds using directing groups.

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