A metal-free multicomponent domino reaction for the highly regioselective synthesis of tetrasubstituted NH-pyrroles from readily available alkylnitriles, arylalkynes, and MeOTf has been developed. A variety of NH-pyrroles were obtained in moderate to good yields under mild conditions. In addition, the reactions using diarylalkynes with electron-rich aryl groups were found to afford isoquinolines.

Cp2TiCl2-catalyzed hydrocarboxylation of alkynes with CO2 (atmospheric pressure) has been reported. A range of alkynes were transformed to the corresponding α,β-unsaturated carboxylic acids in high yields with high regioselectivity. The reaction proceeded with hydrotitanation, transmetalation, and subsequently carboxylation with CO2.

A metal-free oxyamination reaction of alkenes with ambient CO2 is reported. In the presence of I2 and DBU, CO2 is applied in situ as a protecting group to regulate the nucleophilicity of the amino group and facilitate the bicyclization of 4-pentenamines with high chemoselectivity. Moreover, this reaction provided a feasible approach to prepare prolinol carbamates with good tolerance of functional groups and high efficiency under mild conditions.

Rh(III)-catalyzed substrate-controlled transformation of azobenzenes to indazoles and 2-acyl (NH) indoles is achieved via C–H functionalization. Generally, good functional groups tolerance, satisfying yields, and excellent regio-selectivity are achieved in this reaction. Mechanistically, the reaction with acrylates undergoes β-hydride elimination, while the reaction with vinyl ketones or acrylamides undergoes nucleophilic addition. Copper acetate was supposed to play different roles in the β-hydride elimination to furnish indazoles and nucleophilic addition of C–Rh bond to deliver 2-acyl (NH) indoles.

•Transmetalation reactions of Zr to p-block elements and transition-metals were summarized.•Tandem transmetalation and catalytic transmetalation were important supplements for transmetalation process.•Transmetalation enables the further functionalization of ZrC bond.•Synthetic approach to various acyclic and cyclic organometallic complexes.Transmetalation is a fundamental reaction in organometallic chemistry. It provides common and useful methods for preparing various organo-transition metal complexes, which are either used as reagents or catalyst in organic synthesis. Organozirconium complexes have attracted considerable attention owing to their fascinating structural features and unique ZrC bonding. As the booming development of the organozirconium chemistry, transmetalation of organozirconium with other metallic reagents afforded various new types of organometallic complexes, which showed a remarkable advantage in modern organic synthesis. In this review, we would like to summarize the typical examples of transmetalation reactions that originated from organozirconium compounds, which mainly include organic species or ligands from organozirconocenes to p-block elements and transition-metals. In addition, transmetalation reactions beyond the organozirconocenes system, such as zirconium carbene complexes, zirconium pincer complexes, and arylzirconium complexes would be also introduced. Transmetalation reactions that originated from organozirconium included (i) Direct transfer; (ii) Tandem transfer; (iii) Catalytic transfer.Download high-res image (137KB)Download full-size image

External oxidant-free oxidative cross-coupling between arylcopper and alkynylcopper has been performed, which provides a new way for the formation of arylalkyne with high selectivity.

•Unique reactivity of zirconate complexes toward electrophiles.•Diverse reactivity patterns when different electrophiles employed.•Synthesis of novel organic molecules by one-pot multi-component reactions.•Reaction mechanisms for the reductive elimination and cross-coupling.An ate complex is a salt in which the central atom increases its valence or coordination number and becomes anionic. A significant reaction by the ate complexes is a strong nucleophilicity toward electrophiles to form new chemical bonds, which may lead to useful one-pot synthetic methods for building complex molecules. Zirconocene complexes can have a metal center with 14–18 electrons and a coordination number of 3–5. The 14-electron and 16-electron zirconocene complexes have been explored extensively and many applications have been developed in synthetic chemistry. Zirconate complexes with an 18-electron configuration and five-coordinated number have a higher likelihood of forming new CC bonds. The present review concentrates on the zirconate complexes used in organic synthesis. When zirconate complexes are treated with p-chloranil, aldehydes, chloroformates, esters, cinnamates, allyl bromides, or chlorophosphines, they undergo different types of reactions and various organic products are formed in an efficient manner.

Cp2TiCl2-catalyzed regioselective hydrocarboxylation of alkenes with CO2 to give carboxylic acids in high yields has been developed in the presence of iPrMgCl. The reaction proceeds with a wide range of alkenes under mild conditions. Styrene and its derivatives can transform to α-aryl carboxylic acids, and aliphatic alkenes can transform to form alkanoic acids.

Carbon dioxide (CO2), as a waste of manufacture, is a cheap and abundant C1 source. Utilization of CO2 for synthesis of carboxylic acids has been developed. Transition-metal complexes play a key role in catalytic carboxylation reactions employing CO2. This review summarizes recent advances in copper-catalyzed carboxylation reactions using CO2. The contents are arranged based on various substrates: organometallic reagents, aryl iodides, sodium sulfinates, terminal alkynes, arenes, heteroarenes, and unsaturated substrates.

Carbonylation of o-arylanilines utilizing CO2 as a carbonyl source for the synthesis of important phenanthridinones with a free (NH)-lactam motif has been described under metal-free condition. A range of o-arylanilines were transformed to the corresponding phenanthridinones in high yields.

External oxidant-free oxidative cross-coupling between alkenylzirconocene and alkynylcopper reagents has been achieved, which provides a new method for the selective synthesis of highly substituted enynes. In this reaction, no homocoupling products were observed.

Metalloles are derivatives of cyclopentadiene in which the methylene unit is replaced by a heteroatom, such as S, Se, Te, N, P, As, Sb, Bi, Si, Ge, Sn, B, Al, Ga, and so on. Many metallole derivatives have been widely used as photovoltaic cells, organic light emitting diodes (OLEDs), chemical sensors, electrochromic devices, microelectronic actuators, and organic field effect transistors (OFETs). In the meantime, many of them showed promising biological actives. Due to the similarity to cyclopentadiene, the anionic forms of metalloles were also widely explored in coordination chemistry. As a result, development of a general method for the formation of metalloles from available starting materials is highly desired.In this Account, we outline formation of various p-block element metalloles from zirconacyclopentadienes. The zirconacyclopentadienes can be easily prepared from two molecules of alkynes and a low-valent zirconocene species “Cp2Zr(II)” (Cp = cyclopentadienyl). Fagan and Nugent first reported the formation of main group metalloles from zirconacyclopentadiene, which provided a versatile approach for the construction of metalloles, especially for the formation of metalloles in heavier p-block elements. To further expand the substrate scope, a number of stepwise conversions were developed, which involve 1,4-dimetallo- or dihalo-1,3-butadiene as intermediates from zirconacyclopentadienes.Here, four processes are classified based on direct and indirect conversion of zirconacyclopentadienes into metalloles. Direct reaction of zirconacyclopentadienes with element halides afforded heterocycles of main group elements, which provided a versatile method for the synthesis of metalloles. Nonetheless, the reaction scope was restricted to heavier p-block elements such as S, Se, P, As, Sb, Bi, Ge, Sn, Ga, and In. And these reactions usually suffered low yields and long reaction time. Transmetalation of zirconacyclopentadiene with copper chloride greatly enriched the zirconacyclopentadiene chemistry. The synthesis of stannoles and pyrroles from zirconacyclopentadienes has been developed in the presence of CuCl. The direct reaction of the zirconacyclopentadienes with SiCl4 or R2SiCl2 does not give the desired silacyclopendadiene derivatives, even in the presence of CuCl. It can be circumvented by using dilithiated dienes from diiododienes, which are easily prepared by the iodination of zirconacyclopentadienes using CuCl as an additive. Finally, an umpolung strategy, reaction of electrophilic 1,4-diiodo-1,3-butadiene with nucleophilic amine or sulfide reagents, was successfully used in the formation of pyrroles and thiophenes.

A variety of alkenylzirconocenes were efficiently carboxylated by CO2 utilizing the (IMes)CuCl catalyst yielding the corresponding α,β-unsaturated carboxylic acids in good yields. This reaction could be carried out in a one-pot operation via sequential carbozirconation of alkynes and carboxylation using CO2 as starting materials under room temperature.

A copper-promoted tandem reaction of a variety of azobenzenes and allyl bromides via N═N bond cleavage to regioselectively construct quinoline derivatives has been developed. The azobenzenes act as not only construction units but also an oxidant for quinoline formation.

MeOTf-induced carboannulation of alkyl isothiocyanates and aryl alkynes for the synthesis of indenones in good yields under metal-free conditions with C═S bond cleavage is described. The thioalkoxy group at the 3-position of the indenone can also be converted into other functional groups, such as phenyl, methylsulfonyl, amino, and ethoxy groups.

The zirconocene-catalyzed sequential ethylcarboxylation of alkenes using ethylmagnesium chloride and carbon dioxide has been developed. A range of alkenes were transformed into the corresponding carboxylic acids in high yields.

Copper-mediated reaction of oxazirconacyclopentenes with dichlorophenylphosphine afforded 2,5-dihydro-1,2-oxaphosphole in high yields, in which the reaction was performed conveniently in one-pot from an alkyne, carbonyl compound and dichlorophosphine.

The reaction of arylisothiocyanate, alkyltriflate, and alkynes leads to variously substituted quinolines in high yields. The reaction undergoes alkyltriflate-triggered domino electrophilic activation and avoids the use of a transition-metal catalyst. A variety of functional groups are tolerated in the quinoline ring.

MeOTf-induced carboannulation of arylnitriles and aromatic alkynes for synthesis of indenones under metal-free conditions has been described. When ortho-substituted benzonitriles were used, indeno[1,2-c]isoquinolines were formed.

Rh(III)-catalyzed cascade oxidative alkenylation/cyclization of picolinamides and alkenes to furnish pyrido pyrrolone derivatives is described, in which three C–H bonds and one N–H bond broke, while one C–C bond and one C–N bond formed. The reaction proceeded with high yield and high regioselectivity and stereoselectivity. Moreover, copper acetate can also be used in catalytic amounts with O2 serving as the terminal oxidant.

Copper-catalyzed coupling reactions have been recognized as one of the most useful strategies for the formation of C–N bonds. This perspective gives an overview of the recent developments in copper-catalyzed electrophilic amination for the construction of various amines and their derivatives, including the electrophilic amination of various organometallic reagents and direct C–H bonds as well as the annulative electrophilic amination of o-alkynylphenols and o-alkynylanilines.

Copper-catalyzed domino reactions are one of the most useful strategies for the construction of various cyclic compounds. In this Synopsis, we mainly focus on the latest advances in copper-catalyzed cross-coupling or addition-initiated domino reactions in the synthesis of cyclic compounds, including double alkenylation of N- or S-nucleophiles, alkenylation or alkynlation followed by cyclization of amides or amines, addition and cyclization of heteroallenes affording heterocycles, and coupling and cyclization of 1,3-dicarbonyl compounds toward heterocycles.

A novel copper-catalyzed oxidation of arene-fused cyclic amines to the corresponding cyclic imides has been developed. The reaction can be used to synthesize 1,3-disubstituted TPD in high yields.

Copper-mediated electrophilic imination of alkenylzirconocenes generated in situ from alkynes and zirconocenes is accomplished under mild reaction conditions. The reaction can be used to prepare various 2-azadienes.

The CuCl catalyzed direct trifluoromethylation of sp2 C–H bonds has been realized, using the Togni reagent as the CF3 source. This reaction achieves the goal of regio-selectively converting C–H into C–CF3 with ecological and readily available starting materials.

Copper-mediated amidation of alkenylzirconocenes generated in situ from alkynes and zirconocenes with acyl azides is accomplished under mild conditions. The reaction can be used to prepare various enamides.

An effective regioselective cyclotrimerization of terminal alkynes is achieved by the direct utilization of NiCl2·6H2O, Zn, and 2-(benzimidazolyl)-6-(1-(arylimino)ethyl)pyridine in one step under ambient temperature.

Protonated 1,8-diazabicyclo[5,4,0]undec-7-ene as catalyst for cascade addition/cyclization of 2-alkynylaniline and carbon disulfide has been described. This process provides a convenient route for synthesis of a variety of benzo[d][1,3]thiazine-2(4H)-thiones in high yields with high regio- and stereoselectivity at room temperature without metal.

An efficient synthetic approach to variously substituted 2,3-dihydrothiophenes has been developed. The reaction proceeded by copper-catalyzed tandem S-alkylation and S-alkenylation of sodium sulfide with 1,4-diiodobut-1-enes to afford the corresponding 2,3-dihydrothiophene derivatives in high yields. The 2,3-dihydrothiophenes could bear alkyl, aryl as well as heteroaryl substituents. The resulted 2,3-dihydrothiophenes could be further transferred into the corresponding thiophenes by oxidation.

Diaryl thioethers and S-cycles were obtained on the basis of the copper-catalyzed reaction of carbon disulfide and aryl iodides in the presence of DBU. This reaction enables the one-pot synthesis of diaryl thioethers by employing cheap, available, and easy-to-handle carbon disulfide with aryl iodides. The reaction was successfully employed in the construction of sulfur-containing cyclic molecules.

A general method for the synthesis of multiply substituted pyrroles through zirconocene-mediated coupling of two alkynes and an azide in the presence of CuCl has been achieved.

The reaction of alkynylzirconates with α,β-unsaturated carbonyl compounds has been achieved. Reactions of alkynylzirconates with cinnamates afford ester-functionalized multisubstituted dienes, in which the C3 attacks cinnamates via Michael addition. Reactions of alkynylzirconates with benzylideneacetone give (1E,3Z)-dienes, in which benzylideneacetone acts as an electrophile to afford a proton.

Copper-catalyzed electrophilic amination of alkenylzirconocenes is accomplished under mild reaction conditions. The reaction tolerates a wide range of functional groups and can be used to prepare some hindered enamines.

A concise approach to various benzisothiazol-3(2H)-one derivatives has been developed by copper-catalyzed the reaction of o-bromobenzamide derivatives with potassium thiocyanate (KSCN) in water. The reaction proceeds via a tandem reaction with S–C bond and S–N bond formation.

Copper-catalyzed tandem coupling of 1,4-dihalo-1,3-dienes with azoles via an N−H bond and its adjacent C−H bond activation has been described. The reaction exhibits good regioselectivity when unsymmetrical 1,4-dihalo-1,3-diene is employed. This method provided a novel route to the synthesis of nitrogen-bridgehead azolopyridine derivatives.

Copper-catalyzed tandem reaction of ortho-bromobenzamides and isothiocyanates is described, which provides an efficient and practical route for the synthesis of 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones. The optimal condition involved the following parameters: CuI as precatalyst, Cs2CO3 as base, N,N′-dimethylethane-1,2-diamine as ligand, and toluene as solvent, with reaction temperature at 120 °C.

An efficient strategy for the synthesis of a variety of 2-animobenzimidazole derivatives has been developed. The reaction proceeded from o-haloanilines and carbodiimides via copper(I)-catalyzed domino reaction in the presence of tert-butoxide to afford the corresponding 2-animobenzimidazole derivatives in good to excellent yields. o-Haloanilines could be o-iodoaniline, o-bromoaniline, and o-chloroaniline derivatives. Carbodiimides could be symmetrical and unsymmetrical substrates with aryl or alkyl substituents. The reaction exhibited a good regioselectivity when unsymmetrical carbodiimides were employed.

Oxazirconacyclopentenes reacted with but-2-ynedioates in the presence of CuCl via tandem Michael addition/nucleophilic substitution to afford α-methylene-δ-lactone derivatives.

A copper-catalyzed method for the coupling of alkenyl halides with secondary amines has been developed. This protocol used a combination of 10 mol % copper iodide and 20 mol % N,N′-dimethylethane-1,2-diamine as catalyst. The reaction proceeded with various aromatic amines and alkenyl bromides or alkenyl iodides, and the enamines were formed in high yields with excellent regioselectivity and stereoselectivity under the reaction conditions.

An efficient synthetic approach to variously substituted thiophenes has been developed through copper-catalyzed tandem S-alkenylation of potassium sulfide with 1,4-diiodo-1,3-dienes.

Reaction of alkynylzirconates with allyl bromides afforded β-allyl-zirconacyclopentadienes with high selectivity in unique reaction site.

Direct transformation of five-membered zirconacycles to carbocyclic compounds is of great synthetic interest. The reaction of zirconacycles with electrophiles containing at least two reactive functional groups or an oxidant affords various carbocycles through cross coupling, addition, and/or oxidative coupling reactions. In this paper, we present our recent results on the zirconacycle-mediated formation of carbocycles, including: (1) 1,1-cycloaddition of oxalyl dichloride with zirconacycles; (2) benzoquinone-promoted coupling of zirconacyclopentadienes in the presence of CuCl; (3) cycloaddition of zirconacyclopentadienes to quinones; (4) cycloaddition of zirconacyclopentadiene with 2-bromoacrylate, 2-bromoacrylaldehyde and 3-bromofuran-2,5-dione in the presence of CuCl; (5) one-pot coupling of two alkynes and an alkene to form cyclohexene derivatives via zirconacyclopentadienes; and (6) dianionic cycloaddition of decatetraenes with esters or acyl chlorides to form nine-membered carbocycles.

A series of (1,2-diarylvinyl)phosphine ligands were synthesized, and their ruthenium complexes have been prepared. The structure of [(1,2-diphenylvinyl)phosphine](η6-cymene)RuCl2 (C1) was confirmed by X-ray crystallography. Ruthenium (1,2-diarylvinyl)phosphine complexes are highly efficient catalysts for direct ortho arylation of 2-arylpyridine with a range of aryl chlorides (electron-rich and electron-poor aromatic chlorides). Highly controllable formation of monoarylation and diarylation through functionalization of C−H bonds on the aromatic ring were achieved.

Zirconium promoted linear coupling of alkynes to generate bis(allene)s with high yields in the presence of nBuLi and chlorophosphines or trimethylsilyl trifluoromethanesulfonate.

Reaction of [(2-phosphino)ethenyl]zirconocene chloride (1) with CpM(CO)3Cl (M = Mo, W) in THF yielded the [(3-phosphino)propenoyl]dicarbonyl(cyclopentadienyl)metals {CpM(CO)2[(CO)CR═CRPPh2]} (2). When the reaction between [(2-phosphino)ethenyl]zirconocene chloride (1) and CpMo(CO)3Cl was carried out in the presence of a catalytic amount of Pd(CH3CN)2Cl2, [(3-phosphino)propenoyl]dicarbonyl(cyclopentadienyl)molybdenum, {CpMo(CO)2[(CO)CR═CRPPh2]}, was exclusively observed. When [(2-phosphino)ethenyl]zirconocene chloride (1) and MeCpW(CO)3Cl were reacted in the presence of a catalytic amount of CuCl, [(3-phosphino)propenoyl]dicarbonyl(methylcyclopentadienyl)tungsten, {MeCpW(CO)2[(CO)CR═CRPPh2]}, was formed. Their structures are determined by X-ray diffraction analysis.

Reaction of zirconophosphacyclobutenes with PdCl2(CH3CN)2 in THF yields the air- and heat-stable four-membered palladacyclic compounds in dimeric structures, which are characterized by X-ray diffraction.

Zirconocene−alkene complexes Cp2Zr(PMe3)(CH2═CHR) reacted with chlorodiphenylphosphine to form zircono-ethylphosphine derivatives with high regioselectivity, which could be converted into various β-functionalized alkyldiphenylphosphine oxides in the presence of CuCl.

Reaction of alkynes with Cp2ZrBu2 and chlorophosphate in the presence PR3 to form zircono-alkenylphosphonates, which can be converted into various β-functionalized alkenylphosphonates.

Zirconocene–ethylene complex Cp2Zr (CH2=CH2) reacted with chlorophosphate to form zircono-ethylphosphonate, which could be converted into various functionalized ethylphosphonates.

An iodine-catalyzed aerobic-oxidative C-H functionalization of o-alkylazoarenes to afford 2H-indazoles has been developed. CuI was found to be an effective additive to accelerate the regeneration of iodine in the catalytic cycle. This catalytic system is suitable for both electron-rich and electron-deficient azoarenes and tolerates a variety of functional groups with high yields. A gram-scale reaction was successfully conducted, proving the scalability of this reaction.

The MeOTf-catalyzed construction of indanones via arylalkyne–aldehyde metathesis and subsequent Nazarov cyclization has been reported. This reaction represents a sustainable and atom-economical approach for the preparation of indanones from readily available substrates with high stereoselectivity.

Direct cleavage of the NN bond of azo compounds by methyltriflate (MeOTf) leading to benzimidazoles has been described. In this reaction, the MeOTf serves as one carbon unit and inserts into the NN bond to form benzimidazole via cleavage of the NN bond and three C–H bonds and meanwhile formation of three C–N bonds.

MeOTf-induced carboannulation of arylnitriles and aromatic alkynes for synthesis of indenones under metal-free conditions has been described. When ortho-substituted benzonitriles were used, indeno[1,2-c]isoquinolines were formed.

The CuCl catalyzed direct trifluoromethylation of sp2 C–H bonds has been realized, using the Togni reagent as the CF3 source. This reaction achieves the goal of regio-selectively converting C–H into C–CF3 with ecological and readily available starting materials.

Copper-mediated electrophilic imination of alkenylzirconocenes generated in situ from alkynes and zirconocenes is accomplished under mild reaction conditions. The reaction can be used to prepare various 2-azadienes.

A novel copper-catalyzed oxidation of arene-fused cyclic amines to the corresponding cyclic imides has been developed. The reaction can be used to synthesize 1,3-disubstituted TPD in high yields.

Reaction of alkynylzirconates with allyl bromides afforded β-allyl-zirconacyclopentadienes with high selectivity in unique reaction site.

An effective regioselective cyclotrimerization of terminal alkynes is achieved by the direct utilization of NiCl2·6H2O, Zn, and 2-(benzimidazolyl)-6-(1-(arylimino)ethyl)pyridine in one step under ambient temperature.

Carbon dioxide (CO2), as a waste of manufacture, is a cheap and abundant C1 source. Utilization of CO2 for synthesis of carboxylic acids has been developed. Transition-metal complexes play a key role in catalytic carboxylation reactions employing CO2. This review summarizes recent advances in copper-catalyzed carboxylation reactions using CO2. The contents are arranged based on various substrates: organometallic reagents, aryl iodides, sodium sulfinates, terminal alkynes, arenes, heteroarenes, and unsaturated substrates.

An efficient strategy for the synthesis of a variety of 3-substituted isocoumarins has been developed. The reaction proceeded from o-halobenzoic acids and 1,3-diketones via a copper(I)-catalyzed domino reaction in DMF under the action of K3PO4 at 90–120 °C without a ligand to afford the corresponding 3-substituted isocoumarin derivatives in good to excellent yields. o-Halobenzoic acids could be o-iodobenzoic acid, o-bromobenzoic acid, and o-chlorobenzoic acid derivatives. 1,3-Diketones could be alkyl- and aryl-substituted 1,3-diketones.

Zirconium promoted linear coupling of alkynes to generate bis(allene)s with high yields in the presence of nBuLi and chlorophosphines or trimethylsilyl trifluoromethanesulfonate.

The zirconocene-catalyzed sequential ethylcarboxylation of alkenes using ethylmagnesium chloride and carbon dioxide has been developed. A range of alkenes were transformed into the corresponding carboxylic acids in high yields.

Copper-catalyzed coupling reactions have been recognized as one of the most useful strategies for the formation of C–N bonds. This perspective gives an overview of the recent developments in copper-catalyzed electrophilic amination for the construction of various amines and their derivatives, including the electrophilic amination of various organometallic reagents and direct C–H bonds as well as the annulative electrophilic amination of o-alkynylphenols and o-alkynylanilines.

I2-Mediated benzyl C–H functionalization has been developed for the synthesis of 2H-indazoles, which features high efficiency, simple conditions and no need for metals. Mechanistic experiments and DFT calculations have revealed halogen bond assistance and a radical chain process for this reaction. The azo group and the bound iodine cooperate in the hydrogen abstraction step, which circumvents the thermodynamic disfavor of direct hydrogen abstraction by a simple iodine radical.