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We cover the achievements and thought process that have emerged as a result of the recent use of iron salts as catalysts for the oxidative coupling, addition, and functionalization on constructing C−C bonds, C−N bonds, C−O bonds, C−S bonds, and C−P bonds. These transformations concomitantly require a stoichiometric oxidant to activate the catalyst: The low-cost and ubiquity of peroxides is often used as a result of their high oxidative reactivity, resulting in the widespread utilizations of iron catalysis through the initiation of radical processes. Here, we summarize the formation of diverse chemical bonds by using iron oxidative catalysis strategies, including 1) the oxidative coupling strategy and 2) the oxidative addition and functionalization strategy. The oxidative coupling strategy focuses on the formation of one chemical bond in a single reaction, whereas the oxidative addition and functionalization strategy includes the transformations that construct at least two chemical bonds.

A new silver-promoted oxidative ring opening/alkynylation of cyclopropanols with ethynylbenziodoxolones (EBX) is described. This method enables the formation of alkylated alkynes via a sequence of ring opening and alkynylation. Control experiments support a radical mechanism in this silver-promoted method.

A new 1,4-diazabicyclo[2.2.2]octane (DABCO) mediated synthesis of malonates from 3-halopropynoates, alcohols, and water is presented. This method proceeds under mild and metal-free conditions, and represents a new straightforward access to 1,3-dicarbonyl compounds.

Open a new door: The first example of alkene synthesis from alkyl electrophiles with Grignard reagents using the Kumada cross-coupling reaction strategy is reported. This method opens a new door for the Kumada cross-coupling reaction, allowing alkenes to be prepared from the reaction of tosylalkanes with Grignard reagents.

An efficient and reusable Cu2O/PPh3/TBAB (n-Bu4NBr) system for the cross-coupling reactions of aryl and heteroaryl halides with terminal alkynes has been developed. Four types of Cu2O, including bulky Cu2O, cubic Cu2O nanoparticles, octahedral Cu2O nanoparticles, and spherical Cu2O nanoparticles, were examined, and the octahedral Cu2O nanoparticles were found to be the most effective catalyst for the reaction. In the presence of the octahedral Cu2O nanoparticles, PPh3, and TBAB, a variety of aryl and heteroaryl halides were reacted with alkynes including alkynols smoothly in moderate to good yields. Noteworthy is that the Cu2O/PPh3/TBAB system can be recovered and reused several times without loss of any activities.

Oxindoles are an important class of heterocycles with unique biological activity that are found prevalently in numerous natural products and biologically active compounds. For these reasons, much attention has been given to the development of efficient methods for the preparation of such compounds. Traditionally, the practical approaches for the synthesis of oxindoles include the condensation of anilines with carbonyl compounds, such as diethyl ketomalonate, oxalyl chloride, or chloral hydrate, mediated by strong acids or bases. Recently, a step- and atom-economic C–H activation strategy was illustrated to access oxindoles through the difunctionalization of activated alkenes for these purposes. However, many of these transformations suffer from the cost of the transition-metal catalytic systems and/or limited substrate scope. In this review, we describe the recent studies of the difunctionalization of activated alkenes for the synthesis of diverse functionalized oxindoles that involves C–H oxidative radical coupling in the presence of an oxidant. These transformations are initiated either by the carbon radical resulting from the split of the carbon–hydrogen bond (1,2-dicarbofunctionalization) or by the carbon or heteroatom radical arising from the cleavage of the carbon–heteroatom (1,2-dicarbofunctionalization) or heteroatom–heteroatom bond (1,2-carboheterofunctionalization). Importantly, these C–H oxidative radical coupling transformations are generally performed with readily available oxidants and/or inexpensive iron or copper catalysts under neutral reaction conditions. 1 Introduction 2 Synthesis of Oxindoles via 1,2-Dicarbofunctionalization of Alkenes 2.1 1,2-Alkylarylation 2.2 1,2-Aryltrifluoromethylation 2.3 1,2-Carbonylarylation 3 Synthesis of Oxindoles via 1,2-Carboheterofunctionalization of Alkenes 3.1 1,2-Azidoarylation or 1,2-Arylnitration 3.2 1,2-Arylsulfonylation 3.2 1,2-Arylphosphorylation 4 Conclusion

An efficient and copper-free catalyst system for Sonogashira cross-coupling reaction is presented. In the presence of 3 mol-% of Pd(OAc)2 and 6 mol-% of 2-aminopyrimidine-4,6-diol, various aryl iodides and bromides can be coupled smoothly with terminal alkynes to afford the corresponding coupled alkynes in moderate to excellent yields under mild conditions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

An efficient method for palladium-catalyzed homocoupling reaction of terminal alkynes in the synthesis of symmetric diynes is presented. The results showed that both Pd(OAc)(2) and CuI played crucial roles in the reaction. In the presence of 2 mol % Pd(OAc)(2), 2 mol % CuI, 3 equiv of Dabco, and air, homocoupling of various terminal alkynes afforded the corresponding symmetrical diynes in moderate to excellent yields, whereas low yields were obtained without either Pd(OAc)(2) or CuI. Moreover, high TONs (turnover numbers; up to 940 000 for the reaction of phenylacetylene) for the homocoupling reaction were observed. Under similar reaction conditions, cross-coupling of 1-iodo-4-nitrobenzene with phenylacetylene was also carried out smoothly in quantitative yield. However, the presence of CuI disfavored the palladium-catalyzed Sonogashira cross-coupling reactions of the less active aryl iodides and bromides. In the presence of 0.01-2 mol % Pd(OAc)(2), a number of aryl iodides and bromides were coupled with terminal alkynes in good to excellent yields. It is noteworthy that this protocol employs mild, efficient, aerobic, copper-free, and ligand-free conditions.

A novel Lewis acid catalyzed annulation reaction has been established for the synthesis of benzocyclohepta[b]indoles. This method represents a new annulation strategy to a seven-membered carbocyclic ring system from two 3-(1H-isochromen-1-yl)-1H-indole molecules using Cu(OTf)2 catalyst; moreover, the products, benzocyclohepta[b]indoles, can be used as the rapid mercuric ion colorimetric detection reagents.

This new and simple process gives access to primary sulfones by using 1,2-bis(phenylsulfonyl)ethane as the sulfone source, for the first time.

An efficient copper-catalyzed α-aminoxylation of ketones with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) is presented.The copper on iron catalyst can be recovered and reused several times with high catalytic reactivity.

Copper-catalyzed amidation of acids with formamides or acetamide for the selective synthesis of amides with the aid of 1,4-diazabicyclo[2.2.2]octane as the ligand and tert-butyl hydroperoxide as the oxidant is presented. This method is highly compatible with a wide range of acids, including alkyl acids, aryl acids, α,β-unsaturated acids, and amino acids.

A combination of Cu2O nanoparticles with P(o-tol)3 shows highly catalytic activity for the Stille cross-coupling reaction. A series of copper catalysts and ligands were evaluated, and Cu2O nanoparticles combined with P(o-tol)3 provided the best results. In the presence of Cu2O nanoparticles and P(o-tol)3, a variety of aryl halides including aryl chlorides underwent the Stille reaction with organotins smoothly in moderate to excellent yields using inexpensive TBAB (n-Bu4NBr) as the medium. It is noteworthy that the Cu2O/P(o-tol)3/TBAB system can be recovered and reused at least three times without any loss of catalytic activity among the reactions of aryl iodides and activated aryl bromides.

[reaction: see text] PdCl2(PPh3)2 combined with TBAF under solvent-free conditions provided general and fast Sonogashira cross-coupling reactions of aryl halides with terminal alkynes. In particular, this protocol could be applied to the reactions of deactivated aryl chlorides. In the presence of 3 mol % of PdCl2(PPh3)2 and 3 equiv of TBAF, a number of ArX species (X = I, Br, Cl) were coupled with alkynes to afford the corresponding products in moderate to excellent yields under copper-, amine-, and solvent-free conditions.

Tosylalkanes and tosylethanones are used for the couplings to produce the desired target compounds.

The title reaction provides a new and mild approach to a number of indole products of type (III), (V), and (VII).

A simple process is developed for the double nucleophilic substitution of dichloromethane with aryloxymethyl aryl ketones to give functionalized pentanediones in good yields.

A general and selective palladium-catalyzed carbonylation of terminal alkynes method for the synthesis of (Z)-3-haloacrylates is presented. In the presence of a catalytic amount of PdX2 and 5 equiv of CuX2 (X = Cl and Br), terminal alkynes were carbonylated to afford the corresponding (Z)-3-haloacrylates exclusively in moderate to good yields. The results showed that the effect of solvent had a fundamental influence on the chemoselectivity and stereoselectivity of the palladium-catalyzed carbonylation reaction.

The regioselectivity of the present method is based on the N—O group as the directing moiety.

A novel, mild, and selective method for the synthesis of the compounds (III), (V), (VI), (VIII), and (IX) is reported.

Treatment of arylated alkynes of type (I), (III), (V), and (XI) with NBS and water provides a new and general approach to spiro[4,5]trienones present in biologically active compounds.

The oxidative thiolation of N,N-dimethylacetamide (IIa) leads to a variety of sulfides (V) as sole reaction products, while the analogous reaction of N,N-dimethylformamide (VI) and 1-methylpyrrolidin-one (IX) gives rise to a mixture of 2 derivatives.

Ruthenium-catalyzed intramolecular cyclization of an alkyne onto an α-amido C(sp3) carbon atom proceeds smoothly under base-free conditions to give quinolinones (II) and (IV) in moderate yields.

The optimized conditions allow the coupling of various iodoethynes with arylboronic acids under mild aerobic conditions without the need for ligands.

Indeno[1,2-c]chromenes are formed if the substrates bear a terminal aryl group at the alkyne moiety.

Activated aryl fluorides undergo copper-catalyzed etherification with H2O/tetrabutylammonium bromide in the presence of POPh3 and Cs2CO3.

A solvent-free copper/iron-catalyzed N-arylation of nitrogen-containing heterocycles with trimethoxysilanes method for the formation of C–N bonds has been developed. In the presence of Cu, FeCl3, TBAF, and air, a variety of nitrogen-containing heterocycles including imidazoles and triazoles were coupled with aryltrimethoxysilanes and vinyltrimethoxysilane to afford the corresponding products in moderate to excellent yields. It is noteworthy that the reaction is conducted under solvent-free and relatively low Cu/FeCl3 loadings conditions.

Pd(MeCN)2Cl2/PCy3 was found to be an efficient catalytic system for the Suzuki–Miyaura cross‐couplings of aryl chlorides with arylboronic acids under solvent‐free conditions. Furthermore, the presence of the conventional solvents had deleterious effect on the reaction. In the presence of Pd(MeCN)2Cl2, PCy3, and TBAF (tetra‐n‐butylammonium fluoride), a number of aryl chlorides including heteroaryl chlorides were coupled with arylboronic acids or heteroarylboronic acids smoothly to afford the corresponding products in moderate to excellent yields.

A novel and effective protocol for the synthesis of 2-substituted 3-halo-1 H-indoles by PdX 2 /CuX 2 -catalyzed annulations of 2-ethynylbenzeneamines has been developed. In the presence of PdX 2 and CuX 2 , the annulation reactions of a variety of 2-ethynylbenzeneamines were conducted in moderate to good yields. It is noteworthy that only N-acetyl-protected 2-ethynylbenzeneamines can undergo the reaction successfully.

Ligand-free palladium-catalyzed Suzuki–Miyaura cross-couplings between aryl halides and arylboronic acids performed at room temperature are presented. It was found that both solvent and base had a fundamental influence on the reaction, and the most effective system in terms of yield and rate was observed to be the combination of Pd(OAc)2 with MeONa and alcohols. In the presence of Pd(OAc)2 and MeONa, a variety of aryl halides reacted very rapidly with arylboronic acids in good to excellent yields at room temperature in EtOH as the solvent. Moreover, the Pd(OAc)2/MeONa catalytic system could also be applied in couplings between heteroaryl halides and arylboronic acids to provide satisfactory results in MeOH as the solvent after prolonged reaction times. It is noteworthy that the reactions were conducted under mild, aerobic, and ligand-free conditions.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Cy 2 NH·HX was found to improve the cyclization reactions of o-(alk-1 -ynyl)benzoates and (Z)-alk-2-en-4-ynoate with CuX 2 (X = Cl, Br) to synthesize the corresponding 4-haloisocoumarins and 5-bromo-2-pyrone, respectively. In the presence of two equivalents of CuCl 2 , cyclization of methyl 2-(2-phenylethynyl)benzoate was conducted smoothly to afford the corresponding desired product in 83% yield after 24 hours, whereas the yield was enhanced to 91% in eight hours when 0.1 equivalent of Cy 2 NH·HCl was added. Under the standard reaction conditions, a variety of o-(alk-1 -ynyl)benzoates and (Z)-alk-2-en-4-ynoate underwent the cyclization reaction with CUX 2 to provide the corresponding 4-haloisocoumarins and 5-bromo-2-pyrone, respectively, in moderate to excellent yields.

Polymer-supported DABCO–palladium complex was observed as to be efficient and reusable catalytic system for the Suzuki–Miyaura cross-coupling reaction. In the presence of 0.25 mol % of the polymer-supported DABCO–palladium complex, a variety of aryl bromides were coupled with arylboronic acids efficiently in an aqueous ethanol at room temperature under air. Moreover, the reaction was very rapid, and the catalyst could be recovered readily from the reaction by simple filtration and could be reused at least five times.

The Sonogashira cross-coupling of aryl halides with terminal alkynes catalyzed by an inexpensive copper(II) acetate/1,4-diphenyl-1,4-diazabuta-1,3-diene [Cu(OAC) 2 /DAB-Ph] catalytic system is reported. A series of ligands, including diazabutadiene systems, N,N-dimethylglycine, L-proline, ethylenediamine, and phosphines, were evaluated, and 1,4-diphenyl-l,4-diazabuta-1,3-diene provided the best results. In the presence of copper(II) acetate (10 mol%), l,4-diphenyl-l,4-diazabuta-1,3-diene (20 mol%), and tetrabutylammonium fluoride (3 equiv), a number of aryl iodides or bromides were treated smoothly with alkynes to afford the corresponding products in moderate to excellent yields. It is noteworthy that the reaction is conducted under aerobic and solvent-free conditions.

An efficient bromination protocol for the synthesis of α-bromo-β-keto esters has been developed. In PEG-400 (poly(ethylene glycol-400)), a variety of β-keto esters were treated with NBS (N-bromosuccinimide) at room temperature to selectively afford the corresponding α-monobromination products in excellent yields. It is noteworthy that the reaction was conducted under mild, environmentally benign and catalyst-free conditions.

The scope and limitations of the Pd(OAc)2/DABCO (1,4-diaza-bicyclo[2.2.2]octane)-catalyzed Suzuki–Miyaura cross-coupling reactions have been demonstrated. The results showed that the effect of solvent had a fundamental influence on the reaction. In the presence of Pd(OAc)2 and DABCO, both aryl bromides and aryl chlorides all worked well with arylboronic acids to form biaryls, heteroaryl-aryls, and biheteroaryls in moderate to excellent yields using DMF as the solvent. Additionally, the reactions of aryl bromides were conducted under relatively mild conditions.

Efficient and solvent-free copper-catalyzed N-arylations of imidazoles with aryl and heteroaryl halides have been demonstrated. In the presence of CuBr, 2-aminopyrimidine-4,6-diol, and TBAF (n-Bu4NF), a variety of imidazoles underwent the N-arylation reaction with aryl and heteroaryl halides smoothly in moderate to excellent yields. Noteworthy is that the reaction is conducted under solvent-free conditions.

Excellent results have been achieved in the Cu(OAc)2-catalyzed Sonogashira cross-couplings of aryl iodides and activated aryl bromides utilizing TBAF (tetrabutylammonium fluoride) as the base and 4,6-dimethoxypyrimidin-2-amine as the ligand. It is noteworthy that the reaction is conducted under aerobic, solvent-free and palladium-free conditions.

The combination of Pd(OAc) 2 , TBAB and PEG-400 [poly(ethylene glycol-400)] was introduced as a reusable and efficient system for the Suzuki-Miyaura cross-coupling reaction. In the presence of 0.01 to 3 mol% of Pd(OAc) 2 , 10 mol% of TBAB, 2 equivalents of K 2 CO 3 and 4 g of PEG-400, a number of aryl halides were coupled with arylboronic acids efficiently to afford moderate to excellent yields of the corresponding products under ligand-free conditions. Moreover, the system can be reused three times without any loss of catalytic activity.

[reaction: see text] A novel and selective palladium-catalyzed annulation of 2-alkynylphenols method for the synthesis of 2-substituted 3-halobenzo[b]furans is presented. In the presence of PdX(2), CuX(2), and HEt(3)NX, 2-substituted 3-halobenzo[b]furans were selectively obtained as the major products. The mechanism of the reaction was also discussed.

PEG-400 [poly(ethylene glycol-400)] was found to improve the Pd(OAc)2/DABCO-catalyzed aqueous Suzuki–Miyaura and Stille cross-coupling reactions. In the presence of Pd(OAc)2, DABCO, and PEG-400, a variety of aryl halides were coupled with arylboronic acids or organotin compounds efficiently to afford the corresponding cross-coupled products in moderate to excellent yields. The turnover numbers was up to 900,000 for the Suzuki–Miyaura reaction and up to 9800 for the Stille reaction. The catalyst system was also effective for Heck and Sonogashira cross-coupling reactions to some extent.

Pd(OAC) 2 /DABCO was found to be an inexpensive and efficient catalyst system for Hiyama cross-coupling reactions of aryl halides with aryltrimethoxysilanes. In the presence of Pd(OAc) 2 , DABCO, and TBAF, coupling of a number of aryl halides with aryltrimethoxysilanes underwent efficiently to afford the corresponding cross-coupled products in moderate to excellent yields.

The combination of Pd(OAc) 2 and DABCO (triethylenediamine) was observed as an efficient catalytic system for the Heck cross-coupling reaction. In the presence of Pd(OAc) 2 and DABCO, a number of ArX (X = I, Br, and Cl) were coupled with olefins efficiently and selectively to afford the corresponding unsymmetric internal olefins in good to excellent yields. Furthermore, the Pd(OAc) 2 /DABCO-catalyzed Heck cross-coupling reaction provided high TONs up to 1,000,000.