3.7. Palladium Nanoparticles as Catalysts 888 3.8. Other Transition-Metal Complexes 888 3.9. Transition-Metal-Free Reactions 889 4. Applications 889 4.1. Alkynylation of Arenes 889 4.2. Alkynylation of Heterocycles 891 4.3. Synthesis of Enynes and Enediynes 894 4.4. Synthesis of Ynones 896 4.5. Synthesis of Carbocyclic Systems 897 4.6. Synthesis of Heterocyclic Systems 898 4.7. Synthesis of Natural Products 903 4.8. Synthesis of Electronic and Electrooptical Molecules 906

https://www.chem.ccu.edu.tw/~joyce/referance/ericyang/Chem.%20Rev/Chem.%20Rev.%202007,%20107,%20874-922.pdf

The Sonogashira Reaction: A Booming Methodology in Synthetic Organic Chemistry†

ion. The oxidative addition mechanism was originally proposed22i because of the lack of a strong rate dependence on polar factors and on the acidity of the medium. Later, however, the electrophilic substitution mechanism also was proposed. Recently, the oxidative addition mechanism was confirmed by investigations into the decomposition and protonolysis of alkylplatinum complexes, which are the reverse of alkane activation. There are two routes which operate in the decomposition of the dimethylplatinum(IV) complex Cs2Pt(CH3)2Cl4. The first route leads to chloride-induced reductive elimination and produces methyl chloride and methane. The second route leads to the formation of ethane. There is strong kinetic evidence that the ethane is produced by the decomposition of an ethylhydridoplatinum(IV) complex formed from the initial dimethylplatinum(IV) complex. In D2O-DCl, the ethane which is formed contains several D atoms and has practically the same multiple exchange parameter and distribution as does an ethane which has undergone platinum(II)-catalyzed H-D exchange with D2O. Moreover, ethyl chloride is formed competitively with H-D exchange in the presence of platinum(IV). From the principle of microscopic reversibility it follows that the same ethylhydridoplatinum(IV) complex is the intermediate in the reaction of ethane with platinum(II). Important results were obtained by Labinger and Bercaw62c in the investigation of the protonolysis mechanism of several alkylplatinum(II) complexes at low temperatures. These reactions are important because they could model the microscopic reverse of C-H activation by platinum(II) complexes. Alkylhydridoplatinum(IV) complexes were observed as intermediates in certain cases, such as when the complex (tmeda)Pt(CH2Ph)Cl or (tmeda)PtMe2 (tmeda ) N,N,N′,N′-tetramethylenediamine) was treated with HCl in CD2Cl2 or CD3OD, respectively. In some cases H-D exchange took place between the methyl groups on platinum and the, CD3OD prior to methane loss. On the basis of the kinetic results, a common mechanism was proposed to operate in all the reactions: (1) protonation of Pt(II) to generate an alkylhydridoplatinum(IV) intermediate, (2) dissociation of solvent or chloride to generate a cationic, fivecoordinate platinum(IV) species, (3) reductive C-H bond formation, producing a platinum(II) alkane σ-complex, and (4) loss of the alkane either through an associative or dissociative substitution pathway. These results implicate the presence of both alkane σ-complexes and alkylhydridoplatinum(IV) complexes as intermediates in the Pt(II)-induced C-H activation reactions. Thus, the first step in the alkane activation reaction is formation of a σ-complex with the alkane, which then undergoes oxidative addition to produce an alkylhydrido complex. Reversible interconversion of these intermediates, together with reversible deprotonation of the alkylhydridoplatinum(IV) complexes, leads to multiple H-D exchange

Activation of c-h bonds by metal complexes

Collectively, palladium-catalyzed coupling reactions represent some of the most powerful and versatile tools available to synthetic organic chemists. Their widespread popularity stems in part from the fact that they are generally tolerant to a large number of functional groups, which allows them to be employed in a wide range of applications. However, for many years a major limitation of palladium-catalyzed coupling processes has been the poor reactivity of aryl chlorides, which from the standpoints of cost and availability are more attractive substrates than the corresponding bromides, iodides, and triflates. Traditional palladium/triarylphosphane catalysts are only effective for the coupling of certain activated aryl chlorides (for example, heteroaryl chlorides and substrates that bear electron-withdrawing groups), but not for aryl chlorides in general. Since 1998, major advances have been described by a number of research groups addressing this challenge; catalysts based on bulky, electron-rich phosphanes and carbenes have proved to be particularly mild and versatile. This review summarizes both the seminal early work and the exciting recent developments in the area of palladium-catalyzed couplings of aryl chlorides.

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Palladium-Catalyzed Coupling Reactions of Aryl Chlorides

6.4. Polyynes 3123 6.5. Using R-Hydroxy Stannanes 3124 6.6. Using the Hurtley Reaction 3124 6.7. Using a Methylenation Reaction 3125 7. Conclusions and Future Prospects 3125 8. Uncommon Abbreviations 3125 9. Acknowledgments 3125 10. Note Added in Proof 3125 11. References 3126 * Authorstowhomcorrespondenceshouldbeaddressed(evano@chimie.uvsq.fr, nicolas.blanchard@uha.fr). † Université de Versailles Saint Quentin en Yvelines. ‡ Université de Haute-Alsace. Chem. Rev. 2008, 108, 3054–3131 3054

Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis.

https://www.chem.ccu.edu.tw/~joyce/referance/ericyang/Coord.%20Chem.%20Rev/Coord.%20Chem.%20Rev.%202004,%20248,%202337-2364.pdf

Copper in cross-coupling reactions: The post-Ullmann chemistry

Propargyl ethers HCCCH2OR [R = alkyl or-CH(CH8)(OC2H5)] have been isomerized with good yields into the corresponding allenyl ethers CH2CCHOR by warming with potassium tert.-butoxide at 70°.

These allenyl ethers can be metallated with butyllithium in ether or alkali amides in liquid ammonia. In ether, subsequent alkylation with alkyl halides R′Hal affords α-substituted allenyl ethers CH2CC(R′)OR. Alkylation in liquid ammonia produces a mixture of this same compound and the γ-substituted product R′CHCCHOR. In both cases reasonable yields are obtained. Sodamide and potassium amide quickly convert allenyl ethers CH2CCHOR into metallated propargyl ethers MCC-CH2OR (M = Na or K). If alkylation is not performed almost simultaneously with the metallation with sodamide or potassium amide, the only alkylation product obtained is R′CCCH2OR.

Preparation, metallation and alkylation of allenyl ethers

I. General Practical Information. II. Metallation of Acetylenes. III. Functionalization of Metallated Acetylenes with Alkyl Halides, a-Haloethers, Epoxides and Alkyl Orthoformates. IV. Ethynylation and Alkynylation of Carbonyl Compounds. V. Carboxylation, Alkylation and Related Reactions. VI. Silylation, Stannylation and Phosphorylation. VII. Sulfenylations and Related Reactions. VIII. Halogenation and Cyanation. IX. Introduction of the Triple Bond by Elimination and Addition-Elimination Reactions. X. Couplings of Acetylenes Assisted by Copper and Palladium Compounds. XI. Base-Promoted Interconversions of Acetylenes. XII. Miscellaneous Preparations of Acetylenic Derivatives. Instructions for Searching. List of Selected Compounds. Type-Compound-Method Index. References.

Preparative acetylenic chemistry

I. Reactivity of Polar Organometallic Intermediates.- 1 Introduction.- 2 Alkylation.- 2.1 Reactivity-A Qualitative Comparison of the Polar Organometallics.- 2.2 Scope of the Alkylation Reaction.- 2.3 Dialkylation.- 2.4 Remarks on the Reaction Conditions of Alkylations.- 3 Hydroxyalkylation with Epoxides.- 4 Hydroxyalkylation with Carbonyl Compounds.- 5 Formylation with Dimethylformamide.- 6 Carboxylation.- 7 Reaction of Organoalkali Compounds with Carbon Disulfide.- 8 Addition of Organoalkali Compounds to Isocyanates and Isothiocyanates.- 9 Sulfenylation.- 10 Trimethylsilylation.- 11 Reactions of Organometallic Compounds with Chloroformates and Dimethylcarbamoyl Chloride.- 12 Reactions of Organoalkali Compounds with Halogenating Agents.- 13 Conjugate Additions.- II. Metallation of Aromatic and Olefinic Hydrocarbons.- 1 Introduction.- 2 Metallation of Alkylbenzenes and Alkylnaphthalenes.- 3 Dimetallation of Aromatic Compounds.- 4 Metallation of Olefinic Compounds.- 5 Stereochemistry of Allylic Metallations.- 6 Dimetallation of Olefins.- 7 Experiments.- 7.1 Metallation of Toluene with BuLi * t-BuOK in Hexane.- 7.2 Metallation of 1- and 2-Methylnaphthalene with BuLi * t-BuOK.TMEDA in Hexane.- 7.3 ?-Metallation of Ethylbenzene.- 7.4 ?,??-Dimetallation of m-Xylene.- 7.5 Lithiation of Toluene, Xylene, Mesitylene with BuLi * TMEDA..- 7.6 Metallation of Propene and Isobutene.- 7.7 Metallation of Various Olefins with Strongly Basic Reagents.- 7.8 Metallation of Cyclohexene.- 7.9 Dimetallation of Isobutene.- 7.10 Metallation of Isoprene.- 7.11 Metallation of ?-Methylstyrene.- 7.12 Metallation of Indene.- 7.13 Metallation of Cyclopentadiene.- 7.14 Preparation of 1,4-Cyclohexadiene.- 7.15 Allylbenzene.- 8 Selected Procedures from Literature.- III. Metallation of Saturated Sulfur Compounds.- 1 Introduction.- 2 Substrates and Metallation Conditions.- 2.1 S,S-Acetals.- 2.2 Methoxymethyl Phenyl Sulfide.- 2.3 Ethythiomethyl Ethyl Sulfoxide.- 2.4 Orthothioformates.- 2.5 Dialkyl Sulfides and Alkyl Aryl Sulfides.- 2.6 Dialkyl and Alkyl Aryl Sulfoxides and Sulfones.- 3 Experiments.- 3.1 Lithiation of Formaldehyde Dimethylthioacetal with BuLi in THF and Hexane.- 3.2 Lithiation of Formaldehyde Dimethylthioacetal with BuLi * TMEDA in Hexane.- 3.3 Reaction of Lithiated Bis(methylthio)methane with Alkyl Halides.- 3.4 Hydroxyalkylation of Lithiated Bis(methylthio)methane with Epoxides.- 3.5 Reaction of Lithiated 1,3-Dithiane with 1-Bromo-3-chloropropane and Ring Closure of the Coupling Product Under the Influence of Butyllithium.- 3.6 Hydroxymethylation of Bis(methylthio)methane with Paraformaldehyde.- 3.7 Reaction of Lithiated Bis(methylthio)methane with Dimethylformamide and Subsequent Acid Hydrolysis.- 3.8 Reaction of Lithiated Bis(methylthio)methane with Carbon Dioxide.- 3.9 Reaction of Lithiated Bis(methylthio)methane with Dimethyl Disulfide and Trimethylchlorosilane.- 3.10 Lithiation of Methoxymethyl Phenyl Sulfide and Subsequent Reaction with Dimethylformamide.- 3.11 Reaction of Lithiated Bis(methylthio)methane with Methyl Isothiocyanate and N,N-Dimethyl Carbamoyl Chloride.- 3.12 Peterson Olefination Reactions with Lithiated Trimethylsilyl Bis(methylthio)methane. Preparation of Ketene Thioacetals.- 3.13 Conjugate Addition of Lithiated S,S-Acetals and Corresponding S-Oxides to 2-Cyclohexen-1-one and Methyl Acrylate.- 3.14 Lithiation of Dimethyl Sulfide and Methyl Phenyl Sulfide and Subsequent Reaction of the Lithium Compounds with Benzaldehyde and Trimethylchlorosilane.- 3.15 Lithiation of (Trimethylsilylmethyl)Phenyl Sulfide and Subsequent Reaction with Acetone.- 3.16 Dilithiation of Methyl Phenyl Sulfide and Subsequent Trimethylsilylation.- 3.17 Reaction of Bis(methylthio)methane with Potassium Amide in Liquid Ammonia and Subsequent Reaction with Oxirane..- 3.18 Reaction of Dimethylsulfoxide with Sodamide in Liquid Ammonia and Subsequent Alkylation with Bromohexane.- 3.19 Mono-Deuteration of Bis(ethylthio)methane.- 3.20 Lithiation of Methyl Phenyl Sulfoxide with LDA and Subsequent Alkylation with Butyl Bromide.- 3.21 Preparation of Formaldehyde-S,S-Acetals.- 3.22 Preparation of Ethylthiomethyl Ethyl Sulfoxide and Methyl Phenyl Sulfoxide.- 3.23 Preparation of Benzaldehyde Dimethylthioacetal.- 4 Selected Procedures from Literature.- IV. ?-Metallation of Derivatives of Toluene Containing Heterosubstituents.- 1 Scope of this Chapter.- 2 Experiments.- 2.1 Metallation of N,N-Dimethyl-ortho-Toluidine.- 2.2 Synthesis of ortho-Pentylphenol via Potassiation of O-Protected ortho-Cresol.- 2.3 Dimetallation of ortho-Cresol.- 2.4 Metallation of o-and p-Tolunitrile with Alkali Amides in Liquid Ammonia and Alkali Diisopropylamide in THF-Hexane Mixtures.- 2.5 ?-Lithiation of p-Toluene-N,N-Dimethylsulfonamide.- V. Metallation of Heterosubstituted Allylic and Benzylic Compounds.- 1 Introduction.- 2 Substrates and Metallation Conditions.- 2.1 Allylic Amines and Ethers.- 2.2 Allylic and Pentadienylic Sulfur, Silicon and Selenium Compounds.- 2.3 Benzylic Amines, Silanes and Sulfides.- 2.4 Regiochemistry of the Reactions of Allylic Alkali Metal Compounds with Electrophiles.- 3 Experiments.- 3.1 Metallation of N,N-Dialkyl Allylamines with BuLi * TMEDA and BuLi * t-BuOK.- 3.2 Metallation of Allyl t-Butyl Ether with BuLi * t-BuOK.- 3.3 Lithiation of Allyl Trimethylsilane with BuLi * TMEDA.- 3.4 Lithiation of Methyl Allyl Sulfide and Phenyl Allyl Sulfide with BuLi.- 3.5 Metallation of Methyl Isopropenyl Ether with BuLi * t-BuOK.- 3.6 ?-Metallation of Benzyl Dimethylamine with BuLi * t-BuOK.- 3.7 Lithiation of Methyl Benzyl Sulfide and Benzyl Trimethylsilane.- 3.8 Preparation of N,N-Dimethyl Allylamine and N,N-Diethyl Allylamine.- 3.9 Preparation of t-Butyl Allyl Ether.- 3.10 Methyl Allyl Sulfide, Methyl Benzyl Sulfide and Phenyl Allyl Sulfide.- 3.11 Preparation of Allyl Trimethylsilane.- VI. Metallation of Heterocyclic Compounds.- 1 Introduction.- 2 Metallation of Alkyl Derivatives of Pyridine and Quinoline.- 3 Lateral Metallation of 2-Substituted Oxazolines, Thiazolines, Dihydrooxazines and Thiazoles.- 4 Experiments.- 4.1 General Procedure for the Metallation of Mono-, Di- and Trimethyl Pyridines and Quinolines in Liquid Ammonia and the Subsequent Alkylation.- 4.2 Conversion of 2-Methylpyridine, 2,4-Dimethylpyridine, 2,6-Dimethylpyridine and 2,4,6-Trimethylpyridine into the 2-Lithiomethyl Derivatives.- 4.3 Regiospecific Generation of 4-Metallomethylpyridines in Organic Solvents.- 4.4 Metallation of 3-Methylpyridine.- 4.5 Lithiation of 2-Methylthiazoline.- 4.6 Lithiation of 2,4,4,6-Tetramethyl-5,6-dihydro-1,3-oxazine.- 4.7 Dimetallation of 2,6-Dimethylpyridine.- 5 Organic Syntheses Procedures.- VII. Metallation of Aldimines and Ketimines.- 1 Introduction.- 2 Conditions for the Metallation.- 3 Experiments.- 3.1 Lithiation of Aldimines and Ketimines with LDA.- 3.2 Alkylation of Lithiated Imines.- 3.3 Metallation of Aldimines by Sodamide in Liquid Ammonia.- 3.4 Trimethylsilylation and Methylthiolation of Lithiated Imines.- 3.5 Conversion of Imines into Aldehydes and Ketones.- 3.6 Synthesis of ?,?-Unsaturated Aldehydes from Trimethylsilylated Aldimines.- 3.7 Preparation of Aldimines and Ketimines.- 4 Organic Syntheses Procedures.- VIII. Metallation of Nitriles and Isonitriles.- 1 Introduction.- 2 ?-Metallation of Nitriles.- 3 Metallation of Isonitriles.- 4 Experiments.- 4.1 Metallation of Nitriles with Alkali Amide in Liquid Ammonia.- 4.2 Lithiation of Nitriles and Isonitriles in a Mixture of THF and Hexane.- 4.3 Alkylation of Metallated Nitriles in Liquid Ammonia and in Organic Solvents.- 4.4 Reaction of Metallated Nitriles with Aldehydes and Ketones.- 4.5 Reaction of Lithioacetonitrile with Epoxides.- 4.6 Reaction of Lithiomethyl Isocyanide with Hexyl Bromide, Oxirane and Cyclohexanone.- 4.7 Conversion of Acetaldehyde into the Cyanohydrine and Protection of the OH-Group of the Cyanohydrine with Ethyl Vinyl Ether.- IX. Generation of Lithium Halocarbenoids.- 1 Introduction.- 2 Methods of Generation of Lithium Halocarbenoids.- 3 Experimental Conditions and Techniques in Carbenoid Chemistry.- 4 Experiments.- 4.1 Lithiation of Dichloromethane.- 4.2 Lithiation of 1,1-Dichloroalkanes.- 4.3 Lithiation of Dibromomethane.- 4.4 Lithiation of Chloroform.- 4.5 Lithiation of Bromoform.- 4.6 Lithiation of 7,7-Dibromonorcarane.- 4.7 Lithiation of Ethyl Bromoacetate.- X. Metallation of Carbonyl and Thiocarbonyl Compounds.- 1 Introduction.- 2 Mono Metallation of Carbonyl and Thiocarbonyl Compounds.- 3 Other Methods for the Generation of Enolates and Enethiolates.- 4 Dimetallation of Carbonyl and Thiocarbonyl Compounds.- 5 Experiments.- 5.1 Conversions of Ketones into Lithium Enolates and Subsequent Trimethylsilylation (General Procedure).- 5.2 Reaction of 1-Trimethylsilyloxy-l-Heptene with Butyllithium.- 5.3 Metallation of Carboxylic Esters with LDA.- 5.4 Metallation of Carboxylic Esters with Alkali Amides in Liquid Ammonia.- 5.5 Metallation of N-Methylpyrrolidine and ?-Butyrolactone with LDA.- 5.6 Lithiation of Methyl Crotonate.- 5.7 Lithiation of Thiolesters, Thionesters and Dithioesters with LDA (General Procedure).- 5.8 Metallation of Dithioesters with Alkali Amides in Liquid Ammonia.- 5.9 Dimetallation of Carboxylic Acids.- 5.10 Dimetallation of Pentane-2,4-dione with Sodamide in Liquid Ammonia.- 5.11 Dimetallation of Pentane-2,4-dione with LDA.- 5.12 1-Trimethylsilyloxy-l -heptene.- Metallation-Functionalization Index (Vol. 2).- Syntheses of Reagents and Starting Compounds (Vols. 1 and 2)..- Complementary Index (Vols. 1 and 2).- Typical Procedures and Special Techniques (Vols. 1 and 2).- Purification and Storage and Some Reagents and Solvents (Vols. 1 and 2).

Preparative polar organometallic chemistry

Catalysts, Ligands and Reagents Procedures for the Preparation of Halogen Compounds Cross Coupling between 1-Alkynes and 1-Bromoalkynes Copper Catalyzed Aminoalkylation of Acetylenes Copper(I)halide Catalyzed Oxidative Coupling of Acetylenes Copper(I)halide Catalyzed Substitution of sp2-Halogen by Alkoxide Copper Catalyzed Carbon-Carbon Bond Formation by 1,1- and 1,3-Substitution Reactions Nickel Catalyzed Iodo-Dechlorination and Iodo-Debromination of sp2-Halides Nickel and Palladium Catalyzed Cyanation of sp2-Halides and sp2-Triflates Couplings of Acetylenes with sp2-Halides Nickel and Palladium Catalyzed Cross Coupling Reactions with Organometallic Intermediates.

Application of Transition Metal Catalysts in Organic Synthesis

Reaction between lithiated allenic compounds and isothiocyanates, R'N=C=S, in most cases gives exclusively thioimidates with the allenic structure, C=C=CC(SLi)=NR 1 . These intermediates have been used in novel approaches to 2,3-dihydropyridines, pyrroles, quinolines, cyclobutanopyrrolines, and thiophene or dihydrothiophene derivatives. The procedures leading to the heterocycles with a nitrogen atom in the ring involve 5-alkylation followed by simple heating or by treatment with copper(I) halide. 2-Aminothiophenes and 2-imino-2,5-dihydrothiophenes are formed by intramolecular nucleophilic attack of the thiolate moiety on the allenic system and subsequent addition of methyl iodide or protonation. 1 Introduction 2 Generation of Allenic Lithium Compounds 3 Formation of 2,3-Dihydropyridines or Mixtures of 2,3-Dihydropyridines and Pyrroles 4 Directed Synthesis of Pyrroles 5 Synthesis of Quinolines 6 Synthesis of Cyclobutanopyrrolines 7 Synthesis of Thiophene and Dihydrothiophene Derivatives 8 Concluding Remarks.

Lambert Brandsma

Papers

Preparation, metallation and alkylation of allenyl ethers

Preparative acetylenic chemistry

Preparative polar organometallic chemistry

Application of Transition Metal Catalysts in Organic Synthesis

Allenic Compounds and Isothiocyanates as Key Building Units in the Synthesis of Heterocycles