Carbon-carbon Bond-forming Reactions Research Articles

A DFT Study on the Reaction Pathways for CarbonCarbon Bond‐Forming Reactions between Propargylic Alcohols and Alkenes or Ketones Catalyzed by Thiolate‐Bridged Diruthenium Complexes

The reaction pathways of two types of the carbon-carbon bond-forming reactions catalyzed by thiolate-bridged diruthenium complexes have been investigated by density-functional-theory calculations. It is clarified that both carbon-carbon bond-forming reactions proceed through a ruthenium-allenylidene complex as a common reactive intermediate. The attack of pi electrons on propene or the vinyl alcohol on the ruthenium-allenylidene complex is the first step of the reaction pathways. The reaction pathways are different after the attack of nucleophiles on the ruthenium-alkynyl complex. In the reaction with propene, the carbon-carbon bond-forming reaction proceeds through a stepwise process, whereas in the reaction with vinyl alcohol, it proceeds through a concerted process. The interactions between the ruthenium-allenylidene complex and propene or vinyl alcohol have been investigated by applying a simple way of looking at orbital interactions.

SYNTHESIS OF O-SUBSTITUTED BENZOPHENONES BY GRIGNARD REACTION OF 3-SUBSTITUTED ISOCOUMARINS

ABSTRACT A series of o-substituted benzophenones was prepared by efficient method involving the 3-substituted isocoumarins and phenylmagnesium bromide. The reaction was completed in presence of anhydrous ether under dry ice-solvent bath in few hours with modest to good yields.Key words: Isocoumarins, diketones, aryl, phenyl magnesium bromide, ether, dry ice.e-mail: nawaz_f@yahoo.co.in. INTRODUCTION Synthetic and naturally occurring isocoumarins possess important biological properties. They are useful intermediates in the synthesis of a variety of carbocyclic and heterocyclic compounds 1-6 .In continuous of our interest in carbon-carbon bond formation reaction 7-12 ,the present paper presents an efficient method to synthesize o-substituted benzophenones (2) from 3-substitued isocoumarins (1) and phenyl magnesium bromide in presence of anhydrous ether under dry ice-solvent bath. Benzophenone and its derivatives are important intermediates in dyes, pharmaceutical and other chemical industries

Exploration of Molybdenum(V) Chloride as a Lewis Acid Catalyst in Various C-C Bond Formation Reactions

The catalytic activity of Molybdenum(V) chloride as a Lewis acid in carbon-carbon bond formation reactions has been described. The reactions of various substrates viz. aldehydes, benzyl alcohols, glucals and aminals with carbon nucleophiles were studied in the presence of MoCl5 as a catalyst. Progress of all the reactions proceeded smoothly to furnish the corresponding products in good yields. Keywords: Molybdenum(V) chloride, carbon-carbon bond formation, allylation, Lewis acid, glycosylation

Synthesis of Furans, Pyrroles and Thiophenes from a Single Substrate

Five-membered heterocycles are important structural units found in all fields of organic chemistry. The authors demonstrate an sp³-hybridized carbon-carbon bond-forming reaction to produce 1,4-diketones that were further elaborated to methylthio-substituted furans, pyrroles and thiophenes via the Paal-Knorr cyclization in good yields.

Optically Active Chiral Ligands, Ferrocenyloxazolinylphosphines (FOXAPs): Development and Application to Catalytic Asymmetric Reactions

The development of optically active chiral ligands, ferrocenyloxazolinylphosphines (FOXAPs), and their application to catalytic asymmetric reactions are reviewed. FOXAPs have been prepared in high yields from the corresponding chiral oxazolinylferrocenes via diastereoselective lithiation followed by quenching with chlorodiphenylphosphine. They work quite effectively as chiral ligands for a variety of transition-metal-catalyzed asymmetric reactions such as hydrosilylation and transfer hydrogenation of ketones and imines, kinetic resolution of alcohols, carbon-carbon bond-forming reactions and ring-opening reactions.

Metallocenyl Dendrimers and Their Applications in Molecular Electronics, Sensing, and Catalysis

We have investigated the movement of electrons around the peripheries of dendrimers and between their redox termini and electrodes through studies of the electrochemistry of dendrimers presenting metallocenes (and other transition metal sandwich complexes) as terminal groups. Because these compounds can be stabilized in both their oxidized and their reduced forms, their electrochemical and chemical redox processes proceed without decomposition (chemical reversibility). Most interestingly, electrochemical studies reveal that electron transfer within the dendrimers and between the dendrimers and electrodes are both very fast processes when the branches are flexible (electrochemical reversibility). When the dendrimer branches are sufficiently long, the redox events at the many termini of the metallodendrimer are independent, appearing as a single wave in the cyclic voltammogram, because of very weak electrostatic effects. As a result, these metallodendrimers have applications in the molecular recognition, sensing, and titration of anions (e.g., ATP(2-)) and cations (e.g., transition metal complexes). When the recognition properties are coupled with catalysis, the metallodendrimers function in an enzyme-like manner. For example, Pd(II) can be recognized and titrated using the dendrimer's terminal redox centers and internal coordinate ligands. Redox control over the number of Pd(II) species located within a dendrimer allows us to predetermine the number of metal atoms that end up in the form of a dendrimer-encapsulated Pd nanoparticle (PdNP). For hydrogenation of olefins, the efficiency (turnover frequency, TOF) and stability (turnover number, TON) depend on the size of the dendrimer-encapsulated PdNP catalysts, similar to the behavior of polymer-supported PdNP catalysts, suggesting a classic mechanism in which all of the steps proceed on the PdNP surface. On the other hand, Miyaura-Suzuki carbon-carbon bond-forming reactions catalyzed by dendrimer-encapsulated PdNPs proceed with TOFs and TONs that do not depend on the size of the PdNPs. Moreover these catalysts are more efficient when employed in lower (down to "homeopathic") amounts, presumably because of a leaching mechanism whereby Pd atoms escape from the PdNP surface subsequent to oxidative addition of the aryl halide. Under these conditions, the "mother" PdNPs have greater difficulty quenching the extremely active leached Pd atoms because of their low concentration. Although dendrimers presenting catalysts at their branch termini can be recovered and reused readily, their inner-sphere components can lead to steric inhibition of substrate approach. In contrast, star-shaped catalysts do not suffer from such steric problems, as has been demonstrated for water-soluble dendrimers bearing cationic iron-sandwich termini, which are redox catalysts of cathodic nitrate and nitrite reduction in water.

Immobilization of Palladium in Mesoporous Silica Matrix: Preparation, Characterization, and Its Catalytic Efficacy in Carbon−Carbon Coupling Reactions

Palladium(0) has been immobilized into the silica-based mesoporous material to develop catalyst Pd(0)-MCM-41, which is found to be highly active in carbon-carbon coupling reactions. [Pd(NH3)4]2+ ions have been incorporated into the mesoporous material during synthesis of MCM-41 and subsequently upon treatments with hydrazine hydrate Pd2+ ions present in mesoporous silica matrix were reduced to Pd(0) almost instantaneously. The catalyst has been characterized by small-angle X-ray diffraction, N2 sorption, and transmission electron microscopy (TEM). TEM and surface area measurements clearly demonstrate that the immobilization of Pd(0) into the mesoporous silica has a significant effect on pore structure of the catalyst. Nevertheless, after immobilization of palladium the meso-porosity of the material is retained, as evidenced in the nitrogen sorption measurement. The TEM micrograph shows that both MCM-41 and Pd(0)-MCM-41 have similar types of external surface morphology; however, Pd(0)-MCM-41 was less ordered. Pd(0)-MCM-41 showed high catalytic activity toward carbon-carbon bond formation reactions like Heck and Sonogashira coupling, as evidenced in high turn-over numbers. In contrast to many other Pd-based catalysts reported so far, Pd(0)-MCM-41 acts as a truly heterogeneous catalyst in C-C coupling reactions. Notably, the new heterogeneous catalyst is found to be efficient in the activation of arylchloride to give impressive conversion in cross coupling (15-45% for Heck and 30% for Sonogashira) reactions under mild conditions.

Acid–Base Bifunctional Catalysis of Silica–Alumina‐Supported Organic Amines for Carbon–Carbon Bond‐Forming Reactions

Acid-base bifunctional heterogeneous catalysts were prepared by the reaction of an acidic silica-alumina (SA) surface with silane-coupling reagents possessing amino functional groups. The obtained SA-supported amines (SA-NR2) were characterized by solid-state 13C and 29Si NMR spectroscopy, FT-IR spectroscopy, and elemental analysis. The solid-state NMR spectra revealed that the amines were immobilized by acid-base interactions at the SA surface. The interactions between the surface acidic sites and the immobilized basic amines were weaker than the interactions between the SA and free amines. The catalytic performances of the SA-NR2 catalysts for various carbon-carbon bond-forming reactions, such as cyano-ethoxycarbonylation, the Michael reaction, and the nitro-aldol reaction, were investigated and compared with those of homogeneous and other heterogeneous catalysts. The SA-NR2 catalysts showed much higher catalytic activities for the carbon-carbon bond-forming reactions than heterogeneous amine catalysts using other supports, such as SiO2 and Al2O3. On the other hand, homogeneous amines hardly promoted these reactions under similar reaction conditions, and the catalytic behavior of SA-NR2 was also different from that of MgO, which was employed as a typical heterogeneous base. An acid-base dual-activation mechanism for the carbon-carbon bond-forming reactions is proposed.

Chiral Diphosphine and Monodentate Phosphorus Ligands on a Spiro Scaffold for Transition-Metal-Catalyzed Asymmetric Reactions

The preparation of chiral compounds in enantiomerically pure form is a challenging goal in modern organic synthesis. The use of chiral metal complex catalysis is a powerful, economically feasible tool for the preparation of optically active organic compounds on both laboratory and industrial scales. In particular, the metals coordinated by one or more chiral phosphorus ligands exhibit amazing enantioselectivity and reactivity. Many chiral phosphorus ligands have been synthesized and used in transition-metal-catalyzed asymmetric reactions in past decades. However, a large number of reactions still lack effective chiral ligands, and the enantioselectivities in many reactions are substrate-dependent. The development of effective chiral phosphorus ligands, especially ligands having novel chiral backbones, is still an important task in the area of asymmetric catalysis. Molecules containing a spirocyclic framework are ubiquitous in nature. The synthesis of molecules with this spiro structure can be traced back to 100 years ago. However, the use of this spirocyclic framework to construct chiral phosphorus ligands is a recent event. This Account outlines the design and synthesis of a new family of chiral spiro phosphorus ligands including spiro diphosphines and spiro monodentate phosphorus ligands with 1,1'-spirobiindane and 9,9'-spirobifluorene backbone and their applications in transition-metal-catalyzed asymmetric hydrogenation and carbon-carbon bond formation reactions. The chiral spiro diphosphine lgands SDP with a 1,1'-spirobiindane backbone and SFDP with a 9,9'-spirobifluorene backbone, and the spiro monophosphorus ligands including phosphoramidites, phosphites, phosphonites, and phospholane with a 1,1'-spirobiindane backbone were synthesized in good yields from enantiomerically pure 1,1'-spirobiindane-7,7'-diol and 9,9'-spirobifluoren-1,1'-diol. The ruthenium complexes of chiral spiro diphosphine ligands proved to be very effective catalysts for asymmetric hydrogenations of ketones, alpha-arylaldehydes and alpha,beta-unsaturated acids. The rhodium complexes of chiral spiro monophosphorus ligands are highly enantioselective for the asymmetric hydrogenations of alpha- and beta-dehydroamino acid derivatives, alpha-arylethenyl acetamides and non- N-acyl enamines. The spiro monophosphorus ligands were demonstrated to be highly efficient for the Rh-catalyzed asymmetric addition of arylboronic acids to aldehydes and N-tosylarylimines, Pd-catalyzed asymmetric allylation of aldehydes with allylic alcohols, Cu-catalyzed asymmetric ring opening reactions with Grignard reagents, and Ni-catalyzed asymmetric hydrovinylation of styrene derivatives with ethylene. The chiral spiro phosphorus ligands show high enantioselectivities for a wide range of transition-metal-catalyzed asymmetric reactions. In most of these transformations, the enantioselectivities of spiro phosphorus ligands are superior to those obtained by using the corresponding phosphorus ligands with other backbones. These results arise from the intriguing chiral inducement of spiro structures of the ligands.

Applications of Zirconium(IV) Chloride in Organic Synthesis

Zirconium(IV) chloride is used extensively in organic synthesis as an ideal Lewis acid since it is an efficient, stable, inexpensive, environmentally friendly and convenient catalyst for the preparation of useful synthetic intermediates and for use in key steps of natural products synthesis. This review is broadly divided into four sections based on zirconium(IV) chloride mediated reactions (1) carbon-carbon bond-formation reactions, (2) protection and deprotection chemistry, (3) reduction reactions, and (4) other applications. This review is an attempt to cover the important advances in the field of synthetic organic chemistry that have been carried out to date. 1 Introduction 2 Carbon-Carbon Bond-Formation Reactions 3 Protections and Deprotections 4 Reduction Reactions 5 Miscellaneous Reactions 6 Zirconium-Based Reagents and Complexes 7 Conclusions

Proline-catalysed Mannich reactions of acetaldehyde

Small organic molecules recently emerged as a third class of broadly useful asymmetric catalysts that direct reactions to yield predominantly one chiral product, complementing enzymes and metal complexes. For instance, the amino acid proline and its derivatives are useful for the catalytic activation of carbonyl compounds via nucleophilic enamine intermediates. Several important carbon-carbon bond-forming reactions, including the Mannich reaction, have been developed using this approach, all of which are useful for making chiral, biologically relevant compounds. Remarkably, despite attempts, the simplest of all nucleophiles, acetaldehyde, could not be used in this way. Here we show that acetaldehyde is a powerful nucleophile in asymmetric, proline-catalysed Mannich reactions with N-tert-butoxycarbonyl (N-Boc)-imines, yielding beta-amino aldehydes with extremely high enantioselectivities-desirable products as drug intermediates and in the synthesis of other biologically active molecules. Although acetaldehyde has been used as a nucleophile in reactions with biological catalysts such as aldolases and thiamine-dependent enzymes, and has also been employed indirectly, its use as an inexpensive and versatile two-carbon nucleophile in asymmetric, small-molecule catalysis will find many practical applications.

Alpha-olefins as alkenylmetal equivalents in catalytic conjugate addition reactions.

Alpha-olefins as alkenylmetal equivalents in catalytic conjugate addition reactions.

Enamides and Enecarbamates as Nucleophiles in Stereoselective C–C and C–N Bond-Forming Reactions

Because the backbone of most of organic compounds is a carbon chain, carbon-carbon bond-forming reactions are among the most important reactions in organic synthesis. Many of the carbon-carbon bond-forming reactions so far reported rely on nucleophilic attack of enolates or their derivatives, because those nucleophiles can be, in general, readily prepared from the corresponding carbonyl compounds. In this Account, we summarize the recent development of reactions using enamide and enecarbamate as a novel type of nucleophile. Despite their ready availability and their intrinsic attraction as a synthetic tool that enables us to introduce a protected nitrogen functional group, enamide and enecarbamate have rarely been used as a nucleophile, since their nucleophilicity is low compared with the corresponding metal enolates and enamines. A characteristic of enamides and enecarbamates is that those bearing a hydrogen atom on nitrogen are relatively stable at room temperature, while enamines bearing a hydrogen atom on nitrogen are likely to tautomerize into the corresponding imine form. Enamides and enecarbamates can be purified by silica gel chromatography and kept for a long time without decomposition. During the investigation of nucleophilic addition reactions using enamides and enecarbamates, it has been revealed that enamides and enecarbamates bearing a hydrogen atom on nitrogen react actually as a nucleophile with relatively reactive electrophiles, such as glyoxylate, N-acylimino ester, N-acylimino phosphonate, and azodicarboxylate, in the presence of an appropriate Lewis acid catalyst. Those bearing no hydrogen atom on nitrogen did not react at all. The products initially obtained from the nucleophilic addition of enamides and enecarbamates are the corresponding N-protected imines, which can be readily transformed to important functional groups, such as ketones by hydrolysis and N-protected amines by reduction or nucleophilic alkylation. In the nucleophilic addition reactions of enamides and enecarbamates to aldehydes, it was unveiled that the reaction proceeds stereospecifically, that is, (E)-enecarbamate gave anti product and (Z)-enecarbamate afforded syn product with high diastereoselectivity (>97/3). This fact can be rationalized by consideration of a concerted reaction pathway via a hydrogen-involved cyclic six-membered ring transition state. In the addition reactions to N-acylimino phosphonates, much higher turnover frequency was observed when enamides and enecarbamates were used as a nucleophile than was observed when silicon enolates were used. When silicon enolates were used, the intermediates bearing a strong affinity for the catalyst inhibited catalyst turnover, resulting in low enantioslectivity because of the dominance of the uncatalyzed racemic pathway. In the case of nucleophilic addition of enamides and enecarbamate, however, a fast intramolecular hydrogen transfer from the enecarbamate nitrogen may prevent the intermediate from trapping the catalyst for a long time, to afford the product with a high enantioselectivity. In conclusion, enamides and enecarbamates, although originally employed as just N-analogues to silicon enolates, have emerged as remarkably useful nucleophiles in a variety of Lewis acid-catalyzed reactions.

Carbon-carbon bond-forming reactions using alkyl fluorides

Abstract This account reviews C-C bond formation reactions using alkyl fluorides mostly focusing on the transition-metal-catalyzed reactions. These reactions proceed efficiently under mild conditions by the combined use of Grignard reagents and transition-metal catalysts, such as Ni, Cu, and Zr. It is proposed that ate complex intermediates formed by the reaction of these transition metals with Grignard reagents play important roles as the active catalytic species. Organoaluminun reagents react directly with alkyl fluorides in nonpolar solvents at room temperature to form C-C bonds. These studies demonstrate the practical usefulness of alkyl fluorides in C-C bond formation reactions and provide a promising method for the construction of carbon frameworks employing alkyl fluorides. The scope and limitations, as well as reaction pathways, are discussed.

Selective organic synthesis through generation and reactivity control of hyper‐coordinate metal species

This paper is a review of my 40 years of research at Kyoto, Sagamihara, and Yokohama, all based on the generation of hyper-coordinate metal species such as ate complexes and pentacoordinate silicates. The topics are: (i) carbenoid reagents for carbon-carbon bond-forming reactions, (ii) nucleophilic substitution at acetal carbons using aluminate reagents, (iii) preparation of magnesium enolates and its reaction with nitriles, (iv) Cr(II) reagents for reduction of organic halides and highly selective carbon-carbon bond formation, (v) organic synthesis with organosilion reagents/fluoride ions, (vi) cross-coupling reaction of organosilicon compounds, and (vii) silicon-based conjugate addition to alpha,beta-unsaturated carbonyl acceptors.

SA-Supported Organic Amines as Heterogeneous Catalysts

The silica-alumina (SA) supported amines 1 and 2 were developed as heterogeneous organic base catalysts for a variety of carbon-carbon bond-forming reactions. The reaction of amorphous SA with 3-(diethylamino)propyltriethoxysilane in toluene gave the SA-supported amine 1 (SA-NEt2). SA-supported amine 2 (SA-NH2) was also prepared by a similar procedure. SA-NEt2 (1) showed high catalytic activity in the Michael reaction of ethyl cyanoacetate to methyl vinyl ketone (eq. 1) and cyanoethoxycarbonylation of benzaldehyde (eq. 2), respectively. SA-NH2 (2) catalyzed the nitro-aldol reaction of nitromethane with benzaldehyde to give β-nitrostyrene quantitatively (eq. 3).

Fluorinated Alcohols as Solvents, Cosolvents and Additives in Homogeneous Catalysis

The use of fluorinated alcohols as solvents, cosolvents or additives in homogeneous catalysis is reviewed. The effect of these particular compounds on efficiency, regioselectivity and stereoselectivity of metal-catalyzed reactions, as well as on reactions mediated by organocatalysts, is described. Where available in several cases, the effect of fluorous alcohols on the catalytic mechanism is analyzed in detail and rationalized by their unique physical and chemical properties. In most instances, a comparison to the effect of commonly employed solvents is elaborated. 1 Introduction 2 Physical Properties of Fluorinated Alcohols 3 Applications in Homogeneous Catalysis 3.1 Reduction Reactions 3.2 Oxidation Reactions 3.3 Carbon-Carbon Bond-Forming Reactions 3.4 Cycloaddition Reactions 3.5 Metathesis Reactions 3.6 Carbon-Heteroatom Bond-Forming Reactions 3.7 Isomerization Reactions 4 Conclusion

Manganese(III) Acetate: A Versatile Reagent in Organic Chemistry

Free radical reactions have become increasingly important, as well as a very attractive tool, in organic synthesis within the last two decades, due to their powerful, selective, specific, and mild reaction abilities. Mn(OAc)3 mediated oxidative free radical reactions have been extensively developed in the last twenty years. Numerous regio-, chemo-, and stereoselective synthetic methods have been developed in both inter- and intramolecular reactions, and have detailed the progress of Mn(OAc)3 mediated oxidative free radical reactions since the end of the 19th century. The new literature about the new synthetic methods on Mn(OAc)3 mediated carbon-carbon bond formation and carbon-oxygen bond formation reactions has not been extensively reviewed. The present paper summarizes the recent developments in oxidative free radical reactions mediated by Mn(OAc)3. Mn(OAc)3 mediated reactions of conjugated systems (e.g., alkenes, alkynes, 1,3-alkadienes, l,3-alkadiynes, 1-alken-3-ynes) with β-dicarbonyl compounds, Mn(OAc)3 mediated alkylation, such as the oxidative addition of an aldehyde or ketone to alkenes, Mn(OAc)3 mediated free-radical cyclization of alkenes with active methylene compounds in the presence of oxygen to afford the cyclic peroxides; lactone synthesis by the Mn(OAc)3 mediated oxidative addition of carboxylic acids to alkenes, Mn(OAc)3 mediated cyclization of α- (methylthio)acetamides, enamides, and β-keto carboxamides to afford cyclic products. Mn(OAc)3 oxidative free-radical cyclizations of allylic β-dicarbonyl compounds, for example, the cyclization of allylic β-ketoesters to afford the corresponding γ-lactone. The reaction of alkenes with sodium azide in the presence of acetic acid was investigated to Keywords: Free radical reactions, Lactone synthesis, Cycloperoxidation, Oxidative Cyclization, Carbon-Oxygen Bond Formation

Development of Carbon—Carbon Bond‐Forming Reactions Using γ,γ‐Dialkoxyallylic Zirconium Species

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Development of Carbon-Carbon Bond-Forming Reactions using γ, γ-Dialkoxyallylic Zirconium SPecies

Carbon-carbon bond-forming reactions of allylic organometals have been recognized as one of the most fundamental means in organic synthesis, and a number of applications for the synthesis of biologically active molecules have been reported. We have reported the carbon-carbon bond-forming reactions by the use of the allylic and related zirconium species as reactive intermediates. These zirconium species can be generated by treating allylic ethers with zirconocene-butene complex (“Cp2Zr”) through the formation of zirconacyclopropane and the following β-elimination of the alkoxy group. This process was found to be applicable to generate the γ, γ-dialkoxyallylic zirconium species 1 from orthoacrylate derivative. Zirconium species 1 possibly has three reactive sites : One is the γ-position as a typical allyl metal species, the other is the β-position followed by the α-position initiated by nucleophilic character of ketene dialkylacetal moiety and the third one is regioselective coupling reaction at the α-position.Thus, γ, γ-dialkoxyallylic zirconium species 1 can be conveniently prepared by the reaction of triethyl orthoacrylate with “Cp2Zr”. Without an additive, 1 itself reacts with aldehydes and ketones at the γ-position to afford the gem-diethoxy homoallylic alcohol derivatives. Under Lewis acid promoted conditions, this zirconium species 1 reacts with a variety of carbonyl compounds selectively at the β-position in the first step, followed by the cyclopropanation or cyclobutanation reaction to afford the corresponding products mainly depending on electronic nature of substrates or reaction conditions. In the presence of CuCN, reaction of 1 with allylic phosphates proceeded at the α-position of 1 in a highly SN2'-selective manner to give the 5-alkenoates.