Catalytic asymmetric carbon-carbon bond-forming reactions in aqueous media

Use of water as a reaction solvent or co-solvent has received much attention in synthetic organic chemistry. Recently, successful examples of catalytic asymmetric carbon-carbon bond formation in aqueous media have been developed. Most of these examples show characteristic features that are realized only in the presence of water. The role of water in these reactions is also discussed here.     

Catalytic asymmetric synthesis of alpha-amino phosphonates using enantioselective carbon-carbon bond-forming reactions

We have developed highly enantioselelctive reactions of silicon enolates with N-acyl-alpha-iminophosphonates leading to optically active alpha-amino phophonates. A copper (II)-diamine complex was shown to be effective in this reaction, and high levels of yield and selectivity were achieved. It is noteworthy that this reaction opens a way to various biologically important, optically active alpha-amino phosphonate derivatives.     

Chiral oxazolines and their legacy in asymmetric carbon-carbon bond-forming reactions

The studies performed with chiral oxazolines as vehicles for a number of C-C bond-forming reactions are traced back to the early 1970s. The main source of chirality in these studies was derived from chiral, nonracemic amino alcohols which, themselves, were prepared from amino acids. The formation of chiral oxazolines from these materials provided interesting and useful starting materials for these studies.The factors responsible for high optical yields during that era were attributed to rigidity or precomplexation of the reactants, thus providing a more well-defined topography during the reaction course. A number of C-C bond reaction types are described including alkylations, additions, and organometallic reactions. The ee's of many of the products arrived at are well above 90%. This level of ee was virtually unprecedented in the early to mid 1970s. In addition to the synthetic emphasis, several mechanistic questions, arising in other areas, were also undertaken due to the accessibility of the appropriate requisite chiral materials.     

Hydrophobic polymer-supported scandium catalyst for carbon-carbon bond-forming reactions in water

It has been revealed that a hydrophobic polymer-supported scandium(III) catalyst prepared from sulfonated polystyrene resin is an effective catalyst for carbon-carbon bond-forming reactions such as Mukaiyama aldol reactions in water. According to studies on loading levels of scandium, hydrophobicity of the catalyst is a key for the efficient catalysis. The scandium catalyst was successfully recovered and reused. Several ketones instead of aldehydes were also used as substrates in the aldol reactions. Some 1,4-addition reactions also occurred using the scandium catalyst in water.     

Organosulfur compounds: electrophilic reagents in transition-metal-catalyzed carbon-carbon bond-forming reactions

Transition-metal-catalyzed carbon-carbon bond-forming reactions are among the most powerful methods in organic synthesis and play a crucial role in modern materials science and medicinal chemistry. Recent developments in the area of ligands and additives permit the cross-coupling of a large variety of reactants, including inexpensive and readily available sulfonyl chlorides. Their desulfitative carbon-carbon cross-coupling reactions (Negishi, Stille, carbonylative Stille, Suzuki-Miyaura, and Sonogashira-Hagihara-type cross-couplings and Mizoroki-Heck-type arylations) are reviewed together with carbon-carbon cross-coupling reactions with other organosulfur compounds as electrophilic reagents.     

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.     

Scandium-catalyzed carbon-carbon bond-forming reactions of 3-sulfanyl- and 3-selanylpropargyl alcohols

The scandium-catalyzed substitution reactions of the phenylsulfanyl and phenylselanyl propargyl alcohols 3a- i and 7a- h regioselectively proceeded to give the propargylated compounds 4 and 8 in high yields.     

New possibilities for the use of methoxyallene in carbon-carbon bond-forming reactions

Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 198–199, January, 1988.     

Recent advances in transition-metal-free carbon-carbon and carbon-heteroatom bond-forming reactions using arynes

This tutorial review is aimed at highlighting recent developments in transition-metal-free carbon-carbon and carbon-heteroatom bond-forming reactions utilizing a versatile class of reactive intermediates, viz., arynes, which hold the potential for numerous applications in organic synthesis. Key to the success of the resurgence of interest in the rich chemistry of arynes is primarily the mild condition for their generation by the fluoride-induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates. Consequently, arynes have been employed for the construction of multisubstituted arenes with structural diversity and complexity. The versatile transition-metal-free applications of arynes include cycloaddition reactions, insertion reactions and multicomponent reactions. In addition, arynes have found applications in natural product synthesis. Herein, we present a concise account of the major developments that occurred in this field during the past eight years.     

New directing groups for metal-catalyzed asymmetric carbon-carbon bond-forming processes: stereoconvergent alkyl-alkyl Suzuki cross-couplings of unactivated electrophiles

The ability of two common protected forms of amines (carbamates and sulfonamides) to serve as directing groups in Ni-catalyzed Suzuki reactions has been exploited in the development of catalytic asymmetric methods for cross-coupling unactivated alkyl electrophiles. Racemic secondary bromides and chlorides undergo C-C bond formation in a stereoconvergent process in good ee at room temperature in the presence of a commercially available Ni complex and chiral ligand. Structure-enantioselectivity studies designed to elucidate the site of binding to Ni (the oxygen of the carbamate and of the sulfonamide) led to the discovery that sulfones also serve as useful directing groups for asymmetric Suzuki cross-couplings of racemic alkyl halides. To our knowledge, this investigation provides the first examples of the use of sulfonamides or sulfones as effective directing groups in metal-catalyzed asymmetric C-C bond-forming reactions. A mechanistic study established that transmetalation occurs with retention of stereochemistry and that the resulting Ni-C bond does not undergo homolysis in subsequent stages of the catalytic cycle.     

In situ generation of 3,3,3-trifluoropropanal and its use for carbon-carbon bond-forming reactions

The DIBAL reduction of 2-phenylethyl 3,3,3-trifluoro-2-methylpropionate 2 at -78 degrees C afforded the aluminum acetal 3, and this intermediate, on worming up to 0 degrees C, was found to slowly decompose into the corresponding aldehyde 4, which smoothly reacted with appropriate nucleophiles in a one-pot manner in good to excellent yields with up to 93% diastereoselectivity.     

Employing homoenolates generated by NHC catalysis in carbon-carbon bond-forming reactions: state of the art

Homoenolate is a reactive intermediate that possesses an anionic or nucleophilic carbon β to a carbonyl group or its synthetic equivalent. The recent discovery that homoenolates can be generated from α,β-unsaturated aldehydes via N-Heterocyclic Carbene (NHC) catalysis has led to the development of a number of new reactions. A majority of such reactions include the use of carbon-based electrophiles, such as aldehydes, imines, enones, dienones etc. resulting in the formation of a variety of annulated as well as acyclic products. The easy availability of chiral NHCs has allowed the development of very efficient enantioselective variants of these reactions also. The tolerance showed by NHCs towards magnesium and titanium based Lewis acids has been exploited in the invention of cooperative catalytic processes. This tutorial review focuses on these and other types of homoenolate reactions reported recently, and in the process, updates the previous account published in 2008 in this journal.     

Palladium-catalyzed carbon-carbon bond-forming 1,2-ligand migration of organoalanes

A one-pot, two-step process that transforms terminal alkynes into ethyl methyl-substituted benzylic quaternary carbon centers is described. (E)-2,2-Disubstituted-1-alkenyldimethylalanes have been shown to participate in 1,2-alkyl migration from aluminum to carbon with concomitant arylation at the 2-position to furnish ethyl methyl-substituted benzylic quaternary carbon centers, when reacted intramolecularly with aryl halides and triflates in the presence of a Pd(0) catalyst. The protocol is initiated with Cp2ZrCl2-catalyzed methylalumination of terminal alkynes followed by palladium-catalyzed intramolecular arylation of the resulting (E)-2,2-disubstituted-1-alkenyldimethylalanes, leading to 1,2-methyl shift from aluminum to carbon. In that sequence, a total of three new C-C single bonds are made, and two of the three alkyl groups on Me3Al transferred to the substrate on vicinal carbons. This method was applied to a variety of substrates, and the mechanism was investigated by deuterium-labeling experiments, which revealed that protodealumination of the final dialkylaluminum triflate or halide intermediates by CH3CN results in the formation of the fourth bond in the course of the transformation.     

Amino acid catalyzed direct asymmetric aldol reactions: a bioorganic approach to catalytic asymmetric carbon-carbon bond-forming reactions.

Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with commercially available chiral cyclic secondary amines as catalysts. Structure-based catalyst screening identified L-proline and 5,5-dimethyl thiazolidinium-4-carboxylate (DMTC) as the most powerful amino acid catalysts for the reaction of both acyclic and cyclic ketones as aldol donors with aromatic and aliphatic aldehydes to afford the corresponding aldol products with high regio-, diastereo-, and enantioselectivities. Reactions employing hydroxyacetone as an aldol donor provide anti-1,2-diols as the major product with ee values up to >99%. The reactions are assumed to proceed via a metal-free Zimmerman-Traxler-type transition state and involve an enamine intermediate. The observed stereochemistry of the products is in accordance with the proposed transition state. Further supporting evidence is provided by the lack of nonlinear effects. The reactions tolerate a small amount of water (<4 vol %), do not require inert reaction conditions and preformed enolate equivalents, and can be conveniently performed at room temperature in various solvents. In addition, reaction conditions that facilitate catalyst recovery as well as immobilization are described. Finally, mechanistically related addition reactions such as ketone additions to imines (Mannich-type reactions) and to nitro-olefins and alpha,beta-unsaturated diesters (Michael-type reactions) have also been developed.     

Advances in Lewis acid controlled carbon-carbon bond-forming reactions enable a concise and convergent total synthesis of bullatacin

Lewis acids control regioselectivity in the alkylation of epi-chlorohydrin and the stereochemistry of an alkyne addition to set the C24/C23 anti relationship. These advances facilitate an efficient total synthesis of bullatacin in 13.3% overall yield from commercial starting materials.     

Applications of 4,4'-(Me3Si)2-BINAP in transition-metal-catalyzed asymmetric carbon-carbon bond-forming reactions

[structure: see text] A recently developed BINAP derivative with trimethylsilyl substituents on the 4- and 4'-positions of the binaphthyl skeleton, 2,2'-bis(diphenylphosphino)-4,4'-bis(trimethylsilyl)-1,1'-binaphthyl (tms-BINAP), was used in a variety of transition-metal-catalyzed asymmetric carbon-carbon bond-forming reactions. In pi-allylpalladium-mediated reactions, tms-BINAP gave better enantioselectivity than the unsubstituted BINAP, and the origin of the improved enantioselectivity was gained from an X-ray structural study of [Pd(eta(3)-C(3)H(5))((R)-tms-BINAP)]ClO(4).     

Cu(dap)2Cl] as an efficient visible-light-driven photoredox catalyst in carbon-carbon bond-forming reactions

Copper sees the light of day: [Cu(dap)(2)Cl] proved to be an excellent photoredox catalyst for atom-transfer radical addition reactions, as well as for allylation reactions (see scheme), providing an attractive alternative to commonly used iridium- and ruthenium-based catalysts.     

Catalytic reactions involving the cleavage of carbon-cyano and carbon-carbon triple bonds

The catalytic reactions that involve the cleavage of C-CN bonds and carbon-carbon triple bonds are described in this tutorial review. Regarding the cleavage of a C-CN bond, the catalytic reaction can proceed by two different mechanisms: oxidative addition and deinsertion of silyl isocyanide. A carbon-carbon triple bond can be cleaved in the absence of an organic promoter via the formation of unique organometallic species, such as allenylidene and cyclopropyl carbenoid complexes.     

Difluoro-lambda3-bromane-induced oxidative carbon-carbon bond-forming reactions: ethanol as an electrophilic partner and alkynes as nucleophiles

Reported here for the first time are the oxidative couplings of alkynes and primary alcohols yielding conjugated enones. Although the BF3-catalyzed reaction of terminal alkynes with p-trifluoromethylphenyl(difluoro)-lambda3-bromane results in the fluoro-lambda3-bromanation of triple bonds to afford (E)-beta-fluorovinyl-lambda3-bromanes, reaction of an alkyne with the difluoro-lambda3-bromane in the presence of an alcohol and BF3-Et2O affords directly conjugated enones in good yields. The reaction proceeds in a highly stereo- and regioselective manner under metal-free conditions. Interestingly, no formation of enones was detected, when difluoro-lambda3-iodane p-CF3C6H4IF2 was used instead of the lambda3-bromane. A mechanism involving a lambda3-bromane-induced oxidation of an alcohol to an aldehyde, [2 + 2] cyclization with alkynes yielding 2H-oxetes, and finally the electrocyclic ring opening is discussed.