Development Of New Chiral Ligands Research Articles

Bispidine‐Based S,N‐Chiral Ligands for Palladium‐Catalyzed Asymmetric Arylation of Cyclic N‐Sulfonyl Ketimines

AbstractDevelopment of new chiral ligands is essentially important in the field of asymmetric metal catalysis. Bispidines, steming from natural alkaloids, represent an intriguing yet underexplored class of chiral ligands. In this article, we developed a series of bispidine‐based chiral ligands with chirality locked in the side chain, and explore their properties by applying in the palladium‐catalyzed asymmetric addition of arylboric acids to cyclic N‐sulfonyl ketimines. A S,N‐bispidine ligand was found especially efficient, affording a series of chiral benzosultams with a quaternary chiral center in excellent yields with excellent ee values. Density functional theory (DFT) calculations and crystal structure of catalyst helped to propose a reasonable mechanism including a possible transition state model to explain the origin of stereoselectivity.

A New Saddle-Shaped Aza Analog of Tetraphenylene: Atroposelective Synthesis and Application as a Chiral Acylating Reagent

A New Saddle-Shaped Aza Analog of Tetraphenylene: Atroposelective Synthesis and Application as a Chiral Acylating Reagent

Axially Chiral Cyclic Diphosphine Ligand-Enabled Palladium-Catalyzed Intramolecular Asymmetric Hydroarylation

SummaryIn transition metal-catalyzed asymmetric synthesis, enantioselectivity strongly depends on the structures of chiral ligands, so the development of new chiral ligands is crucial. Here, an efficient and highly enantioselective palladium-catalyzed intramolecular hydroarylation has been developed, and a new kind of N-heterocycles, 1H-pyrazolo[5,1-a]isoindol-2(8H)-ones containing a quaternary stereocenter, was prepared in high yields and excellent enantiomeric excess values. The reaction was effectively catalyzed by palladium-diphosphine complexes with numerous functional group tolerance, in which the newly developed axially chiral cyclic diphosphine ligands played key roles in the reactivity and enantioselectivity of the substrates. We believe that the cyclic diphosphine ligands with adjustable dihedral angles will find wide application in asymmetric synthesis.

Development of New Chiral Phosphine Ligands with Helical Environments and Their Application in Asymmetric Catalytic Reactions

The design and development of new chiral ligands to enable precise stereocontrol in a wide variety of reactions is one of the most important branches of organic synthesis. To date, the development of hybrid ligands containing both σ-donating and π-donating groups has attracted considerable attention, with unprecedented reactivities and stereoselectivities being observed. Therefore to develop efficient hybrid chiral ligands with novel structural motifs, we envisage that helicene would be a suitable π-donor efficiently to construct a helical environment around a metal center. In this context, we herein describe our recent efforts to develop a series of novel chiral [5]helicene-derived phosphine ligands (L1, with a 7,8-dihydro[5]helicene core structure, and L2, with a fully aromatic [5]helicene core structure). The prepared ligands, and in particular L1, were found highly effective in the asymmetric allylation of 1,3-diphenylallyl acetate with indoles and etherification with alcohols. Furthermore, in the asymmetric Suzuki-Miyaura coupling reaction, L2 exhibited excellent enantioselectivities. Finally, density functional theory studies were employed to propose a model that accounts for the origin of such high enantioselectivity in these reactions.

Renovation of Optically Active Phenanthrolines as Powerful Chiral Ligands for Versatile Asymmetric Metal Catalysis.

In the field of asymmetric synthesis, the development of new chiral ligands has been regarded as an attractive challenge for decades. Novel chiral ligands can often have a great impact on synthetic protocols. In this context, we are currently interested in the application of 1,10-phenanthroline (phen) as an entirely new class of chiral ligand. To handle this issue, we designed a chiral phen ligand that provides the N,N,O-tridentate coordination of the phen moiety and an additional phenolic hydroxyl group. As phen possesses greater coordination ability with various ions, our chiral phen ligand would be valuable as one of the "privileged" chiral ligands applied to a broad range of metal catalysts and new reactions. This account summarizes the results of the application of the chiral phen ligand to various kinds of metal catalysis.

Recent Advances in Rh-Catalyzed Asymmetric Hydroformylation of Olefins

Abstract Hydroformylation is one of the most important processes of homogeneous catalysis in industry. Asymmetric hydroformylation (AHF) of prochiral alkenes provides an efficient way to the synthesis of optically active aldehydes, which are versatile chiral intermediates for pharmaceuticals, agrochemicals, and other fine chemicals. So far, most of methods reported were focused on the use of Rh(I)-based catalysts, by virtue of their high catalytic activity and excellent chemoselectivity for the aldehydes. A key issue in searching for efficient asymmetric hydroformylation catalysts is the development of new chiral ligands. A number of chiral phosphorus ligands have been successfully developed for Rh(I)-catalyzed AHF reactions. In this review, the recent advances in the development of chiral ligands for the Rh-catalyzed asymmetric hydroformylaion of olefins have been surveyed.

Tetradentate Amine Ligands for Asymmetric Friedel-Crafts Alkylations

The development of new chiral ligands is an ongoing and important process for designing improved catalysts. Based on previous studies using novel tetradentate amine ligands for copper-catalyzed Henry reactions (Chem. Eur. J. 2010, 16, 8259), the authors present a highly asymmetric Friedel-Crafts addition of indoles to nitroalkenes.

Recent Trends in Enantioselective Diorganozinc-Additions to Aldehydes

In recent years, impressive progress has been made in the development of new chiral ligands and in new methodology for Zn-mediated enantioselective additions to aldehydes. The current report aims to present the recent progress in this field. Keywords: transmetalation, phenylzinc reagent, N,N-dibutylnorephedrine, diarylmethanols, enantioselective additions

Synthesis of New Chiral β‐Amino Alcohols Derived from Isomannide and Their Application to the Catalytic Enantioselective Addition of Diethylzinc to Aldehydes.

Enantioselective carbon-carbon bond formation is one of the most interesting challenges in organic synthesis. In recent years, the catalytic enantioselective addition of dialkylzincs to aldehydes has attracted much attention because of its potentials in the preparation of optically active secondary alcohols. Over the past decade, various types of chiral ligands using as catalysts for this reaction have been developed. Among the diverse chiral lignads, chiral amino alcohols are predominant. As other type of ligands, chiral amino thiols, amino thiocyanate, amino thioacetate, iminyl alcohols, oxazolinyl alcohols, amino amides, sulfonamides, phosphoramides, α-hydroxy carboxylic acid and diols such as TADDOLs and BINOLs have been published. Recently we reported the synthesis of various chiral βor γ-amino alcohols derived from inexpensive chiral pools, such as α-D-xylose, α-D-glucose and L-tartaric acid, and D-mannitol. As a continuation of our ongoing project on the development of new chiral ligands from an easy and inexpensive starting materials, we hereby report the synthesis of new β-amino alcohols 3a-f starting from isomannide 1 and their application for the catalytic ethylation to aldehydes. The ligands 3a-f were prepared in 87-98% yield by the treatment of 2 with 2.5 equiv. of dialkylamines under solvent-free conditions for 2-3 h at 45 C (Scheme 1). Subsequently we compared the enantioselectivities of these chiral ligands as catalyst for the enantioselctive addition of diethylzinc to benzaldehyde. Thus, the reaction was carried out by addition of 2 equiv. of diethylzinc in toluene to

Synthesis of New Chiral β-Amino Alcohols Derived from Isomannide and Their Application to the Catalytic Enantioselective Addition of Diethylzinc to Aldehydes

Enantioselective carbon-carbon bond formation is one of the most interesting challenges in organic synthesis. In recent years, the catalytic enantioselective addition of dialkylzincs to aldehydes has attracted much attention because of its potentials in the preparation of optically active secondary alcohols. Over the past decade, various types of chiral ligands using as catalysts for this reaction have been developed. Among the diverse chiral lignads, chiral amino alcohols are predominant. As other type of ligands, chiral amino thiols, amino thiocyanate, amino thioacetate, iminyl alcohols, oxazolinyl alcohols, amino amides, sulfonamides, phosphoramides, α-hydroxy carboxylic acid and diols such as TADDOLs and BINOLs have been published. Recently we reported the synthesis of various chiral βor γ-amino alcohols derived from inexpensive chiral pools, such as α-D-xylose, α-D-glucose and L-tartaric acid, and D-mannitol. As a continuation of our ongoing project on the development of new chiral ligands from an easy and inexpensive starting materials, we hereby report the synthesis of new β-amino alcohols 3a-f starting from isomannide 1 and their application for the catalytic ethylation to aldehydes. The ligands 3a-f were prepared in 87-98% yield by the treatment of 2 with 2.5 equiv. of dialkylamines under solvent-free conditions for 2-3 h at 45 C (Scheme 1). Subsequently we compared the enantioselectivities of these chiral ligands as catalyst for the enantioselctive addition of diethylzinc to benzaldehyde. Thus, the reaction was carried out by addition of 2 equiv. of diethylzinc in toluene to