A novel C2-symmetric bisphosphane ligand with a chiral cyclopropane backbone: synthesis and application in the Rh(I)-catalyzed asymmetric 1,4-addition of arylboronic acids

The synthesis of a novel C₂-symmetric bisphosphane ligand was accomplished starting from trans-(2R,3R)-bis(3′,5′-diphenylphenyl)cyclopropane-1,1-dimethanol as a key intermediate. This ligand was tested in the asymmetric rhodium(I)-catalyzed 1,4-addition to cyclic enones. We also compared the new ligand with a similar phosphane ligand with a less bulky cyclopropane backbone. Good yields (up to 99%) and enantioselectivities (up to 89% ee) were observed. We demonstrated that the presence of a more bulky cyclopropane backbone resulted in a less effective ligand.     

Modification of (1R,2S)-1,2-diphenyl-2-aminoethanol for the highly enantioselective, asymmetric alkylation of N-diphenylphosphinoyl arylimines with dialkylzinc

Experimental studies on the modification of (1R,2S)-1,2-diphenyl-2-aminoethanol, which is used to promote the alkylation of N-diphenylphosphinoyl benzalimine with diethylzinc, revealed that N-monosubstituted amino alcohols exhibited higher enantioselectivities than their N,N-disubstituted counterparts and imino alcohols. Application of the optimal chiral ligand 3c to activate the reaction of N-diphenylphosphinoyl arylimines with diethylzinc and dibutylzinc resulted in excellent enantiomeric selectivities of up to 98% ee. The origin of the experimentally observed enantioselectivities was revealed by density functional calculations (B3LYP/6-31G*) on the transition structures of several model reactions.     

Development of Chiral Spiro P‐N‐S Ligands for Iridium‐Catalyzed Asymmetric Hydrogenation of β‐Alkyl‐β‐Ketoesters

The chiral tridentate spiro P‐N‐S ligands (SpiroSAP) were developed, and their iridium complexes were prepared. Introduction of a 1,3‐dithiane moiety into the ligand resulted in a highly efficient chiral iridium catalyst for asymmetric hydrogenation of β‐alkyl‐β‐ketoesters, producing chiral β‐alkyl‐β‐hydroxyesters with excellent enantioselectivities (95–99.9 % ee) and turnover numbers of up to 355 000.     

Rhodium-catalysed asymmetric hydrosilylation of ketones using HETPHOX ligands

The HETPHOX ligand class was applied to the rhodium-catalysed asymmetric hydrosilylation of a range of substituted acetophenones. Enantioselective hydrosilylation of acetophenone with the tert-butyl substituted HETPHOX ligand gave (R)-phenylethanol in excellent enantioselectivity (84% ee) and in good conversion (80%). When applied to the hydrosilylation of other ketones conversions up to 93% and enantioselectivities up to 88% were observed.     

Phosphite-oxazole/imidazole ligands in asymmetric intermolecular Heck reaction

We describe the application of a new class of ligands--the phosphite-oxazole/imidazole (L1-L5a-g)--in asymmetric intermolecular Pd-catalyzed Heck reactions under thermal and microwave conditions. These ligands combine the advantages of the oxazole/imidazole moiety with those of the phosphite moiety: they are more stable than their oxazoline counterparts, less sensitive to air and other oxidizing agents than phosphines and phosphinites, and easy to synthesize from readily available alcohols. The results indicate that activities, regio- and enantioselectivities, are highly influenced by the type of nitrogen donor group (oxazole or imidazole), the oxazole and biaryl-phosphite substituents and the axial chirality of the biaryl moiety of the ligand. By carefully selecting the ligand components, we achieved high activities, regio- (up to 99%) and enantioselectivities (up to 99%) using several triflate sources. Under microwave-irradiation conditions, reaction times were considerably shorter (from 24 h to 30 min) and regio- and enantioselectivities were still excellent.     

Enantioselective addition of organozinc reagents to ketones catalyzed by grafted isoborneolsulfonamide polymers and titanium isopropoxide

The catalytic enantioselective addition of different organozinc reagents, such as diethylzinc, or in situ generated phenylzinc derivatives to simple aryl methyl ketones was accomplished using titanium tetraisopropoxide and a polymeric ligand grafted with trans-1-phenylsulfonylamino-2-isoborneolsulfonylamidocyclohexane, to give the corresponding tertiary alcohols with enantioselectivities of up to >99% ee. Whereas the highest enantioselectivities were obtained in the ethylation process, the highest chemical yields were obtained in the phenylation process. The ligand could be re-used at least three times without any significant loss of activity.     

Design and synthesis of chiral 1,10-phenanthroline ligand,and application in palladium catalyzed asymmetric 1,4-addition reactions

Pd-catalyzed asymmetric 1,4-addition of phenylboronic acid to α,β-unsaturated carbonyl compounds was developed using chiral 1,10-phenanthroline derivative as ligand. Good yields (up to 97%), and high enantioselectivities (up to 97% ee) were achieved.     

Chiral N-heterocyclic carbene ligands for asymmetric catalytic oxindole synthesis

The Pd-catalysed asymmetric intramolecular alpha-arylation of amide enolates containing heteroatom substituents gives chiral 3-alkoxy or 3-aminooxindoles in high yield and with enantioselectivities up to 97% ee when a new chiral N-heterocyclic carbene ligand is used.     

Catalytic enantioselective allylation of aldehydes via a moisture-tolerant chiral BINOL-In(III) complex

A moisture-tolerant chiral indium complex has been developed to effect good enantioselectivities in the addition of allyltributylstannanes to aldehydes. The allylation of a variety of aromatic, α,β-unsaturated and aliphatic aldehydes resulted in both moderate to good yields and high enantioselectivities (up to 86% ee).     

Asymmetric Friedel–Crafts Alkylation of Electron‐Rich N‐Heterocycles with Nitroalkenes Catalyzed by Diphenylamine‐Tethered Bis(oxazoline) and Bis(thiazoline) ZnII Complexes

The asymmetric Friedel–Crafts alkylation of electron‐rich N‐containing heterocycles with nitroalkenes under catalysis of diphenylamine‐tethered bis(oxazoline) and bis(thiazoline)‐Zn^II complexes was investigated. In the reaction of indole derivatives, the complex of ligand 4 f with trans‐diphenyl substitutions afforded better results than previously published ligand 4 e with cis‐diphenyl substitutions. Excellent yields (up to greater than 99 %) and enantioselectivities (up to 97 %) were achieved in most cases. The complex of ligand 4 d bearing tert‐butyl groups gave the best results in the reactions of pyrrole. Moderate to good yields (up to 91 %) and enantioselectivities (up to 91 %) were achieved in most cases. The origin of the enantioselectivity was attributed to the NH–π interaction between the catalyst and the incoming aromatic system in the transition state. Such an interaction was confirmed through comparison of the enantioselectivity and the absolute configuration of the products in the reactions catalyzed by designed ligands.     

Screening of a modular sugar-based phosphite-oxazoline ligand library in asymmetric Pd-catalyzed heck reactions

We have synthesised a library of phosphite-oxazoline ligands derived from readily available D-glucosamine. These ligands have been successfully screened in the palladium-catalysed Heck reaction of several substrates with high regio- (up to 99 %) and enantioselectivities (ee's up to 99 %) as well as with improved activities under standard thermal conditions. The results indicate that the catalytic performance is highly affected by the oxazoline and biarylphosphite substituents and the axial chirality of the biaryl moiety of the ligand. The Heck reactions were also performed under microwave irradiation conditions, allowing a considerably shorter reaction time (full conversion in minutes) maintaining the excellent regio- and enantioselectivities.     

Catalytic enantioselective allylation of ketones via a chiral indium(III) complex

[reaction: see text] A chiral indium complex has been discovered to effect high enantioselectivities in the addition of allyltributylstannanes to ketones. The allylation of a variety of aromatic, alpha,beta-unsaturated and aliphatic ketones resulted in good yields and high enantioselectivities (up to 92% ee).     

Catalytic enantioselective Diels-Alder reaction via a chiral indium(III) complex

[reaction: see text] A chiral indium complex has been developed to effect high enantioselectivities in catalyzing enantioselective Diels-Alder reaction. The cycloaddition of a variety of cyclic and open-chained dienes to 2-methacrolein and 2-bromoacrolein resulted in good yields and excellent enantioselectivities (up to 98% ee).     

A novel chiral phosphinediamine ligand and asymmetric hydrogenation of acrylic acid derivatives

A novel chiral phosphinediamine ligand (PN₂) was prepared from (S)-1-phenylethylamine and dichloroisopropylphosphine. The rhodium-PN₂ catalyst utilizing selective ligation of the amino unit and electrostatic interaction between the ligand and a substrate gave high enantioselectivities up to 92% ee in asymmetric hydrogenations of acrylic acid derivatives.     

Rhodium-catalyzed Michael addition of arylboronic acids to 3-alkylenyloxindoles: asymmetric synthesis of functionalized oxindoles

The rhodium-catalyzed diastereo- and enantioselective Michael addition of arylboronic acids to 3-alkylenyloxindoles has been developed with (R)-binap as a ligand. A wide variety of the desired functionalized oxindoles are smoothly obtained in high yields (up to 99%) with high enantioselectivities (up to 92% ee) and good diastereoselectivities (up to 82:18).     

Highly enantioselective allylation of aldehydes catalyzed by indium(III)-PYBOX complex

A chiral indium(III)-PYBOX complex prepared from indium triflate and chiral PYBOX has been discovered to effect high enantioselectivities in the addition of allyltributyl stannane to aldehydes. The allylation of a variety of aromatic, alpha,beta-unsaturated, and aliphatic aldehydes resulted in good yields and high enantioselectivities (up to 94% ee).     

Rhodium catalyzed asymmetric 1,4-addition of arylboronic acids to β,γ-unsaturated α-keto ester using chiral tert-butanesulfinylphosphines ligands

Rh-Catalyzed asymmetric 1,4-selective addition of arylboronic acids to β,γ-unsaturated α-keto ester was developed using chiral tert-butanesulfinylphosphine as ligand, good yields (up to 87%), good 1,4-regioselectivities (up to 96:4), and high enantioselectivities (up to 94% ee) were achieved.     

A ferrocenyl-DHIPOH/Cu(OAc)2 complex for diastereo- and enantioselective catalysis of the 1,4-addition of glycine derivatives to alkylidene malonates

A planar chiral ferrocene derivative Fc-DHIPOH served as an excellent N,O- chiral ligand for asymmetric copper catalyzed 1,4-addition of glycine derivatives to alkylidene malonates. The corresponding 1,4-adducts were obtained in high yields with excellent enantioselectivities up to 95% ee.     

Catalytic enantioselective arylation of aryl aldehydes by chiral aminophenol ligands

The catalytic enantioselective arylation of aryl aldehydes using boronic acids as the source of transferable aryl groups is described; the reaction is found to proceed in good yields and in good to high enantioselectivities (up to 99% ee) in the presence of a chiral aminophenol ligand.     

External chiral ligand-mediated enantioselective Peterson reaction of alpha-trimethylsilanylacetate with substituted cyclohexanones

[reaction: see text] The asymmetric Peterson reaction of an alpha-trimethylsilanylacetate with 4-substituted and 3,5-disubstituted cyclohexanones was mediated by an external chiral tridentate ligand to give the corresponding olefins with an axial chirality in high yields and enantioselectivities of up to 85%.