Palladium-catalyzed asymmetric allylic substitution using planar chiral hydrazone ligands

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (3) with a dimethyl malonate–BSA–LiOAc system has been successfully carried out in the presence of planar chiral phosphine-hydrazone ligands such as 2a in good yields with good enantioselectivities (up to 96% ee).     

Palladium-catalyzed asymmetric allylic alkylation using chiral aminophosphine ligands

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate 18 with a dimethyl malonate–BSA–LiOAc system has been successfully carried out in the presence of new chiral aminophosphine ligands 1–5 in good yields with good enantioselectivities (up to 85% e.e.).     

Palladium-catalyzed asymmetric allylic alkylation using chiral hydrazone ligands with ferrocene skeleton

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (4) with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of chiral phosphine-hydrazone ligands such as 3a in good yields with good enantioselectivities (up to 84% ee).     

Palladium-catalyzed asymmetric allylic alkylation using iminophosphine ligands derived from chiral primary 1-ferrocenylalkylamines

The palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propen-1-yl acetate 4 with dimethyl malonate in the presence of chiral iminophosphine ligands 3a–3d derived from chiral primary 1-ferrocenylalkylamines 1 and 2-(diphenylphosphino)benzaldehyde 2 was investigated. Excellent enantioselectivity (up to 97%) was achieved when ligand 3d was used. A mechanism for asymmetric induction in this reaction was proposed by theoretical modeling of the intermediate π-allylpalladium complexes.     

Palladium-catalyzed allylic alkylation using chiral hydrazones as ligands

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (4) with a dimethyl malonate-BSA-LiOAc system and its derivatives has been successfully carried out in the presence of a new chiral hydrazone ligands such as 2-(diphenylphosphino)benzaldehyde SAMP hydrazone (DPPBA-SAMP) (3a) in high yields with high enantioselectives.     

Thioether containing ligands for asymmetric allylic substitution reactions

This review covers reports in the literature on the use of thioether ligands in Pd-catalysed asymmetric allylic substitution reactions from 1996 to June 2006. In the first section, we will cover the results using (S,S)-homo and (S,S)-heterodonor ligands. In the next section, we will present the results using heterodonor (S,X)-ligands, emphasizing the results obtained with (S,N)- and (S,P)-donor ligands. We also discuss any reported mechanistic aspects according to the allylic substitution results.     

Palladium-catalyzed asymmetric tandem allylic substitution using chiral 2-(phosphinophenyl)pyridine ligand

Palladium-catalyzed asymmetric tandem allylic substitution of (Z)-1,4-diacyloxy- and (Z)-1,4-bis(alkoxycarbonyloxy)-2-butene (2a-c) using 2-(phosphinophenyl)pyridine 1 as chiral ligand provided optically active six-membered 2-vinyl-1,4-diheterocyclic compounds with good to high enantioselectivity. For example, the reactions with catechol, 2-(benzylamino)phenol, or 1,2-bis(benzylamino)ethane as a nucleophile gave 2-vinyl-1,4-benzodioxane (71% ee), 4-benzyl-2-vinyl-1,4-benzoxazine (86% ee), and 1,4-dibenzyl-2-vinylpiperazine (86% ee), respectively.     

First chiral phosphoroamidite-phosphite ligands for highly enantioselective and versatile Pd-catalyzed asymmetric allylic substitution reactions

[reaction: see text] A series of phosphite-phosphoroamidite ligands, derived from readily available d-xylose, has been successfully applied for the first time in the Pd-catalyzed allylic substitution of several substrates with different steric and electronic properties, with high enantioselectivities (ee's up to 98) and activities in standard conditions.     

Novel chiral biferrocene ligands for palladium-catalyzed allylic substitution reactions

Eleven novel aminophosphine ligands have been synthesized, all of which contain a chiral 2,2' '-bridged biferroceno unit as part of a biferrocenoazepine substructure. The efficiency of these compounds as chiral auxiliaries in palladium-mediated allylic substitution reactions has been investigated. Depending on the degree of (steric) fit between proper ligands and cyclic or noncyclic substrates, reactions with 46-87% ee were achieved. The molecular structure of a palladium dichloride complex of one of the ligands was determined by X-ray diffraction and compared to its binaphthyl analogue. In the solid state, the azepine substructure of these two complexes adopts totally different conformations with either local C(2) (binaphthyl) or local C(1) (biferrocene derivative) symmetry. These structural changes are well-reproduced by empirical force field calculations and are also reflected in significantly different behavior in asymmetric catalysis.     

Palladium-catalyzed asymmetric allylic substitutions in the presence of chiral phosphine-imine type ligands

Chiral bidentate phosphine-imine type ligand L9 is fairly effective in the asymmetric allylic substitution of 1,3-diphenylpropenyl acetate with dimethyl malonate to give the corresponding adduct in moderate yield and good ee.     

Palladium-catalyzed enantioselective allylic substitution by chiral p,n-heterodonor ligands

Summary Chiral P,N-heterodonor ligands are effective in the enantioselective allylic substitution of 1,2-diphenyl-2-propenyl acetate with dimethylmalonate. The reactions are conveniently carried out at ambient temperature. The excellent levels of enantiomeric excess up to 98% were obtained in good conversion.     

Furanoside thioether–phosphinite ligands for Pd-catalyzed asymmetric allylic substitution reactions

A new series of thioether–phosphinite ligands, easily prepared in a few steps from inexpensive d-(+)-xylose, was tested in the Pd-catalyzed allylic substitution of substrates with different steric properties. The results show that the enantiomeric excesses are strongly dependent on the steric properties of the substituent in the thioether moiety. Enantiomeric excesses of up to 93% with high activities were obtained for the substrate rac-1,3-diphenyl-3-acetoxyprop-1-ene 7 with dimethyl malonate as the nucleophile.     

Palladium-catalyzed asymmetric allylic alkylation with an enamine as the nucleophilic reagent

An enamine can serve as a good nucleophile for palladium-catalyzed asymmetric allylic alkylation, avoiding the use of an unstablilized ketone enolate formed by strong bases. In the presence of a palladium complex of chiral metallocene-based phosphino-oxazoline ligands, the reaction was carried out smoothly with high catalytic activity and excellent enantioselectivity. Different distances between the two Cp rings of ferrocene and ruthenocene affected the catalytic behavior in the reaction. Furthermore, high catalytic activity and good enantioselectivity were also afforded by the ferrocene-based diphosphine ligands with only planar chirality.     

Palladium-catalyzed asymmetric allylic alkylation of indoles by C–N bond axially chiral phosphine ligands

The palladium-catalyzed asymmetric allylic alkylation of indoles with 1,3-diphenyl-2-propenyl acetate using P/N-type ligands such as N-aryl indole, C–N bond axially chiral aminophosphine (aS)-L4, gave the desired products 1 in good yields and with moderate to high enantioselectivities (up to 90% ee).     

Highly modular P-OP ligands in asymmetric allylic substitution

A library of highly modular P-OP ligands have been evaluated in Pd-catalysed allylic substitutions with C- and N-nucleophiles. Catalyst optimisation via a variation of the phosphino and phosphite substituents led to a ‘lead’ catalyst, which efficiently mediated the allylic substitutions when various combinations of substrates and nucleophiles were tested. Ground-state calculations were carried out and these allowed a clearer understanding of the stereochemical outcome of the reaction.     

Furanoside thioether-phosphinite ligands for Pd-catalyzed asymmetric allylic substitution reactions: Scope and limitations

A series of readily available thioether-phosphinite ligands has been tested in the Pd-catalyzed allylic substitution reactions of several acyclic and cyclic allylic substrates (S1-S7). This series of ligands have been designed to uncover their important structural features and to determine the scope of the thioether-phosphinite ligands in these catalytic reactions. Systematic variation of the electronic and steric properties at the thioether moiety provide useful information about the ligand parameters that control the enantiodiscrimination. By carefully selecting the ligand parameters, good enantioselectivities with high activities were obtained for hindered linear substrates S1 and S2 (ee’s up to 95%) and for unhindered cyclic substrates S4 and S5 (ee’s up to 91%).     

Pd-catalyzed asymmetric allylic substitution reactions using P-chirogenic diaminophosphine oxides: DIAPHOXs

This paper describes the development of a new class of chiral phosphorus ligand: aspartic acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs, and their application to several Pd-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed asymmetric allylic alkylation was initially examined in detail using diaminophosphine oxides 1a, resulting in the highly enantioselective construction of quaternary stereocenters. Mechanistic investigations revealed that 1a is activated by N,O-bis(trimethylsilyl)acetamide-induced tautomerization to afford a trivalent diamidophosphite species 12, which functions as the actual ligand. Furthermore, asymmetric allylic amination was examined using Pd-DIAPHOX catalyst systems, providing a variety of chiral allylic amines.     

Furanoside phosphite–phosphoroamidite and diphosphoroamidite ligands applied to asymmetric Cu-catalyzed allylic substitution reactions

A phosphite–phosphoroamidite and diphosphoroamidite ligand library was applied in the Cu-catalyzed allylic substitution of a range of cinnamyl-type substrates using several organometallic nucleophiles. Results indicated that selectivity depended strongly on the ligand parameters (position of the phosphoroamidite group at either C-5 or C-3 of the furanoside backbone, as well as the configuration of C-3, the introduction of a second phosphoroamidite moiety, the substituents and configurations in the biaryl phosphite/phosphoroamidite moieties), the nature of the leaving group of the substrate and the alkylating reagent. Good enantioselectivities (up to 76%) and activity combined with high regioselectivities were obtained.