Reversal in enantioselectivity for the palladium-catalyzed asymmetric allylic substitution with novel metallocene-based planar chiral diphosphine ligands

The novel C₂-symmetric metallocene-based ligands with only planar chirality were synthesized easily and applied in palladium-catalyzed asymmetric allylic substitution with excellent enantioselectivity and high catalytic activity. When two ester groups on Cp rings of the metallocene were replaced by hydroxymethyl groups, opposite configuration of the product was obtained with high catalytic activity and excellent enantioselectivity. The opposite configuration of products was also obtained when the hydroxyl groups were protected as esters or ethers. These results might be attributed to the different configuration of the diphosphine ligands-Pd(II) complexes.     

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.     

Novel chiral P,N-ferrocene ligands in palladium-catalyzed asymmetric allylic alkylations

Novel chiral P,N-ferrocene ligands, 1-diphenylphosphino-1′-oxazolinylferrocenes, were prepared from ferrocene via 1,1′-bis(tributylstannyl)ferrocene and 1-diphenylphosphino-1′-methoxycarbonylferrocene as intermediates, and with this new kind of ligand up to 91% ee with 99% chemical yield was afforded for the palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethylmalonate anion. The complexation behavior of this kind of ligand with dichlorobis(acetonitrile)palladium and bis(μ-chloro)(1,3-diphenyl-η³-allyl)dipalladium was investigated.     

Highly effective chiral phosphorus amidite-olefin ligands for palladium-catalyzed asymmetric allylic substitutions

This paper describes the development of a type of novel P-olefin hybrid ligand by the incorporation of terminal olefins onto phosphorus amidite ligands for palladium-catalyzed asymmetric allylic alkylations of indoles and substitutions with amines to give the desired products in 70-97% yield with 91-98% ee.     

Novel and efficient chiral sulfideoxathiane ligands for palladium-catalyzed asymmetric allylic alkylation

Easily prepared, chiral sulfideoxathiane ligands are described which give excellent enantioselectivity (up to 99% ee) in the Pd-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with a range of alkyl malonate nucleophiles.     

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).     

A new chiral iminophosphine ligand derived from (1S,4S)-fenchone in palladium-catalyzed asymmetric allylic alkylations

A new chiral iminophosphine ligand derived from (1S,4S)-fenchone has been developed, and its usefulness as a chiral ligand in asymmetric synthesis was demonstrated in palladium-catalyzed allylic alkylations.     

Palladium-catalyzed asymmetric allylic nucleophilic substitution reactions using chiral tert-butanesulfinylphosphine ligands

The asymmetric allylic alkylation of racemic 1,3-diphenyl-2-propenyl acetate 3 with dimethyl malonate proceeded smoothly in the presence of lithium acetate, BSA (N,O-bis(trimethylsilyl)acetamide), [Pd(η³-C₃H₅)Cl]₂, and chiral tert-butanesulfinylphosphine ligand 2c to give the allylic alkylation product in good yield and high enantiomeric excess (up to 93% ee), while the enantioselectivities of allylic amination of 3 with various amines were moderate (up to 76% ee).     

Chiral sulfideoxathiane ligands for palladium-catalyzed asymmetric allylic alkylation

Easily prepared, chiral sulfideoxathiane ligands are described, which give excellent enantioselectivities (up to 99% ee) in the Pd-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with a range of alkyl malonate nucleophiles.     

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.     

A novel amphiphilic chiral ligand derived from D-glucosamine. Application to palladium-catalyzed asymmetric allylic substitution reaction in an aqueous or an organic medium, allowing for catalyst recycling

A novel amphiphilic phosphinite-oxazoline chiral compound, 2-methyl-4,5-[4,6-O-benzylidene-3-O-bis[4-((diethylamino)methyl)phenyl]phosphino-1,2-dideoxy-alpha-D-glucopyranosyl]-[2,1-d]-2-oxazoline (1), has been prepared from natural D-glucosamine hydrochloride. The newly prepared complex, [Pd(2-methyl-4,5-[4,6-O-benzylidene-3-O-bis[(4-((diethylmethylammonium)methyl)phenyl)]phosphino-1,2-dideoxy-alpha-D-glucopyranosyl]-[2,1-d]-2-oxazoline)(eta3-C3H5)]3+ x 3BF4- (3), is soluble in water and an efficient catalyst for asymmetric allylic substitution reaction in water or an aqueous/organic biphasic medium (up to 85% ee). This catalytic system offers an easy separation of the aqueous catalyst phase from the product phase and allows recycling of the catalyst phase. In addition, compound 1 also works as an effective ligand for the palladium-catalyzed reaction under conventional homogeneous conditions in an organic medium, in which the catalyst (Pd-1 complex) can be recovered by simple acid/base extraction and reused in the second reaction.     

Ferrocenyl-QUINAP: a planar chiral P,N-ligand for palladium-catalyzed allylic substitution reactions

The new planar chiral P,N-ligands 1a and 1b were prepared via a straightforward enantioselective synthesis using a Negishi cross-coupling and a sulfoxide/lithium exchange. Ligand 1a was successfully applied to Pd-catalyzed allylic alkylation (86% ee) and amination (83% ee) reactions.     

Polymer-supported chiral phosphinooxathiane ligands for palladium-catalyzed asymmetric allylations

Novel polymer-supported chiral ligands of PS–DES, PS–Et, and TentaGel supporting Pd-phosphinooxathianes were prepared and found to provide high levels of enantioselectivity (up to 99% ee) in palladium-catalyzed asymmetric allylic alkylations and aminations.     

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.     

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.     

A new class of chiral P,N-ligands and their application in palladium-catalyzed asymmetric allylic substitution reactions

An efficient and modular synthesis of a series of chiral nonracemic P,N-ligands is reported. The P,N-ligands were prepared from 2-chloro-4-methyl-6,7-dihydro-5H-[1]pyrindine-7-one and a series of substituted chiral C(2)-symmetric 1,2-ethanediols (R = Me, i-Pr, and Ph). The ligands were evaluated for use in catalytic asymmetric synthesis in the palladium-catalyzed allylic substitution reactions of a racemic allylic acetate and dimethyl malonate. In the case of the P,N-ligand (R = Ph), the reaction was found to be highly stereoselective (90% ee).     

Preparation of quarternary ammonium salt-tagged ferrocenylphosphine-imine ligands and their application to palladium-catalyzed asymmetric allylic substitution

A series of novel quarternary ammonium salt-modified chiral ferrocenylphosphine-imine ligands have been synthesized and the molecular structure of BIT5 has been determined by single-crystal X-ray diffraction. The applicability of these ligands in asymmetric C1–C and C1–N bond formation was demonstrated. High enantioselectivity was obtained in the Pd-catalyzed asymmetric substitution of 1,3-diphenyl-2-propenyl acetate, with dimethyl malonate (up to 94.6% ee) and benzylamine (up to 92.6% ee).     

Unexpected reversal of the enantioselectivity using chiral quinolylmethyl- and acridininyloxazolines as ligands for asymmetric palladium-catalyzed allylic alkylation

New chiral quinolylmethyloxazolines and acridininyloxazolines were prepared and assessed in the enantioselective palladium-catalyzed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate. The introduction of a benzo-fused substituent on the pyridine ring not containing the chiral backbone resulted in the switch of the expected chiral sense of enantioselection of the reaction. Enantiomeric excesses up to 78% were obtained.     

Modification of optically active ferrocenylphosphine ligands for palladium-catalyzed asymmetric allylic alkylation

Optically active ferrocenylphosphines containing a functional group on the side chain were effective as ligands for the palladium—catalyzed asymmetric allylic alkylation of 1,3-disubstituted allyl acetates such as l,3-diphenyl-3-acetoxy-l-propene with sodium acetylacetonate and related soft carbon nucleophiles to give the alkylation products of up to 92% ee.