Palladium-catalyzed Allylic Substitution Research Articles

C2-Symmetric bis-thioglycosides as new ligands for palladium-catalyzed allylic substitutions

A new divergent design for the synthesis of optically pure bis-thioglycoside type I is reported. In only two steps a common chiral intermediate with up to eight free alcohols: two primary and six secondary is obtained. From this common intermediate a large number of ligands can be synthesized. A positional scanning like strategy has permitted the rapid discovery of an efficient catalyst for the palladium-catalyzed asymmetric allylation of malonate. Dynamic NMR spectroscopy of a Pd(II) complex has shown that there is an efficient stereochemical control of the sulfur configuration upon coordination to the palladium.

Influence of steric symmetry and electronic dissymmetry on the enantioselectivity in palladium-catalyzed allylic substitutions.

Chiral P,N-ligands with pseudo-C2 and pseudo-Cs symmetry based on chiral pyrrolidine and phospholane rings or on dinaphthatodihydroazepino and dinaphthatodihydrophosphepino moieties were prepared and assessed in the palladium-catalyzed allylic substitutions of allylic acetates. Higher selectivity was achieved with pseudo-C2-symmetric ligands based on the binaphthyl skeleton than with the analogous C2-symmetric P,P- and N,N-analogues. Pseudo-C2-type ligands had properties superior to those of pseudo-meso-type ligands when 1,3-diphenyl-2-propenyl acetate was used as a substrate, whereas the reverse situation was found for 3-cyclohexenyl acetate. Chirally flexible ligands, prepared by substitution of one of the rigid binaphthyl skeletons for a flexible biphenyl system, were found to induce chirality to the same extent as a 1:1 mixture of the rigid ligands.

Synthesis of Novel Chiral Ligands from Amino Acids by the Ugi Reaction.

The Ugi multi-component reaction is employed for the efficient synthesis of chiral ligands starting from amino acids and aryl aldehydes bearing a Lewis-base functionality. Tests on the products as ligands for enantioselective transition metal catalysis gave promising results in the palladium-catalyzed allylic substitution with e.e. values up to 81%.

Synthesis of new sulfur-containing oxazoline ligands and their use in palladium-catalyzed allylic substitution

New chiral sulfur-containing ligands have been prepared and fully characterized. Their structure includes a dibenzothiophene or benzothiophene ring as backbone, where the sulfur atom is enclosed in a strong π-donor structure. The chirality was introduced by oxazoline moieties placed near the sulfur atom. These ligands have been successfully tested in asymmetric palladium-catalyzed allylic substitutions leading to products with ee of up to 77%.

Synthesis and Reactivities of Enantiomerically Pure β‐Hydroxyalkyl and β‐Aminoalkyl Ferrocenyl Sulfides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chiral thienylpyridines as N–S ligands for asymmetric catalysis

Diastereomeric pure thienylpyridines were prepared and assessed in the enantioselective palladium-catalyzed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate and copper-catalyzed cyclopropanation of styrene with ethyl diazoacetate. These ligands provided unreactive palladium catalysts but effective copper catalysts affording however low enantioexcesses.

Dibenzothiophene‐bis(oxazolines): New Sulfur‐Containing Ligands Tested in Asymmetric Palladium‐Catalyzed Allylic Substitutions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Fischer chromium carbene complexes as nucleophiles in palladium-catalyzed allylic substitution reactions

The Pd-catalyzed reaction of carbanions derived from chromium aminocarbene complexes with allylic acetates and carbonates smoothly affords the corresponding allyl-substituted aminocarbenes. On the contrary, the same reaction of the anion derived from pentacarbonyl[(methoxy)methylcarbene]chromium(0) with cinnamyl acetate affords 5-methoxy-1-phenylhexa-1,5-diene, the product of 1-methoxyethen-1-yl group transfer.

Synthesis of novel chiral ligands from amino acids by the Ugi reaction

The Ugi multi-component reaction is employed for the efficient synthesis of chiral ligands starting from amino acids and aryl aldehydes bearing a Lewis-base functionality. Tests on the products as ligands for enantioselective transition metal catalysis gave promising results in the palladium-catalyzed allylic substitution with e.e. values up to 81%.

Synthesis and Reactivities of Enantiomerically Pure β-Hydroxyalkyl and β-Aminoalkyl Ferrocenyl Sulfides

Enantiomerically pure β-hydroxyalkyl and β-aminoalkyl ferrocenyl sulfides have been synthesized in good yields from mercaptoferrocene and amino alcohol derivatives. Primary β-aminoalkyl sulfides allowed the synthesis of tetrahydro-1,4-thiazepines containing the ferrocene moiety with good diastereoselectivity and β-iminoalkyl sulfides. Some of these derivatives have successfully been employed as ligands for palladium-catalyzed allylic substitution, with asymmetric induction of up to 99% ee. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Examining the effect of hemilabile donor groups in non- C2 symmetrical terdentate ligands

The type and position of donor atoms in proline-derived, non- C 2 symmetric, terdentate ligands are found to have significant effects on the enantioselectivity of the palladium-catalysed allylic substitution reaction.

Dibenzothiophene-bis(oxazolines): new sulfur-containing ligands tested in asymmetric palladium-catalyzed allylic substitutions

New asymmetric sulfur-containing ligands based on a dibenzothiophene backbone have been prepared. The chirality was introduced by two oxazoline moieties placed near the sulfur atom. These C 2-symmetric bis(oxazolines) have been successfully tested in asymmetric palladium-catalyzed allylic substitutions leading to up to 77% e.e.

Chiral 2-(2-phenylthiophenyl)-5,6,7,8-tetrahydroquinolines: new N–S ligands for asymmetric catalysis: Palladium-catalyzed allylic alkylation and copper-catalyzed cyclopropanation reactions

Diastereomeric pure 2-(2-phenylthiophenyl)-5,6,7,8-tetrahydroquinolines were prepared and assessed in the enantioselective palladium-catalyzed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate and in the copper-catalyzed cyclopropanation of styrene with ethyldiazoacetate. Enantioselectivity up to 63% was obtained.

Role of planar chirality of S,N- and P,N-ferrocene ligands in palladium-catalyzed allylic substitutions.

Palladium-catalyzed asymmetric allylic substitutions using thioether and phosphino derivatives of ferrocenyloxazoline as ligands have been investigated with a focus on studying the role of planar chirality. In allylic alkylation, up to 98% ee and 95% ee were achieved with S,N- and P,N-ligands, respectively. In allylic amination, 97% ee was realized with P,N-ligands in the presence of TBAF. Several palladium allylic complexes were characterized by X-ray diffraction and/or solution NMR. Thioether derivatives of ferrocenyloxazolines with only planar chirality showed lower enantioselectivity in the allylic alkylation except 5c because of the formation of a new chirality on sulfur atom during the coordination of sulfur with palladium. On the other hand, in the planar chiral P,N-ligands without central chirality, (Sp)-11a-c there was no such disturbance and comparatively higher enantioselectivity in both palladium-catalyzed allylic alkylation and amination was provided.

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.

Concise syntheses of nonracemic gamma-fluoroalkylated allylic alcohols and amines via an enantiospecific palladium-catalyzed allylic substitution reaction.

Alpha-fluoroalkylated allyl mesylates reacted with various carboxylates and amines in the presence of tetrakis(triphenylphosphine)palladium(0) catalyst to give the corresponding gamma-fluoroalkylated (E)-allylic alcohol derivatives and amines, respectively, in excellent yields. In almost all cases, no other regio- and stereoisomers were produced. Application of this palladium-catalyzed allylic substitution reaction to various nonracemic mesylates afforded chiral gamma-fluoroalkylated allylic alcohol derivatives and amines without any loss of enantiomeric excess through the reaction.

An efficient organometallic approach to new carbocyclic nucleoside analogues.

[reaction: see text] A general synthetic approach to monoprotected carbocyclic nucleoside analogues, having the nucleobase attached to a 3-hydroxymethyl-4-trialkylsilyloxymethyl-cyclopent-2-en-1-yl scaffold, was developed. A (racemic) key intermediate was prepared by a cobalt-mediated Pauson-Khand reaction. In the course of the further synthesis, the introduction of the nucleobase was achieved with complete regio- and diastereoselectivity through a palladium-catalyzed allylic substitution.

Palladium-catalyzed allylic substitution reaction: oxidative addition versus dissociation in an olefin–palladium(0) complex

The reaction behavior of a transient olefin–palladium(0) complex after the first allylation was studied. Highly efficient palladium-catalyzed cascade double alkylation of a diallylic substrate is achieved by tuning the ligands. As a result, bidentate ligands which could form cyclic catalysts with a four-methylene bridge between two phosphorus atoms were effective for high selectivity and catalytic activity.

Modular furanoside phosphite ligands for asymmetric Pd-catalyzed allylic substitution.

A series of diphosphite, phosphine-phosphite, and thioether-phosphite ligands 1-5 with a furanoside backbone have been used in the enantioselective palladium-catalyzed allylic substitution of rac-1,3-diphenyl-2-propenyl acetate giving low to high enantioselectivies (from close to 0% to 97% ee). The modular nature of these ligands enables systematic investigations of the effect of the ligand structure on the enantioselectivity. The enantioselectivity is mainly determined by the configuration of the stereogenic center C-3 of the furanose backbone. From this we conclude that the attack of the nucleophile takes place trans toward the donating group at the stereogenic C-5 atom. Systematic variation of the donor group attached to the carbon atom C-5 indicated that the presence of a bulky phosphite functionality has a positive effect on enantioselectivity. Thus, the highest ee's are obtained using the bulky diphosphite ligand 1b containing a xylofuranoside backbone.

Novel ferrocene modified P, N-ligands for enantioselective palladium-catalyzed allylic substitution reactions

Novel ferrocene modified P, N-ligands ( R, R, Sp)- 8 and ( S, S, Sp)- 9 were synthesized conveniently from enantiopure cyclohexanediamine and ( Sp)-2-phosphinoferrocenyl carboxylic acid. They were used as chiral ligands for palladium-catalyzed allylic substitutions of rac-1, 3-diphenylprop-2-enyl acetate with dimethylmalonate and benzylamine. ( R, R, Sp)- 8 was found to be a better ligand containing matched chiralities (central chirality and planar chirality) and showed a higher enantioselectivity.