Palladium-catalyzed Asymmetric Allylations Research Articles

Construction of Enantioenriched Quaternary C-Cl Oxindoles through Palladium-Catalyzed Asymmetric Allylic Substitution with Chloroenolates.

A palladium-catalyzed asymmetric chloroenolate allylation with vinyl benzoxazinanones under mild reaction conditions has been developed, affording a series of optically active 3,3-disubstituted oxindoles exhibiting a chloro-group and a linear aryl amino side chain in good yields with up to 96% ee. Versatile functional group tolerance on the benzene ring has been demonstrated, and the utility of this method was probed by a scale-up synthesis and highlighted by product derivatizations.

Palladium-catalyzed asymmetric allylation via directed migration of remote dienes

Palladium-catalyzed asymmetric allylation via directed migration of remote dienes

Novel BIPHEN H2 based P,S-bidentate phosphoramidite ligand in palladium-catalyzed asymmetric allylation

The reaction of P,S-phosphoramidite bearing (Ra)-BIPHEN H2 core and exocyclic amino sulfide as the new ligand with [Pd(ppp-allyl)Cl]2 in the presence of AgBF4 yielded a cationic metallochelate [Pd(ppp-allyl)(L)]BF4. This new chiral inducer provided up to 90% ee in the Pd-mediated allylic substitution reaction of (E)-1,3-diphenylallyl acetate with various C- and N-nucleophiles. In the Pd-catalyzed amination of 2-diethoxyphosphoryl-1-phenylallyl acetate with aniline, ee values up to 57% were achieved.

Regio- and Enantioselective Palladium-Catalyzed Asymmetric Allylation of N-Fluorenyl Trifluoromethyl Imine.

A palladium-catalyzed asymmetric allylation of N-fluorenyl trifluoromethyl imine with allylic acetates is disclosed. This method provides scalable and efficient access to polysubstituted chiral α-trifluoromethyl amines bearing two adjacent stereocenters and one allyl group in high yields with excellent regio-, diastereo-, and enantioselectivity. Importantly, this method also provides a powerful strategy for the synthesis of both regioisomeric products and the regioselectivity is controlled by the chiral catalysts and optically active substrates.

Palladium-Catalyzed Asymmetric Allylation of α-Amidopyridinium Salts

Palladium-Catalyzed Asymmetric Allylation of α-Amidopyridinium Salts

Palladium-Catalyzed Asymmetric Allylation of Allylic Acetates

Key words asymmetric allylic allylation - asymmetric palladium catalysis - Morita–Baylis–Hillman reaction

Mechanistic insights on cooperative asymmetric multicatalysis using chiral counterions.

Cooperative multicatalytic methods are steadily gaining popularity in asymmetric catalysis. The use of chiral Brønsted acids such as phosphoric acids in conjunction with a range of transition metals has been proven to be effective in asymmetric synthesis. However, the lack of molecular-level understanding and the accompanying ambiguity on the role of the chiral species in stereoinduction continues to remain an unresolved puzzle. Herein, we intend to disclose some novel transition state models obtained through DFT(B3LYP and M06) computations for a quintessential reaction in this family, namely, palladium-catalyzed asymmetric Tsuji-Trost allylation of aldehydes. The aldehyde is activated as an enamine by the action of a secondary amine (organocatalysis), which then adds to an activated Pd-allylic species (transition metal catalysis) generated through the protonation of allyic alcohol by chiral BINOL-phosphoric acid (Brønsted acid catalysis). We aim to decipher the nature of chiral BINOL-phosphates and their role in creating a quaternary chiral carbon atom in this triple catalytic system. The study reports the first transition state model capable of rationalizing chiral counterion-induced enantioselectivity. It is found that the chiral phosphate acts as a counterion in the stereocontrolling event rather than the conventional ligand mode.

Palladium-Catalyzed Asymmetric Allylation of Cyclobutene Derivatives

Palladium-Catalyzed Asymmetric Allylation of Cyclobutene Derivatives

A New Approach to the Synthesis of Peptidomimetic Renin Inhibitors: Palladium-Catalyzed Asymmetric Allylation of Acyclic Alkyl Aryl Ketones

A new approach to the synthesis of Tekturna, a recently marketed drug for hypertension, takes advantage of a modified protocol of the Stoltz palladium-catalyzed asymmetric allylation with a t-BuPHOX ligand for the synthesis of allylated acyclic alkyl aryl ketones. The method led to an α-isopropyl α-allyl aryl ketone in 90% yield and 88 to 91% ee, which was used in the synthesis of an advanced intermediate toward Tekturna. A beneficial effect of protic additives, such as BHT (2,6-di-tert-butyl-p-cresol), on the time and enantioselectivity of the reaction was discovered.

Kinetic Resolution via Palladium-Catalyzed Asymmetric Allylation

Key words axial chiral palladium complexes - allylation - kinetic resolution - Morita–Baylis–Hillman adducts - palladium

Phosphoramidites based on phenyl-substituted 1,2-diols as ligands in palladium-catalyzed asymmetric allylations: the contribution of steric demand and chiral centers to the enantioselectivity

A small family of readily available phosphoramidite ligands, including compounds with P ∗ -stereocenters, has been prepared from phenyl-substituted 1,2-diols as simple and cheap starting materials. Using these ligands, up to 84% ee was achieved in Pd-catalyzed asymmetric allylic substitution. The influence of structural modules such as asymmetric atoms and steric demand on the enantioselectivity is discussed.

Highly enantioselective palladium-catalyzed umpolung allylation of aldehydes

Compared with well-established electrophilic π-allylpalladium chemistry, the catalytic asymmetric reactions via umpolung of π-allylpalladium have received limited success. Although extensive efforts have been devoted, only modest enantioselectivities have been obtained in the palladium-catalyzed asymmetric umpolung allylation reactions. In this context, we disclose a highly enantioselective palladium-catalyzed umpolung allylation of aldehydes with allylic alcohols and their derivatives. By using sterically hindered chiral monodentate spiro phosphite ligands, we have accomplished the asymmetric allylation reaction with high yields and excellent enantioselectivities (up to 97% ee). These results represent the highest level of enantioselectivity for the umpolung allylation reactions. The present palladium-catalyzed asymmetric allylation reaction uses readily available allylic alcohols and their derivatives instead of sensitive allylic organometallic reagents, which provides a competitive alternative approach for preparation of versatile chiral homoallylic alcohols. A preliminary mechanism of palladium-catalyzed umpolung allylation reaction was discussed based on the experimental observations.

ChemInform Abstract: Palladium-Catalyzed Asymmetric Allylations of Chiral Enamines Bearing Phosphine Functionality. Effects of Anionic Counterparts of Allylating Reagents on Asymmetric Induction.

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Palladium-catalyzed asymmetric umpolung allylation of imines with allylic alcohols

A palladium-catalyzed asymmetric umpolung allylation reaction of imines with allylic alcohols has been developed. In the presence of chiral spiro phosphoramidite ligand 4, the allylation was accomplished with high yields and good enantioselectivities. The use of highly stable and easily available allylic alcohols instead of allylic metal reagents facilitated the preparation of chiral homoallylic amines.

From allylic alcohols to chiral tertiary homoallylic alcohol: palladium-catalyzed asymmetric allylation of isatins

A palladium-catalyzed asymmetric allylation of isatins with allylic alcohols as an allyl donor was developed by using chiral spiro phosphoramidite ligands. A variety of chiral tertiary homoallylic alcohols 3-allyl-3-hydroxy-2-oxindoles were prepared directly from allylic alcohols in one step with excellent yields and moderate enantioselectivities. This represents the first catalytic asymmetric allylation of ketones with allylic alcohol as the allylating agent.

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.

Ferrocenylphosphine-amide ligands for palladium-catalyzed asymmetric allylation

A new series of phosphine-amide ligands has been prepared on a ferrocenylethyl backbone. These species are effective for enantioselective palladium-catalyzed substitution reactions of allylic acetates. The modular nature of the ligand design has allowed ready optimization to afford products of up to 98.8% ee.

Polymer-supported Phosphinooxathiane as Ligands for Palladium-catalyzed Asymmetric Allylations

New polymer-supported chiral ligands, PS-DES, PS-Et, and TentaGel supporting phosphinooxathianes were prepared and used in palladium-catalyzed asymmetric allylic alkylation and amination.

P-stereogenic P/N hybrid ligands: a remarkable switch in enantioselectivity in palladium-catalyzed asymmetric allylation

Optically active P-stereogenic phosphine/oxazoline bidentate ligands ( 1 ) were prepared and applied to palladium-catalyzed allylic substitution of 1,3-diphenyl-1-acetoxy-2-propene with dimethyl malonate. The absolute configuration of the allylation product was remarkably switched by changing a palladium/ligand ratio between 1/1 and 1/2.

Novel chiral xylofuranose-based phosphinooxathiane and phosphinooxazinane ligands for palladium-catalyzed asymmetric allylations

Novel chiral xylofuranose-based phosphinooxathiane and phosphinooxazinane ligands were found to provide high levels of enantioselectivity (up to 94% ee) in palladium-catalyzed asymmetric allylic alkylations and aminations.