Kodai Saito

Chiral phosphoric acid-catalyzed oxidative kinetic resolution of indolines based on transfer hydrogenation to imines

The oxidative kinetic resolution of 2-substituted indoline derivatives was achieved by hydrogen transfer to imines by means of a chiral phosphoric acid catalyst. The oxidative kinetic resolution was applicable to racemic alkyl- or aryl-substituted indolines, and the remaining indolines were obtained in good yields with excellent enantioselectivities.

Chiral Copper(II) Phosphate Catalyzed Enantioselective Synthesis of Isochromene Derivatives by Sequential Intramolecular Cyclization and Asymmetric Transfer Hydrogenation of o-Alkynylacetophenones†

Chiral binaphthyl phosphoric acids (CPAs) have been used for the activation of imines through hydrogen-bonding interactions and a range of enantioselective reactions have been developed. Recently, the conjugate base of a CPA has emerged as a chiral counteranion catalyst for asymmetric synthesis, wherein electrostatic interactions are responsible for the high enantioselectivity. This concept has been recognized as a powerful tool, and is termed asymmetric counterion-directed catalysis (ACDC). By using this concept, catalytic reactions which proceed via cationic intermediates can be performed with high enantioselectively by the incorporation of a chiral counteranion into the catalyst. One of the most powerful uses of ACDC involves the incorporation of transition-metal catalysis. The cationic metallic intermediate can form a tight ion pair with the chiral counteranion. Intramolecular cyclization initiated by activation of the alkyne moiety using transition-metal catalysis has been extensively investigated, and cyclized metal-containing intermediates could also be employed for further reactions in a tandem manner. Recently, reactions initiated by alkyne activation, combined with the use of CPA have also been developed. Transition-metal-containing carbonyl ylides are highly reactive intermediates, which are generated by 6-endo-dig cyclization reactions of alkynyl carbonyl compounds. Although the carbonyl ylides are employed for [4+2] and [3+2] cycloaddition reactions, its application to asymmetric synthesis is limited. As far as we know, Iwasawa and coworkers reported the [3+2] cycloaddition reaction of a platinum-carbonyl ylide with vinyl ethers by means of chiral platinum bisphosphine complex, and bicyclic ether structures were efficiently constructed in good yields with excellent enantioselectivities. There are no preceding examples for enantiocontrol of the carbonyl ylide intermediate using the ACDC concept, and the development of asymmetric reactions using metal-containing carbonyl ylide intermediates based on the new concept is thus, an important challenge. More recently, Yao and co-workers reported the Pd(OAc)2/ CPA-catalyzed asymmetric cascade annulation based on an oxa-Diels–Alder cycloaddition using a metal-containing carbonyl ylide intermediate to afford tetrahydronapthalene derivatives with multiple stereogenic centers including quaternary carbon atoms, thus taking advantage of the metallo/ organo binary catalytic methodology. Although a CPA (1)-catalyzed transfer hydrogenation of imines using a hydrogen donor has been recently developed by many research groups, the application of this method for ketones, in place of imines, is limited to a few examples. We could view the carbonyl ylide 3 as an easily hydrogenated intermediate, in which the carbonyl oxygen atom would be strongly activated by a vinylic carbocation (Scheme 1). Our

Enantioselective organocatalytic reductive amination of aliphatic ketones by benzothiazoline as hydrogen donor

The chiral phosphoric acid-catalyzed enantioselective reductive amination of aliphatic ketones with aromatic amines was successfully achieved by the use of benzothiazoline as the hydrogen donor. Corresponding chiral aliphatic amines were obtained with excellent enantioselectivities.

Chiral Phosphoric‐Acid‐Catalyzed Transfer Hydrogenation of Ethyl Ketimine Derivatives by Using Benzothiazoline

Chiral phosphoric acid catalyzed transfer hydrogenation of ketimines derived from propiophenone derivatives and reductive amination of alkyl ethyl ketone derivatives were extensively examined in the presence of two representative hydrogen donors. The excellent enantioselective transfer hydrogenation was achieved by use of benzothiazoline as a hydrogen donor. The theoretical studies elucidated that the unsymmetrical structure of benzothiazoline plays an important role in high enantioselective hydrogenation.

Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis of 2-Substituted 2,3-Dihydro-4-quinolones by a Protecting-Group-Free Approach

Chiral 2-substituted 2,3-dihydro-4-quinolones were synthesized based on the chiral phosphoric acid catalyzed intramolecular aza-Michael addition reaction using N-unprotected 2-aminophenyl vinyl ketones as substrates in good yields with high enantioselectivities.

Asymmetric transfer hydrogenation of ketimines by indoline as recyclable hydrogen donor

The chiral phosphoric acid catalyzed enantioselective transfer hydrogenation of various ketimines was achieved by the use of 2-aryl indoline as the hydrogen donor. Corresponding chiral amines were obtained in good chemical yields with excellent enantioselectivities.

Chiral Phosphoric Acid Catalyzed Kinetic Resolution of Indolines Based on a Self-Redox Reaction.

A strategy for oxidative kinetic resolution of racemic indolines was developed, employing salicylaldehyde derivative as the pre-resolving reagent and chiral phosphoric acid as the catalyst. The iminium intermediate, formed by the condensation reaction of an enantiomer of indoline with salicylaldehyde derivative, was hydrogenated by the same enantiomer of indoline to afford another enantiomer of indoline by a self-redox mechanism. The oxidative kinetic resolution of 2-aryl-substituted indolines proceeded to give enantiomers in good yields with excellent enantioselectivities.

B(C6F5)3-Catalyzed Hydrodesulfurization Using Hydrosilanes--Metal-Free Reduction of Sulfides.

B(C6F5)3-catalyzed hydrodesulfurization of carbon-sulfur bonds was achieved using triethylsilane as the reducing agent. The corresponding products were obtained in good yields under mild reaction conditions. This protocol could be applied to the reduction of sulfides, including benzyl and alkyl sulfides and dithianes, with high chemoselectivities.

Stereospecific Decarboxylative Nazarov Cyclization Mediated by Carbon Dioxide for the Preparation of Highly Substituted 2‐Cyclopentenones

Highly substituted 2-cyclopentenones were stereospecifically and regioselectively constructed with high catalytic efficiency through Lewis-acid catalyzed decarboxylative Nazarov cyclization of the cyclic carbonate derivative, which is prepared by reacting the propargyl alcohol with carbon dioxide in the presence of a silver catalyst. The stereochemistry of the 2-cyclopentenone is strictly controlled by the geometry of the alkene in the starting material. This method is applicable for various substrates.