Seiji Iwasa

Highly enantioselective chlorination of β-keto esters and subsequent S(N)2 displacement of tertiary chlorides: a flexible method for the construction of quaternary stereogenic centers.

Highly enantioselective chlorination of β-oxo esters and subsequent stereospecific substitution of tertiary chlorides are described. Enantioselective chlorination of β-keto esters and malonates was performed using a chiral Lewis acid catalyst prepared from Cu(OTf)(2) and the newly developed spirooxazoline ligand 2 to yield the desired α-chlorinated products with high enantioselectivity (up to 98% ee). Nucleophilic substitution of the resulting chlorides proceeded smoothly to afford a variety of chiral molecules such as α-amino, α-alkylthio, and α-fluoro esters, without loss of enantiopurity. The results of X-ray crystallographic analysis proved that Walden inversion occurs at the chlorinated tertiary carbon center. These results supported the fact that the substitution proceeds via an S(N)2 mechanism.

Enantioselective gem-chlorofluorination of active methylene compounds using a chiral spiro oxazoline ligand.

Highly enantioselective gem-chlorofluorination of active methylene compounds was carried out by using a copper(II) complex of a chiral spiro pyridyl monooxazoline ligand. This reaction yielded α-chloro-α-fluoro-β-keto esters and α-chloro-α-fluoro-β-keto phosphonates with up to 92% ee. The resulting dihalo β-keto ester was converted into various α-fluoro-α-heteroatom-substituted carbonyl compounds via nucleophilic substitution without loss of optical purity. A fully protected β-amino acid with a gem-chlorofluoromethylene function was also synthesized.

Asymmetric Inter‐ and Intramolecular Cyclopropanation Reactions Catalyzed by a Reusable Macroporous‐Polymer‐Supported Chiral Ruthenium(II)/Phenyloxazoline Complex

relatively low to moderate yields have so far been achieved.After an extensive literature survey, we concluded that all ofthe previously reported PSCCs depended on the polymeri-zation of a monomeric chiral ligand or the grafting of a chiralligand onto a polymeric support and subsequent complex-ation with a metal.

Stereoselective Construction of Halogenated Quaternary Stereogenic Centers via Catalytic Asymmetric Diels−Alder Reaction

Highly enantioselective Diels-Alder reactions of alpha-halo-alpha,beta-unsaturated ketones with Lewis acid-activated chiral oxazaborolidine 1 are described. The reaction with alpha-fluoroenones provided the corresponding cyclohexane derivatives having a fluorinated quaternary stereogenic center with up to 99% de and 94% ee. The reaction with alpha-bromo cyclic enones provided the corresponding bromo bicyclic adducts with up to 99% de and 95% ee. A brominated cis-fused bicyclic adduct derived from 2-bromocyclopenten-1-one and Danes diene was converted to the trans-fused bicyclic system via reductive alkylation with the bulky aluminum reagent aluminum tris(2,6-diphenylphenoxide) (ATPH). With this process, formal syntheses of (+)-estrone and norgestrel have been demonstrated.

A mild oxidation method of hydroxamic acids: efficient trapping of acyl nitroso intermediates

Abstract Ruthenium(II)-pyridine-2,6-dicarboxylate (pydic) of 2,6-bis(oxazolinyl)pyridine (pybox-dh) complex catalyzed the hydrogen peroxide oxidation of hydroxamic acid in the presence of cyclopentadiene to give acyl nitroso cycloadducts in 74–99% yield.

Anion-Accelerated Palladium-Mediated Intramolecular Cyclizations: Synthesis of Benzofurans, Indoles, and a Benzopyran

Abstract Substituted benzo-fused heterocycles such as indoles, benzofurans, and a benzopyran were obtained using an intramolecular cross-coupling of vinyl halides with phenols. This transformation represents a new route to these heterocycles and is accomplished using a palladacyclic catalyst under anionic conditions.

Chiral bis(trialkylsiloxymethyloxazolinyl)pyridine ligands. Highly enantioselective 1,3-dipolar cycloaddition reactions

Abstract A series of trialkylsilyl groups containing ligands have been prepared from C2 symmetric 2,6-bis(oxazolinyl)pyridine (pybox-hm) ( 2a ) bearing a hydroxymethyl group on the oxazoline ring. 1, 3-Dipolar cycloaddition reaction of nitrones and oxazolidinone derivatives in the presence of sterically tuned bis(oxazolinyl)pyridine (pybox-tbdmsom 2b , -tipsom 2c and -tbdpsom 2d ) and Ni(II) complexes as a Lewis acid catalyst proceeded smoothly to give the corresponding cycloadducts in 97:3 to >99:1 of endo/exo ratio and 97 to >99% ee for the endo adduct. Steric tuning of the chiral environment of pybox ligands was simply achieved by using silyl protecting groups of the hydroxyl groups. The solubility of the new pybox series 2b–d in organic solvent is dramatically increased; hence, the efficiency of these catalysts enhanced the rate of nitrone 1,3-dipolar cycloaddition. Furthermore, these ligands can make a single-coordinated Ni(pybox) as a catalyst, since clear linear effect between the enantiopurity of the ligand 2c and product 6a was observed.

Highly Enantioselective Synthesis of Cyclopropylamine Derivatives via Ru(II)-Pheox-Catalyzed Direct Asymmetric Cyclopropanation of Vinylcarbamates

The Ru(II)-Pheox-catalyzed asymmetric cyclopropanation of vinylcarbamates with diazoesters resulted in the corresponding cyclopropylamine derivatives in high yield and excellent diastereoselectivity (up to 96:4) and enantioselectivity (up to 99% ee).

Synthesis of 2,6-bis(4R-trialkylsiloxymethyloxazolinyl)pyridines and their use in catalytic asymmetric 1,3-dipolar cycloaddition reactions of nitrones and activated alkenes

Abstract 1,3-Dipolar cycloaddition reaction of aromatic nitrones with 3-alkenoyl-2-oxazolidinones in the presence of chiral 2,6-bis(4 R -trialkylsiloxymethyloxazolinyl)pyridine/Ni(II) system proceeds smoothly with high enantioselectivity in up to 99% ee.

Catalytic asymmetric cyclopropanation of alkenes with diazoesters in protic and biphasic media

Abstract As a C 2 symmetric hydrophilic chiral ligand, a series of 2,6-bis(oxazolinyl)-pyridines ( pyboxs ) bearing a hydroxyalkyl group on the oxazoline ring has been synthesized from readily available amino acid derivatives. Catalytic asymmetric intermolecular cyclopropanation of electron rich terminal alkenes with diazoesters in the presence of hydrophilic pybox ligand, pybox- hm and Ru(II) complex proceeded smoothly in protic or biphasic media to give the corresponding cyclopropanation products in 97:3 to 99:1 trans / cis ratios and 90 to 97% ee. In the case of the intramolecular cyclopropanation reaction of trans -cinnamyl diazoester using Ru(II)(pybox- he ) complex in biphasic medium gave the corresponding cyclopropane ring fused lactone in 52% ee. Steric tuning of the chiral environment of pybox ligands was simply achieved by using a weak interaction between the solvent and the hydroxyl groups of the chiral ligand. The solubility of the new hydrophilic pybox and Ru(II) complexes in protic solvents is dramatically increased; hence, the efficiency of these catalysts enhanced the rate of cyclopropanation. Furthermore, the active catalyst in the water phase can be re-used several times for the cyclopropanation reaction.