Osamu Onomura

First chemo- and stereoselective reduction of imines using trichlorosilane activated with N-formylpyrrolidine derivatives

Abstract Trichlorosilane activated with N -formylpyrrolidine derivatives was found to be an effective reagent for reduction of imines to amines. The reagent showed much higher selectivity toward imino groups than carbonyl groups. The reduction of imines using trichlorosilane activated with optically active N -formylproline derivatives gave enantiomerically enriched amines in moderate optical yields (up to 66% ee).

Catalytic activation of trichlorosilane for efficient and stereoselective reduction of ketones

Abstract Some kinds of N-formyl cyclic amine derivatives were found to be effective activators for trichlorosilane to reduce ketones. Namely, a catalytic amount of these activators were sufficient to complete the reduction of ketones with trichlorosilane, and the reduction of ketones by trichlorosilane with optically active activators gave enantiomerically enriched sec-alcohols in some extent of optical yields (up to 51% ee).

A Convenient Method for Synthesis of Optically Active Methylphenidate from N-Methoxycarbonylpiperidine by Utilizing Electrochemical Oxidation and Evans Aldol-type Reaction

Abstract A new method to prepare optically active methylphenidate starting from piperidine is described. The method consists of a transformation of N -methoxycarbonylated piperidine to the corresponding α-methoxylated carbamate utilizing electrochemical oxidation followed by the coupling reaction with optically active Evans imides to produce optically active methylphenidate derivatives with high stereoselectivity ( erythro / threo =5.3/94.7, the threo isomer; 99.6%ee).

New enantiomerically pure 1,2-dihydropyridine and its use for construction of optically active 2-azabicyclo[2.2.2]octane

Abstract An enantiomerically pure 1,2-dihydropyridine 1 was prepared from l -lysine utilizing anodic oxidation as a key step, and was utilized as a chiral diene synthon of the Diels–Alder reaction. Furthermore, a suitable condition for the Diels–Alder reaction between 1 and N -acryloyloxazolidinone ( 8 ) was exploited. That is, the presence of AlCl 3 efficiently promoted the Diels–Alder reaction to give a cycloadduct with high stereoselectivity, which was converted to an optically active 2-azabicyclo[2.2.2]octane derivative 2 (96.8% ee).

Selective Monobenzoylation of 1,2- and 1,3-Diols Catalyzed by Me2SnCl2 in Water (Organic Solvent Free) under Mild Conditions

We have developed an efficient method for selective monobenzoylation of 1,2- and 1,3-diols in water catalyzed by Me(2)SnCl(2). Treatment of 1,2- and 1,3-diols with benzoyl chlorides, DMT-MM, and potassium carbonate in the presence of a catalytic amount of Me(2)SnCl(2) and DMAP in water at room temperature gave monobenzoates in up to 97% yield.

Efficient synthesis of 3-arylphthalides using palladium-catalyzed arylation of aldehydes with organoboronic acids.

The synthesis of 3-arylphthalides via palladium-catalyzed arylation of aldehydes with organoboronic acids was achieved using the thioether-imidazolinium carbene ligand in good to excellent yields and was carried out using 1.0 mol % of the catalyst with high substrate tolerance.

Efficient Oxidation of 1,2-Diols into α-Hydroxyketones Catalyzed by Organotin Compounds

Electrochemical oxidation of 1,2-diols with a catalytic amount of an organotin compound and a bromide ion as mediators has been developed. Various cyclic and acyclic 1,2-diols were oxidized into the corresponding alpha-hydroxyketones in good to excellent yields without C-C bond cleavage. Also, oxidation with the use of chemical oxidants was accomplished in the presence of a catalytic amount of an organotin compound. These reactions could discriminate 1,2-diols from isolated hydoxyl groups or 1,3-diols. In the case of a conformationally restricted cyclic 1,2-diol, the axial hydroxyl group was oxidized exclusively. Mono-, di-, and trialkylated tin compounds were examined as mediators and dialkylated tin compounds showed higher catalytic activity than mono- and trisubstituted ones. Me(2)SnCl(2) was found to be the most suitable mediator for the selective oxidation.

Effecient Kinetic Resolution of Racemic Amino Aldehydes by Oxidation with N‐Iodosuccinimide

Amino acids are very useful as synthetic building blocks for various biologically active compounds. Recently, several pseudopeptides containing natural or non-natural amino acids have been developed because they have pharmacologically important characteristics. Although natural amino acids are prepared by biochemical techniques such as fermentation, there is scant information on the preparation of non-natural amino acids by using this approach. Among the asymmetric catalytic methods for the synthesis of natural and non-natural amino acids, the kinetic resolution of amino acid derivatives is frequently used. However, there are few examples applicable to the synthesis of various optically active amino acids, including cyclic amino acids, and to the best of our knowledge, there is no chemical oxidation method for their preparation. We report herein the first efficient kinetic resolution of racemic amino aldehydes by oxidation. Recently, we accomplished the oxidative kinetic resolution of 1,2-diols, which was based on their recognition by a copper(II)/(R,R)-Ph-BOX complex (see Scheme 2 for structure), to afford optically active a-ketoalcohols. Moreover, we have reported the asymmetric electrochemical oxidation of N-protected 1,2-amino aldehydes to afford optically active amino acid methyl esters in low yield, but with good enantioselectivity. In line with our previous work, we investigated the reaction conditions for oxidative kinetic resolution of racemic amino aldehydes to improve the yields and enantioselectivities of the optically active amino acids. To our delight, we found a simple method for a highly efficient kinetic resolution of racemic N-protected amino aldehydes. The use of a chiral copper catalyzed oxidation procedue with N-iodosuccinimide (NIS) afforded optically active amino acid methyl esters, including cyclic and acyclic compounds, with high enantioselectivity (Scheme 1). Additionally, instead of recovering the starting material, the corresponding optically active aminoaldehyde dimethyl acetals were preferentially obtained. First, we applied the previous reaction conditions for asymmetric oxidation of 1,2-diols using N-bromosuccinimide (NBS) in the presence of K2CO3 [9a] for the oxidative kinetic resolution of rac-N-benzoyl-2-piperidinecarboaldehyde (rac1a ; Table 1, entry 1). (R)-2 a was obtained with a high

Ether-imidazolium carbenes for Suzuki-Miyaura cross-coupling of heteroaryl chlorides with aryl/heteroarylboron reagents.

Easily accessible and handled ether-imidazolium chlorides were developed as ligand precursors. The coupling reactions of heteroaryl chlorides with aryl/heteroarylboronic acids and esters were catalyzed by the palladium/ether-imidazolium chloride system with high substrate tolerance to give various heterobiaryls in good to excellent yields.

A convenient method for synthesis of optically active 2,3-methanopipecolic acid

Abstract 2,3-Didehydro-1,2-bis(methoxycarbonyl)-6-methoxypiperidine ( 4 ), prepared from l -lysine by using electrochemical oxidation, was cyclopropanated with high diastereoselectivity (96.6% de), and the cyclopropanated product was transformed to optically active 2,3-methanopipecolic acid ( 1 ). In this transformation, the 6-methoxy group of 4 was found to be an effective chiral auxiliary.