Kyoto University · Chemistry
Professor Taichi Kano's research lab specializes in the development of novel chiral organocatalysts for asymmetric synthesis, with a focus on enantioselective transformations such as Mannich reactions, aldol reactions, and cycloadditions. The lab pioneers the use of axially chiral scaffolds—particularly amino trifluoromethanesulfonamides and amino sulfonamides—as highly effective catalysts for achieving high diastereo- and enantioselectivity in C–C and C–N bond formation. Their work emphasizes the design of robust, non-metallic catalysts that enable the synthesis of complex chiral building blocks with applications in natural product synthesis, such as manzacidin A. The lab also explores the synthetic utility of chiral N-heterocyclic carbenes and titanium-BINOL catalysts in enantioselective acylation and cycloaddition reactions.
Figures are computed from collected data and may differ slightly.
A direct asymmetric Mannich reaction using a novel axially chiral amino trifluoromethanesulfonamide (S)-3 has been developed in highly anti-selective and enantioselective manners. Thus, in the presence of a catalytic amount of (S)-3, the reactions between aldehydes and the alpha-imino ester 4 proceed smoothly to give the functional beta-amino aldehydes with significantly higher anti/syn ratio and enantioselectivity than previously possible.
[reaction: see text] The synthetic utility of chiral N-heterocyclic carbenes, which have been used mainly in transition metal-catalyzed reactions as a ligand, was demonstrated by the enantioselective acylation of secondary alcohols.
A titanium BINOLate catalyzed asymmetric 1,3-dipolar cycloaddition reaction between alpha-substituted acroleins and alkyl diazoacetates has been developed. With this methodology in hand, chiral 2-pyrazolines containing a quaternary stereogenic center were obtained in high to excellent enantioselectivities (up to 95% ee). The synthetic utility of the optically enriched 2-pyrazoline thus obtained was demonstrated in the short synthesis of manzacidin A.
A robust binaphthyl-based amino acid ((S)-1) exhibits higher stability and selectivity than proline for the catalysis of a direct asymmetric aldol reaction between aldehydes and acetone (see scheme; DMF=N,N-dimethylformamide). Olefinic, heteroaromatic, and aromatic aldehydes were found to be suitable substrates, with the corresponding aldol adducts being obtained in good yields and excellent enantioselectivities. Supporting information for this article is available on the WWW under http://www.wi
Complementary to proline: An axially chiral amino sulfonamide (S)-1 was successfully applied as the catalyst to the direct cross-aldol reaction between two different aldehydes (see scheme; NMP=N-methylpyrrolidone). This catalyst has the advantage of giving mainly syn products, while proline shows the opposite anti selectivity.
The 1,2-diamine (vicinal diamine) motif is present in a number of natural products with interesting biological activity and in many chiral molecular catalysts. The efficient and stereocontrolled synthesis of enantioenriched vicinal diamines is still a challenge to modern chemical methodology. We report here both syn- and anti-selective asymmetric direct Mannich reactions of N-protected aminoacetaldehydes with N-Boc-protected imines catalyzed by proline and the axially chiral amino sulfonamide (S
Optically active sulfoximines are a promising substance in medicinal chemistry. However, a methodology for preparing chiral sulfoximines in a stereoselective manner has been underdeveloped. Here, we report an asymmetric synthesis of chiral sulfoximines having an aryl group by the newly developed sulfur-selective arylation of easily accessible chiral sulfinamides. The utility of the present method is demonstrated by the asymmetric synthesis of a key intermediate of a COX-2 inhibitor.
A mu-oxo-type chiral bis-Ti(IV) oxide (S,S)-1 can be successfully utilized in the asymmetric 1,3-dipolar cycloaddition reactions between various nitrones 2 and acrolein to give the corresponding isoxazolidines with high to excellent enantioselectivities. For instance, the reaction between nitrone 2 (R = t-Bu) and acrolein in the presence of 10 mol % of bis-Ti(IV) catalyst (S,S)-1 in dichloromethane at -40 degrees C gave the corresponding endo cycloadduct with 97% ee.
A direct asymmetric hydroxyamination reaction of aldehydes with nitrosobenzene was found to be catalyzed by the novel axially chiral secondary amine catalyst (S)-1d. The resulting optically enriched hydroxyamination products were readily converted to beta-amino alcohols or 1,2-diamines in one pot.
Abstract The moderate nucleophilicity of the axially chiral amino sulfonamide ( S )‐ 1 suppresses the problematic side reactions, including aldol reactions, in the asymmetric Mannich reaction of N‐Boc‐protected imines with aldehydes. The corresponding adducts are obtained in good yield and excellent stereoselectivity (see scheme; Boc= tert ‐butoxycarbonyl, Tf=trifluoromethanesulfonyl). magnified image
A direct asymmetric benzoyloxylation of aldehydes with benzoyl peroxide was found to be catalyzed by (S)-2-(triarylmethyl)pyrrolidines (S)-2. This method provides a new approach for the preparation of optically active alpha-benzoyloxyaldehydes as useful chiral building blocks.
Abstract Innovation in drug discovery critically depends on the development of new bioisosteric groups. Chiral sulfoximines, which contain a tetrasubstituted sulfur atom that bears one nitrogen, one oxygen, and two different carbon substituents, represent an emerging chiral bioisostere in medicinal chemistry. Chiral sulfoximines are conventionally prepared by a stereospecific nitrene transfer reaction to chiral sulfoxides; however, the number of readily available chiral sulfoxides remains limite
[reaction: see text] A novel binaphthyl-based diamine (R)-2 was designed and synthesized. A protonic acid-(R)-2 salt catalyst has the advantage of exhibiting unprecedented high exo selectivity in the asymmetric Diels-Alder reaction of alpha,beta-unsaturated aldehydes. For instance, the reaction between cinnamaldehyde and cyclopentadiene in the presence of 12 mol % of binaphthyl-based diamine (R)-2 and 10 mol % of p-TsOH.H(2)O in alpha,alpha,alpha-trifluorotoluene at -20 degrees C gave the corres
A direct asymmetric Mannich reaction using a novel axially chiral amino sulfonamide (S)-3 that is highly anti- and enantioselective has been developed. For instance, in the presence of a catalytic amount of (S)-3, the reactions between aldehydes and alpha-imino esters proceeded smoothly to give anti Mannich products with a significantly higher anti/syn ratio and enantioselectivity than previously possible. By utilizing N-Boc-protected aromatic imines instead of alpha-imino esters, the synthetica
A chemo- and stereoselective asymmetric direct cross-aldol reaction between aliphatic aldehydes and α-chloroaldehydes has been developed as a method for the formation of the sole cross-aldol adduct with both enantio- and diastereocontrol, and either anti- or syn-aldol adducts were obtained in good to excellent stereoselectivities by use of proline or a novel axially chiral amino sulfonamide as catalyst.
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