Yosuke Demizu

Regioselective Protection of Sugars Catalyzed by Dimethyltin Dichloride

The first catalytic process for protection of hydroxyl groups in sugars has been developed. Highly regioselective protection was accomplished along with high chemical yield. The regioselectivity of the benzoylation was realized as an intrinsic character of sugars based on a stereorelationship among their hydroxyl groups. Furthermore, complete protection of alpha-methyl glucoside and beta-methyl xyloside was accomplished.

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

Regioselective introduction of electrophiles into piperidine derivatives at the 4-position

- Regioselective introduction of various electrophiles (aldehydes, ketones, and imines) into piperidine skeleton at the 4-position was achieved with a catalytic amount of Pd(OAc) 2 /PPh 3 in the presence of excess Et 2 Zn. In addition, enantioselective introduction of benzaldehyde into piperidine derivatives was accomplished by using chiral phosphine ligand with moderate enantioselectivity.