2018年度研究成果

5)  Lipase-Catalyzed Dynamic Kinetic Resolution of C1- and C2- Symmetric Racemic Axially Chiral 2,2'-Dihydroxy-1,1'-biaryls

Gamal A. I. Moustafa, Yasuhiro Oki, Shuji Akai, Angew. Chem. Int. Ed., accepted (2018), DOI:10.1002/anie.201804161

Abstract: We have discovered that the racemization of configurationally stable, axially chiral 2,2’-dihydroxy-1,1’-biaryls proceeds with a catalytic amount of a cyclopentadienylruthenium(II) complex at 35–50 °C. Combining this racemization procedure with lipase-catalyzed kinetic resolution led to the first lipase/metal-combo-catalyzed dynamic kinetic resolution of racemic axially chiral biaryls. The method was applied to the synthesis of various enantio-enriched C1- and C2-symmetric biaryl diols in yields of up to 98% and enantiomeric excesses of up to 98%, which paves the way for new developments in the field of asymmetric synthesis.

 

4)  Lipase-catalyzed asymmetric synthesis of naphtho[2,3-c]furan-1(3H)-one derivatives by a one-pot dynamic kinetic resolution/intramolecular Diels–Alder reaction: Total synthesis of (–)-himbacine

Koji Sugiyama, Shinji Kawanishi, Yasuhiro Oki, Marin Kamiya, Ryosuke Hanada, Masahiro Egi, Shuji Akai, Bioorg. Med. Chem., 26, 1378-1386 (2018), DOI:10.1016/j.bmc.2017.08.019

Abstract: One-pot sequential reactions using the acyl moieties installed by enzymatic dynamic kinetic resolution of alcohols have been little investigated. In this work, the acryloyl moiety installed via the lipase/oxovanadium combo-catalyzed dynamic kinetic resolution of a racemic dienol [4-(cyclohex-1-en-1-yl)but-3-en-2-ol or 1-(cyclohex-1-en-1-yl)but-2-en-1-ol] with a (Z)-3-(phenylsulfonyl)acrylate underwent an intramolecular Diels–Alder reaction in a one-pot procedure to produce an optically active naphtho[2,3-c]furan-1(3H)-one derivative (98% ee). This method was successfully applied to the asymmetric total synthesis of (–)-himbacine.

 

3)  オキソバナジウム/加水分解酵素混合触媒による第二級アルコールの動的光学分割:メソポーラスシリカの細孔の活用
Dynamic Kinetic Resolution of Secondary Alcohols by Oxovanadium/Hydrolase Combo-Catalysis: Effective Use of Mesoporous Silicas

赤井周司, ゼオライト, 35, 23-29 (2018); Shuji Akai, Zeolite, 35, 23-29 (2018)

Abstract: The dynamic kinetic resolution (DKR) has gained increasing attention because it is a simple method to obtain optically pure compounds from racemic substrates in quantitative yields. DKR is typically performed by a combination of kinetic resolution of racemates and in situ, continuous, and rapid interconversion between two enantiomers of the substrates, namely, racemization. We recently reported a new DKR method based on the combination of lipase-catalyzed kinetic resolution of racemic secondary alcohols and the V-MPS-catalyzed in situ racemization. In V-MPS, oxovanadium moieties were covalently bound to the inner surface of mesoporous silica (MPS) with a pore size of 2–4 nm. In this article, we introduce the background of why we used MPS, reaction characteristics of V-MPS, advantages of our DKR method, and its synthetic applications.

 

2)  3-(Triflyloxy)benzynes Enable the Regiocontrolled Cycloaddition of Cyclic Ureas to Synthesize 1,4-Benzodiazepine Derivatives

Hideki Kaneko, Takashi Ikawa, Yuta Yamamoto, Sundaram Arulmozhiraja, Hiroaki Tokiwa, Shuji Akai, Synlett, 29, 943-948 (2018), DOI:10.1055/s-0036-1591924

Abstract: A versatile synthesis of 1,4-benzodiazepine derivatives through the reaction of various 3-(trifluoromethanesulfonyloxy)benzynes with N-(p-toluenesulfonyl)imidazolidin-2-ones is reported. This reaction system provides a 1,4-benzodiazepine bearing a trifluoromethanesulfonyloxy group as a single regioisomer among the four possible regioisomers.

 

1)  Synthesis of Optically Active 2,3-Disubstituted Indoline Derivatives through Cycloaddition Reactions between Benzynes and α,β-Unsaturated γ-Aminobutyronitriles

Takashi Ikawa, Yuta Sumii, Shigeaki Masuda, Ding Wang, Yuto Emi, Akira Takagi, Shuji Akai, Synlett, 29, 530–536 (2018), DOI:10.1055/s-0036-1591722

Abstract: We report a method for synthesizing optically active 2,3-disubstituted indolines by the cycloaddition reaction of benzynes with various 4-[(4-toluenesulfonyl)amino]-(E)-but-2-enenitriles, which are readily prepared from the corresponding ʟ-amino acid derivatives.