Non-enzymatic catalytic asymmetric cyanation of acylsilanes

Tagui Nagano; Akira Matsumoto; Ryotaro Yoshizaki; Keisuke Asano; Seijiro Matsubara

doi:10.1038/s42004-022-00662-y

Non-enzymatic catalytic asymmetric cyanation of acylsilanes

Commun Chem. 2022 Mar 31;5(1):45. doi: 10.1038/s42004-022-00662-y.

Authors

Tagui Nagano¹, Akira Matsumoto^{1

2}, Ryotaro Yoshizaki¹, Keisuke Asano³, Seijiro Matsubara⁴

Affiliations

¹ Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto, 615-8510, Japan.
² Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida-Shimoadachi, Sakyo, Kyoto, 606-8501, Japan.
³ Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto, 615-8510, Japan. asano.keisuke.5w@kyoto-u.ac.jp.
⁴ Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto, 615-8510, Japan. matsubara.seijiro.2e@kyoto-u.ac.jp.

Abstract

The asymmetric cyanation of acylsilanes affords densely functionalized tetrasubstituted chiral carbon centers bearing silyl, cyano, and hydroxy groups, which are of particular interest in synthetic and medicinal chemistry. However, this method has been limited to a few enzymatic approaches, which employ only one substrate because of substrate specificity. Here we show the non-enzymatic catalytic asymmetric cyanation of acylsilanes using a chiral Lewis base as an enantioselective catalyst, trimethylsilyl cyanide as a cyanating reagent, and isopropyl alcohol as an additive to drive catalyst turnover. High enantio- and site-selectivities are achieved in a catalytic manner, and a variety of functional groups are installed in optically active acylsilane cyanohydrins, thus overcoming the limitations imposed by substrate specificity in conventional enzymatic methods. A handle for the synthetic application of the products is also established through the development of a catalyst for protecting acylsilane cyanohydrins, which are unstable and difficult to protect alcohols.