Brønsted acid-promoted hydrocyanation of arylalkenes.
Nonactivated arylalkenes are effectively converted to tertiary benzylic nitriles in the presence of triflic acid and trimethylsilyl cyanide. The hydrocyanation reactions result in good to excellent yield when electron-donating groups are substituted on the benzene ring. The reaction conditions are mild and relatively safe, notably without need for handling hazardous hydrogen cyanide gas, providing simple and easy access to tertiary benzylic nitriles. The reaction was applied to the preparation of a PDE4 inhibitor (3) as well as a series of analogues.
Yanagisawa
Arata
A
Chemical Process Research and Development Laboratories, Kyowa Hakko Kirin Co., Ltd., 1-1-53, Takasu-cho, Sakai-ku, Sakai, Osaka 590-8554, Japan. arata.yanagisawa@kyowa-kirin.co.jp
Nezu
Tetsuya
T
Mohri
Shin-ichiro
S