Total Synthesis of (±)-Liphagal via Organic-Redox-Driven Palladium-Catalyzed Hydroxybenzofuran Formation
Eriko Tao1, Masaki Inoue1, Taejoo Jeong1,2
1Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
Abstract:
A synthetic route to liphagal, a natural PI3Kα inhibitor isolated from Aka coralliphaga, was established. The present route features an organic redox process where an alkynylquinone undergoes reductive cyclization in the presence of a hydroquinone derivative such as hydroxyquinol (1,2,4-benzenetriol) and catalytic PdCl2 to provide a substituted benzofuran suitable for accessing the natural product. The benzofuran formation takes place via the redox transformation between the alkynylquinone and the electron-rich hydroquinones followed by the concomitant Pd(II)-catalyzed oxycyclization of the resultant alkynylhydroquinone.
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