Practical preparation of (3S)-hydroxy-5-phenylpentanoic acid: Asymmetric synthesis of (S)-daphneolone and (S)-dihydroyashabushiketol, and formal synthesis of (3 S,5 S)-yashabushidiol B

Abstract

Many linear diarylpentanoids and diarylheptanoids contain a β-hydroxy ketone or 1,3-diol functionality as the structural motif. Reported herein is the asymmetric synthesis of (S)-daphneolone, (S)-dihydroyashabushiketol, and formal synthesis of (3S,5S)-yashabushidiol B as represented examples, employing readily accessible (3S)-hydroxy-5-phenylpentanoic acid. The (3S)-hydroxy-5-phenylpentanoic acid was conveniently prepared by the aldol addition of (R)-acetyloxazolidinone with 3-phenylpropanal affording two diastereomers which were cleanly separated by silica gel column chromatography, followed by the removal of Evans auxiliary of (3'R,4S)-imide. Then, the (S)-acid was converted to Weinreb amide as a privileged acylating agent. Three natural products with the uppermost optical purity were prepared by the treatment of organolithium or organomagnesium reagents, respectively, to the Weinreb amide used in common. We believe that this strategy provides a rapid and convergent method for constructing these classes of molecules of interest.