Synthesis of an Artificial HMG-CoA Reductase Inhibitor NK-104 via a Hydrosilylation–Cross-Coupling Reaction

The hydrosilylation of t-butyl (3R,5S)-3,5-isopropylidenedioxy-6-heptynoate with ClMe2SiH and a platinum catalyst, t-Bu3P·Pt(CH2=CHSiMe2)2O, gave an (E)-vinylsilane in high yield with high regioselectivity. A subsequent cross-coupling reaction with an aryl halide afforded t-butyl (3R,5S,6E)-7-aryl-3,5-isopropylidenedioxy-6-heptenoate. This sequence was applied to the synthesis of a potent HMG-CoA reductase inhibitor, NK-104.