Formal Total Synthesis of Salvinorin A

Abstract

The generation of the quaternary stereocenter at the C9 position of salvinorin A precursors by the Claisen rearrangement was investigated. The required allyl alcohol was prepared from a Wieland-Miescher ketone using a known γ-hydroxylation, reduction of the enone double bond, cyanohydrin formation, and elimination, yielding an unsaturated nitrile. A two-step reduction led to the required allyl alcohol. The subsequent Johnson-Claisen rearrangement provided a mixture of two diastereomeric 1,4-unsaturated esters in a ratio of around 2.6 : 1. The major isomer could be converted to a key intermediate of the Hagiwara synthesis of salvinorin A.