The chemistry of thujone. XVII. The synthesis of ambergris fragrances and related analogues

Abstract

A strategy to utilize the thujone-derived enone 1 for the development of a synthetic route to ambergris fragrances is presented. Thujone (8) is transformed to the tricyclic enone 9, via the Robinson annulation reaction, and the latter is then elaborated to the cis-fused tricyclic intermediates 10, 11, and 12. Extrusion of the isopropyl side chain in 12 is achieved through an initial ozonation reaction and the resulting ketone 14 is then treated with m-CPBA to afford 16. Cyclopropyl ring opening in 16 is performed via initial saponification to the alcohol 17 and the latter is then reacted with FeCl3 and sodium acetate to enone 1. The necessary elaboration of a tetrahydrofuran ring attached to ring B of 1 is achieved through reaction of 1 with vinylmagnesium bromide, alkylation, hydroboration, and final acid-catalyzed ring closure of the 1,5-diol 4. The route affords the opportunity of synthesizing a variety of analogues within the Ambrox series.