Key tricyclic synthetic intermediates for the preparation of the sesquiterpenes alpha- and beta-cedrene.

A completely novel and direct route towards the synthesis of the natural sesquiterpenes alpha-cedrene and beta-cedrene delivered the compounds (3 beta,3a beta,7 beta)-(+/-)-6,6-ethylenedioxy-3,8,8-trimethyl-2,3,3a,4,5,6,7,8-octahydro-3a,7-methanoazulen-2-one, C(16)H(22)O(3), and (3 beta,3a beta,7 beta,8a alpha)-(+/-)-6,6-ethylenedioxy-3,8,8-trimethyl-1,2,3,3a,4,5,6,7,8,8a-decahydro-3a,7-methanoazulen-2-one, C(16)H(24)O(3), at key stages of the preparative programme. Structural elucidation showed the latter compound to have added an H atom to the same face of the cyclopentenone ring as that occupied by the methyl substituent, and also allowed correct isomer identification for further reaction.

Formal total synthesis of (+/-)-alpha- and beta-cedrene by preparation of cedrone. Construction of the tricyclic carbon skeleton by the use of a highly efficient intramolecular Khand annulation.

The cedrene carbon skeleton was rapidly assembled from a simple monocyclic precursor by the strategic use of a high yielding intramolecular Khand cyclization reaction. Further synthetic manipulations provided a concise formal total synthesis of alpha- and beta-cedrene. Reaction: see text.