Total synthesis of (±)-Δ9(12)-capnellene-8β,10α-diol

Abstract

A total synthesis of (±)-Δ⁹⁽¹²⁾-capnellene-8β,10α-diol (1), containing a cis,anti,cis-tricyclo[6.3.0.0^2,6] undecane carbon framework, found in the marine coral Capnella imbricata, is described. Michael addition of the homo-allylic cuprate (21) to 3-methylcyclopentenone, followed by Lewis acid catalysed ‘ene-type’ cyclisation of the resulting specific enol ester (22), first provided an expeditious route to the central bicyclo[3.3.0]octanone intermediate (24). Alkylation of the enolate derived from (24) with 2-chloro-4-iodobut-2-ene (28) then produced compound (29), which was converted into the keto-acetylene (32) using the acetylene ‘zipper’ methodology. When compound (32) was titrated with sodium naphthalene radical anion smooth reductive cyclisation occurred producing the tricyclic allylic alcohol (33). Oxidation of compound (33) with catalytic selenium dioxide then led to the 8-epi-capnellenediol (34). Finally, displacement of the methanesulphonate derived from (34), with potassium superoxide in 18-crown-6, produced (±)-Δ⁹⁽¹²⁾-capnellene-8β,10α-diol (1), which showed ¹H- and ¹³C-n.m.r. spectra in addition to m.s. data identical with naturally derived material.