First Total Synthesis of (−)-Achilleol B: Reassignment of Its Relative Stereochemistry

Abstract

The first total synthesis of (−)-achilleol B was achieved using a convergent approach with a longest linear sequence of 14 steps. Three key steps were employed, including an enantioselective Robinson annelation for the construction of the bicyclic moiety. The monocyclic synthon was prepared through a Ti(III)-mediated cylization of a chiral monoepoxide obtained via asymmetric dihydroxylation of geranylacetone. The asymmetric preparation of these subunits also permitted us to achieve the enantioselective synthesis of elegansidiol, achilleol A, and farnesiferol B.

Easy Access to a Cyclic Key Intermediate for the Synthesis of Trisporic Acids and Related Compounds

“…Cp 2 TiCl 2 can be regenerated by means of the 2,4,6-collidine/TMSCl system either from the Cp 2 Ti(IV)Cl(OAc) generated in the -OAc elimination step or from the titanium alkoxide of VIII. It should be pointed out that the Ti(III)-mediated radical cyclization reactions employing substrates without secondary acetate groups at C-4 lead regioselectively to exocyclic double bonds (Scheme 5) [45,[47][48][49][50]. In contrast, in this study it has been proven that it is possible to change selectively the direction of the formation of the olefin by using a suitable leaving group having in mind the affinity for the oxygen of the Ti atom.…”

“…Finally, the acyclic epoxide 8, which also corresponds to the intermediate III of Scheme 1, was cyclized following the Ti(III)-mediated methodology [39,[45][46][47][48][49][50]. In this case catalytic conditions [51] were employed, involving 0.3 equivalents of Ti(III) and 8.0 equivalents of Mn in THF (0.1 M), with 2,4,6-collidine/TMSCl as regenerating system.…”

Bioinspired terpene synthesis: a radical approach

“…Cyclohexanol 16 has been used in the total synthesis of cyclofarnesane sesquiterpenoid 18 isolated from Artemisia chamaemelifolia, 60 and for the total synthesis of triterpenes achilleol A 63 (19) and B (20) (Scheme 23). 64 3b-Hydroxymanool ( 23), a bicyclic diterpenoid with a labdane skeleton isolated from the fern Gleichenia japonica and other norditerpenes isolated from copaiba oil (21)(22), could be also synthesised using bicycle compound 17 (Scheme 24). 60 Sclareol oxide, a labdane constituent of the essential oils of Salvia sclarea, is also accessible from bicyclic 17.…”

Natural sesquiterpenoids

“…42 The first total syntheses of (AE)-annuionone B and (AE)-tanarifuranonol have been reported, 43 whilst an enantioselective synthesis of farnesiferol B has been achieved. 44 The synthesis, olfactory evaluation and determination of the absolute configuration of the band g-Iralia Ò isomers, two components of an artificial violet odorant, have been carried out. 45 Synthetic applications of an enantioselective protonation in the preparation of (S)-a-damascone have been described.…”