Exaltone ~? (=Cyclopentadecanone) from Isomuscone ~? (=Cyclohexadecanone), a one-C-atom ring-contraction methodology via a stereospecific favorskii rearrangement: Regioselective application to (-)-(R)-muscone

摘要

Treatment of cyclohexadecanone (1g; with I _2 (2.2 mol-euqiv.) and KOH in MeOH) furnished the unsaturated (Z)-ester 2g in 83% yield, via a stereospecific Favorskii rearrangement (Scheme 1). Further treatment with 3-chloroperbenzoic acid (m-CPBA) afforded the unreported epoxy ester 3g (88% yield), which was cleaved in 33% yield to Exaltone ~? (=cyclopentadecanone; 1f) with NaOH in MeOH/H _2O and then HCl at 65°. This methodology was similarly extended to higher (C _(17)) and lower (C _(15) to C _(11)) cyclic ketone analogues, as well as regioselectively to (-)-(R)-muscone (5c) and homomuscone (5f) (Scheme 2). Olfactive properties of the corresponding macrocyclic 1-oxaspiro[2,n]alkanes and -alkenes 4 and 8, resulting from a Coreyi-Chaykovsky oxiranylation, are also presented.