Functionalization of trans-Decalin. II. A Synthesis of dl-Isopetasol from trans-5-Oxodecalin-8a,2-carbolactone

Abstract

Abstract A stereocontrollcd synthesis of dl-isopetasol (1a) from trans-5-oxodecalin-8a,2-carbolactone (2a) is described. The key intermediate, trans-5,5-ethylenedioxy-1β,8aβ-dimethyldecalin-2-one (7b) was prepared by reductive methylation of trans-5,5-ethylenedioxydecahydrocyclopropa[d]naphthalen-2-one (5) for introducing the vicinal two methyl groups at C-1 and C-8a carbon atoms. The cyclopropyl ketone 5 was obtained by reduction of the acetal of 2a followed by (1) tosylation of the primary alcohol, (2) oxidation of the secondary alcohol with Corey’s NCS–DMS reagent, and (3) cyclization with t-BuOK. Reduction of 5 with lithium in liquid ammonia provides initially the corresponding enolate anion, which can be trapped with methyl iodide to give trans-5,5-ethylenedioxy-1α,8aβ-dimethyldecalin-2-one (7a), smoothly. Epimerization of 7a with MeONa in MeOH gave the desired intermediate 7b. Reduction of 7b with lithium in liquid ammonia gives the 2α-alcohol 8b, stereoselectively. The conversion of 8b into 1a was carried out as follows: (1) deacetalization of 8b followed with acetylation, giving trans-6α-acetoxy-4aβ,5β-dimethyldecalin-1-one (9b); (2) reduction of 9b with NaBH4 and subsequent dehydration affording the olefinic acetate 11; (3) oxidation of 11 with CrO3–pyridine complex, giving the enone 12; (4) aldol condensation of 12 with acetone followed by dehydration, isomerization of double bond, and hydrolysis, providing the desired 1a.