31 Stereospecific Synthesis of Some Elemophilane type Sesquiterpenoids
Details
Starting from 2-methyl-cyclohex-2-enone, we succeeded in the stereocontrolled total syntheses of dl-elemophilenolide (III) and dl-furanoelemophilane (IV). The most difficult problem encountered in carrying out the total synthesis of the compounds was a stereoselective introduction of adjacent cis-dimethyl groups to cis-decaline derivative which is a mobile molecule between steroidal and nonsteroidal conformers. Settlement of the problem was achieved by a following pathway. Dields-Alder adduct 2 was methylated to give the carbinols 12 and 13 (1: 1). The carbinol 13 was easily separated from its epimer 12 by the formation of chloromercurial 14. The intramolecular oxymercuration of 13 was influenced by the solvent and reaction time (Table 1). Under an appropriate condition, the carbinol 13 gave an oxide 16 and/or 20 selectively. The oxide 16 was converted to a mixture of ketones 25 and 10 through 18 (scheme 4). The ketone 25 was epimerized to 10 by passing through a short alumina column. Similarly, 20 was converted to cis-dimethyl-cis-decalone derivative 11 via 22. Wolf-Kishner reduction of 10 and acid treatment of the product afforded a ketone 29 which was converted to an unsaturated ester 31 by Reformatsky reaction and followed by dehydration. Oxidation of the ester 31 with (t-BuO)_2CrO_2 yielded an unsaturated ketone 32 which submitted to hydrogenation and saponification to give a ketone 34. Reaction of 34 with sodium acetate in acetic anhydride gave eremophilenolide 35 which was reduced to give furanoeremophilane 36 with NaH_2 Al(OCH_2CH_2OCH_3)_2 in quantitative yield.
