THE SYNTHESIS OF (-)-ROBUSTADIAL-A AND SOME ANALOGS

The naturally occurring chroman derivative, robustadial A, and several analogues have been prepared by a four-step synthesis starting from p hloroglucinol. The synthetic scheme involves as the first step a Fried el-Crafts condensation of an alpha,beta-unsaturated acid derivative wi th phloroglucinol to the corresponding chromanone. The isobutyl group at the 4-position was introduced with methallylzine bromide followed b y hydrogenation, carried out as a one-pot reaction. Finally, both alde hyde functions were attached using dichloromethyl methyl ether and tit anium tetrachloride. Optically pure 6,6-dimethylbicyclo[3.1.1]heptan-2 -ylidene-acetic acid, needed for the synthesis of robustadial, was pre pared from (-)-nopol by two consecutive oxidations in 77% overall yiel d.