Asymmetric synthesis of 4-deoxyverrucarol via two types of ring expansion reactions

Asymmetric synthesis of a trichothecane analogue, 4-deoxyverrucarol (2), wa s carried out through two types of ring expansion reactions. First, synthes is of the racemate of 2 was investigated. Thus, 1-[1-(tert-butyldimethylsil oxy)-ethyl]-1-methoxycarbonyl-2-hexen-4-one (10), prepared by Diels-Alder r eaction, was converted into the cyclopropylidene 15. The cyclobutanone (+/- )-18 was obtained from 15 via dihydroxylation, followed by successive treat ments with SO2CI2 in the presence of imidazole and Florisil. After transfor mation of (+/-)-18 into the vinylcyclobutanol (+/-)-19, the second ring exp ansion reaction was performed with Pd(OAc)(2) to provide the cyclopentanone (+/-)-20. The product was converted into the racemate of 4-deoxyverrucarol (2) through the cyclohexenone (+/-)22, but the diastereoselectivity during the introduction of the double bond was unsatisfactory. The selectivity wa s improved in the case of the asymmetric synthesis. The optically active cy clobutanone (+/-)-18 was prepared via AD reaction of 15 with 73% ee. After the transformation of (+/-)-18 into the cyclohexanone (-)-30 through the pa lladium-mediated ring expansion reaction, (-)-30 was subjected to the diast ereoselective deprotonation reaction using the chiral amide. The key synthe tic intermediate (-)-25 of 4-deoxyverrucarol (2) was synthesized in an opti cally pure form by taking advantage of a kind of kinetic resolution that oc curred during the deprotonation step.