91987-94-9Relevant articles and documents
Asymmetric synthesis of 4-deoxyverrucarol via two types of ring expansion reactions
Miyata, Junji,Nemoto, Hideo,Ihara, Masataka
, p. 504 - 512 (2007/10/03)
Asymmetric synthesis of a trichothecane analogue, 4-deoxyverrucarol (2), was carried out through two types of ring expansion reactions. First, synthesis of the racemate of 2 was investigated. Thus, 1-[1-(tert- butyldimethylsiloxy)-ethyl]-1-methoxycarbonyl-2-hexen-4-one (10), prepared by Diels-Alder reaction, was converted into the cyclopropylidene 15. The cyclobutanone (±)-18 was obtained from 15 via dihydroxylation, followed by successive treatments with SO2Cl2 in the presence of imidazole and Florisil. After transformation of (±)-18 into the vinylcyclobutanol (±)-19, the second ring expansion 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 was improved in the case of the asymmetric synthesis. The optically active cyclobutanone (+)-18 was prepared via AD reaction of 15 with 73% ee. After the transformation of (+)-18 into the cyclohexanone (-)-30 through the palladium-mediated ring expansion reaction, (-)-30 was subjected to the diastereoselective deprotonation reaction using the chiral amide. The key synthetic intermediate (-)-25 of 4-deoxyverrucarol (2) was synthesized in an optically pure form by taking advantage of a kind of kinetic resolution that occurred during the deprotonation step.
