Approaches to the Total Synthesis of Wilfordine

• Main Author: Whitehouse, Darren L
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-1993
• Subjects: Organic chemistry
• ISBN: 9781392087084; 1392087082

(2RS,3SR,4RS,4aRS,8aRS)-3-Diphenylmethylsily1-4a-hydroxymethy1-7-methyl-1-oxo-3,4,4a,5,8,8a-hexahydro-2H-naphthalen-4-diol was prepared from (4SR,4aRS,8aSR)-4a-Hydroxymethyl-1',4-O-isopropylidene-7-methyl-1-oxo-4a,5,8,8a-tetrahydro-4H-naphth-4-ol in four steps as a single diastereoisomer. Minor substrate modifications of the C-4 OH centre of (1SR,4SR,4aRS,8aSR)-1,7-Dimethy1-4a-hydroxymethy1-1',4-O-isopropylidene-1,4,4a,5,8,8a-hexahydronaphthalen-1,4-diol allowed the stereoselective epoxidation of the Δ6,7 double bond to give either epoxide stereoisomer. (1RS,4SR,4aSR,5RS,8aSR)-5,7-Dimethoxy-4a-methoxycarbony1-1,4,4a,5,8,8a-hexahydronaphthalen-1,4-diol was prepared as a single diastereoisomer by Luche reduction of the Diels-Alder adduct of p-benzoquinone and 1,3-dimethoxybuta-1,3-diene. Treatment of this diol with protic acid afforded (3aRS,4SR,7SR,7aRS)-1,3,3a,4,7,7a-Hexahydro-2-methoxy-6-methoxycarbony1-9-oxo-4,7-ethanobenzofuran whose structure was elucidated by X-ray crystallography. Regioselective internal acetalisation of diol ORS ,4SR,4aSR ,5RS,8aSR)-5,7-Dimethoxy-4a-methoxycarbonyl-1,4,4a,5, 8, 8a-hexahydronaphthalen-1,4-diol afforded (1SR,2RS,5RS,6SR,9RS)-5-Hydroxy-9-methoxy-6-methoxyearbonyl-11-oxatricyclo-[4.4.1.0.2.9]undeca-3,7-diene which was used to invert the undesired C-1-OH centre. (1SR,2SR,5SR,6RS,9RS)-1',5-O-Bis(tert-butyldimethylsily1)-6-hydroxymethy1- 9-methoxy-2-methy1-11-oxatricyclo[4.4.1.0.2.9]undeca-3,7-dien-5-ol was prepared from this internal acetal in ten steps as a single diastereoisomer, thus confirming the diastereoselectivity of the methyl addition. The internal acetal was used to prepare (1SR,4RS,8aSR)-8a-Hydroxymethy1-6-oxo-1,1',4-O-tris(tert-butyldimethylsily1)-4,8a-dihydro-1H-naphthalen-1,4-diol, in six steps via dehydrogenation of (1SR,4SR,4aSR,8aRS)-8a-hydroxymethy1-6-oxo-1,11,4-O- tris(tert-butyldimethylsily1)-4,4a,5,8a-tetrahydro-1H-naphthalen-1,4-diol with benzene seleninic anhydride, which was seen as a very promising intermediate for the on-going synthesis of complex polyoxygenated natural products such as wilfordine.