STUDIES ON THE FUNCTIONALIZATION OF CIS-BICYCLO[3.3.0]OCT-7-EN-2-OL - APPROACHES TO THE SYNTHESIS OF SPECIONIN

During studies aimed at finding a synthetic route to specionin, methods have been developed for selective functionalisation of each ring of cis-bicyclo[3.3.0] oct-7-en-2-ol. Various exo-7,8-cis-dihydroxy cis-bicyclo[3.3.0] octan-2-ol derivatives 9a-c were prepared and a 'one-pot' conversion into 9-hydroxy 2,4-diethoxy-3-oxa-cis-bicycle [4.3.0] nonane derivatives 10a, b was developed. Acetonide, bis-tert-butyldimethylsilyl, and dibenzyl-protected 7,8-diol derivatives 13a-c were prepared and converted into the corresponding 7-exo,8-exo-dihydroxy-cis-bicyclo[3,3,0]-2-one derivatives 12a-c. Protected 7,8-dihydroxy-cis-bicyclo[3,3,0]oct-3-en-2-ones 17a-c were prepared in moderate yield from ketones 12a-c. A Wittig-ene reaction sequence was developed whereby ketones 12a-c were converted into enals 22a-c and 23a-c, which were then converted into alcohols 28a-c and 29a-c. Stereoisomers of exo,exo-6,7-bis(benzyloxy)-4-(hydroxymethyl)-cis-bicyclo[3.3.0] oct-2-ene, 28c and 29c were distinguished by H-1 NMR NO studies, while a model reaction sequence for completion of the left-hand ring of specionin was developed using a mixture of acetonides 28a and 29a, leading to epoxide 35 as a mixture of stereoisomers.