Studies on the functionalisation of cis-bicyclo[3.3.0]oct-7-en-2-ol—approaches to the synthesis of specionin

Abstract

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-cisdihydroxy 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-bicyclo[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]octan-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 ¹H NMR NOE 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.