Studies in iridoid synthesis. Chemoselective transformations of cis-1,2,4,6-tetrahydrophthalic anhydride.
In the course of synthetic studies towards the development of diastereoselective routes to secoiridoid aglycones, cis-1,2,4,6-tetrahydrophthalic anhydride was transformed into the corresponding lactone cis-3a,4,7,7a-tetrahydro-3H-isobenzofuran-1-one, which served as a key precursor for a variety of chemoselective synthetic manipulations. Unsuccessful formylation of an ester intermediate resulted in a (E/Z) mixture of vinyl alcohols which were protected as acetates and as a single p-methoxybenzyl (PMB) ether (E) isomer. Dihydroxylation of the cyclohexene motif using OsO(4) led to the unexpected deprotection of the PMB ether. On the other hand, successful formylation of a suitably silyl protected lactonised intermediate was achieved using tert-butoxybis(dimethylamino)methane, or Bredereck's reagent. Tetrabutylammonium fluoride (TBAF) deprotection of a methoxyethoxymethyl (MEM)-ether intermediate serendipitously afforded an approximately 1 : 1 mixture of pyrano-pyranones, which are products of a seldom encountered intramolecular Michael addition, using an oxygen donor, to the terminus of an alpha,beta-unsaturated system, followed by beta-elimination of the MEM moiety.
Stevens
Anne T
AT
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
Bull
James R
JR
Chibale
Kelly
K
D006358:Hot Temperature; D039823:Iridoids / Q000138:chemical synthesis* / Q000737:chemistry*; D010084:Oxidation-Reduction; D010796:Phthalic Anhydrides / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D039823:Iridoids; D010796:Phthalic Anhydrides; C527960:cis-1,2,4,6-tetrahydrophthalic anhydride