Studies in iridoid synthesis. Chemoselective transformations of cis-1,2,4,6-tetrahydrophthalic anhydride?

Organic & Biomolecular Chemistry Pub Date: 2007-12-20 DOI: 10.1039/B716256A

Abstract

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 lactonecis-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 OsO4 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 α,β-unsaturated system, followed by β-elimination of the MEM moiety.

Graphical abstract: Studies in iridoid synthesis. Chemoselective transformations of cis-1,2,4,6-tetrahydrophthalic anhydride
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