The enantioselective synthesis of the exo-spirotetronate subunits of quartromicins D3 (Figure 1) has been previously achieved by a sequence involving Lewis acid catalyzed Diels-Alder reaction. The original strategy, however, requires the installation of the hinder tertiary hydroxyl group in compound 5 (Scheme 1) after the Diels-Alder reaction. Chiral bicyclic dienophile 2 was synthesized in an effect to directly install the required hydroxyl group during the Diels-Alder reaction. The Diels-Alder reaction between dienophile 2 and acyclic (Z)-1,3-diene 1 provided cycloadduct 3 in 70% yield with 5:1 diastereoselectivity favoring the desired exo-isomer. The auxiliary unit of compound 3 was removed by lithium aluminum hydride reduction and provided diol 4 and a-hydroxyl aldehyde 5 in 65% combined yield. Both compounds 4 and 5 can be used to synthesize the exo-spirotetronate subunits of the quartromicins.
New Reactions and Methodology, Materials, Total Synthesis, Process R&D
8:00 PM-10:00 PM, Sunday, 28 August 2005 Washington DC Convention Center -- Hall A, Poster