Evaluation of Furan Photooxygenation as a Device for Construction of the Zaragozic Acid (Squalestatin) Core.

A practical application of the photooxygenation chemistry of 3-substituted furans to construction of the zaragozic acid/squalestatin backbone is described. Although addition of 3-lithiofuran to the tartrate-derived aldehyde 7 proceeds without chelation control to give a 1:1 mixture of diastereomeric alcohols 8, it is demonstrated initially that ready conversion to the polyfunctional intermediate 10 is possible by sequential treatment of 9 with singlet oxygen, sodium borohydride, and triisopropylsilyl triflate. The actual enantiocontrolled route consisted of oxidation of 8 to the ketone and Wittig olefination of the latter in advance of asymmetric dihydroxylation with AD-mix-β. Once this series of transformations had been accomplished, formation of the target product 30 was realized by an entirely comparable photooxygenation.