An “Aprotic” Tamao Oxidation/Syn-Selective Tautomerization Reaction for the Efficient Synthesis of the C(1)–C(9) Fragment of Fludelone

An efficient synthesis of the C(1)–C(9) fragment of fludelone has been developed. The key step is a tandem silylformylation–crotylsilylation/Tamao oxidation sequence that establishes the C(5) ketone, the C(6), C(7), and C(8) stereocenters, and the C(9) alkene in a single operation from a readily accessed starting material. The stereochemical outcome at C(6) depends critically on the development of an “aprotic” Tamao oxidation, which leads to a reversal in the intrinsic diastereoselectivity observed using “standard” Tamao oxidation conditions.