Catalytic Enantioselective α,ß,γ-Trioxygenation.

Applying a catalytic enantioselective aldehyde α-oxygenation condition to an enal substrate led to the discovery of the first α,ß,γ-trifunctionalization cascade of enals. Under optimal conditions, a tryptophan-derived imidazolidinone catalyst in fluorinated aromatic solvents provided α,ß,γ-trioxyaldehydes in up to 51% isolated yield (average of 80% yield per oxygenation step) and 85:15 er. Substitution at the δ position was tolerated, but not at the α, ß, or γ positions. The reaction proceeded through initial TEMPO incorporation at the γ position, and rapid racemization of this intermediate, reversible conjugate addition of water, followed by TEMPO incorporation at the α position to set all three stereocenters with double dynamic kinetic resolution.

anti-Diols from α-oxyaldehydes: synthesis and stereochemical assignment of oxylipins from Dracontium loretense.

Differentially protected 1,2-diols were synthesized by enantioselective aldehyde α-oxygenation followed by organomagnesium or -lithium addition. Contrary to a previous report, the resultant diols possess an anti configuration. Good selectivity was achieved regardless of the hybridization state of the nucleophile or the presence or absence of branching. This method was applied to short syntheses of all possible stereoisomers of two oxylipins from Dracontium loretense with incomplete stereochemical assignments. Spectroscopic comparisons between the synthetic and natural oxylipins led to unambiguous assignments.