Radical α-Oxygenation of Aldehydes

Significance

An asymmetric radical-mediated α-oxygenation of aldehydes has been developed. Using the chiral imidazolidinone salt 3×HBF₄ as catalyst, aldehydes 1 and TEMPO gave α-amino­xylated alcohols 2 in moderate to good yields and enantioselectivities after in situ reduction with NaBH₄. Mechanistically, the reaction is likely to proceed via the radical cation intermediate 4, which can be trapped stereoselectively by TEMPO. The radical cation results from single-electron transfer (SET) oxidation of the initially formed enamine. A catalytic amount of FeCl₃ serves as the SET reagent together with NaNO₂ (30 mol%) and O₂ as terminal cooxidant. The authors propose a stereochemical model consistent with the observed absolute product stereochemistry. The N-O bond of the product can be cleaved with Zn/AcOH to produce the corresponding diols.