Asymmetric Synthesis of 3-Alkyl-3-aryl-oxindoles

Significance

Reported here is the asymmetric synthesis of 3-alkyl-3-aryloxindoles via a hetero-Claisen rearrangement. After developing a racemic synthesis of the process (eq. 1), the authors ­investigated the asymmetric version by treating Garner’s aldehyde 1 with phenylhydroxylamine to obtain (R,Z)-N-phenylnitrone 2 in 87% yield (eq. 2) as a single stereoisomer (confirmed by X-ray analysis). Treatment of nitrone 2 with methylphenyl­ketene at room temperature afforded the corresponding oxindole in 85% yield and 87% ee. The reaction was extended to a series of alkyl aryl ketenes; Garner’s aldehyde 1 was recovered in 78-87% yield. The proposed mechanism is under study in order to understand the enantioselectivity of this transformation.