Organocatalytic Enantioselective Hydroxymethylation of Oxindoles with Paraformaldehyde as C1 Unit

A bifunctional thiourea-tertiary amine-catalyzed asymmetric hydroxymethylation of 3-substituted oxindoles using paraformaldehyde as the C1 unit was developed. A wide scope of oxindoles, bearing C3 sterically congested quaternary carbon centers, were smoothly obtained in good to excellent yields (up to 99%) and high enantioselectivities (up to 91% ee) under mild reaction conditions. A more significant feature of this approach employs cheap and readily available paraformaldehyde as a hydroxymethylation C1 unit, which is activated by chiral bifunctional thiourea organocatalysts.