Hydroxymethylation of Oxindoles

Significance

A thiourea amine bifunctional catalyst promoting hydroxymethylation of oxindoles is presented by the authors. In this transformation, paraformaldehyde was employed as C1 source. With 5 mol% of catalyst 4, the addition of oxindoles 1 to formaldehyde proceeded smoothly at room temperature in 1,2-dichloroethane, furnishing the hydroxymethylation products 3 in high yields and high enantioselectivities. This reaction is proposed to proceed via a double activation mechanism as shown in the Scheme. The N-Boc protecting group is crucial to achieve high enantio-selectivity. Other protecting groups, such as Me or Bn, resulted in very low enantioselectivities.