An enantioselective Mannich reaction between N ‐Boc‐protected pyrazolinone ketimines and 1,3,5‐trisubstituted barbituric acids is developed using a cinchonidine‐derived bifunctional thiourea bearing an oxindole moiety as an organocatalyst. This method provides access to previously unexplored heterocyclic adducts containing both aminopyrazolone and barbiturate motifs and featuring a quaternary stereogenic center. The corresponding products are obtained in good to excellent yields and high enantioselectivities (up to 98:2 er) under mild conditions. An immobilized analogue of the catalyst exhibits comparable performance and is readily recycled. Moreover, its implementation under continuous‐flow conditions enables an operationally simple and productive synthesis of enantioenriched products, highlighting the synthetic utility and sustainability of this protocol.
Sánchez-Molpeceres et al. (Mon,) studied this question.