Construction of Vicinal Tetrasubstituted Stereogenic Centers via a Mannich‐Type Organocatalyzed Addition of Δ2‐Pyrrolin‐4‐ones to Isatin Imines


Advanced Synthesis & Catalysis

Sebastijan Ričko, Anže Meden, Luka CIber, Bogdan Štefane, Franc Požgan, Jurij Svete, Uroš Grošelj

Racemic Δ2‐pyrrolin‐4‐ones (i. e. 4‐pyrrolones), easily available in two steps from N‐protected α‐amino acids, undergo organocatalysed asymmetric Mannich‐type addition to isatin‐derived ketimines to furnish the non‐racemic oxindole‐Δ2‐pyrrolin‐4‐one adducts, stereoselectively (up to 96% eedr≥15:1). The oxindole–pyrrolone products feature vicinal tetrasubstituted carbon stereocenters. The developed protocol has a broad substrate scope and tolerates diverse substituents at position C‐5 in 4‐pyrrolones and at positions N‐1 and C‐5/7 in isatin imines.

Read article: Adv. Synth. Catal., 2018, 360, 1072-1076