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

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% ee, dr≥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