Asymmetric Mannich Reaction of Isatin-Derived Ketimines with α-Fluoroindanones Catalyzed by a Chiral Phase-Transfer Catalyst

J Org Chem. 2024 Apr 5;89(7):4474-4483. doi: 10.1021/acs.joc.3c02668. Epub 2024 Mar 20.

Abstract

A highly enantioselective Mannich reaction of α-fluoroindanones with isatin-derived N-Boc-ketimines catalyzed by a quinine-derived phase-transfer catalyst was developed. A variety of 3-substituted 3-amino-2-oxindoles bearing fluorine-containing, vicinal, tetrasubstituted stereocenters were constructed using this protocol in high yields (83-95%), with moderate to excellent enantioselectivities (66-91%) and high diastereoselectivities (up to >99:1).