Cobalt-Catalyzed Intramolecular Enantioselective Reductive Heck Reaction toward the Synthesis of Chiral 3-Trifluoromethylated Oxindoles

J Org Chem. 2024 Dec 6;89(23):17133-17140. doi: 10.1021/acs.joc.4c01488. Epub 2024 Nov 19.

Abstract

Herein, a cobalt-catalyzed intramolecular enantioselective reductive Heck reaction is disclosed. Starting from N-ortho-iodoaryl-2-(trifluoromethyl)acrylamides, a plethora of chiral oxindoles bearing trifluoromethylated quaternary stereogenic centers at the C3-position are achieved in moderate to good yields (up to 88% yield) and good to excellent enantioselectivities (up to 94% ee) by employing zinc/silane as reducing agent. Other than the trifluoromethyl group, a number of chiral oxindoles bearing alkyl, aryl, and ester groups at C3-position were also obtained albeit in relatively lower enantioselectivities (68-78% ee).