HOTf-catalyzed dehydrative coupling reaction of 3-hydroxyisoindolinones with alkyl ketones†

Abstract

A HOTf-catalyzed Mannich-type dehydrative coupling reaction between 3-aryl-3-hydroxyisoindolinones and unactivated alkyl ketones has been uncovered for the synthesis of C3-alkyl 3,3-disubstituted isoindolinones. Aryl alkyl, alkenyl alkyl, alkynyl alkyl, and alkyl alkyl ketones are suitable to react with a variety of 3-aryl-3-hydroxyisoindolinones to afford the desired products in good-to-high yields. This protocol features the use of an inexpensive catalyst (HOTf), low catalyst loading (only 5 mol%), mild reaction conditions (80 °C), a broad substrate scope (38 examples), and easy elaboration of the products.