Bifunctional Cinchona Alkaloid/Thiourea Catalyzes Direct and Enantioselective Vinylogous Michael Addition of 3‐Alkylidene Oxindoles to Nitroolefins

Abstract

3-Alkylidene oxindoles (methyleneindolinones), be they natural or man-made substances, occupy a preeminent position among the various classes of chemically and medicinally relevant small-molecule scaffolds. Their plural functional architecture featuring a lactam carbonyl flanked by a highly substituted exocyclic double bond renders them enabling intermediates to be elaborated into a myriad of useful nitrogen heterocycles of varied complexity. For example, 3-alkylidene oxindoles can be viewed as electrophilic Michael acceptors, which react with carbon-centered anions to give bsubstituted oxindoles of type A (Scheme 1a). In addition, they can act as electron-poor components in synchronous (Scheme 1b) or stepwise (Scheme 1c) cycloadditive functionalizations, thus opening the way to a wide range of highly valuable 3,3-spirocyclic structures of type B or C. Whereas these protocols have been largely pursued and formed the basis of many synthetic achievements, an “umpolung” option could also be envisaged (Scheme 1d), and capitalizes on the vinylogous pro-nucleophilic character of the alkyl group attached at the b-position of the ylidene. By reacting with the proper acceptors, these nucleophiles furnish olefinic oxindoles of type D, which are functionalized at the most distant point of the molecule (Cγ).