A highly diastereoselective Friedel–Crafts reaction of indoles with isatin-derived N-sulfinyl ketimines towards the efficient synthesis of chiral tetrasubstituted 3-indolyl-3-aminooxindoles

Abstract

A Lewis acid promoted highly diastereoselective asymmetric Friedel-Crafts alkylation of indoles with isatin-derived N-tert-butanesulfinyl ketimines is described. The reaction can be accomplished with ease in the presence of a catalytic amount of Bi(OTf)3, providing a series of 3-indolyl-3-aminooxindoles in excellent diastereoselectivities (up to 98% de) and yields (up to 99%).

1,2-Additions on Chiral N-Sulfinylketimines: An Easy Access to Chiral α-Tertiary Amines

“…In 2015, Xu and co-workers investigated Friedel-Craftstype reactions of indoles with isatin-derived ketimines (Scheme 69). 96 Also in 2015, O'Shea and Das investigated the addition of a broad range of trimethylsilane pro-nucleophiles to a wide range of aldimines and one example of a ketimine (Scheme 70). 97…”

Urea derivative organocatalyzed enantioselective Friedel–Crafts alkylation of α‐naphthols with isatins

“…[26][27][28][29][30][31][32][33] Despite the great achievements in such reactions, the main focus has been on the use of reactive heteroarenes-indoles, pyrroles, and furan as nucleophiles. [34][35][36][37][38][39][40][41][42][43] The application of hydroxylarenes is rare because of their reduced nucleophilicity. [44][45][46][47][48][49][50][51][52][53][54][55] In 2014, Wu et al 56 disclosed the first enantioselective F-C reaction of α-naphthols with isatins employing cinchona derivatives to provide 3-aryl-3-hydroxy-2-oxindoles with 26%-94%ees.…”

“…The asymmetric Friedel–Crafts (F‐C) reaction of isatin is one of the most effective approaches for the synthesis of chiral tetrasubstituted 3‐hydroxyoxindoles 26–33 . Despite the great achievements in such reactions, the main focus has been on the use of reactive heteroarenes–indoles, pyrroles, and furan as nucleophiles 34–43 . The application of hydroxylarenes is rare because of their reduced nucleophilicity 44–55 .…”

Chiral Bis(oxazoline)–Copper Complex Catalyzed Asymmetric Alkenylation of Isatin Imines and 3-Vinylindoles for Construction of Optically Active 3-Alkenyl-3-aminooxindoles

“…So, the development of efficient strategies for the construction of optically active 3-substituted 3-aminooxindole compounds has become a hot research topic in recent years. Among the many excellent catalytic asymmetric methods that have been developed, the catalytic asymmetric nucleophilic addition of a nucleophile to an isatin imine is one of the most straightforward strategies for obtaining 3-substituted 3-aminooxindole derivatives. , For example, syntheses from isatin imines via Mannich, Friedel–Crafts, Morita–Baylis–Hillman, Henry, and Strecker reactions have been well documented. Although much has already been achieved, the development of new reactions of isatin imines is still important to enrich the library of 3-substituted 3-aminooxindole compounds and facilitate pharmaceutical research.…”