Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

Abstract

This review collects the recent developments in the synthesis of chiral 3-substituted 3-amino-2-oxindoles based on enantioselective catalytic nucleophilic additions to isatin imines published since the beginning of 2015.

Keywords: asymmetric synthesis; chiral 3-amino-2-oxindoles; chirality; isatin imines; nucleophilic addition.

Scheme 1

Mannich reaction of N-Boc-isatin imines with ethyl nitroacetate (2) catalyzed by a cinchona alkaloid followed by denitration and synthesis of AG-041R.

Scheme 2

Mannich reaction of N-Boc-isatin imines with 1,3-dicarbonyl compounds catalyzed by a cinchona alkaloid-derived squaramide.

Scheme 3

Mannich reaction of N-alkoxycarbonylisatin imines with acetylacetone catalyzed by a cinchona alkaloid-derived squaramide.

Scheme 4

Mannich reaction of isatin-derived benzhydrylketimines with trimethylsiloxyfuran catalyzed by a phosphoric acid.

Scheme 5

Mannich reaction of N-Boc-isatin imines with acetaldehyde catalyzed by a primary amine.

Scheme 6

Mannich reaction of N-Cbz-isatin imines with aldehydes catalyzed by L-diphenylprolinol trimethylsilyl ether.

Scheme 7

Addition of dimedone-derived enaminones to N-Boc-isatin imines catalyzed by a phosphoric acid.

Scheme 8

Addition of hydroxyfuran-2-one-derived enaminones to N-Boc-isatin imines catalyzed by a phosphoric acid.

Scheme 9

Zinc-catalyzed Mannich reaction of N-Boc-isatin imines with silyl ketene imines.

Scheme 10

Tin-catalyzed Mannich reaction of N-arylisatin imines with an alkenyl trichloroacetate.

Scheme 11

Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with acrolein catalyzed by β-isocupreidine.

Scheme 12

Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with acrolein (35) catalyzed by α-isocupreine.

Scheme 13

Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with maleimides catalyzed by β-isocupreidine.

Scheme 14

Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with nitroolefins catalyzed by a cinchona alkaloid-derived thiourea.

Scheme 15

Friedel–Crafts reactions of N-Boc-isatin imines with 1 and 2-naphthols catalyzed by a cinchona alkaloid-derived thiourea.

Scheme 16

Friedel–Crafts reactions of N-alkoxycarbonyl-isatin imines with 1 and 2-naphthols catalyzed by a cinchona alkaloid-derived squaramide.

Scheme 17

Friedel–Crafts reaction of N-Boc-isatin imines with 6-hydroxyquinolines catalyzed by a cinchona alkaloid-derived thiourea.

Scheme 18

Aza-Henry reaction of N-Boc-isatin imines with nitromethane catalyzed by a bifunctional guanidine.

Scheme 19

Domino addition/cyclization reaction of N-Boc-isatin imines with 1,4-dithiane-2,5-diol (53) catalyzed by a tertiary amine-squaramide.

Scheme 20

Nickel-catalyzed additions of methanol and cumene hydroperoxide to N-Boc-isatin imines.

Scheme 21

Palladium-catalyzed addition of arylboronic acids to N-tert-butylsulfonylisatin imines.