Highly diastereoselective aldol reactions of 3-Fluorooxindoles promoted by MgBr2•OEt2/iPr2NEt

Diastereoselective deacylative aldol reaction of 3-acetyl-3-fluorooxindoles with aldehydes

“…19 3-Fluorooxindoles derivatives have been used, as monofluorinated oxindoleenolates as nucleophiles, in Michael-type additions, 20,21,22,23 in the Tsuji-Trost reactions, 24 and (via detrifluoroacetylative alkylations) in Mannich reaction with chiral N-tert-butanesulfinyl imines 25,26,27 and in Morita-Baylis-Hillman transformations. 28 Focusing our attention in the aldol reaction, involving these types of fluorinated enolates, 3-fluoro-3′-hydroxy-3,3′-bisoxindoles were obtained in high yields by reaction with isatins under mild basic conditions (up to 99 :1 dr, Scheme 1a); 29 αfluoro-β-hydroxyoxindoles were diastereoselectively generated by reaction with aromatic aldehydes using MgBr•OEt2 as Lewis acid (up to 99:1 anti/syn, Scheme 1b); 30 3-fluoro-3hydroxymethyloxindoles were enantioselectively isolated using a Cinchona alkaloid-catalyzed Scheme 1. Aldol reactions involving 3-fluorooxindoles.…”

Organocatalytic Asymmetric Conjugate Addition of Fluorooxindoles to Quinone Methides

“…During recent years, our laboratory has developed various (organo)­catalytic methods that produce multifunctional compounds with high enantio- and diastereoselectivities using fluorinated substrates including fluorooxindoles. − The medicinal value and prospects of Maxipost and other chiral 3-fluorooxindoles, − have received increasing attention from the synthetic community and intriguing procedures that achieve asymmetric C–C bond construction by incorporating the sought-after fluorooxindole motif into versatile scaffolds have been reported. − …”

Chiral Urea-Catalyzed Asymmetric Mannich Reaction of 3-Fluorooxindoles with α-Amidosulfones: Synthesis of Optically Active α-Fluoro-β-amino-oxindoles

“…1,2 How to synthesize optically active organic fluorides by asymmetric catalysis has become an important hot spot in recent years and has attracted attention 3 of chemists. Indolinones are the basic framework for the synthesis of a series of biologically active compounds and drugs, 1,[3][4][5][6][7][8] among which are 3-substituted 3-fluoroindolinones, such as oxindole (Figure 1a) has been an antipsychotic drug candidate, 9 and BM(S)-204352 (Figure 1b) is reported to be a powerful and effective maximum K channel opener. 10 In this context, the construction of chiral 3-substituted 3-fluoroindolinones containing a -amine fragment has aroused great interest among researchers.…”

“…10 In this context, the construction of chiral 3-substituted 3-fluoroindolinones containing a -amine fragment has aroused great interest among researchers. 7,8,11,12 In recent years, some progress has been made. In 2017, Song 13 and co-workers reported the asymmetric Mannich reaction of 3-fluorooxindoles with -amidosulfones via cooperative cation-binding catalysis, and -fluoro--amino-oxindoles were obtained in excellent enantioselectivities and moderate to excellent diastereoselectivities (Scheme 1).…”