Remote Activation of the Nucleophilicity of Isatin

Abstract

The concept of the remote activation of reactivity was first applied in asymmetric organocatalysis. An isatin 3-phenylimine derivative acts as a donor in the thiourea catalyzed asymmetric addition to unsaturated 1,4-ketoesters, affording aza-Michael adducts in high enantiomeric purity and yield.

Comparative analysis of PknB inhibitors for reactivity and toxicity

“…While other PknB inhibitors reported adhere well to PAINS and Lipinski chemical properties, YH-8 revealed a characteristic highly reactive Michael acceptor, with recent organic synthesis methodology reports indicating its use as such [20][21][22][23]. Additional SAR studies by Xu et al indicate that the double bond Michael acceptor linking the ketone and ester moieties was essential for its PknB inhibition.…”

Asymmetric Organocatalytic Aza-Michael Reactions of Isatin Derivatives

“…The compounds 2 were prepared by condensation on isatin and aniline in boiling MeOH with AcOH as a catalyst. 17…”

“…14 In our ongoing research on the asymmet-ric reactions of 1,4-dicarbonyl compounds 15 and oxindole derivatives, 16 we have previously applied the concept of remote activation of the nucleophilicty of isatin for the enantioselective aza-Michael addition. 17 (Scheme 1). It was found that derivatization of isatin (1) to Schiff base 2 was the crucial step for obtaining aza-Michael products 4 in high yields with high enantioselectivity (Scheme 1, path A vs path B), as well as reducing the reaction time and blocking possible by-product formation.…”

Regioselective aza‐Michael additions of 2‐arylidene‐1,3‐diphenylpropan‐1,3‐diones with isatins: Synthesis of N‐diketone‐functionalized isatins

“…[ 6 ] The reported methods mainly utilized active isatin imines as substitutes. [ 7 ] Therefore there is a need to explore effective methods for the aza‐Michael addition of direct using isatins to synthesize N ‐functionalized isatins.…”