RESUMEN
We developed a modular synthesis for 3,3-disubstituted oxindoles, utilising readily accessible nitrones and acrylic acids. This approach facilitates the preparation of a diverse array of oxindoles through the variation of the starting materials. We demonstrated the applicability of this method through a gram-scale reaction and a synthesis of esermethole.
RESUMEN
Stereoselective construction of unprotected ß-amino acids is a significant challenge owing to the lack of methods for the catalytic generation of highly enantioenriched carboxylic acid enolates. In this study, a novel copper-catalyzed diastereo- and enantioselective reductive Mannich-type reaction of α,ß-unsaturated carboxylic acids was developed, which provides a direct and scalable synthetic method for enantioenriched ß2,3,3 -amino acids with vicinal stereogenic centers. The protocol features inâ situ generation of transiently protected carboxylic acids by a hydrosilane and their diastereo- and enantioselective reductive coupling with ketimines. The synthetic utility of this process was demonstrated by a gram-scale reaction and the transformation of ß-amino acids.
RESUMEN
The first enantioselective reductive aldol reaction of unprotected α,ß-unsaturated carboxylic acids was developed by employing a copper/bisphosphine catalyst. The reaction features in situ protection and activation of an α,ß-unsaturated carboxylic acid by a hydrosilane. The copper enolate formed in situ reacts with an alkyl aryl ketone to afford the ß-hydroxy carboxylic acid with excellent enantioselectivity (up to 99 % ee). The corresponding gram-scale reaction with a low catalyst loading and the derivatization of the ß-hydroxy carboxylic acids highlight the practicality of this transformation.