engleski

Preparation of optically active isoindolinones with quaternary stereogenic center bearing three aryl groups in organocatalytic fashion

Stereoselective arylation of diaryl ketimines to afford products containing quaternary stereogenic centers bearing three aryl groups is challenging because of the steric hindrance on such stereocenters. The problem lies in the inherent difficulty for the catalyst to differentiate between two enantiotopic faces of the planar ketimine, due to the lack of sufficient steric difference between two aryl rings. Hence, only few notable examples of preparation of this class of optically active compounds have been reported thus far. In 2012, Hayashi and Nishimura developed an enantioselective arylation of N-sulfonyl diaryl ketimines with arylboroxines in the presence of a chiral rhodium complex. Following this seminal work, several rhodium and palladium catalyzed enantioselective arylations of saccharine derived ketimines have been carried out. However, in the contrast to this elegant examples, there are no reports in literature for the preparation of such compounds in an organocatalytic fashion. Herein, we report a stereoselective arylation of N-acyl diariyl ketimines, mediated by chiral phosphoric acids (CPA). The success of this transformation lies in the in situ generation of the reactive diaryl ketiminium species from isoindolinone alcohols, making it susceptible for the reaction with phenols. Various phenols reacted smoothly, enabling isoindolinone derivatives containing quaternary stereogenic center with three aryl substituents in high yields and enantioselectivities. Mechanism of stereochemical induction will be discussed.

stereoselective ; arylation ; quaternary stereogenic center ; organocatalysis

nije evidentirano