Organocatalyzed Asymmetric Tandem Intramolecular oxa-Michael Addition/Electrophilic Thiocyanation: Synthesis of Chiral α-Thiocyanato Flavanones

An efficient bifunctional cinchona alkaloids-catalyzed asymmetric tandem intramolecular oxa-Michael addition/electrophilic thiocyanation of alkylidene beta-ketoesters with N-thiocyanatosuccinimide (NTS) was developed. A series of chiral alpha-thiocyanato flavanones containing two vicinal stereocenters including an all-carbon quaternary center were prepared in good yields with excellent diastereo- and enantioselectivities (up to 97% ee) under mild conditions, and a successful scale up preparation of our protocol was also demonstrated.

Automated summary

An efficient bifunctional cinchona alkaloids-catalyzed asymmetric tandem intramolecular oxa-Michael addition/electrophilic thiocyanation method was developed for the synthesis of chiral alpha-thiocyanato flavanones with two vicinal stereocenters. The method produced the desired compounds in good yields with excellent diastereo- and enantioselectivities under mild conditions, demonstrating its potential for scale-up.