Asymmetric Michael-initiated ring closing reactions promoted by hydrogen bonding organocatalysis and the synthesis of cannabinoid metabolites

• Main Author: Aitken, Lewis Scott
• Published: University of Reading 2018
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.741110

Hydrogen bonding organocatalysis has been used to develop two novel asymmetric Michael-initiated ring-closing reactions, reported herein. A reaction between vinyl cyanosulfones and bromomalonates, promoted by a novel cupreine organocatalyst, yielded highly substituted cyciopropanes as single diastereomers and with high enantioselectivity (up to 96% ee). The synthetic utility of the cyclopropanes has been demonstrated through the synthesis of biologically-interesting products, such as difficult-to-access amino acids. Also reported is a second Michael-initiated ring-closing reaction, promoted by thiourea organocatalysis and producing substituted chiral cyclopentanes. Moderate yields and enantioselectivity were obtained, though future optimisation of the reaction is likely to yield improvements pharmaceutical project towards the treatment of childhood epilepsy, is reported. These were used in animal studies as part of the pre-clinical research and the results of one such study are reported.