Stereoselective and regioselective functionalisation of protopine alkaloids: the synthesis of 1-substituted O-methyldihydrocryptopines

Abstract

Regio- and diastereo-selective complexation of dihydrocryptopine to the tricarbonylchromium(0) unit proceeds in good yield to give a single diastereoisomer with the chromium attached to the dimethoxyarene ring. An X-ray crystal structure analysis on the product revealed an exo disposition of the metal unit relative to the 14-hydroxy group, O-Methylation gave exo-tricarbonyl(η⁶-O-methyldihydrocryptopine)chromium(0) which was also the exclusive product of the direct complexation of O-methyldihydrocryptopine. Subsequent deprotonation, alkylation (MeI, CH₂N⁺Me₂I^–) and decomplexation gave the corresponding 1-substituted O-methyldihydrocryptopines.