Stereoselective access to bioactive cyclopropanes (+)-PPCC and (1R,2S)-2-aminomethyl-1-arylcyclopropane-1-carboxamides from (−)-levoglucosenone

Abstract

The chiral synthon (−)-levoglucosenone (LGO) obtained from cellulose pyrolysis has been transformed into two known bioactive compounds: the serotonin-norepinephrine-dopamine reuptake inhibitor (1R,2S)-2-(aminomethyl)-N,N-diethyl-1-(naphthalen-2-yl)cyclopropane-1-carboxamide and the σ₋receptor ligand (+)-PPCC. The key steps in the process were the arylation of an LGO derivative via a Suzuki-Miyaura cross-coupling reaction, then cyclopropanation under Johnson-Corey-Chaykovsky conditions. Dehomologation was achieved using Baeyer-Villiger and NaIO₄ mediated oxidation, and then functional group interconversion gave the bioactive cyclopropanes. Several derivatives of each target were developed demonstrating the versatility of the process for aryl and amine group substitution.