Synthesis resolution of 3,4,3'4'-tetramethoxyl-1,1'-1,2,3,4-tetrahydrobisisoquinoline and application in asymmetric alkylation reactions

Abstract

This report describes the synthesis of chiral 3,4,3',4'-tetramethoxyl-1,1'-1,2,3,4-tetrahydrobisisoquinoline. The compound is to be later used as a catalyst in the asymmetric alkylation addition reaction between 2-propargyl acetate and benzaldehyde to form an allylic alcohol. Racemic 3,4,3',4'-tetramethoxyl-1,1'-1,2,3,4-tetrahydrobisisoquinoline was obtained via a three step procedure : First an oxyamide was formed through a reaction between 2(3,4 methoxyphenyl)ethylamine followed by cyclicization of the oxyamide via a Bischler Napieralski reaction and reduction by NaBH4 (Polniaszek’s method). The resulting racemic compound was resolved using (S)-(+)-α-methylbenzyl isocyanate as the resolving agent. A pure diastreomer was obtained through recrystallization in ethanol the diastereomer was then alcoholised under sodium butoxide to give the desired biiisisoquinoline.