Expeditious synthesis of cis-1-methyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo-[3,2h]isoquinoline/[2,3-f]quinoline via azomethine ylide-alkene [3+2] cycloaddition

Abstract

Expeditious syntheses of cis-1-methyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo-[3,2h]isoquinoline /[2,3-f]]quinoline have been developed. The syntheses started with commercially available material and afforded excellent overall yields in straightforward steps. Intramolecular azomethine ylide-alkene [3+2] cycloaddition is the key step in the construction of these pyrroloisoquinoline and pyrroloquinoline scaffolds. This route is much more atom-economic than those reported in the literature and appropriate for scale-up synthesis.

C–H Functionalization of Azines

“…It is well-known that strong bases such as lithium amide − or organolithium − abstract protons from azines to give the corresponding organolithium species. It is notable that C–H acidity was calculated and the relationship with regioselectivity was nicely summarized. − For example, Quéguiner and co-workers reported C3-lithiation of 2-methoxypyridine in the presence of a catalytic amount of secondary amine (Scheme ).…”