Intramolecular Carbolithiation Reactions in the Construction of Medium‐Sized Rings. Synthesis of Pyrroloisoquinolines, Benzazepines, and Benzazocines

Abstract

Abstract Mesityllithium (MesLi) was found to be superior to butyllithium for the formation of aryllithium intermediates by iodine–lithium exchange. Subsequent intramolecular carbolithiation of the 2‐alkenyl‐substituted ortho ‐lithiated N ‐benzylpyrroles proceeded efficiently when the alkene was substituted with an electron‐withdrawing group. The procedure is applicable to the construction of six‐, seven‐, and eight‐membered rings, thus, opening new routes to pyrroloisoquinolines, benzazepines, and benzazocines. Although the use of (–)‐sparteine as a chiral ligand led to low levels of enantioselection, enantiomerically pure isoquinolines could be synthesized by applying this protocol to the related pyrrolidines derived from proline, as the reactions proceeded with complete diastereoselectivity.