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Intramolecular Carbolithiation Reactions in the Construction of Medium‐Sized Rings. Synthesis of Pyrroloisoquinolines, Benzazepines, and Benzazocines
Author(s) -
GarcíaCalvo Oihane,
Coya Estíbaliz,
Lage Sergio,
Coldham Iain,
Sotomayor Nuria,
Lete Esther
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200994
Subject(s) - benzazepines , chemistry , intramolecular force , organolithium compounds , alkene , sparteine , stereochemistry , regioselectivity , lithium (medication) , ligand (biochemistry) , medicinal chemistry , combinatorial chemistry , organic chemistry , catalysis , receptor , medicine , ion , deprotonation , endocrinology , biochemistry
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.