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Application of Copper(I) Iodide/Diorganoyl Dichalcogenides to the Synthesis of 4‐Organochalcogen Isoquinolines by Regioselective CN and CChalcogen Bond Formation
Author(s) -
Stein André L.,
Bilheri Filipe N.,
da Rocha Juliana T.,
Back Davi F.,
Zeni Gilson
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201201618
Subject(s) - chemistry , chalcogen , isoquinoline , regioselectivity , catalysis , ring (chemistry) , trifluoromethyl , medicinal chemistry , sonogashira coupling , organic chemistry , palladium , alkyl
A copper‐catalyzed cyclization of ( ortho ‐alkynyl)benzaldimines with diorganoyl dichalcogenides allowed the synthesis of 4‐organochalcogen isoquinolines, whereas the presence of base in the reaction medium inhibited the product formation producing the undesirable isoquinoline without the organochalcogen atom at the 4‐position. The cyclization reaction was carried out by using CuI (20 %) as a catalyst with diorganoyl dichalcogenides (1.5 equiv) in the presence of DMF at 100 °C. Furthermore, the reaction did not require an argon atmosphere and was carried out in an open flask. The cyclization reaction tolerated a variety of functional groups both in ortho ‐alkynylbenzaldimines and diorganoyl dichalcogenides, such as trifluoromethyl, chloro, fluorine, and methoxyl, to give the six‐membered heterocyclic ring exclusively through a 6‐ endo ‐ dig cyclization process. The organochalcogen group present at the 4‐position of the isoquinoline ring was further subjected to a selective chalcogen–lithium exchange reaction followed by the addition of aldehydes to afford the desired secondary alcohols in good yields. The obtained isoquinolines also proved to be suitable substrates for the Suzuki and Sonogashira coupling conditions affording the corresponding products through CC bond formation.