Application of copper(I) iodide/diorganoyl dichalcogenides to the synthesis of 4-organochalcogen isoquinolines by regioselective C-N and C-chalcogen bond formation.
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 C-C bond formation.
Departamento de Química Orgânica, Laboratório de Síntese Reatividade, Avaliação Farmacológica e Toxicológica de Organocalcogênios, Universidade Federal de Santa Maria Santa Maria, Rio Grande do Sul - 97105-900, Brazil.
André L
AL
Stein
Filipe N
FN
Bilheri
Juliana T
JT
da Rocha
Davi F
DF
Back
Gilson
G
Zeni
D000480:Alkynes / Q000737:chemistry; D002384:Catalysis; D018011:Chalcogens / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D007454:Iodides / Q000737:chemistry*; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D000480:Alkynes; D018011:Chalcogens; D007454:Iodides; D007546:Isoquinolines; D003300:Copper; C073870:cuprous iodide