A detailed study of the intramolecular hydroamination of N-(ortho-alkynyl)aryl-N′-substituted trifluoroacetamidines and bromodifluoroacetamidines

Abstract

The intramolecular hydroamination of N-(ortho-alkynyl)aryl-N′-substituted trifluoroacetamidines and bromodifluoroacetamidines is studied in detail. When the substituents on the alkyne fragment are aryl and alkyl groups, 5-endo-digcyclization occurs utilizing NaAuCl₄·2H₂O as a catalyst, while 6-exo-digcyclization proceeds in the presence of K₂CO₃ as a base. Interestingly, the indole derivatives are afforded with good regioselectivity via a 5-endo-dig pathway catalyzed by Cu(OAc)₂ when ortho-ethynyl appears on the aryl substituent of the amidine. The electrophilic cyclization of the amidines also shows good regioselectivity under the I₂/NaHCO₃ system. At the end, a facile cascade synthesis of fluorinated quinazolones is described viahydroamination/ozonolysis from the corresponding amidine.