Transformation of fluorinated 2-alkynylanilines by various catalytic systems

Abstract

Simple and efficient approaches to the synthesis of fluorinated benzoazaheterocycles with good yields are reported. Firstly a series of polyfluorinated 2-alkynylanilines – the versatile building blocks – was synthesized by the Sonogashira reaction of o-iodoaniline with terminal alkynes. Then the transformations of the obtained 2,3,4-trifluo-6-alkynilanilines in the presence of KOH or PdCl2 in MeCN, and in the presence of monohydrate of p-toluenesulfonic acid (p-TSA•H2O) in MeOH, EtOH or benzene were investigated. It was found that Ph- and n-Bu-containing alkynylanilines by action of PdCl2 in MeCN underwent an intramolecular cyclization reaction to produce the corresponding indoles in high yields. The reaction of KOH with alkynes containing the tertiary alcohol function at the triple bond produced the unsubstituted on the pyrrole ring indole. It was found that fluorinated 2-alkynilanilines can be transformated into indoles, 2-arylketones and 2,3-dihydroquinolines by action of p-TSA•H2O in boiling alcohols, depending on the substituent at the triple bond. The use of benzene as a solvent in the reaction of p-TSA•H2O with polyfluorinated alkynes, bearing an alcohol group resulted in representative series of 2,3-dihydroquinolinones containing a substituents R1 and R2 in the 2nd position of their structure (R = H, H; Me, Me; H, i-Pr; H, Ph).