Iodocyclization Of N-arylpropynamides Mediated By Hypervalent Iodine Reagent: Novel Divergent Synthesis Of Iodinated Quinolin-2-ones And Spiro[4,5]trienones

Quinolines and spiro[4,5]trienones represent important structural motifs,existing in a number of natural products with pharmacological activity.Besides,they are one of the most important intermediates in organic chemistry.In recent years,electrophilic iodocyclization of aryl alkyne compounds has attracted widespread attention by chemists.At present,many methods have been reported to synthesize iodinated quinolin-2-ones and spiro[4,5]trienones,but most of the existing methods use traditional iodine reagent,and still has certain limitation in substrate scope.Herein,we disclosed a novel iodocyclization of N-arylpropynamides mediated by hypervalent iodine reagent to synthesize iodinated quinolin-2-ones and spiro[4,5]trienones.This novel strategy is highlighted by features such as readily availability of the starting materials and mild reaction conditions.We chose N-methyl-N-arylphenylpropiolic amide as the model substrate,preparing iodinated quinolin-2-ones product by using PIFA as oxidant and BF₃·Et₂O as catalyst in PhCl under 80 ^oC conditions through a series of conditions screening.To validate the usability of the substrates,a series of N-arylpropynamides substrates were prepared.Experimental results show that 19 N-arylpropynamides substrates under optimal conditions are converted into iodinated quinolin-2-ones.Moreover,we found that a substrate bearing a para-fluoro group on the aniline ring could be converted to the iodinated spiro[4,5]trienones.In order to explore the universality of this kind of substrate,we prepared a series of compounds and obtained a total of 10 iodinated spiro[4,5]trienones under the same conditions.All the substrates and target molecules were proved by ¹H NMR,¹³C spectra and HRMS.Meanwhile,we also proposed a possible pathway of this iodocyclization reaction.The discovery of intermediate diaryliodonium trifluoroacetates and some experimental facts have proved the rationality of this mechanism.