Synthesis Of 6-alkynyl-6-hydroxyindoloquinazolinone Scaffolds Via Copper Catalyzed Alkynylation Of Tryptanthrins

Propargyl alcohols,of which hydroxyl group and triple bond can be further converted into valuable functional groups via addition,substitution or isomerization transformations,are important building blocks in organic synthesis,thus attracted great attentions during the past few decades.The catalytic addition of terminal alkynes to carbonyls represents a direct and atom-economic way to construct propargylic alcohols,and tremendous efforts have been dedicated to this field by employing different transition metal catalysts as well as aldehydes/ketone electrophiles.Despite these achievements,explorations of valuable synthetic targets bearing propargylic alcohol moiety under mild conditions are still in high demand.On the other hand,indoloquinazolines are interesting targets due to their potential pharmaceutical and biological activities,for which always drive us to explore diverse synthetic methods(Figure 1).Recently,we contributed to this area of research by applying Tryptanthrin,a weak basic indoloquinazoline alkaloid with different bioactivies to a variety of catalytic addition reactions.In this paper,we wish to report a Cu Cl₂·2H₂O catalyzed efficient addition of terminal alkynes to Tryptanthrin,in which a variety of propargyl alcohols with the indoloquinazoline skeleton could be prepared in mild conditions.Different function groups could be well tolerated,and a gram-scale synthesis was achieved under standard reaction conditions.Besides,convenient conversions of adducts to versatile building blocks were also carried out.