Construction Of Several Heterocyclic Molecules Via Tandem Reactions

It is well known that many heterocyclic skeletons are found in many natural products and pharmaceuticals that show excellent biological activities. This thesis is mainly focused on the diversity-oriented synthesis of diverse natural product-like heterocyclic compounds via tandem reactions.Firstly, a practical and convergent synthesis of biologically active 1-(N-acyl)-1-aminoisoquinolines from the domino reaction of 2-alkynylbenzaldoximes with amides was developed. Various acylated 1-aminoisoquinolines were obtained in excellent yields in the presence of silver catalyst(10 mol %) combined with triflicanhydride(Tf2O, 1.1 equivalent).Secondly, an efficient generation of benzosultams via an intramolecular C(sp2)-H bond amination reaction of o-arylbenzenesulfonamides with PhI(OAc)2/I2 under metal-free conditions was described. The reaction conditions tolerated a broad range of substrates, and the transformation afforded a variety of bioactive benzosultams in good to excellent yields. The resulting benzothiazines could be selectively and conveniently converted into the corresponding iodinated derivatives via electrophilic substitution reactions.Thirdly, a Mn(III)-promoted oxidative cyclization of 2-isocyanobiphenyls with diarylphosphine oxides was reported, providing phenanthridin-6-yldiphenylphosphine oxides in good yields. Radical phosphonationand and isocyanide insertion were believed to be involved in the reaction process.Subsequently, a copper-catalyzed direct trifluoromethylation of propiolates was developed, leading to a series of trifluoromethylated coumarins in good yields.Mechanistic studies indicated that the reaction proceeded through a CF3 radical addition to activated alkynes.Finally, the incorporation of the(trifluoromethyl)thio group into the isocoumarin scaffold through a Lewis-acid-mediated electrophilic cyclization reaction of2-(2-alkynyl)benzoates with trifluoromethanesulfanylamide was reported. The transformation proceeded well in the presence of BiCl3 and BF3·Et2O at room temperature, giving rise to a series of 4-[(trifluoromethyl)thio]-1H-isochromen-1-ones in good yields.