PIFA-Mediated Synthesis Of 3-Hydroxy-2,3-dihydroisoquinoline-1,4-dione

The intramolecular cyclization of alkynes possessing a nucleophilic moiety in the proximity of the carbon-carbon triple bond has been reported to be a convenient and effective process for the construction of a variety of heterocycles. For this reason, during the past decades o-(1-alkynyl)benzamide derivatives have been widely studied as a basic enyne-amide system for exploring novel and useful cyclization transformations. The existing strategies involve the transition-metal catalyst, Lewis acid, and base mediated Nnucleophilic or O-nucleophilic attack onto the nearby carbon-carbon triple bond, giving rise to the five- or six-membered heterocyclic compound through 5-exo-dig or 6-endo-dig cyclization, respectively.Recent years, hypervalent iodine reagents have been reported to be a useful tool for the construction of C-C bond and C-heteroatom bond. Also, people have developed new pathways to obtain a variety of heterocycles mediated by hypervalent iodine reagents. This thesis mainly covers the exploration of a new synthetic route to 3-hydroxy-2,3-dihydroisoquinoline-1,4-dione from o-(1-alkynyl)benzamides, which includes the following aspects:1. Based on the results both from literatures and our previous research, a novel approach for the synthesis of 3-hydroxy-2,3-dihydroisoquinoline-1,4-dione was discussed, having never been reported before, through reactions between o-(1-alkynyl)benzamides and PIFA in CH3CN/H2O(1:1 v/v).2. A variety of o-(1-alkynyl)benzamides were converted into 3-hydroxy-2,3-dihydroisoquinoline-1,4-diones under the optimal reaction condition. The impact of different substituted groups on the outcome of the reaction was studied.3. Some substrates bearing a series of electron-withdrawing groups on aryl-ring B could generated pairs of insepratable isomers. We calculated the ratio of each part according to the NMR and further studied the changes of the ratio through NMR carried out at different temperatures.4. We also found the evidence of generating N+ in the reaction process and basically excluded the possibility of diketone’s pathway according to the control experiment.5. Based on the literature and results of control experiments, a reasonable mechanistic pathway was postulated.