The Synthesis Of Nitrogen Containing Benzoheterocyclic Compounds By Benzyne

Xanthene, indole, indoline, N-aryl tetrahydroquinoline and their derivatives haveimportant biological and pharmacological activity, which are widely used in thesynthesis of natural products and pharmaceutical intermediates. Therefore, the organicchemists get great interest in these compounds.Benzyne is a highly active intermediate in organic synthesis. The highelectrophlilcity of benzyne enables it to be widely used in the field of syntheticorganic chemistry and the synthesis of natural products. This paper mainly carried outbased on the insertion-cyclization reaction of benzyne. The main contents includethree parts as follows:1."One-pot" preparation of9-aminoxanthenes.2-(trimethylsilyl) phenyltrifluoromethanesulfonate, as the precursor of benzyne, underwent the effect offluoride ions to generate benzyne in situ, and then xanthene and its derivatives wereprepared through inserting-cyclization reaction of benzyne with salicyl N-tosylimine.9kinds of different substituted9-aminoxanthene compounds were obtained under theoptimization of reaction condition to give84%-99%yields. By further analysis of theexperimental results proposed reaction mechanism was presented that fluoride ionscatalyzed benzyne reacting with salicyl N-tosylimine to obtain different substitutedxanthenes.2. Synthesis of multi-substituted indoles.24kinds of N-aryl substituted indoleswere obtained through insertion-cyclization reaction of-amino ketones with benzyneto give51-99%yields; This reaction can be amplified to gram scale, up to95%yield;The reaction intermediate1,2,3-triphenylindolin-3-ol was isolated. Removing H2O ofthe intermediate, it can be converted to1,2,3-triphenylindole.3. Stereoselective synthesis of tetrahydroquinolines and indolines. Andβ-aminoketone with benzyne through a cascade insertion–cyclization process toafford11kinds of N-aryl tetrahydroquinolines (46-80%yields) with excellentanti-selectivity (anti/syn>25:1); Meanwhile, controlling the reaction conditions, thecoupling of ar nes with-amino ketones produces8kinds of multi-substitutedindolines in high yields (71%-92%) with syn-selectivity (syn/anti>25:1).In summary, based on insertion-cyclization reaction of benzyne, the new methodof synthesis nitrogen benzoheterocyclic compouds such as xanthene, multi-substitutedindole, indoline and N-aryl tetrahydroquinoline had been developed; and theapplication of benzyne had also been expanded.