Constructions Of Several Natural Product-like Compounds Via Tandem Reactions

Skeletons of 1-metheneindenes, indoles and quinazolines are important key structural units of many natural products, which have been extensively found among drug moleculars and antiseptics, and therefore mouting-ever attention has been paid to constructions of these privileged structures. This dissertation mainly centers on methodologies development of constructions of the former three kinds of natural product-like compounds via tandem reactions starting from simple molecules available.Firstly, we have described Cs₂CO₃-prompted three-component reactions of 2-alkyl benzaldehydes, malononitrile and indoles as starting materials to construct mutisubstituted-1-metheneindene in reasonable yields. We also developed the tandem nucleophilic addition and 5-exo-cyclization of (2-(alkynyl)benzylidene)malonates with imidazole derivatives in the presence of t-BuOK, affording the corresponding 1-(1H-imidazol-1-yl)-3-methylene-1H-indene-2,2(3H)-dicarboxylates in good to excellent yields.Secondly, we have reported a novel approach to indole derivatives via multicatalytic tandem Beckmann rearrangement / intramolecular cyclization / halogenation reaction of 1-(2-alkynylphenyl)ketoxime with high efficiency and excellent selectivity. Beckmann rearrangement reaction of the start material in the presence of InCl₃ and CNC gave rise to intermediate 2-alkynylbenzenamide, and then 5-exo-cyclization of the intermediate afforded indole derivatives utilized PdCl₂(MeCN)₂ as Lewis acid to activate triple bonds. The starting materials are easily accessiable and the final product could be further elaborated via known palladium-catalyzed cross-coupling reactions.Finaly, we have disclosed a highly efficient and general method for the generation of 4-sulfanylquinazolines starting from thiols and quinazolin-4-ones in the presence of TsCl as C-OH bond activator without isolation of intermediate. Beside, we have also furnished 4-arylquinazoline derivatives via known palladium-catalyzed cross-coupling reactions employing quinazolin-4-ones and phenyl boronic acids as reaction partners in the presence of TsCl as C-OH bond activator.