CuI-Catalyzed Tandem Carbomagnesiation/Nucleophilic Addition Of Grignard Reagents And Acetylenic Ketones

In this thesis, we studied the one-pot synthesis of highly functionalized tetrasubstituted allylic alcohols via the CuI-catalyzed tandem carbomagnesiation/nucleophilic addition of Grignard reagents and acetylenic ketones. The further transformation of the obtained allylic alcohols was studied and functionalized polysubstituted indenes were obtained by iron-catalyzed intramolecular Friedel-Crafts cyclization of allylic alcohols. The thesis consists of the following two parts:Firstly, we studied CuI-catalyzed carbomagnesiation/nucleophilic addition of Grignard reagents and acetylenic ketones. Polysubstituted allylic alcohols containing carbonyl and carbon-carbon triple bond were synthesized in moderate to good yields by the three-component tandem carbomagnesiation/nucleophilic addition. All products were characterized by 1^H NMR,13^C NMR,IR and HRMS. The molecular structure of compound 2-(diphenylmethylene)-3-hydroxy-1,3,5-triphenylpent-4-yn-1- one (3a) was determined by X-ray diffraction analysis.Secondly, we studied FeCl₃·6H₂O-catalyzed Friedel-Crafts cyclization of allylic alcohols. The further transformation of the obtained allylic alcohols was investigated. The results show that polysubstituted indenes containing carbonyl and carbon-carbon triple bond were synthesized by the FeCl₃·6H₂O-catalyzed intramolecular Friedel-Crafts cyclization of allylic alcohols. All products were characterized by 1^H NMR,13^C NMR,IR and HRMS. The molecular structure of compound (4-chlorophenyl)(1-(4-chlorophenyl)-3-phenyl-1-(2-phenyl-ethynyl)-1^H- inden-2-yl)methanone)(4c) was determined by X-ray diffraction analysis.The tandem carbomagnesiation/nucleophilic addition of Grignard reagents and acetylenic ketones provides a new method for synthesis of polysubstituted allylic alcohols. The method has the advantages of easily available materials, simple manipulation and mild reaction conditions. The highly functionalized allylic alcohols are important intermediates in organic synthesis and are further transformed to polysubstituted indenes by iron-catalyzed intramolecular Friedel-Crafts cyclization, which provides a new method for the synthesis of polysubstituted indene derivatives.