Studies On The Tandem Reactions Via Allene Or Ketenimine Intermediates

As important class of reactive species and useful synthetic intermediates or synthons, both allenes and ketenimines are widely used for the synthesis of complicated molecules, especially for the construction of heterocycles. In this thesis, the recent progresses on the cascade reaction of propargylic alcohols via allene intermediates are reviewed. Based on the reported utilizations of allenes and ketenimines, we developed three new methods for the synthesis of heterocycles. The details are summarized as following:1) Synthesis of 1,2-dihydro-isoquinolinesAn efficient synthesis of 1,3-/1,1-dialkoxy 1,2-dihydroisoquinolines from o-ethynylbenzacetals and sulfonyl azides was developed. The cascade process included copper-catalyzed alkyne-azide cycloaddtion (CuAAC), Dimroth rearrangement,1,5-OR shift/1,5-H shift and 6 π-electrocyclic ring closure. The reaction was mild and afforded the 1,2-dihydroisoquinolines in good yield with a short time. Moreover, the synthesized 1,3-dialkoxy-1,2-dihydroisoquinolines could be easily converted into the isoquinolium salts.2) Synthesis of spiro[indene-benzosultam]sA highly efficient and convenient construction of the spiro[indene-benzosultam] skeleton from propargylic alcohols had been developed. The reaction was easily operated and proceeded in a Lewis acid-catalyzed cascade process, including the trapping of allene carbocation with sulfonamide, electrophilic cyclization, intramolecular Friedel-Crafs alkylation. In the presence of NIS or NBS, iodo/bromo substituted spiro[indene-benzosultam]s also could be prepared in excellent yields.3) Synthesis of spiro[indene-1,1’-isoindolin]-3’-onesAn efficient strategy to synthesize spiro[indene-1,1’-isoindolin]-3’-ones was developed via a sulfuric acid catalyzed reaction of 3-(2-cyanophenyl)propargylic alcohols. The reaction was easily operated and occurred in a cascade way with 100% atom economy, high bond formation efficiency, and high conversion yields. A tentative mechanism was postulated, including Meyer-Schuster Rearrangement of propargylic alcohols, hydrolysis of nitrile, imide formation, Friedel-Craft alkylation. Moreover,2-(3-hydroxy-l-propyne)benzamide could also be converted into the spiro[indene-1,1’-isoindolin]-3’-ones in a’two step one pot’ reaction.