Study Of Cascades Reaction Based On Electron -deficient Olefins:Aregio-And Stereoselective Approach To Functionalized Cyclic Compounds

Cascade reactions was one of efficient synthetic strategies to construction of multi-membered heterocyclic compounds. This dissertation studied the applications of two-component tandem in synthesis of multi-membered heterocyclic compounds from three parts. The first part was on domino reaction of electron-deficient a, a-dicyanoalkenes to 2-halo-1,3-dicarbonyl compounds for synthesis of five-membered heterocyclic compounds. The second part was on tandem reaction of electron deficient benz-a, a-dicyanoalkenes to 3-hydroxyindolin-2-one compounds for synthesis of five membered heterocyclic compounds. The third part was on cascade reactions of electron α-β-unsaturated ketones to 2-halo-1,3-dicarbonyl compounds for synthesis of three-membered heterocyclic compounds.At the beginning, an unexpected domino reaction of a, a-dicyanoalkenes (electron-deficient 2,4-dienes) with 2-halo-1,3-dicarbonyl compounds, employing the readily available N-(4-trifluoro methylbenzyl) (Ⅳ) cinchonium bromide as the phase-transfer catalyst, provides an access to functionalized-cyclopentenes and fulvene derivatives with excellent stereo-selectivities in good yields (up to 80%). The optimized reaction conditions:0.1 mmol electron deficient 2,4-dienes with 0.12 mmol 2-halo-1,3-dicarbonyl compounds in DCM at 15℃ with 20 mmol% Ⅳ as the chiral phase-transfer catalyst and 50 mmol% K2CO3 appeared to be the optimal reaction conditions, the stereoselectivity was dramatically increased and only the E-isomer was obtained. The regio-and stereochemistry of the substituted cyclopentenes and fulvene derivatives were confirmed only the E-isomer by the X-ray diffraction analysis.Next, We have successfully revealed an efficient and highly enantioselective furan-annulation of electron-deficient benz-α, β-dicyanoalkenes to 3-hydroxyindolin-2-one compounds, low cost Cinchonine as the organocatalyst and its direct application in the synthesis of optically active multi -functionalized furan-annulation, with excellent diastereoselectivities (99:1). The optimized reaction conditions:0.1 mmol electron-deficient benz-α, α-dicyanoalkenes and 0.15 mmol.3-hydro-xyindolin-2-one compounds in THF with 20 mmol% Cinchonine at 0℃ for 12 h. The relative configuration of the furan-annulation derivatives were confirmed by the X-ray diffraction analysis.Last, electron-deficient α-β-unsaturated ketones to 2-halo-1,3-dicarbonyl compounds by employing a commercially available, low cost quinine primary amine as the organocatalyst and its direct application in the synthesis of three-membered heterocyclic compounds with good yields (up to 97%), and excellent diastereoselectivities (up to>99:1). The optimized reaction conditions:0.2 mmol electron-deficient α-β-unsaturated ketones with 0.24 mmol 2-halo-1,3-dicarbonyl compounds in DCM at 36℃ with 20 mmol% quinine primary amine as the chiral phase-transfer catalyst and 120 mmol% Cs2CO3 for 40 h.