Michael Reaction At C-3 Of Indoles And The Synthesis Of Bis-indolylmethanes

Indoles are a class of Heterocycle with important physiological function and potent pharmacological activity. The development of new efficient, selective and green synthetic methods of the 3-substituted indole derivatives has attracted sustained attention in organic synthesis due to their important biological activities and key role as versatile building bocks in the synthesis of natural products and therapeutic agents. In this thesis, the development of the carbon-carbon bond formation at C-3 of indoles are reviewed. That PdCl₂(CH₃CN)₂ immobilized in ionic liquid [bmim][BF₄] catalyzes the Michael reaction of indoles with α , β - unsaturated ketones to afford the corresponding β -indolylketones in excellent yields is described and that a mild and efficient electrophilic substitution reaction of indoles with various aldehydes (ketones) under catalysis of sulfamic acid afforded biologically important bisindolymethanes in good yields is developed. The main research results are summarized below:1. A new method that PdCl₂(CH₃CN)₂/[bmim] [BF₄] can efficiently catalyze the Michael reaction of a variety of indoles with α , β - unsaturated ketones is developed. The effect of reaction conditions on the Michael reaction is studied. We found that solvent effect is comparatively obvious and the efficiency of catalyst is better in ionic liquid [bmim][BF₄] than in molecular solvent. The optimized reaction conditions are using 2. 0 mol% PdCl₂(CH₃CN)₂ as catalyst in [bmim][BF₄) at 100 ℃ for 2 h. Under the optimized reaction conditions, we obtained 34 β -indolylketones in good yields and the structures of the products were further established by the X-ray diffraction studies of 3b.2. The PdCl₂(CH₃CN)₂/[bmim] [BF₄] system could be easily recovered after completion of the reaction and recycled in three runs with a gradual decrease in activity. PdCl₂(CH₃CN)₂ is often underestimated phenomenon inLewis acid catalysis. The mechanism of the reaction was investigated and the protons from the hydrolysis of PdCl2 in imidazolium based ionic liquids were identified as the active catalysts.3. A new method that solid acid - sulfamic acid can efficiently catalyze the electrophilic substitution reaction of a variety of indoles with aldehydes (ketones) to give bisindolymethanes is developed. The effect of reaction conditions on the electrophilic substitution reaction is studied. We found that solvent effect is comparatively obvious and the efficiency of catalyst is better in alcohol than in nonproton organic solvent. The optimized reaction conditions are using 50 mol% sulfamic acid as catalyst in methanol or ethanol at room temperature for 1-6 h. Under the optimized reaction conditions, we obtained 35 bisindolymethanes in good yields and the structures of the products were further established by the X-ray diffraction studies of 5g. The sulfamic acid could be easily recovered after completion of the reaction and recycled with no any decrease in activity.