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Asymmetric Propargyl Substitution Reaction Of Copper - Catalyzed Propargyl Alcohol With Enamine

Posted on:2016-02-28Degree:MasterType:Thesis
Country:ChinaCandidate:B WangFull Text:PDF
GTID:2271330479955339Subject:Pesticides
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The propargylic substitution reaction of propargylic alcohol as well as its derivatives with nucleophiles is one of the most useful tools for synthesis of various alkyne moiety-containing molecules, which could easily be further transformed into useful complex compounds. Owing to chiral propargylic-substituted products are important intermediates of many fine chemicals and natural products, asymmetric catalytic propargylic substitution reaction of propargylic alcohol derivatives with nucleophiles has attracted much attention in recent years.Copper-catalyzed asymmetric propargylic substitution of propargylic alcohol derivatives with nucleophiles is one of the most important part of the asymmetric propargylic substitution reactions. Despite these achievements, the carbon-nucleophile of this asymmetric version is still rare. Among various carbon-nucleophiles, the “hard” nucleophile enamine is a quite attractive one.It can be used as a variation of the carbanions, avoiding using a strong base in the reaction process.Herein, we reported the efficient use of “hard” carbon-nucleophileenamines in copper-catalyzed asymmetric propargylic alkylation reaction which could be carried out by using ferrocene chiral tridentate P,N,N-ligands/Cu(I) complex. Then affection of copper precursors and reaction conditions(such as solvent, reaction temperature et. al.) were well studied. According to these screening results, the propargylic substitution reactions were carried out in MeOH at 0 °C in the presence of Cu(CH3CN)4ClO4(5 mol%), tridentate P,N,N ligand(L)(7.5 mol%) and the base i-Pr2 NEt. With these optimized reaction conditions in hand, we evaluated the scope of this method for various enamines and propargylic acetates. 17 β-ethynyl-substituted ketones with high reactivities(up to 95% yield) and excellent enantioselectivities(up to 98% ee) were synthesized. The reaction proceeded smoothly under mild conditions and provided an expedient access to highly valuable chiral propargylic ketone compounds.The bioactivity of insecticidal, herbicidal and antifungal activities of ten title compounds were tested. It was found that some compounds exhibited promising antifungal activities, e.g. the inhibitory rate of compound 3ac was 89% inhibited the growth of Botrytis cinerea at the concentration of 100 ?g/mL, which were obviously better than that of difenoconazole(70%).
Keywords/Search Tags:chiral propargylic ketone compounds, copper-catalyzed, propargylic acetates, enamines, asymmetricpropargylic substitution, chiral P,N,N-ligands, bioactivity
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