Synthesis Of Triazoles,Dihydropyrazoles And Chiral Seven-Lacton Rings Catalyzed By NHCs

Organocatalysis is the third type of chiral catalytic reaction after enzyme catalysis and metal catalysis.It is a bridge between metal organic catalysis and enzyme catalysis,synthetic chemistry and bio-organic chemistry.It is one of the most popular fields in organic synthesis.As an important component of the organic small molecule catalyst,azacarbene catalysts(NHCs)have been the focus of scientists in recent years.NHCs are not only non-toxic and harmless,but also catalyze a wide range of substrates.It provides new methods and strategies for the construction of carbon-carbon bonds and the synthesis of various complex natural products.In view of the advantages of high efficiency,economy and greenness of such catalysts,we have used azacarbene catalytic strategy to design experiments and synthesized three different types of heterocyclic compounds.Part I: NHC-catalyzed 1,3-dipolar cycloaddition reaction of allyl ketones with azidesAs one of the most important heterocyclic structures,1,2,3-triazoles have a wide range of biological activities.Therefore,we designed a NHC-catalyzed 1,3-dipolar cycloaddition reaction of allyl ketones with azides.After a series of conditions screening,a series of 1,4,5-trisubstituted-1,2,3-triazole compounds were synthesized with high yield and high regioselectivity in the presence of a 20 mol% N-heterocyclic carbine catalyst(up to 74%).This stuty opens up a new path for the synthesis of 1,4,5-trisubstituted-1,2,3-triazole compounds.Considering the large variety and ready availability of the starting materials,we believe that this work will have a wide practical use in the future.Part II: NHC-catalyzed cycloaddition of ?,?-unsaturated esters and azidesAs one of the most important structure in biologically active compounds,five-membered nitrogen heterocycles have drawn special attention because of their biological activities.We developed a cycloaddition reaction of ?,?-unsaturated esters with azide catalyzed by N-heterocyclic carbine catalyst.This strategy provides a novel approach to synthesize both 1,2,3-triazoles and dihydropyrazoles simultaneously.After a series of conditions screening,two kinds of five-membered nitrogen heterocyclic compounds were generated with high yield and high regioselectivity(between 46-97%).When the ?-position of the ?,?-unsaturated ester was substituted by aryl or alkyl groups,the 1,4,5-trisubstituted-1,2,3-triazole compounds were obtained;when the ?-position was unsubstituted,the dihydropyrazoline compound were obtained.In addition,we have conducted in-depth research on the mechanism by mass spectrometric(MS)study.The discovery of this method provides an efficient and simple strategy for the synthesis of five-membered nitrogen heterocyclic compounds.Part III: NHC-catalyzed enantioselective [4+3] cycloaddition of ortho-hydroxyphenyl substituted para-quinone methides with isatin-derived enalsCycloaddition reaction is one of the most important tools in organic chemistry,synthetic approaches to five-and six-membered ring systems are common via cycloaddition reactions,while the synthesis of seven-membered ring is relatively less reported.The seven-membered lactone ring and the spirooxindole structure are often present in natural products and biologically active substances,and we have conceived that a line can synthesize compounds containing both important structures.Therefore,the first enantioselective [4+3] cycloaddition of ortho-hydroxyphenyl substituted para-quinone methides has been established by employing isatin derived enals as suitable 3C-synthons under N-heterocyclic carbene catalysis.By using this strategy,biologically important seven-membered lactones have been prepared in good yields(up to 89%)and excellent asymmetric inductions(90-99% ee,> 20:1 dr).This methodology opens a direct entry for the asymmetric synthesis of chiral seven-membered lactones.