Studies On [3 + 2] Cycloaddition Reactions Involving α-aryl Isocyanates And 3-Alkynoates

α-Aryl isocyanates and 3-alkynoates are readily available and highly reactive organic synthons for the construction of various N-containing heterocycles.Five-membered N-containing heterocycles such as pyrroles,pyrazoles,and triazoles are core moieties found in many natural products and biologically active molecules,which are widely applicated in medicines,agrochemicals,dyes,and multifunctional materials fields.In this thesis,we have efficiently synthesized a series of 1,2,4-triazoles,fluoropyrroles,pyrazoles,and imidazoline-fused benzosultams through intermolecular cycloaddition reactions involvingα-aryl isocyanates and 3-alkynoates.Based on these procedures,several natural product analogues and bioactive molecules have been successfully synthesized.Moreover,we focus on the design and synthesis of a novel chiral bifunctional thiourea-phosphine ligand derived from glycosyl,and its application in the synthesis of chiral N-containing heterocycles has been investigated.A brief overview is as follows:Section I:The base-mediated decarboxylation cycloaddition ofα-aryl isocyanates has been disclosed.We have successfully developed a DABCO-mediated decarboxylative annulation reaction ofα-aryl isocyanates with aryl diazonium salts to furnish a series of 1,3-diaryl-1,2,4-triazoles in high yields（up to 98%）.The potential of this method is further demonstrated by the synthesis of bioactive intermediates.On the basis of the experimental data,we proposed a tentative decarboxylation cycloaddition mechanism.In addition,we have disclosed an efficient DBU-mediated regioselective cycloaddition reaction betweenα-aryl isocyanates andα-fluoro-nitro olefins to obtain a series of 4-fluoro-2,3-diaryl-2H-pyrroles in excellent yields.The products can be transformed into 4-fluoro-2,3-diaryl-1H-pyrroles under mild conditions.This method takes advantage of the nitro group as a traceless activating and directing group（TADG）that is released in situ to produce 4-fluoro-2,3-diaryl-2H-pyrroles with complete regioselectivity.The potential of this procedure is further showcased by the synthesis of a molecule with anti-inflammatory activity.Section II:We have successfully developed a novel chiral bifunctional thiourea-phosphine ligand derived from glycosyl and disclosed its application in the asymmetric[3+2]cycloaddition reaction ofα-aryl isocyanates with benzosulfonyl imides.This protocol could provide imidazoline-fused benzosultams with moderate to good diastereoselectivity and enantioselectivity.Section III:We have described a Et₃N-triggered regioselective[3+2]cycloaddition reaction of 3-alkynoates or allenoates with diazo compounds（such as Seyferth Gilbert reagent and diazo carbonyl compounds）to furnish a series of trisubstituted pyrazoles.In this protocol,3-alkynoates act as electrophilic C₂-synthons.The one-pot cycloaddition/alkylation reaction can further have access to the fully substituted pyrazole-3-phosphonates.