Studies On Asymmetric Annulations Catalyzed By N-Heterocyclic Carbenes

N-Heterocyclic carbenes(NHCs)have been widely utilized as organocatalysts in organic synthesis.In this context,the asymmetric annulations catalyzed by NHCs were studied extensively.There are six parts for this thesis:Chapter 1:Research progress on asymmetric catalytic annulations catalyzed by N-heterocyclic carbenesIn recent years,the asymmetric catalytic reactions of N-heterocyclic carbenes(NHCs)play an important role in synthesis of important natural product skeletons and drug molecules.The asymmetric annulations including key intermediates derived from different substrates,the design and synthesis of new substrates,and the co-catalytic annulations combined with other catalysts catalyzed by NHCs were summarized.Chapter 2:Stereoselective Synthesis of Functionalized Tetrahydro-1H-1,2-diazepines by N-Heterocyclic Carbene-Catalyzed[3+4]AnnulationDiazepine-based nitrogen heterocycles are frequently found in numerous bioactive molecules.Owing to the promising biological activities,the development of synthetic methods to these structural motifs has drawn extensive attention.Herein,We have developed an efficiently NHC-catalyzed asymmetric[3+4]annulation of N-Ts hydrazones with 2-bromoenals to synthesize functionalized tetrahydro-1H-1,2-diazepines with two consecutive stereocenters in good yields with excellent diastereo-and enantioselectivities.In addition,the functionalized tetrahydro-1H-1,2-diazepines can also be accessed via the[3+4]cycloaddition reaction of N-Ts hydrazones withα,β-enals catalyzed by NHCs in the presence of an oxidant.Chapter 3:Oxidative NHC Catalysis:Direct Activation ofβsp~3 Carbons of Saturated Acid ChloridesThe development of new NHCs catalysts and activation of new type of substrates have received wide attention.We have developed a new chiral NHC catalyst and applied it to the first activation ofβsp~3 carbon of 3-substituted saturated acid chlorides.Functionalized spirooxindole lactones were obtained with high yields,excellent diastereo-and enantioselectivities.Moreover,δ-valerolactone andδ-valero-lactam were obtained with high yields,excellent enantioselectivities.This approach is remarkably attractive due to the utilization of the product in natural products synthesis and potential pharmaceuticals.In addition,this strategy extends the substrate scope of NHCs catalysis.Chapter 4:Enantioselective Synthesis ofδ-Lactones via the Functionalized Thioether-mediated[3+3]Annulation Catalyzed by NHCsδ-Lactones play an important role in organic synthesis as synthetic intermediates.In this section,we have devoleped an efficiently enantioselective synthesis ofδ-lactones through thioether-mediated[3+3]annulation ofα-bromo-α,β-unsaturated aldehydes with functionalizedα,β-unsaturated ketones catalyzed by NHCs.The target molecules can be converted to other useful organic compounds through simple chemical transformation.In addition,the reaction can be conducted in scale-up synthesis.Chapter 5:Stereoselective Synthesis of Tetrahydropyrano[2,3-c]pyrazoles Catalyzed by NHCsThe pyrazoloδ-lactone skeleton,which exhibist extensively medicinal value,is present in many drug molecules.We have devoleped a stereoselective synthesis of tetrahydropyrano[2,3-c]pyrazoles through[4+2]annulation of diethyl 2-formylcyclo-propane-1,1-dicarboxylate with 4-substituted methylene-1-phenyl-1H-pyrazol-5(4H)-one catalyzed by NHCs.The pyrazoloδ-lactones can be obtained in high yield,excellent diastereo-and enantioselectivities.In addition,the asymmetric reaction has good advantage,such as low catalyst loading and good substrate suitability.Chapter 6:Highly Enantioselective Synthesis of Functionalized Azepino[1,2-α]-indoles via NHC-Catalyzed[3+4]AnnulationLittle effort has been focused on the enantioselective synthesis of azepino[1,2-α]-indoles.It is of widespread interest to develop new entries to synthesize chiral azepino[1,2-α]indoles.We have devoleped an efficiently enantioselective[3+4]annulation for the synthesis of functionalized azepino[1,2-α]indoles catalyzed by NHCs.The cyclo-addition products were achieved in good yields with excellent enantioselectivities.Our studies suggest that the 3-formyl group in the indoles plays a necessary mediated group for this[3+4]annulation.