Synthesis Of Chiral SPINOL-Derived Catalysts And Their Application In Asymmetric Reactions

The design and synthesis of chiral catalysts is an important subject in asymmetric reactions.Asymmetirc phase-transfer catalysis（PTC）has been widely used in enantioselective reactions due to its simple and safe operation,mild reaction conditions,and environmental friendliness,providing an important method to construct chiralα-amino acid compounds.Chiral phosphoric acid catalysis is widely used in the synthesis of chiral compounds owing to its wide substrate scope and diverse reaction types.This thesis focus on the design and synthesis of a series of new chiral spirocyclic quaternary ammonium salts and phosphoric acids from commercially available chiral SPINOL and the application of these catalysts in asymmetric reactions.Section Ⅰ:a series of new chiral spirocyclic quaternary ammonium salts were designed and synthesized,and were employed as phase-transfer catalysts in the asymmetric alkylation reaction of glycine imine with bromomethyl aromatics.By using a chiral spirocyclic quaternary ammonium salt with 3,5-bistrifluoromethylphenyl substituents as the optimal catalyst,a series of chiralα-amino acid derivatives bearing largely hindered substituents and/or fluorinated groups at theα-positions were obtained in up to 94%yield and 99%ee.The products have been conveniently converted into unnatural chiralα-amino acids.Section Ⅱ:a poly-trifluoromethylated chiral spirocyclic phosphoric acid was developed and employed with HFIP to render the catalytic asymmetric Mannich reaction of difluoroenoxysilanes with in-situ formed ketimines.This unique multiple-fluorine system provides rapid access to difluoromethylated tetrasubstituted stereocenters in isoindolones with wide substrate scope under mild conditions.Further synthetic transformations to enantioenrichedα-CF₂H-isoindolones andα-CF₂-decorated fused-isoindolones were also implemented with good efficiency.Section Ⅲ:An asymmetric Aza-Friedel-Crafts reaction of 2-aryl-3H-indol-3-ones with 1-naphthol is described by using poly-trifluoromethylated spirocyclic phosphoric acid as chiral catalyst.The reaction features mild reaction conditions and wide substrate scope,and a series of indolinones containing quaternary carbon chiral centers were obtained in up to 99%yield and 92%ee.By contrast,an asymmetric[3+2]cyclization reaction of 2-aryl-3H-indol-3-ones with 2-naphthol is also realized in the presence of squaramides-chincona derivatives.This reaction employs 1,2-dichloroethane/acetone（2/1）as the solvent,and allows the construction of a series of aza-polycyclic compounds in high yields with good to high diastereo-and enantioselectivities.