Gold Catalyzed Enantioselective Intermolecular [3+2] Dipolar Cycloaddition Of N-allenyl Amides With Nitrones

As the extension of the previous research upon the gold catalyzed intermolecular cycloaddition of N-allenylamide, intermolecular enantioselective [3+2] cycloaddition of N-allenylamides with nitrones was developed via chiral phosphoramidite ligated Au(I) catalysis, giving a series of chiral4-alkylidenyl isoxazolidine derivatives in high yields and excellent enantioselectivities.Isoxazolidine and2,3-dihydroisoxazole are important structural units in a wide variety of biologically active compounds, and are also useful synthetic intermediates for the preparation of various natural products. In this thesis, we have developed an efficient method to construct the multisubstituted chiral2,3-dihydroisoxazoles through gold catalyzed intermolecular enantioselective cycloaddition.Part1:Racemic [3+2] cycloaddition of N-Allenyl amides with nitrones via gold catalysisBased on the previous research, racemic [3+2] cycloaddition of N-allenyl amides with diphenyl nitrones was achieved through PPh3AuC1/AgNTf2catalysis.Part2:Synthesis of chiral phosphoramidite ligated Au(I) catalyst and its application in the enantioselective [3+2] cycloaddition of N-Allenyl amides with nitronesA series of BINOL derived chiral phosphoramidite ligated Au(I) catalysts were synthesized, and were applied in gold catalyzed [3+2] cycloaddition of N-allenyl amides with diphenyl nitrones. By using the optimal gold catalyst, a series of chiral2,3-dihydroisoxazoles were synthesized in high yields and excellent enantioselectivities.Part3:Further transformation of chiral2,3-dihydroisoxazole cycloadducts1,3-Amino alcohols are important structural elements in a diverse range of natural products and pharmaceuticals.The [3+2] cycloaddition, coupled with Raney-nickel reduction, could provide a facile method to synthesize chiral1,3-amine alcohol derivatives.