Study On The Synthesis Of 3-monosubstituted Oxindoles And 3,3'-spirooxindoles

The first part of this dissertation: synthesis of 3-monosubstituted oxindoles Objective: Synthesis of 3-monosubstituted oxindoles in high yields and chemoselectivities from 3-methylene-2-oxindoles through bioreduction of C=C bond.Methods: The investigations begin with a screening of whole cells and co-solvents using 3-methylene-2-oxindole 1.3a as model substrate.With the optimized reaction conditions in hand,we then explored the scope of the substrates,and study on the relationship between the structure of the substrate and the catalytic activity Results:(1)The optimized reaction system using Pseudomonas monteilii ZMU-T17 and ethanol as catalyst and co-solvent,respectively,has been established.(2)Eighteen 3-monosubstituted oxindoles were obtained in up to 82% isolated yields.Conclusion:(1)A new strategy for the synthesis of 3-monosubstituted oxindoles has been developed.(2)Mechanism studies revealed that P.monteilii ZMU-T17 contained a soluble NADH-dependent dehydrogenase and ethanol maybe the hydride source for the reduction of 3-methylene-2-oxindoles.The second part of this dissertation: synthesis of 3,3?-spirooxindoles Objective: The development of an efficient method for the synthesis of CF2H-containing 3,3'-spirooxindoles Methods: Synthesis of CF2H-containing 3,3'-spirooxindoles through the cycloaddition of 3-ylideneoxindole with in situ generated CF2HCHN2.Results:(1)The optimized reaction system for the synthesis of CF2H-containing 3,3'-spirooxindoles has been established.(2)Thirtynine CF2H-containing 3,3'-spirooxindoles were obtained in up to 99% yields with 99:1 dr values.(3)The relative configuration of products were unambiguously determined by X-ray crystallographic analysis.Conclusion: A series of CF2H-containing 3,3'-spirooxindoles have been synthesized through a [3+2] cycloaddition using CF2HCH=N2 as a building block,which provided a facile and practical protocol for the construction of CF2H-containing molecules,as well as pave the way for the discovery of fluorinated pharmaceuticals.