The Study On Cycloaddition Reaction Promoted By Mg(Ⅱ) And Application Into The Synthesis Of Chiral Oxazolidinone Drugs

This thesis aims at the studies on cycloaddition of aryl isocyanates with oxiranes promoted by MgI₂ and application into the synthesis of chiral oxazolidinones. This dissertation consisted of four parts as following:Chapter 1 reviewed the synthetic applications of magnesium diiodide and its complexes in various functional transformations and C?C bond-forming reactions. High Lewis acidity and high oxophilicity are critical factors for the unique reactivity of MgI₂ catalyst. Results and mechanistic discussions on the systematic studies of cycloaddition reaction of various aryl isocyanates with typical oxiranes promoted by MgI₂ etherate [MgI₂·(OEt₂)_n] are documented in chapter two. We investigated the effect of amounts of MgI₂ etherate, solvent and temperature on the cycloaddition of phenyl isocyanate with epichlorohydrin. This magnesium-promoted cycloaddition is mild, efficient, operationally simple and highly regioselective. Iodide counterion, reaction temperature and solvent media (i.e.,THF) are critical factors for the unique reactivity of this catalytic system.Cycloaddition of aryl isocyanates with chiral oxiranes promoted by MgI₂ etherate under solvent-free condition in near quantitative yield was demonstrated in chapter three. A series of novel C-5-substituted 1,2,3-triazole-oxazolidinones were synthesized by in situ"click reaction", which in vitro antibacterial activities against was primarily tested.Synthetic application of MgI₂·(OEt₂)_n-promoted cycloaddition of isocyanates with chiral oxiranes was demonstrated in chapter 4 on an approach for the synthesis of linezolid. Starting from 3,4-difluoro -nitrobenzene, linezolid was prepared through 7 steps in an overall yield of 35%. The key step is cycloaddition of 3-fluoro-4-morpholinyl -phenylisocyanate with (R)-epichlorohydrin promoted by MgI₂ etherate under solvent free condition. This novel synthetic approach is short, efficient and highly stereoselective, which represents a novel and more general methodology for the develpoment of such oxazolidinone drugs from readily available starting materials.