• 10.1021/ja411110f
  • Journal of the American Chemical Society
  • Volume 136
  • January 2014
  • pp 1214-1217

N-Heterocyclic Carbene-Catalyzed [3+4] Cycloaddition and Kinetic Resolution of Azomethine Imines

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The authors describe the syntheses of several optically pure [3+4] cycloaddition product from the reaction of racemic azomethine imines and enals using indanol-derived catalyst D having N-mesityl substituent.  This work pertains to the development of N-Heterocyclic carbene ligands for the constructions of dinitrogen-fused seven membered heterocyclic derivatives that have significant biological activities.  The products have been characterized by 1H, 13C-NMR, HRMS, HPLC spectroscopy; the structures of 3j and racemic 5q product in solid state have been unambiguously confirmed by X-ray diffraction study. This research is detailed investigation of these N-heterocyclic carbene as organo-catalyst for enantioselective and diastereoselective [3+4] cycloaddition reaction and kinetic resolution of azomethine imines via one pot method.

Concerns: The authors observed [3+4] cycloaddition products with impressive ee yet yields of the cycloaddition adduct were in range of 52-84%. Perhaps this indicates that reactants might not completely consumed in the reaction to accomplish full conversion. The optimized reaction conditions mentioned: K2CO3, CH2Cl2/THF for 72-96 h. Certainly, the yields and reaction time can be improved by using solvents such as 1,2-dichloroethane, 1,1,2,2- tetrachloroethane and also increasing the mol% of enals with respect to azomethine imines; the excess unreacted enals are presumably removed by non-polar solvents.    

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