Studies On The[3+2]-Cycloadditions Of Ketenimines With Active Methylene Isocyanides

Imidazole is a nitrogen-containing heterocyclic ring having a nitrogen atom at each of the 1 and 3 positions.It is widely found in natural products and synthetic functional molecules.Imidazole compounds have attracted much attention due to their wide range of uses in medicine,pesticides,artificial materials,artificial receptors,supramolecular ligands,and biomimetic catalysts.Therefore,the synthetic methodological study of imidazole compounds has also been a hotspot.Although much progress has been achieved in this area,a number of synthetic methods for the synthesis of imidazoles have been reported in the literature,the development of new methodlogies for regioselective synthesis of functionalized imidazoles is stilldesirable.The ketimine selected in this paper can be prepared from simple,inexpensive and readily available raw materials,and has good reactivity;The [3+2] cycloaddition reaction with active methyleneisocyanide under mild conditions provides an efficient and simple method for the synthesis of 1,4,5-trisubstituted imidazole derivatives.On the above preliminary results,experimental results and related literature,we propose a possible reaction mechanism.Potassium tert-butoxide draws hydrogen protons from the isocyanoethyl methylene methylene group to form a carbanion intermediate,and then nucleophilically attacks the intermediate carbon carbon atom of the ketimine,which undergoes 5-endo-dig cyclization and 3 Hydrogen migration to 1,4,5-trisubstituted imidazole.It is worth noting that the cyclization of active methylene isocyanate with ketene imine occurs only on the C=N double bond of ketimine,which has high regioselectivity,and the substrate of the cyclization reaction has a wide range.The functional group has good compatibility and the operation is simple.