A Four-Component Synthesis of Highly Substituted Imidazole Derivatives

Addition of lithiated methoxyallene 1 to imines 2 provided allenyl amines 3, which upon reaction with iodine and nitriles furnished dihydroimidazole derivatives 5. Treatment of these intermediates with strong acids such as trifluoromethane sulfonic acid afforded tetrasubstituted imidazole derivatives 6 in good overall yields. Subsequent base-promoted conversion of 1-iodovinyl-substituted compounds 6 into alkynyl-substituted imidazole derivatives 7 proceeded smoothly. Products 6 and 7 are versatile intermediates for further transformations such as palladium-catalyzed coupling reactions.