Pd(0)-Catalyzed Direct C-H Functionalization of 2-H-4-Benzylidene Imidazolones: Friendly and Large-Scale Access to GFP and Kaede Protein Fluorophores.

ABSTRACT

The first one-pot synthesis of N-substituted 2-H-4-benzylidene imidazolones and their subsequent palladium-catalyzed and copper-assisted direct C2-H arylation and alkenylation with aryl- and alkenylhalides are described. This innovative synthesis is step-economical, azide-free, high yielding, highly flexible in the introduction of a variety of electronically different groups, and can be operated on large-scale. Moreover, the method allows direct access to C2-arylated or alkenylated imidazolone-based green fluorescent protein (GFP) and Kaede protein fluorophores, including ortho-hydroxylated models.