Phosphine Supported Ruthenium Nanoparticle Catalyzed Synthesis of Substituted Pyrazines and Imidazoles from α-Diketones

A new methodology has been developed for the synthesis of highly substituted nitrogen heterocycles such as pyrazines and imidazoles starting from alpha-diketones using phosphine supported ruthenium nanoparticles (RuNPs) as catalysts. Ruthenium nanoparticles Ru1-Ru4 supported with different phosphines such as dbdocphos, dppp, DPEphos, and Xantphos are screened, of which Ru1 and Ru4 are found to be the most active. Interestingly, aryl-substituted and alkyl-substituted alpha-diketones produced different products: namely, pyrazine and imidazoles, respectively. This reaction methodology has been applied to the synthesis of a key intermediate (2m) of the marine cytotoxic natural product Dragmacidin B and an estrogen receptor (21). This work represents the first examples of pyrazines prepared by RuNPs.