Palladium- and Ruthenium-Catalyzed Intramolecular Carbene CAr -H Functionalization of γ-Amino-α-diazoesters for the Synthesis of Tetrahydroquinolines.

A synthetic method to prepare tetrahydroquinoline-4-carboxylic acid esters has been developed through the transition-metal-catalyzed intramolecular aromatic C-H functionalization of α-diazoesters. Both [{Pd(IMes)(NQ)}2 ] (IMes=1,3-dimesitylimidazol-2-ylidene, NQ=1,4-naphthoquinone) and the first-generation Grubbs catalyst proved effective for this purpose. The ruthenium catalyst was found to be the most versatile, although in a few cases the palladium complex afforded better yields or selectivities. According to DFT calculations, Pd0 - and RuII -catalyzed sp2 -CAr -H functionalization proceeds through different reaction mechanisms. Thus, the Pd0 -catalyzed reaction involves a Pd-mediated 1,6-H migration from the sp2 -CAr -H bond to the carbene carbon atom, followed by a reductive elimination process. In contrast, electrophilic addition of the ruthenacarbene intermediate to the aromatic ring and subsequent 1,2-proton migration are operative in the Grubbs catalyst promoted reaction.