Rh(III)-catalyzed C6-selective Acylmethylation and Carboxymethylation of 2-Pyridones with Diazo Compounds

Chelation-assisted C6-selective acylmethylation and carboxymethylation of 2-pyridones with diazo carbonyl compounds under [Cp*RhCl2](2)/AgSbF6 catalysis have been developed. Deesterificative C6-acylmethylation of 2-pyridones with diazo tert-butyl ester compounds proceeds effectively with the use of HOAc additive and hexafluoroisopropanol (HFIP) solvent, whereas switching to NaOAc additive and MeOH solvent enables efficient deacylative C6-carboxymethylation of 2-pyridones with alkyl 2-diazo-3-oxobutanoates. The procedures are characterized by excellent regioselectivity, high efficiency, broad substrate scope, wide functional group compatibility and gram-scalability. Preliminary mechanistic experiments are conducted to gain insights into the reaction mechanisms.

Automated summary

Chelation-assisted C6-selective acylmethylation and carboxymethylation of 2-pyridones with diazo carbonyl compounds under [Cp*RhCl2](2)/AgSbF6 catalysis have been developed with excellent regioselectivity, high efficiency, broad substrate scope, wide functional group compatibility and gram-scalability. Preliminary mechanistic experiments are conducted to gain insights into the reaction mechanisms.