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

Abstract

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.

Directing group-assisted selective C–H activation of six-membered N-heterocycles and benzo-fused N-heterocycles

“…71 In 2021, the Xu group disclosed the C6-selective acyl methylation and carboxymethylation of 2-pyridones 74 with diazo carbonyl compounds under Rh(III)-catalysis (Scheme 38). 72 Using AcOH as additive and HFIP as solvent, de-esterificative C-6 acyl methylation 76 of 2-pyridones was observed with diazo tert-butyl ester 75. By using NaOAc as an additive and MeOH as a solvent, deacylative C-6 carboxymethylation 78 of 2-pyridones was formed with alkyl 2-diazo-3oxobutanoates 77.…”

Water-Mediated ortho-Carboxymethylation of Aryl Ketones under Ir(III)-Catalytic Conditions: Step Economy Total Synthesis of Cytosporones A–C

“…In recent years, diazotized Meldrum’s acid has been effectively used as a coupling partner in transition metal-catalyzed C–H alkylation of arenes to synthesize 2-arylacetic acid ester derivatives. − However, the majority of the reports are limited to the substrate having an N -heterocycle as a chelating group . Recently, Lee et al disclosed the only report on the alkylation of aryl ketone with diazotized Meldrum’s acid for the synthesis of ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)­phenyl]­acetate (TMPA) and its structural derivatives .…”