Palladium-Catalyzed C8-H Alkoxycarbonylation Of 1-Naphthylamines

A simple and efficient protocol for palladium-catalyzed C8-H alkoxycarbonylation of 1-naphthylamine derivatives with alkyl chloroformates has been developed.The reaction proceeded smoothly selecting alkyl chloroformates as alkoxycarbonylation reagent,Pd?OAc?₂as catalyst,Na OAc as base,Na I as additive,in toluene under argon at 120? for 12 h,affording the target product successfully?Scheme 1?.The reaction exhibits broad functional group tolerance,high regioselectivity and oxidant-free conditions.Furthermore,the target product features its ease of further functionalization and transformation.For example,the concise synthesis of one BET inhibitor was accomplished via benz[cd]indol-2?1H?-one after multistep transformations from the obtained alkoxycarbonylation product.The addition of radical scavenger of 2,2,6,6-tetramethylpiperidin-1-oxyl?TEMPO?successfully suppressed the reaction.When the reaction were performed in the presence of TEMPO or 2,6-di-tert-butyl-4-methylphenol?BHT?,an adduct of TEMPO and isopropyl chloroformate as the product and an adduct of BHT and N-?naphthalen-1-yl?picolinamide as the product could be detected by HR-MS,respectively.These results suggested that the reaction might involve a radical process.Moreover,the experiment of the kinetic isotope effect?KIE?was carried out,and the result?KIE=0.3?may imply that the C-H bond cleavage might not be involved in the rate-determining step.