A palladium-catalyzed, N-directed C(sp3)-H functionalization and intramolecular lactonization of 2-acyl N-heteroarenes with 2-halobenzoic acids is reported, providing an efficient synthetic route to access N-heteroarene-substituted isocoumarins. The protocol demonstrates a broad substrate scope and chemoselectivity and is tolerant of diverse N-heteroarene and benzoic acid derivatives. The observed inverse kinetic isotope effect is likely a secondary isotope effect resulting from the sp2 to sp3 rehybridization of the acyl methyl carbon, to which the proton or deuteron is attached.
Sonawane et al. (Tue,) studied this question.