The catalytic carbonylation of alkynes is a powerful route to heteroaromatic scaffolds, yet achieving regioselectivity remains challenging. Herein, we report a divergent carbonylative cyclization of 2-alkynylphenol derivatives that affords either coumarins (6-endo-dig) or 2-coumaranones (5-exo-dig) by tuning the palladium-based catalytic system. Pd(OAc)2 in combination with TFA favored coumarins formation with high yield and selectivity (>15:1), whereas electron-deficient species such as Pd(MeCN)4(BF4)2 promoted 2-coumaranones with up to 84% yield and >25:1 selectivity. While many approaches exploit ligand design to steer selectivity, these results highlight counterion effects as a powerful tool to control regioselectivity in palladium-catalyzed carbonylative cyclization, expanding the utility of alkyne carbonylation for the synthesis of biologically relevant heterocycles.
Voronov, A., Sacchelli, F., Olivieri, D., Constantin, A.M., Mazzeo, P.P., Mancuso, R., et al. (2026). Counterion Effects Enable Divergent Pd‐Catalyzed Carbonylative Cyclization of Amide‐Tethered o‐Alkynylphenols. ADVANCED SYNTHESIS & CATALYSIS, 368(11), 1-9 [10.1002/adsc.70517].
Counterion Effects Enable Divergent Pd‐Catalyzed Carbonylative Cyclization of Amide‐Tethered o‐Alkynylphenols
Olivieri, Diego;Mazzeo, Paolo Pio;Carfagna, Carla;Tarroni, Riccardo;
2026
Abstract
The catalytic carbonylation of alkynes is a powerful route to heteroaromatic scaffolds, yet achieving regioselectivity remains challenging. Herein, we report a divergent carbonylative cyclization of 2-alkynylphenol derivatives that affords either coumarins (6-endo-dig) or 2-coumaranones (5-exo-dig) by tuning the palladium-based catalytic system. Pd(OAc)2 in combination with TFA favored coumarins formation with high yield and selectivity (>15:1), whereas electron-deficient species such as Pd(MeCN)4(BF4)2 promoted 2-coumaranones with up to 84% yield and >25:1 selectivity. While many approaches exploit ligand design to steer selectivity, these results highlight counterion effects as a powerful tool to control regioselectivity in palladium-catalyzed carbonylative cyclization, expanding the utility of alkyne carbonylation for the synthesis of biologically relevant heterocycles.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.



