Regioselective Divergent Carbonylative Cyclization of ortho-Alkynylphenols via Palladium Catalysis

The catalytic carbonylation of alkynes has been studied since the seminal work of Walter Reppe in the 1930s. [1] Over time, it has become evident that this transformation can follow diverse mechanistic pathways, depending on the catalyst system, the process type (e.g., oxidative, additive), and the nature of the nucleophile involved. [2] In particular, the carbonylation of alkynes in the presence of oxygen- based nucleophiles offers a practical and efficient route to α,β-unsaturated lactones, carboxylic acids, and esters. [3] Coumarin and its derivatives are privileged scaffolds widely employed in drug discovery due to their broad range of biological activities and structural flexibility. [4] Functionalized coumarins, especially those fused with other heterocycles, serve as valuable platforms for the development of novel hybrid molecules, many of which are key intermediates in pharmaceutical synthesis. Accordingly, the synthesis of chromenone-fused heterocycles remains an active area of research. In this context, we report a divergent carbonylative cyclization of 2-alkynylphenols, enabling the selective synthesis of isomeric coumarins and 2-coumaranones bearing endo and exo double bonds, respectively. Remarkably, the regioselectivity of the process is governed by a cooperative effect involving the Pd(II) center, its counterions, and coordinating ligands.