6‐Methoxypyridine‐Benzoxazole Ligand‐Directed Palladium‐Catalyzed Hydroacetoxylative Cyclization of Alkyne‐Tethered Cyclohexadienones

Comprehensive Summary Ligand‐directed divergent synthesis (LDS) has emerged as a powerful chemical tool for the formation of miscellaneous molecular frameworks from common reactants. Consequently, the rational development of ligands is of great concern. Previously, N , N ‐ligands were shown to direct the reaction pathways of palladium(II)‐catalyzed cascade cyclization of alkyne‐tethered cyclohexadienones with acetic acid, thus forming two types of cis ‐hydrobenzofuran products. In this work, we have reported 6‐methoxypyridine‐benzoxazole ligand‐directed palladium(0)‐catalyzed hydroacetoxylative cyclization of alkyne‐tethered cyclohexadienones with carboxylic acids, providing the structurally novel cis ‐hydrobenzofurans with high yields and broad substrate scope. In this process, carboxylic acids not only serve as hydrogen sources but also act as nucleophiles. Mechanistic investigations and DFT calculations revealed that this reaction was a palladium(0)‐catalyzed hydroacetoxylative cyclization, the hydrogen source was from the proton of the carboxylic acid and the low σ‐donor ability of 6‐methoxypyridine‐benzoxazole ligand proved to be crucial for palladium‐catalyzed hydrogen transfer from carboxylic acids to alkynes and nucleophilic acetoxylation of the palladium enolate.