Rh(III)-catalyzed coupling between acrylic acids and yndienones has been realized for the synthesis of -hydrobenzofuranone. The reaction proceeded in excellent regio- and stereoselectivity under mild and redox-neutral conditions via a sequence of carboxylic acid-directed olefinic C-H activation, alkyne insertion, and Michael addition. Representative products were found to exhibit cytotoxicity toward the A549 cancer cell line at micromolar levels.