A catalytic carboxylic acid-selective aldol reaction with trifluoromethyl ketones was developed. Reversible and selective covalent bond formation between a boron catalyst and a carboxylic acid is key to realizing the unprecedented catalytic aldol reaction of simple carboxylic acids. The reaction proceeded chemoselectively at the α-position of carboxylic acid even in the presence of ketone, ester, or amide functional groups in the donor substrates. The chemoselectivity is beneficial for late-stage derivatizations of biologically relevant compounds, as demonstrated by the conversion of indomethacin and triacetylcholic acid.