A Para-Selective Kolbe-Schmitt Reaction

The Kolbe-Schmitt reaction is the archetypal carboxylation reaction in organic synthesis yet generally suffers from the requirement of high temperatures and CO₂ pressures. We report a Kolbe-Schmitt-type carboxylation of phenols using near equimolar amounts of a CO₂ source at relatively low temperatures. The reaction uses the cesium salt of triphenylacetic acid as a combined source of base and CO₂. Whereas the traditional Kolbe-Schmitt reaction provides products of ortho carboxylation (salicylic acids), this method, which employs cesium salts, delivers high para selectivity to give 4-hydroxybenzoic acids. With the advantage of using near stoichiometric amounts of the carboxylating reagent, we demonstrate a practical and efficient preparation of ¹³C-labeled 4-hydroxybenzoic acid derivatives, thereby opening opportunities for applying Kolbe-Schmitt-type chemistry in the area of carbon isotope labeling.