A Para‐Selective Kolbe–Schmitt Reaction

Abstract

Abstract The Kolbe–Schmitt reaction is the archetypal carboxylation reaction in organic synthesis yet generally suffers from the requirement of high temperatures and CO 2 pressures. We report a Kolbe–Schmitt‐type carboxylation of phenols using near equimolar amounts of a CO 2 source at relatively low temperatures. The reaction uses the cesium salt of triphenylacetic acid as a combined source of base and CO 2 . 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 13 C‐labeled 4‐hydroxybenzoic acid derivatives, thereby opening opportunities for applying Kolbe–Schmitt‐type chemistry in the area of carbon isotope labeling.