The Pd₂(dba)₃-Catalyzed Cross-Coupling Reactions Of Trifluoroethyl Iodide With Boronic Acid Esters

In this thesis, the synthesis of 1,1,1-trifluoro-2-iodoethane and the smooth coupling reactions of 1,1,1-trifluoro-2-iodoethane with aryl and heteroaryl boronic acid esters was studied.1. The synthesis of 1,1,1-trifluoro-2-iodoethane. In a convenient manner, the 1,1,1-trifluoro-2-iodoethane was obtained as an oil by a two-step sequence in an overall 61% yield starting from commercially available trifluoroethanol (Scheme 1).2. The synthesis of aryl and heteroaryl Boronic Acid Esters. Pd(0Ac)2 plus phosphine ligand appeared to be the catalyst system of choice, since this phosphine not only showed a high activity, but is also inexpensive, robust and easy to handle. In combination with KOAc as the base and dioxane as the solvent, excellent yields were obtained (Scheme 2).3. The cross-coupling of boronic acid esters with trifluoroethyl iodide. We now found that for the cross-coupling reactions of aryl and heteroaryl boronic acid esters with trifluoroethyl iodide, which represents an unactivated alkyl halide withoutβ-hydrogens, a much simpler reaction protocol is highly efficient.The cross-coupling reactions of boronic acid esters with trifluoroethyl iodide (2 equiv) is accomplished in>50% yield within 16 h at 60℃, coordinatively tris(dibenzylideneacetone)dipalladium together with CuCl and CsF, in DMF. This protocol is applicable to aryl and heteroaryl boronic acid esters, to give the corresponding trifluoroethylated derivatives. (Scheme 3)...