Synthesis of Substituted Biarylmethanol via Ferrocenyloxime Palladacycles Catalyzed Suzuki Reaction of Chlorophenylmethanol in Water

Abstract

Alcohols are of great importance as cheap and readily available organic materials for the preparation of many pharmaceutical products and fine chemicals. In addition, alcohols as electrophiles instead of alkyl halides in C-C (N) bonds forming reactions are particularly attractive because the process produces only water as byproduct. In spite of the existence of many synthetic routes, there are limited reports involving biarylmethanols. The palladium-catalyzed Suzuki reaction is an extremely efficient method for the construction of biaryl compounds. Among various Pd catalysts, palladacycles are one of the most active catalysts for the coupling reactions. From the economical and environmental points of view, employing readily accessible aryl chlorides and the use of water as a solvent in this reaction offer many advantages. However, there have been a few reports which demonstrated that palladacycles catalyzed Suzuki reaction of limited aryl chlorides in water. To our knowledge, only two accounts has been reported concerning the Suzuki of 4-chlorophenylmethanol in organic solvent. Recently, we have developed a cationic cyclopalladated ferrocenylpyrimidine catalyzed Suzuki reaction of aryl halides and 4-(hydroxymethyl)phenylboronic acid for the synthesis of substituted biarylmethanols in water. However, substrates are limited to the aryl bromides and activated aryl chlorides. To date, there is no report that investigates the Suzuki reaction of chlorophenylmethanol in water. As a continuation of our interest in the synthesis of biarylmethanols, we have prepared a new phosphine adduct of palladacycle 2 from the reaction of cyclopalladated ferrocenyloxime dimer 1 with commercially available 2-dicyclohexylphosphanyl-2'-(N,Ndimethylamino) biphenyl (DCPAB) (Scheme 1) and developed a practical method for the synthesis of biarylmethanols by the Suzuki reaction of chlorophenylmethanol and arylboronic acids in water. Complex 2 is airand moisture-stable, both in solid state and in solution. It was fully characterized by elemental analysis, IR, NMR and ESI-MS. In comparison with the corresponding frequencies of the free ferrocenyloxime, the C=N absorptions of 2 has been shifted to low values (1599 cm), indicating that the N atom is coordinated to palladium. The H NMR spectrum of 2 exhibits more signals than expected, and the P NMR appears two singlets at δ 65.54 and 67.15 ppm, suggesting the existence of isomers in solution. A similar phenomenon was also found in the H NMR