Structural and mechanistic studies of the copper(II)-assisted ortho-hydroxylation of benzoates by trimethylamine N-oxide

• Published in: Journal of organometallic chemistry 2002, Vol.641 (1), p.71-80
• Main Authors: Buijs, Wim, Comba, Peter, Corneli, Danny, Pritzkow, Hans
• Format: Article
• Language: English
• Subjects: Chelate ring size; ortho-Hydroxylation; Reaction mechanism; Salicylic acid; Selectivity
• ISSN: 0022-328X; 1872-8561
• DOI: 10.1016/S0022-328X(01)01291-8

N-benzoyl-2-methylalanine (H 2L 1) is ortho-hydroxylated stereoselectively by trimethylamine N-oxide (TMAO) in the presence of copper(II). The experimental structure of [Cu(L 1)(TMAO) 2] suggests that the oxygen transfer agent TMAO transfers the oxygen atom to copper(II), and (L 1) 2−, coordinated to copper(II) by a carboxylate oxygen and the amide nitrogen donor, is well pre-organized for an oxygen transfer from copper to the ortho carbon atom of the benzene ring. Product analyses as a function of reaction time of the copper(II)-mediated ortho-hydroxylation reaction with H 2L 1 and various derivatives support the suggestion of a reactive copper-oxo or copper-hydroxo intermediate, stabilized by a five-membered chelate with hard carboxylate and N-amide donors. The analysis also suggests that there is a pre-equilibrium with a Cu:L=1:1 ratio, and this might involve Cu/L 2−/TMAO or dicopper complexes. Depending on the ligand H 2L, complexation with the salicylate product may inhibit the ortho-hydroxylation reaction. Trimethylamine N-oxide (TMAO) transfers oxygen to benzoate derivatives, coordinated by copper(II), to selectively yield the corresponding salicylate derivatives. The structure of a precursor with the benzoate derivative and TMAO coordinated to copper(II) supports this mechanism.