Bromoperoxidases and functional enzyme mimics as catalysts for oxidative bromination-A sustainable synthetic approach

The discovery of enzymes that utilize hydrogen peroxide to oxidize bromide under physiological conditions provided a strong stimulus to the field of oxidative bromination. A synthetically useful enzyme, to catalyze the oxidation of bromide, for bromofunctionalization of donor-substituted arenes in solutions of hydrogen peroxide and sodium bromide, is a vanadate(V)-dependent bromoperoxidase from the brown alga Ascophyllum nodosum. This enzyme operates in homogeneous solutions of buffered aqueous tert-butanol (pH 6.2), or, to simplify repetitive use, in a two-phase system after immobilization onto magnetic beads. Synthesis of cyclic bromohydrin ethers (tetrahydrofurans and tetrahydropyrans) and vicinal dibromides from unsaturated hydrocarbons, on the other hand, occurs more effectively in polar aprotic solvents. Under such conditions the more lipophilic tert-butyl hydroperoxide serves as oxidant, which is activated by oxovanadium(V) complexes (functional bromoperoxidase mimics). Protons and bromide ions, which are consumed for in situ generation of bromine, are supplied in organic solution by fragmentation of 3-bromopropionic acids. The structure-reactivity data obtained from oxidations catalyzed by bromoperoxidases and functional enzyme mimics pose a valuable guideline for predicting selectivity in biomimetic synthesis of organobromines from terpenes, acetogenins, and pyrrole alkaloids. (C) 2011 Elsevier B.V. All rights reserved.