A Bite on Catalytic Enantioselective Oxidation of Sulphides with H2O2 in Water

Selectivity in chemical transformation is one of the keys that guide us to green chemistry. As ecological sustainability of a reaction depends on the reagents, solvents and work up, intense work focused on the development of methodologies. This is particularly challenging for asymmetric reactions, and in particular, for oxidation reactions. The use of water and molecular oxygen or hydroxide peroxide as oxidizing agent has been studied so far. However, few highly enantioselective oxidations with molecular oxygen or hydrogen peroxide have been reported: The asymmetric reaction using a chiral catalyst in water without a surfactant is a challenge.

Optically active sulfoxides are subunits of many bioactive compounds, and they also serve as chiral auxiliaries, so there’re methods in the literature for asymmetric sulfoxidation, some of them using aqueous hydrogen peroxide as the oxidant of alkyl aryl sulfides and with good yield and high enantioselectivity. The reaction with Fe(salan) complex (JACS, 2007, 29, 8940) or the one with Al(salalen)Cl (Chem. Commun., 2008, 1704) are very nice examples.

I guess this possibility is depending on the availability of the ligand, and the choose of the proper metal (Fe, Al, Mn…) and solvent for the particular substrate. Although probably the ligands depicted in the quoted papers above are not commercial, other perhaps would suit.

On the other hand, there are other options for catalytic enantioselective oxidation, although perhaps not in pure water.

Among the well know methodologies:

VO(acac)2 + chiral Shiff bases and a peroxide, usually in a two phase system (often the organic solvent which works better is dichloromethane)

Ti(OiPr)4 a ligand (chiral inductor), a base and a peroxide.

Good results with monooxigenases have been also publised.

A much less evolved strategy is the kinetic resolution of the racemic sulphide and further separation of the corresponding sulphone, although there are remarkable examples and can be useful for particular substrates.