Investigations on the Iron‐Catalyzed Asymmetric Sulfide Oxidation

Abstract

The development of an enantioselective sulfide oxidation involving a chiral iron catalyst and aqueous hydrogen peroxide as oxidant is described. In the presence of a simple carboxylic acid, or a carboxylate salt, the reaction affords sulfoxides with remarkable enantioselectivities (up to 96 % ee) in moderate to good yields. The influence of the structure of the additive on the reaction outcome is reported. In the sulfoxide-to-sulfone oxidation a kinetic resolution (with s = 4.8) occurs, which, however, plays only a negligible role in the overall enantioselective process. Furthermore, a positive nonlinear relationship between the ee of the product and that of the catalyst has been found. On the basis of these observations, a possible catalyst structure is proposed.

Mechanism of the Asymmetric Sulfoxidation in the Esomeprazole Process: Effects of the Imidazole Backbone for the Enantioselection

“…[23] Thus, several methods have been developed for the asymmetric oxidation of prochiral sulfides with chiral metal complex catalysts, such as titanium-, [2,[24][25][26][27][28][29][30][31][32][33][34][35][36] manganese-, [37][38][39] vanadium-, [40][41][42][43][44][45][46] iron-, [47][48][49] and aluminium-based [50] systems. Despite the above-mentioned practical importance of the asymmetric sulfoxidation reactions, the basic mechanistic features of the titanium tartrate-based process used for the synthesis of esomeprazole ( Figure 1) remained mainly unexplored.…”

Non‐Heme Imine‐Based Iron Complexes as Catalysts for Oxidative Processes

“…In particular,acleana nd efficient late stage C À Hf unctionalization woulda void the unproductive manipulations necessary for interconverting, protecting andd eprotecting functional groups throughout the synthetic sequence.A lsoo ther oxidative processes,s uch as olefin epoxidation and sulfide oxidation, have received considerable attention for the relevance of epoxides and sulfoxides in synthetic organic procedures. [6][7][8][9][10] Although several methodsf or the preparation of such functionalities have alreadyb een developed, the quest for more general catalytic systems which use more abundant and sustainable reagents is still ongoing.…”

Mononuclear diastereopure non-heme Fe(II) complexes of pentadentate ligands with pyrrolidinyl moieties: Structural studies, and alkene and sulfide oxidation

“…The enantioselectivity obtained with these iron catalysts did not surpass 55% ee. However, very good selectivities up to 96% ee were reported recently by Bolm et al combining either Fe(acac) 3 or vanadium salts with Schiff base ligands in the presence of H 2 O 2 [44].…”

“…Jacobsen et al have found that the presence of an excess of acetic acid (ratio of catalyst:additive = 1:10) could improve the efficiency of alkene epoxidation with H 2 O 2 and an iron catalyst [4a]. Recently, Bolm et al reported enhanced reactivities and selectivities in sulfide oxidation using benzoic acids as additives in sub-stoichiometric amounts (ratio catalyst:additive = 1:0.5) [44]. Following these findings we chose to test two additives, acetic acid and p-anisic acid, for an investigation of their effect on the oxidation of phenyl methyl sulfide (entries 9 and 10).…”