Biomimetic iron-catalyzed asymmetric epoxidation of aromatic alkenes by using hydrogen peroxide

A novel and general biomimetic non-heme Fe-catalyzed asymmetric epoxidation of aromatic alkenes by using hydrogen peroxide is reported herein. The catalyst consists of ferric chloride hexahydrate (FeCl3 center dot 6H(2)0), pyridine-2,6-dicarboxylic acid (H-2-(pydic)), and readily accessible chiral N-arenesulfonyl-N'-benzyl-substituted ethylenediamine ligands. The asymmetric epoxidation of styrenes with this system gave high conversions but poor enantiomeric excesses (ee), whereas larger alkenes gave high conversions and ee values. For the epoxidation of trans-stilbene (1a), the ligands (S,S)-N-(4-toluenesulfonyl)-1,2-diphenylethyl-enediamine ((S,S)-4a) and its N'-benzylated derivative ((S,S)-5a) gave opposite enantiomers of trans-stilbene oxide, that is, (S,S)-2a and (R.R)-2a, respectively. The enantioselectivity of alkene epoxidation is controlled by steric and electronic factors, although steric effects are more dominant. Preliminary mechanistic studies suggest the in situ fort-nation of several chiral Fe-complexes, such as [FeCl(L*)(2)-(pydic)]center dot HCl (L* = (S,S)-4a or (S,S)-5a in the catalyst mixture). which were identified by ESIMS. A UV/Vis study of the catalyst mixture, which consisted of FeCl3 center dot 6H(2)O, H-2(pydic), and (S,S)-4a, suggested the formation of a new species with an absorbance peak at lambda = 465 nm upon treatment with hydrogen peroxide. With the aid of two independent spin traps, we could confirm by EPR spectroscopy that the reaction proceeds via radical intermediates. Kinetic studies with deuterated styrenes showed inverse secondary kinetic isotope effects, with values of k(H)/k(D)=0.93 for the beta carbon and k(H)/k(D)=0.97 for the alpha carbon, which suggested an unsymmetrical transition state with stepwise O transfer. Competitive epoxidation of para-substituted styrenes revealed a linear dual-parameter Hammett plot with a slope of 1.00. Under standard conditions, epoxidation of 1a in the presence of ten equivalents of (H2O)-O-18 resulted in an absence of the isotopic label in (S,S)-2a. A positive nonlinear effect was observed during the epoxidation of la in the presence of (S,S)-5a and (R,R)-5a.