Remote Amino Acid Recognition Enables Effective Hydrogen Peroxide Activation at a Manganese Oxidation Catalyst

Abstract

Precise delivery of a proton plays a key role in O 2 activation at iron oxygenases, enabling the crucial OÀ O cleavage step that generates the oxidizing high-valent metaloxo species. Such a proton is delivered by acidic residues that may either directly bind the iron center or lie in its second coordination sphere. Herein, a supramolecular strategy for enzyme-like H 2 O 2 activation at a biologically inspired manganese catalyst, with a nearly stoichiometric amount (1-1.5 equiv) of a carboxylic acid is disclosed. Key for this strategy is the incorporation of an α,ω-amino acid in the second coordination sphere of a chiral catalyst via remote ammonium-crown ether recognition. The properly positioned carboxylic acid function enables effective activation of hydrogen peroxide, leading to catalytic asymmetric epoxidation. Modulation of both amino acid and catalyst structure can tune the efficiency and the enantioselectivity of the reaction, and a study on the oxidative degradation pathway of the system is presented.

Asymmetric Epoxidation vs syn-Hydroxy-Acyloxylation of Olefins in the Presence of Sterically Demanding Nonheme Manganese Complexes

“…Summarizing the above considerations, the following mechanistic landscape can be proposed (Scheme ). First of all, the putative formally manganese­(V)-oxo active oxidizing species LMn V O ( I ) − is formed via “carboxylic acid-assisted” heterolytic cleavage of the peroxide O–O bond in the initially formed Mn III (OOH) intermediate. ,,, Then, the LMn V O species reacts with the olefinic substrate to give the electron-deficient acyclic intermediates I or II . , Based on the different linear free-energy correlations for less electrophilic catalyst 4 and more electrophilic catalyst 3 (Figure A,B), we conclude that the corresponding transition states have different degrees of the electron deficiency. This may be formally acknowledged by considering the corresponding acyclic intermediates as cationic ( I ) in the case of 3 (cf.…”

“…The latter has been shown to be compulsory for achieving good conversions, also affecting the enantioselectivity of epoxidation. 10,20 These observations, together with isotopic labeling data, implied the involvement of manganese-(V)-oxo carboxylate species as the key reaction intermediate responsible for oxygen transfer, to produce scalemic epoxides. 22,23 Although there have been attempts to modify the ligand scaffolds by replacing pyridyls with other moieties, such as e.g.…”

“…The catalyst systems as above utilize environmentally benign oxidant hydrogen peroxide and require adding carboxylic acid as the cocatalyst. The latter has been shown to be compulsory for achieving good conversions, also affecting the enantioselectivity of epoxidation. , These observations, together with isotopic labeling data, implied the involvement of manganese­(V)-oxo carboxylate species as the key reaction intermediate responsible for oxygen transfer, to produce scalemic epoxides. , …”

“…Asymmetric epoxidation of olefins is a challenging transformation, with the resulting chiral epoxides providing valuable chemical products and versatile building blocks . Bioinspired manganese­(II) complexes with chiral N 4 bis -amino- bis -pyridylmethyl and structurally related ligands have been regarded as prominent catalysts of asymmetric epoxidation, attracting great research interest in recent years. − …”