Bioinspired Manganese and Iron Complexes for Enantioselective Oxidation Reactions: Ligand Design, Catalytic Activity, and Beyond

Abstract

The development of efficient methods for the enantioselective oxidation of organic molecules continues to be an important goal in organic synthesis; in particular, the use of earthabundant metal catalysts and environmentally friendly oxidants in catalytic asymmetric oxidation reactions has attracted significant interest over the last several decades. In nature, metalloenzymes catalyze a wide range of oxidation reactions by activating dioxygen under mild conditions. Inspired by selective and efficient oxidation reactions catalyzed by metalloenzymes, researchers have developed a number of synthetic model compounds that mimic the functionality of metalloenzymes. Among the reported biomimetic model compounds, tetradentate aminopyridine (N4) ligands have emerged as appealing frameworks because of their easy synthesis and facile diversification, and their complexes with metals such as Fe and Mn have proven to be versatile and powerful catalysts for a variety of (enantioselective) oxidation reactions. In this Account, we describe our efforts on the design of chiral N4 ligands and the use of their manganese and iron complexes in asymmetric oxidation reactions with H 2 O 2 as the terminal oxidant, aiming to show general strategies for asymmetric oxidation reactions that can guide the rational design of ligands and relevant metal catalysts. In studies of manganese catalysts, the arylsubstituted (R,R)-mcp [mcp = N,N′-dimethyl-N,N′-bis(pyridine-2-ylmethyl)cyclohexane-1,2-diamine] manganese complexes exhibited high enantioselectivity in the asymmetric epoxidation (AE) of various olefins with H 2 O 2 while requiring stoichiometric acetic acid as an additive for the activation of H 2 O 2 . To address this issue, we established bulkier N4 ligands for this catalytic system in which a catalytic amount of sulfuric acid enables the manganese-complex-catalyzed AE with improved stereocontrol and efficiency. In addition, this system was found to be active for the oxidative kinetic resolution of secondary alcohols. Further exploration of the structure−reactivity relationships has shown that aminobenzimidazole N4 ligands derived from L-proline, in which the conventional pyridine donors are replaced by benzimidazoles, act as promising ligands. These novel C 1 -symmetric manganese catalysts showed dramatically improved activities with unprecedented turnover numbers in the AE reactions. Notably, this class of manganese complexes can catalyze the oxidation of the C−H bonds of spirocyclic hydrocarbons and spiroazacyclic compounds in a highly enantioselective manner, providing ready access to chiral spirocyclic β,β′-diketones and spirocyclic alcohols. Remarkably, iron catalysts with these chiral N4 ligands are effective for AE of olefins, enabling rare examples of highly enantioselective syntheses of epoxides by the iron catalysts. Finally, mechanistic studies provide valuable insights into the roles of the carboxylic acid and sulfuric acid in the catalytic oxidation reactions. Thus, the results described in this Account have demonstrated the ...

Recent Trends and Prospects in Homogeneous Manganese‐Catalysed Epoxidation

“…From then, several modifications occurred in the line of research and many reviews emerged with specific emphasis that covered certain classes of homogeneous Mn‐catalysts. This include (i) bioinspired Mn‐aminopyridine catalysts in olefin epoxidation using different oxidants, [14] (ii) chiral Mn‐aminopyridine catalysts in chemo‐ and stereoselective oxidations using H 2 O 2 , [15] (iii) bioinspired manganese and iron complexes in enantioselective oxidation reactions, [16] and (iv) artificial nonheme iron and manganese oxygenases for enantioselective epoxidation of alkenes and alkane hydroxylation [17] . Despite the aforementioned reports, a comprehensive review summarizing all the recent advances in homogeneous Mn‐catalysed epoxidation will be appreciated.…”

A DFT study on the C–H oxidation reactivity of Fe(iv)–oxo species with N4/N5 ligands derived from l-proline

“…Recently, we have prepared a series of linear polydentate nitrogen ligands, and their iron and manganese complexes have demonstrated an excellent performance in the enantioselective oxidation of C]C and C-H bonds. 26 Among these ligands, two derived from L-proline, namely Pro3Py (pentadentate ligand, N5) and Pro2PyBn (tetradentate ligand, N4), have similar structures (Scheme 1). [27][28][29] Herein, we report calculations on the hydroxylation of cyclohexane (CYH) by synthetic non-haem Fe IV O complexes with both N4/N5 supporting ligands (Pro3Py and Pro2PyBn ligands, Scheme 1).…”

General Access to Modified α‐Amino Acids by Bioinspired Stereoselective γ‐C−H Bond Lactonization

“…[21] Small molecule coordination complexes based on iron and manganese can reproduce the basic aspects of these reactions, inter alia, highly site-selective and enantioselective aliphatic CÀHbond oxidation. [22] This outcome is virtually inaccessible by any other non-enzymatic method and accordingly these bioinspired catalysts are potentially very powerful tools for the development of highly selective CÀHbond functionalization reactions.…”