Site and Enantioselective Aliphatic C−H Oxidation with Bioinspired Chiral Complexes

Abstract

Selective oxidation of aliphatic C−H bonds stands as an unsolved problem in organic synthesis, with the potential to offer novel paths for preparing molecules of biological interest. The quest for reagents that can perform this class of reactions finds oxygenases and their mechanisms of action as inspiration motifs. Among the numerous families of synthetic catalysts that have been explored, complexes with linear tetraazadentate ligands combining two aliphatic amines and two aromatic amine heterocycles display a structural versatility proven instrumental in the design of C−H oxidation reactions showing site and enantioselectivities, not accessible by conventional oxidants. This manuscript makes a review of recent advances in the field.

Reactivity vs. Selectivity of Biomimetic Catalyst Systems of the Fe(PDP) Family through the Nature and Spin State of the Active Iron‐Oxygen Species

“…Though, it is clear now that even relatively subtle electronic effects (alongside with steric effects) should not be discounted when designing novel non‐heme Fe based catalysts for direct oxidation of C−H groups, which glorifies rational ligand‐oriented catalyst design as a potentially highly rewarding investment of efforts. We share the expectation that hon‐heme Fe based catalyst systems are to expand their synthetic utility, [3i] and hope that this account will be of interest for catalytic chemists interested in developing synthetic approaches to late‐stage oxidative functionalization of complex substrates, from both fundamental and practical perspectives.…”

“…This issue needs further investigations. Nevertheless, the consensus mechanisms of Fe(PDP) catalyzed epoxidations (proceeding through rate‐limiting electron transfer, with formation of acyclic, presumably electron‐deficient intermediate) [13c] and C−H oxidations (occurring essentially via oxygen rebound mechanism) [3i,5f] includes the common formally perferryl species (Scheme 1).…”

“…This absence of correlation between spin state and C−H oxidation selectivity is in sharp contrast with the asymmetric epoxidation by the same catalyst systems, in which case the epoxidation enantioselectivity increased when passing from the systems featuring low‐spin perferryl intermediates to those with their high‐spin congeners (see above). Given that the mechanisms of Fe(PDP) catalyzed epoxidations [13c,5f] and aliphatic C−H oxidations [3i,5f] are different (Scheme 1), it appears that whereas the common “reactivity‐selectivity” principle, governed mostly by electronic factors, can be adhered to in the former case for prognostication purposes, [7b] it does not necessarily work in the latter case, which puts forward the crucial role of steric factors in modulating the catalysts’ C−H oxidation selectivity. However, the situation may be different in case of C−H oxidation of more complex substrates; the corresponding case study is described in the next section.…”

Manganese-Catalyzed Regioselective C–H Lactonization and Hydroxylation of Fatty Acids with H2O2

“…Disclosing the mechanistic landscape of these versatile oxidative transformations is of particular interest. Based on the previous background, 11,20,21,38 we believe that the first step, intramolecular C−H bond cleavage, is conducted by the presumably Mn V �O complex (Scheme 1). In this case, the fatty acid serves as both the cocatalytic additive, facilitating the O−O bond heterolysis, 24,36 and as the substrate at the same time.…”

“…It contains the highly sterically demanding benzhydryl substituents as well as strongly electron-donating methoxy substituents at the pyridine moieties of the ligand. X-ray characterization (SI) revealed that 7 featured the same cis -α topology as other catalytically active complexes of the PDP family. ,,,− Complex 7 and a series of other (previously reported) manganese complexes 1 – 6 (Figure ) were probed in the oxidation of n -hexanoic acid with H 2 O 2 (Table ). The reaction conditions were varied to in order to maximize the selectivity for γ-caprolactone.…”