Regioselective Oxidation of Nonactivated Alkyl C–H Groups Using Highly Structured Non-Heme Iron Catalysts

Abstract

Selective oxidation of alkyl C-H groups constitutes one of the highest challenges in organic synthesis. In this work, we show that mononuclear iron coordination complexes Λ-[Fe(CF(3)SO(3))(2)((S,S,R)-MCPP)] (Λ-1P), Δ-[Fe(CF(3)SO(3))(2)((R,R,R)-MCPP)] (Δ-1P), Λ-[Fe(CF(3)SO(3))(2)((S,S,R)-BPBPP)] (Λ-2P), and Δ-[Fe(CF(3)SO(3))(2)((R,R,R)-BPBPP)] (Δ-2P) catalyze the fast, efficient, and selective oxidation of nonactivated alkyl C-H groups employing H(2)O(2) as terminal oxidant. These complexes are based on tetradentate N-based ligands and contain iron centers embedded in highly structured coordination sites defined by two bulky 4,5-pinenopyridine donor ligands, a chiral diamine ligand backbone, and chirality at the metal (Λ or Δ). X-ray diffraction analysis shows that in Λ-1P and Λ-2P the pinene rings create cavity-like structures that isolate the iron site. The efficiency and regioselectivity in catalytic C-H oxidation reactions of these structurally rich complexes has been compared with those of Λ-[Fe(CF(3)SO(3))(2)((S,S)-MCP)] (Λ-1), Λ-[Fe(CF(3)SO(3))(2)((S,S)-BPBP)] (Λ-2), Δ-[Fe(CF(3)SO(3))(2)((R,R)-BPBP)] (Δ-2), Λ-[Fe(CH(3)CN)(2)((S,S)-BPBP)](SbF(6))(2) (Λ-2SbF(6)), and Δ-[Fe(CH(3)CN)(2)((R,R)-BPBP)](SbF(6))(2) (Δ-2SbF(6)), which lack the steric bulk introduced by the pinene rings. Cavity-containing complexes Λ-1P and Λ-2P exhibit enhanced activity in comparison with Δ-1P, Δ-2P, Λ-1, Λ-2, and Λ-2SbF(6). The regioselectivity exhibited by catalysts Λ-1P, Λ-2P, Δ-1P, and Δ-2P in the C-H oxidation of simple organic molecules can be predicted on the basis of the innate properties of the distinct C-H groups of the substrate. However, in specific complex organic molecules where oxidation of multiple C-H sites is competitive, the highly elaborate structure of the catalysts allows modulation of C-H regioselectivity between the oxidation of tertiary and secondary C-H groups and also among multiple methylene sites, providing oxidation products in synthetically valuable yields. These selectivities complement those accomplished with structurally simpler oxidants, including non-heme iron catalysts Λ-2 and Λ-2SbF(6).

New Trends in Oxidative Functionalization of Carbon–Hydrogen Bonds: A Review

“…However, in catalyst systems relying on isostructural Fe catalysts, such evidence was gained by EPR spectroscopy taking advantage of the low-spin (S = 1 / 2 ) structure of known oxoiron(V) intermediates [189]. Costas in recent years has carried out many valuable works on functionalization of carbon-hydrogen bond catalyzed by nonheme complexes with polyamino ligands [190][191][192][193]. Additionally, very important works on complexes with polydentate ligands as catalysts have been reported by Nam and colleagues [194].…”

Ionic liquids as reaction media in catalytic oxidations with manganese and iron pyridyl triazacyclononane complexes

“…While, when anions characterized by higher coordinating ability, such as triflate or acetate (Entries 3,6), were present unsatisfactory or absence of catalytic activity was detected. The hydrophobic character of the IL does not appear crucial, in fact, positive results for olefin conversions have been obtained by using hmimBF 4 and bupyNTf 2 (Entries 8,11). Styrene epoxidation reaction appears not to be a viable process in bupyNTf 2 because of the higher acidity of acetic acid in this medium, which caused ring opening of the epoxide product (Entry 11).…”

“…However due to its low solubility in bmimBF 4 , the oxidation was feasible only in bypyNTf 2 with a quantitative conversion of the substrate and an interesting yield of 89% in the corresponding cis-COT oxide (Entries 2,3). This result once more demonstrates that suited IL's can be found for diverse catalytic processes [51].…”

“…Bioinspired iron and manganese coordination complexes with tetradentate nitrogen based ligands have emerged as powerful alkane and alkene oxidation catalysts, and some of them have also found use in asymmetric catalysis [1][2][3][4][5][6][7][8][9][10][11][12][13]. Iron and manganese complexes containing tetradentate ligands based in the triazacyclononane ring, appended with a methylpyridine arm ( -(6-X-pyridyl)methyl]-4,7-dimethyl-1,4,7-triazacyclononane, and M = Fe, and Mn, Fig.…”

Direct Selective Oxidative Functionalization of C–H Bonds with H2O2: Mn-Aminopyridine Complexes Challenge the Dominance of Non-Heme Fe Catalysts

“…First examples of non-heme-Fe-catalyzed oxidations appeared in early 1990s [24,28]; however, the breakthrough was achieved after 2007, when White with co-workers contributed a series of milestone works, presenting the bipyrrolidine-derived non-heme iron catalyst 1 ( Figure 1) and its structural analogs, ensuring reasonably high level of predictability in the selective oxidation of C(sp 3 )-H groups [29][30][31][32][33][34]. In competitive contribution, Costas and co-workers showed that the introduction of additional steric crowd at the pyridine moieties, as well as manipulating with the symmetry of the chiral ligand can divert the oxidation selectivity from 3° C(sp 3 )-H bonds to stronger 2° C(sp 3 )-H bonds, which is critical for the selective oxygenation of complex molecules such as natural products [35][36][37][38]. The mechanism of non-heme iron catalyzed oxidations has been extensively studied experimentally [39]; it has now been accepted that the C-H oxidation proceeds via the classical rebound mechanism [40] (Figure 1), with participation of the elusive oxoperferryl species [41][42][43][44][45][46][47][48][49].…”