Catalytic C−H Insertions Using Iron(III) Porphyrin Complexes

Abstract

Fe(III), Cu(II), and Ag(II) porphyrin complexes are active catalysts for benzylic and ring C−H insertions by carbene fragments transferred from methyl diazomalonate, 2. Temperatures above 100 °C are required, and yields greater than 70% have been achieved. C−H insertions with cyclohexane and tetrahydrofuran are catalyzed at a lower temperature of 60 °C with 60% yields when para-substituted methyl 2-phenyldiazoacetates, 15a−d, are used as carbene sources. The rate for Fe(TPP)Cl-catalyzed insertion into the C−H bond of cyclohexane was found to be first-order in the concentration of methyl 2-(pchlorophenyl)diazoacetate, p-Cl-MPDA, indicating that formation of a carbene complex is the ratedetermining step. Competition reactions for cyclohexane insertion with para-substituted methyl 2-phenyldiazoacetates correlated linearly with σ+ Hammett parameters with a ρ value of -1.11 ± 0.05 when Fe(TPP)Cl was used as a catalyst, demonstrating that electron-donating para-substituents on the phenyl group of the methyl 2-aryldiazoacetates enhanced reactivity. These data are consistent with the involvement of an electrophilic iron−carbene complex in the catalytic cycle. A mechanistic model for the iron-mediated C−H insertion reactions is proposed. Disciplines Chemistry CommentsReprinted (adapted) with permission from Organometallics 27 (2008): 637, ABSTRACT: C−H insertion reactions between different substrates and diazo reagents were catalyzed by tetratolylporphyrinato methyliridium (Ir(TTP)CH 3 ). The highest yields were achieved for reactions between the bulky diazo reagent methyl 2-phenyldiazoacetate (MPDA) and substrates containing electron-rich C−H bonds. An intermediate metalloporphyrin complex was identified as a metal−carbene complex, Ir(TTP)(C[Ph]CO 2 CH 3 )(CH 3 ) (4), using 1 H NMR and UV/vis absorption spectroscopy. The presence of 4 was further supported by computationally modeling the absorption spectra with time-dependent DFT (6-31G(d,p)/ SBKJC basis set, PBE0 functional). Kinetic studies for C−H insertion reactions using different substrates showed substantial differences in the rate of MPDA consumption, suggesting that carbene transfer is rate-limiting. Furthermore, primary kinetic isotope effects of 3.7 ± 0.3 and 2.7 ± 0.4 were measured using toluene and cyclohexane, respectively. These data are consistent with a mechanism that involves direct C−H insertion rather than a radical rebound pathway.

Bulk gold catalyzed oxidation reactions of amines and isocyanides and iron porphyrin catalyzed N-H and O-H bond insertion/cyclization reactions of diamines and aminoalcohols

“…Iron porphyrins have been found to catalyze a variety of reactions with diazo reagents, including the cyclopropanation of olefins, 52 olefination of carbonyl compounds, 53 and C-H bond activation of aryl compounds. 54 …”

Catalytic asymmetric C–H insertion reactions of α-diazocarbonyl compounds

“…The choice of catalyst for carbene transformation reactions may also comprise a variety of other transition-metal-based complexes including iron, 95 Figure 17). In addition to representing the first example of enantioselective iridium(III)-catalysed C-H insertion, this report was significant in demonstrating the ability of α-alkyl-α-diazoacetates to undergo efficient intermolecular C-H carbene insertion.…”

Functionalization of Carbon–Hydrogen Bonds Through Transition Metal Carbenoid Insertion

“…This suggested a build up of positive charge at the carbon bearing the hydrogen atom undergoing the activation. Davies [9] and Woo [10] conducted Hammett studies with intermolecular C-H insertion reactions. In both cases, the best correlation was obtained vs. s + , with r values of −1.27 and −1.11, respectively.…”

“…One specific type of activated C-H bond that was not examined above, but seemed as though it might be prone toward facile intermolecular carbenoid insertion, was that of benzylic positions [9,10,83]. Initially, Davies and coworkers examined reactions of substituted ethylbenzenes 78 with methyl para-bromophenyldiazoacetate 79 (Scheme 16) [9].…”

“…However, aromatic ring cyclopropanation is sterically blocked if the aromatic ring is at least 1,4-disubstituted. Isopropyl benzene was functionalized in good yield with an achiral iron porphyrin [83], and similar catalysts were also used to functionalize the methyl group of mesitylene, but with nearly equal amounts of aromatic substitution [10].…”