TY - JOUR
T1 - C−H Insertions by Iron Porphyrin Carbene
T2 - Basic Mechanism and Origin of Substrate Selectivity
AU - Khade, Rahul L.
AU - Zhang, Yong
N1 - Publisher Copyright:
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2017/12/14
Y1 - 2017/12/14
N2 - Recent experimental reports of heme carbene C−H insertions show promising results for sustainable chemistry due to good yield and selectivity, low cost of iron, and low/no toxicity of hemes. But mechanistic details are mostly unknown. Despite structural similarity and isoelectronic nature between heme carbene and the FeIV=O intermediate, our quantum chemical studies with detailed geometric and electronic information for the first time reveal an FeII-based, concerted, hydride-transfer mechanism, which is different from the FeIV-based stepwise hydrogen atom transfer mechanism for C−H functionalization by native heme enzymes. A trend of broad range experimental C−H insertion yields (0–88 %) of five different C−H bonds, including mostly non-functionalized moieties, was well reproduced. Results suggest that the substrate selectivity originates from the hydride formation capability. The predicted kinetic isotope effects were also in excellent agreement with experiment. Useful geometry, charge, and energy parameters well correlated with barriers were reported. These results provide the first theoretical evidence that carbene formation is the overall rate-limiting step, and suggest a key role of the formation of strong electrophilic heme carbene in developing heme-based C−H insertion catalysts and biocatalysts.
AB - Recent experimental reports of heme carbene C−H insertions show promising results for sustainable chemistry due to good yield and selectivity, low cost of iron, and low/no toxicity of hemes. But mechanistic details are mostly unknown. Despite structural similarity and isoelectronic nature between heme carbene and the FeIV=O intermediate, our quantum chemical studies with detailed geometric and electronic information for the first time reveal an FeII-based, concerted, hydride-transfer mechanism, which is different from the FeIV-based stepwise hydrogen atom transfer mechanism for C−H functionalization by native heme enzymes. A trend of broad range experimental C−H insertion yields (0–88 %) of five different C−H bonds, including mostly non-functionalized moieties, was well reproduced. Results suggest that the substrate selectivity originates from the hydride formation capability. The predicted kinetic isotope effects were also in excellent agreement with experiment. Useful geometry, charge, and energy parameters well correlated with barriers were reported. These results provide the first theoretical evidence that carbene formation is the overall rate-limiting step, and suggest a key role of the formation of strong electrophilic heme carbene in developing heme-based C−H insertion catalysts and biocatalysts.
KW - C−H activation
KW - carbenoids
KW - density functional calculations
KW - heme proteins
KW - porphyrinoids
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U2 - 10.1002/chem.201704631
DO - 10.1002/chem.201704631
M3 - Article
C2 - 29071754
AN - SCOPUS:85034076670
SN - 0947-6539
VL - 23
SP - 17654
EP - 17658
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 70
ER -