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Title: Beyond ferryl-mediated hydroxylation: 40 years of the rebound mechanism and C–H activation

Since our initial report in 1976, the oxygen rebound mechanism has become the consensus mechanistic feature for an expanding variety of enzymatic C–H functionalization reactions and small molecule biomimetic catalysts. For both the biotransformations and models, an initial hydrogen atom abstraction from the substrate (R–H) by high-valent iron-oxo species (Fe n=O) generates a substrate radical and a reduced iron hydroxide, [Fe n-1–OH ·R]. This caged radical pair then evolves on a complicated energy landscape through a number of reaction pathways, such as oxygen rebound to form R–OH, rebound to a non-oxygen atom affording R–X, electron transfer of the incipient radical to yield a carbocation, R +, desaturation to form olefins, and radical cage escape. These various flavors of the rebound process, often in competition with each other, give rise to the wide range of C–H functionalization reactions performed by iron-containing oxygenases. In this review, we first recount the history of radical rebound mechanisms, their general features, and key intermediates involved. We will discuss in detail the factors that affect the behavior of the initial caged radical pair and the lifetimes of the incipient substrate radicals. Several representative examples of enzymatic C–H transformations are selected to illustrate how the behaviors ofmore » the radical pair [Fe n-1–OH ·R] determine the eventual reaction outcome. Finally, we discuss the powerful potential of “radical rebound” processes as a general paradigm for developing novel C–H functionalization reactions with synthetic, biomimetic catalysts. We envision that new chemistry will continue to arise by bridging enzymatic “radical rebound” with synthetic organic chemistry.« less
Authors:
 [1] ;  [1]
  1. Princeton Univ., NJ (United States)
Publication Date:
Grant/Contract Number:
SC0001298
Type:
Accepted Manuscript
Journal Name:
JBIC Journal of Biological Inorganic Chemistry
Additional Journal Information:
Journal Volume: 22; Journal Issue: 2-3; Related Information: CCHF partners with University of Virginia (lead); Brigham Young University; California Institute of Technology; Colorado School of Mines; University of Maryland; University of North Carolina, Chapel Hill; University of North Texas; Princeton University; The Scripps Research Institute; Yale University; Journal ID: ISSN 0949-8257
Publisher:
Springer
Research Org:
Energy Frontier Research Centers (EFRC) (United States). Center for Catalytic Hydrocarbon Functionalization (CCHF)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
OSTI Identifier:
1397173

Huang, Xiongyi, and Groves, John T. Beyond ferryl-mediated hydroxylation: 40 years of the rebound mechanism and C–H activation. United States: N. p., Web. doi:10.1007/s00775-016-1414-3.
Huang, Xiongyi, & Groves, John T. Beyond ferryl-mediated hydroxylation: 40 years of the rebound mechanism and C–H activation. United States. doi:10.1007/s00775-016-1414-3.
Huang, Xiongyi, and Groves, John T. 2016. "Beyond ferryl-mediated hydroxylation: 40 years of the rebound mechanism and C–H activation". United States. doi:10.1007/s00775-016-1414-3. https://www.osti.gov/servlets/purl/1397173.
@article{osti_1397173,
title = {Beyond ferryl-mediated hydroxylation: 40 years of the rebound mechanism and C–H activation},
author = {Huang, Xiongyi and Groves, John T.},
abstractNote = {Since our initial report in 1976, the oxygen rebound mechanism has become the consensus mechanistic feature for an expanding variety of enzymatic C–H functionalization reactions and small molecule biomimetic catalysts. For both the biotransformations and models, an initial hydrogen atom abstraction from the substrate (R–H) by high-valent iron-oxo species (Fen=O) generates a substrate radical and a reduced iron hydroxide, [Fen-1–OH ·R]. This caged radical pair then evolves on a complicated energy landscape through a number of reaction pathways, such as oxygen rebound to form R–OH, rebound to a non-oxygen atom affording R–X, electron transfer of the incipient radical to yield a carbocation, R+, desaturation to form olefins, and radical cage escape. These various flavors of the rebound process, often in competition with each other, give rise to the wide range of C–H functionalization reactions performed by iron-containing oxygenases. In this review, we first recount the history of radical rebound mechanisms, their general features, and key intermediates involved. We will discuss in detail the factors that affect the behavior of the initial caged radical pair and the lifetimes of the incipient substrate radicals. Several representative examples of enzymatic C–H transformations are selected to illustrate how the behaviors of the radical pair [Fen-1–OH ·R] determine the eventual reaction outcome. Finally, we discuss the powerful potential of “radical rebound” processes as a general paradigm for developing novel C–H functionalization reactions with synthetic, biomimetic catalysts. We envision that new chemistry will continue to arise by bridging enzymatic “radical rebound” with synthetic organic chemistry.},
doi = {10.1007/s00775-016-1414-3},
journal = {JBIC Journal of Biological Inorganic Chemistry},
number = 2-3,
volume = 22,
place = {United States},
year = {2016},
month = {12}
}

Works referenced in this record:

Organometallic alkane CH activation
journal, November 2004

C-H bond activation in heme proteins: the role of thiolate ligation in cytochrome P450
journal, February 2009

The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies
journal, March 2003
  • Groves, J. T.
  • Proceedings of the National Academy of Sciences, Vol. 100, Issue 7, p. 3569-3574
  • DOI: 10.1073/pnas.0830019100