TY - JOUR
T1 - Beyond ferryl-mediated hydroxylation
T2 - 40 years of the rebound mechanism and C–H activation
AU - Huang, Xiongyi
AU - Groves, John Taylor
N1 - Publisher Copyright:
© 2016, The Author(s).
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
KW - C–H activation
KW - Iron
KW - Metal oxo
KW - Oxygenase
KW - Radical
KW - Rebound
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U2 - 10.1007/s00775-016-1414-3
DO - 10.1007/s00775-016-1414-3
M3 - Review article
C2 - 27909920
AN - SCOPUS:85000956229
SN - 0949-8257
VL - 22
SP - 185
EP - 207
JO - Journal of Biological Inorganic Chemistry
JF - Journal of Biological Inorganic Chemistry
IS - 2-3
ER -