Fluorochemicals are a widely distributed class of compounds and have been utilized across a wide range of industries for decades. Given the environmental toxicity and adverse health threats of some fluorochemicals, the development of new methods for their decomposition is significant to public health. However, the carbon–fluorine (C–F) bond is among the most chemically robust bonds; consequently, the degradation of fluorinated hydrocarbons is exceptionally difficult. Here, metalloenzymes that catalyze the cleavage of this chemically challenging bond are reviewed. These enzymes include histidine-ligated heme-dependent dehaloperoxidase and tyrosine hydroxylase, thiolate-ligated heme-dependent cytochrome P450, and four nonheme oxygenases, namely, tetrahydrobiopterin-dependent aromatic amino acid hydroxylase, 2-oxoglutarate-dependent hydroxylase, Rieske dioxygenase, and thiol dioxygenase. While much of the literature regarding the aforementioned enzymes highlights their ability to catalyze C–H bond activation and functionalization, in many cases, the C–F bond cleavage has been shown to occur on fluorinated substrates. A copper-dependent laccase-mediated system representing an unnatural radical defluorination approach is also described. Detailed discussions on the structure–function relationships and catalytic mechanisms provide insights into biocatalytic defluorination, which may inspire drug design considerations and environmental remediation of halogenated contaminants.
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Photocatalytic C–F alkylation; facile access to multifluorinated arenes
C–F functionalizations that provide C–C bonds are challenging synthetic transformations, due in part to the large C–F bond strength, short bond length, nonpolarizable nature, the production of fluoride, and the regioselectivity-in the case of multifluorinated substrates. However, commercially available highly fluorinated arenes possess great synthetic potential because they already possess the C–F bonds in the desired locations that would be difficult to selectively fluorinate. In order to take advantage of this potential, selective C–F functionalizations must be developed. Herein, we disclose conditions for the photocatalytic reductive alkylation of highly fluorinated arenes with ubiquitous and unactivated alkenes. The mild reaction conditions provide for a broad functional group scope, and the reaction is remarkably efficient using just 0.25 mol% catalyst. Finally, we demonstrate the utility of the strategy by converting highly fluorinated arenes to elaborate (hetero)arenes that contain 2–5 C aryl –F bonds via synergistic use of photocatalysis and S N Ar chemistry.
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- Award ID(s):
- 1453891
- NSF-PAR ID:
- 10247705
- Date Published:
- Journal Name:
- Chemical Science
- Volume:
- 6
- Issue:
- 12
- ISSN:
- 2041-6520
- Page Range / eLocation ID:
- 7206 to 7212
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Benzene fluorination increases chemoselectivities for Dewar‐benzenes via 4π‐disrotatory electrocyclization. However, the origin of the chemo‐ and regioselectivities of fluorobenzenes remains unexplained because of the experimental limitations in resolving the excited‐state structures on ultrafast timescales. The computational cost of multiconfigurational nonadiabatic molecular dynamics simulations is also currently cost‐prohibitive. We now provide high‐fidelity structural information and reaction outcome predictions with machine‐learning‐accelerated photodynamics simulations of a series of fluorobenzenes, C6F6‐nHn, n=0–3, to study their S1→S0decay in 4 ns. We trained neural networks with XMS‐CASPT2(6,7)/aug‐cc‐pVDZ calculations, which reproduced the S1absorption features with mean absolute errors of 0.04 eV (<2 nm). The predicted nonradiative decay constants for C6F4H2, C6F6, C6F3H3, and C6F5H are 116, 60, 28, and 12 ps, respectively, in broad qualitative agreement with the experiments. Our calculations show that a pseudo Jahn–Teller distortion of fluorinated benzenes leads to an S1local‐minimum region that extends the excited‐state lifetimes of fluorobenzenes. The pseudo Jahn–Teller distortions reduce when fluorination decreases. Our analysis of the S1dynamics shows that the pseudo‐Jahn–Teller distortions promote an excited‐state
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/C5SC03013G
