skip to main content

Title: 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.  more » « less
Award ID(s):
Author(s) / Creator(s):
; ;
Date Published:
Journal Name:
Chemical Science
Page Range / eLocation ID:
7206 to 7212
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. 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. 
    more » « less
  2. null (Ed.)
    The exceptionally π-basic metal fragments {MoTp(NO)(DMAP)} and {WTp(NO)(PMe3)} (Tp = tris(pyrazolyl)borate; DMAP = 4-(N,N-dimethylamino)pyridine) form thermally stable η2-coordinated complexes with a variety of electron-deficient arenes. The tolerance of substituted arenes with fluorine-containing electron withdrawing groups (EWG; −F, −CF3, −SF5) is examined for both the molybdenum and tungsten systems. When the EWG contains a π bond (nitriles, aldehydes, ketones, ester), η2 coordination occurs predominantly on the nonaromatic functional group. However, complexation of the tungsten complex with trimethyl orthobenzoate (PhC(OMe)3) followed by hydrolysis allows access to an η2-coordinated arene with an ester substituent. In general, the tungsten system tolerates sulfur-based withdrawing groups well (e.g., PhSO2Ph, MeSO2Ph), and the integration of multiple electron-withdrawing groups on a benzene ring further enhances the π-back-bonding interaction between the metal and aromatic ligand. While the molybdenum system did not form stable η2-arene complexes with the sulfones or ortho esters, it was capable of forming rare examples of stable η2-coordinated arene complexes with a range of fluorinated benzenes (e.g., fluorobenzene, difluorobenzenes). In contrast to what has been observed for the tungsten system, these complexes formed without interference of C–H or C–F insertion. 
    more » « less
  3. 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‐statecis‐transisomerization of a πC‐Cbond. We characterized the surface hopping points from our NAMD simulations and identified instantaneous nuclear momentum as a factor that promotes the electrocyclizations.

    more » « less
  4. [RuCp*(1,3,5-R 3 C 6 H 3 )] 2 {Cp* = η 5 -pentamethylcyclopentadienyl, R = Me, Et} have previously been found to be moderately air stable, yet highly reducing, with estimated D + /0.5D 2 (where D 2 and D + represent the dimer and the corresponding monomeric cation, respectively) redox potentials of ca. −2.0 V vs. FeCp 2 +/0 . These properties have led to their use as n-dopants for organic semiconductors. Use of arenes substituted with π-electron donors is anticipated to lead to even more strongly reducing dimers. [RuCp*(1-(Me 2 N)-3,5-Me 2 C 6 H 3 )] + PF 6 − and [RuCp*(1,4-(Me 2 N) 2 C 6 H 4 )] + PF 6 − have been synthesized and electrochemically and crystallographically characterized; both exhibit D + /D potentials slightly more cathodic than [RuCp*(1,3,5-R 3 C 6 H 3 )] + . Reduction of [RuCp*(1,4-(Me 2 N) 2 C 6 H 4 )] + PF 6 − using silica-supported sodium–potassium alloy leads to a mixture of isomers of [RuCp*(1,4-(Me 2 N) 2 C 6 H 4 )] 2 , two of which have been crystallographically characterized. One of these isomers has a similar molecular structure to [RuCp*(1,3,5-Et 3 C 6 H 3 )] 2 ; the central C–C bond is exo , exo , i.e. , on the opposite face of both six-membered rings from the metals. A D + /0.5D 2 potential of −2.4 V is estimated for this exo , exo dimer, more reducing than that of [RuCp*(1,3,5-R 3 C 6 H 3 )] 2 (−2.0 V). This isomer reacts much more rapidly with both air and electron acceptors than [RuCp*(1,3,5-R 3 C 6 H 3 )] 2 due to a much more cathodic D 2 ˙ + /D 2 potential. The other isomer to be crystallographically characterized, along with a third isomer, are both dimerized in an exo , endo fashion, representing the first examples of such dimers. Density functional theory calculations and reactivity studies indicate that the central bonds of these two isomers are weaker than those of the exo , exo isomer, or of [RuCp*(1,3,5-R 3 C 6 H 3 )] 2 , leading to estimated D + /0.5D 2 potentials of −2.5 and −2.6 V vs. FeCp 2 +/0 . At the same time the D 2 ˙ + /D 2 potentials for the exo , endo dimers are anodically shifted relative to those of [RuCp*(1,3,5-R 3 C 6 H 3 )] 2 , resulting in much greater air stability than for the exo , exo isomer. 
    more » « less
  5. Synthetic methods that utilise iron to facilitate C–H bond activation to yield new C–C and C–heteroatom bonds continue to attract significant interest. However, the development of these systems is still hampered by a limited molecular-level understanding of the key iron intermediates and reaction pathways that enable selective product formation. While recent studies have established the mechanism for iron-catalysed C–H arylation from aryl-nucleophiles, the underlying mechanistic pathway of iron-catalysed C–H activation/functionalisation systems which utilise electrophiles to establish C–C and C–heteroatom bonds has not been determined. The present study focuses on an iron-catalysed C–H allylation system, which utilises allyl chlorides as electrophiles to establish a C–allyl bond. Freeze-trapped inorganic spectroscopic methods ( 57 Fe Mössbauer, EPR, and MCD) are combined with correlated reaction studies and kinetic analyses to reveal a unique and rapid reaction pathway by which the allyl electrophile reacts with a C–H activated iron intermediate. Supporting computational analysis defines this novel reaction coordinate as an inner-sphere radical process which features a partial iron–bisphosphine dissociation. Highlighting the role of the bisphosphine in this reaction pathway, a complementary study performed on the reaction of allyl electrophile with an analogous C–H activated intermediate bearing a more rigid bisphosphine ligand exhibits stifled yield and selectivity towards allylated product. An additional spectroscopic analysis of an iron-catalysed C–H amination system, which incorporates N -chloromorpholine as the C–N bond-forming electrophile, reveals a rapid reaction of electrophile with an analogous C–H activated iron intermediate consistent with the inner-sphere radical process defined for the C–H allylation system, demonstrating the prevalence of this novel reaction coordinate in this sub-class of iron-catalysed C–H functionalisation systems. Overall, these results provide a critical mechanistic foundation for the rational design and development of improved systems that are efficient, selective, and useful across a broad range of C–H functionalisations. 
    more » « less