Angewandte
Communications
Chemie
promising complex against popular photo-HAT catalysts will
allow many valuable contrasts and comparisons to be made in
an increasingly well-studied reaction class. The behavior of
cyclooctane shows that the efficiency of uranyl photocatalysts
can outperform that of traditional near-UV photo-HAT
catalysts, while operating under visible light. However, the
substrate must be chosen judiciously.
In summary, a new catalytic method for fluorination of
Figure 3. The uranyl excited state [UO2]2+* reacts with alkanes primar-
ily through hydrogen atom transfer (HAT) and with arenes through
unproductive exciplex decay.
3
À
certain unactivated C(sp ) H bonds was developed. This
method uses low-energy visible light to drive homolytic
À
cleavage of strong C H bonds by an activated uranyl catalyst
and capitalizes on the reactivity of a putative organic radical.
To the best of our knowledge, this chemistry constitutes the
second catalytic transformation based on the HAT reactivity
of a photo-activated uranyl catalyst. Our hope is that the
research described herein will stimulate future efforts to
expand the considerable potential of abundant, yet under-
utilized uranyl complexes in catalysis.
Acknowledgements
This work was supported by NIGMS R01 GM065483 (E.J.S.),
NSF-GRFP DGE 1148900 (J.G.W.), the NSF-CCI Center for
Figure 4. Reactions containing both cyclooctane and toluene (top) or
cyclopentanone (bottom) behave differently with respect to reagent
conversion. The result with toluene suggests that it is an effective
quencher of the uranyl excited state [UO2]2+*.
À
Selective C H Functionalization (CHE-1205646), and
Princeton University.
À
Keywords: C H activation · fluorination ·
hydrogen atom transfer · photocatalysis · uranium
led to a high yield of fluorocyclooctane (74%, Figure 4) and
trace fluorinated cyclopentanone, suggesting that cyclopenta-
none is at best a weak quencher of the uranyl excited state,
[UO2]2+*. If one imagines a slow, but competitive with HAT,
intramolecular
deactivation
pathway
for
carbonyl
compounds, the improved activity of ethyl isovalerate, long
chain esters, and sclareolide compared to cyclopentanone
could be explained by several factors. These might include,
1) additional activation and thus higher rate of reaction of
a methine proton (ethyl isovalerate), 2) a greater number of
potential reactive sites (longer chain substrates), and
3) structural rigidity separating the reactive site from a func-
tional group with the potential to quench (sclareolide).
Regardless of cause, the limited substrate scope of the
uranyl fluorination, while initially disheartening, offers
a number of benefits. Firstly, the (essentially) complete
inertness of short-chain ketones and relative unreactivity of
other carbonyl compounds contrasts with the TBADT-[8] and
acetophenone-mediated[9] reactions, for which they are
excellent substrates. In the substrate admixing experiments
of Figure 4, the selective activation of cyclooctane (BDE
96 kcalmolÀ1)[32] over toluene (BDE 90 kcalmolÀ1)[33] is
interesting and again diverges greatly from arylketone-[9,34]
and TBADT-catalyzed[35] fluorination methods, wherein
benzylic positions are preferentially activated. This highly
discriminating nature of the uranyl catalyst opens the door for
[1] K. L. Kirk, Org. Process Res. Dev. 2008, 12, 305 – 321.
[2] T. Fujiwara, D. OꢀHagan, J. Fluorine Chem. 2014, 167, 16 – 29.
[3] R. Berger, G. Resnati, P. Metrangolo, E. Weber, J. Hulliger,
Chem. Soc. Rev. 2011, 40, 3496 – 3508.
[4] W. G. Hagmann, J. Med. Chem. 2008, 51, 4359 – 4369.
[5] C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 2015, 54, 3216 –
3221; Angew. Chem. 2015, 127, 3261 – 3267.
[6] E. T. McBee, Ind. Eng. Chem. 1947, 39, 236 – 237.
[7] S. Bloom, J. L. Knippel, T. Lectka, Chem. Sci. 2014, 5, 1175 –
1178.
[8] S. D. Halperin, H. Fan, S. Chang, R. E. Martin, R. Britton,
Angew. Chem. Int. Ed. 2014, 53, 4690 – 4693; Angew. Chem.
2014, 126, 4778 – 4781.
[9] J.-B. Xia, C. Zhu, C. Chen, Chem. Commun. 2014, 50, 11701 –
11704.
[10] C. W. Kee, K. F. Chin, M. W. Wong, C.-H. Tan, Chem. Commun.
2014, 50, 8211 – 8214.
[11] R. D. Chambers, M. Parsons, G. Sanford, R. Bowyden, Chem.
Commun. 2000, 959 – 960.
[12] W. Liu, M.-J. Huang, R. J. Nielsen, W. Goddard, J. T. Groves,
Science 2012, 337, 1322 – 1325.
[13] S. Bloom, C. R. Pitts, D. C. Miller, N. Haselton, M. G. Holl, E.
Urheim, T. Lectka, Angew. Chem. Int. Ed. 2012, 51, 10580 –
10583; Angew. Chem. 2012, 124, 10732 – 10735.
[14] M. Rueda-Becerril, C. C. Sazepin, J. C. T. Leung, T. Okbinoglu,
P. Kennepohl, J.-F. Paquin, G. M. Sammis, J. Am. Chem. Soc.
2012, 134, 4026 – 4029.
À
selective fluorination of electronically activated C H bonds
in the presence of bonds that would otherwise be a liability
under previously reported conditions.
A second upside is the enrichment of the sparse literature
describing uranyl photocatalysis. The benchmarking of this
[15] C. K. Prier, D. A. Rankic, D. W. C. MacMillan, Chem. Rev. 2013,
113, 5322 – 5363.
4
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
These are not the final page numbers!