Photocatalytic Dehydroxymethylative Arylation by Synergistic Cerium and Nickel Catalysis

Article abstract of DOI:10.1021/jacs.1c00618

Under mild reaction conditions with inexpensive cerium and nickel catalysts, easily accessible free alcohols can now be utilized as operationally simple and robust carbon pronucleophiles in selective C(sp3)-C(sp2) cross-couplings. Facilitated by automated high-throughput experimentation, sterically encumbered benzoate ligands have been identified for robust cerium complexes, enabling the synergistic cooperation of cerium catalysis in the emerging metallaphotoredox catalysis. A broad range of free alcohols and aromatic halides can be facilely employed in this transformation, representing a new paradigm for the C(sp3)-C(sp2) bond construction between free alcohols and aryl halides with the extrusion of formaldehyde. Moreover, mechanistic investigations have been conducted, leading to the identification of a tribenzoate cerium(III) complex as a viable intermediate.

Full text of DOI:10.1021/jacs.1c00618

pubs.acs.org/JACS
Communication
Photocatalytic Dehydroxymethylative Arylation by Synergistic
Cerium and Nickel Catalysis
Yuegang Chen, Xin Wang, Xu He, Qing An, and Zhiwei Zuo*
Cite This: J. Am. Chem. Soc. 2021, 143, 4896−4902
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: Under mild reaction conditions with inexpensive cerium and nickel catalysts, easily accessible free alcohols can now
be utilized as operationally simple and robust carbon pronucleophiles in selective C(sp3)−C(sp2) cross-couplings. Facilitated by
automated high-throughput experimentation, sterically encumbered benzoate ligands have been identified for robust cerium
complexes, enabling the synergistic cooperation of cerium catalysis in the emerging metallaphotoredox catalysis. A broad range of
free alcohols and aromatic halides can be facilely employed in this transformation, representing a new paradigm for the C(sp3)−
C(sp2) bond construction between free alcohols and aryl halides with the extrusion of formaldehyde. Moreover, mechanistic
investigations have been conducted, leading to the identification of a tribenzoate cerium(III) complex as a viable intermediate.
he development of efficient photocatalysts is central to
the utilization of visible-light energy for sustainable
T
synthesis, yet the exploitation of abundant and economical
metals instead of Ru and Ir remains a prominent challenge.1 In
particular, earth-abundant cerium compounds have emerged as
promising lanthanide photocatalysts, owing to their intriguing
redox capacities to engage single-electron transfer (SET)
activations upon metal-centered charge-transfer excitation or
ligand-to-metal charge-transfer (LMCT) excitation.2 The
recent exploitation of cerium bis(guanidinate) complexes,3
cerium chloride,4 and the oxo-bridged cerium cluster5 as
practical photocatalysts has enabled diverse radical-mediated
transformations with reactive radical acceptors, such as
dehalogenative arylation and borylation, decarboxylative
amination and oxidation, C−C bond cleavage of alkanols,
and C−H functionalization of alkane feedstocks. Nevertheless,
ligand design and modification, one main strategy to tune
photoexcitation and redox properties, has remained relatively
underexploited for cerium,6 in which significant challenges
have been imposed by ligand redistribution, unpredictable
coordination geometry, and variable coordination numbers.7
Herein we describe the synergistic combination of cerium−
LMCT catalysis and nickel catalysis for an unprecedented
dehydroxymethylative cross-coupling, enabled by robust and
sterically demanding benzoate ligands (Figure 1).
Figure 1. Synergistic cerium and nickel catalysis for the dehydrox-
ymethylative arylation of free alcohols.
elusive.10 Encouraged by the generality and selectivity
demonstrated in our recent study of cerium-catalyzed C−C
bond cleavage and alkylations of alkanols,4g we posited that a
practical dehydroxymethylative arylation could be achieved
through the synergistic implementation of metallaphotoredox
C−C bond cleavage has been demonstrated as a versatile but
fickle platform to develop innovative transformations of
feedstock chemicals to streamline the synthesis of complex
molecules.8 Direct dehydroxymethylation of alcohols, in which
the α-C(sp3)−C(sp3) bond is selectively cleaved, remains a
challenging task due to the lack of thermodynamic driving
forces; nevertheless, this reaction provides intriguing oppor-
tunities to harness abundant and readily accessible alcohol
feedstocks for rapid molecular complexity constructions.9 The
implementation of this reactivity mode for transition-metal-
catalyzed cross-coupling, avoiding the discrete prefunctional-
ization of premetalation steps, however, currently remains
Received: January 18, 2021
Published: March 23, 2021
https://doi.org/10.1021/jacs.1c00618
J. Am. Chem. Soc. 2021, 143, 4896−4902
© 2021 American Chemical Society
4896

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
catalysis.11 In our design, cerium−LMCT followed by β-
scission processes would convert alcohols into nucleophilic
alkyl radicals, which could be readily intercepted by a nickel
cross-coupling cycle, establishing a new paradigm for the
C(sp3)−C(sp2) bond construction between free alcohols and
aryl halides with the extrusion of formaldehyde.
We initiated the investigation of the proposed synergistic
catalytic system using N-Boc-prolinol and 4-bromobiphenyl as
template substrates under the irradiation of LED light (center
wavelength, 400 nm; light intensity, 0.30 W/cm2) (Figure 2).
experimentation platform, we were able to evaluate a large
collection of ligands for cerium trichloride, including various
mono-, bi-, tri-, and tetradentate ligands. (Over 190 ligands
were screened; see the Supporting Information for details.)
The rapid, automated evaluation identified benzoate ligands as
effective for enabling the desired dehydroxymethylative
arylation, which were subsequently carried into a second
round of optimization. Interestingly, several previously
reported ligands for cerium catalysis, such as multidentate-
amine-type ligands, were found to be inactive in this
photocatalytic system. Under an operationally simple labo-
ratory setup with enhanced light intensity of 0.51 W/cm2, a
cross-examination of the seven benzoate ligands for cerium
with well-established bipyridine-type ligands for nickel then
revealed the optimal catalyst combination, cerium trichloride
and benzoate L4, with nickel chloride and L10. Notably, the
ortho substitution of the benzoates could affect the efficiency
dramatically, as electron-donating groups with some degree of
steric hindrance exhibit a more positive effect, with isopropyl
groups demonstrating the best efficiency. (See Table S1.)
Further improvement of the catalytic efficiency was observed
when the preformed nickel complex Ni(dMebpy)(H2O)4Cl2
was used instead of the separate addition of the nickel salt and
L10.12 Under the optimal conditions, the desired arylation
product 3 could be obtained in 93% yield, with no α-C−H
arylation or C−O cross-coupling products observed, demon-
strating high levels of chemoselectivity. Moreover, control
experiments revealed that cerium catalyst, nickel catalyst, DPA,
and light are all essential for the desired photoactivity. (See
Table S2.)
With the optimal conditions in hand, we then examined the
generality of this synergistic catalytic system. As demonstrated
in Scheme 1, a broad range of primary alcohols could be
utilized as operationally simple carbon pronucleophiles in the
dehydroxymethylative cross-couplings with 4-bromobiphenyl
under mild reaction conditions, demonstrating an unconven-
tional strategy directly utilizing readily accessible free alcohols
as robust coupling reagents in C(sp3)−C(sp2) constructions.
Importantly, the cleavage of the α-C(sp3)−C(sp3) bond
mediated by the β-scission of alkoxy radicals was universally
achieved with a high level of selectivity, as activated C(sp3)−H
bonds or alkenes were left unscathed, despite their tendencies
to react with alkoxy radicals via hydrogen atom transfer or
addition processes. Commonly occurring functional groups
such as aromatic halides, heteroarenes, alkenes, alkyne, ethers,
and amides can be well-tolerated. Primary alcohols with β-
substitutions can be readily converted into stabilized benzylic-
type radicals by a cerium catalyst to forge a new C−C bond,
and the reaction efficiency was found in correlation with the
electronic and steric properties of the resultant radicals.
Alcohols equipped with electron-rich arenes that would render
more nucleophilic carbon-centered radicals tend to provide
enhanced efficiency (products 5, 14−17), whereas electron-
withdrawing functionalities including nitrile (6), trifluorometh-
yl (7), and ester (8) groups lead to slightly declined yields.
This cross-coupling arylation was sensitive to the steric
hindrance of the alcohol, as the presence of ortho substitutions
of the resultant benzylic radicals such as methyl and chloride
groups has a detrimental effect on the catalytic efficiency and
requires the use of a higher loading of nickel catalyst (products
11−13). Importantly, a variety of homoallylic alcohols can be
selectively activated and utilized as robust allylic nucleophiles
in C(sp3)−C(sp2) cross-couplings (products 18−20). No
Figure 2. Reaction development. Automated high-throughput
experimentation and subsequent cross-examination were carried out
to identify the optimal catalyst combination. See the Supporting
Information for details.
Our initial attempts failed to provide any dehydroxymethyla-
tive arylation product, even with 9,10-diphenylanthracene
(DPA) added as an electron-shuttle; nevertheless, the
detection of biphenyl and 4-chlorobiphenyl confirmed that
the nickel cycle driven by the catalyst composition of NiCl2·
glyme and 2,2′-bipyridine was functional under this condition.
The indication of the cerium−LMCT pathway being inhibited,
possibly by bipyridine, promoted us to search for suitable
cerium photocatalysts to operate synergistically with nickel
catalysis. Distinct from traditional approaches of photoredox
catalysis where iridium/ruthenium photocatalysts need to be
synthesized and purified before evaluation, the LMCT catalysis
mode can harness the in situ formed cerium alkoxide
complexes for direct photoactivation with additional ligands,
providing an advantageous opportunity to conduct rapid
evaluations of ligands for the optimal cerium photocatalyst.
With the assistance of an automated high-throughput
4897
https://doi.org/10.1021/jacs.1c00618
J. Am. Chem. Soc. 2021, 143, 4896−4902

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
a
Scheme 1. Dehydroxymethylative Arylation Scope of Alcohols
a
General reaction conditions: alcohol substrate (0.4 mmol), 4-bromo-1,1′-biphenyl (0.2 mmol), Ni(dMebpy)(H2O)4Cl2 (0.002 mmol), DPA
(0.002 mmol,), L4 (0.07 mmol), CeCl3 (0.02 mmol), Na3PO4 (0.6 mmol), CH3CN (2 mL) and DMSO (0.25 mL), blue LEDs. All yields are
b
isolated yields. Reaction performed with Ni(dMebpy)(H2O)4Cl2 (0.01 mmol).
isomerization of the trisubstituted double bond in product 19
was observed. Moreover, homopropargylic alcohol can be
employed in dehydroxymethylative arylation, albeit with
moderate efficiency, even at an increased loading of nickel
catalyst (21). A variety of primary alcohols with oxygen or
nitrogen functionalities can be accommodated, delivering the
corresponding arylation products (22−26). Primary hydroxyls
appended to the tetrahydroisoquinoline moieties proved to be
efficient functional handles, enabling the direct coupling of
tetrahydroisoquinoline to the aryl bromide.
We were pleased to find that a variety of aromatic bromides
can be accommodated in the dehydroxymethylative arylation.
As shown in Scheme 2, both electron-withdrawing groups
(30−37) and electron-donating groups (38−43) on the aryl
4898
https://doi.org/10.1021/jacs.1c00618
J. Am. Chem. Soc. 2021, 143, 4896−4902

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
Scheme 2. Dehydroxymethylative Arylation Scope of Aryl Halides
Figure 3. Mechanistic studies. (A) Molecular structure of 56 with 30% probability ellipsoids. (B) Evaluation of the catalytic efficiency of the cerium
complex. (C) Stern−Volmer plot based on the steady-state emission experiment. (D) Stern−Volmer plot based on the time-resolved emission
experiment. See the Supporting Information for a detailed description. (E) Proposed catalytic cycle.
4899
https://doi.org/10.1021/jacs.1c00618
J. Am. Chem. Soc. 2021, 143, 4896−4902

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
ring could be incorporated, with trivial differences in catalytic
efficiencies. Furthermore, aryl bromides installed on hetero-
cycles such as indole (48), furan (49), thiophene (50), and
pyridines (51−54) could also be employed as effective
coupling partners. A broad range of functionalities could be
well-tolerated, including halogen atoms (30, 31, 34−37) and
silane (41), ether (33, 38, 47, 53), and ketal groups (43).
Interestingly, the boronic ester functional handle in 44 was
kept intact during this synergistic cross-coupling. Moreover, β-
bromostyrene could be employed for dehydroxymethylative
vinylation under the same set of reaction conditions, although
alkene isomerization was observed in the products.
Encouraged by the generality of this dehydroxymethylative
cross-coupling, we next carried out mechanistic investigations
to elucidate the enabling effect of the benzoates in promoting
cerium/nickel synergistic catalysis. Control experiments have
demonstrated the critical role of benzoate salts. During
optimization, a 3.5:1 benzoate/cerium loading was found to
be optimal, and increased loadings of benzoate would shut
down the dehydroxymethylative arylation. Moreover, the ortho
substitution effect revealed in the optimization study clearly
precludes the benzoate being a mild or soluble base. We were
intrigued by the fact that aromatic carboxylic acids were
previously demonstrated to be viable LMCT substrates and
converted into lactones in the oxidative decarboxylation
developed by the Mashima group.5 Although in their seminal
report, cerium(IV) tert-butoxide was employed as a precatalyst
and an oxo-cerium(IV) cluster was demonstrated as the active
intermediate, this promoted us to investigate whether the
benzoate was consumed in this dehydroxymethylation
reaction. Even after 36 h of irradiation under our conditions,
benzoic acid derived from L4 could be almost completely
recovered (93%) after acidification of the reaction mixture, and
no corresponding lactone could be detected using gas
chromatography−mass spectrometry (GC−MS). (See Figure
S8.)
different patterns of photoactivity, further demonstrating the
intriguing potential and underexploited properties of cerium
catalysis. Importantly, both steady-state and time-resolved
emission quenching experiments revealed the linear photo-
luminescence quenching of the cocatalyst DPA by cerium(III)
complexes.14 As shown in the Stern−Volmer plots, CeL3
alkoxide complexes exhibit higher quenching efficiency
compared with CeL3 complexes at the same concentration,
which indicates a favorable SET between photoexcited DPA
(E* = 1.19 V vs SCE in DMSO) and CeL3 alkoxide for the in
situ generation of Ce(IV)L3(OR) complexes.
In light of these experiments, a synergistic catalytic cycle was
proposed. The coordination of free alcohol with a cerium
benzoate complex followed by photoinduced electron transfer
with DPA generates a photoactive Ce(IV) alkoxide species.
Under LED irradiation, one electron of the higher lying
alkoxide ligand orbital will be promoted to the empty 4f orbital
of cerium, resulting in the homolysis of the Ce−O bond. The
bond homolysis leads to the generation of Ce(III) benzoate
and alkoxy radicals, which would undergo β-scission to form
alkyl radicals. Meanwhile, in the nickel catalytic cycle, low-
valent Ni complexes undergo oxidative addition to generate
Ni(II) aryl complexes. The radical interception with the Ni(II)
aryl complex forms a Ni(III) species that undergoes rapid
reductive elimination to deliver the desired dehydroxymethy-
lative arylation product. The SET events enabled and
coordinated by the DPA cycle, including the reduction of
Ni(I) by a radical anion of DPA and the oxidation of Ce(III)
by excited DPA, have furnished cerium and nickel catalytic
cycles and, more importantly, have established a synergy
between radical generation and conversion.
In summary, the photocatalytic dehydroxymethylative
arylation of free alcohols with aryl halides has been achieved
under mild and practical conditions. Enabled by the synergistic
utilization of cerium and nickel catalysts, the α-C(sp3)−C(sp3)
bond of free alcohols can be selectively cleaved and harnessed
as an unconventional synthon in cross-couplings. Sterically
encumbered benzoate ligands have enabled the incorporation
of cerium catalysts in metallaphotoredox catalysis, providing
intriguing opportunities for the exploitation of abundant
cerium catalysts in sustainable synthesis.
The crystallizations of cerium trichloride with benzoate
ligand L7 resulted in a crystallized compound 56 (Figure 3).
X-ray analysis of 56 revealed that three benzoate ligands were
ligated to the cerium center in the κ2 chelating mode with the
Ce−O bond length ranging from 2.501 to 2.613 Å. Three
solvent molecules of DMSO were also found ligated to the
cerium(III) center. The steric shielding around the cerium
center caused by ortho-substitution groups of the benzoates
probably helped to prevent the formation of dimeric or
polymeric structures that typically prevail in lanthanide
carboxylate complexes,13 rendering multiple open coordination
sites for the in situ ligation of alkoxide. In cyclic voltammogram
measurements, complex 56 showed an irreversible redox wave
in CH3CN/DMSO solution (Ep/2 = 0.46 V vs SCE). Because
of the difficulties in isolating Ce(IV) compounds,7d we were
only able to conduct 1H NMR spectroscopic analysis on the in
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.1c00618.
■
sı
Experimental procedures and compound characteriza-
tion data (PDF)
Accession Codes
CCDC 2056187 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
1
situ formed Ce(IV) carboxylate complexes. (The H NMR
spectrum reveals an approximate carboxylate/Ce ratio of 3:1;
see Figure S11.)
Under the standard reaction conditions, cerium complex 56
demonstrated identical catalytic efficiency compared to the
addition of cerium trichloride with L7. This finding together
with the optimal 3.5:1 ligand/cerium loading that we identified
during the optimization lends support for the in situ formation
of CeL3 alkoxide complexes. The distinct coordination pattern
we observed, in comparison with the oxo-cerium cluster
discovered by the Mashima group, would have resulted in
AUTHOR INFORMATION
Corresponding Author
■
Zhiwei Zuo − State Key Laboratory of Organometallic
Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, China; orcid.org/
0000-0002-3361-3220; Email: zuozhw@sioc.ac.cn
4900
https://doi.org/10.1021/jacs.1c00618
J. Am. Chem. Soc. 2021, 143, 4896−4902

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
with Alkenes through Dual Photoexcitation. J. Am. Chem. Soc. 2018,
140, 13580−13585. (f) Hu, A.; Guo, J.-J.; Pan, H.; Zuo, Z. Selective
functionalization of methane, ethane, and higher alkanes by cerium
photocatalysis. Science 2018, 361, 668−672. (g) Zhang, K.; Chang, L.;
An, Q.; Wang, X.; Zuo, Z. Dehydroxymethylation of Alcohols Enabled
by Cerium Photocatalysis. J. Am. Chem. Soc. 2019, 141, 10556−
10564. (h) Yatham, V. R.; Bellotti, P.; König, B. Decarboxylative
hydrazination of unactivated carboxylic acids by cerium photo-
catalysis. Chem. Commun. 2019, 55, 3489−3492. (i) An, Q.; Wang, Z.;
Chen, Y.; Wang, X.; Zhang, K.; Pan, H.; Liu, W.; Zuo, Z. Cerium-
Catalyzed C−H Functionalizations of Alkanes Utilizing Alcohols as
Hydrogen Atom Transfer Agents. J. Am. Chem. Soc. 2020, 142, 6216−
6226. (j) Chen, Y.; Du, J.; Zuo, Z. Selective C-C Bond Scission of
Ketones via Visible-Light-Mediated Cerium Catalysis. Chem. 2020, 6,
266−279. (k) Lai, X. L.; Shu, X. M.; Song, J.; Xu, H. C.
Electrophotocatalytic Decarboxylative C−H Functionalization of
Heteroarenes. Angew. Chem., Int. Ed. 2020, 59, 10626−10632.
(5) Shirase, S.; Tamaki, S.; Shinohara, K.; Hirosawa, K.; Tsurugi, H.;
Satoh, T.; Mashima, K. Cerium(IV) Carboxylate Photocatalyst for
Catalytic Radical Formation from Carboxylic Acids: Decarboxylative
Oxygenation of Aliphatic Carboxylic Acids and Lactonization of
Aromatic Carboxylic Acids. J. Am. Chem. Soc. 2020, 142, 5668−5675.
(6) Qiao, Y.; Cheisson, T.; Manor, B. C.; Carroll, P. J.; Schelter, E. J.
A strategy to improve the performance of cerium(iii) photocatalysts.
Chem. Commun. 2019, 55, 4067−4070.
(7) (a) Piro, N. A.; Robinson, J. R.; Walsh, P. J.; Schelter, E. J. The
electrochemical behavior of cerium(III/IV) complexes: Thermody-
namics, kinetics and applications in synthesis. Coord. Chem. Rev. 2014,
260, 21−36. (b) So, Y.-M.; Leung, W.-H. Recent advances in the
coordination chemistry of cerium(IV) complexes. Coord. Chem. Rev.
2017, 340, 172−197. (c) Yunlu, K.; Gradeff, P. S.; Edelstein, N.; Kot,
W.; Shalimoff, G.; Streib, W. E.; Vaartstra, B. A.; Caulton, K. G.
Photoreduction of cerium(IV) in octakis(isopropoxo)bis(2-
propanol)dicerium. Characterization and structure of Ce4O(OPr-
iso)13(iso-PrOH). Inorg. Chem. 1991, 30, 2317−2321. (d) Friedrich,
J.; Schneider, D.; Bock, L.; Maichle-Mössmer, C.; Anwander, R.
Cerium(IV) Neopentoxide Complexes. Inorg. Chem. 2017, 56, 8114−
8127. (e) Shirase, S.; Shinohara, K.; Tsurugi, H.; Mashima, K.
Oxidation of Alcohols to Carbonyl Compounds Catalyzed by Oxo-
Bridged Dinuclear Cerium Complexes with Pentadentate Schiff-Base
Ligands under a Dioxygen Atmosphere. ACS Catal. 2018, 8, 6939−
6947.
(8) (a) Dong, G.; Cramer, N. C−C Bond Activation; Springer: 2014;
Vol. 346. (b) Souillart, L.; Cramer, N. Catalytic C−C Bond
Activations via Oxidative Addition to Transition Metals. Chem. Rev.
2015, 115, 9410−9464. (c) Sivaguru, P.; Wang, Z.; Zanoni, G.; Bi, X.
Cleavage of carbon−carbon bonds by radical reactions. Chem. Soc.
Rev. 2019, 48, 2615−2656. (d) Wang, B.; Perea, M. A.; Sarpong, R.
Transition-Metal-Mediated Cleavage of C−C Single Bonds: Making
the Cut in Total Synthesis. Angew. Chem., Int. Ed. 2020, 59, 18898−
18919. (e) Yu, X.-Y.; Chen, J.-R.; Xiao, W.-J. Visible Light-Driven
Radical-Mediated C−C Bond Cleavage/Functionalization in Organic
Synthesis. Chem. Rev. 2021, 121, 506−561. (f) Chen, P.-h.; Billett, B.
A.; Tsukamoto, T.; Dong, G. Cut and Sew” Transformations via
Transition-Metal-Catalyzed Carbon−Carbon Bond Activation. ACS
Catal. 2017, 7, 1340−1360. (g) Souillart, L.; Parker, E.; Cramer, N.
Highly Enantioselective Rhodium(I)-Catalyzed Activation of Enan-
tiotopic Cyclobutanone C−C Bonds. Angew. Chem., Int. Ed. 2014, 53,
3001−3005. (h) Ambler, B. R.; Turnbull, B. W. H.; Suravarapu, S. R.;
Uteuliyev, M. M.; Huynh, N. O.; Krische, M. J. Enantioselective
Ruthenium-Catalyzed Benzocyclobutenone−Ketol Cycloaddition:
Merging C−C Bond Activation and Transfer Hydrogenative Coupling
for Type II Polyketide Construction. J. Am. Chem. Soc. 2018, 140,
9091−9094. (i) Kerschgens, I.; Rovira, A. R.; Sarpong, R. Total
Synthesis of (−)-Xishacorene B from (R)-Carvone Using a C−C
Activation Strategy. J. Am. Chem. Soc. 2018, 140, 9810−9813.
(j) Roque, J. B.; Kuroda, Y.; Göttemann, L. T.; Sarpong, R.
Deconstructive fluorination of cyclic amines by carbon-carbon
cleavage. Science 2018, 361, 171−174. (k) Ota, E.; Wang, H.; Frye,
Authors
Yuegang Chen − School of Physical Science and Technology,
ShanghaiTech University, Shanghai 201210, China
Xin Wang − School of Physical Science and Technology,
ShanghaiTech University, Shanghai 201210, China
Xu He − School of Physical Science and Technology,
ShanghaiTech University, Shanghai 201210, China
Qing An − School of Physical Science and Technology,
ShanghaiTech University, Shanghai 201210, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.1c00618
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(nos. 21772121 and 21971163) for financial support. We
thank Dr. Chengxi Zhang and Chemspeed Technologies AG
for their assistance with the automated experimentation.
REFERENCES
■
(1) (a) Narayanam, J. M. R.; Stephenson, C. R. J. Visible light
photoredox catalysis: applications in organic synthesis. Chem. Soc. Rev.
2011, 40, 102−113. (b) Prier, C. K.; Rankic, D. A.; MacMillan, D. W.
C. Visible Light Photoredox Catalysis with Transition Metal
Complexes: Applications in Organic Synthesis. Chem. Rev. 2013,
113, 5322−5363. (c) Schultz, D. M.; Yoon, T. P. Solar Synthesis:
Prospects in Visible Light Photocatalysis. Science 2014, 343, 1239176.
(d) Hossain, A.; Bhattacharyya, A.; Reiser, O. Copper’s rapid ascent
in visible-light photoredox catalysis. Science 2019, 364, eaav9713.
(e) Larsen, C. B.; Wenger, O. S. Photoredox Catalysis with Metal
Complexes Made from Earth-Abundant Elements. Chem. - Eur. J.
2018, 24, 2039−2058. (f) Glaser, F.; Wenger, O. S. Recent progress
in the development of transition-metal based photoredox catalysts.
Coord. Chem. Rev. 2020, 405, 213129.
(2) (a) Bunzli, J.-C. G.; Piguet, C. Taking advantage of luminescent
̈
lanthanide ions. Chem. Soc. Rev. 2005, 34, 1048. (b) Leonard, J. P.;
Nolan, C. B.; Stomeo, F.; Gunnlaugsson, T. Photochemistry and
Photophysics of Coordination Compounds: Lanthanides. In Photo-
chemistry and Photophysics of Coordination Compounds II; Balzani, V.,
Campagna, S., Eds.; Springer Berlin Heidelberg: Berlin, 2007; pp 1−
43. (c) Qiao, Y.; Schelter, E. J. Lanthanide Photocatalysis. Acc. Chem.
Res. 2018, 51, 2926.
(3) (a) Yin, H.; Carroll, P. J.; Anna, J. M.; Schelter, E. J.
Luminescent Ce(III) Complexes as Stoichiometric and Catalytic
Photoreductants for Halogen Atom Abstraction Reactions. J. Am.
Chem. Soc. 2015, 137, 9234. (b) Yin, H.; Carroll, P. J.; Manor, B. C.;
Anna, J. M.; Schelter, E. J. Cerium Photosensitizers: Structure-
Function Relationships and Applications in Photocatalytic Aryl
Coupling Reactions. J. Am. Chem. Soc. 2016, 138, 5984.
(4) (a) Guo, J.-J.; Hu, A.; Chen, Y.; Sun, J.; Tang, H.; Zuo, Z.
Photocatalytic C−C Bond Cleavage and Amination of Cycloalkanols
by Cerium(III) Chloride Complex. Angew. Chem., Int. Ed. 2016, 55,
15319−15322. (b) Yin, H.; Jin, Y.; Hertzog, J. E.; Mullane, K. C.;
Carroll, P. J.; Manor, B. C.; Anna, J. M.; Schelter, E. J. The
Hexachlorocerate(III) Anion: A Potent, Benchtop Stable, and Readily
Available Ultraviolet A Photosensitizer for Aryl Chlorides. J. Am.
Chem. Soc. 2016, 138, 16266. (c) Qiao, Y.; Yang, Q.; Schelter, E. J.
Photoinduced Miyaura Borylation by a Rare-Earth-Metal Photo-
reductant: the Hexachlorocerate(III) Anion. Angew. Chem., Int. Ed.
2018, 57, 10999. (d) Hu, A.; Guo, J.-J.; Pan, H.; Tang, H.; Gao, Z.;
Zuo, Z. δ-Selective Functionalization of Alkanols Enabled by Visible-
Light-Induced Ligand-to-Metal Charge Transfer. J. Am. Chem. Soc.
2018, 140, 1612−1616. (e) Hu, A.; Chen, Y.; Guo, J.-J.; Yu, N.; An,
Q.; Zuo, Z. Cerium-Catalyzed Formal Cycloaddition of Cycloalkanols
4901
https://doi.org/10.1021/jacs.1c00618
J. Am. Chem. Soc. 2021, 143, 4896−4902

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
N. L.; Knowles, R. R. A Redox Strategy for Light-Driven, Out-of-
Equilibrium Isomerizations and Application to Catalytic C−C Bond
Cleavage Reactions. J. Am. Chem. Soc. 2019, 141, 1457. (l) Xu, Y.; Qi,
X.; Zheng, P.; Berti, C. C.; Liu, P.; Dong, G. Deacylative
transformations of ketones via aromatization-promoted C−C bond
activation. Nature 2019, 567, 373−378. (m) Leger, P. R.; Kuroda, Y.;
Chang, S.; Jurczyk, J.; Sarpong, R. C−C Bond Cleavage Approach to
Complex Terpenoids: Development of a Unified Total Synthesis of
the Phomactins. J. Am. Chem. Soc. 2020, 142, 15536−15547.
(9) (a) Obora, Y.; Anno, Y.; Okamoto, R.; Matsu-ura, T.; Ishii, Y.
Iridium-catalyzed reactions of omega-arylalkanols to alpha,omega-
diarylalkanes. Angew. Chem., Int. Ed. 2011, 50, 8618. (b) Ho, H. A.;
Manna, K.; Sadow, A. D. Acceptorless photocatalytic dehydrogen-
ation for alcohol decarbonylation and imine synthesis. Angew. Chem.,
Int. Ed. 2012, 51, 8607. (c) Olsen, E. P.; Madsen, R. Iridium-catalyzed
dehydrogenative decarbonylation of primary alcohols with the
liberation of syngas. Chem. - Eur. J. 2012, 18, 16023. (d) Modak,
A.; Naveen, T.; Maiti, D. An efficient dehydroxymethylation reaction
by a palladium catalyst. Chem. Commun. 2013, 49, 252. (e) Park, H.-
S.; Kim, D.-S.; Jun, C.-H. Palladium-Catalyzed Carbonylative
Esterification of Primary Alcohols with Aryl Chlorides through
Dehydroxymethylative C−C Bond Cleavage. ACS Catal. 2015, 5, 397.
(f) Wu, X.; Cruz, F. A.; Lu, A.; Dong, V. M. Tandem Catalysis:
Transforming Alcohols to Alkenes by Oxidative Dehydroxymethyla-
tion. J. Am. Chem. Soc. 2018, 140, 10126.
(10) For a selection of seminal findings on the exploitation of C−O
bond cleavage in transition-metal-catalyzed cross-couplings, see:
(a) Cornella, J.; Zarate, C.; Martin, R. Metal-catalyzed activation of
ethers via C−O bond cleavage: a new strategy for molecular diversity.
Chem. Soc. Rev. 2014, 43, 8081−8097. (b) Tollefson, E. J.; Hanna, L.
E.; Jarvo, E. R. Stereospecific Nickel-Catalyzed Cross-Coupling
Reactions of Benzylic Ethers and Esters. Acc. Chem. Res. 2015, 48,
2344−2353. (c) Weix, D. J. Methods and Mechanisms for Cross-
Electrophile Coupling of Csp2 Halides with Alkyl Electrophiles. Acc.
Chem. Res. 2015, 48, 1767−1775. (d) Tobisu, M.; Chatani, N. Cross-
Couplings Using Aryl Ethers via C−O Bond Activation Enabled by
Nickel Catalysts. Acc. Chem. Res. 2015, 48, 1717−1726. (e) Taylor, B.
L. H.; Swift, E. C.; Waetzig, J. D.; Jarvo, E. R. Stereospecific Nickel-
Catalyzed Cross-Coupling Reactions of Alkyl Ethers: Enantioselective
Synthesis of Diarylethanes. J. Am. Chem. Soc. 2011, 133, 389−391.
(f) Harris, M. R.; Konev, M. O.; Jarvo, E. R. Enantiospecific
Intramolecular Heck Reactions of Secondary Benzylic Ethers. J. Am.
Chem. Soc. 2014, 136, 7825−7828. (g) Zhang, X.; MacMillan, D. W.
C. Alcohols as Latent Coupling Fragments for Metallaphotoredox
Catalysis: sp3−sp2 Cross-Coupling of Oxalates with Aryl Halides. J.
Am. Chem. Soc. 2016, 138, 13862−13865. (h) Ye, Y.; Chen, H.;
Sessler, J. L.; Gong, H. Zn-Mediated Fragmentation of Tertiary Alkyl
Oxalates Enabling Formation of Alkylated and Arylated Quaternary
Carbon Centers. J. Am. Chem. Soc. 2019, 141, 820−824. (i) Jia, X.-G.;
Guo, P.; Duan, J.; Shu, X.-Z. Dual nickel and Lewis acid catalysis for
cross-electrophile coupling: the allylation of aryl halides with allylic
alcohols. Chem. Sci. 2018, 9, 640−645. (j) Huang, L.; Ji, T.; Rueping,
M. Remote Nickel-Catalyzed Cross-Coupling Arylation via Proton-
Coupled Electron Transfer-Enabled C−C Bond Cleavage. J. Am.
Chem. Soc. 2020, 142, 3532−3539. (k) Guo, P.; Wang, K.; Jin, W.-J.;
Xie, H.; Qi, L.; Liu, X.-Y.; Shu, X.-Z. Dynamic Kinetic Cross-
Electrophile Arylation of Benzyl Alcohols by Nickel Catalysis. J. Am.
Chem. Soc. 2021, 143, 513−523. (l) Cong, F.; Lv, X.-Y.; Day, C. S.;
Martin, R. Dual Catalytic Strategy for Forging sp2−sp3 and sp3−sp3
Architectures via β-Scission of Aliphatic Alcohol Derivatives. J. Am.
Chem. Soc. 2020, 142, 20594−20599.
Chem., Int. Ed. 2019, 58, 6152−6163. (d) Tellis, J. C.; Primer, D.
N.; Molander, G. A. Single-electron transmetalation in organoboron
cross-coupling by photoredox/nickel dual catalysis. Science 2014, 345,
433−436. (e) Zuo, Z.; Ahneman, D. T.; Chu, L.; Terrett, J. A.; Doyle,
A. G.; MacMillan, D. W. C. Merging photoredox with nickel catalysis:
Coupling of -carboxyl sp3-carbons with aryl halides. Science 2014,
345, 437−440. (f) Shields, B. J.; Doyle, A. G. Direct C(sp3)−H Cross
Coupling Enabled by Catalytic Generation of Chlorine Radicals. J.
Am. Chem. Soc. 2016, 138, 12719−12722.
́
(12) Gutiérrez-Bonet, A.; Tellis, J. C.; Matsui, J. K.; Vara, B. A.;
Molander, G. A. 1,4-Dihydropyridines as Alkyl Radical Precursors:
Introducing the Aldehyde Feedstock to Nickel/Photoredox Dual
Catalysis. ACS Catal. 2016, 6, 8004−8008.
(13) (a) Ouchi, A.; Suzuki, Y.; Ohki, Y.; Koizumi, Y. Structure of
rare earth carboxylates in dimeric and polymeric forms. Coord. Chem.
Rev. 1988, 92, 29−43. (b) Bußkamp, H.; Deacon, G. B.; Hilder, M.;
Junk, P. C.; Kynast, U. H.; Lee, W. W.; Turner, D. R. Structural
variations in rare earth benzoate complexes: Part I. Lanthanum.
CrystEngComm 2007, 9, 394−411. (c) Das, R.; Sarma, R.; Baruah, J.
B. A hexanuclear cerium(IV) cluster with mixed coordination
environment. Inorg. Chem. Commun. 2010, 13, 793−795. (d) Das,
R.; Sarma, R.; Baruah, J. B. Mixed Bridging Coordination Modes of
Cerium(III) Alkylbenzoates. Synth. React. Inorg., Met.-Org., Nano-Met.
Chem. 2011, 41, 165−172.
(14) Arias-Rotondo, D. M.; McCusker, J. K. The photophysics of
photoredox catalysis: a roadmap for catalyst design. Chem. Soc. Rev.
2016, 45, 5803−5820.
(11) (a) Levin, M. D.; Kim, S.; Toste, F. D. Photoredox Catalysis
Unlocks Single-Electron Elementary Steps in Transition Metal
Catalyzed Cross-Coupling. ACS Cent. Sci. 2016, 2, 293−301.
(b) Twilton, J.; Le, C.; Zhang, P.; Shaw, M. H.; Evans, R. W.;
MacMillan, D. W. C. The merger of transition metal and
photocatalysis. Nat. Rev. Chem. 2017, 1, 0052. (c) Milligan, J. A.;
Phelan, J. P.; Badir, S. O.; Molander, G. A. Alkyl Carbon−Carbon
Bond Formation by Nickel/Photoredox Cross-Coupling. Angew.
4902
https://doi.org/10.1021/jacs.1c00618
J. Am. Chem. Soc. 2021, 143, 4896−4902