Visible Light Uranyl Photocatalysis: Direct C-H to C-C Bond Conversion

Article abstract of DOI:10.1021/acscatal.9b00287

Uranyl nitrate hexahydrate performs as an efficient photocatalyst in the direct C-H to C-C bond conversion under blue light irradiation via hydrogen atom transfer (HAT). This uranyl salt enables the remarkable smooth functionalization of unactivated (cycl

Full text of DOI:10.1021/acscatal.9b00287

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Letter
Visible Light Uranyl Photocatalysis: Direct C–H to C–C Bond Conversion
Luca Capaldo, Daniele Merli, Maurizio Fagnoni, and Davide Ravelli
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b00287 • Publication Date (Web): 05 Mar 2019
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ACS Catalysis
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Visible Light Uranyl Photocatalysis: Direct C–H to C–C Bond
Conversion
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Luca Capaldo, Daniele Merli, Maurizio Fagnoni, Davide Ravelli*
Photogreen Lab, Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
ABSTRACT: Uranyl nitrate hexahydrate performs as an efficient photocatalyst in the direct C–H to C–C bond conversion under
blue light irradiation via Hydrogen Atom Transfer (HAT). This uranyl salt enables the remarkable smooth functionalization
of unactivated (cyclo)alkanes, ethers, acetals and amides via radical addition onto electrophilic olefins. Dedicated
electrochemical measurements on compounds and intermediates involved in the process were carried out to support the
mechanistic proposal.
KEYWORDS: C-C bond formation, hydrogen atom transfer, photocatalysis, radical reactions, uranyl cation
Photoredox catalysis has deeply transformed the field of
organic chemistry providing synthesis practitioners with a
plethora of unconventional approaches, mainly based on
radical intermediates.1 These processes rely on the
activation of an organic substrate through a single-electron
transfer (SET) reaction promoted by the excited state of a
purposely added catalyst. Indeed, despite the enhanced
redox properties typical of excited states, the choice of the
substrates is limited by the redox properties of the
employed photocatalyst, albeit the incorporation of suitable
redox-auxiliary groups2 in one reactant facilitates the
desired SET. To circumvent these limitations, notable
efforts have been made to design an indirect photocatalyzed
hydrogen atom transfer (i-HAT),3 where a photocatalytic
cycle promotes the in-situ generation of a thermal H-atom
abstractor (typically, an alkoxy radical RO• or an amine
radical cation R3N•+, Scheme 1).3,4 Another useful approach
to perform an i-HAT is through an intramolecular process,
thus leading to a remote C–H bond functionalization.5
reagent (Scheme 1). Unfortunately, the development of such
approach is severely limited by the scarcity of available
photocatalysts able to promote this chemistry, with the
added burden that most of them require highly energetic UV
light to operate.6,7 Accordingly, there is an urgent need to
develop synthetic protocols via d-HAT occurring under
visible light irradiation, especially with the aim to forge C–C
bonds from strong aliphatic C–H bonds, such as those
embedded in alkanes, which is still considered as one of the
‘Holy Grails’ in synthesis.8
As an example, fluorenone,9a acetophenone9b and uranyl
nitrate hexahydrate10 were recently used to accomplish the
C–H to C–F bond conversion in alkyl aromatics9a or in
alkanes9b,10 (Scheme 2, upper part).
Scheme 2. Examples of Visible-light Photocatalyzed d-
HAT in C–F (upper part) and C–C Bond Formation
(lower part).
Visible Light d-HAT
C-F Bond Formation
Scheme 1. Approaches for the Indirect (i-HAT) or Direct
(d-HAT) Photocatalyzed Hydrogen Atom Transfer
Reaction.
O
F
(5 mol%)
Selectfluor (2.0 equiv)
85%
Indirect HAT (i-HAT)
CH3CN, 23°C, Ar,
h (LED), 6 h
[UO2](NO3)2•6H2O (1 mol%)
PCSET
F
R H
NFSI (1.5 equiv)
X'
X
X H
42% (NMR)
R +
N +
CD3CN, 23°C, Ar,
h (blue LED), 16 h
X = RO ,
C-C Bond Formation
O
O
O
PT
(5 mol%)
Direct HAT (d-HAT)
O
SO2Ph
69%
SO2Ph
K2CO3 (1.1 equiv)
PhO2S
+
direct C-H cleavage
atom-economical
CH2Cl2, rt, Ar,
h (425 nm LED lamp), 24 h
PCHAT
R H
R
operationally simple
CN
CN
32%
Ph
NC
Ph
CN
Eosin Y (2 mol%)
+
A more straightforward route for substrate activation
makes use of a direct photocatalyzed HAT (d-HAT),3 where
the excited photocatalyst cleaves directly a C–H bond in the
Me2CO, 60 °C,
h (18 W LED lamp), 24 h
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Page 2 of 13
On the other hand, the direct, visible-light photocatalyzed extremely mild conditions (Table 2). Interestingly, even
1
2
3
4
5
6
7
8
activation of a C–H bond in (cyclo)alkanes to forge C–C
bonds still remains a challenge and only two cases have
been reported in the literature to date. Firstly, 5,7,12,14-
pentacenetetrone (PT, Scheme 2) was adopted as the
photocatalyst in a radical allylation protocol, where
cycloalkanes were converted into vinyl sulfones in a good
yield by reaction with 1,2-bis(phenylsulfonyl)-2-propene.11
Secondly, it was demonstrated that Eosin Y can function as
an effective photoorganocatalyst for the visible-light
derivatization of cyclohexane (Scheme 2) but, despite the
operational simplicity that allowed to run the reaction on a
large scale by using continuous-flow technology, the yield of
alkylated product was poor and heating at 60 °C was
necessary.12
acyclic isooctane (2,2,4-trimethylpentane, 1f) was
functionalized with a complete regioselectivity towards the
methine site to afford 8 in 68% yield when the
photocatalyst was used in 15 mol% amount. Valeronitrile
gave product 9, confirming the same selectivity towards the
tertiary position. We then shifted our attention to the
functionalization of oxygenated compounds, such as ethers
and acetals, via the visible-light photocatalyzed generation
of -oxy and -dioxy radicals, respectively.
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Table 1. Control Experiments for the Uranyl-
Photocatalyzed C-H to C-C Bond Conversion.
Pushed by our interest in photocatalysis via d-HAT by
polyoxometalates, where an M=O (M: metal) functionality
in the excited state is responsible for the relevant H-atom
abstraction,13 we pursued the search for a robust
photocatalyst that can operate in the visible light region.
Accordingly, we chose uranyl nitrate hexahydrate
[UO2](NO3)2∙6H2O as a valid candidate.14 Since its discovery,
the uranyl cation [UO2]2+ (oxidation state for U: +6) has
received a great deal of attention for its photophysical and
photochemical properties.15 The weak absorption band in
the visible range has been proposed to involve the
excitation of an electron from a π-orbital of the U=O bond to
a non-bonding orbital on the metal center.15c,16 This
transition ultimately leads to the population of a triplet
excited state endowed with free radical character, showing
a lifetime in the microseconds domain and a redox potential
E([UVIO2]2+*/[UVO2]+) of +2.36V vs SCE.15,16 Indeed, the
reactive oxygen site of this state has the capability to
generate C-centered radicals via homolytic cleavage of a C–
H bond in organic compounds,10 especially in alcohols and
arylaldehydes.17 Accordingly, we embarked on a study
aimed to demonstrate that the uranyl cation is a valuable d-
HAT photocatalyst to forge C–C bonds from unactivated C–
H bonds (mainly from (cyclo)alkanes) under visible light
irradiation.
CN
[UO2](NO3)2•6H2O (8 mol%)
Ph
+
Me2CO, rt, air, 24 h
Kessil lamp (456 nm)
CN
CN
consumption (%) Yield (%)a
CN
2a
Ph
1a
5 equiv.
3
2a
Entry Variation from opt. conditions
95, 96b
n.d.
n.d.
n.d.
95
1
2
3
4
5
6
none
100
< 5
< 5
< 5
100
< 5
No light
Dark, 60°Cc
No photocatalyst
N2 sparged solution
TEMPO (1 equiv)
n.d.
a Absolute yields determined by means of calibration curves
with authentic samples (see SI). Isolated yield after flash
column chromatography.
detected. TEMPO: (2,2,6,6-tetramethylpiperidin-1-yl)oxyl.
b
c
Refluxing acetone. n.d.: not
Table 2. Scope of H-donors 1 for the Alkylation of
Benzylidenemalononitrile 2a.a
2-
R
CN
H
[UO2](NO3)2•6H2O (8 mol%)
+
H
R
Ph
Me2CO, rt, air, 24 h
Kessil Lamp 456 nmb
CN
CN
CN
1a-o
2a
3 17
-
Ph
Ph
NC
CN
n =
3
2, 96% ( )
1, 67% ( )
3, 76% ( )
4, 78% ( )
We commenced our investigation by studying the
CN NC
4
addition
of
cyclohexane
(1a)
onto
2-
5
6
7
CN
CN
CN
benzylidenemalononitrile 2a, chosen as a model Michael
acceptor. After routine optimization of the reaction
conditions (see Section 2 in Supporting Information), we
found that uranyl nitrate hexahydrate (8 mol%) in an air-
equilibrated acetone solution of 2a in the presence of 1a (5
equiv) under irradiation at 456 nm (40 W LED; light
intensity: 400 W·m–2) gave the best results, with formation
of the expected adduct 3 in 96% isolated yield (at complete
conversion of 2a). Notably, the residual uranium content in
isolated 3 was determined by an ICP-MS analysis to be < 20
g/kg (see SI for details). We further demonstrated that the
reaction required both light and photocatalyst to occur,
while heating in refluxing acetone in the dark for 24 h did
not afford any product. Moreover, the process was inhibited
in the presence of the radical scavenger TEMPO (see Table
1).
c
d
8, 42% ( )
8
9
68% ( )
68% ( )
n
NC
CN
Ph
NC
CN
Ph
H2N
O
NC
CN
Ph
NC
CN
Ph
CN
O
O
O
O
O
O
O
Ph
14
11
70% (
)
10
12
13
68% ( )
60% (
)
58% (
)
75% (
CN
)
NC
CN NC
CN
Ph
NC
NC
CN
Ph
O
O
O
Ph
Ph
O
N
N
Ph
C6H13
15
15'
f
f
quant.e
15 15'
= 2:1
16
17
)
93% (
)
70% (
ratio
:
a
Reaction conditions: 2a (0.1 M), 1a-o (5 equiv, unless
otherwise noted); the structures of the starting materials are
reported in Section S1 in the SI; isolated yields on a 1 mmol
scale have been reported. b Light intensity: 400 W·m–2 at 5 cm.
Gratifyingly, the functionalization of unactivated
methylene groups in several cycloalkanes occurred
smoothly in excellent yields (see compounds 3-7) under
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ACS Catalysis
c 20 equiv of 1f, [UO2]2+ 15 mol%. d 10 equiv of 1g. e 4 equiv of
formation of adducts 24-25 required long reaction times,
1m. f 1 equiv of aldehyde.
1
2
3
4
5
6
7
8
up to 65 h. Finally, we tested olefins different from styrene
derivatives. In particular, the -disubstitution in
isopropylidene malononitrile 2j and cyclohexylidene
malononitrile 2k caused a slight drop in reactivity and
incomplete conversion of the olefin was observed in the
latter case, with adduct 27 formed in 82% yield (based on
60% conversion of the olefin). When dimethyl ethylidene
malonate 2l was used, the reaction proceeded smoothly,
affording 28 in 82% yield with complete conversion of the
olefin. Reaction of 1a with a conjugated ketone, such as 3-
methylene-2-norbornanone 2m, gave product 29 in 69%
yield as the endo diastereomer, exclusively. In the alkylation
of dimethyl maleate 2n, product 30 was obtained in 60%
yield in Me2CO/H2O 8:2 as the reaction medium.
Adducts 10-13 were then obtained in yields ranging 58-
70%; notably, the photocatalyzed C–H cleavage in 1,3-
dioxolane showed a complete selectivity towards the 2-
position of the oxygenated ring. Methanol was then used as
H-donor for the radical addition onto 2a, which occurred in
75% yield, to afford compound 14 upon spontaneous
cyclization. The functionalization was very efficient with
dimethylformamide (DMF) since addition onto 2a was
quantitative. In the latter case, C–H activation was not
regioselective, since both the adducts deriving from the -
amidoalkyl and the carbamoyl radicals were formed in a 2:1
ratio, respectively (compounds 15 and 15'). Finally, the
protocol could be easily adapted to perform an acylation
starting from aliphatic aldehydes (compounds 16, 17, >
70% yield), here used in an equimolar amount.
9
10
11
12
13
14
15
16
17
18
19
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21
22
23
24
25
26
27
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29
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60
To gain further insights into the HAT step, we performed
a competition experiment in the presence of an equimolar
C6H12/C6D12 (1a/1a-d12) mixture (Figure 1a). A 74:26
mixture of 3 and 3-d11 was obtained, with a kinetic isotope
effect (KIE) value of 2.9 (see also Scheme S2). This result is
in accordance with that available in the literature15e and was
further confirmed by an independent Stern-Volmer
experiment for the quenching of uranyl cation
phosphorescence (see Table S5),15 where a KIE value of 3.5
has been determined.
We then turned our attention to the scope of the olefin, by
choosing 1a as the model H-donor (Table 3). The
substitution pattern on the aromatic ring of the olefin 2a
was first tested. Neither the presence of a chlorine atom
(products 18-20, 63-82% yield), nor the electronic nature
of the substituent (compounds 21-23, ca. 60% yield)
seemed to affect significantly the overall alkylation yield.
However, the presence of an electron-donating group (e.g.
OMe) required a longer irradiation time (96 h) to achieve
complete conversion.
We then focused our attention on the regeneration of the
photocatalyst. We postulate that the catalytic cycle may be
closed (in analogy with other metal-based d-HAT
photocatalysts)6 by an electron transfer process from the
reduced photocatalyst (H+[U]RED = H+[UVO2]+) to the radical
adduct (I•) resulting from the addition of the
photogenerated radical (R•) onto 2. As a matter of fact, the
reaction worked better when -disubstituted styrenes
2a-i were used. Accordingly, to test our hypothesis we
decided to measure the redox potentials of the I•/I– couple
for a set of •(CR)X2 radicals (X = CN or COOR; see Figure 1b).
Thus, we generated in situ enolates –(CR)X2 from the
corresponding active methylene derivatives (including
compound 25, taken as a reference) upon addition of
(nBu4)N+OH– and ran CV experiments (Figure S7).
Interestingly, we found that all the redox couples were
reversible, with moderately positive redox values
E0'(•(CR)X2/–(CR)X2) ≥ + 0.5 V vs SCE, meaning that the
generated intermediates I• are remarkably prone to
reduction. We believe that this interesting feature makes
the closure of the photocatalytic cycle fast and efficient,
compensating the weak reducing power of (protonated)
[UVO2]+ (E1/2([UVO2]+/[UVIO2]2+) = + 0.32 V vs SCE; non-
reversible behavior; Figure S8). The process is likewise
feasible when the adduct radical is stabilized by only one
electron-withdrawing group (to give compounds 29-30),
since the redox potential of the succinonitrile radical
E(NCCH•CH2CN/NCCH–CH2CN taken as a reference was
reported to be + 0.165 V vs SCE19 (Figure 1b). Thus, the
reaction with dimethyl maleate 2n proceeded satisfactorily
in the presence of water, where the uranyl cation showed a
more reversible behavior, with a slightly increased reducing
power, E1/2([UVO2]+/[UVIO2]2+) = + 0.10 V vs SCE (Figure S8).
Table 3. Scope of Electron Poor Olefins 2 for the
Functionalization of Cyclohexane 1a.a
Y
Y
H
Z
[UO2](NO3)2•6H2O (8 mol%)
X
+
Z
Me2CO, rt, air, 24 h
Kessil Lamp 456 nm
X
W
2b-n
W
18-30
1a
NC
NC
CN
CN
18
19
20
2-Cl, 82% (
3-Cl, 73% (
4-Cl, 63% (
)
)
)
X =
21
)
CN, 66% (
Me, 60% (
OMe, 66% (
Cl
22
)
b
23
)
X
COOMe
CN
R
Ph
X
R'
CN
26
54%, R = R' =Me ( )
c
X =
24
CN, 77% (
)
d
e
25
27
)
COOMe, 74% (
)
82%, R-R' = -(CH2)5- (
MeOOC
COOMe
COOMe
COOMe
O
f
g
29
69%, endo (
)
30
60% ( )
28
82% (
)
a
b
Reaction conditions as in Table 2. Complete conversion
c
d
after 96 h. Complete conversion after 30 h. Complete
conversion after 65 h. 60% conversion of olefin 2k was
observed; yield based on the consumed olefin. Complete
conversion after 16 h, only endo diastereoisomer formed.
e
f
g
Reaction performed in Me2CO/H2O 8:2.
Similarly, the decrease of the electrophilicity of the olefin,
resulting from the substitution of a CN with a COOMe
group,18 did not affect the reaction yield, although the
Moreover, we can safely exclude an electron transfer
reaction between H+[U]RED and the olefin since these have a
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ACS Catalysis
redox potential E(2/2•–) more negative than – 0.80 V vs SCE
Page 4 of 13
ASSOCIATED CONTENT
1
2
3
4
5
6
7
8
(Table S6).
Supporting Information. Experimental details about the used
materials, sample preparation, experiments, electrochemical
measurements and analytical data (NMR). This material is
available free of charge via the Internet at http://pubs.acs.org.
a)
H
H
H
NC
C6H12
NC
[U] (8 mol%)
H
CN
D
CN
(5 equiv)
2a
0.1 M
Optimized
conditions
kH / kD = 2.9
+
D
C6D12
Ph
Ph
(5 equiv)
3-d
26%,
3
74%,
11
AUTHOR INFORMATION
Corresponding Author
* E-mail: davide.ravelli@unipv.it
C6H11
CO2Me
CO2Me
Ph
CO2Me
b)
ref. 19 CN
EtO2C
CN
CN
NC
0'
9
I
I
)
E (
/
CO2Me
CN
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
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58
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60
ORCID
V vs SCE
+ 0.1 V
+ 0.3 V
+ 0.5 V
+ 0.7 V
Luca Capaldo: 0000-0001-7114-267X
Daniele Merli: 0000-0003-3975-0127
Maurizio Fagnoni: 0000-0003-0247-7585
Davide Ravelli: 0000-0003-2201-4828
[U]: [UVIO2]2+
[U]RED: [UVO2]+
E1/2([U]RED/[U])
in Me2CO
in Me2CO/H2O 9:1
R
H
1
Funding Sources
c)
[U]*
L. C. and D. R. thank the MIUR for financial support (SIR Project
“Organic Synthesis via Visible Light Photocatalytic Hydrogen
Transfer”; Code: RBSI145Y9R).
d-HAT
R
R1
EWG
EWG
H+[U]RED
- H+
2
R2
[U]
Notes
SET
The authors declare no competing financial interest.
R
EWG
R1
3-30
R2
1
R
EWG
EWG
EWG
I
R1
R2
REFERENCES
I
(1) (a) Photoorganocatalysis in Organic Synthesis, Fagnoni, M.;
Protti, S.; Ravelli, D. Eds.; World Scientific Publishing Co. Pte. Ltd.,
Singapore, 2019, DOI: 10.1142/q0180. (b) Visible Light
Photocatalysis in Organic Chemistry, Stephenson, C. R. J.; Yoon, T. P.;
MacMillan, D. W. C. Eds.; Wiley-VCH, Weinheim, 2018. (c) Strieth-
Kalthoff, F., James, M. J.; Teders, M.; Pitzer, L.; Glorius, F. Energy
Transfer Catalysis Mediated by Visible Light: Principles,
Applications, Directions. Chem. Soc. Rev. 2018, 47, 7190–7202. (d)
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. (e) Parasram, M.; Gevorgyan, V. Visible Light-
Induced Transition Metal-Catalyzed Transformations: Beyond
Conventional Photosensitizers. Chem. Soc. Rev. 2017, 46, 6227–
6240. (f) Xuan, J.; Lu, L.-Q.; Chen, J.-R.; Xiao, W.-J.
Visible-Light-Driven Photoredox Catalysis in the Construction of
Carbocyclic and Heterocyclic Ring Systems. Eur. J. Org. Chem. 2013,
6755–6770. (g) Reckenthäler, M.; Griesbeck, A. G. Photoredox
Catalysis for Organic Syntheses. Adv. Synth. Catal. 2013, 355, 2727–
2744.
3-30
H+
Figure 1. Mechanistic investigation: a) deuteration experiment
for KIE determination; b) redox potentials of the involved
species; c) mechanistic proposal.
A chain reaction mechanism may be excluded as well,
since in most cases the BDE of the C–H bond to be cleaved is
too strong (e.g. in cyclohexane the BDE is ca. 99.5 kcal·mol–
1).20 In addition, an experiment performed in deuterated
acetone allowed us to prove that the solvent does not take
part into the reaction (see Scheme S3 and Figure S11). In
view of the above, our mechanistic proposal is reported in
Figure 1c. In particular, the uranyl cation is excited under
visible-light irradiation and, once in the excited state ([U]*),
is responsible for substrate activation via d-HAT. The thus-
generated C-centered radical is readily intercepted by the
electron-poor olefin 2 to give radical intermediate I•. This
species is then responsible for the re-oxidation of the
reduced form of the photocatalyst (H+[U]RED) to afford the
desired Giese adduct.
(2) (a) Yoshida, J.-i.; Kataoka, K.; Horcajada, R.; Nagaki, A.
Modern Strategies in Electroorganic Synthesis. Chem. Rev. 2008,
108, 2265–2299. (b) Lin, S.; Lies, S. D.; Gravatt, C. S.; Yoon, T. P.
Radical Cation Cycloadditions Using Cleavable Redox Auxiliaries.
Org. Lett. 2017, 19, 368–371.
(3) Capaldo, L.; Ravelli, D. Hydrogen Atom Transfer (HAT): A
Versatile Strategy for Substrate Activation in Photocatalyzed
Organic Synthesis. Eur. J. Org. Chem. 2017, 2017, 2056–2071.
(4) Special issue on “Hydrogen Atom Transfer”, see: Costas, M.;
Bietti, M. Uncovering the Complexity of the Simplest Atom Transfer
Reaction. Acc. Chem. Res. 2018, 51, 2601–2602.
(5) (a) Hu, X.-Q.; Chen, J.-R.; Xiao, W.-J. Controllable Remote C-H
Bond Functionalization by Visible-Light Photocatalysis. Angew.
Chem. Int. Ed. 2017, 56, 1960–1962. (b) Stateman, L. M.; Nakafuku,
K. M.; Nagib, D. A. Remote C–H Functionalization via Selective
Hydrogen Atom Transfer. Synthesis 2018, 50, 1569–1586.
(6) (a) Ravelli, D.; Protti, S.; Fagnoni, M. Decatungstate Anion for
Photocatalyzed “Window Ledge” Reactions. Acc. Chem. Res. 2016,
49, 2232–2242. (b) Ravelli, D.; Fagnoni, M.; Fukuyama, T.;
Nishikawa, T.; Ryu, I. Site-Selective C–H Functionalization by
Decatungstate Anion Photocatalysis: Synergistic Control by Polar
In conclusion, we have demonstrated that uranyl cation
can be used as a visible-light photocatalyst for d-HAT in C–
C bond forming reactions. The present approach is
operationally simple and does not require any additive, thus
confirming the robustness, efficiency and selectivity of the
d-HAT approach for the functionalization of strong C–H
bonds. Notably, (cyclo)alkanes were readily alkylated via
radical addition onto Michael acceptors in good to excellent
yields. Furthermore, the electrochemical study allowed to
propose a mechanistic scenario, where the nature of the
olefin (and of the intermediates formed from it) plays a key
role in the regeneration of the photocatalyst.
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and Steric Effects Expands the Reaction Scope. ACS Catal. 2018, 8,
Ritchie, G. D. A Review of the Effects of Uranium and Depleted
Uranium Exposure on Reproduction and Fetal Development.
Toxicol. Ind. Health 2001, 17, 180–191. (b) Domingo, J. L.
Reproductive and Developmental Toxicity of Natural and Depleted
Uranium: A Review. Reprod. Toxicol. 2001, 15, 603–609.
701–713. (c) Suzuki, K.; Mizuno, N.; Yamaguchi, K. Polyoxometalate
Photocatalysis for Liquid-Phase Selective Organic Functional
Group Transformations. ACS Catal. 2018, 8, 10809−10825. (d)
Tanielian, C. Decatungstate Photocatalysis. Coord. Chem. Rev. 1998,
178–180, 1165−1181. (e) Tzirakis, M. D.; Lykakis, I. N.;
Orfanopoulos, M. Decatungstate as an Efficient Photocatalyst in
Organic Chemistry. Chem. Soc. Rev. 2009, 38, 2609−2621.
(7) Li, H.; Zhang, M.-T. Visible-light-mediated C(sp3)-H activation
by photo-induced hydrogen-atom transfer. J. Photochem. Photobiol.
A: Chem. 2018, 355, 109–113.
1
2
3
4
5
6
7
8
(15) (a) Rabinowitch, E.; Belford, R. L. Spectroscopy and
Photochemistry of Uranyl Compounds, The Macmillan Company,
Pergamon Press, New York, 1964. (b) Jørgensen, C. K.; Reisfeld, R.
Uranyl photophysics. Top. Inorg. Phys. Chem. 1982, 50, 121–171.
(c) Burrows, H. D.; Kemp, T. J. The Photochemistry of the Uranyl
ion. Chem. Soc. Rev. 1974, 3, 139–165. (d) Ghosh, R.; Mondal, J. A.;
Ghosh, H. N.; Palit, D. K. Ultrafast Dynamics of the Excited States of
the Uranyl Ion in Solutions. J. Phys. Chem. A 2010, 114, 5263–5270.
(e) Wang, W.-D; Bakac, A.; Espenson, J. H. Uranium(VI)-Catalyzed
Photooxidation of Hydrocarbons with Molecular Oxygen. Inorg.
Chem. 1995, 34, 6034–6039. (f) Mao, Y.; Bakac, A. Photocatalytic
Oxidation of Toluene to Benzaldehyde by Molecular Oxygen. J. Phys.
Chem. 1996, 100, 4219–4223.
9
(8) Hartwig, J. F. Catalyst-Controlled Site-Selective Bond
Activation. Acc. Chem. Res. 2017, 50, 549–555.
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(9) (a) Xia, J.-B.; Zhu, C.; Chen, C. Visible Light-Promoted Metal-
Free C–H Activation: Diarylketone-Catalyzed Selective Benzylic
Mono- and Difluorination. J. Am. Chem. Soc. 2013, 135, 17494–
17500. (b) Xia, J.-B.; Zhu, C.; Chen, C. Visible Light-Promoted Metal-
free sp3-C–H Fluorination. Chem. Commun. 2014, 50, 11701–
11704.
(10) (a) West, J. G.; Bedell, T. A.; Sorensen, E. J. The Uranyl Cation
as a Visible-Light Photocatalyst for C(sp3)−H Fluorination. Angew.
Chem. Int. Ed. 2016, 55, 8923–8927. (b) Wu, L.; Cao, X.; Chen, X.;
Fang, W.; Dolg, M. Visible-Light Photocatalysis of C(sp3)-H
Fluorination by the Uranyl Ion: Mechanistic Insights. Angew. Chem.
Int. Ed. 2018, 57, 11812–11816.
(16) McGlynn, S. P.; Smith, J. K. The Electronic Structure, Spectra,
and Magnetic Properties of Actinyl Ions: Part I. The Uranyl Ion. J.
Mol. Spectrosc. 1961, 6, 164–187.
(17) (a) Matsushima, R. Mechanism of Quenching of the Uranyl
Fluorescence by Organic Compounds. J. Am. Chem. Soc. 1972, 94,
6010–6016. (b) Sakuraba, S.; Matsushima, R. Photochemical
Reactions of Uranyl Ions with Organic Compounds. II. The
Mechanism of the Photo-Oxidation of Alcohols by Uranyl Ions. Bull.
Chem. Soc. Jpn. 1970, 43, 2359–2363. (c) Sakuraba, S.; Matsushima,
R. Photochemical Reactions of Uranyl Ions with Organic
Compounds. IV. The Uranyl Fluorescence Quenching by Aliphatic
Alcohols. Bull. Chem. Soc. Jpn. 1971, 44, 2915–2918. (d) Matushima,
R.; Mori, K.; Suzuki, M. Photoreactions of the Uranyl Ion with
Arylaldehydes in Solution. Bull. Chem. Soc. Jpn. 1976, 49, 38–41.
(18) Allgäuer, D. S.; Jangra, H.; Asahara, H.; Li, Z.; Chen, Q.; Zipse,
H.; Ofial, A. R.; Mayr, H. Quantification and Theoretical Analysis of
the Electrophilicities of Michael Acceptors. J. Am. Chem. Soc. 2017,
139, 13318−13329.
(11) Kamijo, S.; Kamijo, K.; Maruoka, K.; Murafuji, T. Aryl Ketone
Catalyzed Radical Allylation of C(sp3)–H Bonds under
Photoirradiation. Org. Lett. 2016, 18, 6516–6519.
(12) Fan, X.-Z.; Rong, J.-W.; Wu, H.-L.; Zhou, Q.; Deng, H.-P.; Tan,
J. D.; Xue, C.-W.; Wu, L.-Z.; Tao, H.-R.; Wu, J. EosinꢀY as a Direct
Hydrogen-Atom Transfer Photocatalyst for the Functionalization
of C-H Bonds. Angew. Chem. Int. Ed. 2018, 57, 8514–8518.
(13) De Waele, V.; Poizat, O.; Fagnoni, M.; Bagno, A.; Ravelli, D.
Unraveling the Key Features of the Reactive State of Decatungstate
Anion in Hydrogen Atom Transfer (HAT) Photocatalysis. ACS Catal.
2016, 6, 7174–7182.
(14) Although the handling of uranium salts might trigger an
instinctive concern, it is a common position that the main risks
deriving from their use are associated with chemical toxicity, and
not from radioactivity. Thus, a judicious use of PPE (Personal
Protection Equipment) makes most common uranium compounds,
such as uranyl nitrate or uranyl acetate, no more noxious than any
other heavy metal complex. See: (a) Arfsten, D. P.; Still, K. R.;
(19) Magri, D. C.; Workentin, M. S. Redox Properties of Radicals.
In Encyclopedia of Radicals in Chemistry, Biology and Materials;
Chatgilialoglu, C., Studer, A., Eds.; John Wiley & Sons, 2012, DOI:
10.1002/9780470971253.rad002.
(20) Luo, Y.-R. Handbook of Bond Dissociation Energies in
Organic Compounds, CRC Press, Boca Raton, 2003.
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Direct Hydrogen Atom Transfer (d-HAT)
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Scheme 1. Approaches for the Indirect (i-HAT) or Direct (d-HAT) Photocatalyzed Hydrogen Atom Transfer
Reaction.
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Scheme 2. Examples of Visible-light Photocatalyzed d-HAT in C–F and C–C Bond Formation.
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Figure 1. Mechanistic Investigation: a) Deuteration Experiment for KIE Determination; b) Redox Potentials of
the Involved Species; c) mechanistic Proposal.
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Table 1. Control Experiments for the Uranyl-Photocatalyzed C-H to C-C Bond Conversion.
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Table 2. Scope of H-donors 1 for the Alkylation of 2-Benzylidenemalononitrile 2a.
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Table 3. Scope of Electron Poor Olefins 2 for the Functionalization of Cyclohexane 1a.
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