Substituted Hantzsch Esters as Versatile Radical Reservoirs in Photoredox Reactions

Article abstract of DOI:10.1002/adsc.201701348

Substituted Hantzsch esters can act as radical reservoirs in photoredox reactions, steadily releasing a carbon radical and a hydrogen atom radical in the absence of an additional electron acceptor. We propose that radical release by substituted Hantzsch esters occurs via a mechanism involving an internal redox cycle. Cinnamidecinnamides, styrenes, α,β-unsaturated acids, and diarylethenes could be alkylated smoothly with these reagents. (Figure presented.).

Full text of DOI:10.1002/adsc.201701348

Title: Substituted Hantzsch Esters as Versatile Radical Reservoirs in
Photoredox Reactions
Authors: Fangjun Gu, Wenhao Huang, Xu Liu, Wen-Xin Chen, and Xu
Cheng
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201701348
Link to VoR: http://dx.doi.org/10.1002/adsc.201701348

10.1002/adsc.201701348
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Substituted Hantzsch Esters as Versatile Radical Reservoirs in
Photoredox Reactions
Fangjun Gu,a Wenhao Huang,a Xu Liu,a Wenxin Chen,a Xu Chenga,b*
a
Institute of Chemistry and Biomedical Sciences, Jiangsu Key Laboratory of Advanced Organic Materials, School of
Chemistry and Chemical Engineering, National Demonstration Center for Experimental Chemistry Education, Nanjing
University, Nanjing, 210023, China
E-mail: chengxu@nju.edu.cn
State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin, China
b
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. Substituted Hantzsch esters can act as radical -unsaturated acids, and diarylethenes could be alkylated
reservoirs in photoredox reactions, steadily releasing a smoothly with these reagents.
carbon radical and a hydrogen atom radical in the absence of
an additional electron acceptor. We propose that radical
release by substituted Hantzsch esters occurs via
mechanism involving an internal redox cycle.
Keywords: Photoredox; Radical; Hantzsch ester;
Alkylation
a
Cinnamidecinnamides, styrenes,
HEs as radical reservoirs in photoredox reactions,
with or without an additional electron acceptor; these
reactions appear to proceed via a previously
unexplored electron transfer pathway involving
internal charge flow between various HE species and
the photocatalyst (Scheme 1b).
Introduction
Photoredox catalysis is a powerful strategy for
construction of complex molecules,[1] including
polymers,[2] and for energy storage applications.[3] In
terms of redox catalysis, it is important to match
electron donor and acceptor to keep a smooth
electron transfer.[4] In principle, 1:1 ratio of
donor/acceptor would be adequate in a redox reaction.
Recently, 4-substituted Hantzsch esters (HEs)[5]
[6]
have been used as key electron donors in a variety of
challenging photoredox reactions, such as aromatic
CN substitution (as reported first by Nishibayashi et
al.),[7] intermolecular construction of molecules with
all-carbon quaternary centers,[8] Ni–Ir-catalyzed C–C
bond formation reactions, and other important
transformations.[9] In the our report building
quaternary carbon centers, it was found alkylation of
the electron acceptor -bromoisobutyrophenone with
3.0 equiv of a substituted HE 1a affords a much
higher yield of the target product than the same
reaction conducted with only 1.0 equiv of the HE.[8]
In addition, the product of homo-coupling between
two benzylic radicals is isolated in approximately
20% yield. (Scheme 1a) These results suggested that
some unidentified electron transfer process occurs.[10]
The reason for the imbalance between the amounts of
the electron donor and acceptor in this photoredox
catalytic process, and its implications for reaction
design, have not yet been elucidated. Herein, we
report our detailed study of this phenomenon.
Specifically, we investigated the use of substituted
Scheme 1 a) The different ratio of reactants and
corresponding yields. b) Charge flow between various
substituted HE species (designated [HE]) and a photoredox
catalyst (PC).
Results and Discussion
To investigate if such additional HE could increase
reaction yield in photoredox reactions other than the
-bromoketones, we used HEs 1 in hydroalkylation
reactions of cinnamides 2. (Scheme 2a). The
optimum conditions involved irradiation of
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701348
Advanced Synthesis & Catalysis
cinnamide 2, HE 1 (3.0 equiv), and 0.1 mol % fac-
Ir(ppy)3 with white LEDs for 48 h at room
temperature.[11] Under these conditions, cinnamides
derived from substituted anilines reacted with benzyl
radical to afford 3a-3e in 41% to 66% yields.
Reversed Michael addition selectivity predominated
in all the reactions.[12] Amides derived from
substituted cinnamic acids and p-anisidine were
screened as well and found to give corresponding -
benzylated products 3f-3l
in moderate yields.
Reaction of -phenyl cinnamide gave 3m in 35%
yield. Unprotected cinnamide could also be converted
to expected product 3n under these conditions. HEs
bearing an isopropyl group or a dimethoxymethyl
group gave 3o and 3p, respectively.
Scheme 3 Photoredox dual alkylation of styrenes (a) 4 and
(b) 6 with HE 1a. Reaction conditions: 4 or 6 (0.125
mmol), 1a (0.25 mmol), fac-Ir(ppy)3 (0.1 mol %), DMF
(1.0 mL), under argon, 24 W white LEDs, rt, 48 hours;
isolated yields are provided.
Unprotected carboxylic acids are incompatible
with ionic nucleophilic reagents, so direct ionic
Michael addition reactions of -unsaturated acids
are challenging. We speculated that unsaturated
carboxylic acids could be used as radical Michael
acceptors in photoredox alkylation reactions[13]
(Scheme 4). We found that various acrylic acids 8
with aryl and alkyl substituents at the -position
reacted with HE 1a to afford hydroalkylation
products 9a–9e in moderate to good yields. -N-Boc-
protected amino acids 9f and 9g were also prepared
directly from the corresponding HE. Acid 9h, which
bears an acetal group, was obtained in 72%. In
addition, an -unsaturated ester and an amide
yielded desired products 9i and 9j, respectively, in
excellent yields.
Scheme 2. Photocatalytic hydroalkylations of cinnamides
with 1. Reaction conditions: 2 (0.125 mmol), 1 (0.375
mmol), and fac-Ir(ppy)3 (0.1 mol %), DMF (1.0 mL), 48 h,
under argon, 24 W white LEDs, rt; isolated yields are
provided.
Next, we evaluated if an electron acceptor was
necessary in the photocatatlytic reaction of HE 1. We
evaluated some dibenzylation reactions of styrenes
(Scheme 3). A reaction between styrene (4a) and 2.0
equiv of HE 1a in the presence of 0.1 mol % fac-
Ir(ppy)3 under irradiation by white LEDs afforded
dibenzylation product 5a as the major product (46%
yield). Reactions of several substituted styrenes 4
were also carried out, and products 5b–5e were
obtained in moderate yields (Scheme 3a). When -
phenyl silyl enol ether 6 was used as the substrate, the
same alkylation pattern was observed, and 7 was
obtained in 33% yield (Scheme 3b).
Scheme
4
Photocatalytic alkyl additions to -
unsaturated compounds with HEs 1. Reaction conditions: 8
(0.125 mmol), HE 1 (0.15 mmol), fac-Ir(ppy)3 (0.1 mol %),
DMF (1.0 mL), argon, 24 W white LEDs, rt, 48 h; isolated
yields are provided.
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701348
Advanced Synthesis & Catalysis
To investigate if HEs 1 can fulfill the redox cycle in the
absence of external electron acceptor, we screened external
reagents 10 bearing a redox-sensitive functional group with
1 in photocatalytic reactions. Therefore, we carried out
model reactions between 1 and 1,1-diarylethenes 3
(Scheme 5).[14] We found that a nitro group, as well as
phenol, pyridine, indole, and thiophene moieties, were
unaffected by the reaction conditions, and the
corresponding products (11b–11g) could be obtained in
moderate to good yields. In addition, we evaluated
substrates with acid-labile functional groups. Specifically,
molecules bearing ketal, acetal, or carbamate moieties
could be prepared in good to excellent yields (11h–11k). A
gram-scale reaction afforded 11i in 78% yield, and
antipruritic tolpropamine 11l was prepared in 66% yield
over three steps. Finally, intermolecular construction of the
quaternary carbon center in compound 11m was realized
with Hantzsch nitrile 13.
at which 1a was converted to 13 increased as the
wavelength threshold of the irradiating light was
decreased (Scheme 6c). This trend was similar to the
variation of the UV–vis absorption of 1a with
wavelength threshold, which suggests that excitation
of 1a was important in this fac-Ir(ppy)3-catalyzed
reaction.[15]
0.6
c)
b)
100
80
60
40
20
0
0.4
0.2
0.0
80%
21%
71%
16%
360 380 400 420 440 460 480 500 520
Wavelength (nm)
0
100 200 300 400 500
Time (min)
Scheme 6 Visible-light-induced decomposition of HE 1a.
(a) Decomposition in the presence of 0.1 mol % fac-
Ir(ppy)3 and white light. (b) Temporal dependence of the
conversion of 1a to 13. (c) Conversion of 1a to 13 after 4 h
or irradiation with light having various wavelength
thresholds, along with the UV–vis absorption of 1a for
reference.
To investigate the interaction between 1a and the
photocatalyst, we analyzed the physicochemical
properties of 1a and carried out some control
experiments. First, we measured the oxidation
potential of 1a and found it to be 1.12 V (vs SCE) in
DMF, implying that direct single-electron transfer
(SET) from ground-state 1a to excited-state fac-
Scheme 5. Hydroalkylation of 1,1-diarylethenes 10 with
HEs 1. Reaction conditions: 1,1-diarylethene 10 (0.125
mmol), HE 1 (0.15 mmol), fac-Ir(ppy)3 (0.1 mol %), DMF
( 1.0 mL), under argon, 24 W white LEDs, rt, 48 h;
isolated yields are provided. The reaction solution was
added to the irradiated reaction tube over the course of 24
h.
red
Ir(ppy)3 (E1/2 = 0.31 V vs SCE) was disfavored.
This result was confirmed by a fluorescence
quenching experiment conducted in a microcuvette to
minimize the inner filter effect.[16] No direct
quenching of excited-state fac-Ir(ppy)3 by HE 1a was
observed at either 390 or 450 nm in DMF (Figure 1).
a
3.0
From the above examples, several unusual
properties of HE 1 were noticed. It could provide
alkyl radical even without external electron acceptor.
More HE 1 generated more radical for a reaction.
Photoredox reaction of HE 1 demonstrated significant
compatibility with redox-labile function groups in
basic, neutral and acidic conditions. These
observations prompted us to explore the insight
information on substituted HE 1.
We carried out a reaction of substituted HE 1a and
0.1 mol % fac-Ir(ppy)3 in DMF under irradiation by
white LEDs in the absence of an electron acceptor
(Scheme 6a). We found that conversion of 1a to
pyridine 13 was rapid at the beginning of irradiation
and then slowed slightly as the reaction progressed;
conversion was nearly complete after approximately
8 h (Scheme 6b). In the absence of light, no reaction
occurred, even at prolonged reaction time. The speed
390 nm
450 nm
2.5
2.0
1.5
1.0
0.5
0
5
10
15
20
[1a]/[Ir]
Figure 1 Fluorescence quenching of fac-Ir(ppy)3 by 1a in
DMF in a microcuvette.
Because the fluorescence quenching experiment
indicated that electron transfer from 1a to excited-
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701348
Advanced Synthesis & Catalysis
state Ir(ppy)3 was unlikely, we switched our focus to
the possibility of the involvement of reductive species
that was present only in small amounts derived from
1a in solution. We measured the electron
paramagnetic resonance spectra of 1a in DMF at
room temperature in the presence and absence of
light (470 nm threshold, Scheme 7a). The two spectra
were quite similar and indicated that at least one
radical species was present even in the absence of a
trapping reagent (Scheme 7a). This result was
checked by means of a density functional theory
calculation of 1a at the B3LYP/6-311**(d,p) level of
theory. The C–C bond (1.56 Å) connecting the benzyl
side chain to the dihydropyridine ring was calculated
to be longer than is typical for an sp3 C–C bond
(1.52–1.53 Å),[17] implying that homolytic cleavage
of this bond might be relatively easy (Scheme 7b).
Therefore, we irradiated a solution of 1a in DMF
using light with a 470 nm threshold in the absence of
a photocatalyst for 48 h, and we observed that the
yield of decomposition product 13 was <2% (Scheme
7c). When white LEDs were used as a light source,
the yield increased to 16%. We hypothesized that
under these conditions, decomposition of 1a occurred
via dihydropyridine radical intermediate A and that
this process would be enhanced when HE 1a was in
an excited state. Radical A might be sufficiently
decomposition of 1a in DMF upon irradiation at different
wavelength
thresholds.
(d)
TEMPO-accelerated
decomposition of 1a.
Although the generation of A in the presence of 1a
alone was slow because of an unfavorable ΔH value,
coupling radical generation to a reaction such as SET
to fac-Ir(ppy)3* or radical capture might speed up the
reaction. To verify this hypothesis, we irradiated 1a
in the presence of 3.3 equiv of TEMPO as a trapping
reagent to determine whether such conditions would
result in accelerated fragmentation. After irradiation
with light with a 470 nm threshold for 48 h, gas
chromatography–mass spectrometry revealed an
approximately 9% yield of 13, along with 1,2-
diphenylethane and benzyl and hydrogen atom
adducts of TEMPO as major by-products (Scheme
7d). When we irradiated 1a and TEMPO with white
LEDs, the yield increased markedly (to 20%). This
dependence of the radical generation rate on the light
source might affect the rate of the subsequent SET
between the radical species and the photocatalyst,
which in turn might be responsible for the variable
decomposition rates observed under the conditions
shown in Scheme 7c. This SET-coupled protocol
worked as long as fac-Ir(ppy)3 was effectively excited
(that is, at wavelengths up to 490 nm) .[19]
red
reductive (E1/2 < –1.1 V vs SCE) toward the
excited-state photocatalyst.[18]
Next, to elucidate how the IrII species was converted
back to IrIII, we analyzed the products generated by
decomposition of 1a in the presence of 0.1 mol %
fac-Ir(ppy)3 under irradiation by white LEDs
(Scheme 8). In addition to 13, toluene and 1,2-
diphenylethane were observed as major products by
gas chromatography–mass spectrometry. Hydrogen
gas was detected as well and could be captured by
means of an in situ hydrogenation reaction (Scheme
8a). To determine whether hydrogen gas was
generated by reduction of protons with IrII, we carried
out a reaction using methyl-protected 1a in the
presence of fac-Ir(ppy)3 in DMF containing 2.0 equiv
of D2O (Scheme 8b). The production of D2 under
these conditions suggested that fac-IrII(ppy)3 was
reductive enough to convert D+ to a neutral deuterium
atom. When we carried out the same reaction in the
presence of alkene 10a as an additive, we obtained a
28% yield of alkylation product 11a with 34%
deuterium incorporation (Scheme 8c). Reaction of 1.2
equiv of HE 1a in which approximately 46% of the H
had been replaced with D in the presence of 10a
resulted in the production of 11a with 20% deuterium
incorporation (89% yield, Scheme 8d). A reaction
between 1a and 10a under the standard conditions
except that DMF-d7 was used as the solvent
confirmed that the deuterium did not come from the
solvent (Scheme 8e).
a)
3450
3475
3500
Field (G)
Scheme 7. Investigations of radical species derived from
HE 1a. (a) Electron paramagnetic resonance spectrum of
1a in DMF in the absence of light. (b) Structure of 1a
calculated by density functional theory. (c) Partial
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701348
Advanced Synthesis & Catalysis
Scheme 9 Plausible mechanism for photoredox reaction of
HEs 1.
Conclusion
In summary, we found that substituted HEs could
serve a photoredox radical reservoirs to generate
various carbon radicals in the absence of an external
electron acceptor. The HEs could fragment to form
alkyl radicals and a dihydropyridine radical, which
was reductive enough to generate a catalytic
IrII(ppy)3− species. Back donation of an electron from
IrII to a proton completed the redox cycle in the
absence of external electron acceptor, leading to the
formation of a hydrogen atom, which could undergo
further reaction or be released as hydrogen gas. This
ability of substituted HEs makes them versatile
reagents for photocatalytic hydroalkylation or
dialkylation reactions of various alkenes and can be
expected to lead to the design of additional novel
reactions.
Scheme 8. Investigation of hydrogen atom generation from
1a by reactions in the presence of 0.1 mol % fac-Ir(ppy)3.
(a) Products of the decomposition of HE 1a. (b)
Decomposition of methyl-protected1a in DMF/D2O under
photoredox conditions. (c) Use of 10a to capture a
deuterium atom from D2O. (d) Reaction of ca. 46%
deuterated 1a with 10a under photoredox conditions. (e)
Reaction of 1a and 10a in DMF-d7.
On the basis of these observations, we proposed
the mechanism of reaction involving 1 and 10 in
Scheme 9a. The mechanism starts with fragmentation
of HE 1 into dihydropyridine radical A and alkyl
radical B, a process that is accelerated by the
formation of excited-state 1* (upon irradiation at
<420 nm). Radical A transfers an electron to excited-
state Ir*, giving rise to protonated pyridine C and an
IrII species. The alkyl radical from 1 forms an adduct
with alkene 10, giving intermediate D. Radical D
takes one electron from IrII spices, furnishing carbon
cationic intermediate E. A protonation of E with C
gives product 11. Another pathway was also depicted
in Scheme 9b. The electron transfers from IrII to
protonated pyridine C leads to pyridine 13 and
hydrogen atom. The later then combines with carbon
radical D, producing product 11.
Experimental Section
General Procedure for Synthesis of 3
A solution of fac-Ir(ppy)3 (0.08 mg, 0.1 mol %), a HE 1
(0.375 mmol), and a substituted cinnamide 2 (0.125 mmol)
in DMF (1 mL) was added with a syringe pump over the
course of 24 h to an empty tube equipped with a stirrer bar
with irradiation of 24 W white LEDs under nitrogen. The
reaction mixture was stirred under irradiation at room
temperature for another 24 h and then diluted with H2O
and extracted three times with ethyl acetate. The combined
organic layers were washed with brine, dried over Na2SO4,
and filtered, and the filtrate was concentrated under
reduced pressure. The residue was purified by
chromatography on silica gel.
General Procedure for Syntheses of 5 and 7
A reaction tube equipped with a magnetic stir bar was
charged with fac-Ir(ppy)3 (0.08 mg, 0.1 mol %), a HE 1
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701348
Advanced Synthesis & Catalysis
(0.25 mmol), a substituted styrene (0.125 mmol), and DMF
(1 mL) under nitrogen. The mixture was stirred under
irradiation by 24 W white LEDs at room temperature for
48 hours. The mixture was then diluted with H2O and
extracted three times with ethyl acetate. The combined
organic layers were washed with brine, dried over Na2SO4,
and filtered, and the filtrate was concentrated under
reduced pressure. The residue was purified by
chromatography on silica gel.
Chen, Z.-J. Li, C.-H. Tung, Acc. Chem. Res. 2014, 47,
2177.
[4] a) K. Deuchert, S. Hünig, Angew. Chem. Int. Ed. 1978,
17, 875; Angew. Chem. 1978, 90, 927; b) A. Studer, D.
P. Curran, Angew. Chem. Int. Ed. 2016, 55, 58; Angew.
Chem. 2016, 128, 58.
[5] a) G. Li, R. Chen, L. Wu, Q. Fu, X. Zhang, Z. Tang,
Angew. Chem. Int. Ed. 2013, 52, 8432; Angew. Chem.
125, 8590; b) G. Li, L. Wu, G. Lv, H. Liu, Q. Fu, X.
Zhang, Z. Tang, Chem. Commun. 2014, 50, 6246.
General Procedure for Syntheses of 9 and 11
A reaction tube equipped with a magnetic stir bar was
charged with fac-Ir(ppy)3 (0.08 mg, 0.1 mol %), a HE 1
(0.15 mmol), an -unsaturated acid derivative 8 or diaryl
ethane 10 (0.125 mmol, 1.0 equiv), and DMF (1 mL) under
a nitrogen atmosphere. The mixture was stirred under
irradiation of 24 W white LED strip at room temperature
for 48 hours. Then the mixture was diluted with H2O and
extracted three times with ethyl acetate. The combined
organic layers were washed with brine, dried over Na2SO4,
and filtered, and the filtrate was concentrated under
reduced pressure. The residue was purified by
chromatography on silica gel.
[6] For examples of the use of unsubstituted HEs in
photoredox reactions, see: a) J. M. R. Narayanam, J. W.
Tucker, C. R. J. Stephenson, J. Am. Chem. Soc. 2009,
131, 8756; b) R. S. Andrews, J. J. Becker, M. R. Gagné,
Angew. Chem. Int. Ed. 2010, 49, 7274; Angew. Chem.,
2010, 122, 7432; c) Y. Chen, A. S. Kamlet, J. B.
Steinman, D. R. Liu, Nat. Chem. 2011, 3, 146; d) M.-H.
Larraufie, R. Pellet, L. Fensterbank, J.-P. Goddard, E.
Lacôte, M. Malacria, C. Ollivier, Angew. Chem. Int. Ed.
2011, 50, 4463; Angew. Chem., 2011, 123, 4555; e) L. J.
Rono, H. G. Yayla, D. Y. Wang, M. F. Armstrong, R.
R. Knowles, J. Am. Chem. Soc. 2013, 135, 17735; f) J.
Zhang, Y. Li, F. Zhang, C. Hu, Y. Chen, Angew. Chem.
Int. Ed. 2016, 55, 1872; Angew. Chem. 2016, 128,
1904; g) L. Qi, Y. Chen, Angew. Chem. Int. Ed. 2016,
55, 13312; Angew. Chem. 2016, 128, 13506; h) C.
Wang, K. Harms, E. Meggers, Angew. Chem. Int. Ed.
2016, 55, 13495; Angew. Chem. 2016, 128, 13693; i) K.
N. Lee, Z. Lei, M.-Y. Ngai, J. Am. Chem. Soc. 2017,
139, 5003.
Acknowledgments
This work was supported by the National Science Foundation of
China (nos. 21572099 and 21332005) and the Natural Science
Foundation of Jiangsu Province (no. BK20151379). We
appreciate helpful discussions with Prof. Dr. Weiwei Zhao and
assistance from Dr. Nan Zhang.
References
[1] a) K. Zeitler, Angew. Chem. Int. Ed. 2009, 48, 9785;
Angew. Chem. 2009, 121, 9969; b) J. M. R. Narayanam,
C. R. J. Stephenson, Chem. Soc. Rev. 2011, 40, 102; c)
J. Xuan, W.-J. Xiao, Angew. Chem. Int. Ed. 2012, 51,
6828; Angew. Chem. 2012, 124, 6934; d) C. K. Prier, D.
A. Rankic, D. W. C. MacMillan, Chem. Rev. 2013, 113,
5322; e) Y. Xi, H. Yi, A. Lei, Org. Biomol. Chem. 2013,
11, 2387; f) M. N. Hopkinson, B. Sahoo, J.-L. Li, F.
Glorius, Chem. Eur. J. 2014, 20, 3874; g) D. M.
Schultz, T. P. Yoon, Science 2014, 343; h) M.
Nakajima, E. Fava, S. Loescher, Z. Jiang, M. Rueping,
Angew. Chem. Int. Ed. 2015, 54, 8828; Angew. Chem.
2015, 127, 8952; i) J. C. Tellis, C. B. Kelly, D. N.
Primer, M. Jouffroy, N. R. Patel, G. A. Molander, Acc.
Chem. Res. 2016, 49, 1429; j) K. Nakajima, Y. Miyake,
Y. Nishibayashi, Acc. Chem. Res. 2016, 49, 1946; k) N.
A. Romero, D. A. Nicewicz, Chem. Rev. 2016, 116,
10075; l) K. L. Skubi, T. R. Blum, T. P. Yoon, Chem.
Rev. 2016, 116, 10035; m) C. B. Kelly, N. R. Patel, D.
N. Primer, M. Jouffroy, J. C. Tellis, G. A. Molander,
Nat. Protocols 2017, 12, 472; n) E. Meggers, Angew.
Chem. Int. Ed. 2017, 56, 5668; Angew. Chem. 2017,
129, 5760; o) J. K. Matsui, S. B. Lang, D. R. Heitz, G.
A. Molander, ACS Catal. 2017, 7, 2563.
[7] K. Nakajima, S. Nojima, K. Sakata, Y. Nishibayashi,
ChemCatChem 2016, 8, 1028.
[8] W. Chen, Z. Liu, J. Tian, J. Li, J. Ma, X. Cheng, G. Li,
J. Am. Chem. Soc. 2016, 138, 12312.
[9] a) K. Nakajima, S. Nojima, Y. Nishibayashi, Angew.
Chem. Int. Ed. 2016, 55, 14106; Angew. Chem. 2016,
128, 14312; b) Á. Gutiérrez-Bonet, J. C. Tellis, J. K.
Matsui, B. A. Vara, G. A. Molander, ACS Catal. 2016,
8004.
[10] For detailed discussion, see supporting information.
[11] For details on optimization of the conditions, see
Table S1 in supporting information.
[12] For discussion of this regioselectivity on the basis of
DFT calculations, see section 13 in SI.
[13] For some examples of the use of an unsaturated acid,
see: a) L. Chu, C. Ohta, Z. Zuo, D. W. C. MacMillan,
J. Am. Chem. Soc. 2014, 136, 10886; b) X. J. Tang, Z.
Zhang, W. R. Dolbier, Chem. Eur. J. 2015, 21, 18961.
For example of the addition of N-stabilized methyl
radicals to unsaturated esters, see: c) Y. Miyake, K.
Nakajima, Y. Nishibayashi, J. Am. Chem. Soc. 2012,
134, 3338.
[2] N. Corrigan, S. Shanmugam, J. Xu, C. Boyer, Chem.
Soc. Rev. 2016, 45, 6165.
[14] a) S. Donck, A. Baroudi, L. Fensterbank, J.-P.
Goddard, C. Ollivier, Adv. Synth. Catal. 2013, 355,
1477; b) H. Huo, X. Shen, C. Wang, L. Zhang, P.
Rose, L.-A. Chen, K. Harms, M. Marsch, G. Hilt, E.
Meggers, Nature 2014, 515, 100; c) R. Honeker, R. A.
[3] a) P. Lianos, J. Hazard. Mater. 2011, 185, 575; b) F.
Wang, W.-J. Liang, J.-X. Jian, C.-B. Li, B. Chen, C.-H.
Tung, L.-Z. Wu, Angew. Chem. Int. Ed. 2013, 52,
8134; Angew. Chem. 2013, 125, 8292; d) L.-Z. Wu, B.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701348
Advanced Synthesis & Catalysis
Garza-Sanchez, M. N. Hopkinson, F. Glorius, Chem.
Technology, 1st ed. (Ed.: S. T. Handy), InTech,
Croatia, 2011, p. 401.
Eur. J. 2016, 22, 4395; d) H. Li, C. Shan, C.-H. Tung,
Z. Xu, Chem. Sci. 2017, 8, 2610; e) M. Silvi, C.
Sandford, V. K. Aggarwal, J. Am. Chem. Soc. 2017,
139, 5736
[17] F. H. Allen, O. Kennard, D. G. Watson, L. Brammer,
A. G. Orpen, R. Taylor, J. Chem. Soc. Perkin. Trans.
2 1987, S1-S19.
[15] a) X.-Q. Zhu, Y.-C. Liu, J.-P. Cheng, J. Org. Chem.
1999, 64, 8980-8981; a) J. Jung, J. Kim, G. Park, Y.
You, E. J. Cho, Adv. Synth. Catal. 2016, 358, 74-80;
b) W. Chen, H. Tao, W. Huang, G. Wang, S. Li, X.
Cheng, G. Li, Chem. Eur. J. 2016, 22, 9546-9550.
[18] W. Huang, W. Chen, G. Wang, J. Li, X. Cheng, G. Li,
ACS Catal. 2016, 6, 7471.
[19] For the UV–vis absorption spectrum of fac-Ir(ppy)3 in
DMF, see SI. At 490 nm, the absorption was weak.
[16] K. Pawlak, A. Skrzypczak, G. E. Bialek-Bylka, in
Application s of Ionic Liquids in Science and
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701348
Advanced Synthesis & Catalysis
FULL PAPER
Substituted Hantzsch Esters as Versatile
Radical Reservoirs in Photoredox Reactions
Adv. Synth. Catal. Year, Volume, Page – Page
Fangjun Gu,a Wenhao Huang,a Xu Liu,a Wenxin
Chen,a Xu Chenga,b*
8
This article is protected by copyright. All rights reserved.