C(sp3)-H Bond Acylation with N -Acyl Imides under Photoredox/ Nickel Dual Catalysis

Article abstract of DOI:10.1055/s-0040-1707301

A novel Ni/photoredox-catalyzed acylation of aliphatic substrates, including simple alkanes and dialkyl ethers, has been developed. The method combines C-N bond activation of amides with a radical relay mechanism involving hydrogen-atom transfer. The protocol is operationally simple, employs bench-stable N -acyl imides as acyl-transfer reagents, and permits facile access to alkyl ketones under very mild conditions.

Full text of DOI:10.1055/s-0040-1707301

SYNLETT
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2020, 31, A–F
cluster
A
Modern Nickel-Catalyzed Reactions
T. Kerackian et al.
Cluster
Synlett
C(sp3)–H Bond Acylation with N-Acyl Imides under Photoredox/
Nickel Dual Catalysis
Taline Kerackiana
Synthetic development and mechanistic studies
Antonio Reinaa
Tetiana Krachkoa
Hugo Boddaerta
Didier Bouyssia
Nuno Monteiroa
C(acyl)–C(sp3) bond
LEDs
Ni-catalyzed
C–N bond activation
photocatalytic
HAT
formation
O
O
O
Ir
Ni
CI
H
R
R
N
+
17 examples; up to 71% yield
O
alkanes & ethers
Abderrahmane Amgoune*a,b
0
0
0
0
-
0
0
0
2
-
6
1
9
5
-1
4
1
1
PF6
F3C
F
Key mechanistic insights
Stoichiometric studies:
2Cl
a Univ Lyon, Université Lyon 1, Institut de Chimie et Biochimie
Moléculaires et Supramoléculaires, UMR 5246 du CNRS, 1 rue
Victor Grignard, 69100 Villeurbanne, France
abderrahmane.amgoune@univ-lyon1.fr
b Institut Universitaire de France (IUF), 1 rue Descartes, 75231 Par-
is, France
tBu
tBu
tBu
OH2
N
N
N
OH2
facile C–N bond oxidative addition at Ni(0)
and decarbonylation (X-ray)
N
N
F
F
Ni
Ir
OH2
OH2
N
Catalytic studies:
competence of Ni(I) species
tBu
F
F3C
Published as part of the Cluster Modern Nickel-Catalyzed Reactions
Corresponding Author
Received: 31.07.2020
Accepted after revision: 31.08.2020
Published online: 08.10.2020
tionalized alkyl ketones. Within this context, resonance-de-
stabilized N-acyl imides stand amongst other carbonyl-type
compounds as promising acyl electrophiles5 owing to their
remarkable stability and their documented capability to
engage in nickel-catalyzed cross-coupling reactions
through C–N bond activation to forge C(acyl)–C(sp3)
bonds.6 For instance, in 2017, Molander and co-workers7 re-
ported the use of N-acylsuccinimides as suitable acyl-trans-
fer reagents for photoredox nickel-catalyzed acylation of
functionalized alkyl trifluoroborate nucleophiles.8 This pro-
vided a strong impetus to develop complementary methods
that would exploit other readily available inexpensive ali-
phatic substrates.
DOI: 10.1055/s-0040-1707301; Art ID: st-2020-k0423-c
Abstract A novel Ni/photoredox-catalyzed acylation of aliphatic sub-
strates, including simple alkanes and dialkyl ethers, has been devel-
oped. The method combines C–N bond activation of amides with a rad-
ical relay mechanism involving hydrogen-atom transfer. The protocol is
operationally simple, employs bench-stable N-acyl imides as acyl-trans-
fer reagents, and permits facile access to alkyl ketones under very mild
conditions.
Key words nickel catalysis, photocatalysis, acylation, radical relay, C–
N bond activation, ketones
Taking inspiration from recent progress in cross-electro-
phile coupling reactions, i.e. the direct catalytic joining of
two different electrophiles that avoids the need for pre-
formed carbon nucleophiles,9 we developed a novel dual-
catalytic acylation process using nonactivated alkyl bro-
mides as electrophilic partners for N-acylsuccinimides. The
process was designed to follow a radical relay pathway
where a silyl radical is generated photocatalytically and
serves as an abstracting agent to activate the alkyl bromide
through homolytic C–Br bond cleavage (Scheme 1A).10 An-
other exciting challenge that we subsequently considered
was the design of an alternative strategy that would rely on
the selective C(sp3)–H bond activation of simple alkanes
through a radical hydrogen-atom transfer (HAT) pro-
cess.11,12
Ketones are ubiquitous chemical entities in everyday
life. Found abundantly in nature, ketone groups are also
present in numerous value-added pharmaceuticals and ag-
rochemicals, as well as in fragrances, flavors, and fine
chemicals. Alkyl ketones are extremely important scaffolds
in multistep organic syntheses and offer multiple opportu-
nities for late-stage derivatization of complex molecules.1
The invention of new methods and strategies for the intro-
duction of acyl functionalities into aliphatic backbones is
therefore an ever-present challenge that has significant po-
tential in various fields of chemistry.
Over the last decade, dual visible-light photoredox and
nickel catalysis has emerged as a powerful but operational-
ly simple strategy for achieving, under very mild reaction
conditions, challenging C(sp2)–C(sp3) bond disconnections
that are beyond the reach of classical cross-coupling ap-
proaches.2,3 Hence, this method brings prospects for inno-
vation in the area of catalytic acylation reactions of C(sp3)-
hybridized substrates,4 and thereby offers a new paradigm
for the synthesis of structurally diverse and highly func-
The groups of Doyle and Molander independently
demonstrated that organohalides could serve as both cou-
pling partners and sources of halide radicals that act as po-
tent H-abstracting agents in Ni/photoredox cross-coupling
reactions with aliphatic substrates.13 Inspired by these sem-
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
T. Kerackian et al.
Cluster
Synlett
zoylglutarimide also proved to be a reactive substrate but
gave 3a in a lower yield (entry 9). Notably, by employing up
to five equivalents of cyclohexane, ketone 3a was isolated in
a fair 53% yield after 24 hours of reaction. These conditions
(entry 10) were therefore established as our standard con-
ditions.17 Note that the use of cyclohexane as the solvent
led essentially to no reaction, possibly due to the limited
solubility of the catalyst and base in this reaction medium
(entry 11).
O
O
R
O
Ni cat.
Ir photocat.
R1
R1
Y
+
N
R
R2
R2
abstracting agent
O
hν
alkyl radical
precursor
1° or 2° alkyl ketone
A. Cross-coupling with alkyl bromides (Y = Br; prior work)
C(sp3)–Br bond activation via Br-atom abstraction by silyl radical
Ir/hν
C(sp3)
(Me3Si)3Si
Br
(Me3Si)3SiH
base
Table 1 Reaction of N-Benzoylsuccinimide (1a) with Cyclohexane: Se-
B. Cross-coupling with alkanes (Y = H; this work)
C(sp3)-H bond activation via H-atom abstraction by chlorine radical
lected Experimentsa
blue LEDs
C(sp3)
Cl
H
LiCl
O
O
[Ni] cat I (4 mol%)
[Ir] cat II (0.5 mol%)
O
O
H
Ph
N
+
Ph
K3PO4 (2 equiv)
Na2WO4·2H2O (1 equiv)
LiCl (1 equiv)
C. Photo/Ni catalytic generation of chlorine radical
1a
2a
(3 equiv)
3a
R(CO) [Ni] NSucc
PC/hν
homolysis
benzene, rt, 72 h
Cl
Cl
R(CO) [Ni] Cl
ligand exchange
Entry
Reaction conditions
Yieldb (%) of 3a
1
2
as shown
50
Scheme 1 Ni/Photoredox alkylation of amides with alkyl bromides or
simple alkanes based on a radical relay process
no K3PO4
27c
3
no Na2WO4·2H2O
no K3PO4 or Na2WO4·2H2O
no LiCl
40d
4
18
inal reports, we questioned whether this strategy might be
applicable to the coupling of amides with alkanes in the
presence of an exogenous source of halide anions, e.g. lithi-
um chloride (Scheme 1B).14 We hypothesized that oxidative
addition of the amide to nickel and subsequent succinim-
ide-to-chloride ligand exchange might readily generate an
intermediate acyl–nickel chloride complex that could serve
as source of chlorine radicals through Ni–Cl bond homolysis
(Scheme 1C).12d,15
5
3
6
no Ir photocatalyst
no light (darkness)
no Ni catalyst
0
7
0
8
0
9
N-benzoylglutarimide instead of 1a
cyclohexane (5 equiv), 24 h
cyclohexane as solvent
42
10
11
61 (53)e
1
In our initial exploratory studies,16 we used the coupling
of N-benzoylsuccinimide (1a) with cyclohexane as a model
system (Table 1). We found that the desired cross-coupling
product 3a was formed in optimal yields by using [Ni(dtbb-
py)(H2O)4]Cl2 (I; 4 mol%) (dtbbpy = 4,4′-di-tert-butyl-2,2′-
bipyridine) and Ir{[dF(CF3)ppy]2(dtbbpy)}PF6 (II; 0.5 mol%)
a Reactions were performed in benzene on a 0.6 mmol scale with irradia-
tion by a 40 W blue LED Kessil lamp. See the Supporting Information for
details of the lighting setup.
b Determined by GC-MS with benzophenone as internal standard.
c Na2WO4·2H2O (3 equiv).
d K3PO4 (3 equiv).
e Isolated yield.
[dF(CF3)ppy
=
2-(2,4-difluorophenyl)-5-(trifluorometh-
Having a reliable acylation protocol in hand (Conditions
A), we explored the reactivity of various acyl succinimides
and potential HAT substrates (Scheme 2). Various electron-
rich and electron-neutral aroyl succinimides underwent
coupling with cyclohexane in fair yields (3a–c), whereas
electron-deficient derivatives were found to give signifi-
cantly lower yields (3d and 3e). The scope was expanded to
acyl succinimides bearing alkyl groups, as illustrated by 3f,
thereby providing access to dialkyl ketones. Notably, other
nonactivated cycloalkanes also participated in the coupling
process (3g and 3h). We also attempted the acylation of al-
kyl ethers to access the corresponding -functionalized ke-
tones. For instance, we examined the use of dialkyl ethers
as both alkylating reagents and solvents, as safer alterna-
tives to benzene. In our initial experimental observations
on the coupling of 1a with tetrahydrofuran,16 we found that
yl)pyridine] complexes as a dual-catalytic system under ir-
radiation by a 40 W blue LED lamp. Remarkably, solvent
evaluation indicated that only benzene was suitable for de-
livering the desired ketone. Another critical feature for the
success of the coupling reaction was the need for an exter-
nal source of halogen atom. Lithium chloride was found to
be the most effective source among the salts tested (LiCl,
NaCl, KCl, TBAC, Et3N+Bn Cl–, NH4Cl, and NaBr), and increas-
ing the amount of this additive beyond one equivalent did
not significantly increase the yield. Additionally, the reac-
tion proceeded more efficiently by using a combination of
tripotassium phosphate and sodium tungstate as a dual-
base system (Table 1, entries 1–5).12d Control experiments
revealed that the dual-catalytic system and light irradiation
were essential for this transformation (entries 6–8). N-Ben-
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

C
T. Kerackian et al.
Cluster
Synlett
the new procedure (conditions B) required higher catalysts
loadings (10 mol% of catalyst I; 2 mol% of catalyst II), but
proceeded efficiently without the need for sodium tung-
state as an additive.18 This is illustrated by the synthesis of a
series of 2-acyltetrahydrofurans 3i–l in moderate to good
isolated yields. The same procedure successfully gave cou-
pling products containing cyclic or linear aliphatic ethers
such as 1,4-dioxane, diethyl ether, or 1,2-dimethoxyethane
(3m–q). Notably, a separable 2.3:1 mixture of two regioiso-
meric products 3q and 3q′ was generated by the acylation
of DME.
Interestingly, the byproducts regularly obtained from
the reaction of N-acylsuccinimides with alkanes were the
symmetrical dialkyl ketones deriving from homocoupling
of the alkane, together with the corresponding C(Ar)–C(sp3)
bond-formation products. A series of experiments were
carried out to gain information on the reaction pathway
and the origin of these products (Scheme 3). As a prototyp-
ical example, the coupling of N-benzoylsuccinimide (1a)
with cyclohexane afforded the desired cross-coupling prod-
uct (3a), along with small amount of cyclohexylbenzene
(4a; ≤10%) and dicyclohexylmethanone (3f; ≤20%), suggest-
ing the occurrence of a decarbonylative pathway.5g,9d Ac-
cordingly, an excess of 1a (10 equiv) was found to react
spontaneously with (dtbbpy)Ni(COD) (1 equiv) to afford a
mixture of complexes assigned to the corresponding Ni(II)-
aryl complex III and the Ni(II)-acyl complex (IV) in a 3:2 ra-
tio (1H NMR), together with the dicarbonyl complex (dtbb-
py)Ni(CO)2 (V) (Scheme 3A).16 By adjusting the stoichiome-
try of (dtbbpy)Ni(COD) (1.5 equiv) and 1a (1 equiv), the
Ni(II)-aryl complex III could be obtained selectively and iso-
lated for full characterization, including single-crystal X-ray
diffraction analysis (Scheme 3A).19 The molecular structure
of III displays a square-planar geometry of the nickel center,
and represents a unique example of structural characteri-
zation of a Ni(II)–NSucc complex formed by a C–N bond oxi-
dative addition–decarbonylation sequence of amides with
Ni(0).20 All attempts to generate the acyl complex IV selec-
tively or to isolate it from the reaction mixture were unsuc-
cessful. This result indicates that N-acylsuccinimides un-
dergo spontaneous oxidative addition to Ni(0) followed by
facile decarbonylation, providing a plausible pathway to the
symmetrical dialkyl ketones21 and the decarbonylative
products.22 Comparatively, the reaction of benzoyl chloride
with (dtbbpy)Ni(COD) led exclusively to the corresponding
acyl-Ni(II) chloride complex VI.16,12b
O
O
O
H
R1
[Ni] cat. I/[Ir] cat. II
R1
N
R
+
R
base/LiCl
blue LEDs
R2
R2
O
conditions A or B
1
2
3
O
O
O
tBu
MeO
3a; 53% (A)
3c; 58% (A)
3b; 64% (A)
O
O
O
NC
MeO2C
3d; 18% (A)
3e; 16% (A)
3f; 52% (A)
O
O
MeO
3h; 35% (A)
3g; 53% (A)
O
O
O
O
O
O
We then compared the catalytic activity of complex I
with that of other potent nickel catalytic intermediates
(Scheme 3B). Surprisingly, the use of Ni(COD)2 with dtbbpy
as an exogenous ligand instead of complex I resulted in a
very low 8% reaction yield. Furthermore, no reaction was
observed with the Ni(II)-aryl intermediate III. On the other
hand, the nickel(II)-acyl chloride complex VI was found to
be catalytically competent, affording very similar results to
those with complex I. Notably, only trace amounts of the
desired product were observed in the absence of LiCl, con-
firming its key role in the reaction, probably through suc-
cinimide-to-chloride exchange at nickel. At this stage, the
involvement in the catalytic cycle of active paramagnetic
species generated in situ from nickel(II) complexes was en-
visioned. Indeed, as recently demonstrated by the group of
Hazari,23 paramagnetic Ni(I) species with bipyridine ligands
can participate as key intermediates in nickel-catalyzed
C(sp2)–C(sp3) bond-forming reactions. We decided to ex-
amine this possibility, and we prepared the [(dtbb-
py)Ni(Cl)]2 dimer VII by the reported procedure.16 Remark-
MeO
3i; 37% (A); 53% (B)
3j; 58% (B)
3k; 47% (B)
O
O
O
O
O
O
O
F
O
3l; 66% (B)
3m; 49% (A); 61% (B)
3n; 49% (B)
O
O
O
α
α'
O
O
O
O
MeO
O
3o; 71% (B)
3p; 37% (B)
3q/3q'; 69% (B); α/α' = 2.3:1
Scheme 2 Scope of N-acylsuccinimides and alkanes. Reagents and con-
ditions A: 0.6 mmol scale; Ni cat I (4 mol%), Ir cat II (0.5 mol%), K3PO4 (2
equiv), Na2WO4·2H2O (1 equiv), LiCl (1 equiv), alkane (5 equiv), ben-
zene (0.1 M), 40 W blue LED Kessil lamp (455 nm), 24–48 h. Reagents
and conditions B: 0.4 mmol scale Ni cat I (10 mol%), Ir cat II (2 mol%),
K3PO4 (1.5 equiv); LiCl (1 equiv), alkane as solvent (0.125 M), 30 W blue
LED lamp (450 nm), 24–48 h. Isolated yields are reported.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

D
T. Kerackian et al.
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Synlett
ably, the paramagnetic nickel species VII was found to be
catalytically active and performed more efficiently than the
nickel(II)-dichloro complex I.
These preliminary experiments suggest that the nickel-
catalyzed acylation of C(sp3)–H bonds with N-acylsuccin-
imides does not follow the same pathway as that proposed
A. Evidence for nickel-promoted spontaneous decarbonylative pathway of
N-acyl-succinimides
tBu
tBu
tBu
O
O
N
N
N
N
O
Ph
N
N
N
Ph
O
rt
Ni
Ni
Ni
+
+
Ph
O
N
N
O
O
O
tBu
tBu
III
60
100
IV
tBu
40
-
10.0 equiv
1.0 equiv
1.0 equiv
1.5 equiv
+
(dtbbpy)Ni(CO)2
(V)
III (X-ray)
B. Evaluation of catalytic activity of nickel complexes for the acylation of
cyclohexane with N-acylsuccinimide
O
Ph
[Ni] cat (10 mol%)
Ph
+
O
O
O
[Ir] cat II (1 mol%)
H
LiCl (1 equiv)
Ph
N
+
3a
4a
O
K3PO4 (2 equiv)
Na2
WO4·2H2O (1 equiv)
benzene, rt, 24 h
30 W blue LEDs
2a
1a
+
(5 equiv)
3f
Catalysts and associated yields (%)a of 3a; 4a; 3f
2Cl
tBu
tBu
tBu
tBu
OH2
Ni
N
N
N
N
N
OH2
OH2
Ph
N
Ni
Ni
O
N
OH2
O
tBu
tBu
I
formed in situ
III
55; 8; 18
8; 2; 0
0; 0; 0
19; 8; 3 (no LiCl)
tBu
tBu
tBu
tBu
O
N
N
N
N
Cl
Cl
Ph
Ni
Ni
Ni
Cl
N
N
tBu
tBu
VII
VI
54; 8; 10
78; 11; 10
2; 1; 0 (no LiCl)
a Yields determined by GC-MS with benzophenone as an internal standard
Scheme 3 (A) Reaction of 1a with (dtbbpy)Ni(COD) and (B) the catalytic behavior of several nickel species
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

E
T. Kerackian et al.
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for other acyl substrates. In related coupling processes in-
volving chloroformates and acyl chlorides as substrates re-
ported by the groups of Doyle12d and Shibasaki,12b the oxi-
dative addition of the acyl substrate proceeds at Ni(0) spe-
cies. With N-acylsuccinimides, although oxidative addition
of the C–N bond to Ni(0) readily occurs, our experiments
suggest that the C–N bond-activation step proceeds at Ni(I)
during the catalysis. Further mechanistic studies are clearly
necessary to confirm the specific behavior of these acyl
substrates, which might be exploited to design complemen-
tary mechanistic sequences.24
In summary, we have described a new acylation reac-
tion of C(sp3)–H bonds by using bench-stable N-acyl imide
substrates. The dual-catalytic process combines nickel-cata-
lyzed C–N bond activation with photocatalytic HAT, and
provides operationally simple access to valuable alkyl ke-
tones. Notably, N-acylsuccinimides were shown to undergo
ready C–N bond oxidative addition to Ni(0), followed by de-
carbonylation, under mild conditions. Identification of by-
products of the acylation reaction suggested that the devel-
opment of decarbonylative cross-coupling pathways under
mild conditions by using photoredox/Ni catalysis can be en-
visioned. Further investigations are underway to achieve a
better understanding of the reaction mechanism.
(3) For overviews of recent photoredox methods for ketone synthe-
sis, see: (a) Chalotra, N.; Sultan, S.; Shah, B. A. Asian J. Org. Chem.
2020, 9, 863. (b) Lee, K. N.; Ngai, M.-Y. Chem. Commun. 2017, 53,
13093.
(4) For reviews of metal-catalyzed acylative cross-coupling reac-
tions for ketone synthesis, see: (a) Dieter, R. K. Tetrahedron
1999, 55, 4177. (b) Gooßen, L. J.; Rodriguez, N.; Gooßen, K.
Angew. Chem. Int. Ed. 2008, 47, 3100. (c) Buchspies, J.; Szostak,
M. Catalysts 2019, 9, 53. (d) Ogiwara, Y.; Sakai, N. Angew. Chem.
Int. Ed. 2020, 59, 574.
(5) For general illustrations of the reactivity of twisted amides as
acylating reagents, see: (a) Meng, G.; Shi, S.; Szostak, M. Synlett
2016, 2530. (b) Pace, V.; Holzer, W.; Meng, G.; Shi, S.;
Lalancette, R.; Szostak, R.; Szostak, M. Chem. Eur. J. 2016, 22,
14494. (c) Shi, S.; Szostak, M. Synthesis 2017, 49, 3602.
(d) Osumi, Y.; Liu, C.; Szostak, M. Org. Biomol. Chem. 2017, 15,
8867. (e) Meng, G.; Szostak, M. Eur. J. Org. Chem. 2018, 2018,
2352. (f) Szostak, R.; Szostak, M. Org. Lett. 2018, 20, 1342.
(g) Liu, C.; Szostak, M. Org. Biomol. Chem. 2018, 16, 7998.
(6) For selected examples, see: (a) Simmons, B. J.; Weires, N. A.;
Dander, J. E.; Garg, N. K. ACS Catal. 2016, 6, 3176. (b) Liu, X.;
Hsiao, C.-C.; Guo, L.; Rueping, M. Org. Lett. 2018, 20, 2976.
(c) Yu, C.-G.; Matsuo, Y. Org. Lett. 2020, 22, 950. (d) Zhuo, J.;
Zhang, Y.; Li, Z.; Li, C. ACS Catal. 2020, 10, 3895. For an example
of aryl ketone synthesis, see: (e) Ni, S.; Zhang, W.; Mei, H.; Han,
J.; Pan, Y. Org. Lett. 2017, 19, 2536.
(7) Amani, J.; Alam, R.; Badir, S.; Molander, G. A. Org. Lett. 2017, 19,
2426.
(8) For similar strategies making use of acyl chlorides or carboxylic
acids as electrophilic partners, see: (a) Amani, J.; Sodagar, E.;
Molander, G. A. Org. Lett. 2016, 18, 732. (b) Amani, J.; Molander,
G. A. J. Org. Chem. 2017, 82, 1856. (c) Amani, J.; Molander, G. A.
Org. Lett. 2017, 19, 3612. (d) Levernier, E.; Corcé, V.;
Rakotoarison, L.-M.; Smith, A.; Zhang, M.; Ognier, S.; Tatoulian,
M.; Ollivier, C.; Fensterbank, L. Org. Chem. Front. 2019, 6, 1378.
(9) For a review of acylative cross-electrophile coupling reactions,
see: Moragas, T.; Correa, A.; Martin, R. Chem. Eur. J. 2014, 20,
8242. For rare examples of cross-electrophile coupling reactions
employing amides, see refs. 6c–e.
Funding Information
Financial support from the Université de Lyon, IDEXLYON project
(ANR-16_IDEX-0005) and the Agence Nationale de la Recherche (ANR-
JCJC-2016-CHAUCACAO) is gratefully acknowledged. T.K. thanks the
French Ministry of Higher Education and Research for a doctoral fel-
lowship.
U
n
iversité
d
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Ly
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n
(A
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0
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enceNatio
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Acknowledgment
(10) Kerackian, T.; Reina, A.; Bouyssi, D.; Monteiro, N.; Amgoune, A.
Org. Lett. 2020, 2240.
We thank Guillaume Pilet [(LMI), UMR 5615 CNRS-UCBL] for X-ray
diffraction measurements, and C. Duchamp (Centre Commun de
Spectrométrie de Masse, Université Lyon 1) for mass spectrometry
analyses.
(11) For seminal papers on HAT-mediated Ni/photoredox cross-cou-
pling reactions, see: (a) Zuo, Z.; Ahneman, D. T.; Chu, L.; Terrett,
J. A.; Doyle, A. G.; MacMillan, D. W. C. Science 2014, 345, 437.
(b) Shaw, M. H.; Shurtleff, V. W.; Terrett, J. A.; Cuthbertson, J. D.;
MacMillan, D. W. C. Science 2016, 352, 1304. For general reviews
of HAT-mediated photocatalytic reactions, see: (c) Capaldo, L.;
Ravelli, D. Eur. J. Org. Chem. 2017, 2056. (d) Capaldo, L.; Lafayette
Quadri, L.; Ravelli, D. Green Chem. 2020, 22, 3376.
(12) For selected papers on acylation reactions based on HAT-medi-
ated Ni/photoredox cross-coupling reactions, see: (a) Joe, C. L.;
Doyle, A. G. Angew. Chem. Int. Ed. 2016, 55, 4040. (b) Sun, Z.;
Kumagai, N.; Shibasaki, M. Org. Lett. 2017, 19, 3727. (c) Kang, B.;
Hong, S. H. Chem. Sci. 2017, 8, 6613. (d) Ackerman, L. K. G.;
Martinez Alvarado, J. I.; Doyle, A. G. J. Am. Chem. Soc. 2018, 140,
14059. (e) Schirmer, T. E.; Wimmer, A.; Weinzierl, F. W. C.;
König, B. Chem. Commun. 2019, 55, 10796. (f) Krach, P. E.;
Dewanji, A.; Yuan, T.; Rueping, M. Chem. Commun. 2020, 56,
6082.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1707301.
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References and Notes
(1) Siegel, H.; Eggersdorfer, M. In Ullmann's Encyclopedia of Indus-
trial Chemistry; Bohnet, M., Ed.; Wiley-VCH: Weinheim, 2000,
DOI: 10.1002/14356007.a15_077.
(2) For reviews, see: (a) Twilton, J.; Le, C.; Zhang, P.; Shaw, M. H.;
Evans, R. W.; MacMillan, D. W. C. Nat. Rev. Chem. 2017, 1, 0052.
(b) Milligan, J. A.; Phelan, J. P.; Badir, S. O.; Molander, G. A.
Angew. Chem. Int. Ed. 2019, 58, 6152. (c) Zhu, C.; Yue, H.; Chu, L.;
Rueping, M. Chem. Sci. 2020, 11, 4051.
(13) (a) Heitz, D. R.; Tellis, J. C.; Molander, G. A. J. Am. Chem. Soc.
2016, 138, 12715. (b) Shields, B. J.; Doyle, A. G. J. Am. Chem. Soc.
2016, 138, 12719. (c) Nielsen, M. K.; Shields, B. J.; Liu, J.;
Williams, M. J.; Zacuto, M. J.; Doyle, A. G. Angew. Chem. Int. Ed.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

F
T. Kerackian et al.
Cluster
Synlett
2017, 56, 7191. For other illustrative examples, see: (d) Huang,
L.; Rueping, M. Angew. Chem. Int. Ed. 2018, 57, 10333. (e) Shen,
Y.; Gu, Y.; Martin, R. J. Am. Chem. Soc. 2018, 140, 12200.
(f) Cheng, X.; Lu, H.; Lu, Z. Nat. Commun. 2019, 10, 3549.
(g) Santos, M. S.; Corrêa, A. G.; Paixão, M. W.; König, B. Adv.
Synth. Catal. 2020, 2367. For examples involving carbonyl-type
electrophiles, see refs. 12b and 12d
magnetic
Ir{[dF(CF3)ppy]2(dtbbpy)}PF6
stirrer
bar
was
(0.008
charged
mmol,
with
mg),
9
[Ni(dtbbpy)(H2O)4]Cl2 (0.04 mmol, 18.7 mg), K3PO4 (0.6 mmol,
127 mg), LiCl (0.4 mmol, 17 mg), N-benzoylsuccinimide (0.4
mmol, 81.3 mg), and anhyd THF (3.2 mL, 0.125 M). The vial was
sparged with argon then sealed, and the stirred mixture was
irradiated by a 30 W blue LED lamp (450 nm; EvoluChem Pho-
toRedOx Box device) for 24 h at RT. To remove solid residues, the
mixture was filtered through a short pad of Celite with CH2Cl2
as eluent. The volatiles were removed under vacuum and the
crude residue was purified by column chromatography [silica
gel cyclohexane–EtOAc (10:1)] to give a colorless oil; yield: 37.5
mg (53%). The 1H NMR and 13C NMR spectra were consistent
with the values reported in the literature.12b
(14) Doyle showed that external sources of chlorine atom such as
TBACl can be used to cross-couple electrophiles that do not
contain chloride (e.g., aryl triflates, bromides, or iodides); see
refs. 13b and 13c.
(15) (a) Hwang, S. J.; Powers, D. C.; Maher, A. G.; Anderson, B. L.;
Hadt, R. G.; Zheng, S.-L.; Chen, S.-Y.; Nocera, D. G. J. Am. Chem.
Soc. 2015, 137, 6472. (b) Hwang, S. J.; Anderson, B. L.; Powers, D.
C.; Maher, A. G.; Hadt, R. G.; Nocera, D. G. Organometallics 2015,
34, 4766.
(19) CCDC 2018793 contains the supplementary crystallographic
data for complex III. The data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/getstructures.
(20) A single precedent has been reported for the formation of an
acyl nickel(II) complex by amide C−N bond activation in which,
after a ligand exchange between the transient amidate complex
and a chloride ion, a Ni(II) chloride complex was isolated and
structurally characterized; see: Hu, J.; Zhao, Y.; Liu, J.; Zhang, Y.;
Shi, Z. Angew. Chem. Int. Ed. 2016, 55, 8718.
(21) The formation of alkyl ketones deriving from a decarbonylative
process with ethyl chloroformate has been recently reported;
see: Shi, R.; Hu, X. Angew. Chem. Int. Ed. 2019, 58, 7454.
(22) For the coupling of N-benzoylsuccinimide (1a) with cyclohex-
ane, 4a could also be formed by direct attack of the cyclohexyl
radical on benzene. See the Supporting Information for more
details.
(16) See the Supporting Information for more details.
(17) Cyclohexyl(phenyl)methanone (3a); Typical Procedure A
In an argon-filled glovebox, a 10 mL Schlenk tube equipped
with
a
magnetic stirrer bar was charged with
(0.003 mmol, 3.2 mg),
Ir{[dF(CF3)ppy]2(dtbbpy)}PF6
[Ni(dtbbpy)(H2O)4]Cl2 (0.024 mmol, 11.2 mg), K3PO4 (1.2 mmol,
254 mg), Na2WO4·2 H2O (0.6 mmol, 200 mg), LiCl (0.6 mmol, 25
mg), N-benzoylsuccinimide (0.6 mmol, 122 mg), cyclohexane
(3.0 mmol, 325 L), and anhyd benzene (6 mL). The sealed
vessel was taken out of the glovebox, and the stirred mixture
was irradiated by a 40 W blue LED Kessil lamp (455 nm) for 24
hours at RT. To remove solid residues, the mixture was filtered
through a short pad of Celite with CH2Cl2 as the eluent. The vol-
atiles were removed under vacuum and the crude residue was
purified by column chromatography [silica gel, cyclohexane–
EtOAc (10:1)] to give a colorless oil; yield: 60 mg (53%). The 1H
NMR and 13C NMR spectra were consistent with values reported
in the literature.8b
(23) Mohadjer Beromi, M.; Brudvig, G. W.; Hazari, N.; Lant, H. M. C.;
Mercado, B. Q. Angew. Chem. Int. Ed. 2019, 58, 6094.
(24) During the final stage of the preparation of this manuscript, a
similar protocol for the acylation of C(sp3)–H bonds with N-
acylsuccinimides was published, see: Lee, G. S.; Won, J.; Choi, S.;
Baik, M.-H.; Hong, S. H. Angew. Chem. Int. Ed. 2020, 59, 16933.
(18) Phenyl(tetrahydrofuran-2-yl)methanone (3i); Typical Proce-
dure B
On the bench top, an 8 mL scintillation vial equipped with a
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F