Ketone-Assisted Ruthenium(II)-Catalyzed C-H Imidation: Access to Primary Aminoketones by Weak Coordination

Article abstract of DOI:10.1021/acscatal.6b00711

The ruthenium(II)-catalyzed intermolecular C-H imidation with weakly coordinating ketones provided step-economical access to synthetically useful primary aminophenones. The azide-free C-H imidation strategy occurred with ample scope and excellent function

Full text of DOI:10.1021/acscatal.6b00711

Subscriber access provided by UNIV OF GEORGIA
Letter
Ketone-Assisted Ruthenium(II)-Catalyzed C–H Imidation:
Access to Primary Aminoketones by Weak Coordination
Keshav Raghuvanshi, Daniel Zell, Karsten Rauch, and Lutz Ackermann
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b00711 • Publication Date (Web): 15 Apr 2016
Downloaded from http://pubs.acs.org on April 15, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
ACS Catalysis is published by the American Chemical Society. 1155 Sixteenth Street
N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 6
ACS Catalysis
1
2
3
4
5
6
7
8
9
Ketone-Assisted Ruthenium(II)-Catalyzed C–H Imidation: Access to
Primary Aminoketones by Weak Coordination
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
54
55
56
57
58
59
60
Keshav Raghuvanshi, Daniel Zell, Karsten Rauch, and Lutz Ackermann*
Institut für Organische und Biomolekulare Chemie, GeorgꢀAugustꢀUniversität,
Tammannstraße 2, 37077 Göttingen, Germany
Supporting Information Placeholder
ABSTRACT: The ruthenium(II)ꢀcatalyzed intermolecular C–H imidation with weaklyꢀcoordinating ketones provided stepꢀ
economical access to synthetically useful primary aminophenones. The azideꢀ
free C–H imidation strategy occurred with ample scope and excellent functional
group tolerance to efficiently deliver densely substituted aminophenones.
KEYWORDS: C–H activation • heterocycles • mechanism • nitrogenation • ruthenium
Aminophenones are key structural motifs in natural product
syntheses, medicinal chemistry, crop protection or material
sciences,1 and represent versatile intermediates in organic
synthesis.2 As a consequence, methods that allow for the effiꢀ
cient preparation of decorated aminophenones continue to be
in high demand.3 The development of new chemical transforꢀ
mations based on the catalytic functionalization of otherwise
inert C–H bonds has the potential to dramatically simplify the
synthesis of complex molecules.4 For instance, transition
Figure 1. Azide-free C–H Imidation by weakly-
coordinating ketones
metalꢀcatalyzed C–H amidations have emerged as an increasꢀ
ingly viable alternative to the palladiumꢀcatalyzed5 aminations
of aryl halides.6 Particularly, ruthenium(II) complexes have in
recent years been identified as powerful tools for C–H nitroꢀ
At the outset of our studies, we tested various reaction paꢀ
rameters for the envisioned rutheniumꢀcatalyzed C–H amiꢀ
dation of ketone 1a (Table 1).21 Among a variety of additives,
copper(II) acetate proved most effective for the synthesis of
product 3a (entries 1–8). The dimeric complex [RuCl2(pꢀ
cymene)]2 outperformed [Ru2(hp)4Cl] and [Ru2(OAc)4Cl]
(entries 8–11). Typical cobalt, palladium or rhodium catalysts
failed short in delivering the desired product 3a (entries 12–
14), highlighting the challenging nature of the ketoneꢀassisted
C–H nitrogenation.
genations, largely exploiting strongly coordinating directing
groups that are difficult to remove7 or modify.8 In spite of
major advances in rutheniumꢀcatalyzed C–H nitrogenations by
inter alia Chang,9,10 Jiao,11 Yu,12 Sahoo,13 Patureau14a and
Ackermann,14b ruthenium(II)ꢀcatalyzed C–H amidations15 with
weakly coordinating16 directing groups17,18 continue to be
scarce, and limited to azideꢀbased chemistry.8 Within our
program on sustainable C–H functionalizations,19 we have
now developed the first azideꢀfree ruthenium(II)ꢀcatalyzed20
C–H nitrogenation by weak ketone coordination, on which we
report herein (Figure 1). The successful use of challenging
ketones illustrates the beneficial features associated with raꢀ
ther inexpensive ruthenium(II) catalysts. The transformative
nature of our C–H activation platform provided stepꢀ
economical access to primary aminophenones – key intermeꢀ
diates in the synthesis of various bioactive heteroarenes.
ACS Paragon Plus Environment

ACS Catalysis
Scheme 1. Ruthenium(II)-Catalyzed C–H Imidation.
Page 2 of 6
Table 1. Ruthenium(II)-Catalyzed C–H Imidationa
1
2
3
4
5
6
7
8
9
entry catalyst
additive
3a [%]
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
54
55
56
57
58
59
60
1
[RuCl2(pꢀcymene)]2
ꢀꢀꢀ
ꢀꢀꢀ
14
23
19
21
ꢀꢀꢀ
27
78
9
2
[RuCl2(pꢀcymene)]2
[RuCl2(pꢀcymene)]2
[RuCl2(pꢀcymene)]2
[RuCl2(pꢀcymene)]2
[RuCl2(pꢀcymene)]2
[RuCl2(pꢀcymene)]2
[RuCl2(p-cymene)]2
[Ru2(hp)4Cl]
NaOAc
3
KOPiv
4
CsOAc
5
LiOAc
6
Mn(OAc)2•H2O
Zn(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
Cu(OAc)2•H2O
7
8
9
10
11
12
13
14
[Ru2(OAc)4Cl]
ꢀꢀꢀ
23
ꢀꢀꢀ
16
ꢀꢀꢀ
ꢀꢀꢀ
[Cp*CoI2(CO)]
[Cp*RhCl2]2
The synthetic utility of the ruthenium(II)ꢀcatalyzed imidaꢀ
tion protocol was illustrated by providing efficient access to
the valuable primary aminophenones 4 with synthetically
useful overall yields ranging from 56 to 74% for the twoꢀstep
procedure (Scheme 2).
Pd(OAc)2
a Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), catalyst
(5.0 mol %), AgSbF6 (20 mol %), additive (0.5 equiv), 1,4ꢀ
dioxane (2.0 mL), 100 °C, 24 h, yield of isolated product.
Scheme 2. Facile Access to Primary Aminophenones 4.21
With the optimized catalytic system in hand, we tested its
versatility by probing the influence of the arene substitution
pattern on the C–H imidation regime. Pleasingly, a range of
ketones 1 with diverse electronic properties provided the imꢀ
idophenones 3 by weak ketone assistance (Scheme 1). Hence,
paraꢀsubstituted ketones 1b–1i were chemoꢀselectively conꢀ
verted to the monoꢀimidated products 3. The robustness of the
versatile ruthenium(II) C–H activation catalyst was reflected
by fully tolerating valuable functional groups, including fluoꢀ
ro, chloro, bromo, and iodo substituents. These features should
prove instrumental for further postꢀsynthetic diversification of
the thus obtained imidophenones 3. The C–H imidation strateꢀ
gy was also found amenable to the gramꢀscale synthesis of
products 3a–c. C–H imidations with naphthalene derivatives
1j and 1k illustrated the excellent positional selectivity of the
C–H functionalization protocol, in that products 3j and 3k
were formed as the sole products, respectively. High levels of
siteꢀselectivity were observed within intramolecular competiꢀ
tion experiments with metaꢀsubstituted arenes 1l–1p as well.
Substitutions on the aromatic moiety of imidating reagents 2
were likewise tolerated under the optimized reaction condiꢀ
tions (Scheme S1 in the Supporting Information).21 In contrast,
the methylꢀ, isoꢀpropylꢀ or phenylꢀsubstituted phenones 1 thus
far failed to deliver the imidated products 3.22 Yet, the robust
ruthenium(II) catalyst was not limited to carbocyclic aromatic
compounds. Indeed, the C–H imidation of thiophene 1q
proved viable as well, occurring with excellent levels of posiꢀ
tional control.
The unique value of our C–H activation approach was
showcased by the chemoꢀdivergent access to a wealth of bioꢀ
active heterocyles, such as indoles 5,23 quinolines 6,24
quinazolines 7,25 and diazepines 8,26 in a stepꢀeconomical
fashion (Scheme 3).
ACS Paragon Plus Environment

Page 3 of 6
ACS Catalysis
Scheme 3. Diversification of products 4. (a) 4, Scheme 4. Summary of Mechanistic Findings.
1
2
3
4
ArCOCH2Br, DMF, 100 °C, 16 h. (b) 4, ArC≡CH, InCl3
(a) intermolecular competition experiments
(20 mol %), CH3CN, 90 °C, 24 h.21
2
[RuCl2(p-cymene)]2
t-Bu
(5 mol %)
AgSbF6
O
O
O
PMP
5
6
7
8
(20 mol %)
t-Bu
t-Bu
t-Bu
R
N
H
O
+
Me
N
Cu(OAc)2•H2O
1,4-dioxane
100 °C, 24 h
t-Bu
F/Me
H
Me
Me
NPhth
F
F
NPhth
: 8%
Ph
O
5a: 81%
1b 1f
3b
3f
:
: 26%
N
H
8
N
H
R
e
f
2
9
.
(a)
[
5b: 89%
2
[RuCl2(p-cymene)]2
5
)
]
a
(
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
54
55
56
57
58
59
60
(5 mol %)
AgSbF6
(20 mol %)
O
O
O
R
N
t-Bu
O
F/Me
t-Bu
t-Bu
NPhth
t-Bu
(b)
N
Ref. [24]
+
R
Cu(OAc)2•H2O
1,4-dioxane
100 °C, 24 h
NPhth
H
Me
N
Ph
R
NH2
7b
]
6a: 81%
4
4
(
2
[
b
1l 1n
:
3l
3n
: 6%
: 32%
.
f
)
e
R
R
N
t-Bu
(b) Hammett plot analysis
(b)
2
N
[RuCl2(p-cymene)]2
(5 mol %)
O
O
Ar
N
Ph
AgSbF6
(20 mol %)
t-Bu
R
R
7a
t-Bu
t-Bu
6b
: 94%
Cu(OAc)2•H2O
1,4-dioxane
100 °C, 24 h
H
NPhth
MeO
N
Ph
1
3
6c: 84%
In consideration of the unique selectivity features displayed
by the ketoneꢀassisted ruthenium(II)ꢀcatalyzed C–H imidation,
we performed mechanistic studies to delineate the catalyst's
mode of action. To this end, intermolecular competition experꢀ
iments between differently substituted arenes 1 indicated that
electronꢀrich arenes 1 reacted preferentially (Scheme 4a),
which was further illustrated by a Hammett value of
ρ = ꢀ3.3
(Scheme 4b).21 This observation can be rationalized in terms
of a baseꢀassisted, intermolecular electrophilic substitution
(BIES)ꢀtype C–H metalation event to be operative.27 C–H imidaꢀ
tions conducted in the presence of an isotopically labeled coꢀ
solvent were suggestive of a reversible H/Dꢀexchange (Scheme
4c). A kinetic isotope effect (KIE) of kH/kD ≈ 1.8 was determined
by means of the initial rates for independent reactions of subꢀ
strates 1a and [D]5ꢀ1a (Scheme 4d).
(c) H/D exchange
46% D
24% D
H/D
2
[RuCl2(p-cymene)]2
(5 mol %)
AgSbF6
(20 mol %)
H
O
H
O
H/D
O
t-Bu
t-Bu
NPhth
[D]n-3b: 46%
t-Bu
+
Cu(OAc)2•H2O
1,4-dioxane:CD3OD
(5:1)
Me
Me
Me
H/D
[D]n-1b: 13%
1b
100 °C, 24 h
(d) KIE study
2
[RuCl2(p-cymene)]2
(5 mol %)
O
O
AgSbF6
(20 mol %)
t-Bu
t-Bu
NPhth
H4/D4
H5/D5
Cu(OAc)2•H2O
1,4-dioxane
100 °C, 24 h
1a/[D]5-1a
3a/[D]4-3a
kH/kD = 1.8
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 6
Based on our mechanistic findings, we propose the rutheniꢀ
Notes
1
2
um(II)ꢀcatalyzed C–H nitrogenation to commence by a facile
The authors declare no competing financial interest.
BIESꢀtype27 C–H ruthenation by the cationic ruthenium(II)
ACKNOWLEDGMENT
3
monocarboxylate complex 9 (Scheme 5). Hence, the
Cu(OAc)2 serves as an effective additive for the formation of
the cationic ruthenium(II) carboxylate catalyst 9. The thusꢀ
formed cyclometalated intermediate 10 is subsequently coorꢀ
dinated by the imidating reagent 2. Thereafter, the N–O cleavꢀ
age delivers the cationic complex 11, which finally regenerꢀ
ates the catalytically active species 9, thereby liberating the
desired product 3. While the exact working mode of the N–O
cleavage step awaits more detailed analysis, an oxidative
addition6j pathway represents a viable alternative to an isohypꢀ
sic transformation.
4
5
6
7
8
9
Support by the European Research Council under the European
Community’s Seventh Framework Program (FP7 2007–
2013)/ERC Grant agreement no. 307535, DFG (SPP 1807) and
the DAAD (fellowship to K.R.) is gratefully acknowledged.
REFERENCES
(1) (a) Cheng, J.; Kamiya, K.; Kodama, I. Cardiovasc. Drug Rev.
2001, 19, 152ꢀ160. (b) Candeias, N. R.; Branco, L.ꢀC.; Gois, P. M. P.;
Fonso, C. A. M. A.; Trindade, A.ꢀF. Chem. Rev. 2009, 109, 2703ꢀ
2732.
(2) Larock, R.ꢀC. Comprehensive Organic Transformations, Wileyꢀ
VCH, Weinheim, 1999.
(3) (a) Ricci, A. Amino Group Chemistry, WileyꢀVCH, Weinheim,
2008. (b) Ricci, A. Modern Amination Methods, WileyꢀVCH, Weinꢀ
heim, 2007.
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
54
55
56
57
58
59
60
Scheme 5. Proposed Catalytic Cycle
(4) Representative recent reviews on C–H activation: (a) Kim, J.ꢀK.;
Shin, K.; Chang, S. Top. Organomet. Chem. 2016, 55, 29ꢀ51. (b)
Moselage, M.; Li, J.; Ackermann, L. ACS Catal. 2016, 6, 498ꢀ525. (c)
Song, G.; Li, X. Acc. Chem. Res. 2015, 48, 1007ꢀ1020. (d) Kuhl, N.;
Schroeder, N.; Glorius, F. Adv. Synth. Catal. 2014, 356, 1443ꢀ1460.
(e) Girard, S, ꢀA.; Knauber, T.; Li, C.ꢀJ. Angew. Chem. Int. Ed. 2014,
53, 74ꢀ100. (f) Nakamura, E.; Hatakeyama, T.; Ito, S.; Ishizuka, K.;
Ilies, L.; Nakamura, M. Org. React. 2014, 83, 1ꢀ209. (g) Rouquet, G.;
Chatani, N. Angew. Chem. Int. Ed. 2013, 52, 11726ꢀ11743. (h) Arockꢀ
iam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012, 112, 5879ꢀ
5918. (i) Satoh, T.; Miura, M. Chem. Eur. J. 2010, 16, 11212ꢀ11222.
(j) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147ꢀ1169.
(k) Giri, R.; Shi, B.ꢀF.; Engle, K.ꢀM.; Maugel, N.; Yu, J.ꢀQ. Chem.
Soc. Rev. 2009, 38, 3242ꢀ3272. (l) Ackermann, L.; Vicente, R.;
Kapdi, A. Angew. Chem. Int. Ed. 2009, 48, 9792ꢀ9826. (m) Bergman,
R, G. Nature 2007, 446, 391ꢀ393, and references cited therein.
(5) (a) Surry, D.ꢀS.; Buchwald, S. L. Chem. Sci. 2011, 2, 27ꢀ50. (b)
Hartwig, J. F. Acc. Chem. Res. 2008, 41, 1534ꢀ1544.
(6) For representative examples see: (a) Hermann, G.ꢀN.; Becker, O.;
Bolm, C. Angew. Chem. Int. Ed. 2016, 55, 3781ꢀ3784. (b) Park, J.;
Chang, S. Angew. Chem. Int. Ed. 2015, 14103ꢀ14107. (c) Liang, Y.;
Liang, Y.ꢀF.; Tang, C.; Yuan, Y.; Jiao, N. Chem. Eur. J. 2015, 21,
16395ꢀ16399 (d) Mei, R., Loup, J.; Ackermann, L. ACS Catal. 2016,
6, 793ꢀ797. (e) Hwang, H.; Kim, J.; Jeong, J.; Chang, S.; J. Am.
Chem. Soc. 2014, 136, 10770ꢀ10776. (f) Park, S.ꢀH., Kwak, J.; Shin,
K.; Ryu, J.; Park, Y.; Chang, S. J. Am. Chem. Soc. 2014, 136, 2492ꢀ
2502. (g) Kim, H.; Ajitha, M.ꢀJ.; Lee, Y.; Ryu, J.; Kim, J.; Lee, J.;
Jung, Y.; Chang, S. J. Am. Chem. Soc. 2014, 136, 1132ꢀ1140. (h)
Gandeepan, P.; Parthasarthy, K.; Cheng, C.ꢀH. J. Am. Chem. Soc.
2010, 132, 8569ꢀ8571. (i) Shin, K.; Baek, Y.; Chang, S. Angew.
Chem. Int. Ed. 2013, 52, 8031ꢀ8036. (j) Yu, S.; Wan, B.; Li, X. Org.
Lett. 2013, 15, 3706ꢀ3709. (k) Kwak, J.; Ohk, Y.; Jung, Y.; Chang, S.
J. Am. Chem. Soc. 2012, 134, 17778ꢀ17788. (l) Ryu, J.; Shin, K.;
Park, S.ꢀH.; Kim, J.ꢀY.; Chang, S. Angew. Chem. Int. Ed. 2012, 51,
9904ꢀ9908. (m) Kim, J.ꢀY.; Park, S.ꢀH.; Ryu, J.; Cho, S.ꢀH.; Kim, S.ꢀ
H.; Chang, S. J. Am. Chem. Soc. 2012, 134, 9110ꢀ9113. (n)
Grohmann, C.; Wang, H.; Glorius, F. Org. Lett. 2012, 14, 656ꢀ659.
(o) Ng, K.ꢀH.; Zhou, Z.; Wu, W.ꢀY. Org. Lett. 2012, 14, 272ꢀ275. (p)
Gandeepan, P.; Hung, C.ꢀH.; Cheng, C.ꢀH. Chem. Commun. 2012, 48,
9379ꢀ9381. (q) Yoo, E.ꢀJ.; Ma, S.; Mei, T.ꢀS.; Chan, K, S.ꢀL.; Yu, J. ꢀ
Q. J. Am. Chem. Soc. 2011, 133, 7652–7656. (r) Ng, K.ꢀH.; Zhou, Z.;
Yu, W.ꢀY. Org. Lett. 2011, 14, 272ꢀ276. (s) Ng, K.ꢀH.; Chan, A. S.ꢀ
C.; Yu, Y.ꢀW. J. Am. Chem. Soc. 2010, 132, 12862ꢀ12866, and referꢀ
ences cited therein.
In summary, we have reported on the first azideꢀfree rutheꢀ
nium(II)ꢀcatalyzed C–H amidation by weakly coordinating
ketone assistance. The synthetic utility of the C–H activation
protocol was reflected by giving expedient access to synthetiꢀ
cally useful primary aminophenones, and enabling stepꢀ
economical late stage diversifications. The operationally simꢀ
ple protocol featured high catalytic efficacy and excellent
functional group tolerance, while detailed mechanistic studies
were indicative of a BIESꢀtype27 C–H ruthenation.
ASSOCIATED CONTENT
Supporting Information
Experimental procedures, characterization data, 1H and 13C NMRꢀ
spectra for compounds.
(7) (a) Zhang, F.; Spring, D.ꢀR. Chem. Soc. Rev. 2014, 6906ꢀ6919. (b)
Rousseau, G.; Breit, B. Angew. Chem. Int. Ed. 2011, 50, 2450ꢀ2494.
(8) For reviews on rutheniumꢀcatalyzed nitrognations, see: (a) Dana,
S.; Yadav, M. R.; Sahoo, A. K. Top. Organomet. Chem. 2016, 55,
189ꢀ215. (b) Louillat, M.ꢀL.; Patureau, F.ꢀW. Chem. Soc. Rev. 2014,
AUTHOR INFORMATION
Corresponding Author
* E-mail: Lutz.Ackermann@chemie.uni-goettingen.de
ACS Paragon Plus Environment

Page 5 of 6
ACS Catalysis
43, 901ꢀ910. (c) Thirunavukkarasu, V. S.; Kozhushkov, S. I.; Ackerꢀ
mann, L. Chem. Commun. 2014, 50, 29ꢀ39.
2012, 14, 6206ꢀ6209. (h) Kakiuchi, F.; Yamamoto, Y.; Chatani, N.;
Murai, S. Chem. Lett. 1995, 24, 681ꢀ687, and references cited therein.
(16) For reviews on weaklyꢀcoordinating directing groups, see: (a)
Engle, K. M.; Mei, T. S.; Wasa, M.; Yu, J.ꢀQ. Acc. Chem. Res. 2012,
45, 788ꢀ802. (b) Sarkar, S. De.; Liu, W.; Kozhushkov, S. I.; Ackerꢀ
mann, L. Adv. Synth. Catal. 2014, 356, 1461ꢀ1479.
(17) Huang, Z.; Lim, H.ꢀN.; Mo, F.; Young, M.ꢀC.; Dong, G. Chem.
Soc. Rev. 2015, 44, 7764ꢀ7786. (b) Zheng, Q.ꢀZ.; Jiao, N. Tetrahe-
dron Lett. 2014, 55, 1121ꢀ1126.
1
2
3
4
5
6
(9) Shin, K.; Kim, H.; Chang, S. Acc. Chem. Res. 2015, 48, 1040ꢀ
1052.
(10) (a) Shin, K.; J. Ryu, J.; Chang, S. Org. Lett. 2014, 16, 2022ꢀ
2025. (b) Kim, J.; Kim, J.; Chang, S. Chem. Eur. J. 2013, 19, 7328ꢀ
7333.
(11) Zheng, Q.ꢀZ.; Liang, Y.ꢀF., Qin, C.; Jiao, N. Chem. Commun.
2013, 49, 5654ꢀ5656.
7
8
9
(12) Shang, M.ꢀZ.; Sun, S.ꢀH.; Zheng, S.; Dai H.ꢀX.; Yu, J.ꢀQ. Org.
Lett. 2013, 15, 5286ꢀ5289.
(18) Xiao, B.; Gong, T.ꢀJ.; Xu, J.; Liu, Z.ꢀJ.; Liu, L. J. Am. Chem.
Soc. 2011, 133, 1466ꢀ1474.
(19) (a) Ackermann, L. Acc. Chem. Res. 2014, 47, 281ꢀ295; (b) L.
Ackermann, Synlett 2007, 507ꢀ526.
(13) (a) Kommu, N.; Kumar, A.ꢀS.; Raveendra, J.; Vikas, D.ꢀG.;
Sahoo, A. K. Chem. Asian. J. 2015, 9, 846ꢀ864. (b) Yadav, M.ꢀR.;
Shankar, M.; Ramesh, E.; Ghosh, K.; Sahoo, A. K. Org. Lett. 2015,
17, 1886ꢀ1889. (c) Bhanuchandra, M.; Yadav, M.ꢀR.; Rit, R.ꢀK.;
Kuram, M.ꢀR.; Sahoo, A. K. Chem. Commun. 2013, 49, 5225ꢀ5227.
(d) Yadav, M.ꢀR.; Rit, R.ꢀK.; Sahoo, A. K. Org. Lett. 2013, 15, 1638ꢀ
1641. (e) For a recent sequential transformation, see: Ghosh, K.; Rit,
R. K.; Ramesh, E.; Sahoo, A. K., Angew. Chem. Int. Ed. 2016, 55,
DOI:10.1002/anie.201600649.
(14) (a) Louillat, M.ꢀL.; Biafora, A.; Legros, F.; Patureau, F.ꢀW.
Angew. Chem. Int. Ed. 2014, 53, 3505ꢀ3509. (b) Thirunavukkarasu,
V. S.; Raghuvanshi, K.; Ackermann, L. Org. Lett. 2013, 15, 3286ꢀ
3289.
(15) For representative examples of C–H functionalizations other than
amidations by weak coordination, see: (a) Muralirajan, K.; Parthasaraꢀ
thy, K.; Cheng, C.ꢀH. Angew. Chem. Int. Ed. 2011, 50, 4169ꢀ4172.
(b) Shan, G.; Yang, X.; Ma, L.; Rao, Y. Angew. Chem. Int. Ed. 2012,
51, 13070ꢀ13074. (c) Mo, F.; Trzepkowski, L.ꢀJ.; Dong, G. Angew.
Chem. Int. Ed. 2012, 51, 13075ꢀ13079. (d) Yang, F.; Rauch, K.;
Kettelhoit, K.; Ackermann, L. Angew. Chem. Int. Ed. 2014, 53,
11285ꢀ11288. (e) Choy, P.ꢀY.; Kwong, F.ꢀY. Org. Lett. 2013, 15,
270ꢀ273. (f) Singh, K. S.; Dixneuf, P. H. Organometallics 2012, 31,
7320ꢀ7323. (g) Thirunavukkarasu, V. S.; Ackermann, L. Org. Lett.
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
54
55
56
57
58
59
60
(20) For recent reviews on ruthenium(II)ꢀcatalyzed C–H functionaliꢀ
zations, see: (a) Ackermann, L. Org. Process Res. Dev. 2015, 18, 260ꢀ
269. (b) Bruneau, C. Top. Organomet. Chem. 2015, 48, 195ꢀ236. (c)
Sarkar, S, De.; Liu, W.; Kozhushkov, S. I.; Ackermann, L. Adv.
Synth. Catal. 2014, 356, 1461ꢀ1479. (d) Li, B.; Dixneuf, P, H. Chem.
Soc. Rev. 2013, 42, 5744ꢀ5767. (e) Ackermann, L.; Vicente, R. Top.
Curr. Chem. 2010, 292, 211ꢀ229, and references cited therein.
(21) For detailed information, see the Supporting Information.
(22) Reactions performed with orthoꢀmethylꢀsubstituted phenones 1
gave as of yet unsatisfactory results under otherwise identical condiꢀ
tions.
(23) Jones, C.ꢀD.; Suárez, T. J. Org. Chem. 1972, 37, 3621ꢀ3625.
(24) Chandra, T.; Verma, R. K.; Singh, M. S. Chem. Asian. J. 2012, 7,
778ꢀ787.
(25) Yan, Y.; Zhang, Y.; Feng, C.; Zha, Z.; Wang, Z. Angew. Chem.
Int. Ed. 2012, 51, 8077ꢀ8081.
(26) Teslivikhovsky, D.; Buchwald, S. L. J. Am. Chem. Soc. 2011,
133, 14228ꢀ14231.
(27) (a) Mei, R.; Loup, J.; Ackermann, L. ACS Catal. 2016, 6, 498ꢀ
525. (b) Tirler, C.; Ackermann, L. Tetrahedron 2015, 71, 4543ꢀ4551.
(c) Ma, W.; Mei, R.; Tenti, G.; Ackermann, L. Chem. Eur. J. 2014,
20, 15248ꢀ15251.
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 6
1
2
3
4
5
6
7
8
9
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
54
55
56
57
58
59
60
105x41mm (300 x 300 DPI)
ACS Paragon Plus Environment