Direct Catalytic Alcoholysis of Unactivated 8-Aminoquinoline Amides

Article abstract of DOI:10.1021/acscatal.7b00442

Direct catalytic alcoholysis of unactivated amides is one of the most difficult challenges in organic chemistry, and an applicable method for cleaving amides used as directing groups in regioselective functionalization reactions has not been reported. Herein, we report direct catalytic alcoholysis of 8-aminoquinoline amides, which are highly effective directing groups in regioselective functionalization reactions. The reactions proceeded with a simple combination of substrates, air-stable catalysts, and alcohols, affording the corresponding esters in good yields with broad functional group tolerance. Highly chemoselective cleavage of the 8-aminoquinoline amides in the presence of related carbonyl functionalities and preliminary mechanistic studies are also described.

Full text of DOI:10.1021/acscatal.7b00442

Subscriber access provided by University of Newcastle, Australia
Letter
Direct Catalytic Alcoholysis of Unactivated 8-Aminoquinoline Amides
Toru Deguchi, Hai-Long Xin, Hiroyuki Morimoto, and Takashi Ohshima
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.7b00442 • Publication Date (Web): 28 Mar 2017
Downloaded from http://pubs.acs.org on March 28, 2017
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
Direct Catalytic Alcoholysis of Unactivated 8-Aminoquinoline Am-
ides
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
Toru Deguchi, HaiꢀLong Xin, Hiroyuki Morimoto* and Takashi Ohshima*
Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi 3ꢀ1ꢀ1 Higashiꢀku, Fukuoka, Japan, 812ꢀ8582.
ABSTRACT: Direct catalytic alcoholysis of unactivated amides is one of the most difficult challenges in organic chemistry, and an
applicable method for cleaving amides used as directing groups in regioselective functionalization reactions has not been reported.
Herein we report direct catalytic alcoholysis of 8ꢀaminoquinoline amides, highly effective directing groups in regioselective funcꢀ
tionalization reactions. The reactions proceeded with a simple combination of substrates, airꢀstable catalysts, and alcohols, affordꢀ
ing the corresponding esters in good yield with broad functional group tolerance. Highly chemoselective cleavage of the 8ꢀ
aminoquinoline amides in the presence of related carbonyl functionalities and preliminary mechanistic studies are also described.
KEYWORDS: alcoholysis, amides, homogeneous catalysis, chemoselectivity, 8-aminoquinoline
Amides are ubiquitous functionalities and important strucꢀ
tural motifs in organic molecules, such as proteins, polymers,
and biologically active compounds, due to their high stability.
Amides have recently also been used as reliable directing
groups for regioselective functionalization reactions.1 Enhancꢀ
ing the utility of these functionalization reactions, selective
transformation of the directing group amides into more useful
carbonyl groups, such as esters, is an important issue. In most
cases, however, harsh reaction conditions with stoichiometric
amounts of strong acids or bases are used, which limit the
functional group compatibility. Another option is to attach an
activating functionality, such as a tertꢀbutoxycarbonyl group,
before the cleavage, but such indirect methods require addiꢀ
tional reaction steps as well as additional reagents.
ic alcoholysis of 8ꢀaminoquinoline amides. Broad functional
group tolerance was achieved due to the nature of the catalytic
conditions. Chemoselective cleavage of the 8ꢀaminoquinoline
amides in the presence of related functionalities and prelimiꢀ
nary mechanistic studies are also described.
Scheme 1. Direct Catalytic Alcoholysis of Unactivated Am-
ides
Zn(OTf)2 (5 mol %)
(EtO)2CO (2 equiv)a
HO
O
O
CbzHN
OMe
CbzHN
N
OnBu
nBuOH, reflux
H
R1
O
R1
Ni(cod)2 (10 mol %)
SIPr (10 mol %)b
O
H
R2
O
R2
R4OH
N
+
+
Ar
N
OR4
Direct catalytic alcoholysis of unactivated amides is a stepꢀ
economical way to convert directing group amides into more
useful esters.2 The development of such potentially useful
transformations, however, is hampered by the following facꢀ
tors: (1) low reactivity of unactivated amides due to their high
stability produced by delocalization of nitrogen lone pairs, (2)
low nucleophilicity of alcohols compared with amines,3 and
(3) thermodynamic stability of the starting materials compared
with the products. Although the recent seminal contributions
from Mashima (N to O acyl transfer and Lewis acid catalysis)4
and Garg and Houk (oxidative addition of Ni(0))5 offer possiꢀ
ble solutions (Scheme 1), neither of these strategies has been
applied for the catalytic cleavage of directing group amides for
regioselective functionalization reactions. In addition, high
chemoselectivity is desirable for removing directing group
amides in the presence of related carbonyl functionalities.
Based on our continued interest in the cleavage of unactivated
amides6 as well as chemoselective catalytic transformations,7
we hypothesized that simultaneous catalytic activation of diꢀ
recting group amides and alcohols through a Lewis acidꢀ
Brønsted base bifunctional activation mode8 would allow us to
overcome the limitations of the presently available direct cataꢀ
lytic alcoholysis reactions. Herein we report the direct catalytꢀ
R3
toluene, 80 °C
Ar
R3
Ni(tmhd)2
(1–15 mol %)
O
O
R4OH
R1
N
+
+
H2N
R1 OR4
80–120 °C
this work
H
N
N
1
3
recoverable
2
aReference 4a. bReference 5a.
To test our hypothesis, we selected 8ꢀaminoquinoline amide
1a, a highly effective and frequently used directing group amꢀ
ide introduced by Daugulis,9 as a model substrate, for which a
catalytic cleavage method is unknown.10 We screened several
catalysts reported to coordinate with 8ꢀaminoquinoline amꢀ
ides9,11 with methanol (2a) as a solvent, and found that nickꢀ
el(II) triflate11a and cobalt(II) acetylacetonate11b afforded the
product 3a, albeit in low yield (Table 1, entries 1–4). These
results led us to examine nickel(II) acetylacetonate,11d and we
obtained a much better yield (entry 5). Further screening of
metal acetylacetonates revealed that nickel(II) was the most
effective metal among the tested metal acetylacetonates (enꢀ
tries 3–7). Examination of other nickel(II) diketonate catalysts
revealed
that
nickel(II)
bis(2,2,6,6ꢀtetramethylꢀ3,5ꢀ
heptanedionate) (Ni(tmhd)2) had the best reactivity (entries 8–
ACS Paragon Plus Environment

ACS Catalysis
10), and an optimal result was obtained by increasing the reacꢀ
Page 2 of 6
Ni(tmhd)2
(5 mol %)
O
O
1
2
3
4
5
6
7
8
tion time to 24 h to afford ester 3a in 94% isolated yield (entry
11). Notably, Ni(cod)2 did not efficiently promote the reaction
(entry 12), suggesting that Ni(0) is not the active species under
the present reaction conditions.12
R1
N
+
MeOH
R1 OMe
H
80–100 °C
12–48 h
N
1
2a
3
O
aStandard conditions: 0.25 mmol of 1a, 5 mol % of catalyst
in 0.10 M of MeOH (2a) at 80 °C for 12 h. bDetermined by 1H
N
O
H
c
d
N
NMR analysis of the crude reaction mixture. For 24 h. Isoꢀ
lated yield. OTf = trifluoromethanesulfonate. acac = acetyꢀ
lacetonate. hfacac = 1,1,1,5,5,5ꢀhexafluoroacetylacetonate.
dbm = 1,3ꢀdiphenylꢀ1,3ꢀpropanedionate. tmhd = 2,2,6,6ꢀ
tetramethylꢀ3,5ꢀheptanediaonate. cod = 1,4ꢀcyclooctadiene.
n.r. = no reaction.
N
1a
H
80 °C, 24 h, 92%a, 87%b
100 °C, 24 h, 97%c
N
1b
9
100 °C, 24 h, 97% (1.4 g)
+ 8-aminoquinoline 92% (0.79 g)
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
Br
O
O
Table 1. Optimization of Reaction Conditionsa
N
H
N
H
N
Me
1c
N
1d
catalyst
(5 mol %)
O
O
100 °C, 24 h, 85%
80 °C, 12 h, 95%
+
MeOH
N
OMe
OH
O
O
H
80 °C, 12 h
N
N
N
1a
2a
3a
H
H
N
N
Cl
entry
catalyst
yield
(%)b
n.r.
entry
catalyst
yield
(%)b
n.r.
57
1e
1f
100 °C, 24 h, 76%
100 °C, 48 h, 76%d
SiiPr3
O
1
2
3
Pd(OAc)2
Ni(OTf)2
7
8
9
Pt(acac)2
NC
26
Ni(hfacac)2
Ni(dbm)2
N
O
N
H
N
MeO
Co(acac)2· 20
2H2O
52
H
N
O
4
5
Fe(acac)3
Ni(acac)2
n.r.
10
11c
Ni(tmhd)2
Ni(tmhd)2
85
1h
1g
80 °C, 24 h, 87%
100 °C, 24 h, 84%
45
95
(94)d
O
6
Pd(acac)2
n.r.
12
Ni(cod)2
15
Me
Under these optimized reaction conditions, we first examꢀ
ined the substrate scope of 8ꢀaminoquinoline amides 1
(Scheme 2). It is noted that most of these 8-aminoquinoline
amides 1 used in this study (11 out of 14) are regioselective
functionalization products reported in the literature.13 Alkyl,
α,βꢀunsaturated and arylꢀsubstituted 8ꢀaminoquinoline amides
reacted to give methyl esters 3 in good yields. The reaction
with 1a proceeded even in the presence of 1 equiv of water,
under air or with 1 mol % of catalyst loading, without a signifꢀ
icant reduction of the yield. The reaction conditions were apꢀ
plicable for a gramꢀscale synthesis of 3b with 92% recovery of
8ꢀaminoquinoline. αꢀTetrasubstituted amide 1g also gave the
product 3g. Broad functional groups were tolerated such as
alkene, alkyne, chloro, bromo, hydroxy, cyano and methoxꢀ
ycarbonyl moieties, most of which are susceptible to either
conventional acidic/basic conditions or other amideꢀcleaving
conditions reported in the literature.5,10 Furthermore, structurꢀ
ally complex amide 1i afforded the corresponding ester 3i in
good yield.
N
H
MeO
Me
N
H
1i
Me
100 °C, 48 h, 81%e
H
H
OMe
H
MeO
aWith 1 equiv of H2O. Under air. With 1 mol % of catalyst.
dWith 15 mol % of catalyst in DMSO (1.0 M). eWith 10 mol % of
catalyst.
b
c
Next, we examined the scope of alcohols. Primary alcohols
such as ethanol and 1ꢀbutanol gave esters 3 in high yields unꢀ
der similar reaction conditions, whereas secondary and tertiary
alcohols gave esters 3 in reduced yields (Scheme 3 (a)). Altꢀ
hough these simple esters can be used as intermediates for a
variety of further transformations, we also developed oneꢀpot,
direct catalytic alcoholysisꢀcatalytic transesterification reacꢀ
tions using nickel(II) and iron(III) catalysts14 to demonstrate
the feasibility of alcohols (Scheme 3 (b)). As a result, a variety
of esters 3 were obtained from 1.5 equivalents of primary,
secondary and tertiary alcohols in good twoꢀstep yields withꢀ
out isolation of the intermediate methyl ester 3b.
Scheme 2. Scope of 8-Aminoquinoline Amides
Scheme 3. Scope of Alcohols
ACS Paragon Plus Environment

Page 3 of 6
ACS Catalysis
(a)
Ni(tmhd)2
(5 mol %)
(a)
Ni(tmhd)2
(5 mol %)
O
O
O
O
1
R4OH
N
H
OR4
R1
N
N
H
+
+
MeOH
R1 OMe
2
80–100 °C
12–24 h
N
N
3
4
1
2a
3
1a
2
3j (R4 = Et): 100 °C, 48 h, 94%
3k (R4 = nBu): 120 °C, 24 h, 94%
3l (R4 = iPr): 120 °C, 48 h, 67%a
3m (R4 = tBu): 120 °C, 48 h, 9%a,b
O
H
N
5
6
3q
80 °C, 12 h, 89%
N
H
O
N
1q
7
8
9
(b)
Ni(tmhd)2
(5 mol %)
O
O
3r
+
MeOH
O
O
H
N
OMe
100 °C, 12 h
82% yield, 97% ee
100 °C
24 h
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
N
H
tBuO
N
N
N
5
H
H
(+ 14% 1r)
1b
2a
3b (crude)
O
N
1r (97% ee)
[(salen)Fe(III)]2O
(5 mol %)
Me
3n (R4 = Bn): 92%
R4OH (1.5 equiv)
3o (R4 = (–)-menthyl): 85%
3p (R4 = 1-adamantyl): 61%c
(all yields are in 2 steps)
O
O
3s
PhCl (0.14 M)
reflux, 24–48 h
one-pot
OR4
O
100 °C, 24 h, 78%
N
(+ 20% 1s
)
N
a10 mol % of Ni(tmhd)2 were used. Determined by H NMR
analysis of the crude mixture. c10 mol % of the iron(III) catalyst
were used.
b
1
H
O
N
1s
(b)
HCl
(1 equiv)
O
To test whether our Ni(II) catalysis is highly chemoselective
for 8ꢀaminoquinoline amides, we examined competitive reacꢀ
tions using 8ꢀaminoquinoline amides containing related carꢀ
bonyl group functionalities (Scheme 4 (a)). We found that
aromatic and aliphatic amides, an imide and tertꢀbutyl carbaꢀ
mate remained intact during the cleavage of 8ꢀaminoquinoline
amides, demonstrating the highly chemoselective nature of the
present reaction conditions. It is also noteworthy that no raceꢀ
mization of 3r was observed, implying that the present reacꢀ
tion conditions are less basic than conventional cleavage conꢀ
ditions. The mildness of the current conditions was further
demonstrated with amide 1t having a TBSꢀprotected hydroxy
group, for which our catalytic reaction conditions provided the
desired product 3t in good yield while conventional acidꢀ
ic/basic conditions gave undesired TBSꢀdeprotected byproduct
4t as the major product (Scheme 4 (b)). In addition, treatment
of amide 1u under our reaction conditions gave the desired
ester 3u in 90% yield whereas acidic conditions previously
used for the cleavage of 8ꢀaminoquinoline amides10a,b provided
undesired Bocꢀdeprotected byproduct 4u.
HO
MeOH
rt, 2 h
N
H
3
N
4t
97%
Ni(tmhd)2
(5 mol %)
O
O
TBSO
MeOH
N
TBSO
3
100 °C, 24 h
OMe
H
N
3
3t
82%
1t
NaOMe
(1 equiv)
3t
+
4t
59%
+
1t
33%
MeOH
3%
90 °C, 24 h
HCl
O
N
(2 equiv)
ClH3N
3
MeOH
50 °C, 6 h
H
N
4u
72%
Ni(tmhd)2
(5 mol %)
O
O
H
N
H
N
tBuO
tBuO
OMe
N
3
3
MeOH
H
Scheme
4.
Chemoselective
Alcoholysis
of
8-
O
O
N
80 °C, 24 h
Aminoquinoline Amides
3u
90%
1u
BF3•OEt2
(1 equiv)
3u
+
4u
26%
+
1u
31%
MeOH
50 °C, 24 h
26%
To elucidate the mechanism of the observed chemoselectiviꢀ
ty, we performed preliminary mechanistic studies (Scheme 5).
First, simple Lewis acidic catalysts Zn(OTf)2 and Sc(OTf)3
previously used for alcoholysis of amides4 were not effective;
nor was a catalytic amount of BF3·OEt2, which is an effective
reagent for cleaving 8ꢀaminoquinoline amides (eq. 1).10b These
results and the results with Ni(II) catalysts shown in Table 1
suggest that the observed reactivity of Ni(tmhd)2 is not solely
dependent on the Lewis acidity of the metal catalysts. Second,
the coordination mode of 8ꢀaminoquinoline amides was invesꢀ
tigated using amide 5a (lacking nitrogen atom on the aminoꢀ
quinoline ring) and 6a (without the amide N–H moiety);
cleavage of 5a did not proceed at all, while reaction with 6a
proceeded faster than that of 1a (eq. 2). These results suggestꢀ
ed that coordination of quinoline to the Ni(II) catalyst is essenꢀ
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 6
tial, while formation of the metalꢀamide bond may not always In summary, we developed a concise catalytic method to seꢀ
1
2
3
4
5
6
7
8
be necessary for promoting the alcoholysis reaction, although
different mechanism could be operative between NꢀH amide
1a and NꢀMe amide 6a since formation of the metalꢀamide
bond is proposed in most Niꢀcatalyzed C–H activation reacꢀ
tions for promoting regioselective functionalization.15 Third,
we examined the effects of 8ꢀaminoquinoline and acetyꢀ
lacetone, both of which are good ligands for the Ni(II) center.
Indeed, these additives reduced the reactivity (eq. 3), suggestꢀ
ing reversible and competitive binding to the Ni(II) center
with 8ꢀaminoquinoline amides and 8ꢀaminoquinoline as well
as acetylacetone.
lectively transform 8ꢀaminoquinoline amides into esters. This
is the first effective direct catalytic alcoholysis reaction for
cleaving directing group amides used in regioselective funcꢀ
tionalization reactions with rarely used Ni(II) diketonate cataꢀ
lysts, and this reaction system is useful because only 8ꢀ
aminoquinoline amides, alcohols, and commercially available
airꢀstable Ni(II) diketonate catalysts were used to provide esꢀ
ters with high chemoselectivity and broad functional group
tolerance. Further elucidation of the reaction mechanism as
well as application of this strategy to related reactions are in
progress.
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
Scheme 5. Preliminary Mechanistic Studies
ASSOCIATED CONTENT
Supporting Information
catalyst
(5 mol %)
O
O
(1)
OMe
N
H
The Supporting Information is available free of charge on the
ACS Publications website.
MeOH
80 °C, 12 h
N
3a
1a
Zn(OTf)2: 6%
Sc(OTf)3: 14%
BF3•OEt2: 3%
Experimental details, characterization data and copies of spectra
of compounds (PDF)
Ni(acac)2
(20 mol %)
O
O
AUTHOR INFORMATION
Corresponding Authors
(2)
(3)
N
R3
OEt
EtOH
100 °C, 12 h
X
3j
*Eꢀmail: hmorimot@phar.kyushuꢀu.ac.jp
*Eꢀmail: ohshima@phar.kyushuꢀu.ac.jp
Notes
1a (R3 = H, X = N)
5a (R3 = H, X = CH)
6a (R3 = Me, X = N)
81% from 1a
n.r. from 5a
99% from 6a
Ni(acac)2 (20 mol %)
additive (1.0 equiv)
The authors declare no competing financial interest.
O
O
N
OEt
ACKNOWLEDGMENT
H
N
EtOH
100 °C, 12 h
This work was supported by a GrantꢀinꢀAid for Scientific Reꢀ
search on Innovative Area (JSPS KAKENHI Grant No.
JP15H05846 in Middle Molecular Strategy), GrantꢀinꢀAid for
Scientific Research (B) (JSPS KAKENHI Grant No. JP24390004
for T.O.) and (C) (JSPS KAKENHI Grant No. JP15K07860 for
H.M.) from JSPS, Platform for Drug Discovery, Informatics, and
Structural Life Science from AMED, and Naito Foundation. We
thank R. Horikawa for [(salen)Fe(III)]2O catalyst and the research
group of Prof. Go Hirai at Kyushu University for the use of a
polarimeter.
3j
1a
additive = 8-aminoquinoline: 57%
additive = acetylacetone: 4%
Based on these results and information from the literature,16
we propose the following possible catalytic cycle (Scheme 6):
(diketonato)Ni(II) act as
a Brønsted base to produce
(alkoxo)Ni(II) species,16 followed by coordination with 8ꢀ
aminoquinoline amide 1 to give intermediate I through coorꢀ
dination of the quinoline.15 After cleavage of the amide bond
via intermediate II and the release of ester 3, the resulting
(alkoxo)(amido)Ni(II) III reacts with 8ꢀaminoquinoline amide
1 to close the catalytic cycle. The importance of such a Lewis
acidꢀBrønsted base bifunctional nature is distinguishable from
the reported direct catalytic alcoholysis of amides. Further
investigation of the details, such as the kinetics and nature of
the Ni(II) species, is underway.
REFERENCES
(1) For selected reviews on directing group amides: (a) Rouquet,
G.; Chatani, N. Angew. Chem., Int. Ed. 2013, 52, 11726–11743. (b)
Daugulis, O.; Roane, J.; Tran, L. D. Acc. Chem. Res. 2015, 48, 1053–
1064. (c) Liu, J.; Chen, G.; Tan, Z. Adv. Synth. Catal. 2016, 358,
1174–1194.
(2) For selected recent examples of alcoholysis of amides, see: (a)
Bröhmer, M. C.; Mundinger, S.; Bräse, S.; Bannwarth, W. Angew.
Chem., Int. Ed. 2011, 50, 6175–6177. (b) Hutchby, M.; Houlden, C.
E.; Haddow, M. F.; Tyler, S. N. G.; LloydꢀJones, G. C.; Bookerꢀ
Milburn, K. I. Angew. Chem. Int. Ed. 2012, 51, 548–551. (c) Siddiki,
S. M. A. H.; Touchy, A. S.; Tamura, M.; Shimizu, K.ꢀi. RSC Adv.
2014, 4, 35803–35807. (d) Balachandra, C.; Sharma, N. K. Org. Lett.
2015, 17, 3948–3951. (e) Yamada, K.; Karuo, Y.; Tsukada, Y.;
Kunishima, M. Chem.—Eur. J. 2016, 22, 14042–14047. (f) Adachi,
S.; Kumagai, N.; Shibasaki, M. Chem. Sci. 2017, 8, 85–90.
Scheme 6. A Possible Catalytic Cycle
R4O
R1
R
R
R
R
N
O
N
[NiII]
O
O
O
O
[NiII]
1
and 2
R1
N
II
N
R4OH
2
R4O [NiII]
O
I
(3) Based on Mayr’s reactivity parameters, the difference of nucleꢀ
ophilicity between amines and alcohols is about 105 orders of magniꢀ
tude.
For
details,
see:
H2N
O
http://www.cup.lmu.de/oc/mayr/reaktionsdatenbank/ accessed on
Dec. 15, 2016.
(4) (a) Kita, Y.; Nishii, Y.; Higuchi, T.; Mashima, K. Angew.
Chem., Int. Ed. 2012, 51, 5723–5726. (b) Kita, Y.; Nishii, Y.; Onoue,
A.; Mashima, K. Adv. Synth. Catal. 2013, 355, 3391–3395. (c) Atkinꢀ
son, B. N.; Williams, J. M. J. Tetrahedron Lett. 2014, 55, 6935–6938.
N
HN
R4O [NiII]
III
R1 OR4
N
O
3
R1
N
H
N
1
ACS Paragon Plus Environment

Page 5 of 6
ACS Catalysis
(d) Nishii, Y.; Akiyama, S.; Kita, Y.; Mashima, K. Synlett 2015, 26,
1831–1834.
1
(5) (a) Hie, L.; Nathel, N. F. F.; Shah, T. K.; Baker, E. L.; Hong,
X.; Yang, Y.ꢀF.; Liu, P.; Houk, K. N.; Garg, N. K. Nature 2015, 524,
79–83. (b) Hie, L.; Baker, E. L.; Anthony, S. M.; Desrosiers, J.ꢀN.;
Senanayake, C.; Garg, N. K. Angew. Chem., Int. Ed. 2016, 55, 15129–
15132.
2
3
4
5
(6) (a) Shimizu, Y.; Morimoto, H.; Zhang, M.; Ohshima, T. Angew.
Chem., Int. Ed. 2012, 51, 8564–8567. (b) Shimizu, Y.; Noshita, M.;
Mukai, Y.; Morimoto, H.; Ohshima, T. Chem. Commun. 2014, 50,
12623–12625. (c) Noshita, M.; Shimizu, Y.; Morimoto, H.; Ohshima,
T. Org. Lett. 2016, 18, 6062–6065.
(7) For reviews on chemoselectivity, see: (a) Afagh, N. A.; Yudin,
A. K. Angew. Chem., Int. Ed. 2010, 49, 262–310. (b) Mahatthananꢀ
chai, J.; Dumas, A. M.; Bode, J. W. Angew. Chem., Int. Ed. 2012, 51,
10954–10990. For our recent contributions regarding catalystꢀ
controlled chemoselectivity, see: (c) Uesugi, S.; Li, Z.; Yazaki, R.;
Ohshima, T. Angew. Chem., Int. Ed. 2014, 53, 1611–1615. (d) Tokuꢀ
masu, K.; Yazaki, R.; Ohshima, T. J. Am. Chem. Soc. 2016, 138,
2664–2669.
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
(8) Review: (a) Shibasaki, M.; Kumagai, N. in Cooperative Cataly-
sis: Designing Efficient Catalysts for Synthesis, Peters, R. Ed., Wileyꢀ
VCH, 2015, pp. 1–34. For similar activation mode in Cu(II)ꢀmediated
alcoholysis of amides, see: (b) Barrera, I. F.; Mawell, C. I.; Nererov,
A. A.; Brown, R. S. J. Org. Chem. 2012, 77, 4156–4160.
(9) Zaitsev, V. G.; Shabashov, D.; Daugulis, O. J. Am. Chem. Soc.
2005, 127, 13154–13155. See also ref. 1.
(10) For acidꢀpromoted direct alcoholysis of 8ꢀaminoquinoline amꢀ
ides, see: (a) Ano, Y.; Tobisu, M.; Chatani, N. J. Am. Chem. Soc.
2011, 133, 12984–12986. (b) Tran, L. D.; Daugulis, O. Angew.
Chem., Int. Ed. 2012, 51, 5188–5191. For an ozonolysis approach,
see: (c) Berger, M.; Chauhan, R.; Rodrigues, C. A. B.; Maulide, N.
Chem.—Eur. J. 2016, 22, 16805–16808.
(11) (a) Aihara, Y.; Chatani, N. J. Am. Chem. Soc. 2013, 136, 898–
901. (b) Grigorjeva, L.; Daugulis, O. Org. Lett. 2014, 16, 4684–4687.
(c) Shang, R.; Ilies, L.; Matsumoto, A.; Nakamura, E. J. Am. Chem.
Soc. 2013, 135, 6030–6032. (d) Wu, X.; Zhao, Y.; Ge, H. J. Am.
Chem. Soc. 2014, 136, 1789–1792.
(12) We also examined cleavage of 1a with Ni(cod)2/SIPr and
Ni(cod)2/terpy catalysts under the reported conditions,5 but only trace
or no 3a was detected. See Supporting Information for details.
(13) 1a, 1c, 1s: (a) Shabashov, D.; Daugulis, O. J. Am. Chem. Soc.
2010, 132, 3965–3972. 1b, 1i, 1t: (b) Gou, Q.; Zhang, Z.ꢀF.; Liu, Z.ꢀ
C.; Qin, J. J. Org. Chem. 2015, 80, 3176–3186. 1e: (c) Shang, R.;
Ilies, L.; Asako, S.; Nakamura, E. J. Am. Chem. Soc. 2014, 136,
14349–14352. 1f: (d) Singh, B. K.; Jana, R. J. Org. Chem. 2016, 81,
831–841. 1g: (e) Reddy, M. D.; Watkins, E. B. J. Org. Chem. 2015,
80, 11447–11459. 1h: (f) Ano, Y.; Tobisu, M.; Chatani, N. J. Am.
Chem. Soc. 2011, 133, 12984–12986. 1u: (g) Gurak, J. A. Jr.; Yang,
K. S.; Liu, Z.; Engle, K. M. J. Am. Chem. Soc. 2016, 138, 5805–5808.
The functionalized positions of 8ꢀaminoquinoline amides 1 are sumꢀ
marized in the Supporting Information.
(14) Horikawa, R.; Fujimoto, C.; Yazaki, R.; Ohshima, T. Chem.—
Eur. J. 2016, 22, 12278–12281.
(15) For the formation of related Ni(II) intermediates, see: Misal
Castro, L. C.; Chatani, N. Chem. Lett. 2015, 44, 410–421 and referꢀ
ences cited therein.
(16) For generation of (κ2ꢀacetylacetonato)(methoxo)Ni(II) species
from Ni(acac)2 in methanol, see: (a) Ginsberg, A. P.; Bertrand, J. A.;
Kaplan, R. I.; Kirkwood, C. E.; Martin, R. L.; Sherwood, R. C. Inorg.
Chem. 1971, 10, 240–246. (b) Darensbourg, M.; Buonomo, R. M.;
Reibenspies, J. H. Z. Kristallogr. 1995, 210, 469–470. Although the
structure of the active Ni(II) species is yet to be clarified, we assume
that oligomeric Ni(II) species is likely to be involved in the catalytic
cycle because of the feasibility of the formation of µꢀalkoxoꢀbridged
oligomeric Ni(II) species. It is also noted that our reaction proceeded
even with a catalytic amount of nickelocene (50% yield under the
conditions in Table 1), which is known to react with alcohols to give
(alkoxo)nickel(II) species: (c) Slushkov, A. M.; Petrov, B. I.; Domꢀ
rachev, G. A. Russ. Chem. Bull. 1987, 36, 385–388.
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 6
1
2
3
4
5
6
7
8
9
tBu
tBu
tBu
O
O
O
O
Ni
tBu
Ni(tmhd)2
O
(1–15 mol %)
O
R4OH
R1
N
+
+
H2N
80–120 °C
12–48 h
H
R1 OR4
N
N
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
R1: alkyl, alkenyl, aryl
61–97%
20 examples
recoverable
R4: Me, Et, nBu, iPr
other 1°/2°/3°-alkyl esters accecible via one-pot catalytic transesterification
compatible functional groups
alkene, alkyne, Cl, Br, OH, OTBS, CN, CO2Me, BocNH, amides, imide
ACS Paragon Plus Environment