Palladium-Catalyzed C8-H Acylation of 1-Naphthylamines with Acyl Chlorides

Article abstract of DOI:10.1021/acs.orglett.9b00283

A facile and efficient protocol for palladium-catalyzed regioselective C8-H acylation of 1-naphthylamine derivatives with acyl chlorides has been developed. The reaction exhibits broad functional group tolerance, and both aromatic and α,β-unsaturated acyl

Full text of DOI:10.1021/acs.orglett.9b00283

Letter
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Palladium-Catalyzed C8‑H Acylation of 1‑Naphthylamines with Acyl
Chlorides
Xiaomeng Yu, Fan Yang,* Yusheng Wu,* and Yangjie Wu*,†
†
,†
,‡
†The College of Chemistry and Molecular Engineering, Henan Key Laboratory of Chemical Biology and Organic Chemistry, Key
Laboratory of Applied Chemistry of Henan Universities, Zhengzhou University, Zhengzhou 450052, People’s Republic of China
‡
Tetranov Biopharm, LLC & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450052,
People’s Republic of China
*
S Supporting Information
ABSTRACT: A facile and efficient protocol for palladium-catalyzed regioselective C8-H acylation of 1-naphthylamine
derivatives with acyl chlorides has been developed. The reaction exhibits broad functional group tolerance, and both aromatic
and α,β-unsaturated acyl chlorides can be effectively coupled with 1-naphthylamines. Moreover, the picolinamide moiety as a
bidentate directing likely plays a key role in this regioselective transformation.
he carbonyl moiety is a ubiquitous structural scaffold
Scheme 1. Direct C8-H Functionalization of 1-
Naphthylamines
T
found in natural products, functional materials, and
1
pharmaceuticals. Moreover, aryl ketones have also exhibited
considerable practical value in industrial application. There-
fore, the development of an effective aromatic arylation
protocol has attracted a great deal of attention from synthetic
chemists.
In the past decades, transition-metal-catalyzed direct C−H
bond acylation under the assistance of a directing group has
emerged as a reliable and valuable tool for the synthesis of
2
various ketone compounds. Compared with the traditional
Friedel−Crafts acylation reaction, there are some obvious
advantages of this approach, such as broad functional group
3
tolerance, excellent regioselectivity, and high atom economy.
Specifically, since Daugulis developed picolinamide (PA) as
4
a bidentate directing group in 2005, the direct C8-H
functionalization on the naphthalene skeleton of 1-naphthyl-
amines has been successfully achieved, and various catalytic
versions have been developed within recent years, such as
5
6
7
8
alkylation, arylation, etherification, amination, esterifica-
9
10
11
12
tion, cyanation, chalcogenation, and alkenylation
Scheme 1a). For example, in 2016, our group reported a
5c
(
inactivated alkenes. However, reports for the direct C8-H
acylation of 1-naphthylamines remain rare up to now.
facile and efficient palladium-catalyzed C8-H amination of 1-
naphthylamines employing simple secondary aliphatic amines
The recent research interest in our group mainly focuses on
the C-H functionalization of aromatic skeletons at an unusual
site, especially the C4 or C5 position of 8-aminoquinoline
8c
as the amination reagents. Subsequently, an efficient protocol
for the direct C8−H etherification with arylboronic acids was
7
b
described by the group of Punniyamurthy. Recently,
Chatani’s group demonstrated rhodium(I)-catalyzed C8-H
bond alkylation with various alkenes including some
Received: January 23, 2019
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b00283
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
1
3
14
8c
derivatives and the C4 or C8 site of 1-naphthylamides
derivatives. Inspired by the above-mentioned previous report
and our own work, we envisioned developing a simple and
efficient reaction pattern for regioselective C8-H bond
acylation of 1-naphthylamine derivatives under the assistance
of the picolinamide (PA) moiety (Scheme 1b).
product in a higher yield of 75% (Table 1, entries 10−15).
Control experiments indicated that palladium catalyst and base
were proven to be essential to this reaction (Table 1, entries 16
and 17). The molecular structure of 3aa was unambiguously
confirmed by single-crystal X-ray diffraction study.
With the optimized reaction conditions in hand, the
applicability of 1-naphthylamine derivatives in this acylation
was examined, and the results are summarized in Scheme 2.
The acylation of N-(naphthalen-1-yl)picolinamide 1a with
benzoyl chloride 2a was first conducted in 1,2-dichloroethane
(
DCE) in the presence of NaOAc under the catalysis of
Pd(OAc) at 120 °C, and gratifyingly, the desired product 3aa
was obtained in 29% yield (Table 1, entry 1). Further
Scheme 2. Scope of 1-(Naphthalenyl)picolinamides
2
Table 1. Optimization of the Reaction Conditions ,
a b
b
entry
catalyst
base
additive
yield (%)
c
1
Pd(OAc)2
Pd(OAc)2
PdCl2
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaHCO3
Na CO
29
49
33
41
57
42
38
25
49
52
57
60
75
61
68
nr
2
3
4
5
6
7
8
9
Pd(PPh3)4
Pd (dba)
2
3
3
3
3
3
3
3
3
Generally, the reaction showed broad functional group scope
and could tolerate diverse electron-donating and -withdrawing
substituents in the pyridine ring or the naphthalene moiety,
generating the corresponding products in moderate to good
yields (3ba−3na). The electronic effect at the C4 site of the
naphthalene ring would dominate the reaction process (3la vs
Pd (dba)
2
Pd (dba)
2
2
3
Pd (dba)
2
KHCO3
Pd (dba)
2
K PO4
3
10
11
12
13
14
15
16
17
Pd (dba)
2
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
PPh3
Pd (dba)
2
Xphos
Johnphos
AgSbF6
AgNTf2
AgI
3
oa). For example, the substrate bearing a weak electron-
Pd (dba)
2
withdrawing group such as a bromine atom resulted in the
Pd (dba)
2
3
product (3la) in a high yield of 77%; when there was a strong
Pd (dba)
2
3
electron-withdrawing group (NO ) at the C4 site, the
2
Pd (dba)
2
3
reactivity was switched off and little product (3oa) was
observed. Unfortunately, the products 3pa and 3qa cannot be
obtained due to the strong steric hindrance of a methyl group
at the C2 site and a hydrogen atom at the C8 site, respectively.
Subsequently, the scope of acyl chlorides were examined
under the standard reaction conditions. As showed in Scheme
Pd (dba)
2
3
NaOAc
nr
a
Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), catalyst (5 mol
), additive (20 mol %), and base (0.2 mmol) in the mixture of
toluene and 1,4-dioxane (1:1) (1.5 mL) at 120 °C under air for 24 h.
%
b
c
Isolated yield based on 1a. DCE (1 mL).
3
, generally, substrates bearing electron-donating groups
resulted in the target products in slightly higher yields
(63%−75%) than those (39−61%) of substrates containing
electron-withdrawing groups (3aa−3ac vs 3ad−3ai). Notably,
α,β-unsaturated acyl chloride could also provide the product
3aj in a moderate yield 64%. However, this reaction could not
be applicable to aliphatic acyl and 2-naphthoyl chlorides (3ak
and 3al).
Several control experiments were conducted in order to gain
insight into the mechanism (Scheme 4). Initially, the designed
substrates (4a, 5a, 6a, 7a) bearing N- or N,O-chelating groups
were performed under the standard reaction conditions, and
screening results of various solvents disclosed that a mixture of
toluene and 1,4-dioxane (1:1) as the solvent was the optimal
choice (see the Supporting Information). Subsequently,
different palladium catalysts were examined, and Pd (dba)
showed the best catalytic activity in this reaction, affording the
product 3aa in 57% yield (Table 1, entry 5 vs entries 2−4).
Unfortunately, other organic and inorganic bases did not
provide better results (Table 1, entries 6−9, and the
Supporting Information). Finally, a series of additives were
2
3
screened, and the addition of AgSbF could result in the
6
B
DOI: 10.1021/acs.orglett.9b00283
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. Scope of Various Acyl Chlorides
heated in EtOH for 12 h in the presence of the NaOH, the
compound 8a was obtained in 66% yield (Scheme 5a). A gram-
scale reaction of C8-H acylation was performed under the
standard conditions, affording the product (3aa) in a yield of
48% (Scheme 5b).
Scheme 5. Synthetic Applications
On the basis of the above-mentioned results and previous
8c,11a
reports,
a plausible mechanism is illustrated in Scheme 6.
Scheme 6. Proposed Reaction Mechanism
Scheme 4. Mechanistic Studies
Initially, Pd (dba) would be oxidized into Pd(II) species by
2
3
AgSbF , and the coordination of amide 1a with Pd(II) species
6
affords an intermediate A in the presence of base.
Subsequently, the cleavage of the ortho C−H bond smoothly
proceeds, generating a five-membered cyclopalladated(II)
intermediate B. Oxidative addition of a C−Cl bond of the
chlorocarbonyl group to the intermediate B results in a Pd(IV)
intermediate C, the reductive elimination of which takes place
to afford an intermediate D. Ligand dissociation of the
intermediate D finally occurs to furnish the product 3aa and
regenerate the active Pd(II) species to fulfill the catalytic cycle.
In summary, we have developed an efficient protocol for
palladium-catalyzed regioselective C8-H bond acylation of 1-
naphthylamine derivatives with abundant and commercially
available acyl chlorides, thereby providing a feasible access to
benzo[cd]indoles. In this reaction, oxidant is not essential.
Moreover, the reaction exhibits broad functional group
tolerance, and both aromatic and α,β-unsaturated can be
effectively coupled with 1-naphthylamines.
no products were observed, indicating that the N,N-bidentate
directing group should be essential in this transformation. The
addition of radical scavengers such as 2,2,6,6-tetramethyl-1-
piperidinyloxy (TEMPO) and 2,6-di-tert-butyl-4-methylphenol
(
BHT) did not inhibit this reaction, and therefore, this
reaction maybe not involve a radical process. Furthermore, the
experiment for calculating the kinetic isotope effect (KIE) was
carried out (see the Supporting Information), and the
corresponding KIE value (k /k = 1) may imply that the
H
D
C−H bond cleavage of the arene ring should be not involved
in the rate-limiting step, and therefore, oxidative addition of
benzoyl chloride (2a) to the Pd(II) center may be the rate-
determining step.
Furthermore, to demonstrate the synthetic utility of this
protocol, the removal of the directing group and a gram-sale
reaction were investigated. After acylated product 3aa was
C
DOI: 10.1021/acs.orglett.9b00283
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(
6) (a) Huang, L. H.; Li, Q.; Wang, C.; Qi, C. Z. J. Org. Chem. 2013,
ASSOCIATED CONTENT
■
78, 3030. (b) Nadres, E. T.; Santos, G. I. F.; Shabashov, D.; Daugulis,
*
S
Supporting Information
O. J. Org. Chem. 2013, 78, 9689. (c) Odani, R.; Hirano, K.; Satoh, T.;
Miura, M. J. Org. Chem. 2013, 78, 11045. (d) Takamatsu, K.; Hirano,
K.; Miura, M. Angew. Chem., Int. Ed. 2017, 56, 5353.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b00283.
(7) (a) Roane, J.; Daugulis, O. Org. Lett. 2013, 15, 5842. (b) Roy, S.;
Pradhan, S.; Punniyamurthy, T. Chem. Commun. 2018, 54, 3899.
(c) Han, J. N.; Du, C.; Zhu, X. J.; Wang, Z. L.; Zhu, Y.; Chu, Z. Y.;
Niu, J. L.; Song, M. P. Beilstein J. Org. Chem. 2018, 14, 2090.
Experimental details, characterization, and NMR spectra
of all products (PDF)
(8) (a) Li, Q.; Zhang, S. Y.; He, G.; Ai, Z. Y.; Nack, W. A.; Chen, G.
Accession Codes
Org. Lett. 2014, 16, 1764. (b) Pradhan, S.; De, B. P.; Punniyamurthy,
T. J. Org. Chem. 2017, 82, 4883. (c) Li, Z. X.; Sun, S. Y.; Qiao, H. J.;
Yang, F.; Zhu, Y.; Kang, J. X.; Wu, Y. S.; Wu, Y. J. Org. Lett. 2016, 18,
CCDC 1884982 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
4
(
594.
9) Lan, J. Y.; Xie, H. S.; Lu, X. X.; Deng, Y. F.; Jiang, H. F.; Zeng,
W. Org. Lett. 2017, 19, 4279.
10) (a) Guan, D. H.; Han, L.; Wang, L. L.; Song, H.; Chu, W. Y.;
(
Sun, Z. Z. Chem. Lett. 2015, 44, 743. (b) Wang, L. L.; Yang, M. X.;
Liu, X. C.; Song, H.; Han, L.; Chu, W. Y.; Sun, Z. Z. Appl. Organomet.
Chem. 2016, 30, 680. (c) Song, H.; Liu, X. C.; Wang, C. L.; Qiao, J.
Y.; Chu, W. Y.; Sun, Z. Z. Asian J. Org. Chem. 2017, 6, 1693.
AUTHOR INFORMATION
■
Corresponding Authors
(
11) (a) Iwasaki, M.; Kaneshika, W.; Tsuchiya, Y.; Nakajima, K.;
*
*
*
E-mail: yangf@zzu.edu.cn.
E-mail: yusheng.wu@tetranovglobal.com.
E-mail: wyj@zzu.edu.cn.
Nishihara, Y. J. J. Org. Chem. 2014, 79, 11330. (b) Xiong, Y. S.; Yu, Y.;
Weng, J.; Lu, G. Org. Chem. Front. 2018, 5, 982.
(
12) Grigorjeva, L.; Daugulis, O. Angew. Chem., Int. Ed. 2014, 53,
0209.
13) (a) Qiao, H. J.; Sun, S. Y.; Yang, F.; Zhu, Y.; Zhu, W.; Dong, Y.
X.; Wu, Y. S.; Kong, X. T.; Jiang, L.; Wu, Y. J. Org. Lett. 2015, 17,
086. (b) Sun, M. M.; Sun, S. Y.; Qiao, H. J.; Yang, F.; Zhu, Y.; Kang,
1
(
ORCID
Yusheng Wu: 0000-0001-7023-9541
Yangjie Wu: 0000-0002-0134-0870
Notes
6
J. X.; Wu, Y. S.; Wu, Y. J. Org. Chem. Front. 2016, 3, 1646. (c) Qiao,
H. J.; Sun, S. Y.; Yang, F.; Zhu, Y.; Kang, J. X.; Wu, Y. S.; Wu, Y. J.
Adv. Synth. Catal. 2017, 359, 1976. (d) Qiao, H. J.; Sun, S. Y.; Zhang,
Y.; Zhu, H. M.; Yu, X. M.; Li, Z. X.; Yang, F.; Wu, Y. S.; Wu, Y. J. Org.
Chem. Front. 2017, 4, 1981.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(14) (a) Bai, P. R.; Sun, S. Y.; Li, Z. X.; Qiao, H. J.; Su, X. X.; Yang,
We are grateful to the National Natural Science Foundation of
China (Nos. 21102134, 21172200) for financial support.
F.; Wu, Y. S.; Wu, Y. J. J. Org. Chem. 2017, 82, 12119. (b) Zhu, H. M.;
Sun, S. Y.; Qiao, H. J.; Yang, F.; Kang, J. X.; Wu, Y. S.; Wu, Y. J. Org.
Lett. 2018, 20, 620.
REFERENCES
■
(
1
1) (a) Masson, P. J.; Coup, D.; Millet, J.; Brown, N. L. J. Biol. Chem.
995, 270, 2662. (b) Romines, K. R.; Freeman, G. A.; Schaller, L. T.;
Cowan, J. R.; Gonzales, S. S.; Tidwell, J. H.; Andrews, C. W.;
Stammers, D. K.; Hazen, R. J.; Ferris, R. G.; Short, S. A.; Chan, J. H.;
Boone, L. R. J. Med. Chem. 2006, 49, 727. (c) Sharmoukh, W.; Ko, K.
C.; Noh, C.; Lee, J. Y.; Son, S. U. J. Org. Chem. 2010, 75, 6708.
(
1
d) Yus, M.; Gonzal
13, 5595.
2) For selected examples of transition-metal-catalyzed direct C−H
bond acylation under the assistance of a directing group, see:
ez-Gomez, J. C.; Foubelo, F. Chem. Rev. 2013,
́ ́
(
(
(
a) Fang, P.; Li, M. Z.; Ge, H. B. J. Am. Chem. Soc. 2010, 132, 11898.
b) Kochi, T.; Urano, S.; Seki, H.; Mizushima, E.; Sato, M.; Kakiuchi,
F. J. Am. Chem. Soc. 2009, 131, 2792. (c) Liu, P. M.; Frost, C. G. Org.
Lett. 2013, 15, 5862. (d) Szabo, F.; Daru, J.; Simko, D.; Nagy, T.;
́
́
Stirling, A.; Novak, Z. Adv. Synth. Catal. 2013, 355, 685. (e) Ma, Y.
N.; Tian, Q. P.; Zhang, H. Y.; Zhou, A. X.; Yang, S. D. Org. Chem.
Front. 2014, 1, 284. (f) Pi, C.; Cui, X. L.; Liu, X. Y.; Guo, M. X.;
Zhang, H. Y.; Wu, Y. J. Org. Lett. 2014, 16, 5164. (g) Yu, S. J.; Li, Y.
Z.; Kong, L. H.; Zhou, X. K.; Tang, G. D.; Lan, Y.; Li, X. W. ACS
Catal. 2016, 6, 7744. (h) Sharma, U. K.; Gemoets, H. P. L.; Schro
F.; Noel, T.; Van der Eycken, E. V. ACS Catal. 2017, 7, 3818.
i) McAteer, D. C.; Javed, E.; Huo, L.; Huo, S. Q. Org. Lett. 2017, 19,
606. (j) Jing, K.; Li, Z. Y.; Wang, G. W. ACS Catal. 2018, 8, 11875.
̈
der,
̈
(
1
(
3) Sartori, G.; Maggi, R. Chem. Rev. 2006, 106, 1077.
(4) Zaitsev, J. V. G.; Shabashov, D.; Daugulis, O. J. Am. Chem. Soc.
2
(
2
005, 127, 13154.
5) (a) Huang, L. H.; Sun, X. D.; Li, Q.; Qi, C. Z. J. Org. Chem.
014, 79, 6720. (b) Shang, R.; Ilies, L.; Nakamura, E. J. Am. Chem.
Soc. 2015, 137, 7660. (c) Rej, S.; Chatani, N. ACS Catal. 2018, 8,
699.
6
D
DOI: 10.1021/acs.orglett.9b00283
Org. Lett. XXXX, XXX, XXX−XXX