Gold(III)-catalyzed 1,4-nucleophilic addition: Facile approach to prepare 2-amino-1,4-naphthalenedione and 6-amino-5,8-quinolinedione derivatives

Article abstract of DOI:10.1055/s-0028-1088116

An efficient approach is developed to prepare different 2-amino-1,4-naphthalenedione and 6-amino-5,8-quinolinedione derivatives regioselectively by Au(III)-catalyzed 1,4-nucleophilic addition and subsequent oxidation. A wide variety of primary, secondary, and aromatic amines, as well as allylamine and 2-butynylamine are well tolerated under the mild conditions to give products in moderate to good yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1088116

LETTER
1099
Gold(III)-Catalyzed 1,4-Nucleophilic Addition: Facile Approach to Prepare
2-Amino-1,4-naphthalenedione and 6-Amino-5,8-quinolinedione Derivatives
S
ynthesis of 2-A
m
h
ino-1,4-nap
u
hthalenedion
n
e
and 6-A
m
h
ino-5,8-quin
u
olinedione
D
i
e
rivatives Jiang, Shaozhong Wang*
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093,
P. R. of China
Fax +86(25)83317761; E-mail: wangsz@nju.edu.cn
Received 23 January 2009
instead of amines, the Friedländer products obtained.
Abstract: An efficient approach is developed to prepare different
NaAuCl4·2H2O could also catalyze conjugated addition of
2-amino-1,4-naphthalenedione and 6-amino-5,8-quinolinedione
derivatives regioselectively by Au(III)-catalyzed 1,4-nucleophilic
addition and subsequent oxidation. A wide variety of primary, sec-
a,b-unsaturated ketones with indole and pyrrole.10 In-
spired by the above results, we envisaged that preparation
ondary, and aromatic amines, as well as allylamine and 2-butynyl- of 2-amino-1,4-naphthalene-dione and 6-amino-5,8-qui-
amine are well tolerated under the mild conditions to give products
in moderate to good yields.
nolinedione derivatives directly from amines and 1,4-
naphthalenedione (1) and 5,8-quinolinedione (2) by gold-
catalyzed regioselective 1,4-nucleophilic addition and
subsequent oxidation.
Key words: sodium tetrachloroaurate, 2-amino-1,4-naphthalene-
dione, 6-amino-5,8-quinolinedione
O
O
H
Considerable attention was given to the assembly of 2-
amino-1,4-naphthalenedione and 6-amino-5,8-quino-
linedione due to the presence of such structural frame-
works in natural products and biologically important
compounds.1,2 Generally, the amino group was installed
into the quinones by 1,4-nucleophilic addition or by
nucleophilic substitution from the corresponding halo-
substituted counterparts.3 Although the former approach
looks more attractive from a viewpoint of sustainable de-
velopment, owing to the redox properties of quinones, the
approach usually suffered from low conversion in con-
junction with tedious purifications and the requirement of
using excess quinones as oxidant. To overcome these
N
Ph
benzylamine, O2 (1.013 bar)
conditions
O
O
1
3a
Scheme 1
Table 1 Different Conditions Screened
Entry
Reaction conditionsa
Yield (%)
1
2
3
4
5
6
10 mol% PtCl2, toluene, 100 °C, 2 h
46
55
69
70
74
76
80
35
5 mol% AuPPh3OTf, Cl2(CH2)2, 80 °C, 2 h
4
problems, metal salts such as Cu(OAc)2 , CeCl3,5 and
5 mol% NaAuCl4·2H2O, MeCN, 80 °C, 2 h
5 mol% NaAuCl4·2H2O, THF, 60 °C, 2 h
5 mol% NaAuCl4·2H2O, EtOH, 80 °C, 1 h
1 mol% NaAuCl4·2H2O, EtOH, 80 °C, 1 h
1 mol% NaAuCl4·2H2O, EtOH, 80 °C, 1 h
10 mol% TFA, EtOH, 80 °C, 1 h
6
7
Ni(OAc)2 as well as molecular I2 were employed to cat-
alyze the 1,4-nucleophilic addition of 1,4-naphthalene-
dione and 5,8-quinolinedione under air/O2 atmosphere or
ultrasound conditions. However, limitations still exist,
and it is necessary to develop more efficient approaches.
In recent decade, gold(I) and gold(III) salts have emerged 7b
as versatile catalysts to carry out a variety of cycloisomer-
8b
ization reactions of substrates containing alkyne, alkene,
and allene units. Such reactions were accompanied by the a The ratio of benzyamine/1,4-naphthalenedione is 1:1, unless men-
formation of different C–C, C–O, and C–N bonds.8 In ad-
tioned.
b The ratio is 1.3:1.
dition, Au(III) shows Lewis acid property in various
chemical transformations. As one of the simplest gold(III)
salts, NaAuCl4·2H2O can activate selectively the carbonyl
group in some condensation and addition reactions.
Arcadi9 reported that NaAuCl4·2H2O could catalyze con-
densation of 1,3-diones involving b-ketoester and b-di-
ketones with amines to form b-enaminoesters and b-
enaminoketones. When 2-amino arylketones were used
We chose benzylamine and 1,4-naphthalenedione as a
model system and began the studies by optimizing the
conditions (Scheme 1, Table 1).11 The reaction was ini-
tially performed in toluene at 100 °C by using 10 mol%
PtCl2 as the catalyst. The expected product was obtained
in 46% yield after 2 hours (entry 1). When the gold(I) spe-
cies AuPPh3OTf was employed, the yield increased to
55% (entry 2). While the catalyst was switched to
NaAuCl4·2H2O, different solvents including MeCN,
THF, and EtOH were screened. Among them, ethanol
SYNLETT 2009, No. 7, pp 1099–1102
x
x.
x
x.
2
0
0
9
Advanced online publication: 26.03.2009
DOI: 10.1055/s-0028-1088116; Art ID: W01209ST
© Georg Thieme Verlag Stuttgart · New York

1100
C. Jiang, S. Wang
LETTER
gave the best yield (entries 3–5). Attempt to reduce the yields of the adducts were 65% and 75%, respectively (en-
amount of NaAuCl4·2H2O from 5 mol% to 1 mol% result- tries 1, 2). Allylamine and 2-butynylamine gave the ad-
ed in almost little change of the yield (entry 6). Using 1.3 ducts in 85% and 70% yield, which illustrated that the
equivalents of benzylamine led to a moderate increase in double bond and triple bond were tolerated under the
the yield (entry 7). In addition, when TFA was used in- reaction conditions (entries 3, 4). Besides primary amines,
stead of gold catalysts, the efficiency became inferior (en- secondary amines also worked well (entry 5). However,
try 8).
aromatic amines reacted differently according to the sub-
stituents on the benzene ring (entries 6–8). For the sub-
strates with electron-donating group (OMe), the yield was
high (up to 88%), while substrates with electron-with-
drawing group (CO2Et) gave a lower yield. After screened
various amines, we changed the 1,4-naphthalenedione to
5,8-quinolinedione and investigated the regioselectivity
of the reaction. When 5,8-quinolinedione was used, in
principle there are two alternative pathways which can
lead to the formation of isomeric mixtures. However, in
our catalytic system, 6-amino-substituted 5,8-quino-
linedione was achieved without any 7-amino adduct de-
tected. Primary and secondary amines as well as aromatic
amines underwent regioselectively cascade 1,4-nucleo-
philic addition and oxidation at room temperature in a
yield ranging from 60– 70% (entries 9–13).
O
O
O
NaAuCl4⋅2H2O (1 mol%), O2 (1.013 bar)
NR1R2
HNR1R2 (1.3 equiv), EtOH
X
X
O
3b–n
X = CH, N
Scheme 2
Using the optimized conditions,12 the scope of the
Au(III)-catalyzed sequential 1,4-nucleophilic addition
and oxidation of 1,4-naphthalenedione was screened
(Scheme 2, Table 2). Primary amines containing an in-
dole unit or possessing a chiral center could undergo the
reaction with 1,4-naphthalenedione smoothly, and the
Table 2 NaAuCl4·2H2O-Catalyzed 1,4-Nucleophilic Addition–Oxidation of 1,4-Naphthalenedione and 5,8-Quinolinedione
Entry
Amine
Product
Conditions
Yield (%)
O
H
N
NH2
NH
1
80 °C, 1 h
65
N
H
O
O
3b
H
N
NH2
2
3
4
80 °C, 2 h
50 °C, 2 h
80 °C, 2 h
75
85
70
Ph
O
O
3c
H
N
NH2
O
O
3d
H
N
NH2
O
O
3e
3f
N
5
80 °C, 1 h
58
N
H
O
Synlett 2009, No. 7, 1099–1102 © Thieme Stuttgart · New York

LETTER
Synthesis of 2-Amino-1,4-naphthalenedione and 6-Amino-5,8-quinolinedione Derivatives
1101
Table 2 NaAuCl4·2H2O-Catalyzed 1,4-Nucleophilic Addition–Oxidation of 1,4-Naphthalenedione and 5,8-Quinolinedione (continued)
Entry
6
Amine
Product
Conditions
80 °C, 4 h
Yield (%)
63
O
H
N
NH2
O
O
3g
3h
3i
NH2
H
N
7
8
80 °C, 3 h
80 °C, 4 h
25 °C, 1 h
25 °C, 1 h
25 °C, 1 h
25 °C, 1 h
88
50
62
60
64
60
OMe
O
OMe
NH2
O
H
N
CO2Et
O
CO2Et
O
H
N
NH2
9
N
O
O
3j
N
10
11
12
N
N
H
O
O
3k
O
O
N
N
H
N
O
O
3l
H
N
NH2
N
O
O
3m
NH2
H
N
13
25 °C, 2 h
70
N
OMe
O
OMe
3n
The proposed mechanism for the formation of 2-amino- group of the quinones by Au(III) facilitated the nucleo-
1,4-naphthalenediones and 6-amino-5,8-quinolinediones philic addition step. For 5,8-quinolinedione, the coordina-
from different amines with 1,4-naphthalenedione and 5,8- tion of Au(III) with the nitrogen and 8-carbonyl group
quinolinedione consists of 1,4-uncleophilic addition fol- determines the regioselectivity and outcome of the reac-
lowed by oxidation (Scheme 3). Activation of carbonyl
Synlett 2009, No. 7, 1099–1102 © Thieme Stuttgart · New York

1102
C. Jiang, S. Wang
LETTER
O
OH
OH
O
O
O
HNR1R2
NR1R2
NR1R2
NR1R2
[O]
X
X
X
X
OH
Au
O
Scheme 3
(6) (a) Yoshida, K.; Ishiguro, M.; Honda, H.; Yamamoto, M.;
Kubo, Y. Bull. Chem. Soc. Jpn. 1988, 61, 4335.
tion. Under atmospheric oxygen, the adduct amino-hydro-
quinones can be oxidized to quinones.13
(b) Yoshida, K.; Yamamoto, M.; Ishiguro, M. Chem. Lett.
To summarize, an efficient approach is developed to
prepare different 2-amino-1,4-naphthalenedione and 6-
amino-5,8-quinolinedione derivatives regioselectively by
Au(III)-catalyzed 1,4-nucleophilic addition and subse-
quent oxidation. Amines such as allyl and propargyl
amines which are well tolerated under the conditions gave
moderate to good yields as well as different substituted
primary, secondary, and aromatic amines. Further explo-
ration of this approach is in progress.
1986, 1059.
(7) Liu, B.; Ji, S.-J. Synth. Commun. 2008, 38, 1201.
(8) For reviews, see: (a) Gorin, D. J.; Toste, F. D. Nature
(London) 2007, 446, 395. (b) Hashmi, A. S. K. Chem. Rev.
2007, 107, 3180. (c) Arcadi, A. Chem. Rev. 2008, 108,
3266. (d) Jimenez-Nunez, E.; Echavarren, A. M. Chem. Rev.
2008, 108, 3326. (e) Li, Z.; Brouwer, C.; He, C. Chem. Rev.
2008, 108, 3239. (f) Fürstner, A.; Davies, P. W. Angew.
Chem. Int. Ed. 2007, 46, 3410. (g) Zhang, L.; Sun, J.;
Kozmin, S. A. Adv. Synth. Catal. 2006, 348, 2271.
(9) (a) Arcadi, A.; Chiarini, M.; Di Giuseppe, S.; Marinelli, F.
Synlett 2003, 203. (b) Atechian, S.; Nock, N.; Norcross,
R. D.; Ratni, H.; Thomas, A. W.; Verron, J.; Masciadri, R.
Tetrahedron 2007, 63, 2811. (c) Arcadi, A.; Bianchi, G.;
Di Giuseppe, S.; Marinelli, F. Green Chem. 2003, 5, 64.
(10) (a) Arcadi, A.; Binanchi, G.; Chiarini, M.; D’Anniballe, F.
Synlett 2004, 944. (b) Hashmi, A. S. K.; Salathe, R.; Frey,
W. Eur. J. Org. Chem. 2007, 1648. (c) Alfonsi, M.; Arcadi,
A.; Bianchi, B.; Marinelli, F.; Nardini, A. Eur. J. Org. Chem.
2006, 2393. (d) Fukuda, Y.; Utimoto, K.; Nozaki, H.
Heterocycles 1987, 25, 297. (e) Hashmi, K.; Rudolph, M.;
Schymura, S.; Visus, J.; Frey, W. Eur. J. Org. Chem. 2006,
4905.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
We thank Natural Science Foundation of China (20802034) and 973
program (2007CB936404) for financial support.
References and Notes
(11) When the reaction performed in DMF without any catalyst,
the yield reported is 72% after 24 h. For the reference, see:
Aristoff, P. A.; Johnson, P. D. J. Org. Chem. 1992, 57, 6234.
(12) General Procedures for the Preparation of 2-Amino-1,4-
naphthalenediones (3a–i) and 6-Amino-5,8-quinoline-
diones (3j–n)
(1) (a) Lin, T.-S.; Xu, S.-P.; Zhu, L.-Y.; Cosby, L.; Sartonelli, A.
J. Med. Chem. 1989, 32, 1467. (b) Stefanska, B.;
Dzieduszycka, M.; Martelli, S.; Antonini, I.; Borowski, E.
J. Org. Chem. 1993, 58, 1568. (c) Konoshima, T.; Kozuka,
M.; Koyama, J.; Okatani, T.; Tagahara, K.; Tokuda, H.
J. Nat. Prod. 1989, 52, 987. (d) Lin, T.-S.; Xu, S.-P.; Zhu,
L.-Y.; Divo, A.; Sartonelli, A. J. Med. Chem. 1991, 34,
1634.
(2) (a) Nagaoka, H.; Kishi, Y. Tetrahedron 1981, 37, 3873.
(b) Lanz, T.; Tropf, S.; Marner, F.-J.; Schröder, J.; Schröder,
G. J. Biol. Chem. 1991, 266, 9971.
(3) Kutyrev, A. A. Tetrahedron 1991, 47, 8043.
(4) Dix, J. P.; Vögtle, F. Chem. Ber. 1981, 114, 638.
(5) (a) Cuerva, J. M.; Cardenas, D. J.; Echavarren, A. M.
J. Chem. Soc., Perkin Trans. 1 2002, 1360. (b) Peterson,
J. R.; Zjawiony, J. K.; Liu, S.; Hufford, C. D.; Clark, A. M.;
Rogers, R. D. J. Med. Chem. 1992, 35, 4069.
1,4-Naphthalenedione (1.0 mmol) or 5,8-quinolinedione
(1.0 mmol) and NaAuCl4·2H2O (0.01 mmol) were dissolved
in EtOH (2.0 mL) under oxygen atmosphere. Then the amine
(1.3 mmol) was added to the above solution by syringe. The
formed solution was heated at 80 °C or run at r.t. for a certain
time (monitored by TLC). After cooling, the mixture was
poured into H2O (20 mL), and extracted with CH2Cl2 (3 × 15
mL). The combined organic extract was dried by anhyd
MgSO4, and the solvent was removed by distillation. The
crude products obtained were purified by flash chromatog-
raphy to give 2-amino-1,4-naphthalenediones and 6-amino-
5,8-quinolinediones.
(13) Oxidation of hydroquinone by Au nanoclusters: Miyamura,
H.; Shiramizu, M.; Matsubara, R.; Kobayashi, S. Chem. Lett.
2008, 37, 360.
Synlett 2009, No. 7, 1099–1102 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.