Synthesis of 2-substituted 9,10-anthraquinones

Article abstract of DOI:10.1080/00397911.2013.786090

A convenient preparation of racemic 2-substituted 9,10-anthraquinones that included 2-triazoylethyl skeleton 1 and 2-alkylethyl skeleton 6 is reported. The products were obtained in good yields by a three-or four-step synthetic route based on a sequence of N-bromosuccinimide (NBS)-mediated bromination of 2-ethyl-9,10-anthraquinone 2, nucleophilic substitution, and CuI-catalyzed 1,3-dipolar cycloaddition or alkylation/reductive desulfonylation. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]

Full text of DOI:10.1080/00397911.2013.786090

This article was downloaded by: [Laurentian University]
On: 05 September 2013, At: 10:30
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Synthesis of 2-substituted 9,10-
anthraquinones
Meng-Yang Chang a & Hang-Yi Tai a
a Department of Medicinal and Applied Chemistry , Kaohsiung
Medical University , Kaohsiung , Taiwan
Published online: 05 Sep 2013.
To cite this article: Meng-Yang Chang & Hang-Yi Tai (2013) Synthesis of 2-substituted 9,10-
anthraquinones, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 43:24, 3363-3372
To link to this article: http://dx.doi.org/10.1080/00397911.2013.786090
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 43: 3363–3372, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.786090
SYNTHESIS OF 2-SUBSTITUTED
9,10-ANTHRAQUINONES
Meng-Yang Chang and Hang-Yi Tai
Department of Medicinal and Applied Chemistry, Kaohsiung Medical
University, Kaohsiung, Taiwan
GRAPHICAL ABSTRACT
Abstract A convenient preparation of racemic 2-substituted 9,10-anthraquinones that
included 2-triazoylethyl skeleton 1 and 2-alkylethyl skeleton 6 is reported. The products
were obtained in good yields by a three- or four-step synthetic route based on a sequence
of N-bromosuccinimide (NBS)–mediated bromination of 2-ethyl-9,10-anthraquinone 2,
nucleophilic substitution, and CuI-catalyzed 1,3-dipolar cycloaddition or alkylation=
reductive desulfonylation.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Alkynes; azides; dipolar cycloaddition; heterocycles; nucleophilic substitution
INTRODUCTION
Miscellaneous anthraquinone (anthracene-9,10-dione) derivatives are
important condensed three-ring arenes in combinatorial drug discovery libraries;
physcion, emodin, fallacinal, teloschistin, chrysophanol, and xanthorin abound in
lichens and some plants, from which they can be easily isolated.[1] The function-
alization of substituted anthraquinones has been restricted to a narrow choice of
chemical transformations[2] due to the inertness of this skeleton to common electro-
philic substitution reactions.[3] The reductive Claisen rearrangement reaction of
allyloxyanthraquinones has become a standard method for introducing the alkyl
groups onto the nucleus of this skeleton.[4] However, there is no example of struc-
tures containing both triazole and anthraquinone moieties. 1,2,3-Triazoles have
received considerable attention in the search for new drugs in pharmacology, and
Received January 16, 2013.
Address correspondence to Meng-Yang Chang, Department of Medicinal and Applied Chemistry,
Kaohsiung Medical University, Kaohsiung 807, Taiwan. E-mail: mychang@kmu.edu.tw
3363

3364
M.-Y. CHANG AND H.-Y. TAI
several efforts have been made to optimize methods for their preparation. Based on
this reason, the synthesis of triazoles with the conjugated anthraquinone moieties
was explored by the CuI-promoted 1,3-dipolar cycloaddition.[5,6]
DISCUSSION
Herein, an easy and rapid synthetic route was investigated for preparing a series
of racemic N-triazolyl-conjugated 2-ethyl-9,10-anthraquinones 1 (see Scheme 1). As
shown in Scheme 2, a convenient three-step synthesis of skeleton 1 from
2-ethyl-9,10-anthraquinone 2 is described. It involves (i) a-bromination of com-
pound 2 with N-bromosuccinimide (NBS) in AcOH; (ii) nucleophilic substitution
of the benzylic bromide with NaN3; and (iii) the regioselective CuI-catalyzed
1,3-dipolar cycloaddition reaction of the resulting azide with different alkynes.
First, NBS-mediated treatment of compound 2 or 2a in boiling AcOH for 5 h
provided a sole compound, 3 or 3a, in 89% or 66% yield.[7] 1-Nitro-2-ethyl-
9,10-anthraquinone could be provided by nitration of compound 2 with fuming
HNO3 and H2SO4 in 76% yield.[8] Nucleophilic substitution of bromine atom in
compound 3 or 3a, with different nucleophiles 4a–g, was investigated subsequently.
Initially, treatment of compound 3 with NaN3 4a in acetone gave compound 5a in
76% yield. When compound 3 was treated with NaCN 4f or NaOEt 4g, the complex
mixture was observed to change with the reaction time, temperature, or solvent. By
changing the nucleophile to sodium p-toluenesulfinic salt 4b, compounds 5b and 5f
were isolated in 60% and 51% yield when compound 3 or 3a was used as a substrate.
The expected 3-S-substituted compound 5c or 5d was obtained in good yield
(NaSCN 4c, ꢀ81%; NaSPh 4d, ꢀ88%) by the abovementioned methodology. When
compound 3 was treated with poorer nucleophile (NaOAc 4e), compound 5e was
produced in 63% yield. We believed that a stronger nucleophile, such as NaCN 4f
or NaOEt 4g, could not be easily introduced into the benzylic position of compound
3 via an intermolecular nucleophilic substitution as it might attack the carbonyl
group to form labile adducts or abstract the proton to generate the dehydrobromi-
nated olefinic products. The desired compounds 1a–h were achieved via
CuI-promoted 1,3-dipolar cycloaddition of compound 5a with several alkynes 6a–
h. Eight commercially available alkynes 6a–h were examined in the preparation of
skeleton 1, as shown in Table 1.
Scheme 1. Synthetic approach to the skeleton 1.

2-SUBSTITUTED 9,10-ANTHRAQUINONES
3365
Scheme 2. Nucleophilic substitution of compound 2.
Based on the model of a cycloaddition reaction for the preparation of com-
pound 1a, we examined the reaction of compound 5a and ethynylbenzene (6a) at
80 ꢁC for 10 h in the presence of CuI without the addition of other reagents. Com-
pound 1a was obtained only in 35% yield. When 2.0 equivalents of Et3N were added
to the reaction mixture and the heating at 80 ꢁC was continued for 2 h, the yield of
product was increased to 52%. This result confirmed that the addition of Et3N could
increase the yield and cut the reaction time efficiently. In another experiment, when
sodium ascorbate was added to the reaction mixture and the heating was continued
at 80 ꢁC for 4–6 h, the yield of product was increased to only 42%. Under the pre-
viously mentioned CuI-promoted reaction condition, the second regioisomer of tria-
zole was not observed during the cycloaddition procedure. The possible reason
might be that steric hindrance was a key factor affecting the regiochemical pro-
cedure. Based on these results, treatment of compound 5a with different alkynes
6b–h was further examined.
Compounds 1b–h with 1-triazolylethyl group were obtained in good yields of
60–92% via the CuI-promoted the regioselective 1,3-cycloaddition of compound 5a
with the alkynes 6b–h in the presence of Et3N.[9] The yields of products and purity
were determined after chromatographic purification. The structures of compounds
1a–h were assigned on the basis of NMR spectroscopy. According to the synthetic
experience, some variations on the carbon C2 of anthraquinone skeleton using the
alkylation reaction of compound 5b by different halogen derivatives 7a–e in the pres-
ence of NaH was studied (Table 2).
In the first case, the C-allylation of compound 5b with allyl bromide (7a) in the
presence of 3.3 equivalents of NaH did not proceed in anhydrous tetrahydrofuran
(THF) at rt for 10 h, and the starting material 5b was recovered in its majority. When
3.3 equivalents of NaI were added to the reaction at rt and the reaction was carried
out for 5 h, product 8a was isolated in 60% yield. When the same reaction was
performed at the reflux temperature, the yield of compound 8a was increased to
88%. The results showed that the addition of excess amounts of NaI and the elevated

3366
M.-Y. CHANG AND H.-Y. TAI
Table 1. Synthesis of triazolyl-conjugated anthraquinones 1a–ha
Entry
Alkyne 6
Product 1 = yield (%)
1
6a
1a = 52
2
6b
6c
6d
1b = 79
1c = 80
1d = 92
3
4
5
6e
1e = 62
(Continued )

2-SUBSTITUTED 9,10-ANTHRAQUINONES
3367
Table 1. Continued
Alkyne 6
Entry
Product 1 = yield (%)
6
6f
1f = 60
7
6g
1g = 79
8
6h
aThe products 1a–h were >95% pure as judged by 1HNMR analysis.
1h = 80
reaction temperature could increase the yield and efficiently promote the SN2-type
alkylation reaction. With the results in hand, compounds 8b–e could also be obtained
in good yields of 79–90%. The attempts to extend this alkylation reaction to a second-
ary alkyl halide (e.g., isopropyl or isobutyl halide) were unsuccessful. To afford the
derivatives of 2-substituted 9,10-anthraquinones 9a–e, the reductive desulfonylation
of compounds 8a–e was carried out in boiling anhydrous MeOH using the freshly pre-
pared sodium amalgam. The appropriate products 9a–e were obtained in good yields
(84–92%). In particular, compounds 9c and 9d were obtained as a mixture of Z- and
E-isomers under the reductive desulfonylation conditions.[10] However, attempts to
treat compound 5f with NaH and MeI failed to yield the desired methylated product.
We believed that the nitro group on the C1 position of compound 5f should be a key
factor in stabilizing the generated carbanion, so that the methylation was unsuccessful.
In summary, we have successfully presented a concise three- or four-step
synthetic methodology for producing a series of novel racemic 2-triazoylethyl or
2-alkylethyl 9,10-anthraquinone derivatives 1a–h and 9a–e involving NBS-mediated
benzylic bromination of 2-ethyl-9,10-anthraquinone 2, nucleophilic substitution with
NaN3 or sodium p-toluenesulfinic salt, and the CuI-catalyzed 1,3-dipolar cycloaddi-
tion reaction or alkylation=reductive desulfonylation. More important, the overall
prepared procedures are shorter, high-yielding, and more efficient for synthesizing
the skeleton of triazolyl-conjugated anthraquinones.

3368
M.-Y. CHANG AND H.-Y. TAI
Table 2. Synthesis of 2-substituted anthraquinones 9a–ea
Entry
R3X 7
Product 8 = yield (%)
Product 9 = yield (%)
1
7a
7b
8a = 88
9a = 90
2
8b = 90
9b = 88
3
4
5
7c
7d
7e
8c = 82
8d = 79
8e = 85
9c = 84
9d = 86
9e = 92
aThe products 8a–e and 9a–e were >95% pure as judged by 1HNMR analysis.
EXPERIMENTAL
Synthesis of Skeleton 5
A nucleophile 4a–g (1.0 mmol) was added to a stirred solution of compound 3
or 3a (0.3 mmol) in the mixture of solvents of acetone=water (10 mL, v=v ¼ 9=1;
NaN3 4a; NaSCN 4c), 1,4-dioxane=water (10 mL, v=v ¼ 4=1; NaSO2Tol 4b; NaSPh
4d) or THF=HOAc (10 mL, v=v ¼ 9=1; NaOAc 4e) at rt. The reaction mixture was
stirred at reflux for 6–10 h. The reaction solvent was evaporated. The residue was
extracted with EtOAc (3 ꢂ 30 mL). The combined organic layers were washed with
brine, dried, filtered, and evaporated under reduced pressure to afford the crude
product. Purification on silica gel (hexanes=EtOAc ¼ 6=1–1=1) afforded compounds

2-SUBSTITUTED 9,10-ANTHRAQUINONES
3369
1
5a–f. All of the new compounds were characterized by infrared (IR), H NMR,
13C NMR, and high-resdution mass spectrometry (HRMS). Representative data
of 2-[1-(toluene-4-sulfonyl)ethyl]anthraquinone (5b) are as follows: Yellowish solid;
yield: 60% (70 mg); mp ¼ 184–185 ꢁC (recrystallized from hexanes and EtOAc);
Rf ¼ 0.3 (hexanes=EtOAc, 3=1); IR (CHCl3): nmax 3278, 3022, 1732, 1660, 1601,
1450 cmꢃ1. HRMS (ESI, Mþ þ 1) calcd. for C23H19O4S: 391.1004 found: 391.1012,
1H NMR (400 MHz, CDCl3): d 8.31–8.26 (m, 2H), 8.22 (d, J ¼ 8.0 Hz, 1H), 8.01
(d, J ¼ 2.0 Hz, 1H), 7.83–7.78 (m, 2H), 7.70 (dd, J ¼ 2.0, 8.0 Hz, 1H), 7.49 (d,
J ¼ 8.0 Hz, 2H), 7.22 (d, J ¼ 8.0 Hz, 2H), 4.41 (q, J ¼ 7.2 Hz, 1H), 2.38 (s, 3H),
1.82 (d, J ¼ 7.2 Hz, 3H); 13C NMR (100MHz, CDCl3): d 182.65, 182.44, 145.15
(2ꢂ), 140.64, 134.88, 134.25 (2ꢂ), 133.47, 133.38, 133.34, 133.35, 129.62 (2ꢂ), 129.14
(2ꢂ), 128.16, 127.39, 127.27, 127.25, 65.79, 21.59, 14.17. Anal. calcd. for C23H18O4S:
C, 70.75; H, 4.65. Found: C, 70.98; H, 4.82.
Synthesis of Skeleton 1
CuI (190mg, 1.0 mmol), Et3N (200mg, 2.0 mmol), and different alkynes 6a–h
(1.0 mmol) were added to a solution of compound 5a (110mg, 0.4 mmol) in
anhydrous dimethylformamide (DMF, 4 mL) at rt. The reaction mixture was stirred
at 80ꢁC for 2 h, then cooled to rt. Saturated NaHCO3(aq) (5 mL) was added to
the reaction mixture, and the solvent was evaporated under reduced pressure. The resi-
due was extracted with EtOAc (3ꢂ 30mL). The combined organic layers were washed
with brine, dried, filtered, and evaporated under reduced pressure to afford the crude
product. Purification on silica gel (hexanes=EtOAc ¼ 2=1–1=2) afforded compounds
1a–h. Representative data of 2-[1-(4-phenyl[1,2,3]triazol-1-yl)ethyl]anthraquinone
(1a) are as follows: Yellowish solid; yield: 52% (79 mg); mp¼ 188–189 ꢁC (recrystallized
from hexanes and EtOAc); Rf ¼ 0.4 (hexanes=EtOAc, 3=1). HRMS (ESI, Mþ þ 1)
1
calcd; for C24H18N3O2: 380.1399; found: 380.1343. H NMR (400MHz, CDCl3): d
8.31–8.27 (m, 4H), 7.83–7.78 (m, 5H), 7.67 (dd, J ¼ 2.0, 8.0 Hz, 1H), 7.42–7.38 (m,
2H), 7.33–7.29 (m, 1H), 6.03 (q, J ¼ 6.8 Hz, 1H), 2.13 (d, J ¼ 6.8 Hz, 3H); 13C NMR
(100MHz, CDCl3): d 182.62, 182.38, 148.16, 146.36 (2ꢂ), 134.36, 134.27, 133.96,
133.34 (2ꢂ), 132.10, 130.32, 128.81 (2ꢂ), 128.34, 128.28, 127.30 (2ꢂ), 125.72 (2ꢂ),
124.89, 118.32, 59.83, 21.12. Anal. calcd. for C24H17N3O2: C, 75.97; H, 4.52; N,
11.08. Found: C, 76.22; H, 4.84; N, 11.31.
Synthesis of Skeleton 8
NaH (60% in oil, 40 mg, 1.0 mmol) and NaI (142 mg, 1.0 mmol) were added to
a solution of compound 5b (117 mg, 0.3 mmol) in anhydrous THF (10 mL) at rt.
After 10 min, alkyl halide 7a–e (1.0 mmol) was added the reaction mixture at rt.
The reaction mixture was stirred at reflux for 5 h, then cooled to rt. Saturated
NaHCO3(aq) (5 mL) was added to the reaction mixture, and the solvent was evapo-
rated under reduced pressure. The residue was extracted with EtOAc (3 ꢂ 30 mL).
The combined organic layers were washed with brine, dried, filtered, and evaporated
under reduced pressure to afford crude product. Purification on silica gel (hexanes=
EtOAc ¼ 4=1–2=1) afforded compounds 8a–e. Representative data of 2-[1-methyl-
1-(toluene-4-sulfonyl)but-3-enyl]anthraquinone (8a) are as follows: Yellowish solid;

3370
M.-Y. CHANG AND H.-Y. TAI
yield: 88% (113 mg); mp ¼ 164–165 ꢁC (recrystallized from hexanes and EtOAc);
Rf ¼ 0.3 (hexanes=EtOAc, 3=1); IR (CHCl3): nmax 3374, 3152, 1726, 1662, 1578cmꢃ1
;
HRMS (ESI, Mþ þ 1) calcd for C26H23O4S 431.1317; found 431.1322. H NMR
(400MHz, CDCl3): d 8.34–8.27 (m, 2H), 8.25 (d, J ¼ 8.4 Hz, 1H), 8.11 (d, J ¼ 2.0 Hz,
1H), 7.93 (dd, J ¼ 2.0, 8.4 Hz, 1H), 7.85–7.79 (m, 2H), 7.29 (d, J ¼ 8.0 Hz, 2H), 7.14
(d, J ¼ 8.0 Hz, 2H), 5.42–5.31 (m, 1H), 5.17 (dd, J ¼ 1.2, 15.6 Hz, 1H), 5.05 (dd,
J ¼ 1.2, 10.8 Hz, 1H), 3.48 (dd, J ¼ 6.4, 14.4 Hz, 1H), 2.90 (dd, J ¼ 8.4, 14.4 Hz, 1H),
2.36 (s, 3H), 1.82 (s, 3H); 13C NMR (100MHz, CDCl3): d 182.75, 182.56, 145.12,
142.09, 135.00, 134.50, 134.35, 134.27, 133.43, 132.87, 132.78, 131.54, 130.62, 130.39
(2ꢂ), 129.23 (2ꢂ), 127.87, 127.30, 127.24, 126.92, 120.73, 68.78, 38.26, 21.57, 19.36.
Anal. calcd. for C26H22O4S: C, 72.54; H, 5.15. Found: C, 72.78; H, 5.43.
1
Synthesis of Skeleton 9
A freshly prepared Na(Hg) (100 mg) was added to a solution of compounds
8a–e (0.1 mmol) in anhydrous MeOH (10 mL) at rt. After 5 min, the reaction mixture
was stirred at reflux for 2 h, and then cooled to rt. Saturated NaHCO3(aq) (5 mL) was
added to the reaction mixture, and the solvent was evaporated under reduced press-
ure. The residue was extracted with DCM (3 ꢂ 30 mL). The combined organic layers
were washed with brine, dried, filtered, and evaporated under reduced pressure to
afford crude product. Purification on silica gel (hexanes=EtOAc ¼ 4=1–2=1) afforded
compounds 9a–e. Representative data of 2-(1-methylbut-3-enyl)anthraquinone (9a).
are as follows: Yellowish gum; yield: 90% (25 mg); Rf ¼ 0.4 (hexanes=EtOAc, 8=1); IR
(CHCl3): nmax 3332, 3167, 1727, 1668, 1595cmꢃ1. HRMS (ESI, Mþ þ 1) calcd, for
1
C19H17O2: 277.1228; found: 277.1234. H NMR (400MHz, CDCl3): d 8.31–8.28 (m,
3H), 8.24 (d, J ¼ 8.0 Hz, 1H), 7.81–7.76 (m, 2H), 7.62 (dd, J ¼ 2.0, 8.0 Hz, 1H),
5.75–5.65 (m, 1H), 5.03–4.97 (m, 2H), 3.03–2.98 (m, 1H), 2.47–2.37 (m, 2H), 1.35
(d, J ¼ 7.2 Hz, 3H); 13C NMR (100MHz, CDCl3): d 182.41, 182.94, 154.11, 135.99
(2ꢂ), 134.00, 133.89, 133.56, 133.53, 133.06, 131.72, 127.52, 127.14, 127.09, 125.60,
116.82, 42.09, 40.09, 21.07.
SUPPORTING INFORMATION
Experimental data and scanned photocopies of 1H and 13C NMR spectral data
are provided. This material can be found via the Supplementary Content section of
this article’s Web page.
ACKNOWLEDGMENT
The authors thank the National Science Council of the Republic of China for
financial support.
REFERENCES
1. Huneck, S.; Yoshimura, I. Identification of Lichen Substances; Springer-Verlag: Berlin, 1996.
2. (a) House, H. O.; Koepsell, D. G.; Campbell, W. J. Chemistry of carbanions, XXIV:
Comparison of stereochemistry in alkylation and the Michael reaction. J. Org. Chem.
1972, 37, 1000–1003; (b) Carissimo-Rietsch, F.; Schmitz, C.; Aubry, J.-M. Double

2-SUBSTITUTED 9,10-ANTHRAQUINONES
3371
condensation of dilithiated N-methylbenzamide with anthraquinones: Access to
the diphenylanthracenic structure. Tetrahedron Lett. 1991, 32, 3845–3846; (c) Huang,
H.-S.; Huang, K.-F.; Li, C.-L.; Huang, Y.-Y.; Chiang, Y.-H.; Huang, F.-C.; Lin, J.-J.
Synthesis, human telomerase inhibition, and anti-proliferative studies of a series of
2,7-bis-substituted amido-anthraquinone derivatives. Bioorg. Med. Chem. 2008, 16,
6976–6986; (d) Diaz, M. C.; Illescas, B. M.; Seoane, C.; Martin, N. Synthesis and
electron-donor ability of the first conjugated p-extended tetrathiafulvalene dimers.
J. Org. Chem. 2004, 69, 4492–4499.
3. For the reviews of the related compounds with the skeleton of naphthoquinone, see (a)
Piggot, M. J. Naphtho[2,3-c]furan-4,9-diones and related compounds: Theoretically
interesting and bioactive natural and synthetic products. Tetrahedron 2005, 61, 9929–
9954; (b) Brimble, M. A.; Nairn, M. R.; Prabaharan, H. Synthetic strategies towards
pyranonaphthoquinone antibiotics. Tetrahedron 2000, 56, 1937–1992; (c) Jacobs, J.;
Tehrani, K. A.; De Kimpe, N. A survey of synthetic routes towards 2-azaanthraquinones.
Tetrahedron 2011, 66, 9459–9471; (d) Ibis, C.; Tuyun, A. F.; Ozsoy-Gunes, Z.; Bahar, H.;
Stasevych, M. V.; Musyanovych, R. Y.; Komarovska-Porokhnyavets, O.; Novikov, V.
Synthesis and biological evaluation of novel nitrogen- and sulfur-containing hetero-
1,4-naphthoquinones as potent antifungal and antibacterial agents. Eur. J. Med. Chem.
2011, 46, 5861–5867.
4. (a) Cava, M. P.; Ahmed, Z.; Benfaremo, N.; Murphy, R. A.; Malley Jr., G. J. O.
Anthraquinone dye intermediates as precursors of aklavinone-type anthracyclinones.
Tetrahedron 1984, 40, 4767–4776; (b) Rao, J. A.; Cava, M. P. A new route to annelated
dihydrofurofurans: Synthesis of 6,8-dideoxyversicolorin A. J. Org. Chem. 1989, 54,
2751–2753; (c) Hauser, F. M.; Hawawasam, P. Regio- and stereospecific syntheses of
4-deoxyadriamycinone and 4,6-dideoxyadriamycinone from a common intermediate. J.
Org. Chem. 1988, 53, 4515–4519.
5. For reviews on the Huisgen 1,3-dipolar cycloaddition, see (a) Bock, V. D.; Hiemstra, H.;
van Maarrseveen, J. H. CuI-catalyzed alkyne–azide ‘‘click’’ cycloadditions from
a mechanistic and synthetic perspective. Eur. J. Org. Chem. 2006, 51–68; (b) Moses,
J. E.; Moorhouse, A. D. The growing applications of click chemistry. Chem. Soc. Rev.
2007, 36, 1249–1262; (c) Becer, C. R.; Hoogenboom, R.; Schubert, U. S. Click chemistry
beyond metal-catalyzed cycloaddition. Angew. Chem., Int. Ed. 2009, 48, 4900–4908; (d)
Amblard, F.; Cho, J. H.; Schinazi, R. F. Cu(I)-catalyzed huisgen azideꢃalkyne 1,3-dipolar
cycloaddition reaction in nucleoside, nucleotide, and oligonucleotide chemistry. Chem.
Rev. 2009, 109, 4207–4220; (e) Moorhouse, A. D.; Moses, J. E. Click chemistry and
medicinal chemistry: A case of ‘‘cyclo-addiction.’’ ChemMedChem 2008, 3, 715–723; (f)
Angell, Y. L.; Burgess, K. Peptidomimetics via copper-catalyzed azide–alkyne
cycloadditions. Chem. Soc. Rev. 2007, 36, 1674–1689; (g) do Nascimento, W. S.; Camara,
C. A.; de Oliveira, R. N. Synthesis of 2-(1H-1,2,3-triazol-1-yl)-1,4-naphthoquinones from
2-azido-1,4-naphthoquinone and terminal alkynes. Synthesis 2011, 3220–3224.
6. (a) Tornoe, C. W.; Christennsen, C.; Meldal, M. Peptidotriazoles on solid phase:
[1,2,3]-Triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of
terminal alkynes to azides. J. Org. Chem. 2002, 67, 3057–3064; (b) Rostovtsev, V. V.;
Green, L. G.; Fokin, V. V.; Sharpless, K. B. A stepwise huisgen cycloaddition process:
copper(I)-catalyzed regioselective ‘‘ligation’’ of azides and terminal alkynes. Angew.
Chem., Int. Ed. 2002, 41, 2596–2599.
7. Scholl, R.; Potschiwauscheg, J.; Lenko, J. Synthetische Versuche in der Pyranthronreihe.
Monatsh. Chem. 1911, 32, 687–710.
8. (a) Bi, N.-M.; Ren, M.-G.; Song, Q.-H. Photo-Ritter reaction of arylmethyl bromides
in acetonitrile. Synth. Commun. 2010, 40, 2617–2623; (b) Nanayakkara, N. P. D.;
Schrader, K. K. Synthesis of water-soluble 9,10-anthraquinone analogues with potent

3372
M.-Y. CHANG AND H.-Y. TAI
cyanobactericidal activity toward the musty-odor cyanobacterium Oscillatoria perornata.
J. Agric. Food Chem. 2008, 56, 1002–1007.
9. Schramn, H.; Saak, W.; Hoenke, C.; Christoffers, J. Synthesis of triazolyl-substituted
3-aminopiperidines by Huisgen-1,3-dipolar cycloaddition—New scaffolds for combina-
torial chemistry. Eur. J. Org. Chem. 2010, 1745–1753.
10. (a) Wada, A.; Tode, C.; Hiraishi, S.; Tanaka, Y.; Ohfusa, T.; Ito, M. Retinoids and related
compounds 18: A convenient synthesis of retinoic acid analogs having an anthraquinone
ring. Synthesis 1995, 1107–1110; (b) For reviews on the desulfonylation reaction, see
Najera, C.; Yus, M. Desulfonylation reactions: Recent developments. Tetrahedron 1999,
55, 10547–10658.