Pd(OAc)2-catalyzed macrocyclization of 1,2-diazonaphthoquinones with cyclic ethers

Article abstract of DOI:10.1021/ol500222s

Pd(OAc)₂ was found to be an efficient catalyst for the macrocyclization of 1,2-diazonaphthoquinones and cyclic ethers. This transformation serves as an efficient method for the synthesis of protected 1,2-naphthalenediols.

Full text of DOI:10.1021/ol500222s

Letter
pubs.acs.org/OrgLett
Pd(OAc)2‑Catalyzed Macrocyclization of 1,2-Diazonaphthoquinones
with Cyclic Ethers
Mitsuru Kitamura,* Masato Kisanuki, Koichi Kanemura, and Tatsuo Okauchi
Department of Applied Chemistry, Kyushu Institute of Technology, 1-1 Sensuicho, Tobata, Kitakyushu, 804-8550 Japan
S
* Supporting Information
ABSTRACT: Pd(OAc)2 was found to be an efficient catalyst
for the macrocyclization of 1,2-diazonaphthoquinones and
cyclic ethers. This transformation serves as an efficient method
for the synthesis of protected 1,2-naphthalenediols.
compounds 1 and five- or six-membered ring cyclic acetals was
achieved, which was designed by [N]-endo-trig cyclization ([N]
= 8 or 9).5b
α-Diazocarbonyl compounds are easily decomposed to the
corresponding α-carbonylcarbenes or metal carbenes via
photoirradiation, electrophilic activation, or the treatment of
metal complexes.1 Thus formed, these carbenes are electro-
philic and readily react with various nucleophilic Lewis bases to
generate the corresponding ylides, which are widely used in
organic synthesis.1 For example, oxonium ylides are formed via
the reaction of these carbenes and cyclic ethers, and then
Stevens-type rearrangement,2 polymerization,3or macrocycliza-
tion4−6 proceeds subsequently. In the presence of a Rh-catalyst,
carbenes formed from relatively stable diazo compounds, such
as 2-diazo-1,3-dicarbonyl compounds 1, react with cyclic ethers
followed by preferential macrocyclization via oxonium ylide 2
to give the large cyclic ethers 3 and 4 with more than two
molecules incorporated (Scheme 1, Paths a and b).5,6 Although
there are few reports on the formation of medium-sized ring
products 5 via the intramolecular cyclization of ylide 2 (Path
c),5a recently, Rh-catalyzed cyclization of 2-diazo-1,3-dicarbonyl
Previously, we developed an efficient synthetic method for
the preparation of 1,2-diazonaphthoquinones via diazo-transfer
with 2-azido-1,3-dimethylimidazolinium salts7 and have been
investigating the metal-catalyzed synthesis of substituted-
naphthol derivatives using these products.8 Pd(OAc)2 is
found to be an efficient catalyst for several coupling reactions
of 1,2-diazonaphthoquinones.8a,b During the evaluation of the
stability of 2-diazonaphthoquinone 6a9 in the presence of a
catalytic amount of Pd(OAc)2 in various solvents (CH2Cl2,
toluene, benzene, CH3CN, and THF) at reflux, the unexpected
formation of 8-membered cyclic ether 7a and 13-membered
cyclic ether 8a was observed in THF. We were intrigued by this
uncommon formation of medium-sized rings and anticipated
that this transformation could be a new method for the
synthesis of protected 1,2-naphthalenediols. Similar to catechol
derivatives, 1,2-naphthalenediols are attractive candidates as
aromatic functional materials (or their building blocks), such as
for use in solar cells, metal ligands, and antioxidants.10
However, to date, only a few synthetically useful processes
have been reported for the synthesis of 1,2-naphthalenediols.11
Therefore, the generality and efficiency of this Pd(OAc)2-
catalyzed cyclization of 1,2-diazonaphthoquinones with THF
were explored. In addition, the Pd(II) catalyst was efficient for
the macrocyclization of 1,2-diazonaphthoquinones and oxetane.
Initially, the reaction of 2-diazonaphthoquinone 6a and THF
was examined under several reaction conditions (Table 1).
First, several palladium catalysts were examined (Table 1,
entries 1−8). When 10 mol % Pd(OAc)2 was used, 6a was
consumed within 10 min, and cyclic ethers 7a and 8a were
Scheme 1. Rh-Catalyzed Formation of Macro Cyclic Ethers
via the Reaction of 2-Diazo-1,3-dicarbonyl Compounds 1
and Small Cyclic Ethers
Received: December 6, 2013
Published: March 3, 2014
© 2014 American Chemical Society
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Letter
the cyclization products were decreased slightly (Table 1, entry
5). The addition of a halide anion has been reported to be
effective in some Pd-catalyzed reactions.12 Although 6a was
consumed with 2.5 mol % Pd(OAc)2 in the presence of an
equimolar amount of LiCl, cyclic ethers 7a and 8a were not
obtained (Table 1, entry 6). Use of PdCl2 and Pd(OCOCF3)2
resulted in low yields of both products (Table 1, entries 7 and
8).
Table 1. Metal-Catalyzed Macrocyclization of 2-
Diazonaphthoquinone 6a with THF
a
Interestingly, while only the Rh catalysts were reported to be
effective for the metal-catalyzed macrocyclization reaction of
cyclic ethers and α-carbonylcarbenes,5,6 they were not efficient
for the cyclization of 6a and THF (Table 1, entries 9−11).
The series of Cu reagents examined for the reaction,
including Cu(OAc)2, CuCl2, Cu(OTf)2, and Cu(OTf)·C6H6,
also did not provide the cyclized products 7a and 8a (Table 1,
entries 12−15), although a minor amount of C−H insertion
product 9 was formed in the reactions with Cu(OTf)2 and
Cu(OTf)·C6H5 (Table 1, entries 14 and 15, respectively).
On the basis of these results, the optimum cyclization
conditions were determined to be Pd(OAc)2 (2.5 mol %) in
THF at reflux.
Next, the scope and limitations of the Pd(OAc)2-catalyzed
cyclization of 1,2-diazonaphthoquinones and THF were
examined (Table 2). The substrate 2-diazonaphthoquinone
6b bearing an electron-withdrawing group at the C-4 position
gave cyclization products 7b and 8b in 16% and 21% yields,
respectively (Table 2, entry 1). On the other hand, 4-methoxy-
2-diazonaphthoquinone 6c was completely consumed within 20
min, but the expected cyclization products were not generated,
and dimerization product 11 was obtained in 10% yield (Table
2, entry 2). Introduction of a C-3 substituent was, however,
efficient for the selective formation of 8-membered ring cyclic
ethers 7, as shown in Table 2, entries 3 and 4. The reactions of
1-diazonaphthoquinones 109 also proceeded smoothly and
selectively to give 8-membered cyclic ethers 7 in good to high
yields (Table 2, entries 5−9). Simple 1-diazonaphthoquinone
10a gave 7a in 45% yield, accompanied by 2% of the 13-
membered cyclic ether 8a (Table 2, entry 5). The reaction of 6-
bromo-1-diazonaphthoquinone 10b gave 8-membered ether 7f
entry
metal cat.
time
7a (%)
8a (%)
1
2
3
4
Pd(OAc)2 (10 mol %)
Pd(OAc)2 (5 mol %)
Pd(OAc)2 (2.5 mol %)
Pd(OAc)2 (1 mol %)
Pd(OAc)2 (2.5 mol %)
Pd(OAc)2 (2.5 mol %)
PdCl2 (2.5 mol %)
10 min
40 min
1.5 h
6.5 h
3.5 h
2.5 h
2.5 h
1 h
29
27
33
13
21
0
26
28
36
9
b
5
c
31
0
6
7
20
21
21
25
trace
13
5
8
Pd(OCOCF3)2 (2.5 mol %)
Rh2(OAc)4 (1 mol %)
Rh2(OCOCF3)4 (1 mol %)
d
9
3 h
trace
e
10
11
12
13
14
15
2.5 h
2 h
4
f
g
Rh2(Oct)4 (1 mol %)
11
h
Cu(OAc)2 (2.5 mol %)
CuCl2 (2.5 mol %)
3 h
0
0
i
2.5 h
3 h
0
0
j
Cu(OTf)2 (2.5 mol %)
Cu(OTf)·C6H6 (2.5 mol %)
0
0
k
2.5 h
0
0
b
a
Reaction conditions: 6a (0.5 mmol) in THF (2 mL) at reflux. The
reaction was performed at 45 °C. LiCl (1.0 equiv) was added. 6a was
recovered in 28% yield. 6a was recovered in 19% yield.
Rh2(OCOC7H15)4. 6a was recovered in 39% yield. 6a was
recovered in 92% yield. 6a was recovered in 80% yield. 9 was
obtained in 9% yield. 6a was recovered in 32% yield. 9 was obtained
in 3% yield. 6a was recovered in 25% yield.
c
d
e
f
g
h
i
j
k
obtained in 29% and 26% yields, respectively. As shown in
Table 1, entries 1−4, the amount of Pd(OAc)2 could be
reduced to 2.5 mol % (Table 1, entry 3). At 45 °C, the yields of
a
Table 2. Pd(OAc)2-Catalyzed Macrocyclization of 1,2-Diazonaphthoquinones 6 and 10 with THF
entry
R1
R2
Cl
R3
6 or 10
time
1 h
7
(%)
16
8
(%)
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
Br
H
H
H
6b
7b
7c
7d
7e
7a
7f
8b
8c
8d
8e
8a
8f
21
0
b
OMe
H
6c
20 min
2 h
0
CH2OTBS
CO2Me
H
6d
60
55
45
53
78
84
35
0
H
6e
1 h
5
H
10a
10b
10c
10d
10e
1.5 h
1.5 h
2 h
2
H
H
0
CH2OTBS
CO2Me
CO2Ph
H
7d
7e
7g
8d
8e
8g
0
H
20 min
1.5 h
0
H
0
a
b
Reaction conditions: 6 or 10 (0.5 mmol), Pd(OAc)2 (2.5 mol %) in THF (2 mL) at reflux. 11 was obtained in 10% yield.
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Letter
as the sole product in 53% yield (Table 2, entry 6). With these
substrates, introduction of an appropriate substituent at the C-3
position also clearly improved the yield of cyclic ether 7 (Table
2, entries 7 and 8). In the reaction of 3-siloxymethyl-1-
diazonaphthoquinone 10c, cyclic ether 7d was formed in 78%
yield (Table 2, entry 7), and the reaction of 3-methoxy-
carbonyl-1-diazonaphthoquinone 10d gave 8-membered cyclic
ether 7e in 84% yield (Table 2, entry 8). However, the
corresponding of phenyl ester 10e afforded cyclic ether 7g in a
lower yield (35%) (Table 2, entry 9).
Scheme 2. Pd(OAc)2-Catalyzed Cyclization of 1,2-
Diazonaphthoquinones 6a and 10a with THP
We also examined the Pd(OAc)2-catalyzed reaction of 1,2-
diazonaphthoquinones and oxetane (Table 3). In the reaction
Table 3. Pd(OAc)2-Catalyzed Macrocyclization of 1,2-
Diazonaphthoquinones 6a and 10a with Oxetane
a
Scheme 3. Possible Reaction Mechanism
entry
1
6a or 10a
time
12 (%)
13 (%)
6a
3 h
66
0
0
5
b
c
2
6a
3.5 h
20 h
0
d
3
10a
26
a
Reaction conditions: 6a or 10a (0.5 mmol), Pd(OAc)2 (2.5 mol %)
b
in oxetane (2 mL) at reflux. Rh2(OAc)4 (1 mol %) was used instead
of Pd(OAc)2. 6a was recovered in 84% yield. 10a was recovered in
c
d
34% yield.
cyclization (Path B). The C-3 substituted substance R1 can
more easily attain the required conformation of III for 8-exo-
cyclization as compared to the C-3 unsubstituted substance.
For the reaction of 1-diazonaphthoquinone 10 and THF, the
hydrogen at the C-8 position in 10 is assumed to function
similarly to C-3 substituent R1 in 2-diazonaphthoquinone 6,
resulting in the selective formation of exo-cyclization product 7.
Compared to the reaction with THF, the reaction with THP
gave lower yields of cyclic ethers, and different selectivity in the
formation of cyclic ethers (medium-sized cyclic ether/macro
cyclic ether) was observed, which would be attributed to the
cyclization mode, that is 8-exo-tet/10-endo-tet cyclization for
THF vs 9-exo-tet/11-endo-tet cyclization for THP.
In conclusion, we developed a new method for the synthesis
of medium-sized/macrocyclic ethers via the reaction of
diazonaphthoquinones in the presence of a catalytic amount
of Pd(OAc)2. This transformation also serves as an efficient
method for the preparation of protected 1,2-naphthalenediols.
Further studies on the Pd(OAc)2-catalyzed cyclization
reaction of diazonaphthoquinones with heterocyclic com-
pounds are in progress.
of 2-diazonaphthoquinone 6a, 15-membered cyclic ether 12
was formed in 66% yield after stirring for 3 h at reflux.13
A
similar Rh2(OAc)4-catalyzed reaction has been reported for 2-
diazo-1,3-dicarbonyl compounds.6b However, Rh2(OAc)4 was
ineffective for the cyclization of diazonaphthoquinone 6a, as
shown in Table 3, entry 2. In addition, the reaction of 1-
diazonaphthoquinone 10a was slower than that of 2-diazo-
naphthoquinone 6a, and 15-membered product 12 was formed
in just 26% yield along with acyclic ether 13 (5%) after stirring
for 20 h (Table 3, entry 3).
In addition, the 1,2-diazonaphthoquinones also reacted with
tetrahydropyrane (THP) in the presence of a catalytic amount
of Pd(OAc)2 to afford a mixture of 9-membered cyclic ether 14
and 15-membered ether 15 (Scheme 2).
In Scheme 3, a possible reaction mechanism is depicted for
the Pd(OAc)2-catalyzed formation of medium-sized cyclic
ethers (7, 14) and macrocyclic ethers (8, 15) from 2-
diazonaphthoquinone 6 in cyclic ether (THF, THP). First,
Pd(OAc)2 reacts with diazonaphthoquinone 6 to form Pd(II)
carbene complex I.14 In the case of the reaction in THF,
nucleophilic attack of THF on carbene complex I proceeds to
form oxonium ylide II,15 which may be aromatic palladium
naphtholate II′. Successively, II reacts with THF giving III.
Since 5 endo-tet cyclization is highly disfavered commonly,16 8-
membered cyclic ether 7 is not formed directly from II, but is
formed by 8-exo-tet cyclization of III (Path A). Macrocyclic
ether 8 is formed from the same intermediate III by 10-endo-tet
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and characterization data, including
1H and 13C NMR spectra for new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
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Letter
Duan, X.-H.; Zhou, P.-X.; Ali, S.; Luo, J.-Y.; Liang, Y.-M. Angew. Chem.,
Int. Ed. 2012, 51, 1370. (p) Xiao, Q.; Wang, B.; Tian, L.; Yang, Y.; Ma,
J.; Zhang, Y.; Chen, S.; Wang, J. Angew. Chem., Int. Ed. 2013, 52, 9305.
(q) Yang, K.; Zhang, J.; Cheng, B.; Zhao, L.; Zhai, H. Org. Lett. 2013,
15, 808. (r) Khanna, A.; Premachandra, I. D. U. A.; Sung, P. D.; Van
Vranken, D. L. Org. Lett. 2013, 15, 3158. (s) Khanna, A.;
Premachandra, I. D. U. A.; Sung, P. D.; Van Vranken, D. L. Org.
Lett. 2013, 15, 3694.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: kita@che.kyutech.ac.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Support for this work by the Naito Foundation is gratefully
acknowledged.
(15) Padwa, A.; Hornbuckle, S. F. Chem. Rev. 1991, 91, 263.
(16) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734.
■
REFERENCES
■
(1) For reviews, see: (a) Ye, T.; McKervey, M. A. Chem. Rev. 1994,
94, 1091. (b) Doyle, M. P.; Ye, T.; McKervey, M. A. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds; John Wiley &
Sons: New York, 1998. (c) Zhang, Z.; Wang, J. Tetrahedron 2008, 64,
6577.
(2) Nozaki, H.; Takaya, H.; Noyori, R. Tetrahedron 1966, 22, 3393.
(3) (a) Ihara, E.; Saiki, K.; Goto, Y.; Itoh, T.; Inoue, K.
Macromolecules 2010, 43, 4589. (b) Ihara, E.; Hara, Y.; Itoh, T.;
Inoue, K. Macromolecules 2011, 44, 5955.
(4) Kirmse, W.; Lelgemann, R. Chem. Ber. 1991, 124, 1865.
(5) (a) Cenini, S.; Cravotto, G.; Giovenzana, G. B.; Palmisano, G.;
Tollari, S. Tetrahedron 1999, 55, 6577. (b) Ballesteros-Garrido, R.; Rix,
D.; Besnard, C.; Lacour, J. Chem.Eur. J. 2012, 18, 6626.
(6) (a) Zeghida, W.; Besnard, C.; Lacour, J. Angew. Chem., Int. Ed.
2010, 49, 7253. (b) Rix, D.; Ballesteros-Garrido, R.; Zeghida, W.;
Besnard, C.; Lacour, J. Angew. Chem., Int. Ed. 2011, 50, 7308.
(7) Kitamura, M.; Tashiro, N.; Sakata, R.; Okauchi, T. Synlett 2010,
2503.
(8) (a) Kitamura, M.; Sakata, R.; Okauchi, T. Tetrahedron Lett. 2011,
52, 1931. (b) Kitamura, M.; Kisanuki, M.; Sakata, R.; Okauchi, T.
Chem. Lett. 2011, 40, 1129. (c) Kitamura, M.; Kisanuki, M.; Okauchi,
T. Eur. J. Org. Chem. 2012, 905. (d) Kitamura, M.; Araki, K.;
Matsuzaki, H.; Okauchi, T. Eur. J. Org. Chem. 2013, 5045.
(9) In this manuscript, 2-diazonaphthoquinone means 2-diazo-
1(2H)-naphthalenone derivative and 1-diazonaphthoquinone means 1-
diazo-2(1H)-naphthalenone derivative.
(10) (a) Stahl, P.; Kissau, L.; Mazitschek, R.; Huwe, A.; Furet, P.;
Giannis, A.; Waldmann, H. J. Am. Chem. Soc. 2001, 123, 11586. (b) Lu,
T.; Shao, P.; Mathew, I.; Sand, A.; Sun, W. J. Am. Chem. Soc. 2008,
130, 15782. (c) Madan, S.; Cheng, C. J. Org. Chem. 2006, 71, 8312.
(11) (a) Platt, K. L.; Oesch, F. J. Org. Chem. 1983, 48, 265.
(b) Zambrano, J. L.; Dorta, R. Synlett 2003, 1545. (c) Crandall, J. K.;
Zucco, M.; Kirsch, R. S.; Coppert, D. M. Tetrahedron Lett. 1991, 32,
5441.
(12) Fagnou, K.; Lautens, M. Angew. Chem., Int. Ed. 2002, 41, 26.
(13) For a photoinduced similar macrocyclization of the
diazoquinone and oxetane, see ref 4. The maximum yield of the
macrocyclic compound was 16%.
(14) (a) Anciaux, A. J.; Hubert, A. J.; Noels, A. F.; Petiniot, N.;
Teyssie, P. J. Org. Chem. 1980, 45, 695. (b) Denmark, S. E.; Stavenger,
R. A.; Faucher, A.-M.; Edwards, J. P. J. Org. Chem. 1997, 62, 3375.
(c) Greenman, K. L.; Carter, D. S.; Van Vranken, D. L. Tetrahedron
2001, 57, 5219. (d) Broring, M.; Brandt, C. D.; Stellwag, S. Chem.
̈
Commun. 2003, 2344. (e) Alben
Per
ez-Mateo, A. Chem.Eur. J. 2005, 11, 1565. (f) Greenman, K. L.;
Van Vranken, D. L. Tetrahedron 2005, 61, 6438. (g) Lopez-Alberca, M.
P.; Mancheno, M. J.; Fernandez, I.; Gomez-Gallego, M.; Sierra, M. A.;
Torres, R. Org. Lett. 2007, 9, 1757. (h) Devine, S. K. J.; Van Vranken,
D. L. Org. Lett. 2007, 9, 2047. (i) Barluenga, J.; Moriel, P.; Valdes, C.;
́
iz, A. C.; Espinet, P.; Manrique, R.;
́
́
́
́
̃
́
Aznar, F. Angew. Chem., Int. Ed. 2007, 46, 5587. (j) Chen, S.; Wang, J.
Chem. Commun. 2008, 4198. (k) Peng, C.; Wang, Y.; Wang, J. J. Am.
Chem. Soc. 2008, 130, 1566. (l) Xiao, Q.; Ma, J.; Yang, Y.; Zhang, Y.;
Wang, J. Org. Lett. 2009, 11, 4732. (m) Zhang, Z.; Liu, Y.; Gong, M.;
Zhao, X.; Zhang, Y.; Wang, J. Angew. Chem., Int. Ed. 2010, 49, 1139.
(n) Zhang, Z.; Liu, Y.; Ling, L.; Li, Y.; Dong, Y.; Gong, M.; Zhao, X.;
Zhang, Y.; Wang, J. J. Am. Chem. Soc. 2011, 133, 4330. (o) Chen, Z.-S.;
1557
dx.doi.org/10.1021/ol500222s | Org. Lett. 2014, 16, 1554−1557