Synthesis of spiro compounds through tandem oxidative coupling and a framework rearrangement reaction

Article abstract of DOI:10.1021/ol902571p

(Figure Presented) A highly efficient oxidative coupling of 2-naphthois and a rearrangement tandem reaction to afford unique spiro compounds In the presence of FeCl₃-6H₂O in up to 88% yield have been developed.

Full text of DOI:10.1021/ol902571p

ORGANIC
LETTERS
2010
Vol. 12, No. 2
256-258
Synthesis of Spiro Compounds through
Tandem Oxidative Coupling and a
Framework Rearrangement Reaction
Daisuke Sue,† Takeo Kawabata,† Takahiro Sasamori,† Nobuhiro Tokitoh,† and
Kazunori Tsubaki*,‡
Institute for Chemical Research, Kyoto UniVersity, Uji, Kyoto, 611-0011, Japan, and
Graduate School of Life and EnVironmental Science, Kyoto Prefectural UniVersity,
Sakyo, Kyoto, 606-8522, Japan
tsubaki@kpu.ac.jp
Received November 5, 2009
ABSTRACT
A highly efficient oxidative coupling of 2-naphthols and a rearrangement tandem reaction to afford unique spiro compounds in the presence
of FeCl3·6H2O in up to 88% yield have been developed.
Due to the applicability and utility of binaphthyl skeletons
in asymmetric synthesis and/or supramolecular chemistry,
oxidative coupling reactions of 2-naphthols to 2,2′-binaphthol
derivatives are one of the most well-studied reactions.1
Although numerous coupling conditions have been reported,
Fe(III) compounds, especially FeCl3, are most common in
this type of reaction.2 We report an unprecedented tandem
reaction, which consists of oxidative coupling of 2-naphthols
and a subsequent framework rearrangement promoted by
FeCl3·6H2O, to afford extraordinary spiro compounds.3
† Kyoto University.
Figure 1. Unexpected formation of spiro compound (3) and X-ray
‡ Kyoto Prefectural University.
structure of 3.
(1) For general reviews: (a) Cepanec, I. Synthesis of Biaryls; Elsevier
Science, 2004. (b) Brunel, J. M. Chem. ReV. 2005, 105, 857–897. (c)
Smrcˇina, M.; Pola´kova´, J.; Vyskocˇil, S.; Kocˇovsky´, P. J. Org. Chem. 1993,
58, 4534–4538. (d) Li, X.; Hewgley, J. B.; Mulrooney, C. A.; Yang, J.;
Kozlowski, M. C. J. Org. Chem. 2003, 68, 5500–5511. (e) Matsushita, M.;
Kamata, K.; Yamagushi, K.; Mizuno, N. J. Am. Chem. Soc. 2005, 127,
6632–6640. (f) Hewgley, J. B.; Stahl, S. S.; Kozlowski, M. C. J. Am. Chem.
Soc. 2008, 130, 12232–12233.
During the coupling reaction of 2-naphthol (1) under longstand-
ing FeCl3 (later, we found that it absorbed moisture) in CH2Cl2,
(3) Similar rearrangement products were reported as byproduct under
(a) anodic oxdation: Malkowsky, I. M.; Rommel, C. E.; Wedeking, K.;
Fro¨hlich, R.; Bergander, K.; Nieger, M.; Quaiser, C.; Griesbach, U.; Pu¨tter,
H.; Waldvogel, S. R. Eur. J. Org. Chem. 2006, 241–245. (b) Cu(II)
autoxidation: Ling, K.-Q.; Lee, Y.; Macikenas, D.; Protasiewicz, J. D.; Sayre,
L. M. J. Org. Chem. 2003, 68, 1358–1366.
(2) (a) Bolm, C.; Legros, J.; Paih, J. L.; Zani, L. Chem. ReV. 2004, 104,
6217–6254. (b) Toda, F.; Tanaka, K.; Iwata, S. J. Org. Chem. 1989, 54,
3007–3009. (c) Ding, K.; Wang, Y.; Zhang, L.; Wu, Y.; Matsuura, T.
Tetrahedron 1996, 52, 1005–1010. (d) Wang, K.; Lu¨, M.; Yu, A.; Zhu, X.;
Wang, Q. J. Org. Chem. 2009, 74, 935–938.
10.1021/ol902571p  2010 American Chemical Society
Published on Web 12/10/2009

an unknown byproduct as well as binaphthol (2), the major product,
were generated. The byproduct had (i) a mass of 284 amu by mass
spectrometry, which is two mass units less than normal product 2,
(ii) a sharp absorption at 1805 cm-1 in the IR spectrum, (iii) a
signal at 175 ppm in 13C NMR, and (iv) an unsymmetric structure
in 1H NMR. Despite this information, we were initially unable to
determine the structure of this byproduct. Herein we report the
structure of byproduct (3) using X-ray analysis (Figure 1). The
structure contains a spiro skeleton derived from the degradation
of one naphthalene ring. Due to the importance of spiro skeletons
in synthetic chemistry as well as understanding of the reaction
mechanism, we delved into the reaction.
With the optimal reaction conditions in hand, we then studied
the generality of substrates for the tandem reaction using various
2-naphthols (Table 2). First, we studied a series of substituents
Table 2. Synthesis of Spiro Compounds though 2-Naphtholsa
Initially, we examined a variety of oxidants under reflux for 5 h
using 2-naphthol (1) and the oxidant (5 equiv) (Table SI-1,
Supporting Information). The reaction proceeded smoothly only
when FeCl3·6H2O was used as an oxidant to afford desired
compound 3 in 77% isolated yield. In contrast, other oxidants
especially such as anhydrous FeCl3 and Fe(NO3)3·9H2O, which
contained water molecules, gave a messy product mixture, and 3
could not be isolated. Spiro 3 was obtained in 32% yield using a
combination of anhydrous FeCl3 and additional water (6 equiv).
Table 1. Solvent Effects on the Tandem Reaction of 2-Naphthol
(1)a
isolated yield (%)
entry
solvent
temp (°C)
1
2
3
1
2
3
4
5
6
7
8
9
DMF
THF
dioxane
DME
CH3CN
toluene
CHCl3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
60
reflux
60
60
60
60
reflux
rt
reflux
reflux
reflux
97
42
65
50
12
-
-
92
-
-
45
27
39
63
71
-
8
-
-
-
-
-
-
-
-
15
37
-
77
84
64
a Reaction conditions: 2-naphthols 4-11 (0.3 mmol) and FeCl3·6H2O
(1.2 mmol) in CH2Cl2 (3.0 mL) under reflux conditions for 2-24 h. (b)
Binaphthol 19 was isolated in 83% yield (see Table 3, entry 2).
on the 3-position of 2-naphthols (entries 1-3). The electron-
donating methyl group and weak electron-withdrawing phenyl
group on the 3-position gave corresponding spiro compounds
12 and 13 in 72% and 86% yields, respectively (entries 1 and
2), whereas 2-naphthol possessing a strong electron-withdrawing
methoxycarbonyl group was converted into corresponding
binaphthol 19 in 83% yield. This data indicate that the second
rearrangement step is suppressed in the presence of an electron-
withdrawing group on the 3-position of 2-naphthol. In contrast,
for compound 5, the second rearrangement step proceeded faster
than the first oxidative coupling step because the corresponding
binaphthol could not be detected by a TLC reaction tracking.
Regarding the tolerance for functional groups on the 6- or
7-position of the 2-naphthol, the corresponding tandem reactions
proceeded smoothly from electron-donating groups4 (entries 4,
6, and 7) to weak electron-withdrawing group such as bromine
(entry 5). Furthermore, not only the naphthalene ring but also
the phenanthrene ring is applicable for the tandem reaction in
good yield (88%, entry 8).
10b
11c
-
-
a Reaction conditions: 1 (40 mg), FeCl3·6H2O (5 equiv), in proper solvent
(2 mL) for 5 h. b FeCl3·6H2O (4 equiv) was used. c FeCl3·6H2O (3 equiv)
was used, and the reaction time was 12 h.
Next, we investigated the effect of solvent (Table 1). Large
solvent effects were observed. Starting 2-naphthol (1) was recov-
ered in DMF (entry 1), whereas the reactions were terminated at
the oxidative coupling stage to give 2,2′-binaphthol (2) in 27-63%
under ethereal solvents or acetonitrile (entries 2-5). In the case of
toluene, desired spiro compound 3 was obtained as the minor
product (15%) with binaphthol (71%) as the major product. In
chlorinated solvents, spiro compound 3 was predominantly gener-
ated over binaphthol 2. In particular, in dichloromethane under
reflux conditions, 3 was obtained in 77% yield (entry 9), whereas
at ambient temperature, the desired product was not obtained and
binaphthol 2 was formed in 8% yield (entry 8). Using a reduced
oxidant, a bell-shaped relationship between the yield of 3 and the
equivalent of FeCl3·6H2O was observed (entries 9-11), and finally
the optimal reaction conditions were achieved by FeCl3·6H2O (4
equiv) at reflux conditions in dichloromethane (entry 10).
Next we investigated the mechanistic aspects of the rear-
rangement step promoted by FeCl3·6H2O (Table 3). From entries
(4) Although Hammett sigma value of OAc group (σ ) 0.31) indicates
that OAc is an electron-withdrawing group. In this reaction, OBz group
acted as an electron-donating group, probably by its large resonance
effect.
Org. Lett., Vol. 12, No. 2, 2010
257

1-4, we chose C2-symmetrical binaphthols as the starting
materials. As expected (Table 2, entry 3), binaphthols with
strong electron-withdrawing groups on their naphthalene rings,
especially 19 and 20, were inert under the rearrangement
conditions. Compounds 2 (R ) H) and 21 (R ) Br) were
readily transformed into corresponding spiro compounds 3 and
22 in 87% and 69% yields, respectively. From entries 5-8, a
variety of binaphthols 23-26 with different substituents on their
3,3′-positions were examined. Binaphthol with one formyl group
23 greatly suppressed rearrangement (entry 5). In the case of
compound 24, two spiro compounds 27a and 27b were isolated,
where 27a, which was derived from degradation of the
nonsubstituted naphthalene ring, prevailed over 27b, which was
attributed to migration of the Br-substituted naphthalene ring
(27a/27b ) 67/33). Binaphthols 25 and 26 were transformed
into spiro compounds through rearrangement of the substituted
naphthalene rings as major products (28a/28b ) 24/76, 29a/
29b ) 19/81, respectively, entries 7 and 8).
Scheme 1
.
Proposed Mechanism for the Rearrangement of
2,2′-Binaphthol Derivatives
second one-electron oxidation, and a subsequent pinacol-type
rearrangement generates the corresponding spiro compounds.3
Because electron-withdrawing groups prevent radical formation,
the rate-determining step should be generation of intermediate A.
Table 3. Synthesis of Spiro Compounds though
2,2′-Binaphtholsa
Figure 2. Biaryl and spiro compounds in natural products.
In conclusion, we have developed a highly efficient oxidative
coupling of 2-naphthols and a rearrangement tandem reaction
to afford unique spiro compounds in the presence of
FeCl3·6H2O. Because the starting materials are readily available
and FeCl3·6H2O is inexpensive, this tandem reaction should be
highly valuable in synthetic chemistry. It is especially worth-
while to note that this rearrangement reaction is associated with
two types of natural products, biaryl compounds such as
blestriarene C5 and spiro compounds like dendrochrysanene,6
which are isolated from distinct origins (Figure 2). Hence, we
are currently investigating the synthesis of dendochrysanene
using this rearrangement as a key step.
Acknowledgment. This work was partly supported by
Sekisui Chemical Co. Ltd.
Supporting Information Available: Full experimental
details, characterization of all new compounds, and CIF of
compound 3. This material is available free of charge via
the Internet at http://pubs.acs.org.
a Reaction conditions: 2-naphthols 2, 19-21, 23-26 (0.3 mmol), and
FeCl3·6H2O (1.5 mmol) in CH2Cl2 (3.0 mL) under reflux conditions for
5 h. b Isolated yield. c No reaction. d Because 28a and 28b could not be
isolated by recycling HPLC, it is a combined yield of 28a and 28b.
OL902571P
e
1
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Calculated by integrating the corresponding signals in the H NMR.
Scheme 1 shows a plausible mechanism for the rearrange-
ment step. Dibenzylradical intermediate A is generated through
one-electron oxidations by FeCl3·6H2O. The hydroxy oxygen
on the upper naphthalene reacts with the carbonyl group on
the lower naphthalene of A. Intermediate B is afforded by
(6) (a) Yamaki, M.; Bai, L.; Kato, T.; Inoue, K.; Takagi, S.; Yamagata,
Y.; Tomita, K. Phytochemistry 1993, 33, 1497–1498. (b) Yang, L.; Qin,
L.-H.; Bligh, S. W. A.; Bashall, A.; Zhang, C.-F.; Zhang, M.; Wang, Z.-T.;
Xu, L.-S. Bioorg. Med. Chem. 2006, 14, 3496–3501.
258
Org. Lett., Vol. 12, No. 2, 2010