Tandem ring expansion of alkenyl benzocyclobutenol derivatives into substituted naphthols

Article abstract of DOI:10.1002/anie.200602428

(Chemical Equation Presented) Twice expanded: Substituted naphthols were prepared in a novel synthetic route starting from alkenyl benzocyclobutenol derivatives. The conversion includes two successive ring-enlargement processes (A→B→C; see scheme). The ha

Full text of DOI:10.1002/anie.200602428

Communications
Table 1: 4!5 Ring enlargement triggered by the halogenation of diol
derivative 1.
Polyaromatic Compounds
DOI: 10.1002/anie.200602428
Tandem Ring Expansion of Alkenyl
Benzocyclobutenol Derivatives into Substituted
Naphthols**
Entry
Conditions
Yield [%]
90
cis/trans
Toshiyuki Hamura, Takeaki Suzuki,
Takashi Matsumoto, and Keisuke Suzuki*
1
2
ICl, THF, 08C!RT
1.6:1
NBS, CH2Cl2, ꢀ78!ꢀ108Cquant.
3.2:1
Ac=acetyl, NBS=N-bromosuccinimide.
In our continuing studies on the synthesis of polyaromatic
compounds,[1] we previously reported thermal conversion of
alkenyl benzocyclobutene A into functionalized naphthol C
by tandem electrocyclic reactions [Eq. (1)].[2] We report
acetoxy groups. Similarly, bromination of 1 was also effective
(1.5 equivalents NBS, CH2Cl2, ꢀ78!ꢀ108C) and gave bro-
momethyl indanone 2b in quantitative yield (Table 1,
entry 2).
The second step, 5!6 ring enlargement, is the intra-
molecular Barbier-type reaction of halomethyl indanone and
subsequent Grob fragmentation[5] of the resulting cyclopro-
panol intermediate (Table 2).[6]
Table 2: 5!6 Ring enlargement by an intramolecular Barbier-type
reaction and subsequent Grob fragmentation of halomethyl indanone 2.
Entry Conditions
t [h] Yield of 3 [%] Yield of 4 [%]
herein a process that is capable of converting the same
starting material A into isomeric naphthol E [Eq. (2)]. The
process involves two successive ring enlargements (A!D!
E): the halonium ion (X+) induces ring expansion of alkenyl
benzocyclobutene A (four-membered ring) to indanone D
(five-membered ring), and SmI2 promotes expansion of D to
naphthol E (six-membered ring) with concomitant elimina-
tion of ROSmI2.
1
2
3
THF/HMPA[a]
THF/HMPA,[a] BF3·Et2O[b] 2.5
3CN[cH]
8
15[d]
–
–
78
82
79
C
4
[a] 11–14% HMPA. [b] 2.0–2.5 equivalents. [c] SmI2 in CH3CN. [d] Cyclo-
propanol 3 has the trans configuration with respect to the hydroxy and
acetoxy groups on the five-membered ring. HMPA=hexamethyl phos-
phoramide.
This tandem 4!5!6 ring-enlargement process starts with
the 4!5 ring enlargement triggered by the halogenation of
diol derivative 1 (Table 1).[3] When alcohol 1 was treated with
ICl (1.5 equivalents) in THF (08C!RT), the ring enlarge-
ment occurred smoothly to give iodomethyl indanone 2a in
90% yield as a mixture of stereoisomers (Table 1, entry 1).[4]
An NOE study showed that the major product of 2a has the
cis configuration with respect to the iodomethyl and the
Indanone 2a-cis was used for the initial model study,
which revealed several sets of suitable conditions. Upon
treatment of 2a-cis with SmI2 (0.1m in THF) in THF/HMPA,
the starting material was quickly consumed, thereby giving
naphthol 4 in 78% yield and a sizable amount of cyclo-
propanol 3 (Table 2, entry 1).[7] Monitoring of the reaction by
TLC showed the initial formation of cyclopropanol 3, which
was gradually consumed to give naphthol 4. The process is
ꢀ
rationalized by selective cleavage of the C1 C2 bond and
[*] Dr. T. Hamura, T. Suzuki, Dr. T. Matsumoto, Prof. Dr. K. Suzuki
Department of Chemistry
elimination of samarium acetate. Although prolonged reac-
tion time and/or higher reaction temperature was incapable of
driving the in situ conversion of cyclopropanol 3 to the final
product 4, we were pleased to find that the conversion was
facilitated by the presence of BF3·Et2O (Table 2, entry 2) or
by the use of CH3CN as the solvent (Table 2, entry 3), thus
giving naphthol 4 in high yield.[8,9]
Tokyo Institute of Technology, and SORST
Japan Science and Technology Agency (JST)
2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551 (Japan)
Fax: (+81)3-5734-2788
E-mail: ksuzuki@chem.titech.ac.jp
[**] This research was partially supported by the 21st Century COE
program and Grant-in-Aid for Young Scientists (B). T.S. is grateful to
JSPS for a predoctoral fellowship.
With these results in hand, we attempted to carry out the
two consecutive reactions in one pot, which proved to be
successful. Thus, alcohol 1 was treated with ICl (1.4 equiv-
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
6294
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Chemie
alents) in THF at 08C, and the reaction was stirred for
40 minutes at room temperature. The reaction mixture was
again chilled to 08C, and 3.4 equivalents of SmI2 (0.07m in
CH3CN) was added. Subsequent stirring at room temperature
for four hours cleanly gave naphthol 4 as the sole product in
97% yield [Eq. (3)]. The almost quantitative yield in this
indanone 15, which was smoothly converted into the corre-
sponding ketone 16 by the Barbier reaction. ICl was
ineffective in this case and gave only a complex mixture of
products, presumably because of the instability of the
intermediary tertiary alkyl iodide.
The process is applicable to the synthesis of natural-
product-like structures, such as angucycline-type tetracycle 18
(Scheme 1).[13] After treatment of compound 17,[11] which has
particular instance implies that both isomers of the initially
formed indanones 2a-cis and 2a-trans took part in the second
5!6 ring enlargement. Importantly, this one-pot procedure
gave a higher yield of 4 than the overall yield by the reactions
that were performed separately.
Table 3 shows the application of this one-pot protocol to
various substrates. Under the same conditions, the reaction of
compound 5, isomeric to 1, also proceeded smoothly (Table 3,
Table 3: One-pot preparation of substituted naphthols.
Entry
Benzocyclobutene[a]
Product
Yield [%]
85
1
5
10
2
3
6
7
11
12
96
88
Scheme 1. Divergent sSynthesis of isomeric tetracyles 18 and 20.
Lower left: molecular structure of 21; thermal ellipsoids set at 50%
probability (O red, I green). PPTS=pyridinium p-toluenesulfonate;
imid.=imidazole.
4
5
8
9
12
13
77
78
a dihydronaphthalene substituent, with ICl (THF, 08C!RT,
0.5 hours), the reaction was warmed to 408C, and HMPA and
subsequently SmI2 (0.1m in THF, 10 minutes) were added to
afford the angular tetracycle 18[11] in 75% yield. It should be
noted that this one-pot reaction proceeded smoothly even
though the intermediates that are involved should have highly
strained polycyclic structures.
[a] Conditions: ICl, THF, 08C!RT (20–40 minutes), then SmI2 in
CH3CN, 08C!RT (1.5–4 hours).
entry 1). Likewise, the reaction of a-styryl alcohol 6 gave
naphthol 11 in 96% yield (Table 3, entry 2). The reactions
worked well with substrates 7 and 8, which have one
additional methyl group at the b position of the olefin with
E or Z geometry, and afforded the tetrasubstituted naphtha-
lene 12 in high yields (Table 3, entries 3 and 4).[10] Arylated
substrate 9[11] also underwent smooth ring expansion to give
78% yield of aryl naphthalene 13 (entry 5).
Furthermore, the process of successive ring enlargement
proved to be applicable to substrates with more highly
substituted olefinic moieties [Eq. (4)]. Treatment of 14 with
NBS in the presence of silica gel[12] gave the bromoisopropyl
It is thus interesting to note the X-ray structure of
spiroketone 21[14] (the major isomer), which was obtained by
interception of the above process at the initial iodination
stage (92% yield, major/minor 2.4:1). The structure is
intriguing in relation to the synthesis of polycyclic natural
products containing a spiro center.[15] The stereoselectivity of
the iodination was enhanced to 5.6:1 by employing
ꢀ
BnMe3N+ICl2 as the iodinating agent.
This process constitutes one of the two complementary
processes that allow divergent syntheses of isomeric polyar-
omatic compounds from a single starting material. Indeed, the
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Communications
isomeric angular tetracycle 20[11] was accessible from the same
alcohol 17 in high yield by silylation, thermolysis, and
desilylation of the initially formed ring-expanded product
[see Eq. (1)].
In summary, we have described a facile synthesis of
substituted polyaromatic compounds by successive ring
expansion of alkenyl benzocyclobutenes. Further studies are
currently in progress.
d) G. A. Molander, Y. L. HuØrou, G. A. Brown, J. Org. Chem.
2001, 66, 4511 – 4516; e) P. Dowd, W. Zhang, Chem. Rev. 1993,
93, 2091 – 2115; related 5!6 ring enlargement of methanoin-
dane to aryl naphthalene was also reported: f) K. Wakasugi, Y.
Nishii, Y. Tanabe, Tetrahedron Lett. 2000, 41, 5937 – 5942; g) I.
Takemura, T. Matsumoto, K. Suzuki, Tetrahedron Lett. 2006, 47,
6677 – 6679.
[7] When the reaction was performed without HMPA, the yield of 4
decreased to 46% and was accompanied by cyclopropanol 3
(16%).
[8] This 5!6 ring enlargement was applicable to the bromo
substrate 2b (SmI2 in THF/HMPA, BF3·Et2O), giving naphtha-
lene 4 in 48% yield.
Experimental Section
General experimental procedures for the synthesis of naphthols (one-
pot procedure): A solution of acetate 1 (121 mg, 0.489 mmol) in THF
(2.0 mL) was added to a solution of ICl (114 mg, 0.702 mmol) in THF
(1.5 mL) at 08C. The reaction was stirred for 40 min at room
temperature. SmI2 (0.07m in CH3CN, 24 mL, 1.7 mmol) was added to
the reaction mixture at 08C, and the temperature raised to room
temperature. After 4 h, the reaction was quenched with saturated
aqueous NH4Cl. The products were extracted with EtOAc (3 ”
10 mL), and the combined organic extracts were washed with brine,
dried over Na2SO4, and concentrated in vacuo. The residue was
purified by silica gel flash column chromatography (hexane/EtOAc =
9:1) to give naphthol 4 (89.3 mg, 97.0%).
[9] Concentration of SmI2 in CH3CN was 0.07m (iodometric
titration); recently, solvent effects of SmI2-mediated reactions
were reported: a) B. Hamann, J.-L. Namy, H. B. Kagan, Tetra-
hedron 1996, 52, 14225 – 14234; b) P. R. Chopade, T. A. Davis,
E. Prasad, R. A. Flowers II, Org. Lett. 2004, 6, 2685 – 2688.
[10] Previously, we reported the thermolysis of alkenyl benzocyclo-
butenes that have alkyl groups at the b position of the olefin with
Z geometry, whereby mainly a 1,7-hydrogen shift occurred to
give the ring-opened 1,3-diene derivatives as the major products;
see references [2c] and [2d].
[11] For details, see the Supporting Information.
[12] H. Konishi, K. Aritomi, T. Okano, J. Kiji, Bull. Chem. Soc. Jpn.
1989, 62, 591 – 593.
[13] a) J. Rohr, R. Thiericke, Nat. Prod. Rep. 1992, 9, 103 – 137;
b) M. C. Carreæo, A. Urbano, Synlett, 2005, 1 – 25.
Received: June 16, 2006
Published online: August 28, 2006
[14] CCDC-611287 (21) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Keywords: halogenation · polyaromatic compounds ·
reductive coupling · ring expansion · strained molecules
.
[15] M. Sannigrahi, Tetrahedron 1999, 55, 9007 – 9071.
[1] a) D. Astruc, Modern Arene Chemistry, Wiley-VCH, Weinheim,
2002; b) C. B. de Koning, A. L. Rousseau, W. A. L. van Otterlo,
Tetrahedron 2003, 59, 7 – 36.
[2] a) T. Matsumoto, T. Hamura, M. Miyamoto, K. Suzuki, Tetrahe-
dron Lett. 1998, 39, 4853 – 4856; b) T. Hamura, M. Miyamoto, T.
Matsumoto, K. Suzuki, Org. Lett. 2002, 4, 229 – 232; c) T.
Hamura, M. Miyamoto, K. Imura, T. Matsumoto, K. Suzuki,
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Ishikawa, H. Tsuruta, S. Kuwahara, N. Harada, K. Suzuki,
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Chem. Rev. 2003, 103, 1539 – 1602, and references therein.
[3] Starting compounds were readily available from various benzo-
cyclobutenones; see: a) T. Hosoya, T. Hasegawa, Y. Kuriyama,
T. Matsumoto, K. Suzuki, Synlett 1995, 177 – 179; b) T. Hamura,
T. Hosoya, H. Yamaguchi, Y. Kuriyama, M. Tanabe, M.
Miyamoto, Y. Yasui, T. Matsumoto, K. Suzuki, Helv. Chim.
Acta 2002, 85, 3589 – 3604; see also references [2b], [2c].
[4] For a related iodonium-mediated ring expansion of alkenyl
cyclobutanols, see: a) H. Nemoto, M. Shiraki, K. Fukumoto, J.
Org. Chem. 1996, 61, 1347 – 1353; related acid-catalyzed ring
expansions of alkenyl cyclobutenols and alkenyl benzocyclobu-
tenols were also reported; see: b) G. B. Stone, L. S. Liebeskind,
J. Org. Chem. 1990, 55, 4614 – 4622; c) H. Ziehe, R. Wartchow,
H. Butenschön, Eur. J. Org. Chem. 1999, 823 – 835.
[5] a) C. A. Grob, Angew. Chem. 1969, 81, 543 – 554; Angew. Chem.
Int. Ed. Engl. 1969, 8, 535 – 622; b) C. A. Grob, W. Baumann,
Helv. Chim. Acta 1955, 38, 594 – 603.
[6] For reviews of SmI2-mediated Barbier reactions, see: a) G. A.
Molander, C. R. Harris, Chem. Rev. 1996, 96, 307 – 338; b) A.
Krief, A. M. Laval, Chem. Rev. 1999, 99, 745 – 777; related
reductive cyclization of bromoalkyl ketones and subsequent ring
opening of cycloalkanol derivatives were reported: c) E. Hase-
gawa, H. Tsuchida, M. Tamura, Chem. Lett. 2005, 1688 – 1689;
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