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Skeletal rearrangement of all-carbon spiro skeletons mediated

by a Lewis acidw
Fei Zhao,a Chao Wang,a Lantao Liu,ab Wen-Xiong Zhanga and Zhenfeng Xi*ac
Received (in Cambridge, UK) 20th July 2009, Accepted 21st August 2009
First published as an Advance Article on the web 11th September 2009
DOI: 10.1039/b914619a

Mediated by AlCl3, substituted spiro[4.5]deca-tetraenes under-

went novel and selective skeletal rearrangement to generate
indene derivatives in high to excellent yields.
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Selective carbon–carbon bond1 and carbon–hydrogen bond2

cleavage reactions are of great importance both fundamentally
and practically. Achievements in these areas have been much
more realized in a wide variety of functionalized or highly
active compounds than in those unfunctionalized or thermo-
dynamically stable systems, probably due to the extreme
difficulty to cut C–C or C–H bonds without any mediation
or facilitation by active substituents or special structures. For
example, there are many reports on breaking C–C bonds in
small rings;3,4 reports also appeared on the cleavage of C–C
bonds in cyclopentadienyl ligands in metallocenes5,6 or
aromatic compounds,7 whereas research on the cleavage of
C–C bonds in those all-carbon medium cyclic compounds
has been very rare in the literature,1 although interesting
transformations, surprising mechanisms, or synthetically
useful protocols can be expected from these reactions. As
our continuous interest in cleavage and synthetic applications
of unactivated chemical bonds6,8,9, we would like to report
herein our preliminary results on Lewis acid10 mediated
skeletal rearrange-ment of all-carbon cyclic compounds
spiro[4.5]deca-tetraene 1 or 1 0 yielding indene derivatives 211
via sequential cleavage of both C–C and C–H bonds
(Scheme 1). Notably, different from the strained spiro
compounds,12 in our results the inert sp2–sp3 C–C bond of
the stable cyclopentadiene moiety was cleaved under mild
conditions. To the best of our knowledge, this is the first
example of such skeletal rearrangements.
All-carbon spiro compounds 1 and 1 0 could be readily
prepared in high yields from 1-lithio-4-aryl-1,3-butadienes.13,14
Treatment of 1a with 1 equivalent of AlCl3 in CH2Cl2 resulted
in the formation of an indene derivative 2a15 in 92% isolated
yield (path A, Scheme 2), while a similar procedure using 1a 0
produced the same indene derivative 2a in 71% isolated yield
Scheme 1 Cleavage of C–C and C–H bonds in all-carbon spiro
compounds.
(path B, Scheme 2), implying the reaction of both spiro
compounds 1a and 1a 0 may have similar reaction pathways
leading to the indene derivative mediated by AlCl3. Employing
directly a mixture of 1a and 1a 0 as starting materials under the
above condition again afforded the same indene derivative 2a
as the only product in 80% isolated yield (path C, Scheme 2).z
In situ NMR experiment demonstrated that 2a was formed in
the reaction mixture before quenching and work-up.
Consequently, as listed in Table 1, spiro compounds 1b–1e,
and 1b 0 –1e 0 could be transformed into the corresponding
indene derivatives 2b–2e or 2c 0 in good to excellent isolated
yields following the procedure as described above. It is noticeable
that a mixture of 1b and 1b 0 afforded 2b as the sole product,
whilst a mixture of 1c and 1c 0 gave two isomeric products 2c
and 2c 0 in 73% combined isolated yield. These results are
informative for the skeletal rearrangement mechanisms.
As a fundamental reaction in organic chemistry, the
reaction of Lewis acids such as AlCl3, which have an
electron-deficient nature, with CQC double bond would result
in the formation of reactive carbon cation species.10 Thus, for
the skeletal rearrangement of spiro compounds 1 or 1 0 to
indene derivatives 2, a proposed mechanism including
intermediacy of carbon cation species is exhibited in Scheme 3.
The intermediate 3, formed through the CQC bond in the six-
membered ring of 1 coordinating to AlCl3,16 would trigger an

a
Beijing National Laboratory for Molecular Sciences (BNLMS),
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry, Peking University,
Beijing 100871, China. E-mail: zfxi@pku.edu.cn;
Fax: +86 10 62751708; Tel: +86 10 62759728
b
Institute of Chemistry, Chinese Academy of Sciences, Beijing,
100190, China
c
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai, 200032, China
w Electronic supplementary information (ESI) available: Experimental
details and scanned NMR spectra of all new products. See DOI:
10.1039/b914619a Scheme 2 AlCl3-Mediated formation of indene 2a from 1a and 1a 0 .

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 View Article Online

Table 1 Synthesis of indene derivatives 2 from spiro compounds 1

Entry 1 and 1 0 (ratio of 1:1 0 ) Indene 2

1
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Scheme 3 A proposed mechanism.

Scheme 4 Two reaction pathways of cyclization of 5c.

mechanism, but also provide an alternative route to synthesize

indene derivatives.
4 In summary, we have reported in this paper a facile and
efficient Lewis-acid-mediated skeletal rearrangement of
unstrained spiro[4.5]deca-tetraene to generate indene derivates
via tandem cleavage of allylic C–H and inert C–C bonds.
Further investigation on the mechanism, scope and applications
are in process.
intramolecular proton transfer via ring-openning process and
aromatization of 4, to give the diene 5. In succession, with the
Table 2 Synthesis of indene derivatives 2 from 5
existance of Lewis acid, an intramolecular Friedel–Crafts
reaction of 5 would herein take place and afford 2 as the final
product. Indeed, diene 5 was observed during utilizing in situ
NMR to track the reaction. According to this mechanism, it is
quite reasonable that in the case of 1c and 1c 0 , 2c and 2c 0 were
obtained as a mixture via cyclization of 5c with different
regio-selectivity (Scheme 4). Although this result is helpful
for testifying the possibility of the above mechanism, yet other
reaction pathways still can not be ruled out (see supporting
informationw). Diene 5 Ar Indene 2 (isolated yield)
In order to get further evidence in support of the above 5a Ph 2a (85%)
proposed reaction mechanisms, we began to investigate the 5b 2 0 -Tolyl 2b (60%)
5c 3 0 -Tolyl 2c + 2c 0 (total 78%, 6:4)
reaction between dienes 513a and AlCl3. As shown in Table 2,
treated with AlCl3, dienes 5a–5d could be converted into
2a–2c, 2c 0 or 2f in good to excellent yield. It is worth
emphasizing that the ratio of 2c and 2c 0 acquired from 5c is 5d 4 0 -Tolyl
completely identical with the one from reaction of 1c and 1c 0 ,
which can be explained as the dicussion above (Scheme 4).
Hence, these results not only support the above propounded

6570 | Chem. Commun., 2009, 6569–6571 This journal is 

c The Royal Society of Chemistry 2009

This work was supported by the National Natural Science
Foundation of China and the Major State Basic Research
Development Program (2006CB806105). The Cheung Kong
Scholars Programme, Qiu Shi Science & Technologies
Foundation, Dow Corning Corporation, Eli Lilly China and
BASF are gratefully acknowledged.
Notes and references
z A typical procedure for synthesis of indene derivatives 2 from spiro
compounds 1. To a solution of a mixture of 1 and 1 0 (1 mmol in total) in
dichloromethane (5 mL) was added AlCl3 (133 mg, 1 mmol). The
reaction mixture was stirred at 0 1C for 1 h. After quenching with
water, the mixture was extracted with hexane. The extract was washed
with brine and dried over MgSO4. The solvent was then evaporated
in vacuo and the residue was purified by column chromatography
(silica gel, hexane) to afford the product 2. 2a: Colorless liquid,
Published on 11 September 2009. Downloaded on 27/10/2014 18:22:34.
isolated yield 80% (194 mg); 1H NMR (300 MHz, CDCl3, Me4Si):
d 0.28 (t, J = 7.5 Hz, 3H, CH3), 0.54–0.58 (m, 1H, CH2), 0.68
(t, J = 6.6 Hz, 3H, CH3), 0.72–0.78 (m, 1H, CH2), 1.13 (t, J = 7.5 Hz,
3H, CH3), 1.16 (t, J = 7.5 Hz, 3H, CH3), 1.64–1.88 (m, 4H, CH2), 2.24
(qd, J = 7.5, 1.5 Hz, 2H, CH2), 2.53 (q, J = 7.5 Hz, 2H, CH2),
7.08–7.20 (m, 4H, CH); 13C NMR (75 MHz, CDCl3, Me4Si): d 7.97
(1 CH3), 13.92 (1 CH3), 13.99 (1 CH3), 14.46 (1 CH3), 16.83 (1 CH2),
18.21 (1 CH2), 18.68 (1 CH2), 30.25 (1 CH2), 40.00 (1 CH2), 58.67
(1 quart C), 117.89 (1 CH), 120.92 (1 CH), 123.76 (1 CH), 125.90 (1 CH),
139.56 (1 quart C), 145.89 (1 quart C), 147.28 (1 quart C), 149.63
(1 quart C); HRMS(ESI) calcd for [C18H26]H+: 243.2107; found
243.2102.
1 For recent reviews on C–C bond cleavage, see: (a) M. Rubin,
M. Rubina and V. Gevorgyan, Chem. Rev., 2007, 107, 3117;
(b) Y. J. Park, J.-W. Park and C.-H. Jun, Acc. Chem. Res., 2008,
41, 222; (c) C. Nájera and J. M. Sansano, Angew. Chem., 2009, 121,
2488; C. Nájera and J. M. Sansano, Angew. Chem., Int. Ed., 2009,
48, 2452.
2 For recent reviews on C–H bond cleavage, see: (a) F. Kakiuchi and
N. Chatani, Adv. Synth. Catal., 2003, 345, 1077; (b) K. Godula and
D. Sames, Science, 2006, 312, 67; (c) L. Ackermann, Top.
Organomet. Chem., 2007, 24, 35; (d) K. R. Campos, Chem. Soc.
Rev., 2007, 36, 1069; (e) H. M. L. Davies and J. R. Manning,
Nature, 2008, 451, 417; (f) J. C. Lewis, R. G. Bergman and
J. A. Ellman, Acc. Chem. Res., 2008, 41, 1013; (g) B. Li, S. Yang
and Z. Shi, Synlett, 2008, 7, 949; (h) C.-J. Li, Acc. Chem. Res.,
2009, 42, 335.
3 For recent examples on C–C bond cleavage in three-membered
rings, see: (a) M. Shi, L.-P. Liu and J. Tang, J. Am. Chem. Soc.,
2006, 128, 7430; (b) P. A. Wender, L. O. Haustedt, J. Lim,
J. A. Love, T. J. Williams and J.-Y. Yoon, J. Am. Chem. Soc.,
2006, 128, 6302; (c) V. Bagutski, N. Moszner, F. Zeuner,
U. K. Fischer and A. de Meijere, Adv. Synth. Catal., 2006, 348,
2133; (d) C. Aı̈ssa and A. Fürstner, J. Am. Chem. Soc., 2007, 129,
14836; (e) Z.-X. Yu, P. H.-Y. Cheong, P. Liu, C. Y. Legault,
P. A. Wender and K. N. Houk, J. Am. Chem. Soc., 2008, 130, 2378;
(f) P. Mauleón, J. L. Krinsky and F. D. Toste, J. Am. Chem. Soc.,
2009, 131, 4513; (g) L. Liu and J. Zhang, Angew. Chem., Int. Ed.,
2009, 48, 6093.
This journal is 
c The Royal Society of Chemistry 2009
View Article Online
4 (a) For recent examples on C–C bond cleavage in four-memdered
rings, see: T. Matsuda, M. Shigeno and M. Murakami, J. Am.
Chem. Soc., 2007, 129, 12086; (b) T. Seiser and N. Cramer, Angew.
Chem., Int. Ed., 2008, 47, 9294; (c) C. Winter and N. Krause,
Angew. Chem., Int. Ed., 2009, 48, 2460.
5 (a) A. Tillack, W. Baumann, A. Ohff, C. Lefeber,
A. Spannennberg, R. Kempe and U. Rosenthal, J. Organomet.
Chem., 1996, 520, 187; (b) T. L. Dzwiniel and J. M. Stryker, J. Am.
Chem. Soc., 2004, 126, 9184.
6 (a) Z. Xi, K. Sato, Y. Gao, J. Lu and T. Takahashi, J. Am. Chem.
Soc., 2003, 125, 9568; (b) T. Takahashi, Y. Kuzuba, F. Kong,
K. Nakajima and Z. Xi, J. Am. Chem. Soc., 2005, 127, 17188;
(c) T. Takahashi, Z. Song, K. Sato, Y. Kuzuba, K. Nakajima and
K. Kanno, J. Am. Chem. Soc., 2007, 129, 11678; (d) T. Takahashi,
Z. Song, Y.-F. Hsieh, K. Nakajima and K. Kanno, J. Am. Chem.
Soc., 2008, 130, 15236.
7 (a) A. L. Crombie, Jr., J. L. Kane, K. M. Shea and
R. L. Danheiser, J. Org. Chem., 2004, 69, 8652; (b) P. Panne and
J. M. Fox, J. Am. Chem. Soc., 2007, 129, 22.
8 (a) X. Sun, C. Wang, Z. Li, S. Zhang and Z. Xi, J. Am. Chem. Soc.,
2004, 126, 7172; (b) T. Yu, X. Sun, C. Wang, L. Deng and Z. Xi,
Chem.–Eur. J., 2005, 11, 1895; (c) C. Wang, J. Yuan, G. Li,
Z. Wang, S. Zhang and Z. Xi, J. Am. Chem. Soc., 2006, 128,
4564; (d) C. Wang, L. Deng, J. Yan, H. Wang, Q. Luo, W. Zhang
and Z. Xi, Chem. Commun., 2009, 4414.
9 (a) T. Takahashi, Z. Xi, Y. Obora and N. Suzuki, J. Am. Chem.
Soc., 1995, 117, 2665; (b) T. Takahashi, Z. Xi, R. Fischer, S. Huo,
C. Xi and K. Nakajima, J. Am. Chem. Soc., 1997, 119, 4561;
(c) Z. Xi, R. Fischer, R. Hara, W.-H. Sun, Y. Obora, N. Suzuki,
K. Nakajima and T. Takahashi, J. Am. Chem. Soc., 1997, 119,
12842.
10 C. Wang and Z. Xi, Chem. Soc. Rev., 2007, 36, 1395.
11 For selected examples on synthesis of indenes, see: (a) Z. Xi,
R. Guo, S. Mito, H. Yan, K. Kanno, K. Nakajima and
T. Takahashi, J. Org. Chem., 2003, 68, 1252; (b) H. Tsukamoto,
T. Ueno and Y. Kondo, Org. Lett., 2007, 9, 3033; (c) D. Zhang,
Z. Liu, E. K. Yum and R. C. Larock, J. Org. Chem., 2007, 72, 251;
(d) X. Zhou, H. Zhang, X. Xie and Y. Li, J. Org. Chem., 2008, 73,
3958; (e) Z. A. Khan and T. Wirth, Org. Lett., 2009, 11, 229.
12 (a) K. M. Joly, B. M. Kariuki, D. M. Coe and L. R. Cox,
Organometallics, 2005, 24, 358; (b) T. Matsuda, T. Tsuboi and
M. Murakami, J. Am. Chem. Soc., 2007, 129, 12596.
13 (a) T. Takahashi, W.-H. Sun, C. Xi, H. Ubayama and Z. Xi,
Tetrahedron, 1998, 54, 715; (b) Z. Wang and Z. Xi, Synlett, 2006,
1275; (c) L. Liu, Z. Wang, F. Zhao and Z. Xi, J. Org. Chem., 2007,
72, 3484.
14 For reviews on reactions and applications of 1-lithio-1,3-
butadiene, see: (a) W.-X. Zhang and Z. Xi, Pure Appl. Chem.,
2009, 81, 235; (b) Z. Xi, Bull. Chem. Soc. Jpn., 2007, 80, 1021.
15 X. Sun, K.-J. Izumi, C.-Q. Hu and G.-Q. Lin, Chin. J. Chem., 2006,
24, 430.
16 For examples on interaction between Lewis acid and CQC double
bonds, see: (a) T. Tsuchimoto, S. Kamiyama, R. Negoro,
E. Shirakawa and Y. Kawakami, Chem. Commun., 2003, 852;
(b) Y.-J. Jiang, Y.-Q. Tu, E. Zhang, S.-Y. Zhang, K. Cao and
L. Shi, Adv. Synth. Catal., 2008, 350, 552; (c) J. Barluenga,
A. Fernández, F. Rodrı́guez and F. J. Fañanás, J. Organomet.
Chem., 2009, 694, 546.
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