Lewis-acid-catalyzed rearrangement of arylvinylidenecyclopropanes: Significant influence of substituents and electronic nature of aryl groups

Article abstract of DOI:10.1021/jo061899r

Lewis-acid-catalyzed reactions of arylvinylidenecyclopropanes having three substituents at the corresponding cyclopropyl rings have been investigated thoroughly. The reaction products are highly dependent on the substituents at the corresponding cyclopropyl rings and the electronic nature of the aryl groups. For arylvinylidenecyclopropanes bearing two alkyl groups at the C-1 position (R¹, R², R³ = aryl; R⁴ = H; R⁵, R⁶ = alkyl), naphthalene derivatives were formed in the presence of Lewis-acid Eu(OTf)₃ in DCE at 40 °C. For arylvinylidenecyclopropanes in which R¹, R², R³ = aryl and R⁴, R⁵ = alkyl (syn/anti isomeric mixtures), the corresponding 6aH-benzo[c]fluorine derivatives were formed in the syn-configuration via a double intramolecular Friedel-Crafts reaction when all of the aryl groups do not have electron-withdrawing groups or the corresponding indene derivatives were obtained via an intramolecular Friedel-Crafts reaction as long as one electron-deficient aryl group was attached. For arylvinylidenecyclopropanes in which R¹, R², R ³, R⁴ = aryl and R⁵ = alkyl or H, the corresponding indene derivatives were obtained exclusively via a sterically demanding intramolecular Friedel-Crafts reaction. Lewis-acid effects and mechanistic insights have been discussed on the basis of experimental investigations.

Full text of DOI:10.1021/jo061899r

Lewis-Acid-Catalyzed Rearrangement of
Arylvinylidenecyclopropanes: Significant Influence of Substituents
and Electronic Nature of Aryl Groups
Yun-Peng Zhang,† Jian-Mei Lu,‡ Guang-Cai Xu,† and Min Shi*,†,‡
School of Chemistry & Molecular Engineering, East China UniVersity of Science and Technology, 130
Meilong Road, Shanghai 200237, China, and State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, China
mshi@mail.sioc.ac.cn
ReceiVed September 13, 2006
Lewis-acid-catalyzed reactions of arylvinylidenecyclopropanes having three substituents at the corre-
sponding cyclopropyl rings have been investigated thoroughly. The reaction products are highly dependent
on the substituents at the corresponding cyclopropyl rings and the electronic nature of the aryl groups.
For arylvinylidenecyclopropanes bearing two alkyl groups at the C-1 position (R1, R2, R3 ) aryl; R4 )
H; R5, R6 ) alkyl), naphthalene derivatives were formed in the presence of Lewis-acid Eu(OTf)3 in DCE
at 40 °C. For arylvinylidenecyclopropanes in which R1, R2, R3 ) aryl and R4, R5 ) alkyl (syn/anti
isomeric mixtures), the corresponding 6aH-benzo[c]fluorine derivatives were formed in the syn-
configuration via a double intramolecular Friedel-Crafts reaction when all of the aryl groups do not
have electron-withdrawing groups or the corresponding indene derivatives were obtained via an
intramolecular Friedel-Crafts reaction as long as one electron-deficient aryl group was attached. For
arylvinylidenecyclopropanes in which R1, R2, R3, R4 ) aryl and R5 ) alkyl or H, the corresponding
indene derivatives were obtained exclusively via a sterically demanding intramolecular Friedel-Crafts
reaction. Lewis-acid effects and mechanistic insights have been discussed on the basis of experimental
investigations.
Introduction
connected by a cyclopropyl ring, and yet they are thermally
stable and reactive substances. Therefore, thermal and photo-
chemical skeletal conversions of vinylidenecyclopropanes 1 have
attracted much attention from mechanistic, theoretical, spec-
troscopic, and synthetic viewpoints.1,2 Recently, we have been
investigating the Lewis-acid- or Brønsted-acid-catalyzed/medi-
Vinylidenecycloproanes 1 are one of the most remarkable
organic compounds known. They have an allene moiety
† East China University of Science and Technology.
‡ Chinese Academy of Sciences.
10.1021/jo061899r CCC: $37.00 © 2007 American Chemical Society
Published on Web 12/15/2006
J. Org. Chem. 2007, 72, 509-516
509

Zhang et al.
SCHEME 1. Lewis-Acid-Catalyzed Rearrangement of
ated ring-opening reactions of methylenecyclopropanes (MCPs),
another kind of molecule having surprising stability along with
a high level of strain,3 and found some novel reaction patterns
of these substrates.4-6 Vinylidenecyclopropanes 1, as similar
substrates with MCPs, are of synthetic interest due to the
attractive feature that they have multiple possibilities for both
reactions of the three strained bonds (two proximal and one
distal bonds) in the cyclopropyl rings and the allene bonds.7,8
Thus far, we found that aryl-monosubstituted vinylidenecyclo-
propanes 1 (R1, R3 ) aryl; R2 ) alkyl; R4 ) H; R5 ) H or
alkyl) or aryl-disubstituted ones (R1, R2, R3 ) aryl; R4 ) H; R5
) H or alkyl) undergo interesting rearrangements in the presence
of Lewis acids such as Sn(OTf)2 to give the corresponding
naphthalene derivatives 2 in good to high yields in 1,2-
dichloroethane (DCE) (Scheme 1).7a Moreover, short thereafter,
we also reported arylvinylidenecyclopropanes 1 having three
substituents at the corresponding cyclopropyl rings to provide
easy access to the corresponding 6aH-benzo[c]fluorine deriva-
tives 3 (R1, R2, R3 ) aryl; R4, R5 ) alkyl) via a double
intramolecular Friedel-Crafts reaction or a 1-methyl-3-phenyl-
1H-indene derivative 4a (R1 ) R2 ) R3 ) R4 ) C6H5; R5 )
Me for 1a) via an intramolecular Friedel-Crafts reaction in good
Arylvinylidenecyclopropanes 1
(1) (a) Poutsma, M. L.; Ibarbia, P. A. J. Am. Chem. Soc. 1971, 93, 440-
450. (b) Smadja, W. Chem. ReV. 1983, 83, 263-320. (c) Hendrick, M. E.;
Hardie, J. A.; Jones, M., Jr. J. Org. Chem. 1971, 36, 3061-3062. (d) Sugita,
H.; Mizuno, K.; Saito, T.; Isagawa, K.; Otsuji, Y. Tetrahedron Lett. 1992,
33, 2539-2542. (e) Mizuno, K.; Sugita, H.; Kamada, T.; Otsuji, Y. Chem.
Lett. 1994, 449-452 and references therein. (f) Sydnes, L. K. Chem. ReV.
2003, 103, 1133-1150. (g) Akasaka, T.; Misawa, Y.; Ando, W. Tetrahedron
Lett. 1990, 31, 1173-1176. (h) Mizuno, K.; Sugita, H.; Isagawa, K.; Goto,
M.; Otsuji, Y. Tetrahedron Lett. 1993, 34, 5737-5738. (i) Mizuno, K.;
Nire, K.; Sugita, H.; Otsuji, Y. Tetrahedron Lett. 1993, 34, 6563-6566.
(j) Mizuno, K.; Sugita, H.; Hirai, T.; Maeda, H. Chem. Lett. 2000, 1144-
1145. (k) Mizuno, K.; Nire, K.; Sugita, H.; Maeda, H. Tetrahedron Lett.
2001, 42, 2689-2692. (l) Mizuno, K.; Maeda, H.; Sugita, H.; Nishioka,
S.; Hirai, T.; Sugimoto, A. Org. Lett. 2001, 3, 581-584. (m) Mizuno, K.;
Sugita, H.; Hirai, T.; Maeda, H.; Otsuji, Y.; Yasuda, M.; Hashiguchi, M.;
Shima, K. Tetrahedron Lett. 2001, 42, 3363-3366. (n) Maeda, H.; Zhen,
L.; Hirai, T.; Mizuno, K. ITE Lett. Batteries, New Technol. Med. 2002, 3,
485-488.
to high yields in the presence of Lewis acids such as Sn(OTf)2
under mild conditions (Scheme 1).7b,8 These findings provide
novel and alternative synthetic protocols in the preparation of
a variety of aromatic compounds on the basis of the substituted
manner of arylvinylidenecyclopropanes 1. Although preliminary
results on the Lewis-acid Sn(OTf)2-catalyzed arylvinylidenecy-
clopropanes 1 have already been communicated,7 herein we
describe the full details on the scope and limitations as well as
mechanistic insights of this Lewis-acid-catalyzed interesting
rearrangement of multisubstituted arylvinylidenecyclopropanes
1. In this paper, significant substituent effects on the aromatic
rings and the influence of substituents on the cyclopropyl rings
will be discussed in detail.
(2) For synthesis of vinylidenecyclopropanes, see: (a) Isagawa, K.;
Mizuno, K.; Sugita, H.; Otsuji, Y. J. Chem. Soc., Perkin Trans. 1 1991,
2283-2285 and references therein. (b) Al-Dulayymi, J. R.; Baird, M. S.
J. Chem. Soc., Perkin Trans. 1994, 1, 1547-1548. Other papers related to
vinylidenecyclopropanes: (c) Maeda, H.; Hirai, T.; Sugimoto, A.; Mizuno,
K. J. Org. Chem. 2003, 68, 7700-7706. (d) Pasto, D. J.; Brophy, J. E.
J. Org. Chem. 1991, 56, 4556-4559. (e) Pasto, D. J.; Miles, M. F. J. Org.
Chem. 1976, 41, 425-432. (f) Pasto, D. J.; Miles, M. F.; Chou, S.-K.
J. Org. Chem. 1977, 42, 3098-3101. (f) Pasto, D. J.; Borchardt, J. K.;
Fehlper, T. P.; Baney, H. F.; Schwartz, M. E. J. Am. Chem. Soc. 1976, 98,
526-529. (g) Pasto, D. J.; Chen, A. F.-T.; Clurdaru, G.; Paquette, L. A. J.
Org. Chem. 1973, 38, 1015-1026. (h) Pasto, D. J.; Borchardt, J. K. J. Am.
Chem. Soc. 1974, 96, 6937-6943.
(5) For the Lewis-acid-mediated cycloaddition of MCPs with activated
ketone or aldehyde, see: (a) Shi, M.; Xu, B. Tetrahedron. Lett. 2003, 44,
3839-3842. For the MgI2-mediated ring expansions of methylenecyclo-
propyl amides and imides, see: (b) Lautens, M.; Han, W. J. Am. Chem.
Soc. 2002, 124, 6312-6316. (c) Lautens, M.; Han, W.; Liu, J. H.-C.
J. Am. Chem. Soc. 2003, 125, 4028-4029. For the cycloaddition of MCPs
activated by a carbonyl group with allyltrimethylsilane in the presence of
TiCl4, see: (d) Monti, H.; Rizzotto, D.; Leandri, G. Tetrahedron 1998, 54,
6725-6738. For the cycloaddition of gem-dialkoxy-substituted MCPs with
aldehydes and imines upon heating, see: (e) Yamago, S.; Nakamura, E.
J. Org. Chem. 1990, 55, 5553-5555. (f) Yamago, S.; Yanagawa, M.;
Nakamura, E. Chem. Lett. 1999, 879-880.
(6) For some related Lewis-acid- or Brønsted-acid-mediated reactions
of MCPs, see: (a) Peron, G. L. N.; Kitteringham, J.; Kilburn, J. D.
Tetrahedron Lett. 1999, 40, 3045-3048. (b) Miura, K.; Takasumi, M.;
Hondo, T.; Saito, H.; Hosomi, A. Tetrahedron Lett. 1997, 38, 4587-4590.
(c) Peron, G. L. N.; Kitteringham, J.; Kilburn, J. D. Tetrahedron Lett. 2000,
41, 1615-1618. (d) Patient, L.; Berry, M. B.; Kilburn, J. D. Tetrahedron
Lett. 2003, 44, 1015-1017. (e) Peron, G.; Norton, D.; Kitteringham, J.;
Kilburn, J. D. Tetrahedron Lett. 2001, 42, 347-349. (f) Patient, L.; Berry,
M. B.; Coles, S. J.; Hursthouse, M. B.; Kilburn, J. D. Chem. Commun.
2003, 2552-2553. (g) Siriwardana, A. I.; Nakamura, I.; Yamamoto, Y.
Tetrahedron Lett. 2003, 44, 4547-4550. (h) Rajamaki, S.; Kilburn, J. D.
Chem. Commun. 2005, 1637-1639.
(3) For recent reviews, see: (a) Nakamura, I.; Yamamoto, Y. AdV. Synth.
Catal. 2002, 344, 111-129. (b) Brandi, A.; Cicchi, S.; Cordero, F. M.;
Goti, A. Chem. ReV. 2003, 103, 1213-1269.
(4) For some of the Lewis-acid- or Brønsted-acid-mediated transforma-
tions of MCPs in this laboratory, see: (a) Shi, M.; Xu, B. Org. Lett. 2002,
4, 2145-2148. (b) Huang, J.-W.; Shi, M. Tetrahedron 2004, 60, 2057-
2062. (c) Shao, L.-X.; Shi, M. Eur. J. Org. Chem. 2004, 426-430. (d)
Chen, Y.; Shi, M. J. Org. Chem. 2004, 69, 426-431. (e) Shao, L.-X.; Shi,
M. AdV. Synth. Catal. 2003, 345, 963-966. (f) Shi, M.; Chen, Y. J. Fluorine
Chem. 2003, 122, 219-227. (g) Huang, J.-W.; Shi, M. Tetrahedron Lett.
2003, 44, 9343-9347. (h) Shi, M.; Chen, Y.; Xu, B.; Tang, J. Green Chem.
2003, 5, 85-88. (i) Shi, M.; Xu, B. Tetrahedron Lett. 2003, 44, 3839-
3842. (j) Xu, B.; Shi, M. Org. Lett. 2003, 5, 1415-1418. (k) Shi, M.; Shao,
L.-X.; Xu, B. Org. Lett. 2003, 5, 579-582. (l) Shi, M.; Chen, Y.; Xu, B.;
Tang, J. Tetrahedron Lett. 2002, 43, 8019-8024. (m) Huang, J.-W.; Shi,
M. Synlett 2004, 2343-2346. (n) Shao, L.-X.; Huang, J.-W.; Shi, M.
Tetrahedron 2004, 60, 11895-11901. (o) Shi, M.; Xu, B.; Huang, J.-W.
Org. Lett. 2004, 6, 1175. (p) Shao, L.-X.; Xu, B.; Huang, J.-W.; Shi, M.
Chem. Eur. J. 2006, 12, 510-517.
(7) (a) Xu, G.-C.; Ma, M.; Liu, L.-P.; Shi, M. Synlett 2005, 1869-1872.
(b) Xu, G.-C.; Liu, L.-P.; Lu, J.-M.; Shi, M. J. Am. Chem. Soc. 2005, 127,
14552-14553.
(8) For isomerization of alkenylidenecyclopropanes catalyzed by Lewis
acids, see: Fitjer, L. Angew. Chem., Int. Ed. Engl. 1975, 14, 360-361.
510 J. Org. Chem., Vol. 72, No. 2, 2007

Rearrangement of ArylVinylidenecyclopropanes
TABLE 1. Lewis-Acid Eu(OTf)3-Catalyzed Rearrangement of
Arylvinylidenecyclopropanes 1 in DCE at 40 °C
TABLE 3. Sn(OTf)2-Catalyzed Rearrangement of
Arylvinylidenecyclopropanes 1p-v in DCE at 80 °C
entry
1 (R1/R2/R3/R4/R5)
4, yield (%)b
1
2
3
4
5
6
7
1p (C6H5/C6H5/p-CIC6H4/Me/Me) (1:2)a
1q (C6H5/C6H5/p-BrC6H4/Me/Me) (1:2)a
1r (p-FC6H4/p-FC6H4/p-CIC6H4/Me/Me) (2:1)a
1s (p-FC6H4/p-FC6H4/p-MeC6H4/Me/Me) (syn)
1t (p-FC6H4/p-FC6H4/C6H5/Me/Me) (1:3)a
1u (p-CIC6H4/p-CIC6H4/C6H5/Me/Me) (3:2)a
1v (C6H5/C6H5/p-FC6H4/Me/Me) (1:1)a
4b, 91
4c, 97
4d, 95
4e, 88
4f, 97
4g, 96
4h, 91
a Syn:anti. b Isolated yields.
a Isolated yields.
TABLE 2. Sn(OTf)2-Catalyzed Rearrangement of
Arylvinylidenecyclopropanes 1k-o in DCE at 80 °C
FIGURE 1. ORTEP drawing of 4b.
ate to good yield in the presence of a variety of Lewis acids
(Supporting Information). We found that these optimized
reaction conditions are to carry out the reaction in DCE at 40
°C using Eu(OTf)3 (10 mol %) as a catalyst (Table SI-1, entry
7). In oxygen-atom-containing solvents such as THF, methanol,
and DMF, no reaction occurred, presumably due to their
coordinative nature to Lewis acids to deactivate the catalytic
abilities.
Next, we carried out the reaction of a variety of arylvi-
nylidenecyclopropane derivatives 1c-j in the presence of Eu-
(OTf)3 under these optimized conditions. The results including
arylvinylidenecyclopropane 1b are summarized in Table 1. As
can be seen from Table 1, the corresponding rearranged products
2b-i, naphthalene derivatives, were obtained in moderate to
good yields within 3 h (Table 1, entries 1-9). For spiro-type
arylvinylidenecyclopropane derivatives 1g and 1h, the corre-
sponding naphthalene derivatives 2f and 2g were obtained in
67% and 64% yields, respectively (Table 1, entries 6 and 7).
For arylvinylidenecyclopropane derivatives 1i and 1j bearing
electron-withdrawing groups on the benzene rings of R1 and
R2, similar rearrangements also took place to give the corre-
sponding naphthalene derivatives 2h and 2i in moderate yields
(Table 1, entries 8 and 9).
entry
1 (R1/R2/R3/R4/R5)
3, yield (%)b
1
2
3
4
5
1k (C6H5/C6H5/C6H5/Me/Me) (1:2)a
3a, 74
3b, 84
3c, 82
3d, 47
3e, 96
1l (C6H5/C6H5/p-MeC6H4/Me/Me) (1:1)a
1m (C6H5/C6H5/p-MeOC6H4/Me/Me) (9:1)a
1n (p-MeC6H4/p-MeC6H4/C6H5/Me/Me) (1:3)a
1o (C6H5/C6H5/C6H5/Et/Me) (1:1)a
a Syn:anti. b Isolated yields.
Results and Discussion
Lewis-Acid-Catalyzed Rearrangement of Aryl-Disubsti-
tuted Arylvinylidenecyclopropanes 1 For Which R1, R2, R3
) Aryl; R4 ) H; and R5, R6 ) Alkyl. We first attempted to
examine the Lewis-acid-catalyzed rearrangement of aryl-disub-
stituted arylvinylidenecyclopropanes 1b-j bearing 1,1-dialkyl
groups and a 2-aryl group at the corresponding cyclopropyl ring
(R1, R2, R3 ) aryl; R4 ) H; R5, R6 ) alkyl). An initial
examination was carried out using arylvinylidenecyclopropane
1b (R1, R2, R3 ) C6H5; R4 ) H; R5, R6 ) Me) as substrate in
the presence of a variety of Lewis acids in DCE and other
solvents. The results are summarized in Table SI-1, and the
corresponding naphthalene derivative 2a was formed in moder-
A plausible mechanism for rearrangement of arylvinylidenecy-
clopropanes 1b-j in the presence of Lewis acid has been
described in the previous communication via a vinyl-group-
J. Org. Chem, Vol. 72, No. 2, 2007 511

Zhang et al.
SCHEME 2. Lewis-Acid-Catalyzed Rearrangement of Arylvinylidenecyclopropanes 1p-v
TABLE 4. Zr(OTf)4-Catalyzed Rearrangement of
Arylvinylidenecyclopropanes 1 in DCE at 40 °C
SCHEME 3. Lewis-Acid Yb(OTf)3- or Sc(OTf)3-Catalyzed
Rearrangement of Arylvinylidenecyclopropane 1a
entry
1 (R1/R2/R3/R4/R5)
4, yield (%)a
1
2
3
4
5
6
7
8
9
10
1a (C6H5/C6H5/C6H5/C6H5/Me)
4a, 98
4i, 95
4j, 97
4k, 90
4l, 94
4m, 91
4n, 96
4o, 95
4p, 76
4q, 83
1w (C6H5/C6H5/p-CIC6H4/p-CIC6H4/Me)
1x (C6H5/C6H5/p-FC6H4/p-FC6H4/Me)
1y (C6H5/C6H5/p-MeC6H4/p-MeC6H4/Me)
1z (C6H5/C6H5/p-MeOC6H4/p-MeOC6H4/Me)
1aa (p-FC6H4/p-FC6H4/C6H5/C6H5/Me)
1ab (p-MeC6H4/p-MeC6H4/C6H5/C6H5/Me)
1ac (C6H5/C6H5/C6H5/C6H5/H)
1ad (C6H5/C6H5/p-CIC6H4/p-CIC6H4/H)
1ae (C6H5/C6H5/p-MeC6H4/p-MeC6H4/H)
a Isolated yields.
of aryl groups of this kind of substrates dramatically affects
the reaction pattern. In this full paper we attempted to correct
our conclusion because the structures of the products derived
from arylvinylidenecyclopropanes having electron-deficient
aromatic group were misassigned.12 For example, we found that
for arylvinylidenecyclopropanes 1k-o in which aromatic groups
of R1, R2, and R3 have no electron-deficient substituents on the
benzene ring and the cyclopropyl ring, the corresponding 6aH-
benzo[c]fluorine derivatives 3a-e can be obtained in moderate
stabilized zwitterionic intermediate,9,10 intramolecular Friedel-
Crafts reaction, 1,3-proton shift, and aromatization.7a
Lewis-Acid-Catalyzed Rearrangement of Arylvinylidenecy-
clopropanes 1 For Which R1, R2, R3 ) Aryl and R4, R5 )
Alkyl. Previously, we reported that using arylvinylidenecyclo-
propanes 1 having three substituents at the C-1 and C-2 positions
(R1, R2, R3 ) aryl; R4, R5 ) alkyl) (syn/anti isomeric mixtures)
as substrates, an interesting rearrangement took place to give
6aH-benzo[c]fluorine derivatives 3 stereoselectively with syn-
configuration in DCE in the presence of Sn(OTf)2 upon heating
at 80 °C.7b Further studies revealed that the electronic nature
(11) For the mechanism of the 1,3-proton shift, see: Carey, F. A.;
Sundburg, R. J. AdVanced Organic Chemistry, 3rd ed.; Plenum Press: New
York, 1990; pp 609-613.
(12) In our previous communication, the structures of products 2b, 2c,
and 2f have been misassigned. This misassignment is simply due to our
carelessness. Since the structures of 6aH-benzo[c]fluorine derivative 3a and
1-methyl-3-phenyl-1H-indene derivative 4a have been determined by X-ray
diffraction, we overlooked the NMR spectroscopic data of the products
derived from arylvinylidenecyclopropanes 1b, 1c, and 1f, which have
electron-deficient aromatic moieties.
(9) (a) In Dicoordinated Carbocations; Rappoport, Z., Stang, P. J., Eds.;
John Wiley & Sons: New York, 1997; pp 137-138. (b) Olah, G. A.; Reddy,
V. P.; Prakash, G. K. S. Chem. ReV. 1992, 92, 69-95.
(10) Bollinger, J. M.; Brinich, J. M.; Olah, G. A. J. Am. Chem. Soc.
1970, 92, 4025-4033.
512 J. Org. Chem., Vol. 72, No. 2, 2007

Rearrangement of ArylVinylidenecyclopropanes
SCHEME 4. Sn(OTf)2-Catalyzed Rearrangement of Unsymmetric Arylvinylidenecyclopropanes 1af, 1ag, and 1ah
SCHEME 5. Lewis-Acid-Catalyzed Rearrangement of
Arylvinylidenecyclopropane 1ai
substituents on the benzene ring or cyclopropyl ring, we found
that the rearranged products were indene derivatives 4b-h
obtained via an intramolecular Friedel-Crafts reaction under
standard conditions (Table 3). In order to unambiguously
confirm this drastic difference on the reaction product due to
the electronic nature on the aromatic rings of arylvinylidenecy-
clopropanes, X-ray diffraction of 4b was carried out. The
ORTEP drawing of 4b is shown in Figure 1.13
A rational explanation of this drastic difference can be
attributed to the nature of Friedel-Crafts reaction.14 For
arylvinylidenecyclopropanes 1k-o having no electron-deficient
aromatic substituents, the corresponding 6aH-benzo[c]fluorine
derivatives 3 were formed with a syn-configuration via a double
intramolecular Friedel-Crafts reaction as described in the
previous communication.7b
(13) The crystal data of 4b has been deposited in CCDC with number
295457. Empirical formula: C25H21Cl. Formula weight: 356.87. Crystal
color, habit: colorless, prismatic. Crystal dimensions: 0.423 × 0.270 ×
0.201 mm. Crystal system: monoclinic. Lattice type: primitive. Lattice
parameters: a ) 11.0128(11) Å, b ) 9.9609(10) Å, c ) 18.4801(18) Å, R
) 90°o, â ) 102.407(2)°, γ ) 90°, V ) 1979.9(3) Å3. Space group: P2-
(1)/c. Z ) 4. Dcalcd ) 1.197 g/cm3. F000 ) 752. Diffractometer: Rigaku
AFC7R. Residuals: R, Rw: 0.0456, 0.0972. The crystal data of 3a and 4a
can be found in the Supporting Information of the previous communication
(ref 7b).
to good yields via a double intramolecular Friedel-Crafts
reaction as those described in the previous paper (Table 2).7b
However, for arylvinylidenecyclopropanes 1p-v, as long as one
of the aromatic groups of R1, R2, or R3 has electron-withdrawing
(14) (a) Fleming, I. Chemtracts: Org. Chem. 2001, 14, 405-406. (b)
Chevrier, B.; Weis, R. Angew. Chem. 1974, 86, 12-21.
J. Org. Chem, Vol. 72, No. 2, 2007 513

Zhang et al.
SCHEME 6. Summary of Lewis-Acid-Catalyzed Rearrangement of Arylvinylidenecyclopropanes 1
For arylvinylidenecyclopropanes 1p-v having at least one
electron-deficient aromatic compound, similar to the previous
examples,7 the corresponding cyclopropyl ring-opened zwitte-
rionic intermediate B-1 or the resonance-stabilized zwitterionic
intermediates C′-1 and C-1 are formed from the initial zwitte-
rionic intermediate A-1. Intramolecular Friedel-Crafts reaction
with the aromatic R3 group at the C-1 position takes place to
produce zwitterionic intermediate D′-1, which affords the
corresponding zwitterionic intermediate E-1 via an allylic
rearrangement. Subsequent 1,3-proton shift along with release
of the Lewis acid via zwitterionic intermediate F-1 produces
the corresponding indene derivative 4 (Scheme 2). When R3 is
an electron-deficient aromatic moiety and R1 and R2 are
electron-neutral aromatic moieties (phenyl groups) or electron-
rich aromatic moieties (4-methylphenyl groups), the correspond-
ing zwitterionic intermediate C-1 is not as stable as that when
R3 is an electron-neutral aromatic moiety (phenyl group) or
electron-rich aromatic moiety (4-methylphenyl group) since in
this case the corresponding zwitterionic intermediate C-1 is more
stabilized by the electron-rich aromatic moiety from the point
of view of the stabilization of cationic intermediate. Sterically,
intramolecular Friedel-Crafts reaction can more easily take
place with the aromatic R3 group at the C-1 position than that
with the aromatic R1 or R2 group in zwitterionic intermediate
C′-1. Therefore, intramolecular Friedel-Crafts reaction takes
place from zwitterionic intermediate C′-1 with the aromatic R3
group at the C-1 position to give the corresponding indene
derivative 4 (Scheme 2). When R3 is an electron-neutral or
electron-rich aromatic moiety and R1 and/or R2 are electron-
deficient aromatic moieties/moiety, the subsequent intramo-
lecular Friedel-Crafts reaction cannot easily take place from
zwitterionic intermediate C-1 to provide the corresponding
zwitterionic intermediates D-1 and D′′-1 because intramolecular
Friedel-Crafts reaction takes place more easily for electron-
rich aromatic moiety,14 although the corresponding zwitterionic
intermediate C-1 is more stabilized by the electron-rich aromatic
moiety of R3 group. This is why in the case of arylvinylidenecy-
clopropanes 1p-v having electron-deficient aromatic moieties
(R1 and R2 or R3), the corresponding indene derivatives 4 are
exclusively formed.
Lewis-Acid-Catalyzed Rearrangement of Arylvinylidenecy-
clopropanes 1 For Which R1, R2, R3, R4 ) Aryl and R5 )
Alkyl or H. In addition, for arylvinylidenecyclopropanes 1
bearing two aromatic groups at the C-1 position, only one case
514 J. Org. Chem., Vol. 72, No. 2, 2007

Rearrangement of ArylVinylidenecyclopropanes
of Lewis-acid Yb(OTf)3 or Sc(OTf)3. Subsequently, intramo-
lecular Friedel-Crafts reaction of intermediate C-2 stabilized
by two aromatic R3 and R4 groups with the aromatic R1 or R2
group produces the cyclized zwitterionic intermediate D-2,
which affords the corresponding zwitterionic intermediate E-2
via an allylic rearrangement. In the presence of Lewis-acid Yb-
(OTf)3 or Sc(OTf)3, the second sterically demanding intramo-
lecular Friedel-Crafts reaction of intermediate E-2 with the
aromatic R3 group does not take place to give the corresponding
6aH-benzo[c]fluorine derivative. Alternatively, the 1,4-proton
shift along with the release of Lewis acid takes place to produce
the corresponding 1,2-dihydro-naphthalene derivative 5a.15 Since
R3 and R4 are not hydrogen atoms, it is impossible to give the
corresponding naphthalene derivative via aromatization from
zwitterionic intermediate E-2. Therefore, 1,2-dihydro-naphtha-
lene derivative 5a becomes the corresponding thermodynami-
cally favored product in this case. This result suggests that the
employed Lewis acids also play an important role in this
reaction. For the same arylvinylidenecyclopropane substrate,
different Lewis acid can produce different products even under
similar reaction conditions.
Mechanistic Discussion. In order to clarify the significant
substituent effects on the rearrangement of arylvinylidenecy-
clopropanes catalyzed by Lewis acid, we attempted to synthesize
unsymmetric arylvinylidenecyclopropanes 1af and 1ag bearing
electron-deficient aromatic moieties to examine their rearrange-
ment under our standard conditions. With unsymmetrical
arylvinylidenecyclopropane 1af as the substrate under these
optimized conditions, we found that 2-(2,2-diarylvinyl)-1-
methyl-3-methyl-1H-indene derivative 4r can be obtained in
62% yield as a mixture of E- and Z-isomers along with 6aH-
benzo[c]fluorine derivative 3f in 31% yield (Scheme 4). For
unsymmetrical arylvinylidenecyclopropane 1ag, which has a
p-chlorophenyl group at the C-1 position of the cyclopropyl
ring, 2-(2,2-diarylvinyl)-1-methyl-3-methyl-1H-indene derivative
4s was obtained in 99% yield exclusively as a mixture of E-
and Z-isomers (Scheme 4). These results suggest that the double
intramolecular Friedel-Crafts reaction from zwitterionic inter-
mediate C-1af indeed selectively takes place with the phenyl
group to give the corresponding 6aH-benzo[c]fluorine derivative
3f along with another sterically favored intramolecular Friedel-
Crafts reaction with the phenyl group at the C-1 position from
zwitterionic intermediate C′-1af to produce the corresponding
indene derivative 4r. In the case of arylvinylidenecyclopropane
1ag, the corresponding zwitterionic intermediate C-1ag is not
as stable due to the electron-deficient p-chlorophenyl group,
and therefore, the sterically favored intramolecular Friedel-
Crafts reaction with the p-chlorophenyl group at the C-1 position
from zwitterionic intermediate C′-1ag exclusively takes place
to produce the corresponding indene derivative 4s in high yield
(Scheme 4). For arylvinylidenecyclopropane 1ah bearing two
strongly electron-donating methoxy groups on the benzene rings
and an electron-deficient p-chlorophenyl group at the C-1
position of the cyclopropyl ring, the subsequent intramolecular
Friedel-Crafts reaction still exclusively proceeds through the
sterically favored way to give the corresponding indene deriva-
tive 4t in 94% yield under standard conditions (Scheme 4).
These results obtained in the above control experiments can
explain the subtle substituent effects in this interesting Lewis-
FIGURE 2. Difference in two kinds of intramolecular Friedel-Crafts
reactions.
has been reported using 1a (R1 ) R2 ) R3 ) R4 ) C6H5; R5 )
Me) as substrate to give the corresponding 1-methyl-3-phenyl-
1H-indene derivative 4a in good yield in DCE in the presence
of Sn(OTf)2 in our previous short communication.7b Therefore,
we further optimized these reaction conditions and synthesized
a variety of arylvinylidenecyclopropanes 1w-ae bearing two
aromatic groups at the C-1 position for this reaction. These
reaction conditions were optimized in a similar manner as those
described above. The results are summarized in Table SI-2
(Supporting Information). Zr(OTf)4 is the most effective catalyst
to give 4a in 98% yield at 40 or 80 °C within 5 h (Table SI-2,
entries 7 and 8). Solvent effects have also been examined with
Zr(OTf)4 (10 mol %) at 40 °C in toluene, MeCN, THF, ethanol,
DMF, and hexane. We found that the best reaction conditions
are to carry out the reaction in DCE at 40 °C using Zr(OTf)4
(10 mol %) as a catalyst (Table SI-2, Supporting Information).
Next, we carried out reaction of a variety of arylvinylidenecy-
clopropanes 1w-ae (R1, R2, R3, R4 ) aryl; R5 ) alkyl or H)
under these optimized conditions. The results including arylvi-
nylidenecyclopropane 1a are summarized in Table 4. As can
be seen from Table 4, the corresponding rearranged products
indene derivatives, 4a and 4i-q, were obtained in good to high
yields within 5 h in DCE at 40 °C for arylvinylidenecyclopro-
panes 1w-ae having either electron-rich or electron-deficient
aromatic moieties (Table 4). In this case, when R5 does not
have a substituent (R5 ) H for 1ac-ae), the corresponding
indene derivatives 4o-q were also obtained in 76-95% yields
under standard conditions (Table 4, entries 8-10).
In this case, sterically, the subsequent intramolecular Friedel-
Crafts reaction with the aromatic R3 or R4 group at the C-1
position can easily take place to produce the corresponding
indene derivative 4 as described in the previous communication.7b
Lewis-Acid Effects on the Rearrangement of Arylvi-
nylidenecyclopropanes 1 For Which R1, R2, R3, R4 ) aryl
and R5 ) alkyl. Interestingly, we found that when Yb(OTf)3
or Sc(OTf)3 was used in the rearrangement of arylvinylidenecy-
clopropane 1a, the rearranged product 5a, 2-ethylidene-1,1,4-
triphenyl-1,2-dihydro-naphthalene, was formed as a mixture of
Z:E isomers in higher yields rather than the indene derivative
in DCE at 40 or 80 °C (Scheme 3). The structure of 5a was
determined by spectroscopic data (Supporting Information). The
reaction conditions were examined in a similar manner as that
described above. The results are summarized in Table SI-3
(Supporting Information). The best reaction conditions are found
when the reaction is carried out in DCE using Yb(OTf)3 as a
catalyst at 80 °C (Table SI-3, entry 4). The reaction mechanism
is also shown in Scheme 3. The corresponding cyclopropyl ring-
opened zwitterionic intermediate B-2 or the resonance-stabilized
zwitterionic intermediates C′-2 and C-2 are formed similarly
from the initial zwitterionic intermediate A-2 in the presence
(15) For arylvinylidenecyclopropanes 1w, 1x, 1z, and 1aa, similar
products can be isolated in moderate yields along with some unidentified
byproducts (Table SI-4 in the Supporting Information).
J. Org. Chem, Vol. 72, No. 2, 2007 515

Zhang et al.
acid-catalyzed rearrangement of arylvinylidenecyclopropanes 1.
The stability of zwitterionic intermediate, electronic nature of
aromatic group, and sterically demanding intramolecular Friedel-
Crafts reaction play key roles in this reaction.
of intramolecular Friedel-Crafts reaction will not take place
(Figure 2). However, intramolecular Friedel-Crafts reaction of
carbocation in zwitterionic intermediate C′ with an aromatic
R3 group is a sterically favored and no electronic nature
demanding process. Therefore, even for an electron-deficient
aromatic moiety this kind of intramolecular Friedel-Crafts
reaction can easily take place (Figure 2). The difference in the
electronic nature and steric requirement of the two kinds of
intramolecular Friedel-Crafts reactions produces different
products. In addition, for the same arylvinylidenecyclopropane
substrate, different Lewis acid can produce different products
even under similar reaction conditions. At the present stage,
the influence of the metal nature in the Lewis acids is not
understood very well. Efforts are in progress to elucidate further
mechanistic details of these reactions and understand their scopes
and limitations. Work along this line is currently in progress.
Moreover, when using arylvinylidenecyclopropane 1ai as the
substrate under standard conditions, complicated products were
formed from which none of the identified compound can be
cleanly isolated (Scheme 5). This may be due to the fact that
the corresponding zwitterionic intermediate C′-1ai, derived from
the initial zwitterionic intermediates A-3 and B-3, is not as stable
as the corresponding zwitterionic intermediate bearing an alkyl
group at the C-2 position. In addition, only one phenyl group
is at the C-1 position of the cyclopropyl ring. Therefore, the
sterically demanding intramolecular Friedel-Crafts reaction
does not have enough room to take place to give the corre-
sponding indene derivative as a major product, although for
arylvinylidenecyclopropanes 1ac-ae bearing two aromatic
groups at the C-1 position this type of intramolecular Friedel-
Crafts reaction can easily take place to produce the correspond-
ing indene derivatives in good yields. Moreover, in the course
of the formation of the corresponding 6aH-benzo[c]fluorine
derivative 3g from zwitterionic intermediate C-1ai, the related
zwitterionic intermediate D-3 or E-3 is not as stable as the
corresponding zwitterionic intermediate bearing an alkyl group
at the C-2 position. Therefore, the second intramolecular
Friedel-Crafts reaction cannot easily take place to give the
corresponding 6aH-benzo[c]fluorine derivative 3g as a major
product via the corresponding zwitterionic intermediate F-3. In
any sense, there is no major reaction pathway in the rearrange-
ment of arylvinylidenecyclopropane 1ai catalyzed by Lewis acid.
Many products would be produced in small amounts due to the
fact that there is no major reaction course under our standard
conditions. This result suggests that the structure and stability
of the cationic intermediate in the corresponding zwitterionic
intermediate are important in this reaction.
In conclusion, we identified an efficient Lewis-acid-catalyzed
rearrangement of arylvinylidenecyclopropanes 1 having three
substituents at the cyclopropyl ring to provide easy access to
naphthalene derivatives 2 through an intramolecular Friedel-
Crafts reaction, or 6aH-benzo[c]fluorine derivatives 3 via a
double intramolecular Friedel-Crafts reaction, or the corre-
sponding indene derivative 4 via a sterically favored intramo-
lecular Friedel-Crafts reaction under mild reaction conditions
in good to excellent yields depending on the substituents at the
cyclopropyl ring and the electronic nature of the aryl groups.
The corresponding reaction mechanisms have been discussed
on the basis of the control experiments and related investigations.
In addition, the scope and limitations have been disclosed in
this paper. Since the reaction pattern of the present reactions is
complicated, the corresponding simply summarized reaction
mechanism and reaction pathways are shown in Scheme 6.
Intramolecular Friedel-Crafts reaction of carbocation in zwit-
terionic intermediate C with an aromatic R1 or R2 group is a
sterically disfavored and electronic nature demanding process.
Therefore, for an electron-deficient aromatic moiety, this kind
Experimental Section
1
General Remarks. Melting points are uncorrected. H and 13
C
NMR spectra were recorded at 300 and 75 MHz, respectively. Mass
spectra were recorded by EI, MALDI, and ESI methods, and HRMS
was measured by EI method. CHN microanalyses were recorded
on an analyzer. Organic solvents used were dried by standard
methods when necessary. Commercially obtained reagents were
used without further purification. All reactions were monitored by
TLC plates. Flash column chromatography was carried out using
300-400 mesh silica gel at increased pressure.
Typical Reaction Procedure for the Preparation of Diarylvi-
nylidenecyclopropanes. A mixture of Bu4NHSO4 (10 mmol) and
powdered NaOH (80 g) was added to a tetrahydrofuran (THF, 50
mL) solution containing 1,1-dibromo-2,2-diphenylcyclopropane (10
mmol) and an excess of 1,1-diphenylprop-1-ene (12 mmol). The
mixture was vigorously stirred at room temperature for 24 h. Flash
column chromatography of the resulting mixture on silica gel gave
product 1a (31%) as a white solid.
Typical Reaction Procedure for the Rearrangement of Di-
arylvinylidenecyclopropanes to 4. To a solution of diarylvi-
nylidenecyclopropane 1a (76.8 mg, 0.2 mmol) in 1,2-dichloroethane
(DCE) (2.0 mL) was added Zr(OTf)4 (13.7 mg, 0.02 mmol), and
the reaction mixture was stirred for 5 h at 40 °C (monitored by
TLC). After the starting material diarylvinylidenecyclopropane 1a
was consumed, the solvent was removed under reduced pressure
and the residue subjected to a flash column chromatography to give
the desired product 4a (75.3 mg, 98%) as a white solid.
Acknowledgment. We thank the Shanghai Municipal Com-
mittee of Science and Technology (04JC14083, 06XD14005),
Chinese Academy of Sciences (KGCX2-210-01), East China
University of Science and Technology of Changjiang Scholar-
ship, and National Natural Science Foundation of China for
financial support (20472096, 203900502, and 20672127).
Supporting Information Available: Experimental details, IR,
13C and 1H NMR spectroscopic and analytic data for 2-5, and X-ray
crystal data of 4b. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO061899R
516 J. Org. Chem., Vol. 72, No. 2, 2007