Ring-opening reaction of methylenecyclopropanes derived from methylenecyclopropyl aldehydes through cope rearrangement

Article abstract of DOI:10.1002/ejoc.201000880

Tandem Wittig reaction/Cope rearrangement of methylenecyclopropyl aldehydes 1 with cinnamyltriphenylphosphonium bromide afforded a convenient method for the synthesis of cyclopentene derivatives 2 in moderate yields in a one-pot manner. Dialkyl 2-[(2-meth

Full text of DOI:10.1002/ejoc.201000880

FULL PAPER
DOI: 10.1002/ejoc.201000880
Ring-Opening Reaction of Methylenecyclopropanes Derived from
Methylenecyclopropyl Aldehydes through Cope Rearrangement
Xiang-Ying Tang,[a] Yin Wei,*[a] and Min Shi*[a]
Keywords: Cyclization / Rearrangement / Small ring systems / Wittig reactions
Tandem Wittig reaction/Cope rearrangement of methylene-
cyclopropyl aldehydes 1 with cinnamyltriphenylphosphon-
ium bromide afforded a convenient method for the synthesis
of cyclopentene derivatives 2 in moderate yields in a one-pot
manner. Dialkyl 2-[(2-methylenecyclopropyl)methylene]-
malonates 3 derived from methylenecyclopropyl aldehydes 1
could produce two kinds of cyclopentene derivatives, 4 and
5, in good total yields through a thermally induced Cope re-
arrangement upon heating at 100 °C. Plausible reaction
mechanisms are discussed on the basis of previous reports
and on control experiments.
Cope rearrangement of MCP methylenemalonates 3 to fur-
nish the corresponding cyclopentene derivatives 2, 4, and 5
in moderate yields.
Introduction
Methylenecyclopropanes (MCPs) are widely used as
building blocks in organic synthesis because of their ready
accessibility as well as their diverse reactivity, which is
driven by the relief of ring strain.[1] The ring-opening reac-
tions of MCPs are synthetically useful in the construction
of complex product structures and have been extensively
studied.[2] Over the past decades, Lewis acids and transi-
tion-metal-catalyzed reactions involving ring opening of
MCPs to form a variety of carbocycles and heterocycles
have been extensively investigated.[3] However, the ring-
opening reactions of MCPs by thermally induced re-
arrangements are relatively limited due to fact that high
temperature is usually required because of the very large
activation energy.[3] Previously, we reported a synthetic
route to 2,3-disubstituted pyrrolamides by ring-opening re-
cyclization of benzylidene and alkylidenecyclopropanecarb-
aldehydes with hydrazides.[4] In addition, we also reported
an efficient method to stereospecifically synthesize trans-
substituted cyclopentene derivatives in moderate to good
yields by using the Cope rearrangement of readily available
MCP alkenyl ketone derivatives (Scheme 1).[5] On the basis
of the previous work, we hypothesized that MCPs with an
activated alkene moiety might also be suitable substrates for
the ring-opening process upon heating. Herein, we wish to
report our investigations on the ring-opening reactions of
methylenecyclopropyl aldehydes 1 with cinnamyltriphenyl-
phosphonium bromide as well as on the thermally induced
Scheme 1. Previous studies on the ring-opening reactions of MCP
derivatives.
Results and Discussion
We started our work on the synthesis of MCP com-
pounds with an activated alkene moiety by undertaking a
Wittig reaction of MCP aldehyde 1a with cinnamyltriphen-
ylphosphonium bromide in tetrahydrofuran (THF) using n-
butyllithium (nBuLi) as base without heating. To our sur-
prise, the cyclopentene derivative 2a, rather than the ex-
pected MCP alkene, was obtained in 77% yield after usual
workup and purification by column chromatography on sil-
ica gel, suggesting that the tandem sequence of Wittig reac-
tion/Cope rearrangement could take place easily at room
temperature (Table 1, entry 1). Further investigation re-
vealed that the base played an important role in this reac-
tion. The reaction also took place with strong inorganic
bases (NaH, NaOH, and KOH), giving the corresponding
cylcopentene derivative 2a in 15–58% yields (Table 1, en-
tries 2, 4, and 5). However, other bases, such as tBuOK and
[a] State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, P. R. of China
Fax: +86-21-64166128
E-mail: Mshi@mail.sioc.ac.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000880.
View this journal online at
wileyonlinelibrary.com
6038
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 6038–6042

Formation and Ring-Opening of Methylenecyclopropanes
Et3N, did not promote the reaction (Table 1, entries 3 and Table 2. Scope of the reaction.
6). When the reaction was conducted in other solvents, such
as Et2O, hexane, or 1,4-dioxane, the corresponding cyclo-
pentene product 2a was obtained in 7–60% yields using
nBuLi as base (Table 1, entries 7–9).
Table 1. Tandem Wittig reaction/Cope rearrangement of phospho-
nium salt with MCP aldehyde 1a.
Entry
R
Yield of 2 [%][a]
1
2
3
4
5
6
7
8
pBrC6H4
pClC6H4
pPhC6H4
3,4,5-(MeO)3C6H2
(Z)-1a, C6H5
pMeOC6H4
3,4-Me2C6H3
(E) and (Z)-nC7H15
55
64
77
66
62
63
73
69
Entry
Base
Solvent
Yield of 2a [%][a]
[a] Isolated yield.
1
2
3
4
5
6
7
8
9
nBuLi
NaH
tBuOK
NaOH
KOH
THF
THF
THF
THF
THF
THF
Et2O
hexane
1,4-dioxane
77
58
traces
15
21
n.r.
7
Et3N
nBuLi
nBuLi
nBuLi
60
36
[a] Isolated yield.
With these optimized reaction conditions in hand
(Table 1, entry 1), we then examined the generality of the
reaction by using a variety of MCP aldehydes 1 and by
using nBuLi as base in THF. The results are shown in
Table 2. The MCP aldehydes 1c–d and 1e–g having electron-
withdrawing or electron-donating group on the benzene
rings, gave the corresponding cyclopentene derivatives 2c–d
and 2e–g in 62–77% yields, respectively (Table 2, entries 2–
4 and 6–7). For MCP aldehyde 1b, bearing an electron-
withdrawing bromine atom at the para-position of the ben-
zene ring, the corresponding cyclopentene product 2b was
formed in 50% yield. In this case, the slightly lower yield
might be due to a Br–Li exchange, giving some unidentified
byproducts (Table 2, entry 1). We also examined alkyl group
substituted substrate 1h (R1 = C7H15) and found its reac-
tion with cinnamyltriphenylphosphonium bromide gave the
cyclopentene product 2h in 69% yield (Table 2, entry 8).
Moreover, it should also be noted that, using (Z)-2-benzyl-
idenecyclopropanecarbaldehyde (Z)-1a as the substrate, the
same product 2a as that derived from (E)-1a could be
formed in 62% yield under identical conditions, indicating
the broad substrate generality of this reaction (Table 2, en-
try 5).
Scheme 2. Tandem Horner–Wadsworth–Emmons olefination/Cope
rearrangement of MCP aldehyde 1b with dimethyl cinnamylphos-
phonate.
In addition, compound 2b could be easily transformed
into the synthetically more interesting aziridine derivative.
In the presence of 2-aminoisoindoline-1,3-dione and
PhI(OAc)2, 2b could react with the nitrene generated in situ,
to deliver the corresponding aziridine derivative 2bЈ in 38%
yield (Scheme 3).[7] The structure of 2bЈ was unambiguously
confirmed by X-ray single-crystal analysis[8] (CIF data are
presented in the Supporting Information). On the basis of
this structural analysis, the two substituents on the cyclo-
pentene ring were identified as adopting a trans arrange-
ment.
A control experiment was conducted to obtain the reac-
tion intermediate by treating MCP aldehyde 1b (1.0 equiv.)
with dimethyl cinnamylphosphonate (1.2 equiv.)[6] in the
presence of NaH (1.2 equiv.) in THF for 3 h at room tem-
perature (Scheme 2). We found that cyclopentene derivative
2b was obtained in 39% yield, however, the MCP alkenyl
intermediate could not be isolated, which further proved
Scheme 3. Azacyclopropanation of 2b.
On the basis of previous studies,[4,5] a plausible mecha-
that the Cope rearrangement of alkene-activated MCP took nism for the formation of 2 is outlined in Scheme 4. Ac-
place too fast to allow isolation of the intermediate at room cording to this scheme, the Wittig reaction of MCP alde-
temperature (Scheme 2).
hyde 1 with cinnamyltriphenylphosphonium bromide (or
Eur. J. Org. Chem. 2010, 6038–6042
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6039

X.-Y. Tang, Y. Wei, M. Shi
FULL PAPER
Scheme 4. A plausible reaction mechanism.
dimethyl cinnamylphosphonate) affords MCP alkenyl inter- products at 100 °C (Table 3, entries 5–7). It should also be
mediate A in the presence of a base, which undergoes a noted that the formation of 5c was greatly affected by the
Cope rearrangement via a chair-like transition state (TS) to addition of a radical inhibitor such as TEMPO (see the
give the corresponding cyclopentene product 2a. In the Supporting Information). Furthermore, the structure of 5c
chair-like transition state, the steric interaction between the was unambiguously determined by X-ray single-crystal
substituents is minimal.
analysis,[9] and its CIF data are presented in the Supporting
Having obtained good results in the tandem Wittig reac- Information.
tion/Cope rearrangement of methylenecyclopropyl alde-
Table 3. Rearrangement of MCP methylenemalonate diesters 3.
hydes 1 with cinnamyltriphenylphosphonium bromide, we
then investigated the ring-opening reactions of other MCP
derivatives, such as MCP alkenyl derivatives with two ester
groups. The Knoevenagel condensation of MCP aldehyde
with methylmalonate afforded MCP methylenemalonate di-
methyl ester 3a, which could be isolated by column
chromatography on silica gel and was stable at room tem-
perature (20 °C). Heating 3a at 100 °C for 20 min led to
the formation of two products, which were identified as the
normal cyclopentene product 4a (33% yield), generated
through the Cope rearrangement, and a second cyclopen-
tene product 5a (36% yield), which was formed as a pair of
E and Z isomers (Table 3, entry 1). When R2 was changed
to a benzyl group (Bn) or a p-bromobenzyl (pBrBn) group,
both 4 and 5 were also formed in good total yields with the
latter being formed as the major products (Table 3, entries
2 and 3). Similarly, using (Z)-dimethyl 2-[(2-benzylidenecy-
[a] Isolated yield. [b] The reaction time was reduced to 5 min. [c]
No product was obtained, probably due to its instability.
A plausible mechanism for the formation of 4 and 5 is
clopropyl)methylene]malonate [(Z)-3a] as substrate, the outlined in Scheme 5. Cyclopentenes 4 are formed through
same products 4a and 5a were obtained in 30 and 35% the Cope rearrangement of 3 in a manner similar to that of
1
yields, respectively (Table 3, entry 4). On the basis of H intermediate A shown in Scheme 4. Alternatively, substrate
NMR spectroscopic data, the ratios of E and Z isomers 3 can also generate a biradical species C through intermedi-
of products 5 were determined to be almost 1:1 (see the ate B upon heating,[10] followed by a recombination of the
Supporting Information for details). In the case of MCPs two radicals to give cyclopentene 5 as a mixture of E and
3d–f, which were derived from the Knoevenagel condensa- Z isomers. In this case, the biradical species C is stabilized
tion of MCP aldehydes with Meldrum’s acid (2,2-dimethyl- by the diester and allyl groups, leading to the product 5
1,3-dioxane-4,6-dione), these reactions proceeded rapidly to as a major product. Other MCP alkenyl substrates cannot
give the corresponding cyclopentene products 4d–f in 32– provide such strong stabilization of the biradical species as
49% yield within 5 min without formation of products 5, occurs in 3, resulting in Cope rearrangement exclusively to
probably due to the instability of the latter cyclopentene give cyclopentene 4 as the product.
Scheme 5. A plausible reaction mechanism.
6040
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 6038–6042

Formation and Ring-Opening of Methylenecyclopropanes
(51.3), 154 (46.3), 153 (43.5), 152 (34.9), 115 (36.7), 91 (46.2).
HRMS (EI): calcd. for C20H18 [M]+ 258.1409; found 258.1398.
Compound 2bЈ: Yellow solid (38 mg, 38%); m.p. 165–167 °C. 1H
In conclusion, we have explored a tandem Wittig reac-
tion/Cope rearrangement of methylenecyclopropyl alde-
hydes 1 with cinnamyltriphenylphosphonium bromide at
room temperature in the presence of base, affording an ef- NMR (CDCl3, 300 MHz, TMS): δ = 3.12–3.13 (m, 1 H), 3.63 (d,
J = 6.0 Hz, 1 H), 3.96–3.99 (m, 1 H), 5.10–5.11 (m, 1 H), 6.09–
6.12 (m, 1 H), 6.33–6.44 (m, 1 H), 6.29–6.38 (m, 2 H), 7.15 (d, J
= 8.0 Hz, 2 H, ArH), 7.18–7.26 (m, 4 H, ArH), 7.39–7.42 (m, 2 H,
ArH), 7.56–7.63 (m, 5 H, ArH) ppm. 13C NMR (CDCl3, 100 MHz,
TMS): δ = 48.2, 50.2, 51.0, 57.8, 122.8, 128.1, 128.5, 128.6, 128.9,
129.4, 129.9, 131.2, 131.5, 133.9, 135.6, 136.2, 144.0, 157.0 ppm.
ficient synthetic protocol for the preparation of function-
alized cyclopentene derivatives in moderate yields. More-
over, two kinds of cyclopentene products were obtained
simultaneously using MCP methylenemalonate diesters 3 as
substrates. In addition, the rearrangement of substrates 3d–
f, which were derived from the Knoevenagel condensation
of MCP aldehydes with Meldrum’s acid, gave 4 in moderate
yields. Potential uses and an extension of the scope of the
methodology are under investigation.
IR (CH Cl ): ν = 3059, 3025, 3000, 2954, 2920, 2876, 1712, 1631,
˜
2
2
1600, 1577, 1502, 1449, 1361, 1220 cm–1. MS (EI): m/z (%) = 496
(1.4) [M]+, 264 (74.5), 263 (100.0), 165 (26.3), 154 (33.9), 153 (27.1),
116 (35.7), 104 (27.2). HRMS (EI): calcd. for C28H21N2O2Br [M]+
496.0786; found 496.0789.
Compound 4a: Yellow oil (23 mg, 33%). 1H NMR (CDCl3,
400 MHz, TMS): δ = 3.10 (s, 3 H, CH3), 3.78 (s, 3 H, CH3), 4.78
(s, 1 H, CH), 4.92 (t, J = 2.0 Hz, 1 H, CH), 5.20 (d, J = 2.0 Hz, 1
H, CH), 6.16 (dd, J = 5.6, 2.0 Hz, 1 H, CH), 6.56 (d, J = 5.6 Hz,
1 H, CH), 7.18–7.27 (m, 5 H, ArH) ppm. 13C NMR (CDCl3,
100 MHz, TMS): δ = 51.9, 53.1, 53.4, 72.6, 109.3, 127.1, 127.9,
Experimental Section
General Procedure for the Tandem Wittig Reaction/Cope Rearrange-
ment of Methylenecyclopropyl Aldehydes 1 with Cinnamyltriphenyl-
phosphonium Bromide: Cinnamyltriphenylphosphonium bromide
(0.6 mmol) and freshly distilled THF (5.0 mL) were added into a
Schlenk tube. After cooling to 0 °C, nBuLi (1.6  in hexane,
0.6 mmol) was added dropwise and the reaction was stirred for an
additional 1 h at 0 °C. After the addition was complete, MCP alde-
hyde 1 (0.5 mmol) in THF (1.0 mL) was added dropwise. The reac-
tion mixture was stirred for 3 h and then the solution was slowly
warmed to room temp. The solvent was removed under reduced
pressure and the residue was purified by a flash column chromatog-
raphy to give cyclopentene products 2.
129.6, 133.5, 137.9, 140.0, 154.3, 169.1, 170.2 ppm. IR (CH Cl ): ν
˜
2
2
= 3085, 3062, 3031, 3002, 2952, 1737, 1637, 1494, 1454, 1434, 1249,
1208 cm–1. MS (EI): m/z (%) = 272 (20.3) [M]+, 213 (22.5), 212
(68.5), 181 (26.2), 180 (19.5), 154 (30.6), 153 (100.0), 152 (50.4).
HRMS (EI): calcd. for C16H16O4 [M]+ 272.1049; found 272.1048.
Compound 5a: Pair of diastereoisomers, syn:anti = 1:1. Yellow oil
1
(26 mg, 36%). H NMR (CDCl3, 400 MHz, TMS): δ = 3.32 (d, J
= 2.4 Hz, 1 H), 3.48 (d, J = 2.4 Hz, 1 H), 3.76 (s, 3 H, CH3), 3.77
(s, 3 H, CH3), 6.17 (dd, J = 5.6, 0.8 Hz, 0.5 H), 6.30 (dd, J = 5.6,
0.8 Hz, 0.5 H), 6.37 (br. s, 0.5 H), 6.44–6.47 (m, 1 H, CH), 6.89
(dd, J = 5.6, 0.8 Hz, 0.5 H), 7.20–7.39 (m, 5 H, ArH) ppm. 13C
NMR (CDCl3, 100 MHz, TMS): δ = 36.8, 38.6, 52.9, 53.0, 64.5,
66.7, 121.5, 123.2, 126.6, 126.8, 128.1, 128.2, 128.3, 128.5, 132.6,
133.6, 136.6, 137.3, 137.8, 139.5, 142.8, 143.7, 170.7, 170.8 ppm.
General Procedure for the Tandem Horner–Wadsworth–Emmons
Olefination/Cope Rearrangement of MCP Aldehydes 1 with Di-
methyl Cinnamylphosphonate: NaH (0.48 mmol) and freshly dis-
tilled THF (2.0 mL) were added into a Schlenk tube and then di-
methyl cinnamylphosphonate (0.4 mmol) in THF (1.0 mL) was
added dropwise at room temp. The reaction mixture was heated to
reflux for approximately 10 min, then cooled to room temp. MCP
aldehyde 1 in THF (1.0 mL) was added and the reaction mixture
was stirred at room temp. for 3 h. The solvent was removed under
reduced pressure and the residue was purified by flash column
chromatography.
IR (CH Cl ): ν = 3088, 3062, 3024, 2954, 2843, 1738, 1638, 1597,
˜
2
2
1494, 1434, 1257, 1197, 1167 cm–1. MS (EI): m/z (%) = 272 (21.5)
[M]+, 213 (30.8), 212 (34.7), 181 (15.1), 154 (24.9), 153 (100.0), 152
(14.6), 121 (33.6). HRMS (EI): calcd. for C16H16O4 [M]+ 272.1049;
found 272.1050.
Supporting Information (see also the footnote on the first page of
this article): Spectroscopic data of all the new compounds and de-
tailed descriptions of experimental procedures as well as X-ray
crystal data of 2bЈ and 5c.
General Procedure for the Preparation of 2bЈ: To a Schlenk tube
was added 2b (0.2 mmol), CH2Cl2 (4.0 mL), phthalhydrazide
(0.3 mmol), and iodosobenzene diacetate (0.3 mmol). The reaction
mixture was stirred at 0 °C for 2 h, then the solvent was removed
under reduced pressure and the residue was purified by flash col-
umn chromatography.
Acknowledgments
We thank the Shanghai Municipal Committee of Science and Tech-
nology (08dj1400100–2), the National Basic Research Program of
China (973)-2009CB825300, and the National Natural Science
Foundation of China for financial support (20472096, 20872162,
20672127, 20821002, and 20732008).
General Procedure for the Rearrangement of MCP Methylenemalon-
ate Diesters 3: To a Schlenk tube was added 3 (0.2 mmol) and tolu-
ene (2.0 mL), then the reaction mixture was stirred at 100 °C for
20 min. The solvent was removed under reduced pressure and the
residue was purified by flash column chromatography.
Compound 2a: Yellow oil (99 mg, 77%). 1H NMR (CDCl3,
400 MHz, TMS): δ = 3.60–3.62 (m, 1 H), 3.63–3.65 (m, 1 H), 4.57
(s, 1 H), 5.02 (d, J = 2.4 Hz, 1 H), 6.07–6.09 (m, 1 H), 6.21 (dd, J
= 16.0, 7.6 Hz, 1 H, CH), 6.31–6.38 (m, 2 H), 7.20–7.25 (m, 4 H,
ArH), 7.28–7.35 (m, 6 H, ArH) ppm. 13C NMR (CDCl3, 100 MHz,
TMS): δ = 55.8, 59.2, 105.9, 126.2, 126.3, 127.2, 128.1, 128.4, 128.5,
[1] For selected reviews on MCPs, see: a) M. Lautens, W. Klute,
W. Ta m , Chem. Rev. 1996, 96, 49–92; b) A. de Meijere, S. I.
Kozhushkov, A. F. Khlebnikov, Top. Curr. Chem. 2000, 207,
89–147; c) P. Binger, P. Wedemann, S. I. Kozhushkov, A.
de Meijere, Eur. J. Org. Chem. 1998, 113–119; d) A. de Meijere,
S. I. A. Kozhushkov, Eur. J. Org. Chem. 2000, 3809–3822; e) I.
Nakamura, Y. Yamamoto, Adv. Synth. Catal. 2002, 344, 111–
129; f) A. Brandi, S. Cicchi, F. M. Cordero, A. Goti, Chem.
Rev. 2003, 103, 1213–1270; g) E. Nakamura, S. Yamago, Acc.
129.8, 131.8, 134.3, 137.3, 139.1, 144.3, 157.5 ppm. IR (CH Cl ): ν
˜
2
2
= 3059, 3027, 3000, 2923, 1712, 1600, 1494, 1452, 1361, 1221,
1178 cm–1. MS (EI): m/z (%) = 258 (100.0) [M]+, 167 (93.8), 165
Eur. J. Org. Chem. 2010, 6038–6042
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6041

X.-Y. Tang, Y. Wei, M. Shi
FULL PAPER
Chem. Res. 2002, 35, 867–877; h) L.-X. Shao, M. Shi, Curr.
Org. Chem. 2007, 11, 1135–1137; i) M. Rubin, M. Rubina, V.
Gevorgyan, Chem. Rev. 2007, 107, 3117–3179; j) S. Yamago, E.
Nakamura, Org. React. 2002, 61, 1–217; k) A. de Meijere, S. I.
Kozhushkov, T. Spath, M. von Seebach, S. Lohr, H. Nuske, T.
Pohomann, M. Es-Sayed, S. Brase, Pure Appl. Chem. 2000, 72,
1745–1756; l) X. Greary, Acc. Chem. Res. 2006, 39, 761–771;
m) A. de Meijere, P. von Zezschwitz, S. Brse, Acc. Chem. Res.
2005, 38, 413–422; n) A. de Meijere, S. I. Kozhushkov, D.
Faber, V. Bagutskii, R. Boese, T. Haumann, R. Walsh, Eur. J.
Org. Chem. 2001, 3607–3614.
[3]
To the best of our knowledge, thermally induced rearrange-
ment of MCPs are rare, and high temperature is usually re-
quired. However, vinylcyclopropane has been investigated ex-
tensively and there are a few examples, see: a) K. N. Houk, M.
Nendel, O. Wiest, J. W. Storer, J. Am. Chem. Soc. 1997, 119,
10545–10546; b) J. E. Baldwin, S. Bonacorsi, J. Am. Chem. Soc.
1996, 118, 8258–8265; c) J. J. Gajewski, Hydrocarbons Thermal
Isomerizations; Academic: New York, 1980, pp. 81–87.
X.-Y. Tang, M. Shi, J. Org. Chem. 2009, 74, 5983–5986.
X.-Y. Tang, M. Shi, J. Org. Chem. 2010, 75, 902–905.
For the preparation of dimethyl cinnamylphosphonate, see: A.
Virginie, L. Hind, R. Sylvie, R. Gerard, Tetrahedron 2007, 63,
10059–10066.
[4]
[5]
[6]
[2] For selected examples on the reactions of MCPs, see: a) B. Hu,
S. Y. Xing, Z. W. Wang, Org. Lett. 2008, 10, 5481–5484; b) M.
Shi, L.-P. Liu, J. Tang, Org. Lett. 2006, 8, 4043–4046; c) M.
Shi, B. Xu, J.-W. Huang, Org. Lett. 2004, 6, 1175–1178; d) X.
Huang, Y. Yang, Org. Lett. 2007, 9, 1667–1670; e) M. Lautens,
W. Han, J. H. Liu, J. Am. Chem. Soc. 2003, 125, 4028–4029; f)
M. Lautens, Y. Ren, J. Am. Chem. Soc. 1996, 118, 10668–
10669; g) L. Yu, J. D. Meng, L. Xia, R. Guo, J. Org. Chem.
2009, 74, 5087–5089; h) S. Ma, J. Zhang, Angew. Chem. 2003,
115, 193–197; Angew. Chem. Int. Ed. 2003, 42, 183–187; i) S.
Ma, L. Lu, J. Zhang, J. Am. Chem. Soc. 2004, 126, 9645–9660;
j) L. Lu, G. Chen, S. Ma, Org. Lett. 2006, 8, 835–838; k) M. E.
Scott, M. Lautens, J. Org. Chem. 2008, 73, 8154–8162; l) C.
Taillier, M. Lautens, Org. Lett. 2007, 9, 591–593; m) E. Smo-
lensky, M. Kapon, M. S. Eisen, Organometallics 2007, 26,
4510–4527; n) V. V. Diev, T. Q. Tung, A. P. Molchanov, Eur. J.
Org. Chem. 2009, 525–530; o) B. Hu, J. L. Zhu, S. Y. Xing, J.
Fang, D. Du, Z. W. Wang, Chem. Eur. J. 2009, 15, 324–327; p)
V. Bagutski, A. de Meijere, Adv. Synth. Catal. 2007, 349, 1247–
1255; q) X.-C. Hang, Q.-Y. Chen, J.-C. Xiao, Eur. J. Org. Chem.
2008, 1101–1106; r) I. Nakamura, B. H. Oh, S. Saito, Y. Yama-
moto, Angew. Chem. 2001, 113, 1338–1340; Angew. Chem. Int.
Ed. 2001, 40, 1298–1300; s) T. Kurahashi, A. de Meijere, An-
gew. Chem. Int. Ed. 2005, 44, 7881–7884; t) X. Huang, H.
Zhou, Org. Lett. 2002, 4, 4419–4422; u) M. Gulias, J. Durán,
F. López, L. Castedo, J. L. Mascareñas, J. Am. Chem. Soc.
2007, 129, 11026–11027; v) T. Matsuda, T. Tsuboi, M. Murak-
ami, J. Am. Chem. Soc. 2007, 129, 11596–11597; w) M. Shirak-
ura, M. Suginome, J. Am. Chem. Soc. 2009, 131, 5060–5061;
x) N. Hayashi, Y. Hirokawa, I. Shibata, M. Yasuda, A. Baba,
J. Am. Chem. Soc. 2008, 130, 2912–2913; y) S. Xing, W. Pan,
C. Liu, J. Ren, Z. Wang, Angew. Chem. 2010, 122, 3283–3286;
Angew. Chem. Int. Ed. 2010, 49, 3215–3218; z) M. Jiang, L.-P.
Liu, M. Shi, Y. Li, Org. Lett. 2010, 12, 116–119.
[7] Following the same procedure reported previously, see: Yu. Y.
Liang, L. Jiao, Y. Wang, Y. Chen, L. Ma, J. Xu, S. Zhang, Z.-
X. Yu, Org. Lett. 2006, 8, 5877–5879.
[8] The X-ray crystal data of 2bЈ: CCDC-753354 contains the sup-
plementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Empirical formula: C28H21BrN2O2; formula weight: 497.38,
crystal size: 0.395ϫ0.366ϫ0.237 mm, crystal color: colorless,
habit: prismatic, crystal system: triclinic, lattice type: primitive,
lattice parameters: a = 10.460(2) Å, b = 11.346(2) Å, c =
12.007(2) Å, α = 107.158(4)°, β = 97.017(4)°, γ = 115.095(3)°;
3
¯
V = 1181.6(4) Å , space group: P1; Z = 2; Dcalc = 1.398 g/
cm3, F(000) = 508, R1 = 0.0525, wR2 = 0.1222, diffractometer:
Rigaku AFC7R.
[9] The X-ray crystal data of 5c: CCDC-738021 contains the sup-
plementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Empirical formula: C28H21Br3O4, formula weight: 661.18, crys-
tal size: 0.388ϫ0.321ϫ0.169 mm, crystal color: colorless,
habit: prismatic, crystal system: monoclinic, lattice type: primi-
tive, lattice parameters: a = 11.9629(14) Å, b = 6.0979(7) Å, c
= 35.689(4) Å, α = 90°, β = 92.149(2)°, γ = 90°; V =
2601.6(5) Å3, space group: P21/n, Z = 4, Dcalc = 1.688 g/cm3,
F(000) = 1304, R1 = 0.0520, wR2 = 0.1156, diffractometer:
Rigaku AFC7R.
[10] a) H. M. Frey, Adv. Phys. Org. Chem. 1966, 4, 147; b) H. M.
Frey, R. Walsh, Chem. Rev. 1969, 69, 103–124.
Received: June 18, 2010
Published Online: September 13, 2010
6042
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 6038–6042