Lewis acid-catalyzed cascade reactions of arylmethylenecyclopropanes with 1,1,3-triarylprop-2-yn-1-ols or their methyl ethers

Article abstract of DOI:10.1021/ol7022592

(Chemical Equation Presented) Arylmethylenecyclopropanes 1 can react with 3-methoxy-1,3,3-triarylprop-1-yne 2 or 1,1,3-triarylprop-2-yn-1-ol 2-OH to give the corresponding functionalized methylenecyclobutene, cyclobutane, and cyclopropane derivatives in t

Full text of DOI:10.1021/ol7022592

ORGANIC
LETTERS
2007
Vol. 9, No. 25
5187-5190
Lewis Acid-Catalyzed Cascade
Reactions of
Arylmethylenecyclopropanes with
1,1,3-Triarylprop-2-yn-1-ols or Their
Methyl Ethers
Liang-Feng Yao† and Min Shi*,†,‡
School of Chemistry & Molecular Engineering, East China UniVersity of Science and
Technology, 130 Mei Long Lu, Shanghai 200237, China, and State Key Laboratory of
Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy
of Sciences, 354 Fenglin Road, Shanghai, China, 200032
mshi@mail.sioc.ac.cn
Received September 14, 2007
ABSTRACT
Arylmethylenecyclopropanes 1 can react with 3-methoxy-1,3,3-triarylprop-1-yne 2 or 1,1,3-triarylprop-2-yn-1-ol 2-OH to give the corresponding
functionalized methylenecyclobutene, cyclobutane, and cyclopropane derivatives in the presence of Lewis acid BF3 OEt2 under mild conditions.
A plausible Meyer Schuster rearrangement mechanism has been proposed.
‚
−
Methylenecyclopropanes (MCPs) are highly strained but
readily accessible molecules that serve as useful building
blocks in organic synthesis.1 MCPs undergo a variety of ring-
opening/cycloaddition reactions in the presence of transition
metals or Lewis acids because the relief of ring strain can
provide a powerful thermodynamic driving force.2,3 Thus far,
a number of interesting cycloadditions and ring enlargements
of MCPs have been explored. For example, Yamamoto et
al. reported cycloaddition reactions of MCPs with aldehydes
and imines, using a palladium catalyst, that afforded the
corresponding tetrahydrofuran and pyrrolidine skeletons in
good yields.4 In addition, we and others have developed a
number of heterocycle-forming reactions from MCPs and
(2) Selected recent articles about transition metal-catalyzed reactions of
MCPs: (a) Camacho, D. H.; Nakamura, I.; Saito, S.; Yamamoto, Y. J. Org.
Chem. 2001, 66, 270. (b) Lautens, M.; Meyer, C.; Lorenz, A. J. Am. Chem.
Soc. 1996, 118, 10676. (c) Lautens, M.; Ren, Y. J. Am. Chem. Soc. 1996,
118, 9597. (d) Saito, S.; Masuda, M.; Komagawa, S. J. Am. Chem. Soc.
2004, 126, 10540. (e) Shi, M.; Wang, B.-Y.; Huang, J.-W. J. Org. Chem.
2005, 70, 5606. (f) Nakamura, I.; Itagaki, H.; Yamamoto, Y. J. Org. Chem.
1998, 63, 6458. (g) Tsukada, N.; Hibuya, A.; Nakamura, I.; Yamamoto, Y.
J. Am. Chem. Soc. 1997, 119, 8123. (h) Suginome, M.; Matsuda, T.; Ito,
Y. J. Am. Chem. Soc. 2000, 122, 11015. (i) Scott, M. E.; Bethuel, Y.;
Lautens, M. J. Am. Chem. Soc. 2007, 129, 1482.
† East China University of Science and Technology.
‡ Chinese Academy of Sciences.
(1) For recent reviews, see: (a) Nakamura, I.; Yamamoto, Y. AdV. Synth.
Catal. 2002, 344, 111. (b) Brandi, A.; Cicchi, S.; Cordero, F. M.; Goti, A.
Chem. ReV. 2003, 103, 1213. (c) Nakamura, E.; Yamago, S. Acc. Chem.
Res. 2002, 35, 867. For the synthesis of MCPs, see: Brandi, A.; Goti, A.
Chem. ReV. 1998, 98, 598.
(3) Selected recent articles about Lewis acid-mediated reactions of
MCPs: (a) Shi, M.; Xu, B. Org. Lett. 2002, 4, 2145. (b) Xu, B.; Shi, M.
Org. Lett. 2003, 5, 1415. (c) Huang, X.; Zhou, H.-W. Org. Lett. 2002, 4,
4419. (d) Huang, J.-W.; Shi, M. Tetrahedron Lett. 2003, 44, 9343 and
references cited therein.
10.1021/ol7022592 CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/08/2007

aldehydes or imines as well as ring enlargements of MCPs
in the presence of Lewis or Brønsted acids.5,6 Herein, we
wish to report an interesting Lewis acid-catalyzed cascade
reaction of MCPs 1 with 3-methoxy-1,3,3-triarylprop-1-yne
2 or 1,1,3-triarylprop-2-yn-1-ol 2-OH to produce function-
alized methylenecyclobutene, cyclobutane, and cyclopropane
derivatives 3, 4, and 5 in moderate to good yields under mild
conditions.
Initial examinations with diphenylmethylenecyclopropane
(1a, 0.2 mmol) and 3-methoxy-1,3,3-triphenylprop-1-yne (2a,
0.2 mmol) as the substrates in the presence of various Lewis
acids (10 mol %) in 1,2-dichloroethane (DCE) were aimed
at determining the best catalyst for this intermolecular
reaction and the results of these experiments are summarized
in Table 1. We found that when using Bi(OTf)3 and Sn-
a Brønsted acid, trace of 3a was produced (Table 1, entry
1). However, in the presence of BF3‚OEt2 under identical
conditions, 3a was produced in 34% yield within 6 h (Table
1, entry 6). Increasing the employed amounts of BF3‚OEt2
or raising the reaction temperature did not improve the yields
of 3a under identical conditions (Table 1, entries 7-11).
Next, we attempted to improve the yield of 3a by adjusting
the ratios of 1a and 2a as well as by prolonging the reaction
time. The results are shown in Table 2. As can be seen from
Table 2. Further Optimization of the Reaction Conditions
Table 1. Optimization of the Reaction Conditions
entry
x
y
solvent
time (h)
yield of 3a (%)a
1
2
1
1
1
1
1
1
1
1
1
1
1.5
2
DCE
6
8
54
DCE
65
3
2.5
3
DCE
10
10
10
12
12
24
24
24
41
4
DCE
52
5
2
DCE
58
6
2
Toulene
MeCN
THF
trace
complex
NR
7
2
entrya
Lewis acid
temp (°C)
time (h)
yield of 3a (%)b
8
2
9
2
pentane
EtOH
trace
NR
1
2
TfOH
rt
rt
rt
rt
rt
rt
rt
rt
rt
40
60
12
8
trace
18
10
2
Bi(OTf)3
Sc(OTf)3
Yb(OTf)3
Sn(OTf)2
BF3‚OEt2
BF3‚OEt2
BF3‚OEt2
BF3‚OEt2
BF3‚OEt2
BF3‚OEt2
3
8
complex
NR
13
a Isolated yields.
4
24
12
6
5
6
34
7
6
32c
33d
13e
Table 2, when 1a (1.0 equiv) and 2a (1.5 equiv) were used,
3a was produced in 54% yield within 6 h and when 1a (1.0
equiv) and 2a (2.0 equiv) were used, 3a was produced in
65% yield after 8 h (Table 2, entries 1 and 2). The use of an
excess amount of 2a facilitates this reaction because 2a itself
can rearrange to an allenic product in the presence of Lewis
acid. Further increasing the amount of 2a and prolonging
the reaction time did not improve the yield of 3a (Table 2,
entries 3 and 4). Solvent effects have been examined with
BF3‚OEt2 (10 mol %) at room temperature in dichlo-
romethane (DCM), toluene, acetonitrile, THF, pentane, and
ethanol. In THF or ethanol, no reaction occurred (Table 2,
entries 8 and 10). In toluene and pentane, a trace of 3a was
formed, and in MeCN, complex product mixtures were
obtained (Table 2, entries 6, 7, and 9). We found that DCM
is also the solvent of choice to give 3a in 58% yield under
otherwise identical conditions (Table 2, entry 5). Therefore,
the optimized reaction conditions are to carry out the reaction
in DCE or DCM at room temperature with 1a (1.0 equiv)
and 2a (2.0 equiv) in the presence of BF3‚OEt2 (10 mol %)
for 8 h.
8
6
9
6
10
11
6
34
33
6
a All reactions were carried out with 1a (0.2 mmol), 2a (0.2 mmol), and
Lewis acid (10 mol %) in various solvents (2.0 mL). b Isolated yields.
c BF3‚OEt2 (20 mol %) was used. d BF3‚OEt2 (100 mol %) was used.
(OTf)2 (10 mol %) as Lewis acids, an interesting functonal-
ized methylenecyclobutene derivative 3a was formed in 18%
and 13% yields at room temperature, respectively, although
no reaction occurred, or complex product mixtures were
obtained with use of Yb(OTf)3 or Sc(OTf)3 (10 mol %) as a
Lewis acid (Table 1, entries 2-5). In the presence of TfOH,
(4) (a) Camacho, D. H.; Nakamura, I.; Saito, S.; Yamamoto, Y. Angew.
Chem., Int. Ed. 1999, 38, 3365-3367. (b) Nakamura, I.; Oh, B. H.; Saito,
S.; Yamamoto, Y. Angew. Chem., Int. Ed. 2001, 40, 1298. (c) Oh, B. H.;
Nakamura, I.; Saito, S.; Yamamoto, Y. Tetrahedron Lett. 2001, 42, 6203.
(d) Oh, B. H.; Nakamura, I.; Saito, S.; Yamamoto, Y. Heterocycles 2003,
61, 247. (e) Brase, S.; de Meijere, A. Angew. Chem., Int. Ed. Engl. 1995,
34, 2545. (f) Nakamura, I.; Nemoto, T.; Yamamoto, Y.; de Meijere, A.
Angew. Chem., Int. Ed. 2006, 45, 5176.
(5) (a) Shi, M.; Xu, B.; Huang, J.-W. Org. Lett. 2004, 6, 1175. (b) Shi,
M.; Shao, L.-X.; Xu, B. Org. Lett. 2003, 5, 579. (c) Shao, L.-X.; Xu, B.;
Huang, J.-W.; Shi, M. Chem. Eur. J. 2006, 12, 510. (d) Huang, J.-W.; Shi,
M. Synlett 2004, 2343. (e) Patient, L.; Berry, M. B.; Kilburn, J. D.
Tetrahedron Lett. 2003, 44, 1015.
(6) (a) Ma, S.-M.; Zhang, J.-L. J. Am. Chem. Soc. 2003, 125, 12386. (b)
Lautens, M.; Han, W. J. Am. Chem. Soc. 2002, 124, 6312. (c) Lautens, M.;
Han, W.; Liu, J. H.-C. J. Am. Chem. Soc. 2003, 125, 4028. (d) Scott, M.
E.; Han, W.; Lautens, M. Org. Lett. 2004, 6, 3309. (e) Scott, M. E.; Lautens,
M. Org. Lett. 2005, 7, 3045. Ring enlargement of MCPs: (f) Shi, M.; Liu.
L. P.; Tang, J. J. Am. Chem. Soc. 2006, 128, 7430. (g) Furstner, A.; Aissa,
C. J. Am. Chem. Soc. 2006, 128, 6306.
Under these optimal reaction conditions, we next carried
out this methylenecyclobutene-forming reaction using a
variety of starting materials 1 and 3-methoxy-1,3,3-triaryl-
prop-1-ynes 2. The results are summarized in Table 3. As
can be seen from Table 3, the corresponding methylenecy-
clobutene derivatives 3 were obtained in 40-65% yields
(Table 3, entries 1-8). Substituents on the aromatic rings
of 1 and 2 have little influence on the reaction. By using
5188
Org. Lett., Vol. 9, No. 25, 2007

Scheme 1. Proposed Mechanism for the Formation of 3
Table 3. Construction of Methylenecyclobutenes from 1 and 2
entry
1
R1/R2
R3/R4
R5 yield of 3 (%)a
p-ClC6H4/
C6H5, 1b
2a
2a
2a
2a
Me
Me
Me
Me
Me
Me
Me
Me
3b, 55
3c, 56
3d, 54
3e, 59
3f, 65b
3g, 40c
3h, 63
3i, 54d
2
3
4
5
6
7
8
p-MeC6H4/
p-MeC6H4, 1c
p-ClC6H4/
p-ClC6H4, 1d
p-FC6H4/
Interestingly, as for monoaromatic group substituted MCP
1f, an allenic group attached cyclobutane derivative 4a, which
was unambiguously determined by X-ray diffraction (Figure
2),10 was formed in 40% yield at room temperature (20 °C)
p-FC6H4, 1e
1a
p-MeOC6H4/
p-MeOC6H4, 2b
p-FC6H4/
1a
1a
1a
p-FC6H4, 2c
p-MeC6H4/
p-MeC6H4, 2d
p-MeC6H4/
C6H5, 2e
9
10
11
1a
1a
1a
2a-OH
H
H
H
3j, 36
3k, 30
3l, 50
2c-OH
2d-OH
a Isolated yields. b 15% of 1a was recovered. c 10% of 1a was recovered.
d 10% of 1a was recovered and mixtures of cis- and trans-isomer (1:1) were
obtained.
1,1,3-triarylprop-2-yn-1-ols 2a-OH, 2c-OH, and 2d-OH, in
which R5 ) H, as the substrates, the corresponding methyl-
enecyclobutene derivatives 3j, 3k, and 3l (R5 ) H) were
obtained in 30-50% yields (Table 2, entries 9-11). Product
Figure 2. ORTEP drawing of 4a.
1
structures of 3a-l were determined by H and 13C NMR
spectroscopic data, HRMS, microanalysis. Furthermore, the
X-ray crystal structure of 3a was determined and its CIF
data are presented in the Supporting Information (Figure 1).7
(Table 4, entry 1). For monoaromatic group substituted MCPs
1g-j, similar results were obtained for other 3-methoxy-
1,3,3-triarylprop-1-ynes 2 or 1,1,3-triaryl-prop-2-yn-1-ols
2-OH under identical conditions (Table 4, entries 2-7). As
for aliphatic MCP 1k, a similar adduct 4h was obtained in
52% yield (Table 4, entry 8).
In addition, under the standard conditions at -20 °C, the
corresponding cyclopropane derivatives 5 bearing an allenic
moiety were formed in 30-55% yields for MCPs 1f-h and
1l, indicating the formation of cationic intermediate B shown
in Scheme 1 (Table 5).
On the basis of the above results, a plausible reaction
mechanism for the formation of 4 and 5 is outlined in Scheme
(7) The crystal data of 3a have been deposited in the CCDC with number
644870. Empirical formula, C38H32O; formula weight, 504.64; crystal color/
habit, colorless/prismatic; crystal system, triclinic; lattice type, primitive;
lattice parameters, a ) 10.9684(13) Å, b ) 11.1701(14) Å, c ) 12.9433-
(15) Å, R ) 87.150(2)°, â ) 67.964(2)°, γ ) 81.135(2)°, V ) 1452.3(3)
Å3; space group, P1h; Z ) 2; Dcalc ) 1.154 g/cm3; F000 ) 536; diffractometer,
Rigaku AFC7R; residuals R/Rw, 0.0524/0.1271.
Figure 1. ORTEP drawing of 3a.
(8) Swaminathan, S.; Narayanan, K. V. Chem. ReV. 1971, 71, 429.
(9) For a review of cyclopropylmethyl cations, see: Richey, H. G., Jr.
In Carbonium Ions; Olah, G. A., Schleyer, P. v. R., Eds.; Wiley-
Interscience: New York, 1972; Vol. III, Chapter 25.
(10) The crystal data of 4a have been deposited in the CCDC with
number 650905. Empirical formula, C39H34O2; formula weight, 534.66;
crystal color/habit, colorless/prismatic; crystal system, monoclinic; lattice
type, primitive; lattice parameters, a ) 11.9815(12) Å, b ) 28.144(3) Å, c
) 9.7933(10) Å, R ) 90°, â ) 111.828(2)°, γ ) 90°, V ) 3065.6(5) Å3;
space group, P2(1)/c; Z ) 4; Dcalc ) 1.158 g/cm3; F000 ) 1136;
diffractometer, Rigaku AFC7R; residuals R/Rw, 0.0520/0.1163.
A plausible reaction mechanism is outlined in Scheme 1.
In the presence of BF3‚OEt2, 2a produces cationic intermedi-
ate A via a Meyer-Schuster rearrangement,8 which reacts
with MCP 1 to afford intermediate B stabilized by two
aromatic rings and one cyclopropane group.9 Intramolecular
cyclization gives intermediate C, which undergoes nucleo-
philic attack by the counteranion to provide product 3.
Org. Lett., Vol. 9, No. 25, 2007
5189

Scheme 2. Plausible Mechanism for the Formation of 4 and 5
Table 4. Construction of Cyclobutane Derivatives from MCPs
1f-j and Aldehydes
a Ratio of 1:2 ) 1:2. b Isolated yields.
2. The addition of cationic intermediate A to monoaromatic
group substituted MCP 1 produces intermediate D, which
undergoes ring expansion to give intermediate E at higher
temperature (rt, 20 °C). The nucleophilic attack by the
counteranion provides product 4. On the other hand, at lower
In conclusion, we have found an interesting procedure
where diarylmethylenecyclopropanes and monoaromatic
group substituted methylenecyclopropanes react with 3-meth-
oxy-1,3,3-triarylprop-1-ynes or 1,1,3-triarylprop-2-yn-1-ols
to provide functionalized methylenecyclobutene derivatives
and cyclobutane or cyclopropane derivatives bearing an
allenic moiety catalyzed by Lewis acid under mild conditions.
A plausible reaction mechanism has been proposed that is
based on a Meyer-Schuster reaction pathway. With use of
this procedure, a series of novel functionalized methylenecy-
clobutene derivatives and cyclobutane or cyclopropane
derivatives were obtained selectively, with easily available
reagents under mild conditions, in moderate to good yields.
Further studies regarding the mechanistic details and scope
of this process are in progress.
Table 5. Formation of Cyclopropane Derivatives 5
entrya
R6
yield of 5 (%)b
1
2
3
4
o-BnOC6H4, 1f
5a, 55
5b, 40
5c, 35
5d, 30
o-MeOC6H4, 1g
o-TBDPSOC6H4, 1h
p-MeOC6H4, 1l
a Ratio of 1:2 ) 1:2. b Isolated yields.
Acknowledgment. We thank the Shanghai Municipal
Committee of Science and Technology (04JC14083 and
06XD14005), Chinese Academy of Sciences (KGCX2-210-
01), and the National Natural Science Foundation of China
for financial support (20472096, 203900502, 20672127, and
20732008).
temeparture (-20 °C), nucleophilic attack by the counter-
anion at intermediate D takes place to provide product 5
directly, presumably due to the higher reaction temperature
perhaps facilitating the ring-expansion process.
The difference in stability and steric bulkiness of cationic
intermediates B and D causes the different reaction pathway
between diarylmethylenecyclopropanes 1a-e and monoaro-
matic group substituted MCPs 1f-j. The intramolecular
rearrangement of intermediate D and the reaction of R- with
intermediate D can more easily take place, therefore exclu-
sively affording 4 and 5 in moderate to good yields,
respectively (Scheme 2).
Supporting Information Available: Spectroscopic data
of all the new compounds in Tables 1-5, the detailed
descriptions of experimental procedures, and X-ray data for
compounds 3a and 4a. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL7022592
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Org. Lett., Vol. 9, No. 25, 2007