Switchable reactions of cyclopropanes with enol silyl ethers. Controllable synthesis of cyclopentanes and 1,6-dicarbonyl compounds

Article abstract of DOI:10.1021/jo901340v

(Chemical Equation Presented) Cu(SbF₆)₂-catalyzed reaction of 2-substituted cyclopropane-1,1-dicarboxylates 1 with enol silyl ethers 2 can be readily controlled: the reaction undergoes a cycloaddition to provide substituted cyclopent

Full text of DOI:10.1021/jo901340v

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Switchable Reactions of Cyclopropanes with Enol Silyl Ethers.
Controllable Synthesis of Cyclopentanes and 1,6-Dicarbonyl Compounds
Jian-Ping Qu, Chao Deng, Jian Zhou, Xiu-Li Sun, and Yong Tang*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 345 Lingling Lu, Shanghai 200032
tangy@mail.sioc.ac.cn
Received June 24, 2009
Cu(SbF6)2-catalyzed reaction of 2-substituted cyclopropane-1,1-dicarboxylates 1 with enol silyl
ethers 2 can be readily controlled: the reaction undergoes a cycloaddition to provide substituted
cyclopentane derivatives 3 in excellent yields with high diastereoselectivities in the presence of
complex 8/Cu(II); however, the same substrates afford acyclic 1,6-dicarbonyl products 4 via a
cycloaddition-ring-opening reaction in up to 92% yield in the absence of ligand 8. The mechanism
1
for the ligand-switchable reactions was investigated by both control experiments and H NMR
studies. The substrate scope and limitation of the tunable transformation were also examined.
Introduction
stereochemistry of the cyclopropanation reaction of tellur-
onium allylides with R,β-unsaturated esters and amides,
providing a facile synthesis of two geometrical isomers
of multifunctionalized 3-vinylcyclopropane derivatives.2c
The control of reaction pathways for selective synthesis of
different products from the same starting materials1-9 has
attracted much attention since such research not only max-
imizes the diverse utility of reactants but also benefits the
understanding of reaction mechanism. In our previous stu-
dies on this subject, we reported that HMPA could switch the
(4) Selected examples of tuning the enantioselectivity with different
transition metals: (a) Nishibayashi, Y.; Segawa, K.; Takada, H.; Ohe, K.;
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Masumoto, S.; Yamasaki, S.; Hamashima, Y.; Kanai, M.; Du, W.; Curran,
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K. A. Chem.;Eur. J. 2002, 8, 1888. (e) Johannsen, M.; Jørgensen, K. A.
Tetrahedron 1996, 52, 7321. (f) Kanai, M.; Koga, K.; Tomioka, K. J. Chem.
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(6) Selected examples of tuning the enantioselectivity with different
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126, 5585. (d) Sibi, M. P.; Gorikunti, U.; Liu, M. Tetrahedron 2002, 58, 8357.
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(a) Busacca, C. A.; Grossbach, D.; So, R. C.; O’Brien, E. M.; Spinelli, E. M.
Org. Lett. 2003, 5, 595. (b) Busacca, C. A. J. Org. Chem. 2004, 69, 5187.
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Org. Chem. 2001, 5, 719. (b) Flanagan, S. P.; Guiry, P. J. J. Organomet.
Chem. 2006, 691, 2125.
(2) Examples of tuning diastereoselectivities in catalytic asymmetric
reactions: (a) Liao, W.-W.; Li, K.; Tang, Y. J. Am. Chem. Soc. 2003, 125,
13030. (b) Tang, Y.; Huang, Y.-Z.; Dai, L.-X.; Chi, Z.-F.; Shi, L.-P. J. Org.
Chem. 1996, 61, 5762. (c) Ye, S.; Yuan, L.; Huang, Z.-Z.; Tang, Y.; Dai, L.-X.
J. Org. Chem. 2000, 65, 6257. (d) Evans, D. A.; MacMillan, D. W. C.;
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ꢀ
(c) Hoarau, O.; Ait-Haddou, H.; Daran, J. C.; Cramailere, D.; Balavoine,
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ꢀ
(3) Reviews of tuning the enantioselectivity: (a) Reference 1a. (b) Zanoni,
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7684 J. Org. Chem. 2009, 74, 7684–7689
Published on Web 09/17/2009
DOI: 10.1021/jo901340v
r
2009 American Chemical Society

Qu et al.
JOCArticle
We also observed solvent-reversed enantioselectivity in
the Friedel-Crafts reaction of indole with arylidene malo-
nates catalyzed by trisoxazoline (TOX)-derived copper
complex5c and temperature-controlled diastereoselectivity
in the 1,3-dipolar cycloaddition of nitrones with arylidene
malonates.2k
Donor-acceptor cyclopropanes have been frequently
used in many synthetic transformations, owing to the unique
reactivity of the cyclopropane moiety.10-21 For example,
these cyclopropanes can undergo various cycloadditions,
such as the [3 þ 2] cycloadditions with aldehydes,11 aryl
isocyanides,12 cyanopyridine,13 diazene derivatives,14 imi-
nes15 and indoles,16 [3 þ 3] cycloadditions with nitrones17
and azomethine imines,18 and [4 þ 3] cycloadditions with
isobenzofurans.19 Among the cycloadditions developed, the
TABLE 1. Effects of Lewis Acidsa
entry
Lewis acid
convb (%)
3a/4ab
99/1
4/96
dr (3a)b
1
2
Yb(OTf)3 xH2O
53
>99
>99
>99
>99
91
82/18
3
Sc(OTf)3
In(OTf)3
Ga(OTf)3
Sn(OTf)2
Cu(OTf)2
Cu(SbF6)2
FeCl3
321
4
11/89
8/92
4/96
1/99
1/99
67/33
1/99
5
6
7
8
>99 (73c)
27
36
87/13
d
9
TiCl4
aReaction conditions: 1a (52.5 mg, 0.2 mmol), 2a (76.9 mg, 0.4 mmol),
Lewis acid (0.04 mmol), CH2Cl2 (1.0 mL), room temperature, 12 h.
bDetermined by 1H NMR. cIsolated yield. d-78 °C, 24 h. When the
reaction was performed at room temperature, the reaction was compli-
cated.
(8) Hydrogen-bond-directed reversal of enantioselectivity: Zeng, W.;
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J. Org. Chem. 2006, 71, 2524. (b) Lutz, F.; Igarashi, T.; Kawasaki, T.; Soai,
K. J. Am. Chem. Soc. 2005, 127, 12206. (c) Mao, J.; Wan, B.; Zhang, Z.;
Wang, R.; Wu, F.; Lu, S. J. Mol. Catal. A 2005, 225, 33. (d) Danjo, H.;
Higuchi, M.; Yada, M.; Imamoto, T. Tetrahedron Lett. 2004, 45, 603.
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Campos, K. R.; Connell, B. T.; Staples, R. J. J. Am. Chem. Soc. 1999, 121,
669. (g) Ashimori, A.; Overman, L. E. J. Org. Chem. 1992, 57, 4571.
(10) The first addition of enolates to cyclopropanes: (a) Bone, W. A.;
Perkin, W. H. J. Chem. Soc. 1895, 67, 108. For reviews, see: (b) Danishefsky,
S. Acc. Chem. Res. 1979, 12, 66. (c) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.;
Yip, Y.-C. Chem. Rev. 1989, 89, 165. (d) Reissig, H.-U.; Zimmer, R. Chem.
Rev. 2003, 103, 1151. (e) Yu, M.; Pagenkopf, B. L. Tetrahedron 2005, 61, 321.
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Rev. 2003, 103, 2597. (h) Paquette, L. A. Chem. Rev. 1986, 86, 733. (i) Reissig,
H. U. Top. Curr. Chem. 1988, 144, 73. (j) Rubin, M.; Rubina, M.; Gevorgyan,
V. Chem. Rev. 2007, 107, 3117.
reactions of cyclopropanes with enols are reported to afford
cyclopentane derivatives and/or 1,6-dicarbonyl compounds,
depending on substrates.21,22 Very recently, we found that
the product of cyclopropane-1,1-dicarboxylate with enol
silyl ether can be tuned very well by ligand providing
cyclopentanes23 and 1,6-dicarbonyl compounds respectively
with excellent selectivity. Herein, we wish to report the
results in detail.
Results and Discussion
(11) (a) Shi, M.; Yang, Y.-H.; Xu, B. Tetrahedron 2005, 61, 1893.
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Meijere, A. J. Org. Chem. 2007, 72, 7504.
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Lewis Acid Effect. Using diethyl 2-phenylcyclopropane-
1,1-dicarboxylate 1a as a model substrate,21 we first evalu-
ated different Lewis acids as catalysts. The reaction of 1a
with enol silyl ether 2a was performed in methylene chloride
at room temperature under nitrogen atmosphere in the
presence of 20 mol % of Lewis acid. For a clear comparison,
reactions were all quenched after 12 h, followed by 1H NMR
analysis of the crude products. As shown in Table 1, Lewis
acids influence strongly the reaction and the product dis-
tribution. For example, although metal perchlorate hydrates
failed to promote the reaction,24 metal triflates worked well
in this reaction (entries 1-6). Yb(OTf)3 xH2O afforded
3
cycloaddition adduct 3a as the sole product in moderate
conversion with good diastereoselectivity (entry 1). The
other triflates screened gave the ring-opening adduct 4a as
the main product in excellent conversion (entries 2-6). In
particular, only product 4a was obtained when Cu(OTf)2
was used (entry 6). Cu(SbF6)2, prepared from CuCl2 and
(18) Perreault, C.; Goudreau, S. R.; Zimmer, L. E.; Charette, A. B. Org.
Lett. 2008, 10, 689.
(19) (a) Ivanova, O. A.; Budynina, E. M.; Grishin, Y. K.; Trushkov, I. V.;
Verteletskii, P. V. Angew. Chem., Int. Ed. 2008, 47, 1107. (b) Chagarovskiy,
A. O.; Budynina, E. M.; Ivanova, O. A.; Grishin, Y. K.; Trushkov, I. V.;
Verteletskii, P. V. Tetrahedron 2009, 65, 5385.
(20) Other reagents react with donor-acceptor cyclopropanes to give
cyclopentanes: (a) Reference 11b and references cited therein. (b) Graziano,
M. L.; Chiosi, S. J. Chem. Res., Synop. 1989, 44. (c) Yu, M.; Pagenkopf, B. L.
J. Am. Chem. Soc. 2003, 125, 8122. (d) Yu, M.; Pagenkopf, B. L. Org. Lett.
2003, 5, 5099.
(21) Wang et al. reported Sc(OTf)3-catalyzed reaction of donor-acceptor
cyclopropane-1,1-diesters with enol silyl ethers, affording1,6-dicarbonyl
compounds. See: Fang, J.; Ren, J.; Wang, Z.-W. Tetrahedron Lett. 2008,
49, 6659.
(22) (a) Miura, K.; Fugmai, K.; Oshima, K.; Utimoto, K. Tetrahedron
Lett. 1988, 29, 5135. (b) Singleton, D. A.; Church, K. M.; Lucero, M. J.
Tetrahedron Lett. 1990, 31, 5551. (c) Saigo, K.; Shimada, S.; Shibasaki, T.;
Hasegawa, M. Chem. Lett. 1990, 1093. (d) Komatsu, M.; Suehiro, I.;
Horiguchi, Y.; Kuwajima, I. Synlett 1991, 771. (e) Horiguchi, Y.; Suehiro,
I.; Sasaki, A.; Kuwajima, I. Tetrahedron Lett. 1993, 34, 6077. (f) Sugita, Y.;
Kawai, K.; Hosoya, H.; Yokoe, I. Heterocycles 1999, 51, 2029. (g) Sugita, Y.;
Kawai, K.; Yokoe, I. Heterocycles 2000, 53, 657. (h) Sugita, Y.; Kawai, K.;
Yokoe, I. Heterocycles 2001, 55, 135. (i) Takasu, K.; Nagao, S.; Ihara, M.
Adv. Synth. Catal. 2006, 348, 2376.
(23) For the synthesis applications of cyclopentanes, see: (a) Silva, L. F.
Tetrahedron 2002, 58, 9137. (b) Das, S.; Chandrasekhar, S.; Yadav, J. S.;
Gree, R. Chem. Rev. 2007, 107, 3286. (c) Hudlicky, T.; Price, J. D. Chem. Rev
1989, 89, 1467.
(24) For details, see the Supporting Information.
J. Org. Chem. Vol. 74, No. 20, 2009 7685

Qu et al.
JOCArticle
FIGURE 1. Monitoring the Cu(SbF6)2-catalyzed reaction between 1a and 2b in DCM by 1H NMR.
SCHEME 1. Proposed Process of Cycloaddition-Ring-Opening Reaction
AgSbF6 in situ,25 could also promote the reaction to full
conversion with a ratio of 4a/3a up to 99/1 and product 4a
was isolated in 73% yield. Thus, the reaction product can be
controlled by a simple choice of Lewis acid. To further
improve the yield, we examined the effects of solvents, and
methylene chloride (DCM) proved to be the optimal for the
solvents screened.24
TABLE 2. Effects of the Ester Groups in Cyclopropane 1 and the Silyl
Groups in Enol Silyl Ether 2a
entry
R1
R2
convb (%)
3/4b
dr (3)b
Since the product distribution is Lewis acid dependent, on
the basis of the observation, we speculate that this reaction
proceeds via a Lewis acid catalyzed [3 þ 2] cycloaddition to
afford product 3a, which further gives product 4a by a ring-
opening reaction under the catalysis of the same Lewis acid,
similar to the mechanism as Wang proposed.21 To test this
hypothesis, the effects of the ester group in cyclopropane 1 and
the silyl group in enol silyl ether 2 on the reaction selectivity
were examined by using Cu(SbF6)2 as a catalyst. As shown in
Table 2, the bulky silyl group (TBS vs TMS) in compounds 2
slowed down the ring-opening reaction, affording cyclopen-
tanes 3 as major products (entries 1-4, Table 2). The case of
using ethyl ester 1a and tert-butyl silyl ether 2b as substrates
gave product 3 with the satisfying selectivity (3/4 up to 87/13
and dr up to 90/10) (entry 3).
1
2
3
4
Et (1a)
Me (1b)
Et (1a)
Me (1b)
TMS (2a)
TMS (2a)
TBS (2b)
TBS (2b)
>99
>99
>99
>99
48/52
20/80
87/13
76/24
88/12
87/13
90/10
91/9
aReaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), CuCl2 (5.4 mg, 0.04
mmol, 20%), AgSbF6 (27.4 mg, 0.08 mmol), CH2Cl2 (1.0 mL), room
temperature, 2 h. bDetermined by 1H NMR.
spectra demonstrated, cyclopropane (1a) disappeared in
1 h, and cycloaddition adduct 3b (unique peaks at 3.03, 2.51
ppm) formed with a 3b/4a ratio of >95/5. Two hours later,
new signals appeared at 3.14 and 2.40 ppm, which correspond
to the representative chemical shifts of acyclic compound 4a.
After 21 h, the product 3b disappeared and was transformed
into 4a completely, suggesting that the reaction proceeded in a
stepwise manner: the initial [3 þ 2] cycloaddition afforded
product 3b, and then the following ring-opening reaction of3b
gave product 4a (Scheme 1).
To gain insight into the reaction pathway, 1H NMR was
1
used to monitor the reaction (Figure 1). As the H NMR
(25) Evans, D. A.; Kozlowski, M. C.; Murry, J. A.; Burgey, C. S.;
Campos, K. R.; Connell, B. T.; Staples, R. J. J. Am. Chem. Soc. 1999, 121,
669.
Effects of Ligand and Reaction Time. By 1H NMR study
and the experimental observation described above, there
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Qu et al.
JOCArticle
FIGURE 2. Ligands screened for the [3 þ 2] cycloaddition.
TABLE 3. Effects of Ligand and Reaction Time on the Product
Distribution of the Reaction of 1a with Enol Silyl Ether 2aa
(entry 7). Of the bidentate and tridentate ligands examined,
ligands 7, 9, and 10 could promote the cycloaddition. Inter-
estingly, when we tried to synthesize bisoxazoline 8 by a
Zn(OTf)2-mediated reaction between 2-aminoethanol and
2-(4-(trifluoromethyl)phenyl)malononitrile, only complex 8/
Zn(II) was obtained. Although the complex 8/Zn(II) in the
absence of Cu(SbF6)2 could not catalyze the cycloaddition
(entry 9), the [3 þ 2] cycloaddition reaction worked smoothly
in the presence of catalytic 8/Zn(II) and Cu(SbF6)2, and the
ring-opening reaction was almost suppressed. In this case,
the cycloaddition adduct 3a was obtained in 85% yield with
good diastereoselectivity (dr = 94/6) (entry 11). Both 8/
Zn(II) with Cu(OTf)2 and 11/ Cu(SbF6)2 could promote the
reaction affording the desired product 3a with good diaster-
eoselectivity (entries 12 and 13).
Substrate Scope. Under the optimal conditions, we next
evaluated the generality of this tunable reaction between enol
silyl ethers with cyclopropanes. As shown in Table 4, the
ester groups on cyclopropanes 1 slightly influenced the yields
of the cycloaddition (entry 1 vs 3 and entry 2 vs 4, Table 4).
Compared with TMS-protected enol, TBS-protected enol
gave higher yield and better diastereoselectivity probably
due to the steric hindrance. TIPS-protected enol silyl ethers
diminished both the yield and diastereoselectivity. Thus, we
chose the TBS-protected enol ethers for this study. All
reactions of both electron-deficient and electron-rich 4-aryl
cyclopropanes proceeded smoothly in excellent yields with
good diastereoselectivities (entries 5-9). The cycloaddi-
tion reaction of styryl-substituted enol silyl ether gave the
product 3j in 78% yield with a diastereomeric ratio of 91/9
(entry 10). Diethyl 2-vinyl cyclopropane-1,1-dicarboxylates
reacted smoothly, giving the desired product 3k in moderate
yield and diastereoselectivity (entry 11). 2-Furylcyclopro-
pane gave complicated products at room temperature but
underwent the reaction smoothly to afford the desired
product 3l in 65% yield at -45 °C. Raising the temperature
to -25 °C improved the diastereoselectivity, but the yield
decreased (entry 12). When the enol silyl ether was changed
to (3,4-dihydronaphthalen-1-yloxy)trimethylsilane, two
stereoisomers 3m were isolated (entry 13). Silyl enol ether
of phenyl ethyl ketone also worked very well, in which the
two isomers could be separated in 55% and 24% yields. The
structures of the products were determined by NMR. The
entry Lewis acid ligand time (h) convb (%) 3a/4ab dr (3a)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Cu(SbF6)2 no
Cu(SbF6)2 no
Cu(SbF6)2 Et3N
Cu(SbF6)2 pyridine
Cu(SbF6)2 DBU
2
12
24
24
24
12
24
24
24
24
48
12
24
24
24
100
100
0
0
0
100
<1
54
0
48/52 88/12
<1/99
Cu(SbF6)2
Cu(SbF6)2
Cu(SbF6)2
no
5
6
87/13 85/15
7
96/4
92/8
8c
Cu(SbF6)2 8c
Cu(SbF6)2 8c
85 >99/1
100 (85d) >99/1
94/6
94/6
89/11
92/8
92/8
86/14
Cu(OTf)2
Cu(SbF6)2 11
Cu(SbF6)2
Cu(SbF6)2 10
8
82
100 >99/1
67 93/7
19 >99/1
93/7
9
aReaction conditions: 1a (52.5 mg, 0.2 mmol), 2a (76.9 mg, 0.4 mmol),
CuCl2 (2.7 mg, 0.02 mmol, 10%), AgSbF6 (13.7 mg, 0.04 mmol), ligand
(0.02 mmol), CH2Cl2 (1.0 mL), room temperature, monitored by TLC
for entries 1 and 2, CuCl2 (5.4 mg, 0.04 mmol, 20 mol%), AgSbF6 (27.4 mg,
0.08 mmol); bDetermined by 1H NMR; cComplex 8/Zn(II) (6.2 mg,
0.009 mmol); dIsolated yield.
is possibility to tune the product by careful choice of the
reaction time. As shown in Table 3, reaction time influences
the product distribution strongly using Cu(SbF6)2 as a
catalyst. For instance, a mixture of products 3a and 4a was
obtained with a ratio of 48/52 when the reaction was
quenched in 2 h, and only the ring-opening product 4a was
observed with a good stereoselectivity after 12 h of reaction
(entry 1 vs 2). Since the Lewis acid catalysts proved to
influence the reaction distribution (Table 1) and ligand can
modulate the Lewis acidity of the catalyst, we envisioned that
ligand might suppress the ring-opening reaction of product 3
in an easy way and also improve the diastereoselectivity of
the cycloaddition reaction. Thus, we screened several nitro-
gen-containing ligands with different structures shown in
Figure 2. As summarized in Table 3, monodentate ligands
such as pyridine, Et3N, and DBU failed to promote the
reaction (entries 3-5). Pyridine derivative 6 is also inert
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Qu et al.
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TABLE 4. Switchable Reactions of Cyclopropanes with Enol Silyl Ethersa
aMethod 1 (with 8/Zn(II), for 3): 1 (0.2 mmol), 2 (0.4 mmol), CuCl2 (2.7 mg, 0.02 mmol, 10%), AgSbF6 (13.7 mg, 0.04 mmol), complex 8/Zn(II) (6.2
mg, 0.009 mmol), CH2Cl2 (1.0 mL), rt, monitored by TLC. Method 2 (without ligand, for 4): 1 (0.2 mmol), 2 (0.4 mmol), CuCl2 (5.4 mg, 0.04 mmol,
20%), AgSbF6 (27.4 mg, 0.08 mmol), CH2Cl2 (1.0 mL), rt, monitored by TLC. bIsolated yield. cDetermined by 1H NMR using crude product before flash
chromatography. d0.5 mmol scale. e1.0 mmol scale. fTrimethyl(1-phenylvinyloxy)silane was used instead of tert-butyldimethyl(1-phenylvinyloxy)silane.
gCu(SbF6)2/[8/Zn(II)] = 5 mol %/2.3 mol %, -45 °C. hCu(SbF6)2/[8/Zn(II)] = 5 mol %/2.3 mol %, -25 °C. i-25 °C. jTwo isomers obtained with a ratio
of 70/30. k0.4 mmol scale. Isolated yields of two major isomers were 55% and 24%, respectively. lTwo isomers obtained with a ratio of 75/25.
SCHEME 2. [3 þ 2] Reaction of Enol Silyl Ether 2b with Chiral
structure of 3d was further confirmed by single-crystal X-ray
diffraction analysis.24 For the cycloaddition-ring-opening
Cyclopropane 1a
reaction of cyclopropanes 1 with enol silyl ethers 2, the ester
groups of cyclopropanes slightly influenced the yield of the
reaction (entries 1-4, Table 4). The electronic character of
the aryl group on the cyclopropanes had strong effects on the
yields of the reaction (entries 5-9). Cyclopropanes with
electron-withdrawing aryl groups gave the desired products
in moderate yields (entries 5-7). Those with electron-donat-
ing groups underwent the ring-opening reactions smoothly
in excellent yields (entries 8, 9). 2-Vinyl, 2-styryl, and 2-
furylcyclopropane-1,1-dicarboxylates reacted with tert-
butyldimethyl(1-phenylvinyloxy)silane affording the desired
products in relatively low yields (entries 10-12). (3,4-Dihy-
dronaphthalen-1-yloxy)trimethylsilane gave 4k in 47% yield
with poor diastereoselectivity (entry 13). Silyl enol ether of
phenyl ethyl ketone also was a suitable substrate, and the
reaction with cyclopropanes 1a afforded cycloaddition-ring-
opening diastereoisomers 4l with a ratio of 75/25 (entry 14).
Noticeably, we used optically active 1a17e with 77% ee
instead of its racemic isomers to run the reaction with enol
silyl ether 2b in the presence of Cu(SbF6)2/8. It was found
that the chirality was transferred to the product completely
and cyclopentane derivative 3b was obtained with 77% ee in
92% yield (Scheme 2).
Conclusion
In summary, although the reaction of enol silyl ethers with
2-substituted cyclopropane-1,1-dicarboxylates has been re-
ported to give 1,6-dicarbonyl compounds,21 we have devel-
oped a strategy to control the products of this reaction by the
choice of ligand/Lewis acid system. In the presence of ligand
8/Zn(II), the cycloaddition between enol silyl ethers with
7688 J. Org. Chem. Vol. 74, No. 20, 2009

Qu et al.
JOCArticle
cyclopropanes catalyzed by Cu(SbF6)2 gave the pentasub-
stituted cyclopentane derivatives 3 with excellent diastereos-
electivities in most cases. In the absence of the ligand, the
same reaction afforded linear 1,6-dicarbonyl compounds.
This method provides a good example for the reaction
control. In addition, the mechanism for the current ligand-
switchable reaction was investigated in detail by both control
experiments and 1H NMR studies. The mild reaction condi-
tions, cheap and easily available catalyst, and the syntheti-
cally useful products make this method potentially useful in
organic synthesis. Endeavors to develop the highly enantio-
selective version are now ongoing in our laboratory.
3029, 2981, 2958, 2903, 1732, 1604, 1497, 1448, 1367, 1252, 1100,
1072, 987, 844, 755, 699.
Representative Procedure (without Ligand and 4a as an
Example). To an oven-dried Schlenk reaction tube were added
cyclopropane diester 1a (52.5 mg, 0.20 mmol), CuCl2 (5.4 mg,
0.04 mmol), AgSbF6 (27.4 mg, 0.08 mmol), and CH2Cl2
(1.0 mL), followed by enol silyl ethers 2b (93.7 mg, 0.40 mmol)
under nitrogen atmosphere. The resulting mixture was stirred at
room temperature for 23 h. After the reaction was complete
(monitoring by TLC), the solution was passed through a short
silica gel column, which was further eluted with CH2Cl2
(50 mL). The combined elution was concentrated under reduced
pressure, and the residue was purified by flash chromatography
on silica gel (petroleum ether/ethyl acetate, v/v, 10/1) to give the
pure 4a as colorless oil: yield 76.5 mg (80%); 1H NMR
(300 MHz, CDCl3) δ 7.88 (d, J = 7.5 Hz, 2H), 7.54 (t, J =
7.5 Hz, 1H), 7.42 (t, J = 7.5 Hz, 2H), 7.32-7.18 (m, 5H), 4.22
(q, J = 7.2 Hz, 2H), 4.12-3.96 (m, 2H), 3.44-3.23 (m, 3H),
3.14 (dd, J = 5.1, 9.9 Hz, 1H), 2.44-2.35 (m, 1H), 2.28-2.18 (m,
1H), 1.28 (t, J = 7.2 Hz, 3H), 1.18 (t, J = 7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 197.9, 169.3, 169.2, 142.6, 136.9, 133.0,
128.6, 128.5, 128.0, 127.8, 126.9, 61.4, 61.3(7), 50.1, 45.7, 38.9,
35.0, 14.1, 13.9; LRMS-ESI (m/z) [M þ Na]þ 405.0; HRMS-ESI
[M þ Na]þ calcd for C23H26O5Na 405.1672, found 405.1679; IR
(KBr, cm-1) 2957, 2924, 2851, 1731, 1688, 1449, 1371, 1268.
Experimental Section
Representative Procedure (with Ligand and 3a as an Example).
To cyclopropane diester 1a (52.5 mg, 0.20 mmol) was added a
solution of CuCl2/AgSbF6 (2.7 mg, 0.02 mmol/13.7 mg, 0.04
mmol) and 8/Zn(II) (6.2 mg, 0.009 mmol) in DCM (1.0 mL),
followed by pumping of enol silyl ether 2a (76.9 mg, 0.40 mmol),
under nitrogen atmosphere. The resulting solution was stirred until
the cyclopropane diester 1a was completely consumed (48 h,
monitoring by TLC, petroleum ether/ethyl acetate = 10/1, v/v).
Then the mixture was passed through a short silica gel column and
eluted with CH2Cl2 (50 mL). The combined elution was concen-
trated under reduced pressure, and the residue was purified by flash
chromatography on silica gel (petroleum ether/ethyl acetate, v/v,
50/1) to give the pure 3a as colorless oil: yield 65.9 mg (85%); 1H
NMR (300 MHz, CDCl3) δ 7.77 (d, J = 6.9 Hz, 2H), 7.43-7.23
(m, 8H), 4.38-4.21 (m, 2H), 3.85-3.66 (m, 3H), 3.35 (dd, J = 8.4,
13.5 Hz, 1H), 3.07 (t, J = 12.6 Hz, 1H), 2.42 (dd, J = 5.1, 12.6 Hz,
1H), 2.27 (dd, J = 10.8, 13.5 Hz, 1H), 1.37 (t, J = 7.2 Hz, 3H), 0.89
(t, J = 6.9 Hz, 3H), -0.08 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
171.5, 169.1, 143.5, 142.1, 128.5, 128.2, 127.5, 127.4, 127.1, 126.5,
88.9, 71.3, 61.1, 60.9, 47.6, 42.8, 41.5, 14.1, 13.5, 1.7; LRMS-ESI
(m/z) [M þ Na]þ 477.1; HRMS-ESI [M þ Na]þ calcd for
C26H34O5SiNa 477.2068, found 477.2075; IR (KBr, cm-1) 3062,
Acknowledgment. We are grateful for the financial sup-
port from the Natural Sciences Foundation of China (Nos.
20821002 and 20672131), the Major State Basic Research
Development Program (Grant No. 2009CB825300), the
Chinese Academy of Sciences, and the Science and Technol-
ogy Commission of Shanghai Municipality.
Supporting Information Available: CIF files and crystal-
lographic data, general synthetic procedures and characteriza-
tion, and spectral data for key compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 74, No. 20, 2009 7689