First example of highly stereoselective synthesis of 1,2,3-trisubstituted cyclopropanes via chiral selenonium ylides

Article abstract of DOI:10.1002/chem.200801936

As the first example of the application of chiral selenonium ylides in asymmetric cyclopropanation, a new strategy for the highly stereoselective synthesis of chiral 1,2,3-trisubstituted cyclopropanes via selenonium ylides is described. The reaction affor

Full text of DOI:10.1002/chem.200801936

DOI: 10.1002/chem.200801936
First Example of Highly Stereoselective Synthesis of 1,2,3-Trisubstituted
Cyclopropanes via Chiral Selenonium Ylides
Hai-Yang Wang,[a] Fei Yang,[a] Xin-Liang Li,[b] Xue-Ming Yan,[a] and Zhi-Zhen Huang*[a]
Abstract: As the first example of the
application of chiral selenonium ylides
in asymmetric cyclopropanation, a new
strategy for the highly stereoselective
synthesis of chiral 1,2,3-trisubstituted
cyclopropanes via selenonium ylides is
described. The reaction afforded three
stereoisomers of chiral 1,2,3-trisubsti-
tuted cyclopropanes with good yields,
excellent diastereoselectivities, very
high enantioselectivities (up to >99%
ee), good generality and recyclability of
chiral selenides. The possible pathways
and models of the asymmetric cyclo-
propanation via the chiral selenonium
ylides were also proposed to rationalize
the excellent enantioselectivities and
diastereoselectivities.
Keywords: chiral selenides · cyclo-
propanation · diastereoselectivity ·
enantioselectivity · ylides
Introduction
with excellent enantioselectivities up to 96% ee.[5] Tang
et al. performed the reaction of chiral sulfonium ylides with
a,b-unsaturated compounds, affording chiral 1,2,3-trisubsti-
tuted cyclopropanes with excellent diastereoselectivities and
enantioselectivities up to 99% ee.[6a,b] We had employed a
camphor-derived sulfonium ylide to achieve a controllable
enantioselective synthesis of chiral 1,2-disubstituted cyclo-
propanes with the enantioselectivities up to 95% ee.[6c] Be-
cause chiral sulfonium ylides have the tendency to initiate
rearrangement reactions, the yields of the asymmetric cyclo-
propanation are sometimes not satisfactory.[6] Hence, chiral
telluronium ylides were used in the asymmetric cyclopropa-
nation to give chiral cyclopropanes in the yields up to 99%
with excellent diastereoselectivities and enantioselectivi-
ties.[6d,e] Nevertheless, chiral telluride, as the precursor of tel-
luronium ylide, is unstable and this make it difficult to re-
cover and reuse. Although the works concerning cyclopro-
panations via achiral selenonium ylides were done before,[7]
to the best of our knowledge, no case on the asymmetric cy-
clopropanation via selenonium ylides was reported. There-
fore, we envisioned to synthesize chiral selenonium ylides,
examine their reactive, diastereoselective and enantioselec-
tive properties in asymmetric cyclopropanation and develop
a new and practical strategy for the highly stereoselective
synthesis of chiral 1,2,3-trisubstituted vinylcyclopropanes.
Chiral cyclopropanes are important building blocks in or-
ganic synthesis; these chiral structure units are commonly
found in biologically active natural products.[1] Although
many researches have been carried out for the synthesis of
cyclopropanes, the development of new highly stereoselec-
tive synthesis of multisubstituted cyclopropanes is still a
challenging subject due to the difficulties in controlling re-
gioselectivities, diastereoselectivities and enantioselectivi-
ties.[2] Among the reported methods for the asymmetric syn-
thesis of cyclopropanes, the chiral ylide route is becoming
one of the most important methods.[3–6] In 2000, Aggarwal
et al. revealed that chiral sulfonium ylides formed in situ
under the catalysis of transitional metal could react with
a,b-unsaturated compounds to give chiral 1,2,3-trisubstituted
cyclopropanes with excellent enantioselectivities.[4] MacMil-
lan et al. found that under the catalysis of chiral secondary
amines, the reaction of sulfonium ylides with a,b-unsaturat-
ed compounds gave chiral 1,2,3-trisubstituted cyclopropanes
[a] Dr. H.-Y. Wang, F. Yang, X.-M. Yan, Prof. Z.-Z. Huang
School of Chemistry and Chemical Engineering
Nanjing University, Nanjing 210093 (China)
Fax : (+86)25-8368-6231
E-mail: huangzz@nju.edu.cn
[b] Dr. X.-L. Li
Results and Discussion
Basilea Pharmaceutica China Ltd, No.638 Xiushan Road, Haimen
226100 (China)
Initially, cheap d-camphor was employed as a starting mate-
rial to react with lithium diisopropylamide (LDA) and then
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FULL PAPER
with phenylselenenyl bromide, followed by the reduction
with diisobutylaluminium hydride (DIBAH), affording cam-
phor-derived selenide 1 (Scheme 1).[8] However, the experi-
ment showed that selenide 1 was unable to react with allyl
bromide 4 to form desired selenonium salt. Then, camphor-
derived selenide 2a was prepared by the similar protocol as
that of selenide 1.[8] Further treatment of selenide 2a with
sodium hydride, followed by the reaction with methyl iodide
gave a new camphor-derived selenide 2b in excellent yield
(Scheme 1). Moreover, it was found that treatment of d-
camphor with 2 equiv LDA, followed by the reaction with
methylselenenyl bromide, afforded endo-a-methylseleno
camphor 3 in good yields. The reduction of 3 with DIBAH
furnished another new camphor-derived selenide 5 in a satis-
factory yield.[8] Quite different from selenide 1, selenide 2a,
2b and 5 could react with allyl bromide 4 quickly in 2 h to
give exo-camphor-derived selenonium salt 6a and 6b and
endo-selenonium salt 7, respectively, in excellent yields
(Scheme 1). The structures of exo-salt 6a, 6b and endo-salt
7, were determined by the single crystal X-ray analysis of
exo-salt 6a and endo-salt 7.[9]
group) could be obtained (entries 5 and 11, Table 1). En-
couraged by the result, we selected LiHMDS as a base due
to its analogous structure to LDA. Gratifyingly, the yield of
the asymmetric cyclopropanation via camphor-drived sele-
nonium ylides was greatly improved (entries 7 and 12,
Table 1). The effects of solvents on yields were also studied
and the results showed that, when 3 equiv of HMPA (based
on LiHMDS) was used, the yields of cyclopropane 9a were
improved further (entries 8 and 13, Table 1).
Table 1. Optimization of asymmetric cyclopropanation performed by
exo-selenonium salts 6.[a]
Entry
6
Base
Solvent
Yield [%][b] cis/trans[c] ee [%][d]
1
6a NaOH
6a NaOH
6a tBuOK
6a NaH
THF
CH3CN
THF
0
0
0
0
–
–
–
–
–
–
–
–
2[e]
3
4
THF
5
6
7
8
6a LDA
6a LDA
6a LiHMDS THF
THF
toluene
25
20
81
95:5
94:6
97:3
>99:1
–
90
88
90
91
–
6a LiHMDS THF/HMPA 92
9
6b NaOH
6b tBuOK
6b LDA
6b LiHMDS THF
6b LiHMDS THF/HMPA 90
THF
THF
THF
0
0
16
74
10
11
12
13
–
–
95:5
97:3
98:2
77
80
87
[a] The reaction was performed with the ratio of salt/base/8a 1:2:1 at
À788C for 5 h. [b] Isolated yields. [c] Determined by 1H NMR or GC.
[d] Determined by chiral HPLC using a Chiralcel OD-H or AD-H
column. [e] The reaction was performed at 08C for 2 h.
After the optimal reaction conditions were established,
various a,b-unsaturated carbonyl compounds were exam-
ined in the asymmetric cyclopropanation via exo-camphor-
derived selenonium ylides. It was found that selenonium
salts 6a and 6b could react with the solution of LiHMDS in
THF/HMPA to generate chiral selenonium ylides in situ,
followed by the reaction with a,b-unsaturated esters 8a–h
and a,b-unsaturated ketones 8i–l at À788C, affording cis-
(1R,2R,3R)-trisubstituted cyclopropanes 9 in good to excel-
lent yields (Table 2). Moreover, the diastereoselectivities of
the cyclopropanation were high (d.r. 90:10–>99:1) with
dominant cis configuration. The substrate generality was
demonstrated by several examples. When selenonium salts
6a was employed, various a,b-unsaturated carbonyl com-
pounds 8 led to excellent enantioselectivities (91–99% ee)
and selenonium salts 6b led to good enantioselectivities
(81–90% ee). This result suggests that the hydroxy group
may play a more important role than methoxy group in the
asymmetric induction. The absolute configurations of cis-cy-
clopropanes 9 were assigned by the comparisons of the signs
of optical rotations and the results of chiral HPLC with
those of known compounds.[6d] No rearrangement side-prod-
uct was obtained. It is noteworthy that, compared with the
Scheme 1. Synthesis of exo- and endo-camphor-derived selenonium salts
6a, 6b and 7.
With the new chiral selenonium salt 6a and 6b at hand,
we chose (E)-methyl cinnamate 8a as a model a,b-unsatu-
rated compound to probe the reaction conditions for asym-
metric cyclopropanation via chiral selenonium ylides. Initial-
ly, common bases such as sodium hydroxide, potassium tert-
butoxide and sodium hydride were examined in the reaction
in different solvents and no cyclopropanation product was
obtained. Then, we were pleased to find that, when LDA
was used as a base, a small amount of cis-1,2,3-trisubstituted
cyclopropane 9a (cis is relative to 1-methoxycarbonyl
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Z.-Z. Huang et al.
Table 2. Stereoselective synthesis of cis-(1R,2R,3R)-trisubstituted cyclopropanes 9 via exo-camphor-derived se-
alkoxy anion (or methoxyl
group for 6b) and ylidic carb-
anion of the exo-selenonium
ylide from exo-selenonium
lenonium ylides.[a]
salts 6, forming
a six-mem-
bered ring similar to a boat
form (Figure 1). The R group
should be positioned above the
six-membered ring because the
Newman projection shows that
if the R group is at the hydro-
gen position, which is below
the ring, it suffers a steric re-
pulsion from camphor. Then,
the molecule of a,b-unsaturat-
Entry
6
8
R1
R2
Yield [%][b]
cis/trans[c]
ee [%][d]
1
2
3
4
5
6
7
8
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6b
6b
6b
6b
8a
8b
8c
8d
8e
8 f
8g
8h
8i
8j
8k
8l
8a
8c
8 f
8i
C6H5
OMe
OMe
OMe
OMe
OMe
OEt
92
91
87
70
86
93
86
83
90
85
92
81
90
84
91
80
>99:1
>99:1
98:2
90:10
>99:1
>99:1
90:10
95:5
97:3
92:8
>99:1
95:5
98:2
91
>99
92
>99
95
93
>99
93
91
92
>99
95
87
4-BrC6H4
4-MeC6H4
4-MeOC6H4
Furyl
C6H5
4-MeC6H4
Furyl
OEt
OEt
9
C6H5
C6H5
C6H5
C6H5
C6H5
OMe
OMe
OEt
10
11
12
13
14
15
16
4-ClC6H4
4-BrC6H4
4-MeC6H4
C6H5
4-MeC6H4
C6H5
ed compound
from the back of the lithium
coordinated six-membered
8 approaches
ring. The end of carbonyl
group is directed towards the
bicycle since it is smaller than
aryl group. The approach of
hydrogen of this end towards
97:3
>99:1
90:10
81
90
81
C6H5
C6H5
[a] The reaction was performed with the ratio of salt/base/8 1:2:1 at À788C for 3–5 h. [b] Isolated yields.
[c] Determined by 1H NMR or GC. [d] Determined by chiral HPLC using a Chiralcel OD-H or AD-H
column.
diastereoselectivities in the asymmetric epoxidation via
chiral selenonium ylides (d.r. 1:1 to 13:1),[8c,10c] the diastereo-
selectivities in the asymmetric cyclopropanation via seleno-
nium ylides are much higher. Moreover, chiral selenide 2a
and 2b could be recovered conveniently in yields of 54–
81% in order to re-use them since they are stable under at-
mosphere.
Table 3. Stereoselective synthesis of cis-(1S,2S,3S)-trisubstituted cyclo-
propanes 9’ via an endo-camphor-derived selenonium ylide.[a]
Entry
8
R1
R2
Yield [%][b] cis/trans[c] ee [%][d]
Encouraged by the high diastereoselectivities and excel-
lent enantioselectivities of the cyclopropanation via an exo-
selenonium ylide, we also employed endo-selenonium salt 7
to perform asymmetric cyclopropanation. It was found that
endo-salt 7 could also react smoothly with various a,b-unsa-
turated carbonyl compounds 8 to afford cis-(1S,2S,3S)-tri-
substituted cyclopropanes 9’ in good yields with excellent
diastereoselectivities (d.r. 90:10– >99:1) (Table 3). To our
delight, endo-salt 7 also led to very high enantioselectivities
(up to >99% ee). Moreover, the chiral endo-selenide 5
could be recovered in yields similar to those of chiral exo-
selenide 2. The enantioselectivities of the cyclopropanation
with endo-salt 7 are opposite to those with exo-salt 6a and
6b, which was observed in sulfonium ylides as well.[6a,b]
Therefore, the two enantiomers of cis-cyclopropanes 9 and
9’ could be obtained by the choice of exo-selenonium salt 6
or endo-salt 7.
Compared with the corresponding camphor-derived sulfo-
nium salts, the asymmetric cyclopropanation of camphor-de-
rived selenonium salts 6 and 7 with a,b-unsaturated com-
pounds 8 gave predominantly cis-cyclopropanes 9 instead of
trans-cyclopropanes under our reaction conditions.[6a,b] This
result and the excellent asymmetric induction can be ration-
alized as follows. The lithium cation coordinated by HMPA
in the reaction system can coordinate further to both the
1
2
3
4
5
6
7
8
8a
C6H5
OMe
OMe
90
88
83
84
82
81
90
81
95:5
>99:1
98:2
>99:1
90:10
98:2
>99
95
>99
85
97
70
8b 4-BrC6H4
8c
8e
8g
4-MeC6H4 OMe
furyl OMe
4-MeC6H4 OEt
8h furyl
8i
8l
OEt
C6H5
C6H5
4-MeC6H4 C6H5
97:3
95:5
94
>99
[a] The reaction was performed with the ratio of salt/base/8 1:2:1 at
À788C for 3–5 h. [b] Isolated yields. [c] Determined by 1H NMR or GC.
[d] Determined by chiral HPLC using a Chiralcel OD-H or AD-H
column.
the bond connecting selenium and camphor led to a favora-
ble approach of carbonyl group towards a selenium lone
pair. Simultaneously, the aryl group happens to approach a
small hydrogen. This approach and successive bond forma-
tion results in cis-(1R,2R,3R)-cyclopropane 9. A similar ex-
planation can account for the origin of the excellent enan-
tioselectivities and diastereoselectivities of the cyclopropa-
nation performed with endo-selenonium salt 7 for cis-
(1S,2S,3S)-cyclopropane 9’.[11]
It is well-known that C2-symmetric structures frequently
have good asymmetric inductions. Metzner et al. reported
that (2R,5R)-dimethyltetrahydrothiophene,[10a,b] (2R,5R)-di-
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Stereoselective Synthesis of Cyclopropanes
FULL PAPER
Table 4. Stereoselective synthesis of trans-(1R,2R,3S)-trisubstituted cy-
clopropanes 10 via a C2-symmetric selenonium ylide.[a]
Figure 1. Mechanistic depiction of asymmetric cyclopropanation via an
exo-camphor-derived selenonium ylide.
Entry
8
R1
8c 4-MeC6H4 CO2Me
8i C6H5 COC6H5
R2
Yield [%][b] cis/trans[c] ee [%][d]
1
2
3
4
5
6
7
8
93
92
89
91
90
80
82
83
98:2
97:3
98:2
>99:1
95:5
>99:1
96:4
81
97
99
98
98
51
85
81
methyltetrahydroselenophene[10c] 11 and (2R,5R)-diethylte-
trahydrotellurophene[10d] could initiate an efficient asymmet-
ric conversion of aldehydes via corresponding ylides, afford-
ing trans-epoxides with excellent enantioselectivities. We
found that (2R,5R)-dimethyltetrahydrotellurophene[10e] led
to excellent enantioselectivities in the asymmetric synthesis
of trans-epoxides via a ylide route. Tang et al. reported that
C2-symmetric telluronium ylides generated in situ from
(2R,5R)-dimethyltetrahydrotellurophene could undergo
asymmetric cyclopropanation with high diastereoselectivities
and excellent enantioselectivities.[6d] However, to the best of
our knowledge, there is no report on the asymmetric cyclo-
propanation via a C2-symmetric selenonium ylide.
8j 4-ClC6H4 COC6H5
8k 4-BrC6H4 COC6H5
8l 4-MeC6H4 COC6H5
8m C6H5
8n C6H5
CON
CN
G
8o 4-BrC6H4 CN
96:4
[a] The reaction was performed with the ratio of salt/base/8 2.5:3:1 at
À788C for 4–5 h. [b] Isolated yields. [c] Determined by 1H NMR or GC.
[d] Determined by chiral HPLC using a Chiralcel OD-H or AD-H
column.
It was found that (2R,5R)-dimethyltetrahydroselenophene
11 could react smoothly with allyl bromide 4 and NaBPh4 in
a one-pot reaction to afford the desired selenonium salt 12
in a satisfactory yield. The structure of salt 12 was confirmed
by single crystal X-ray diffraction.[9] Further experiments
showed that when LiTMP and THF/toluene was employed
as a base and a solvent, respectively, the C2-symmetric sele-
nonium salt 12 could react smoothly with various a,b-unsa-
turated compounds, such as a,b-unsaturated ester 8c, a,b-
unsaturated ketones 8i–l, a,b-unsaturated amide 8m and
a,b-unsaturated nitriles 8n–o, affording the corresponding
trans-(1R,2R,3S)-cyclopropanes 10 in good yields with wide
generality, high diastereoselectivities (d.r. 95:5– >99:1) and
excellent enantioselectivities (up to 99% ee) (Table 4). The
absolute configurations of trans-cyclopropanes 10 were as-
signed by the comparisons of the signs of optical rotations
and the results of chiral HPLC with those of known com-
pounds.[6]
Compared with the corresponding C2-symmetric telluroni-
um salt, which led to cis-(1S,2S,3S)-cyclopropanes 9’ or
trans-(1S,2S,3R)-cyclopropanes 10’, C2-symmetric selenoni-
um salt 12 furnished trans-(1R,2R,3S)-cyclopropanes 10
under our reaction conditions (Table 4).[6d] This and the ex-
cellent asymmetric induction can be rationalized as follows.
The R group is distant from the methyl group below the tet-
rahydroselenophene ring in order to avoid the steric repul-
sion (Scheme 2).[10a] The molecule of a,b-unsaturated com-
pound 8 approaches the ylidic carbanion from the direction
without the methyl group, which is below the tetrahydrose-
lenophene ring, in order to decrease their repulsions. The
lithium cation here coordinates with both ylidic anion and
carbonyl group to form a six-membered ring similar to a
chair form. This approach and the successive bonding via
the transition state 13 results in trans-(1R,2R,3S)-cyclopro-
panes 10.[11]
Scheme 2. Proposed transition state of asymmetric cyclopropanation via
a C2-symmetric selenonium ylide.
Conclusion
We have developed a new strategy for the highly stereose-
lective synthesis of chiral 1,2,3-trisubstituted cyclopropanes
via selenonium ylides, which is the first example of the ap-
plication of chiral selenonium ylides in the asymmetric syn-
thesis of enantiomerically enriched cyclopropanes. This
strategy has the advantages of a facile synthesis and recycla-
bility of chiral selenides, good yields, high generality, con-
trollable diastereoselectivities and enantioselectivities, excel-
lent diastereoselectivities and very high enantioselectivities.
The strategy has therefore great potential for practical appli-
cation in organic synthesis. The possible pathways and
models of the asymmetric cyclopropanation via the chiral
selenonium ylides were also proposed to rationalize their ex-
cellent enantioselectivities and diastereoselectivities.
Experimental Section
Synthesis of camphor-derived selenide 3: A solution of nBuLi (2.0m,
24 mmol) in hexane at À788C was added to a solution of diisopropyl-
amine (4.85 g, 48 mmol) in THF (80 mL).[8] After stirring for 5 min, a solu-
tion of d-camphor (3.65 g, 24 mmol) in THF (8 mL) was added dropwise.
The reaction was stirred at À788C for 1 h and then the solution of meth-
ylselenenyl bromide (5.01 g, 28.8 mmol) in THF (10 mL) was added. The
reaction mixture was stirred at this temperature for another 1 h and then
poured into an aqueous HCl (0.5n, 400 mL). After extraction with Et2O
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Z.-Z. Huang et al.
(3ꢁ100 mL), the organic layer was washed with water, a saturated solu-
tion of sodium hydrogen carbonate and a saturated solution of sodium
chloride, and dried over anhydrous MgSO4. After the solvent was re-
moved by evaporation, the residue was separated by column chromatog-
raphy (silica gel, Et2O/petroleum ether 1:20) to afford selenide 3 (5.02 g,
85%) as a colorless oil. 1H NMR (CDCl3): d = 3.64 (d, J=3.6 Hz, 1H),
2.20 (s, 3H), 1.95–1.80 (m, 2H), 1.80–1.65 (m, 1H), 1.55–1.40 (m, 1H),
1.40–1.20 (m, 1H), 1.02 (s, 3H), 0.93 (s, 3H), 0.91 ppm (s, 3H); 13C NMR
(CDCl3): d = 217.6, 57.9, 48.0, 47.4, 46.6, 30.4, 23.2, 19.50, 19.49, 9.6,
4.8 ppm; MS (EI): m/z: 246 [M]+, 203, 200, 135, 123, 83, 55; elemental
analysis calcd (%) for C11H18OSe: C 53.88, H 7.40; found: C 53.81, H
7.38.
P21, a=7.5550(15), b=10.023(3), c=14.4230(19) ꢂ; a=90.00, b=
101.29(3), g=908; V=1071.0(4) ꢂ3, Z=2, 1calcd =1.366 gcmÀ3
,
T=
291(2) K, FAHCTUNGTREG(NNUN 000)=452, q=1.44–25.968, 3638 measured reflections, 3638
independent reflections, 2778 reflections with I
Flack parameter=0.01(2).
> 2s(I), Rint =0.000;
[9]
Selenonium salt 12: The mixture of (2R,5R)-2,5-dimethyltetrahydrosele-
nophene 11[10c] (4.0 g, 24.5 mmol), allyl bromide 4 (4.7 g, 24.5 mmol) and
NaBPh4 (8.4 g, 24.5 mmol) in methanol was stirred under nitrogen for
8 h. The solid was collected and washed with methanol and Et2O to
afford selenonium salt 12 (10.4 g, 71%) as a white solid. M.p. 147–1498C;
1H NMR (CDCl3): d = 7.39 (s, 8H), 7.02 (t, J=6.9 Hz, 8H), 6.89 (t, J=
6.9 Hz, 4H), 5.83 (d, J=18.3 Hz, 1H), 5.46–5.35 (m, 1H), 2.89–2.87 (m,
1H), 2.64–2.59 (m, 2H), 2.36 (t, J=9.6 Hz, 1H), 1.85–1.84 (m, 2H), 1.18–
1.15 (m, 5H), 0.84–0.82 (m, 3H), 0.09 ppm (s, 9H); 13C NMR (CDCl3): d
= 164.9, 164.3, 163.4, 163.0, 144.5, 136.1, 131.5, 125.8, 125.79, 125.8, 122.1,
61.8, 58.9, 39.4, 38.6, 38.3, 18.9, 15.4, À1.7 ppm; HRMS (ESI, positive
mode): m/z: calcd for C12H25SeSi [MÀBPh4]: 277.0885; found: 277.0887.
X-ray structure analysis: C36H45BSeSi, M=595.58; monoclinic, space
group P21, a=9.2690(19), b=10.982(2), c=16.726(3) ꢂ; a=90.00, b=
Synthesis of camphor-derived selenide 5: A solution of diisobutylalumini-
um hydride (12 mL, 25% wt/wt, 21 mmol) in toluene was added dropwise
to
a solution of selenide 3 (3.44 g, 14.0 mmol) in dichloromethane
(60 mL).[8] After the reaction mixture was stirred at room temperature
for 0.5 h, the resulting mixture was poured into a saturated aqueous
NH4Cl (180 mL) and extracted with petroleum ether (3ꢁ150 mL). The
organic layer was washed with aqueous NaHCO3 (2.0m, 3ꢁ100 mL) and
dried over anhydrous MgSO4. After the solvent was evaporated, the resi-
due was purified by column chromatography (silica gel, ethyl acetate/pe-
troleum ether 1:10) to give camphor-derived selenide 5 (2.53 g, 73%) as
a colorless oil. 1H NMR (CDCl3): d = 3.78 (dd, J=9.3, 1.8 Hz, 1H),
3.67–3.73 (m, 1H), 2.76 (s, 1H), 1.91 (s, 3H), 1.84–1.71 (m, 1H), 1.70–
1.51 (m, 1H), 1.39–1.20 (m, 2H), 1.19–1.03 (m, 1H), 0.95 (s, 3H), 0.91 (s,
3H), 0.88 ppm (s, 3H); 13C NMR: d = 73.1, 52.6, 50.4, 28.0, 25.2, 25.0,
23.6, 18.4, 18.3, 13.9, 4.6 ppm; MS (EI): m/z: 248 [M]+, 233, 177, 135,
109, 95, 43; elemental analysis calcd (%) for C11H20OSe: C 53.44, H 8.15;
found: C 53.38, H 8.10.
96.08(3), g=90.008; V=1693.0(6) ꢂ3, Z=2, 1calcd =1.168 gcmÀ3
293(2) K, F(000)=628, q=1.22–25.308, 3462 measured reflections, 3252
, T=
AHCTUNGTRENNUNG
independent reflections, 2186 reflections with I
Flack parameter=0.01(2).
> 2s(I), Rint =0.024;
General procedure for the asymmetric synthesis of cis-1,2,3-trisubstituted
cyclopropane 9 or 9’: A solution of LiHMDS (1.0m in toluene, 2.0 mL,
2.0 mmol) and HMPA (1.08 g, 6.0 mmol) at was added À788C to a sus-
pension of selenonium salts 6 or 7 (1.0 mmol) in THF (10 mL). After the
mixture was stirred for 5 min, a solution of a,b-unsaturated compounds 8
(1.0 mmol) in THF (1 mL) was added. The reaction mixture was stirred
at this temperature for 3–5 h and then the reaction was quenched with
water. The mixture was filtered through a short silica gel column fol-
lowed by wash with ethyl acetate. The filtrate was concentrated and the
residue was purified by flash chromatography (silica gel, Et2O/petroleum
ether) to afford cis-1,2,3-trisubstituted cyclopropane 9 or 9’.
General procedure for the preparation of selenonium salts 6a, 6b or 7:
The solution of camphor-derived selenide 2a, 2b or 5 (9.7 mmol) and
allyl bromide 4 (1.88 g, 9.7 mmol) in acetone (5 mL) was stirred at 08C
for 2 h. The solid was collected and washed with Et2O (5 mLꢁ2) to
afford selenonium salt 6a, 6b or 7, respectively.
General procedure for the asymmetric synthesis of trans-1,2,3-trisubsti-
tuted cyclopropane 10: To a solution of LiTMP (0.6 mmol, 1m) in
hexane, which was prepared by the reaction of 2,2,6,6-tetramethyl piperi-
dine with the solution of n-butyl lithium in hexane in situ, was added a
solution of selenonium salt 12 (298 mg, 0.5 mmol) in toluene/THF
(2.2 mL, 1:10 v/v) at À788C. The resulting mixture was stirred for 5 min
under nitrogen, and then a solution of a,b-unsaturated compounds 8
Selenonium salt 6a: Yield: 4.20 g, 94%; white solid, m.p. 146–1488C;
1H NMR (CDCl3): d = 6.56 (d, J=18.3 Hz, 1H), 6.40–6.28 (brs, 1H),
6.10–5.97 (m, 1H), 4.81 (dd, J=6.6, 4.2 Hz, 1H), 4.70–4.55 (m, 1H),
4.10–3.95 (m, 2H), 2.62 (s, 3H), 2.00–1.85 (m, 2H), 1.62–1.50 (m, 1H),
1.20 (s, 3H), 1.20–1.05 (m, 2H), 1.01 (s, 3H), 0.86 (s, 3H), 0.12 ppm (s,
9H); 13C NMR (CDCl3): d = 148.6, 131.0, 76.6, 65.2, 50.2, 47.8, 47.4,
44.4, 31.8, 28.7, 21.2, 21.1, 14.1, 11.3, À1.5, À1.56, À1.62 ppm; MS (ESI,
79
positive mode): m/z: 361.1 [MÀ Br]+; elemental analysis calcd (%) for
(0.2 mmol) in THFACHTUNTRGNEUNG(0.3 mL) was added. After the reaction mixture was
stirred at À788C for 4–5 h, the reaction was quenched with water. The
mixture was filtrated through a short silica gel column followed by wash
with dichloromethane (20 mL). The filtrate was concentrated and the res-
idue was purified by flash chromatography (silica gel, Et2O/petroleum
ether) to give trans-1,2,3-trisubstituted cyclopropane 10.
C17H33BrOSeSi: C 46.36, H 7.55; found: C 46.43, H 7.60. X-ray structure
analysis: C17H33OBrSeSi, M=440.39; monoclinic, space group P21; a=
7.4872(12), b=10.1296(17), c=14.419(2) ꢂ; a=90.00, b=103.117(2), g=
90.008; V=1065.0(3) ꢂ3, Z=2, 1calcd =1.373 gcmÀ3
,
T=291(2) K, F-
ACHTUNGTRENNUNG(000)=452, q=2.48–25.998, 5825 measured reflections, 3182 independent
reflections, 2423 reflections with I > 2s(I), Rint =0.033; Flack parame-
ter=0.026(17).[9]
Selenonium salt 6b: Yield: 4.10 g, 93%; white solid, m.p. 159–1608C;
1H NMR (CDCl3): d = 6.19–6.10 (m, 1H), 5.96 (d, J=18.3 Hz, 1H), 3.97
(d, J=6.7 Hz, 2H), 3.44 (s, 3H), 3.25–3.05 (m, 2H), 2.01 (s, 3H), 1.94 (d,
J=3.9 Hz, 1H), 1.87–1.75 (m, 1H), 1.60–1.45 (m, 1H), 1.15 (s, 3H), 1.10–
1.02 (m, 2H), 0.93 (s, 3H), 0.80 (s, 3H), 0.09 ppm (s, 9H); 13C NMR
(CDCl3): d = 141.0, 136.2, 92.0, 61.6, 52.9, 51.8, 50.7, 47.6, 35.7, 34.0,
29.9, 21.8, 12.2, 5.5, 1.5, À1.5 ppm; MS (ESI, positive mode): m/z: 375.1
Acknowledgement
We thank the National Natural Science Foundation of China for its finan-
cial support of the project 20572042 and 20872059.
79
[MÀ Br]+; elemental analysis calcd (%) for C18H35BrOSeSi: C 47.58, H
7.76; found: C 47.52, H 7.83.
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Selenonium salt 7: Yield: 3.89 g, 91%; white solid, m.p. 149–1518C.
1H NMR (CDCl3): d = 6.52 (d, J=18.3 Hz, 1H), 6.09–5.98 (m, 2H), 4.75
(dd, J=10.5, 6.3 Hz, 1H), 4.69–4.62 (m, 1H), 4.53–4.38 (m, 1H), 4.32–
4.28 (m, 1H), 2.49 (s, 3H), 2.22–2.15 (m, 1H), 2.00–1.80 (m, 2H), 1.85–
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0.11 ppm (s, 9H); 13C NMR (CDCl3): d = 147.1, 131.4, 71.7, 64.3, 50.4,
48.8, 46.9, 42.1, 25.3, 25.2, 20.1, 18.3, 13.0, 12.9, À0.2, À1.5, À1.7 ppm; MS
79
(ESI, positive mode): m/z: 361.0 [MÀ Br]+; elemental analysis calcd
(%) for C17H33BrOSeSi: C 46.36, H 7.55; found: C 46.41, H 7.61. X-ray
structure analysis: C17H33BrOSeSi, M=440.39; monoclinic, space group
3788
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 3784 – 3789

Stereoselective Synthesis of Cyclopropanes
FULL PAPER
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Received: September 19, 2008
Published online: February 19, 2009
Chem. Eur. J. 2009, 15, 3784 – 3789
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3789