Organocatalytic asymmetric cyclopropanation of α,β-unsaturated aldehydes with arsonium ylides

Article abstract of DOI:10.1016/j.tetasy.2007.10.007

A novel organocatalytic asymmetric cyclopropanation of α,β-unsaturated aldehydes with arsonium ylides using diphenylprolinol silylether as a catalyst is described. A variety of chiral cyclopropyl aldehydes are obtained in moderate to good yields with up t

Full text of DOI:10.1016/j.tetasy.2007.10.007

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 18 (2007) 2462–2467
Organocatalytic asymmetric cyclopropanation of a,b-unsaturated
aldehydes with arsonium ylides
Yun-Hui Zhao,a,b Gang Zhaob,* and Wei-Guo Caoa,*
aDepartment of Chemistry, Shanghai University, Shanghai 200444, China
bLaboratory of Modern Synthetic Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, PR China
Received 31 August 2007; accepted 2 October 2007
Abstract—A novel organocatalytic asymmetric cyclopropanation of a,b-unsaturated aldehydes with arsonium ylides using diphenylpro-
linol silylether as a catalyst is described. A variety of chiral cyclopropyl aldehydes are obtained in moderate to good yields with up to 99:1
dr (diastereomeric ratio) and 99% ee under simple and mild reaction conditions.
ꢀ 2007 Elsevier Ltd. All rights reserved.
O
1. Introduction
NC
CN
KF·2H2O
DME
CN
CN
Ph3As
ArCH
C
+
Br
Cyclopropanes and their derivatives are not only common
structures found in many natural and biologically active
compounds,1 but also versatile building blocks1a,2 for
organic synthesis, because of their unique combination of
reactivity and structural properties. Significant progress
has been made in the use of a vast array of organometallic
carbenoids3 for the preparation of these types of com-
pounds. On the other hand, several stabilized ylides have
also been employed successfully for this purpose. For in-
stance, Corey4 pioneered the use of sulfonium ylides, while
Aggarwal5 has developed the asymmetric cyclopropanation
of electron-deficient alkenes mediated by chiral sulfides.
Recently, Dai and Tang6 utilized chiral telluronium and
sulfonium ylides for the enantioselective synthesis of vinyl-
cyclopropanes. Gaunt7 disclosed an organocatalytic enan-
tioselective cyclopropanation via ammonium ylides. More
recently, MacMillan et al.8 realized a highly enantioselec-
tive organocatalytic cyclopropanation reaction between
stabilized sulfonium ylides and a,b-unsaturated aldehydes
by using 2-carboxylic acid dihydroindole as the catalyst.
Most recently, Arvidsson9 employed (S)-(ꢀ)-indoline-
2-yl-1H-tetrazole and novel aryl sulfonamides as new
catalysts for the enantioselective organocatalytic cyclo-
Ar COPh
Scheme 1. Stereoselective cyclopropanation reaction of electron-deficient
olefins.11b
reaction between halomalonates or 2-halo-b-keto esters
and enals. Our group11 has accomplished the highly stereo-
selective synthesis of cyclopropanes with arsonium ylides
and electron-deficient olefins (Scheme 1). Still interested
in the chemistry of arsonium ylides and inspired by other
studies in organocatalytic asymmetric cyclopropanation
reactions4–10 of stabilized ylides and the great achievements
of asymmetric iminium catalysis chemistry,12 we envisioned
that a combination of the iminium catalysis with arsonium
ylides would provide access to cyclopropanes with high
enantioselectivity. Herein we report our studies using this
strategy.
2. Results and discussion
Our initial experiment was carried out using 20 mol % of
TMS-protected diphenylprolinol 3 as the catalyst, and
chloroform as solvent. The reaction between cinnamalde-
´
propanation of a,b-unsaturated aldehydes, while Cordav-
a10 reported a chiral amine catalyzed cyclopropanation
˚
hyde and arsonium salts, in the presence of 4 A MS, gave
*
the cyclopropane product in very low yield (19%), but with
excellent enantioselectivity (95% ee) (Table 1, entry 1).
Corresponding authors. E-mail addresses: zhaog@mail.sioc.ac.cn;
wgcao@staff.shu.edu.cn
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.10.007

Y.-H. Zhao et al. / Tetrahedron: Asymmetry 18 (2007) 2462–2467
2463
Table 1. Optimization of organocatalytic asymmetric cyclopropanations of a,b-unsaturated aldehydesa
Ph
Ph
OTMS
O
O
Ph
N
H
CHO
3
Ph3As
+
Br
Cs2CO3, 0.5 equiv,
CHCl3
Ph
Ph
CHO
2a
1a
4a
Entry
Catalyst
Solvent
Arsonium salt
Cs2CO3
% yieldb
drc
30:1
% eed
1
2
3
4
5
0.2
1.0
0.2
0.2
0.2
0.3
0.3
0.3
0.3
0.3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
Toluene
Toluene
CHCl3
1.0
1.0
1.0
1.5
2.0
1.0
1.0
1.0
1.0
1.0
—
—
19
82
54
24
20
66
60
58
55
52
95
98
96
96
94
99
98
98
99
98
>99:1
16:1
>99:1
32:1
18:1
25:1
20:1
25:1
20:1
0.5
1.5
2.0
0.5
0.5
0.5
0.5
0.5
6
7e
8
9e
10f
a
˚
Reaction conditions: unless specified, a mixture of cinnamaldehyde (0.2 mmol), catalyst, and 4 A MS (100 mg) in chloroform (4 mL) was stirred for
30 min at room temperature before the arsonium salt and Cs2CO3 (50 mol %) were added, and then the stirring was continued for 24 h at room
temperature.
b Isolated yield.
c Determined by chiral HPLC or 1H NMR analysis.
d Determined by chiral HPLC analysis.
e Reaction carried out at 0 ꢁC.
f
˚
No 4 A MS was added.
Encouraged by this result, we performed another experi-
ment using 1 equiv of catalyst 3. We were delighted to find
that the reaction took place smoothly and gave the product
in 82% yield and 98% ee. Based on the above results, we
supposed that TMS-protected diphenylprolinol 3 served
not only as a catalyst, but also as a base, which deproto-
nated the arsonium salts to yield arsonium ylides. There-
fore, in order to decrease the loading of catalyst and
increase the efficiency of the reaction, a base was chosen
as an additive for this reaction. As shown in Table 1, when
50 mol % of cesium carbonate was added, the yield in-
creased to 54% and the enantioselective excess was 96%
(Table 1, entry 3). Attempts, which increased the amount
of arsonium salts to 150 mol % or 200 mol %, or used lesser
amounts of base, resulted in low yields13 (Table 1, entries 4
and 5). When the amount of catalyst was increased to
30 mol %, a 66% yield was obtained. The effects of solvent
and reaction temperature were also studied. Under opti-
mized conditions (1.0 equiv cinnamaldehyde, 1.0 equiv
arsonium salt, 50 mol % of cesium carbonate, and
30 mol % of catalyst), the desired cyclopropane could be
produced in up to 99% ee and in 66% yield (Table 1, entry
6). To the best of our knowledge, this is the first example of
enantioselective cyclopropanation based on arsonium salts.
A comparison with the literature data of the specific rota-
potassium hydroxide (80% ee, Table 2, entry 4), while the
yields were lower. Additionally, it seems that the diastereo-
selectivity decreased alongside an increase in the basicity of
the bases (Table 2, entries 1–4).
Table 2. Screening of bases for the organocatalytic asymmetric cyclo-
propanation of a,b-unsaturated aldehydes and arsonium ylidesa
Ph
Ph
OTMS
O
Ph
O
N
H
CHO
3
Ph3As
Br
+
Base,CHCl3
Ph
Ph
CHO
1a
4a
2a
Entry
Base (mol %)
% yieldb
drc
% eed
1
2
Li2CO3
Na2CO3
K2CO3
KOH
CsF
DMAP
Et3N
Pyridine
DABCO
DBU
50
50
50
100
100
50
100
100
50
44
80
72
12
54
56
28
40
34
53:1
38:1
29:1
2:1
49:1
16:1
3:1
10:1
5:1
NDe
98
98
99
80
99
98
98
99
98
ND
3
4
5
6
7
8
9
10
100
Trace
tion value revealed that the absolute configuration of com-
a Reaction conditions: unless specified, a mixture of cinnamaldehyde
25
pound 4a was (1R,2S,3R) {½aꢁD ¼ ꢀ167:7 (c 1.0, CHCl3),
˚
(0.2 mmol), catalyst (30 mol %), and 4 A MS (100 mg) in chloroform
lit. (1R,2S,3R)-4a [a]D = ꢀ165.7 (c 1.0, CHCl3)7}.
(4 mL) was stirred for 30 min at room temperature before the arsonium
salt and base were added, and then the stirring was continued for 24 h at
room temperature.
Next, a variety of organic and inorganic bases were
screened for this reaction. The results are summarized in
Table 2. Sodium carbonate (50 mol %) gave the best yield
(80% yield, Table 2, entry 2) and 98% ee. Other bases also
gave nearly the same ee values (98–99% ee) except for
b Isolated yield.
c Determined by chiral HPLC or 1H NMR analysis.
d Determined by chiral HPLC analysis.
e Not determined.

2464
Y.-H. Zhao et al. / Tetrahedron: Asymmetry 18 (2007) 2462–2467
Table 3. Scope of the organocatalytic enantioselective asymmetric cyclopropanation reaction of a,b-unsaturated aldehydesa
R1
Ph
O
Ph
N
H
O
OTMS
CHO
3
Ph3As
Br
+
Na2CO3,CHCl3
R2
R2
R1
CHO
1
2
4
Entry
R1
R2
Product
% yieldb
drc
38:1
11:1
25:1
19:1
>99:1
5:1
% eed
1
2
3
4
5
6
7
8
9
H
F
Cl
Br
NO2
Me
MeO
H
H
Br
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
n-Pr
n-Pr
4a
4b
4c
4d
4e
4f
80
73
65
80
70
51
55
50
67
61
98
97
96
96
98
98
98
78
96
95
4g
4h
4i
>99:1
2:1
4:1
10
4j
>99:1
a
˚
Reaction conditions: unless specified, a mixture of cinnamaldehyde (0.2 mmol), catalyst (30 mol %), and 4 A MS (100 mg) in chloroform (4 mL) was
stirred for 30 min at room temperature before the arsonium salt and Na2CO3 (50 mol %) were added, after which stirring was continued for 24 h at room
temperature.
b Isolated yield.
c Diastereoselectivity determined by chiral HPLC or 1H NMR analysis.
d Determined by chiral HPLC analysis.
Under the optimized reaction conditions above, the scope
of the reaction between arsonium ylide reagents and a,b-
unsaturated aldehydes was investigated. The results are
summarized in Table 3. Generally, by using TMS-protected
diphenylprolinol derivative 3 as the catalyst, the reactions
between a range of readily available arsonium salts and
a,b-unsaturated aldehydes provided cyclopropane prod-
ucts in moderate yields and excellent ee values. For exam-
ple, arsonium salts 1 bearing electron-withdrawing groups
(EWG) (R1 = EWG) gave the corresponding cyclopro-
panes 4 in good yields (Table 3, entries 2–5), while arso-
nium salts 1 bearing electron-donating-groups (EDG)
(R1 = EDG) usually provided slightly lower yields of cyclo-
propanes 4 (Table 3, entries 6 and 7). In addition, as shown
in Table 3, the reactions of aromatic a,b-unsaturated alde-
hyde worked well to provide the corresponding products
with high enantioselectivity (96–98% ee, Table 3, entries
1–7), while the use of crotonaldehyde as a substrate
resulted in poorer enantioselectivity (78% ee, Table 3, entry
8).
group led to no reaction, and low conversion was observed
for the arsonium salts with an ester group. We presume
that it was due to the low acidity of the a-proton of these
groups.
Based on the above results, a possible mechanism for the
asymmetric organocatalytic cyclopropanation is proposed
(Scheme 3). Firstly, the a,b-unsaturated aldehyde is acti-
vated by the amine catalyst 3 through the formation of
the reactive iminium intermediate (I).11c,d Then, as a
nucleophile, the arsonium ylides attack the b-carbon of
the a,b-unsaturated aldehyde to form the enamine inter-
mediate (II). An intramolecular SN2 substitution takes
place to form the cyclopropyl enamine intermediate
(III). Finally, the intermediate (III) is hydrolyzed to
produce the desired cyclopropane and release the amine
catalyst 3 simultaneously.
3. Conclusion
In conclusion, we have developed a novel enantioselective
organocatalytic cyclopropanation reaction between arso-
nium ylides and a,b-unsaturated aldehydes with a diphen-
ylprolinol silyl ether as catalyst. The reaction conditions
were very mild while the corresponding cyclopropanes
could be obtained in moderate to good yields and with high
enantioselectivities. Further applications of this new pro-
cess in asymmetric synthesis are currently in progress.
Other types of arsonium salts were also investigated under
similar reaction conditions (Scheme 2). Unfortunately,
replacing the benzoyl group with a nitrile group or a phenyl
Ph
R3
Ph
N
CHO
H
OTMS
Ph3As
R3 Br
+
Na2CO3,CHCl3
Ph
Ph
CHO
Ph3AsCH2CO2Me
Br
4. Experimental
Ph3As CH2CN
Ph AsCH Ph
Br
Br
3
2
0% conversion
0% conversion
low conversion
General: Analytical TLC was carried out on precoated sil-
ica gel plates. Column chromatography was conducted
with 300–400 mesh silica gel. NMR spectra were recorded
Scheme 2. Other arsonium ylides applied in the organocatalytic cyclo-
propanations of a,b-unsaturated aldehydes.

Y.-H. Zhao et al. / Tetrahedron: Asymmetry 18 (2007) 2462–2467
2465
O
Br
Ph3As
Base
Ar
Ar
Ph
Ph
OTMS
O
H2O
N
Ph3As
O
R
I
R
Ph
Ph
OTMS
Ph
Ph
Ph
O
H
O
N
H
N
Ph
OTMS
OTMS
N
Ar
Ar
H
Ph3As
H
3
II
Ph3As
CHO
R
R
H
Transoid Approach
O
III
R
Ar
Ph
Ph
OTMS
N
H2O
AsPh3
O
R
Ar
Scheme 3. Mechanism of the asymmetric organocatalytic cyclopropanation of a,b-unsaturated aldehydes.
1
at 300 MHz for H NMR using SiMe4 as an internal stan-
dard in CDCl3 and 75 MHz for 13C NMR. Enantiomeric
excesses were determined by chiral HPLC analysis. Optical
rotations were measured on a JASCO 1030 polarimeter.
All solvents were used directly without further purification.
were reported in the literature.8 The diastereomeric and
enantiomeric ratios were determined by HPLC analysis
of the alcohol, obtained by NaBH4 reduction of the
aldehyde, using a Chiracel OJ column (22 ꢁC, 254 nm,
90:10 hexane/2-propanol, 1 mL/min); tmajor = 26.8 min,
tminor = 21.7 min.
4.1. General procedure for the organocatalytic asymmetric
cyclopropanation of cyclopropyl aldehyde 4a
4.3. (1R,2S,3R)-2-(4-Fluorobenzoyl)-3-phenyl-cyclopropane-
carbaldehyde 4b
˚
To a suspension of 100 mg of 4 A MS in chloroform
25:0
(CHCl3, 4 mL) were added successively aldehydes
(0.2 mmol) and TMS-protected diphenylprolinol derivative
(20 mg, 0.06 mmol) at room temperature. After stirring for
30 min, 0.2 mmol of the arsonium salt and sodium carbon-
ate (10.6 mg, 0.1 mmol) was added to the reaction mixture.
The mixture was stirred at room temperature for 24 h until
the starting material disappeared. The mixture was then
eluted with CH2Cl2 (20 mL) through Celite; the filtrate
was washed successively with HCl (0.5 M, 4 mL), saturated
NaHCO3 (2 · 8 mL), and brine (10 mL), and then dried
over MgSO4. Removal of the solvent under reduced pres-
sure afforded the crude product. The latter was directly
purified by flash chromatography on silica gel (CH2Cl2/
hexane 2:3) to afford the pure cyclopropyl 4, which was
Yellow oil, ½aꢁD ¼ ꢀ137:1 (c 1.0, CHCl3), IR (film) 3065,
3035, 2856, 2259, 1705, 1674, 1599, 1505, 1424, 1224, 1154,
1
851, 614 cmꢀ1; H NMR (300 MHz, CDCl3) 9.58 (d, 1H,
J = 6.3 Hz), 8.01–8.05 (m, 2H), 7.14–7.40 (m, 7H), 3.61
(dd, 1H, J = 6.0, 6.0 Hz), 3.42 (dd, 1H, J = 6.0, 9.3 Hz),
2.69 (ddd, 1H, J = 6.0, 6.3, 9.3 Hz); 13C NMR (75 MHz,
CDCl3) d 197.9, 193.7, 136.9, 131.3, 131.2, 129.0, 127.8,
126.6, 116.2, 115.9, 40.8, 36.8, 32.5; LRMS (EI): m/e 123,
95, 145, 239, 115, 212, 75, 117; HRMS (EI) exact mass cal-
culated for (C17H13FO2) requires m/z 268.0900, found m/z
268.0907. The diastereomeric and enantiomeric ratios were
determined by HPLC analysis of the alcohol, obtained
by NaBH4 reduction of the aldehyde, using a Chiracel
AS-H column (22 ꢁC, 254 nm, 90:10 hexane/2-propanol,
1 mL/min); tmajor = 16.7 min, tminor = 13.6 min.
1
confirmed by the comparison of the H NMR data with
the reported one in the literature. The ee value was deter-
mined by chiral HPLC analysis.
4.4. (1R,2S,3R)-2-(4-Chlorobenzoyl)-3-phenyl-cyclopropane-
carbaldehyde 4c
4.2. (1R,2S,3R)-2-Benzoyl-3-phenyl- cyclopropanecarb-
aldehyde 4a8
26:3
Yellow oil, ½aꢁD ¼ ꢀ86:4 (c 1.0, CHCl3), IR (film) 3052,
2926, 2844, 1705, 1673, 1589, 1505, 1427, 1403, 1224,
25:5
Yellow oil; ½aꢁD ¼ ꢀ167:7 (c 1.0, CHCl3); IR (film) 3063,
1126, 1092, 1012, 997, 754, 697 cmꢀ1 1H NMR
;
3035, 2855, 1709, 1676, 1598, 1582, 1458, 1377, 1224 cmꢀ1
;
(300 MHz, CDCl3) d 9.57 (d, 1H, J = 6.3 Hz), 7.92–7.95
(d, 2H, J = 8.1 Hz), 7.21–7.48 (m, 7H), 3.61 (dd, 1H,
J = 6.0, 6.0 Hz), 3.40 (dd, 1H, J = 6.0, 9.3 Hz), 2.69
(ddd, 1H, J = 6.0, 6.3, 9.3 Hz); 13C NMR (75 MHz,
CDCl3) d 197.9, 194.0, 140.4, 136.9, 135.2, 129.9, 129.2,
1H NMR (300 MHz, CDCl3) d 9.59 (d, J = 6.3 Hz, 1H),
8.01–7.96 (m, 2H), 7.61–7.16 (m, 8H), 3.60 (dd, J = 6.0,
6.0 Hz, 1H), 3.48 (dd, J = 6.0, 9.1 Hz, 1H), 2.68 (ddd,
J = 6.0, 6.3, 9.1 Hz, 1H); 13C NMR and MS spectral data

2466
Y.-H. Zhao et al. / Tetrahedron: Asymmetry 18 (2007) 2462–2467
129.0, 127.8, 126.6, 40.9, 36.8, 32.7; LRMS (EI) m/e 139,
111, 141, 115, 145, 75, 255, 113; HRMS (EI) exact mass
calculated for (C17H13ClO2) requires m/z 284.0604, found
m/z 284.0596. The diastereomeric ratio was determined
145.2, 137.1, 134.3, 129.6, 129.0, 128.7, 127.6, 126.6, 40.9,
36.8, 32.4, 21.8; LRMS (EI) m/e 119, 91, 115, 65, 221,
235, 120, 208; HRMS (EI) exact mass calculated for
(C18H16O2) requires m/z 264.1150, found m/z 264.1157.
The diastereomeric ratio was determined by 1H NMR.
The enantiomeric ratio was determined by HPLC analysis
of the alcohol, obtained by NaBH4 reduction of the alde-
hyde, using a Chiracel AS-H column (21 ꢁC, 254 nm,
90:10 hexane/2-propanol, 1 mL/min); tmajor = 17.8 min,
tminor = 15.1 min.
1
by H NMR; the enantiomeric ratio was determined by
HPLC analysis of the alcohol, obtained by NaBH4 reduc-
tion of the aldehyde, using a Chiracel AS-H column
(23 ꢁC, 254 nm, 90:10 hexane/2-propanol, 1 mL/min);
tmajor = 15.7 min, tminor = 13.6 min.
4.5. (1R,2S,3R)-2-(4-Bromobenzoyl)-3-phenyl-cyclopropane-
carbaldehyde 4d
4.8. (1R,2S,3R)-2-(4-Methoxylbenzoyl)-3-phenyl-cyclo-
propanecarbaldehyde 4g
26:3
Yellow oil, ½aꢁD ¼ ꢀ80:6 (c 1.0, CHCl3), IR (film) 2926,
24:7
2844, 1704, 1671, 1585, 1505, 1428, 1403, 1223, 1071,
Yellow oil, ½aꢁD ¼ ꢀ174:6 (c 1.0, CHCl3), IR (film) 2933,
1
996, 753, 697 cmꢀ1; H NMR (300 MHz, CDCl3) d 9.57
2837, 1703, 1662, 1585, 1510, 1428, 1355, 1261, 1235,
1
(d, 1H, J = 6.0 Hz), 7.86–7.84 (d, 2H, J = 8.1 Hz), 7.39–
7.36 (d, 2H, J = 8.7 Hz), 7.39–7.20 (m, 5H), 3.61 (dd, 1H,
J = 6.0, 6.0 Hz), 3.40 (dd, 1H, J = 6.0, 9.3 Hz), 2.69
(ddd, 1H, J = 6.0, 6.3, 9.3 Hz); 13C NMR (75 MHz,
CDCl3) 197.9, 194.4, 136.7, 135.5, 132.2, 130.0, 129.2,
129.0, 127.8, 126.6, 40.9, 36.8, 32.7; LRMS (EI) m/e 183,
185, 115, 145, 155, 157, 192, 76; HRMS (EI) exact mass
calculated for (C17H13BrO2) requires m/z 328.0099, found
m/z 328.0105. The diastereomeric and enantiomeric ratios
were determined by HPLC analysis of the alcohol,
obtained by NaBH4 reduction of the aldehyde, using a
Chiracel AS-H column (22 ꢁC, 254 nm, 90:10 hexane/2-
propanol, 1 mL/min); tmajor = 17.4 min, tminor = 15.3 min.
1167 cmꢀ1; H NMR (300 MHz, CDCl3) d 9.57 (d, 1H,
J = 6.3 Hz), 8.00–7.97 (d, 2H, J = 8.7 Hz), 7.36–7.26 (m,
5H), 6.97–6.94 (d, 2H, J = 8.7 Hz), 3.88 (s, 3H), 3.58 (dd,
1H, J = 6.0, 6.0 Hz), 3.44 (dd, 1H, J = 6.0, 9.1 Hz), 2.68
(ddd, 1H, J = 6.0, 6.3, 9.1 Hz); 13C NMR (75 MHz,
CDCl3) d 198.4, 193.4, 164.1, 137.2, 130.9, 129.9, 128.9,
127.6, 126.6, 114.0, 55.6, 40.8, 36.7, 32.2; LRMS (EI) m/e
135, 77, 115, 107, 92, 136, 251, 224; HRMS (EI) exact mass
calculated for (C18H16O3) requires m/z 280.1099, found
m/z 280.1092. The diastereomeric and enantiomeric ratios
were determined by HPLC analysis of the alcohol,
obtained by NaBH4 reduction of the aldehyde, using a
Chiracel OD-H column (22 ꢁC, 254 nm, 90:10 hexane/
2-propanol, 1 mL/min); tmajor = 18.2 min and tminor
=
4.6. 1(R,2S,3R)-2-(4-Nitrobenzoyl)-3-phenyl-cyclopropane-
carbaldehyde 4e
21.3 min.
4.9. (1R,2S,3R)-2-Benzoyl-3-methyl-cyclopropanecarb-
aldehyde 4h8
26:1
Yellow oil, ½aꢁD ¼ ꢀ119:1 (c 1.0, CHCl3), IR (film) 3059,
2925, 2854, 1705, 1681, 1603, 1525, 1500, 1427, 1346, 1319,
24:9
1220, 998, 856, 741, 697 cmꢀ1
;
1H NMR (300 MHz,
Light yellow oil, ½aꢁD ¼ ꢀ6:1 (c 1.0, CHCl3), IR (film)
CDCl3) d 9.55 (d, 1H, J = 6.3 Hz), 8.29–8.26 (d, 2H,
J = 8.1 Hz), 8.09–8.06 (d, 2H, J = 9.0 Hz), 7.30–7.16 (m,
5H), 3.58 (dd, 1H, J = 6.0, 6.0 Hz), 3.38 (dd, 1H, J = 6.0,
9.1 Hz), 2.71 (ddd, 1H, J = 6.0, 6.3, 9.1 Hz); 13C NMR
(75 MHz, CDCl3) d 197.4, 194.2, 141.1, 136.3, 129.9,
129.5, 129.1, 128.1, 126.5, 124.1, 41.0, 37.2, 33.2; LRMS
(EI) m/e (rel %) 135 (100), 150 (34), 77 (31), 115 (31), 266
(24), 145 (22), 92 (20), 104 (19); HRMS (EI) exact mass cal-
culated for (C17H13NO4) requires m/z 295.0845, found m/z
3061, 2966, 2931, 1709, 1673, 1598, 1581, 1450, 1226,
1
1074, 1021 cmꢀ1; H NMR (300 MHz, CDCl3) d 9.36 (d,
1H, J = 6.3 Hz), 7.99–7.97 (d, 2H, J = 7.8 Hz), 7.63–7.26
(m, 3H), 3.00 (dd, 1H, J = 6.0, 8.5 Hz), 2.56 (m, 1H),
2.10 (ddd, 1H, J = 6.3, 6.3, 8.7 Hz), 1.36 (d, 3H,
J = 6.0 Hz); 13C NMR and MS spectral data were reported
in the literature.8 The diastereomeric ratio was determined
1
by H NMR. The enantiomeric ratio was determined by
HPLC analysis of the alcohol, obtained by NaBH4 reduc-
1
295.0836. The diastereomeric ratio was determined by H
tion of the aldehyde, using a Chiracel OD column (23 ꢁC,
254 nm, 90:10 hexane/2-propanol, 1 mL/min); tmajor
11.5 min, tminor = 10.8 min.
NMR. The enantiomeric ratio was determined by HPLC
analysis of the alcohol, obtained by NaBH4 reduction of
the aldehyde, using a Chiracel AS-H column (23 ꢁC,
254 nm, 90:10 hexane/2-propanol, 1 mL/min); tmajor
36.2 min, tminor = 26.9 min.
=
=
4.10. (1R,2S,3R)-2-Benzoyl-3-propyl-cyclopropanecarb-
aldehyde 4i8
25:4
4.7. (1R,2S,3R)-2-(4-Methylbenzoyl)-3-phenyl-cyclopropane-
carbaldehyde 4f
Light yellow oil, ½aꢁD ¼ ꢀ16:4 (c 1.0, CHCl3), IR (film)
2959, 2929, 2872, 1706, 1667, 1609, 1579, 1449, 1371,
1264, 1227, 1178, 1011 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 9.37 (d, 1H, J = 6.3 Hz), 8.03–7.97 (m, 2H), 7.63–7.26 (m,
3H), 3.00 (dd, 1H, J = 5.9, 8.3 Hz), 2.55–2.53 (m, 1H),
2.16–2.09 (m, 1H), 1.60–1.46 (m, 4H), 0.96 (m, 3H); 13C
NMR and MS spectral data were reported in the litera-
ture.8 The diastereomeric ratio was determined by 1H
NMR. The enantiomeric ratio was determined by HPLC
analysis of the alcohol, obtained by NaBH4 reduction of
25:8
Yellow oil, ½aꢁD ¼ ꢀ81:4 (c 1.0, CHCl3), IR (film) 3030,
2926, 2852, 1704, 1667, 1606, 1500, 1428, 1360, 1231,
1
1183, 753, 697 cmꢀ1; H NMR (300 MHz, CDCl3) d 9.58
(d, 1H, J = 6.3 Hz), 7.91–7.89 (d, 2H, J = 8.4 Hz), 7.36–
7.21 (m, 7H), 3.60 (dd, 1H, J = 6.0, 6.0 Hz), 3.47 (dd,
1H, J = 6.0, 9.1 Hz), 2.66 (ddd, 1H, J = 6.0, 6.3, 9.1 Hz),
2.43 (s, 3H); 13C NMR (75 MHz, CDCl3) d 198.3, 194.7,

Y.-H. Zhao et al. / Tetrahedron: Asymmetry 18 (2007) 2462–2467
2467
6. (a) Ye, S.; Huang, Z. Z.; Xia, C. A.; Tang, Y.; Dai, L. X. J.
Am. Chem. Soc. 2002, 124, 2432; (b) Liao, W. W.; Li, K.;
Tang, Y. J. Am. Chem. Soc. 2003, 125, 13030.
7. (a) Papageorgiou, C. D.; Ley, S. V.; Gaunt, M. J. Angew.
Chem., Int. Ed. 2003, 42, 828; (b) Papageorgiou, C. D.;
Cubillo de Dios, M. A.; Ley, S. V.; Gaunt, M. J. Angew.
Chem., Int. Ed. 2004, 43, 4641.
the aldehyde, using a Chiracel AD column (21 ꢁC, 254 nm,
90:10 hexane/2-propanol, 1 mL/min); tmajor = 13.7 min,
tminor = 15.1 min.
4.11. (1R,2S,3R)-2-(4-Bromobenzoyl)-3-propyl-cyclopro-
panecarbaldehyde 4j
8. Kunz, R. K.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005,
127, 3240.
26:5
Yellow oil, ½aꢁD ¼ ꢀ38:6 (c 1.0, CHCl3), IR (film) 2960,
9. (a) Hartikka, A.; Arvidsson, P. I. J. Org. Chem. 2007, 72,
2929, 2872, 1704, 1670, 1585, 1568, 1437, 1400, 1362,
1221, 1174, 1070, 1026, 1008, 994, 844, 784 cmꢀ1 1H
;
´
´
5874; (b) Hartikka, A.; Slosarczyk, A. T.; Arvidsson, P. I.
Tetrahedron: Asymmetry 2007, 18, 1403.
NMR (300 MHz, CDCl3) d 9.36 (d, 1H, J = 6.3 Hz),
7.87–7.83 (dd, 2H, J = 8.4, 10.5 Hz), 7.65–7.62 (d, 2H),
2.98–2.94 (dd, 1H, J = 5.9, 8.2 Hz), 2.54–2.48 (m, 1H),
2.17–2.10 (m, 1H), 1.62–1.46 (m, 4H), 0.96 (m, 3H); 13C
NMR (75 MHz, CDCl3) d 199.1, 195.2, 135.8, 132.1,
129.8, 129.0, 40.1, 34.5, 34.1, 29.4, 22.0, 13.7; LRMS (EI)
m/e 183, 253, 144, 157, 41; HRMS (EI) exact mass calcu-
lated for (C14H15BrO2) requires m/z 294.0255, found m/z
294.0249. The diastereomeric and enantiomeric ratios were
determined by HPLC analysis of the alcohol, obtained by
NaBH4 reduction of the aldehyde, using a Chiracel
OD-H column (21 ꢁC, 254 nm, 90:10 hexane/2-propanol,
1 mL/min); tmajor = 16.8 min, tminor = 18.4 min.
10. Rios, R.; Sunden, H.; Vesely, J.; Zhao, G. L.; Dziedzic, P.;
´
Cordova, A. Adv. Synth. Catal. 2007, 349, 1028.
11. (a) Ren, Z. J.; Ding, W. Y.; Cao, W. G.; Wang, S. H.; Huang,
Z. J. Synth. Commun. 2002, 32, 3143; (b) Ren, Z. J.; Cao, W.
G.; Ding, W. Y.; Wang, Y.; Wang, L. L. Synth. Commun.
2004, 34, 3785; (c) Ren, Z. J.; Cao, W. G.; Ding, W. Y.; Shi,
W. Synth. Commun. 2004, 34, 4395; (d) Ren, Z. J.; Cao, W.
G.; Ding, W. Y.; Wang, Y. Synthesis 2005, 2718; (e) Ren, Z.
J.; Cao, W. G.; Chen, J.; Ding, W. Y.; Wang, Y. Synth.
Commun. 2005, 35, 3099.
12. (a) Brown, S. P.; Brochu, M. P.; Sinz, C. J.; MacMillan, D.
W. C. J. Am. Chem. Soc. 2003, 125, 10808; (b) Marigo, M.;
Franzen, J.; Poulsen, T. B.; Zhuang, W.; Jørgensen, K. A. J.
Am. Chem. Soc. 2005, 127, 6964; (c) Marigo, M.; Wabnitz,
T. C.; Fielenbach, D.; Jørgensen, K. A. Angew. Chem., Int.
Ed. 2005, 44, 794; (d) Hayashi, Y.; Gotoh, H.; Hayashi, T.;
Shoji, M. Angew. Chem., Int. Ed. 2005, 44, 4212; (e) Yang,
J. W.; Hechavarria Fonseca, M. T.; Vignola, N.; List, B.
Angew. Chem., Int. Ed. 2005, 44, 108; (f) Wang, W.; Li, H.;
Wang, J.; Zu, L. S. J. Am. Chem. Soc. 2006, 128, 10354; (g)
Marigo, M.; Bertelsen, S.; Landa, A.; Jørgensen, K. A. J.
Am. Chem. Soc. 2006, 128, 5475; (h) Brandau, S.; Landa,
A.; Franzen, J.; Marigo, M.; Jørgensen, K. A. Angew.
Chem., Int. Ed. 2006, 45, 4305; (i) Carlone, A.; Marrigo, M.;
North, C.; Landa, A.; Jørgensen, K. A. Chem. Commun.
2006, 4928; (j) McCooey, S. H.; McCabe, T.; Connon, S. J.
J. Org. Chem. 2006, 71, 7494; (k) Zu, L. S.; Li, H.; Xie, H.
X.; Wang, J.; Jiang, W.; Tang, Y.; Wang, W. Angew. Chem.,
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L. S.; Jiang, W.; Wang, W. Org. Lett. 2007, 9, 965; (m)
Acknowledgments
The generous financial support from the National Natural
Science Foundation of China (Nos. 20532040 and
20672135), QT Program, and Excellent Young Scholars
Foundation of NSFC (20525208) are gratefully
acknowledged.
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13. Preliminary studies revealed that product 4a could undergo
further Witting type reactions in the presence of an excess of
arsonium salt under our reaction conditions. Further thor-
ough study is currently in progress and will be reported in due
time.