The first asymmetric catalytic halo aldol reaction of β-iodo allenoates with aldehydes by using chiral salen catalyst

Article abstract of DOI:10.1016/j.tetasy.2005.03.038

The first asymmetric catalytic halo aldol reaction of β-iodo allenoates with aldehydes was established. The reaction was successfully achieved by using (R,R)-SalenAlCl as the chiral catalyst and LiI as an additive at 0°C in dichloromethane. Moderate to good yields and up to 62% ee were obtained. The new system showed a good substrate scope in which both aromatic aldehydes and aliphatic aldehydes can be employed. The reaction provided the first catalytic and enantioselective approach to chiral β-iodo Baylis-Hillman ester adducts.

Full text of DOI:10.1016/j.tetasy.2005.03.038

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 1757–1762
The first asymmetric catalytic halo aldol reaction of b-iodo
allenoates with aldehydes by using chiral salen catalyst
Dianjun Chen, Li Guo, S. R. S. Saibabu Kotti and Guigen Li*
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA
Received 14 February 2005; accepted 22 March 2005
Abstract—The first asymmetric catalytic halo aldol reaction of b-iodo allenoates with aldehydes was established. The reaction was
successfully achieved by using (R,R)-SalenAlCl as the chiral catalyst and LiI as an additive at 0 ꢀC in dichloromethane. Moderate to
good yields and up to 62% ee were obtained. The new system showed a good substrate scope in which both aromatic aldehydes and
aliphatic aldehydes can be employed. The reaction provided the first catalytic and enantioselective approach to chiral b-iodo Baylis–
Hillman ester adducts.
ꢁ
2005 Published by Elsevier Ltd.
1
. Introduction
Very recently, we established an enantioselective ap-
proach to b-halo MBH ester adducts by reacting b-halo
aluminum allenoate with aldehydes. The reaction was
6
The asymmetric aldol reaction is amongst the most
important carbon–carbon bond formations in organic
chemistry. Surprisingly, there has been little work re-
ported so far on the asymmetric halo aldol reaction.
Over the past few years, we and others have reported
various halo aldol reactions and their asymmetric ver-
successfully conducted with Et AlI as the iodine source
2
1
–3
and Lewis acid promoter (Scheme 1). A stoichiometric
amount (1.3 equiv) of (R,R)-salen was used as the chiral
ligand. However, this method suffered from the use of a
stoichiometric amount of chiral ligand, which prevented
its utility for economic reasons. Thus, to achieve an
asymmetric catalytic version of this reaction is both
worthwhile and challenging. Herein we report our preli-
minary results on the asymmetric catalytic synthesis of
b-halo MBH ester adducts (Scheme 2).
4
–6
sions. Among these reactions, the halo aldol reactions
of allenolates/allenoates with aldehydes resulted in
b-halo Morita–Baylis–Hillman (MBH) ketone/ester
adducts, which are building blocks of chemical and bio-
logical importance due to an array of functional groups
7
,8
in their structures.
2
. Results and discussion
OH
O
I
O
(
R,R)-Salen (1.3 eq.)
+
RCHO + Et AlI
2
R
OEt
The present catalytic reaction differs from the stoichio-
6
metric process previously reported by us in the follow-
ing aspects. First, the present system is an asymmetric
catalytic process (20 mol % of the chiral complex was
used as the catalyst), while the previous one was a chiral
OEt
DCM, -20˚C
Scheme 1. Ligand-controlled asymmetric synthesis of b-halo MBH
ester adducts.
OH
O
I
O
(
R,R)-SalenAlCl (20 mol%)
LiI (1 eq.), CH Cl , 0˚C
+
RCHO + TMSI
R
OEt
5
OEt
2
2
0-62 %ee
Scheme 2. Asymmetric catalytic synthesis of b-halo MBH ester adducts.
*
0
Corresponding author. Tel.: +1 806 742 3015; fax: +1 806 742 1289; e-mail: guigen.li@ttu.edu
957-4166/$ - see front matter ꢁ 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2005.03.038

1758
D. Chen et al. / Tetrahedron: Asymmetry 16 (2005) 1757–1762
ligand-controlled asymmetric process, in which a stoi-
chiometric amount (1.3 equiv) of chiral ligand was em-
ployed. In addition, the chiral Lewis acid catalyst used
in the present catalytic system is commercially available
and inexpensive. Second, in the present reaction, TMSI
was used to generate the allenoates. In contrast, in the
In the beginning, we tried to reduce the loading of chiral
6
,9
salen ligand and perform the reaction using condi-
tions directly based on the conditions of previous halo
aldol reactions. Unfortunately, the catalytic reaction of
b-halo aluminum allenoate with aldehydes under similar
conditions resulted in very limited success. Since a N-
C F CO oxazaborolidine catalyst has been successfully
previous reaction, Et AlI was first combined with chiral
2
3 7
salen to generate a chiral reagent, which was then treat-
ed with ethyl propiolate in situ to generate the chiral
allenoates. Thirdly, lithium iodide was found to be an
effective additive to enhance the catalytic effectiveness.
Finally, the present catalytic process is easier to perform
but gives similar yields and ees compared with the previ-
ous process, as shown in Tables 1–3.
used in the asymmetric catalytic synthesis of b-halo
4a
MBH ketone adducts, we turned our attention to uti-
lize it as the catalyst to the reaction of aldehydes and
silyl allenoates, which were generated by treating ethyl
propiolate with iodo trimethylsilane (TMSI). Surpris-
ingly, no enantioselectivity was observed.
Since chiral salen ligands have been successfully used in
the previous b-halo aluminum allenoate-based asym-
metric system to introduce the chirality, they were next
6
Table 1. Results of chiral catalyst selection
utilized to replace the N-C F CO oxazaborolidine cata-
3 7
OH
O
I
O
Cat*
lyst to activate the addition of silyl allenoates onto alde-
hydes. A series of chiral salen complexes and other
chiral complexes were tested (Fig. 1) using benzaldehyde
as the model substrate. We were pleased to find that this
effort resulted in encouraging enantioselectivity and
chemical yields as listed in Table 1. Meanwhile, the Z/E
selectivity was also controlled very well, essentially, only
Z isomers were observed for each case.
+
PhCHO + TMSI
Ph
OEt
o
OEt
DCM, 0 C
*
a
b
Entry
Cat
Amount (mol %)
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1e
1e
1f
2
20
20
20
20
10
20
40
20
20
20
20
0
0
—
—
—
32
52
62
65
55
—
29
2
0
42
54
74
73
70
0
M
1a CrCl
1
1
1
1
1
b
c
d
e
f
MnCl
Col
AlI
AlCl
N
O
N
M
1
1
0
1
3
21
74
t-Bu
O
Bu-t
4
Al-O-Al-salen
Bu-t
t-Bu
a
Yields after purification via column chromatography.
Determined by chiral HPLC using chiral OD-H or AD column with
isopropyl alcohol and hexane as the mobile phase.
b
O
O
O
O
AlI
TiCl2
Ti(OEt)2
O
Ph
O
Table 3. Results of the catalytic process with aliphatic aldehydes as the
substrates
Entry Substrate
Product
ee
Yield
b
(%)
2
3
4
a
(
%)
Figure 1. Different chiral complexes used as the catalysts.
OH
O
O
I
O
1
62
31
As shown in Table 1, among the six salen complexes
which were examined, (R,R)-SalenAlCl 1e was proven
to be the best catalyst for this reaction. Interestingly,
catalysts 1a–c did not give any desired product under
this system while salenAlI 1d gave only moderate yields
and inferior ee. Although complexes 2 and 3 have been
OEt
H
1
3
OH
O
2
OEt
56
56
50
44
H
1
4
I
1
0
successfully utilized in other aldol reactions, catalyst 2
for this reaction afforded no product whereas 3 gave
poor chemical yield and ee (21% yield and 29% ee,
respectively). Meanwhile, catalyst 4 gave a good yield
OH
O
I
O
3
OEt
42(59)
H
1
5
(74%), but only afforded 3% ee. It should be mentioned
OH
O
I
that Jacobsen et al. have successfully utilized catalyst 1f
as the catalyst for the highly enantioselective Michael
addition of a,b-unsaturated imides with an excellent ee
O
4
OEt
21
H
1
6
11
achieved. However, in the current catalytic system
the use of 1f did not result in performance superior to
a
Determined by chiral HPLC using a chiral OD-H or AD column with
isopropyl alcohol and hexane as the mobile phase.
1e. Also, there was no obvious improvement in either
ee or chemical yields when the loading of 1e was in-
creased to 40 mol %.
b
The yields are given after purification via column chromatography.
Yields in parentheses are recovered yields.

D. Chen et al. / Tetrahedron: Asymmetry 16 (2005) 1757–1762
1759
Table 2. Results of the catalytic process with aromatic aldehydes as the substrates
OH
O
I
O
(
R,R)-SalenAlCl (20 mol%)
+
RCHO + TMSI
R
OEt
o
OEt
LiI (1 eq.), CH Cl , 0 C
2 2
a
b
Entry
1
Substrate
Product
Reaction time (h)
30
ee (%)
62
Yield (%)
OH
O
I
CHO
74
OEt
1
OH
O
I
2
3
Me
CHO
Me
OEt
30
30
54
62
76(88)
82(94)
2
OH
O
I
CHO
OEt
3
OH
O
CHO
4
5
OEt
48
44
53
58
76(89)
70(92)
I
4
OH
O
Ph
CHO
Ph
OEt
I
5
OH
O
I
6
7
MeO
F
CHO
MeO
F
OEt
6
48
28
59
58
40(91)
73(85)
OH
O
CHO
OEt
I
7
OH
OH
O
8
9
Cl
CHO
CHO
CHO
Cl
OEt
30
30
36
44
57
55
70(84)
75(92)
75(82)
74(80)
I
8
O
Br
Br
OEt
I
9
OH
O
c
1
0
1
F3C
F3C
OEt
53
1
0
I
OH
O
I
CHO
1
OEt
50
50
Br
Br
11
OH
O
I
CHO
1
2
OEt
12
44
54(87)
NC
NC
a
b
c
Determined by chiral HPLC using chiral OD-H or AD column with isopropyl alcohol and hexane as the mobile phase.
Yields after purification via column chromatography. Yields in parentheses are yields after the unreacted aldehydes were recovered.
The compound was first protected by methanesulfonyl group, then the enantiomeric excess was determined by chiral HPLC.
6
The absolute configuration of the product was deter-
mined by chemical correlation, as demonstrated in
Scheme 2. The asymmetric induction can be explained
based on the similar activation situation of the aldehyde,

1760
D. Chen et al. / Tetrahedron: Asymmetry 16 (2005) 1757–1762
in which the si face of the aldehyde is open to the car-
bonyl attack by the b-iodo silyl allenoate intermediate
Similar to our previous Et AlI-based stoichiometric
2
asymmetric process, limited success was realized for ali-
phatic aldehydes. As shown in Table 3, compared with
the previous system, lower yields were obtained for the
four aliphatic cases, which were examined, though high-
er enantioselectivities were obtained. Furthermore, a,b-
unsaturated aldehydes, such as cinnamaldehyde and
crotonaldehyde, which resulted in the desired products
with 33–48% ee in the previous system, failed to give
any halo aldol product under the current catalytic sys-
tem. The aldehydes listed in Table 3 generally took
1
2
(
Scheme 3).
OMe
O
I
OH
O
I
OMe
O
a
b
Ph
OH
Ph
OEt
Ph
OEt
I
OMe
OMe
Ph COOMe
c
d
4
8 h for the reaction to complete.
Ph
COOH
Scheme 3. Absolute configuration determination: (a) MeI, Ag
MeCN, reflux for 4 h; (b) NaOH, MeOH/H O, rt; (c) H IO , RuCl
CCl /MeCN/H O (v/v, 1:1:2); (d) MeOH, TMSCl.
2
O,
2
5
6
2
,
3. Conclusion
4
2
In summary, the first asymmetric catalytic halo aldol
reaction of b-iodo allenoate with aldehydes has been
established. The reaction provided the first catalytic
and enantioselective approach to chiral b-iodo Baylis–
Hillman ester adducts. Moderate enantioselectivity and
useful yields were obtained for a variety of aromatic
aldehydes. Aliphatic aldehydes also showed promising
results for this asymmetric reaction.
Based on the preliminary results described above, efforts
were then made to optimize the catalytic conditions. At
first, several solvents were tested and it was found that
CH Cl was the solvent of choice. The reaction did not
2
2
proceed at all in THF, CH CN, or acetone. In toluene
3
the reaction did proceed, but poor yield and ee (<45%
yield and <40% ee, respectively) were obtained. In
CH Cl the reaction gave similar chemical yields and ee
2
2
at 0 and at À20 ꢀC, but did not proceed at À78 ꢀC.
4. Experimental
Interestingly, LiI was found to be a beneficial additive,
which can promote the reaction at a faster rate and
improve chemical yields as well, thus making the crude
product easier to purify via column chromatography.
One molar aqueous HCl was used in the previous system
to quench the reaction and cleave the resulting silyl
intermediates into the halo aldol products, but it did
not result in complete cleavage for the present system.
It was then found that the solution of 1 M citric acid
in MeOH is superior, which gave higher yields and com-
plete cleavage.
4.1. Typical reaction procedure
In a dry vial, trimethylsilyl iodide (TMSI) (0.1 mL,
0.72 mmol) was added dropwise into a 2.5 mL CH Cl
2
2
solution of ethyl propiolate (0.075 mL, 0.75 mmol) under
inert gas protection. The resulting solution was stirred at
room temperature for 2–3 h. It was then transferred into
a 3 mL CH Cl solution of Salen aluminum chloride
2
2
(0.06 g, 0.1 mmol), lithium iodide (0.067 g, 0.5 mmol),
and benzaldehyde (0.05 mL, 0.5 mmol) at À78 ꢀC. The
reaction mixture was brought to 0 ꢀC bath after 10 min
and stirred for 24 h. The reaction was quenched by the
addition of 3 mL of 1 M citric acid/MeOH solution.
After 10 min, 5 mL of water was added and the two
phases were separated. The aqueous phase was extracted
with 3 · 15 mL of EtOAc, the combined organic phase
then washed with brine and dried with anhydrous
sodium sulfate. Purification by flash chromatography
Based on the optimized reaction conditions, the reaction
was carried out in CH Cl at 0 ꢀC with 20 mol % of
2
2
(
R,R)-SalenAlCl as the catalyst and LiI (1.0 equiv) as
an additive. Various aldehydes were subjected to this
reaction to explore the scope of substrates, the results
are listed in Tables 2 and 3.
(EtOAc/hexane, v/v, 1/5) provided the pure product.
As revealed in Table 2, the reaction worked well for a
large scope of aromatic aldehydes. However, when 2-
and 4-nitrobenzaldehydes were employed as the sub-
strates, there was only a tiny amount of desired products
observed. This phenomenon is difficult to explain at the
current stage. A possible hypothesis is that the newly
formed C(sp )–C(sp ) bonds of the silyl aldol intermedi-
ates dissociated back to the starting materials,
nitrobenzaldehydes.
Compound 1: Isolated as a colorless oil (123 mg, 74%
1
yield). H NMR (500 MHz, CDCl ) d = 7.29–7.38 (m,
3
5H), 7.26 (s, 1H), 5.54 (d, J = 6.0 Hz, 1H), 4.20 (q,
J = 7.0 Hz, 2H), 2.85 (d, J = 6.0 Hz, 1H), 1.22 (t,
1
3
J = 7.0 Hz, 3H);
C
NMR (125 MHz, CDCl3)
3
2
d = 166.1, 145.3, 140.4, 128.9, 128.5, 126.8, 87.1, 76.5,
61.7, 14.2.
Compound 2: Isolated as a colorless oil (131 mg, 76%
1
The reactions of the aromatic substrates shown in Table
2
the starting materials stopped being consumed. The
aldehydes with electron-withdrawing groups on their
aromatic rings proceeded at faster rates than those with
electron-donating groups, which was anticipated.
yield). H NMR (500 MHz, CDCl ) d = 7.199–7.24 (m,
3
generally took 24–48 h to reach the stage at which
3H), 7.13–7.18 (m, 2H), 5.51 (d, J = 5.5 Hz, 1H), 4.20
(q, J = 7.0 Hz, 2H), 2.78 (d, J = 5.5 Hz, 1H), 2.34 (s,
1
3H), 1.23 (t, J = 7.0 Hz, 3H); C NMR (125 MHz,
3
CDCl ) d = 165.9, 145.2, 138.1, 137.1, 129.3, 126.5,
86.4, 76.3, 61.4, 21.1, 13.9.
3

D. Chen et al. / Tetrahedron: Asymmetry 16 (2005) 1757–1762
1761
Compound 3: Isolated as a colorless oil (157 mg, 82%
J = 7.0 Hz, 2H), 3.21 (d, J = 6.0 Hz, 1H), 1.23 (t,
J = 7.0 Hz, 3H);
1
13
yield). H NMR (500 MHz, CDCl ) d = 7.98–8.04 (m,
C
NMR (125 MHz, CDCl3)
3
1
(
H), 7.80–7.90 (m, 2H), 7.57–7.62 (m, 1H), 7.44–7.56
m, 3H), 7.05 (d, J = 1.5 Hz, 1H), 6.32 (d, J = 4.5 Hz,
d = 165.6, 144.2, 144.1, 130.3 (q), 126.8, 126.2, 125.5
(q), 125.0, 122.9, 88.1, 75.7, 61.7, 13.9.
1
1
H), 4.23 (q, J = 7.0 Hz, 2H), 2.85 (d, J = 4.5 Hz, 1H),
.20 (t, J = 7.0 Hz, 3H); C NMR (125 MHz, CDCl3)
1
3
Compound 11: Isolated as a colorless oil (152 mg, 74%
1
d = 166.3, 145.1, 135.3, 133.8, 130.5, 129.2, 128.8,
26.6, 125.9, 125.3, 124.8, 123.4, 87.4, 72.4, 61.5, 13.9.
yield). H NMR (500 MHz, CDCl ) d = 7.53–7.57 (m,
3
1
1H), 7.47–7.51 (m, 1H), 7.32–7.37 (m, 1H), 7.17–7.22
(m, 1H), 7.16 (d, J = 1.5 Hz, 1H), 5.91 (d, J = 3.5 Hz,
1H), 4.25 (m, 2H), 3.07 (d, J = 4.5 Hz, 1H), 1.26 (t,
Compound 4: Isolated as a colorless oil (145 mg, 76%
yield). H NMR (500 MHz, CDCl ) d = 7.80–7.85
1
13
J = 7.0 Hz, 3H);
C
NMR (125 MHz, CDCl3)
3
(
m, 4H), 7.46–7.51 (m, 2H), 7.39–7.43 (m, 1H), 7.29
d, J = 1.0 Hz, 1H), 5.70 (d, J = 5.5 Hz, 1H), 4.18 (q,
d = 165.9, 143.5, 138.9, 133.0, 129.8, 128.4, 127.9,
123.1, 88.2, 74.5, 61.6, 14.0.
(
J = 7.0 Hz, 2H), 3.03 (d, J = 6.0 Hz, 1H), 1.20 (t,
J = 7.0 Hz, 3H);
1
3
C
NMR (125 MHz, CDCl3)
Compound 12: Isolated as a colorless oil (96 mg, 54%
1
d = 165.9, 145.0, 137.4, 133.13, 133.12, 128.5, 128.1,
yield). H NMR (500 MHz, CDCl ) d = 7.67–7.70 (m,
3
1
1
27.7, 126.4, 126.3, 125.6, 124.3, 87.2, 76.3, 61.5,
3.9.
1H), 7.58–7.63 (m, 2H), 7.46–7.50 (m, 1H), 7.43 (m,
1H), 5.57 (d, J = 5.5 Hz, 1H), 4.23 (q, J = 7.0 Hz, 2H),
1
3
3.17 (d, J = 6.0 Hz, 1H), 1.26 (t, J = 7.0 Hz, 3H);
C
Compound 5: Isolated as a colorless oil (142 mg, 70%
NMR (125 MHz, CDCl ) d = 165.4, 143.8, 141.9,
131.8, 130.8, 130.1, 129.4, 118.5, 112.7, 88.4, 75.5,
61.8, 14.0.
3
1
yield). H NMR (500 MHz, CDCl ) d = 7.56–7.60 (m,
3
4
(
H), 7.39–7.46 (m, 4H), 7.33–7.38 (m, 1H), 7.32
d, J = 1.5 Hz, 1H), 5.59 (d, J = 5.5 Hz, 1H), 4.22 (q,
J = 7.0 Hz, 2H), 2.9103 (d, J = 5.5 Hz, 1H), 1.24
t, J = 7.0 Hz, 3H); C NMR (125 MHz, CDCl3)
d = 165.9, 144.9, 141.2, 140.5, 139.1, 128.8, 127.5,
27.3, 127.1, 127.0, 87.0, 76.0, 61.5, 14.0.
Compound 13: Isolated as a colorless oil (48 mg, 31%
1
(
yield). H NMR (500 MHz, CDCl ) d = 7.09 (d,
3
J = 1.0 Hz, 1H), 4.38 (q, J = 6.5 Hz, 1H), 4.33 (q,
J = 7.0 Hz, 2H), 2.46 (d, J = 6.5 Hz, 1H), 1.56–1.68
1
(
m, 2H), 1.24–1.45 (m, 7H), 0.90 (t, J = 7.0 Hz, 3H);
C NMR (125 MHz, CDCl ) d = 166.4, 146.9, 84.2,
1
3
Compound 6: Isolated as a colorless oil (72 mg, 40%
3
1
yield). H NMR (500 MHz, CDCl ) d = 7.21–7.28 (m,
75.1, 61.4, 35.8, 27.6, 22.4, 14.1, 13.9.
3
3
(
1
H), 6.84–6.90 (m, 2H), 5.50 (d, J = 5.5 Hz, 1H), 4.20
q, J = 7.0 Hz, 2H), 3.80 (s, 3H), 2.73 (d, J = 5.0 Hz,
Compound 14: Isolated as a colorless oil (66 mg, 44%
1
H), 1.23 (t, J = 7.0 Hz, 3H); C NMR (125 MHz,
3
1
yield). H NMR (500 MHz, CDCl ) d = 7.02 (d,
3
CDCl ) d = 165.9, 159.5, 145.4, 132.2, 127.9, 114.0,
J = 1.0 Hz, 1H), 4.32 (q, J = 7.0 Hz, 2H), 4.08 (td,
J = 7.0, 1.0 Hz, 1H), 2.47 (d, J = 7.0 Hz, 1H), 1.84
3
8
6.0, 75.7, 61.4, 55.3, 14.0.
(o, J = 6.5 Hz, 1H), 1.36 (t, J = 7.0 Hz, 3H), 0.96 (d,
J = 6.5 Hz, 3H), 0.90 (d, J = 6.5 Hz, 3H); C NMR
1
3
Compound 7: Isolated as a colorless oil (128 mg, 73%
1
yield). H NMR (500 MHz, CDCl ) d = 7.27–7.34 (m,
(125 MHz, CDCl ) d = 166.7, 146.2, 84.3, 80.9, 61.5,
3
3
3
H), 7.01–7.07 (m, 2H), 5.53 (d, J = 5.0 Hz, 1H), 4.20
q, J = 7.0 Hz, 2H), 2.87 (d, J = 5.5 Hz, 1H), 1.23 (t,
32.8, 19.2, 17.5, 14.1.
(
J = 7.0 Hz, 3H);
1
3
C
NMR (125 MHz, CDCl3)
Compound 15: Isolated as a colorless oil (71 mg, 42%
1
d = 165.8, 163.5, 161.6, 144.9, 135.9, 128.4, 128.3,
15.6, 115.5, 86.9, 75.6, 61.5, 14.0.
yield). H NMR (500 MHz, CDCl ) d = 6.99 (d,
3
1
J = 1.0 Hz, 1H), 4.33 (q, J = 7.0 Hz, 2H), 4.08 (t,
J = 7.0 Hz, 1H), 2.49 (d, J = 7.0 Hz, 1H), 1.90–1.97
(m, 1H), 1.69–1.80 (m, 2H), 1.64–1.68 (m, 1H), 1.55–
1.60 (m, 1H), 1.46–1.54 (m, 1H), 1.38 (t, J = 7.0 Hz,
Compound 8: Isolated as a colorless oil (128 mg, 70%
yield). H NMR (500 MHz, CDCl ) d = 7.25–7.34 (m,
5
1
3
1
3
H), 5.50 (d, J = 5.5 Hz, 1H), 4.20 (q, J = 7.0 Hz, 2H),
C
3H), 1.06–1.27 (m, 3H), 0.92–1.01 (m, 2H); C NMR
(125 MHz, CDCl ) d = 166.6, 145.9, 84.4, 80.4, 61.5,
42.4, 29.5, 28.2, 26.2, 26.0, 25.8, 14.1.
1
3
3
.06 (d, J = 5.5 Hz, 1H), 1.24 (t, J = 7.0 Hz, 3H);
3
NMR (125 MHz, CDCl ) d = 165.7, 144.6, 138.7,
3
1
34.0, 128.7, 127.9, 87.3, 75.5, 61.6, 13.9.
Compound 16: Isolated as a colorless oil (33 mg, 21%
1
Compound 9: Isolated as a colorless oil (154 mg, 75%
yield). H NMR (500 MHz, CDCl ) d = 7.04 (d,
3
1
yield). H NMR (500 MHz, CDCl ) d = 7.45–7.50 (m,
J = 1.0 Hz, 1H), 4.31 (q, J = 7.0 Hz, 2H), 4.23 (dd,
J = 5.5, 1.0 Hz, 1H), 2.66 (d, J = 6.0 Hz, 1H), 1.37 (t,
3
2
J = 5.5 Hz, 1H), 4.20 (q, J = 7.0 Hz, 2H), 3.06 (d,
H), 7.28–7.32 (m, 1H), 7.18–7.24 (m, 2H), 5.48 (d,
1
J = 7.0 Hz, 3H), 0.90 (s, 9H); C NMR (125 MHz,
3
1
3
J = 6.0 Hz, 1H), 1.24 (t, J = 7.0 Hz, 3H); C NMR
125 MHz, CDCl ) d = 165.7, 144.5, 139.2, 131.7,
CDCl ) d = 167.6, 145.3, 85.3, 82.8, 61.5, 36.1, 25.6,
3
(
14.0.
3
1
28.2, 122.2, 87.5, 75.6, 61.6, 13.9.
Compound 10: Isolated as a colorless oil (149 mg, 75%
Acknowledgments
1
yield). H NMR (500 MHz, CDCl ) d = 7.61 (d,
3
J = 8.5, 2H), 7.47 (d, J = 8.5 Hz, 2H), 7.35 (d,
J = 1.0 Hz, 1H), 5.58 (d, J = 6.0 Hz, 1H), 4.21 (q,
We gratefully acknowledge the National Institutes
of Health (CA 99995-1) and the Robert A. Welch

1762
D. Chen et al. / Tetrahedron: Asymmetry 16 (2005) 1757–1762
Foundation (D-1361) for the generous support of this
work. We also thank Cody Timmons for his assistance.
6. Chen, D.; Timmons, C.; Liu, J.; Headley, A. D.; Li, G.
Eur. J. Org. Chem. 2004, 15, 3330–3335.
7
. (a) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem.
Rev. 2003, 103, 811–891; (b) Ciganek, E. Org. React. 1997,
51, 201–350; For a review regarding b-branched Baylis–
Hillman adduct synthesis see: (c) Li, G.; Hook, J.; Wei,
H.-X. In Recent Research Developments in Organic &
Bioorganic Chemistry; Transworld Research Network,
2001; Vol. 4, pp 49–61.
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