Quinidine derived organocatalysts for the nucleophile promoted asymmetric [4+2] cycloaddition reaction of salicyl N-tosylimine with allenic esters

Article abstract of DOI:10.1016/j.tetasy.2011.06.030

Cinchona alkaloid derived catalyst cat. 5 prepared from β-isocupreidine (b-ICD) was found to be a fairly effective organocatalyst for the nucleophilic promoted asymmetric [4+2] cycloaddition reaction of salicyl N-tosylimines and allenic esters to give the

Full text of DOI:10.1016/j.tetasy.2011.06.030

Tetrahedron: Asymmetry 22 (2011) 1239–1248
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Quinidine derived organocatalysts for the nucleophile promoted
asymmetric [4+2] cycloaddition reaction of salicyl N-tosylimine
with allenic esters
Cheng-Kui Pei a, Min Shi a,b,
⇑
a Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Cinchona alkaloid derived catalyst cat. 5 prepared from b-isocupreidine (b-ICD) was found to be a fairly
effective organocatalyst for the nucleophilic promoted asymmetric [4+2] cycloaddition reaction of salicyl
N-tosylimines and allenic esters to give the corresponding adducts in up to 80% yield, 87% ee.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 8 June 2011
Accepted 30 June 2011
Available online 4 August 2011
1. Introduction
yield through thiocarbonylation using Lawesson’s reagent9
(Scheme 1). Both cat. 15 and cat. 16 could be synthesized from
2H-1-Chromenes or chromans are an important class of oxygen-
ated heterocycles, which have attracted much synthetic interest
because of the biological activity of naturally occurring representa-
tives.1,2 The synthesis of 2H-1-chromenes or chromans via the
cyclization of suitably elaborated phenyl ethers commonly suffers
from a lack of regioselective control at the key cyclization step. Re-
cently, the reactions of salicyl aldehydes or salicylaldimines with
various conjugated olefins,3 allenic ketones, or esters4–6 to give dif-
ferently substituted chromenes or chromans have been reported.
As a consequence, the exploitation of an efficient and novel cata-
lytic asymmetric method for the synthesis of these compounds is
highly desirable. In recent years, asymmetric methods that allow
rapid access to this molecular architecture have attracted much
attention because this asymmetric synthetic protocol is valuable
in organic synthesis and chemical biology/medicinal chemistry.
Herein, we report the synthesis of a series of quinidine derived
organocatalysts and their applications in the reactions of salicyl
N-tosylimine with various allenic esters, to give substituted chro-
mans in good yields (up to 85% yield) and good ee values (up to
87% ee) under mild reaction conditions.
compound 7 via a Buchwald–Hartwig cross-coupling reaction in
50% yield and 25% yield, respectively (Scheme 2).
Initially, we used salicyl N-tosylimine 1a (1.0 equiv) and allenic
esters 2a (1.2 equiv) as the substrates and multifunctional cin-
chona alkaloid b-isocupreidine (b-ICD) (Fig. 1) (10 mol %) as the
catalyst in tetrahydrofuran (THF) to examine the reaction out-
come; the results are shown in Table 1, entry 1. It was found that
the corresponding substituted product 3aa was obtained in 80%
yield along with 10% ee at room temperature (25 °C) (Table 1, entry
1). We next turned our attention to screen other multifunctional
cinchona alkaloid derived organocatalysts cat. 1–cat. 3 (Fig. 1) in
this reaction and found that the desired product 3aa was formed
in 50–60% yields along with 5–20% ee values (Table 1, entries 2–4).
Since these cinchona alkaloids derived catalysts are not partic-
ularly effective in this particular asymmetric substituted reaction,
we attempted to use other multifunctional cinchona alkaloid de-
rived organocatalysts (Fig. 1) in this reaction (Schemes 1 and 2).
Therefore, using these new cinchona alkaloids derived organocata-
lysts, we investigated the reaction of 1a with 2a in the presence of
cat. 4–cat. 16 in THF at 25 °C and found that the substituent of the
R0 group had a significant affect on the outcome of the reaction. We
found that our organocatalysts cat. 4–cat. 7 (10 mol %), in which R0
is an aliphatic group, could produce the corresponding product 3aa
in moderate to good yields along with 50–64% ee values (Table 1,
entries 5–8). For example, 3aa was formed in 85% yield and 64%
ee in the presence of organocatalyst cat. 5 (R0 = CH3 and R00 = H)
(Table 1, entry 6). The substituent on the aromatic R0 group can
also have a significant affect on the reaction outcome. Introducing
either no groups or strongly electron-donating methoxy groups at
the 2-position or 3- and 5-position of the benzene ring (organocat-
alysts cat. 8–cat. 10) afforded the corresponding product 3aa in
low ee values (Table 1, entries 9–11). Using organocatalyst cat.
2. Results and discussion
Cinchona alkaloids derived catalysts b-isocupreidine (b-ICD)
and cat. 1–cat. 3 are known compounds and were synthesized
according to the previous literature (Fig. 1).7 Chiral catalysts cat.
4–cat. 13 were synthesized from b-ICD according to our previous
work (Fig. 1).8 Cat. 5 could also be transformed to cat. 14 in 51%
⇑
Corresponding author. Fax: +86 21 64166128.
E-mail address: Mshi@mail.sioc.ac.cn (M. Shi).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.06.030

1240
C.-K. Pei, M. Shi / Tetrahedron: Asymmetry 22 (2011) 1239–1248
O
H
O
H
O
H
CF3
N
S
N
N
N
N
N
N
N
H
N
H
CF3
OH
NH2
cat. 1
cat. 2
β-ICD
O
H
cat. 4: R' = H, R" = H
O
O
cat. 5: R' = CH3, R" = H
N
O
H
cat. 6: R' = CH2CH3, R" = H
cat. 7: R' = CH(CH3)2, R" = H
cat. 8: R' = C6H5, R" = H
N
H
N
H
N
N
CF3
R''
N
N
H
cat. 9: R' = 2-MeOC6H4, R" = H
cat. 10: R' = 3,5-(MeO)2C6H3, R" = H
cat. 11: R' = 4-BrC6H4, R" = H
cat. 12: R' = CH2C6H5, R" = H
cat. 13: R' = (S)-CHMeC6H5, R" = H
S
R'
cat. 3
CF3
O
O
S
O
N
H
H
H
N
N
N
N
N
H
N
CH3
N
S
cat. 15
cat. 14
cat. 16
Figure 1. Multifunctional cinchona alkaloid derivatives.
O
O
S
H
H
N
N
Lawesson's reagent
N
N
THF, reflux, 30
51%
h
H
N
H
N
CH3
CH3
O
cat. 5
cat. 14
Scheme 1. The synthetic route for the preparation of cat. 14.
11, in which the aromatic R0 group has a bromine atom at the
4-position in this reaction furnished 3aa in 72% yield and 54% ee
(Table 1, entry 12). Organocatalysts cat. 12 and cat. 13, in which
R0 is a benzyl group or a substituted benzyl group and R’’ is a
hydrogen atom, were also effective catalysts in this reaction,
affording 3aa in 88% yield with 60% ee and 73% yield with 51%
ee, respectively (Table 1, entries 13 and 14). Furthermore, using
organocatalyst cat. 14 with a thiocarbonyl group as the catalyst
produced the corresponding product 3aa in 85% yield along with
54% ee (Table 1, entry 15). Organocatalysts cat. 15 and cat. 16, in
which the quinoline ring has a piperidyl substituent or an anth-
racenyl substituent, both catalyzed this reaction smoothly, afford-
ing 3aa in 54% yield with 35% ee and 60% yield with 34% ee,
respectively (Table 1, entries 16 and 17). Therefore, the optimal
organocatalyst was identified as cat. 5 (10 mol %) in this asymmet-
ric [4+2] cycloaddition reaction to give the corresponding product
in good yield along with a good ee value (64% ee).
Having identified the best organocatalyst for this reaction, we
next carried out the reaction of 1a with 2a catalyzed by cat. 5 in
various solvents to examine the solvent effects in this reaction
and the results are summarized in Table 1. It was found that
Et2O was the solvent of choice in comparison with those reactions
carried out in other organic solvents, such as dichloromethane
(DCM), CH3CN, 1,4-dioxane, tetrahydrofuran (THF), toluene, and
EtOAc (Table 2, entries 1–7). The reactant 1a decomposed during
the reaction without the formation of 3aa in CH3OH (Table 2, entry
8). In other ether solvents, such as methyl tert-butyl ether and
isopropyl ether, compound 3aa was formed in 75% yield along with
45% ee and 27% yield along with 57% ee, respectively (Table 2,
entries 9 and 10). When lowering the reaction temperature to
0 °C ꢀ ꢁ20 °C, the reactions became sluggish and no improvement
could be observed in Et2O (Table 2, entries 11 and 12). Moreover,
we also attempted to add some additives such as diisopropylethyl-
amine (DIEA), p-toluenesulfonic acid (TsOH) and benzoic acid in

C.-K. Pei, M. Shi / Tetrahedron: Asymmetry 22 (2011) 1239–1248
1241
SH
O
S
O
H
H
N
N
N
Pd2(dba)3, Xantphos, DIEA,
1,4-dioxane, 90 oC, 18 h,
50%
N
OTf
cat. 15
O
H
N
H
N
N
Pd2(dba)3, dppf, NaOtBu,
toluene, 80 oC, 18 h
25%
N
cat. 16
Scheme 2. The synthetic route for the preparation of cat. 15 and cat. 16.
Table 3, when salicyl N-tosylimines 1 bearing electron-withdraw-
ing groups at the benzene ring were employed as the substrates,
the reactions proceeded smoothly to give the desired products 3
in 56–85% yields along with 10–39% ee values (Table 3, entries
1–4). As for salicyl N-tosylimine 1f and 1g, which had electron-
donating groups on the benzene ring, the corresponding products
were formed in 82% yield along with 74% ee and 80% yield along
with 69% ee, respectively, perhaps due to electronic properties
(Table 3, entries 5 and 6). Other sulfonyl groups such as 4-nitro-
benzenesulfonyl (Ns), 4-bromobenzenesulfonyl (Bs) and 2,4,6-tri-
isopropylbenzenesulfonyl were also suitable substituents in this
reaction to give the corresponding products 3ha, 3ia, and 3ja in
50–69% yields along with 43–61% ee values (Table 3, entries 7–
9). Changing the ester moiety of the allenic esters from OEt to
OMe, OtBu, or OiPr could improve the reaction outcomes, affording
the desired products 3ab, 3ac, and 3ad in 75–85% yield along with
64–70% ee values (Table 3, entries 10–12). Applying isopropyl 2,3-
butadienoate 2d to this asymmetric [4+2] cycloaddition reaction,
as for the salicyl N-tosylimines with electron-withdrawing groups
on the benzene ring, gave the corresponding products in 21–80%
yields along with 21–76% ee values (Table 3, entries 13–16). As
for other salicyl N-tosylimines 1f, 1g, 1k, and 1l, which had elec-
tron-donating groups on the benzene ring, the reactions proceeded
smoothly to give the desired products 3fd, 3gd, 3kd, and 3ld in 65–
80% yields along with 64–87% ee values (Table 3, entries 17–20).
Using other sulfonyl groups such as 4-nitrobenzenesulfonyl (Ns),
4-bromobenzenesulfonyl (Bs) and 2,4,6-triisopropylbenzenesulfo-
nyl as the substrates afforded the desired products in 69–72% yield
along with 55–65% ee values (Table 3, entries 21–23).
Table 1
Reaction of ethyl 2,3-butadienoate 2a with salicyl N-tosylimine 1a in the presence of
cinchona alkaloids derived catalystsa
Ts
Ts
N
HN
6
3
6
CO2Et
1
5
4
1
5
4
cat. (10 mol%)
+
MS 4Å, THF,
25 °C, 24 h
CO2Et
2
2
OH
O
3aa
2a
Cat
3
1a
Entry
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
b-ICD
80
62
51
50
90
85
70
75
85
68
85
72
88
73
85
54
60
10
20
5
10
51
64
57
50
9
cat. 1
cat. 2
cat. 3
cat. 4
cat. 5
cat. 6
cat. 7
cat. 8
cat. 9
cat. 10
cat. 11
cat. 12
cat. 13
cat. 14
cat. 15
cat. 16
9
10
11
12
13
14
15
16
17
10
6
54
60
51
54
35
34
a
All reactions were carried out using 1a (0.10 mmol) and 2a (0.12 mmol) in THF
(2.00 mL) for 24 h.
b
Isolated yield.
Determined by chiral HPLC analysis.
c
The absolute configurations of products 3 were unequivocally
assigned as (R) by X-ray diffraction of 3cd which bears a bromine
atom on the benzene ring. Its ORTEP drawing is shown in
Figure 2.10
order to improve the enantiomeric excess of 3aa in Et2O at 25 °C.
However, no improvements were observed under the standard
conditions (Table 2, entries 13–15). Overall, this asymmetric
[4+2] cycloaddition reaction should be carried out at 25 °C in
Et2O using organocatalyst cat. 5 (10 mol %) as the catalyst.
The generality of this asymmetric [4+2] cycloaddition reaction
was examined using a variety of salicyl N-tosylimines 1 and allenic
esters 2 at 25 °C under the optimal conditions, and the results of
these experiments are summarized in Table 3. As can be seen from
Based on previous mechanistic studies by our group,6a a transi-
tion-state model was proposed and is shown in Figure 3. In the
transition state, the substrate is bound anti to the quinoline ring
of the organocatalyst cat. 5 to minimize the steric interactions
and so the allenic ester may attack the Si-face of the imine, conse-
quently providing the corresponding asymmetric [4+2] cycloaddi-
tion products predominantly in the (R)-configuration.

1242
C.-K. Pei, M. Shi / Tetrahedron: Asymmetry 22 (2011) 1239–1248
Table 2
Optimization of the reaction conditionsa
O
H
N
N
H
N
Ts
Ts
CH3
N
HN
6
O
6
CO2Et
5
4
1
2
1
5
4
cat. 5 (10 mol%)
+
MS 4Å, solvent,
additive, 24 h
CO2Et
2
OH
O
3aa
2a
3
3
1a
Entry
Temp (°C)
Solvent
Additive
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
25
25
25
25
25
25
25
25
25
25
0
THF
DCM
—
—
—
—
—
—
—
—
—
—
—
—
85
75
80
75
90
75
85
Trace
75
27
90
86
90
Complex
65
64
55
42
50
64
50
60
—
45
57
64
64
64
—
CH3CN
1.4-Dioxane
Et2O
Toluene
EtOAc
CH3OH
tBuOMe
iPrOiPr
Et2O
Et2O
Et2O
Et2O
Et2O
9
10d
11d
12d
13
14
15
ꢁ20
25
25
25
DIEA
TsOH
PhCOOH
64
a
b
c
All reactions were carried out using 1a (0.10 mmol) and 2a (0.12 mmol) in solvent (2.00 mL) for 24 h.
Isolated yield.
Determined by chiral HPLC analysis.
Reaction was carried out for 36 h.
d
by EI, ESI, MALDI and HRMS was measured on a HP-5989 instru-
ment. Organic solvents used were dried by standard methods
when necessary.
3. Conclusion
In conclusion, we have reported the first example of asymmet-
ric [4+2] cycloaddition reaction of salicyl N-tosylimines and allenic
esters in the presence of cinchona alkaloid derived catalyst cat. 5 in
Et2O under mild conditions, affording the corresponding adducts in
good yields along with moderate to good enantioselectivities. The
multiplied functionalized 2H-1-chromenes or chromans obtained
are useful building blocks in a variety of organic synthetic se-
quences. Efforts are currently in progress to use these novel multi-
functional quinidine derived organocatalysts for other asymmetric
catalysis.
4.2. General procedure for the synthesis of cat. 4–cat. 13
Cinchona alkaloid derived catalysts cat. 4–cat. 13 are known
compounds and were synthesized according to the literature.8
4.2.1. 60-Formamide-b-ICD cat. 4
1H NMR (400 MHz, CDCl3, TMS) d 1.04 (t, J = 7.6 Hz, 3H), 1.28
(dd, J = 12.4, 6.4 Hz, 1H), 1.53–1.58 (m, 1H), 1.64–1.78 (m, 4H),
2.18 (br s, 1H), 2.68 (d, J = 13.2 Hz, 1H), 2.97–2.99 (m, 2H), 3.47
(d, J = 6.4 Hz, 1H), 3.58 (d, J = 13.2 Hz, 1H), 6.04 (s, 1H), 6.15 (br s,
1H), 7.78 (d, J = 4.4 Hz, 1H), 8.17 (d, J = 8.8 Hz, 1H), 8.23 (br s,
1H), 8.37 (d, J = 8.8 Hz, 1H), 8.52 (s, 1H), 8.97 (d, J = 4.4 Hz, 1H).
4. Experimental
4.1. General remarks
4.2.2. 60-N-Methylformamide-b-ICD cat. 5
Melting points were determined on a digital melting point
apparatus and are uncorrected. Optical rotations were determined
at 589 nm (sodium D line) by using a Perkin-Elmer-341 MC digital
1H NMR (300 MHz, CDCl3, TMS) d 1.02 (t, J = 7.5 Hz, 3H), 1.26
(m, 1H), 1.54–1.73 (m, 5H), 2.16 (br s, 1H), 2.67 (d, J = 13.5 Hz,
1H), 2.95–2.97 (m, 2H), 3.02 (d, J = 4.8 Hz, 3H), 3.45–3.54 (m,
2H), 6.01 (s, 1H), 7.65 (br s, 1H), 7.78 (d, J = 4.5 Hz, 1H), 8.13 (d,
J = 9.3 Hz, 1H), 8.22–8.25 (m, 1H), 8.34 (s, 1H), 8.96 (d, J = 4.5 Hz,
1H).
polarimeter; [a .
]D-values are given in unit of 10 degꢁ1 cm2 gꢁ1 1H
NMR spectra were recorded on a Bruker AM-300 and AM-400 spec-
trometer for solution in CDCl3 with tetramethylsilane (TMS) as an
internal standard; coupling constants J are given in Hz. 19F and 31
P
NMR spectra were recorded on a Bruker AM-300 and AM-400 spec-
trophotometers with complete proton decoupling spectrophotom-
eters. Infrared spectra were recorded on a Perkin-Elmer PE-983
spectrometer with absorption in cmꢁ1. Flash column chromatogra-
phy was performed using 300–400 mesh silica gel. For thin-layer
chromatography (TLC), silica gel plates (Huanghai GF254) were
used. Chiral HPLC was performed on a SHIMADZU SPD-10A vp ser-
ies with chiral columns (Chiralpak AD-H and IC-H columns 4.6 x
250 mm, (Daicel Chemical Ind., Ltd)). Mass spectra were recorded
4.2.3. 60-N-Ethylformamide-b-ICD cat. 6
1H NMR (400 MHz, CDCl3, TMS) d 1.11 (t, J = 7.6 Hz, 3H), 1.29 (t,
J = 7.2 Hz, 3H), 1.63 (dd, J = 13.6, 6.8 Hz, 1H), 1.83–1.88 (m, 2H),
2.01–2.07 (m, 2H), 2.09 (dd, J = 10.2, 6.8 Hz, 1H), 2.56 (br s, 1H),
3.25 (d, J = 13.2 Hz, 1H), 3.50–3.62 (m, 4H), 4.30–4.33 (m, 2H),
6.39 (s, 1H), 7.80 (d, J = 4.4 Hz, 1H), 8.17 (d, J = 8.8 Hz, 1H), 8.49
(d, J = 8.8 Hz, 1H), 8.65 (t, J = 5.2 Hz, 1H), 8.69 (s, 1H), 9.00 (d,
J = 4.4 Hz, 1H).

C.-K. Pei, M. Shi / Tetrahedron: Asymmetry 22 (2011) 1239–1248
1243
Table 3
Substrate scope of the reactions of organocatalyst cat. 5 catalyzed asymmetric [4+2] cycloaddition reaction of 1 with 2a
O
H
N
N
H
R2
R2
N
CH3
HN
N
6
3
6
O
CO2R3
1
1
5
4
5
cat. 5 (10 mol%)
R1
R1
+
CO2R3
MS 4Å, Et2O,
25oC, 24 h
4
2
2
O
3
OH
3
2
1
Entry
No.
R1
R2
R3
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
1b
1c
1d
1e
1f
1g
1h
1i
5-Cl
5-Br
Ts
Ts
Ts
Ts
Ts
Ts
Ns
Bs
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
3ba, 82
3ca, 65
3da, 85
3ea, 56
3fa, 82
3ga, 80
3ha, 65
3ia, 69
37
39
20
10
74
69
43
61
3,5-Cl2
3,5-Br2
3-OMe
5-OMe
H
H
9
1j
H
Et (2a)
3ja, 50
50
O
S
O
10
11
12
13
14
15
16
17
18
19
20
21
22
1a
1a
1a
1b
1c
1d
1e
1f
1g
1k
1l
1h
1i
H
H
H
5-Cl
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ns
Bs
Me (2b)
tBu (2c)
iPr (2d)
iPr (2d)
iPr (2d)
iPr (2d)
iPr (2d)
iPr (2d)
iPr (2d)
iPr (2d)
iPr (2d)
iPr (2d)
iPr (2d)
3ab, 85
3ac, 75
3ad, 80
3bd, 80
3cd, 72
3dd, 27
3ed, 21
3fd, 79
3gd, 75
3kd, 80
3ld, 65
3hd, 69
3id, 72
64
65
70
67
76
38
21
76
64
87
72
65
64
5-Br
3.5-Cl2
3.5-Br2
3-OMe
5-OMe
3-Me
3,5-tBu2
H
H
23
1j
H
iPr (2d)
3jd, 70
55
O
S
O
a
b
c
All reactions were carried out using 1 (0.10 mmol) and 2 (0.12 mmol) in Et2O (2.00 mL) for 24 h.
Isolated yield.
Determined by chiral HPLC analysis.
O
N
H
O
R3O2C
Ts
H
N
N
H
R1
N
O
Figure 3. A plausible transition-state model.
4.2.4. 60-N-Isopropylformamide-b-ICD cat. 7
1H NMR (400 MHz, CDCl3, TMS) d 1.03 (t, J = 7.6 Hz, 3H), 1.30–
1.32 (m, 7H), 1.58–1.83 (m, 5H), 2.20 (br s, 1H), 2.70 (d,
J = 13.6 Hz, 1H), 3.03–3.04 (m, 2H), 3.54–3.55 (m, 1H), 3.62–3.65
(m, 1H), 4.39–4.43 (m, 1H), 6.10 (s, 1H), 7.77 (d, J = 4.4 Hz, 2H),
8.15 (d, J = 8.8 Hz, 1H), 8.35 (d, J = 8.8 Hz, 1H), 8.54 (s, 1H), 8.96
(d, J = 4.4 Hz, 1H).
Figure 2. ORTEP drawing of 3cd.

1244
C.-K. Pei, M. Shi / Tetrahedron: Asymmetry 22 (2011) 1239–1248
4.2.5. 60-N-Phenylformamide-b-ICD cat. 8
4.3.1. 60-N-Methylethanethioamide-b-ICD cat. 14
1H NMR (300 MHz, CDCl3, TMS) d 1.05 (t, J = 7.2 Hz, 3H), 1.40–
1.48 (m, 1H), 1.68–1.78 (m, 4H), 1.91–1.97 (m, 1H), 2.35 (br s,
1H), 2.99 (d, J = 12.9 Hz, 1H), 3.31–3.34 (m, 2H), 4.05–4.07 (m,
2H), 6.33 (s, 1H), 7.05 (t, J = 6.6 Hz, 1H), 7.23–7.27 (m, 2H), 7.77–
7.83 (m, 3H), 8.21 (d, J = 9.0 Hz, 1H), 8.54 (d, J = 8.4 Hz, 1H),
8.97–9.01 (m, 2H), 10.15 (s, 1H).
A yellow solid (38.2 mg, 51% yield); ½a D20
¼ ꢁ75:1 (c 0.55,
ꢂ
CHCl3); mp 153–155 °C; 1H NMR (400 MHz, CDCl3, TMS) d 1.04
(t, J = 7.2 Hz, 3H), 1.21–1.25 (m, 1H), 1.52–1.56 (m, 1H), 1.65–
1.70 (m, 4H), 2.15 (br s, 1H), 2.64 (d, J = 13.6 Hz, 1H), 2.95–2.97
(m, 2H), 3.37 (d, J = 4.4 Hz, 3H), 3.48–3.56 (m, 2H), 5.89 (s, 1H),
7.69 (d, J = 4.0 Hz, 1H), 8.07 (d, J = 8.8 Hz, 1H), 8.15 (br s, 1H),
8.69 (d, J = 8.8 Hz, 1H), 8.87 (d, J = 4.0 Hz, 1H), 9.80 (br s, 1H); 13C
NMR (100 MHz, CDCl3) d 7.3, 23.2, 23.5, 27.3, 32.8, 34.2, 46.1,
54.1, 56.9, 72.4, 77.3, 116.8, 119.6, 124.0, 130.2, 131.3, 136.9,
4.2.6. 60-N-(2-Methoxyphenyl)formamide-b-ICD cat. 9
1H NMR (400 MHz, CDCl3, TMS) d 1.03 (t, J = 7.6 Hz, 3H), 1.21–
1.25 (m, 1H), 1.45–1.60 (m, 1H), 1.63–1.75 (m, 4H), 2.09 (br s,
1H), 2.62 (d, J = 13.6 Hz, 1H), 2.95–2.98 (m, 2H), 3.49–3.56 (m,
2H), 3.88 (s, 3H), 6.04 (s, 1H), 6.85–6.94 (m, 1H), 6.98–7.02 (m,
1H), 7.06–7.10 (m, 1H), 7.82 (d, J = 4.0 Hz, 1H), 8.15–8.23 (m,
2H), 8.45 (d, J = 7.6 Hz, 1H), 8.56 (s, 1H), 8.82 (s, 1H), 9.00 (d,
J = 4.8 Hz, 1H).
145.2, 148.8, 151.4, 157.1, 196.1; IR (neat)
m 3218, 2959, 1590,
1555, 1502, 1459, 1356, 1130, 1099, 1064, 1007, 854, 796 cmꢁ1
;
MS (ESI) m/e 368 (M+H); HRMS (ESI) for C21H26N3OS (M+H):
368.1791; found: 368.1789.
4.4. General procedure for the synthesis of cat. 15
A
flame-dried flask provided with a water-cooled reflux
4.2.7. 60-N-(3,5-Dimethoxyphenyl)formamide-b-ICD cat. 10
1H NMR (400 MHz, CDCl3, TMS) d 1.00 (t, J = 7.6 Hz, 3H), 1.20–
1.31 (m, 1H), 1.50–1.51 (m, 1H), 1.61–1.75 (m, 4H), 2.13 (br s,
1H), 2.56 (d, J = 13.6 Hz, 1H), 2.87–2.89 (m, 2H), 3.41–3.46 (m,
2H), 3.63 (s, 6H), 5.95 (s, 1H), 6.09 (t, J = 2.0 Hz, 1H), 7.08 (d,
J = 2.0 Hz, 2H), 7.76 (d, J = 4.4 Hz, 1H), 8.16 (d, J = 8.8 Hz, 1H),
8.41 (dd, J = 2.0 Hz, 8.8 Hz, 1H), 8.61 (s, 1H), 8.95 (d, J = 4.4 Hz,
1H), 9.78 (s, 1H).
condenser was charged with Pd2dba3 (18.8 mg, 0.02 mmol,
0.04 equiv), xantphos (5.0 mg, 0.03 mmol, 0.06 equiv), and
1,4-dioxane (1.0 mL). The condenser was capped with a rubber
septum, evacuated, and backfilled with argon. This evacuation/
backfilled sequence was repeated once more. Diisopropylethyl-
amine (DIEA) (79.5 mg, 1.4 equiv), anthracen-9-ylmethanethiol
(148 mg, 0.66 mmol, 1.5 equiv) and triflate 7 (200 mg, 0.44 mmol,
1.0 equiv) in solution in 1,4-dioxane (1.5 mL) were then added.
The evacuation/backfilled sequence was performed twice. The
mixture was then stirred at 100 °C for 16 h until the starting triflate
had been completely consumed, as judged by TLC. The reaction
was then cooled to room temperature, diluted with ethyl acetate,
filtered on Celite, and concentrated in vacuo. The crude material
was purified by flash chromatography (eluent: DCM/MeOH = 30:1)
to give cat. 15 as a yellow solid (116.0 mg, 50%).
4.2.8. 60-N-(4-Bromophenyl)formamide-b-ICD cat. 11
1H NMR (400 MHz, CDCl3, TMS) d 1.06 (t, J = 7.2 Hz, 3H), 1.25–
1.29 (m, 1H), 1.54–1.58 (m, 1H), 1.67–1.73 (m, 4H), 2.17 (br s,
1H), 2.67 (d, J = 13.6 Hz, 1H), 2.96–2.99 (m, 2H), 3.39 (d,
J = 6.0 Hz, 1H), 3.58 (d, J = 13.6 Hz, 1H), 5.95 (s, 1H), 7.33 (d,
J = 8.8 Hz, 2H), 7.66 (d, J = 8.8 Hz, 1H), 7.74 (d, J = 4.4 Hz, 1H),
8.13 (d, J = 8.8 Hz, 1H), 8.44 (dd, J = 8.8 Hz, 1.6 Hz, 1H), 8.58 (s
1H), 8.91 (d, J = 4.4 Hz, 1H), 10.09 (s, 1H).
4.4.1. 60-Anthracen-9-ylmethanethiol-b-ICD cat. 15
A yellow solid (116.0 mg, 50%); ½a D20
ꢂ
¼ þ57:0 (c 0.30, CHCl3);
4.2.9. 60-N-Benzylformamide-b-ICD cat. 12
mp 158–159 °C; 1H NMR (400 MHz, CDCl3, TMS)
d
0.99 (t,
1H NMR (400 MHz, CDCl3, TMS) d 1.00 (t, J = 7.2 Hz, 3H), 1.19–
1.26 (m, 1H), 1.49–1.52 (m, 1H), 1.59–1.74 (m, 4H), 2.14 (br s,
1H), 2.59 (d, J = 13.6 Hz, 1H), 2.89–2.92 (m, 2H), 3.39 (d,
J = 6.4 Hz, 2H), 3.53 (d, J = 13.6 Hz, 2H), 4.60 (dd, J = 5.6, 14.8 Hz,
1H), 4.70 (dd, J = 5.6, 14.8 Hz, 1H), 5.98 (s, 1H), 7.18 (t, J = 7.2 Hz,
1H), 7.25 (t, J = 7.2 Hz, 2H), 7.37 (d, J = 7.2 Hz, 2H), 7.73 (d,
J = 4.4 Hz, 1H), 8.14 (d, J = 8.8 Hz, 1H), 8.44 (d, J = 8.8 Hz, 1H),
8.52 (s, 1H), 8.92 (d, J = 4.4 Hz, 1H), 9.05 (t, J = 5.6 Hz, 1H).
J = 7.6 Hz, 3H), 1.16–1.20 (m, 1H), 1.41–1.46 (m, 1H), 1.53–1.70
(m, 4H), 2.06 (br s, 1H), 2.52 (d, J = 13.2 Hz, 1H), 2.84–2.89 (m,
2H), 3.26 (d, J = 5.6 Hz, 1H), 3.39 (d, J = 13.2 Hz, 1H), 5.21 (s, 2H),
5.81 (s, 1H), 7.38–7.46 (m, 4H), 7.70–7.74 (m, 2H), 7.92–7.96 (m,
3H), 8.04 (d, J = 8.8 Hz, 1H), 8.20 (d, J = 8.8 Hz, 2H), 8.35 (s, 1H),
8.86 (d, J = 4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 7.3, 23.5,
24.1, 27.3, 31.9, 32.8, 46.4, 54.5, 56.3, 72.8, 77.1, 119.6, 122.4,
123.9, 125.0, 125.9, 126.1, 127.2, 127.7, 129.0, 130.0, 130.6,
130.9, 131.3, 136.5, 143.9, 146.6, 149.8; IR (neat)
m 2963, 2922,
4.2.10. 60-(S)-N-(1-Phenylethyl)formamide-b-ICD cat. 13
1H NMR (400 MHz, CDCl3, TMS) d 1.00 (t, J = 7.2 Hz, 3H), 1.23–
1.28 (m, 1H), 1.53–1.57 (m, 1H), 1.62–1.68 (m, 6H), 1.73–1.76
(m, 1H), 2.16 (br s, 1H), 2.62 (d, J = 13.6 Hz, 1H), 2.96–3.00 (m,
2H), 3.48 (d, J = 6.0 Hz, 1H), 3.57 (d, J = 13.6 Hz, 1H), 5.45–5.52
(m, 1H), 6.04 (s, 1H), 7.22 (t, J = 7.2 Hz, 1H), 7.28–7.34 (m, 4H),
7.49 (d, J = 7.2 Hz, 2H), 7.74 (d, J = 4.4 Hz, 1H), 8.12 (d, J = 8.8 Hz,
1H), 8.39 (d, J = 8.8 Hz, 1H), 8.61 (s, 1H), 8.72 (d, J = 8.0 Hz, 1H),
8.93 (d, J = 4.4 Hz, 1H).
1747, 1730, 1586, 1492, 1448, 1350, 1103, 1064, 1017, 800,
726 cmꢁ1; MS (ESI) m/e 517 (M+H); HRMS (ESI) for C34H33N2OS
(M+H): 517.2308; found: 517.2309.
4.5. General procedure for the synthesis of cat. 16
A
flame-dried flask provided with a water-cooled reflux
condenser was charged with Pd2dba3 (18.8 mg, 0.02 mmol,
0.04 equiv), 1,10-bis(diphenylphosphino)ferrocene (dppf) (16.6 mg,
0.03 mmol, 0.06 equiv), and toluene (1.0 mL). The condenser was
capped with a rubber septum, evacuated, and backfilled with argon.
This evacuation/backfilled sequence was repeated once more. Next,
NaOtBu (63.4 mg, 0.66 mmol, 1.5 equiv), piperidine (57.6 mg,
0.66 mmol, 1.5 equiv), and triflate 7 (200 mg, 0.44 mmol, 1.0 equiv)
in a solution in toluene (1.5 mL) were added. The evacuation/back-
filled sequence was performed twice. The mixture was then stirred
at 80 °C for 16 h until the starting triflate had been completely con-
sumed, as judged by TLC. The reaction was then cooled to room tem-
perature, diluted with ethyl acetate, filtered on Celite, and
concentrated in vacuo. The crude material was purified by a flash
4.3. General procedure for the synthesis of cat. 14
A mixture of cat. 5 (70.2 mg, 0.2 mmol), Lawesson’s reagent
(90.0 mg, 1.2 equiv), and THF (3.0 mL) was refluxed at 70 °C for
30 h under an argon atmosphere. The mixture was washed with
H2O and then extracted with Et2O. The organic phase was dried
over Na2SO4 and concentrated under reduced pressure. The crude
material was purified by silica gel column chromatography (elu-
tion with DCM/MeOH = 20:1) to give cat. 14 as a yellow solid
(38.2 mg, 51% yield).

C.-K. Pei, M. Shi / Tetrahedron: Asymmetry 22 (2011) 1239–1248
1245
chromatography (eluent:DCM:MeOH = 25:1) togive cat. 16 as a yel-
low solid (41.5 mg, 25%).
4.7.1. Ethyl 2-methyl-4-(4-methylphenylsulfonamido)-4H-
chromene-3-carboxylate 3aa
A white solid (34.8 mg, 90%); mp 138–140 °C; This is a known
compound.6a 1H NMR (400 MHz, CDCl3, TMS) d 1.21 (t, J = 7.2 Hz,
3H), 2.38 (s, 3H), 2.39 (s, 3H), 3.86–3.90 (m, 1H), 4.06–4.11 (m,
1H), 5.30 (d, J = 6.4 Hz, 1H), 5.59 (d, J = 6.4 Hz, 1H), 7.00–7.04 (m,
2H), 7.18 (d, J = 8.4 Hz, 2H), 7.22–7.26 (m, 1H), 7.33–7.35 (m,
4.5.1. 60-Piperidine-b-ICD cat. 16
A yellow solid (41.5 mg, 25%); ½a D20
¼ þ27:0 (c 0.50, CHCl3); mp
ꢂ
138–139 °C; 1H NMR (400 MHz, CDCl3, TMS) d 1.07 (t, J = 7.2 Hz,
3H), 1.42–1.47 (m, 1H), 1.61–1.67 (m, 2H), 1.74–1.81 (m, 8H),
1.99–2.04 (m, 1H), 2.38 (br s, 1H), 2.96 (d, J = 13.2 Hz, 1H), 3.27–
3.30 (m, 1H), 3.39–3.47 (m, 5H), 4.00–4.04 (m, 2H), 6.09 (s, 1H),
7.13 (d, J = 2.8 Hz, 1H), 7.50 (dd, J = 9.6 Hz, 2.8 Hz, 1H), 7.64 (d,
J = 3.6 Hz, 1H), 7.97 (d, J = 9.6 Hz, 1H), 8.69 (d, J = 4.8 Hz, 1H); 13C
NMR (100 MHz, CDCl3) d 7.3, 23.1, 23.7, 24.2, 25.8, 27.4, 29.7,
32.9, 46.4, 50.5, 54.4, 56.3, 72.6, 77.2, 103.5, 119.3, 122.5, 126.6,
1H), 7.54 (d, J = 8.4 Hz, 2H); ½a D20
¼ þ6:9 (c 1.20, CHCl3) (64% ee);
ꢂ
Chiralcel AD-H, hexane/iPrOH = 75:25, 0.7 mL/min, 254 nm,
tmajor = 44.34 min, tminor = 48.57 min.
4.7.2. Ethyl 6-chloro-2-methyl-4-(4-methylphenylsulfon-
amido)-4H-chromene-3-carboxylate 3ba
white solid (34.5 mg, 82%); mp 144–146 °C; 1H NMR
130.8, 141.5, 143.2, 146.7, 150.4; IR (neat)
m 2963, 2928, 1617,
A
1509, 1454, 1346, 1256, 1097, 1017, 800, 691 cmꢁ1; MS (ESI) m/e
378 (M+H); HRMS (ESI) for C24H32N3O (M+H): 378.2540; found:
378.2543.
(400 MHz, CDCl3, TMS) d 1.26 (t, J = 7.2 Hz, 3H), 2.40 (s, 6H),
3.97–4.04 (m, 1H), 4.10–4.16 (m, 1H), 5.23 (d, J = 6.0 Hz, 1H),
5.47 (d, J = 6.0 Hz, 1H), 6.96 (d, J = 8.8 Hz, 1H), 7.08 (d, J = 2.8 Hz,
1H), 7.15 (dd, J = 2.8 Hz, 8.8 Hz, 1H), 7.19 (d, J = 7.6 Hz, 2H), 7.49
(d, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 14.2, 19.7, 21.5,
47.7, 60.8, 102.9, 117.7, 120.9, 126.6, 129.2, 129.3, 129.4, 139.0,
4.6. Characterization data for the new salicyl N-tosylimines
4.6.1. N-(2-Hydroxybenzylidene)-4-nitrobenzenesulfonamide
1h
143.1, 149.2, 163.1, 166.2; IR (neat)
m 3308, 2962, 1733, 1682,
1521, 1348, 1324, 1277, 1259, 1225, 1154, 986, 764, 656 cmꢁ1
;
A yellow solid; mp 152–154 °C; 1H NMR (400 MHz, CDCl3, TMS)
d 7.01–7.07 (m, 2H), 7.54–7.58 (m, 2H), 8.19 (d, J = 9.6 Hz, 2H), 8.41
(d, J = 9.6 Hz, 2H), 9.12 (s, 1H), 10.60 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 116.4, 118.2, 120.7, 124.6, 129.2, 135.9, 138.4, 143.9,
MS (ESI) m/e 444 (M+Na); HRMS (ESI) for C20H20NNaClO5S
(M+Na): 444.0643; found: 444.0646. ½a D20
¼ þ17:8 (c 0.40, CHCl3)
ꢂ
(37% ee); Chiralcel IC, hexane/iPrOH = 70:30, 0.6 mL/min, 254 nm,
tmajor = 20.86 min, tminor = 25.70 min.
162.5, 173.4; IR (neat)
m 1737, 1607, 1583, 1511, 1493, 1387,
1347, 1297, 1276, 1252, 1180, 1098, 886, 830, 756 cmꢁ1; MS
(ESI) m/e 307 (M+H); HRMS (ESI) for C13H10N2NaO5S (M+Na):
329.0203; found: 329.0193.
4.7.3. Ethyl 6-bromo-2-methyl-4-(4-methylphenylsulfonamido)-
4H-chromene-3-carboxylate 3ca
A white solid (30.2 mg, 65%); mp 145–146 °C; This is a known
compound.6a 1H NMR (400 MHz, CDCl3, TMS) d 1.27 (t, J = 7.2 Hz,
3H), 2.41 (s, 6H), 4.00–4.05 (m, 1H), 4.13–4.18 (m, 1H), 5.22 (d,
J = 6.0 Hz, 1H), 5.46 (d, J = 6.0 Hz, 1H), 6.91 (d, J = 8.8 Hz, 1H),
7.18–7.20 (m, 3H), 7.29 (m, 1H), 7.49 (d, J = 8.5 Hz, 2H).
4.6.2. 4-Bromo-N-(2-hydroxybenzylidene)benzenesulfonamide
1i
A white solid; mp 147–149 °C 1H NMR (400 MHz, CDCl3, TMS) d
6.99–7.04 (m, 2H), 7.50–7.56 (m, 2H), 7.69–7.71 (m, 2H), 7.83–7.85
(m, 2H), 9.11 (s, 1H), 10.71 (s, 1H); 13C NMR (100 MHz, CDCl3) d
116.4, 118.0, 120.4, 129.2, 129.3, 132.7, 135.6, 137.1, 137.8,
½
a 2D0
ꢂ
¼ þ17:1 (c 0.40, CHCl3) (39% ee); Chiralcel OJ-H, hex-
ane/iPrOH = 80:20,
0.7 mL/min,
214 nm,
tmajor = 13.73 min,
tminor = 18.23 min.
162.2, 172.2; IR (neat)
m 1741, 1624, 1593, 1509, 1389, 1327,
1258, 1159, 1088, 817, 763, 645 cmꢁ1; MS (ESI) m/e 340 (M+H);
4.7.4. Ethyl 6,8-dichloro-2-methyl-4-(4-methylphenylsulfon-
amido)-4H-chromene-3-carboxylate 3da
HRMS (ESI) for C13H11BrNO3S (M+H): 339.9638; found: 339.9648.
A white solid (38.7 mg, 85%); mp 132–134 °C; This is a known
compound.6a 1H NMR (400 MHz, CDCl3, TMS) d 1.26 (t, J = 7.2 Hz,
3H), 2.41 (s, 3H), 2.46 (s, 3H), 3.99–4.05 (m, 1H), 4.10–4.17 (m,
1H), 5.17 (s, 1H), 5.49 (s, 1H), 7.05–7.06 (m, 1H), 7.21 (d,
J = 8.0 Hz, 2H), 7.26–7.27 (m, 1H), 7.52 (d, J = 8.0 Hz, 2H);
4.6.3. N-(2-Hydroxybenzylidene)-2,4,6-triisopropylbenzene-
sulfonamide 1j
A yellow solid; mp 143–146 °C; 1H NMR (400 MHz, CDCl3, TMS)
d 1.26 (d, J = 6.8 Hz, 6H), 1.20 (d, J = 6.8 Hz, 12H), 2.92 (sept,
J = 6.8 Hz, 1H), 4.28 (sept, J = 6.8 Hz, 2H), 7.01 (d, J = 6.8 Hz, 2H),
7.22 (s, 2H), 7.49 (d, J = 8.0 Hz, 2H), 9.11 (s, 1H), 10.91 (s, 1H);
13C NMR (100 MHz, CDCl3) d 23.5, 24.6, 29.8, 34.2, 116.7, 117.7,
120.2, 124.0, 130.7, 135.2, 137.0, 151.1, 154.2, 161.8, 170.2; IR
½
a 2D0
ꢂ
¼ þ11:9 (c 1.05, CHCl3) (20% ee); Chiralcel IC, hex-
ane/iPrOH = 70:30,
0.5 mL/min,
254 nm,
tmajor = 19.59 min,
tminor = 24.86 min.
(neat)
m 1743, 1619, 1591, 1559, 1488, 1457, 1427, 1389, 1357,
1317, 1275, 1039, 807, 672 cmꢁ1; MS (ESI) m/e 388 (M+H); HRMS
4.7.5. Ethyl 6,8-dibromo-2-methyl-4-(4-methylphenylsulfon-
(ESI) for C22H30NO3S (M+H): 388.1941; found: 388.1931.
amido)-4H-chromene-3-carboxylate 3ea
A
white solid (29.2 mg, 56%); mp 148–149 °C; 1H NMR
(400 MHz, CDCl3, TMS) d 1.26 (t, J = 6.8 Hz 6H), 2.41 (s, 3H), 2.45
(s, 3H), 3.99–4.06 (m, 1H), 4.10–4.17 (m, 1H), 5.31 (s, 1H), 5.48
(s, 1H), 7.19–7.22 (m, 3H), 7.51 (d, J = 8.0 Hz, 2H), 7.54 (d,
J = 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 14.1, 19.6, 21.5, 47.7,
61.0, 103.7, 111.1, 116.7, 122.5, 126.7, 129.4, 131.4, 134.9, 138.7,
4.7. General procedure for the reaction of salicyl N-tosylimine
1a with ethyl 2,3-butadienoate 2a in the presence of cat. 5
A solution of salicyl N-tosylimine 1a (27.6 mg, 0.1 mmol), ethyl
2,3-butadienoate 2a (13.6 lL, 0.12 mmol), MS 4 Å (50.0 mg) in Et2O
143.2, 146.9, 163.1, 165.7; IR (neat)
m 3312, 2987, 1797, 1680,
(2.0 mL) was stirred at 25 °C for 24 h in the presence of organocat-
alyst cat. 5 (3.5 mg, 10 mol %) under an argon atmosphere. The
reaction was monitored by TLC. When 1a disappeared, the solvent
was removed under reduced pressure and the residue was purified
by flash chromatography (eluent: EtOAc/petroleum ether = 1:4) to
yield 3aa (34.8 mg, 90%) as a colorless solid.
1581, 1462, 1396, 1380, 1343, 1299, 1156, 1074, 758, 655 cmꢁ1
;
MS (ESI) m/e 565 (M+H); HRMS (ESI) for
C20H19NNaBr2O5S
(M+H): 565.9243; found: 545.9228. ½a D20
¼ þ6:7 (c 0.90, CHCl3)
ꢂ
(10% ee); Chiralcel IC, hexane/iPrOH = 80:20, 0.7 mL/min, 254 nm,
tmajor = 26.23 min, tminor = 35.03 min.

1246
C.-K. Pei, M. Shi / Tetrahedron: Asymmetry 22 (2011) 1239–1248
4.7.6. Ethyl 8-methoxy-2-methyl-4-(4-methylphenylsulfon-
amido)-4H-chromene-3-carboxylate 3fa
522.2285; found: 522.2285. ½a D20
¼ ꢁ13:2 (c 1.10, CHCl3) (50%
ꢂ
ee); Chiralcel OD-H, hexane/iPrOH = 99:1, 0.7 mL/min, 230 nm,
A white solid (34.5 mg, 82%); mp 144–146 °C; This is a known
compound.6a 1H NMR (400 MHz, CDCl3, TMS) d 1.22 (t, J = 7.2 Hz,
3H), 2.35 (s, 3H), 2.40 (s, 3H), 3.85–3.93 (m, 4H), 4.05–4.13 (m,
1H), 5.04 (d, J = 6.8 Hz, 1H), 5.64 (d, J = 6.8 Hz, 1H), 6.81–6.83 (m,
1H), 6.97–7.00 (m, 2H), 7.21 (d, J = 8.0 Hz, 2H), 7.61 (d, J = 8.0 Hz,
tmajor = 14.78 min, tminor = 11.73 min.
4.7.11. Methyl 2-methyl-4-(4-methylphenylsulfonamido)-4H-
chromene-3-carboxylate 3ab
A
white solid (33.7 mg, 85%); mp 127–129 °C; 1H NMR
2H); ½a 2D0
ꢂ
¼ þ17:2 (c 0.40, CHCl3) (74% ee); Chiralcel IC, hex-
(400 MHz, CDCl3, TMS) d 2.38 (s, 3H), 2.39 (s, 3H), 3.42 (s, 3H),
5.27 (s, 1H), 5.56 (s, 1H), 7.01–7.06 (m, 2H), 7.19–7.27 (m, 3H),
7.41 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 19.6, 21.4, 47.6, 51.3, 102.7, 116.2, 120.3,
124.8, 126.7, 129.0, 129.2, 129.6, 139.2, 142.6, 150.4, 163.5,
ane/iPrOH = 70:30,
0.7 mL/min,
214 nm,
tmajor = 40.29 min,
tminor = 61.29 min.
4.7.7. Ethyl 6-methoxy-2-methyl-4-(4-methylphenylsulfon-
amido)-4H-chromene-3-carboxylate 3ga
166.6; IR (neat) m 3275, 2988, 1696, 1633, 1489, 1434, 1329,
A
white solid (34.5 mg, 82%); mp 144–146 °C; 1H NMR
1275, 1261, 1151, 1066, 926, 788, 750, 615 cmꢁ1; MS (ESI) m/e
(400 MHz, CDCl3, TMS) d 1.22 (t, J = 7.2 Hz, 3H), 2.39 (s, 6H), 3.65
(s, 3H), 3.89–3.96 (m, 1H), 4.08–4.14 (m, 1H), 5.11 (d, J = 6.0 Hz,
1H), 5.56 (d, J = 6.0 Hz, 1H), 6.74–6.81 (m, 2H), 6.97 (d, J = 8.0 Hz,
396 (M+H); HRMS (ESI) for C19H19NNaO5S (M+H): 396.0876;
found: 396.0880. ½a D20
¼ ꢁ7:8 (c 0.35, CHCl3) (64% ee); Chiralcel
ꢂ
AD-H, hexane/iPrOH = 75:25, 0.7 mL/min, 254 nm, tmajor = 45.39
min, tminor = 18.49 min.
1H), 7.18 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H); ½a D20
¼ þ14:5
ꢂ
(c 0.40, CHCl3) (69% ee); Chiralcel AD-H, hexane/iPrOH = 60:40,
0.7 mL/min, 214 nm, tmajor = 26.13 min, tminor = 30.63 min.
4.7.12. tert-Butyl 2-methyl-4-(4-methylphenylsulfonamido)-
4H-chromene-3-carboxylate 3ac
4.7.8. Ethyl 2-methyl-4-(4-nitrophenylsulfonamido)-4H-
A
white solid (31.1 mg, 75%); mp 143–145 °C; 1H NMR
chromene-3-carboxylate 3ha
(400 MHz, CDCl3, TMS) d 1.46 (s, 9H), 2.33 (s, 3H), 2.38 (s, 3H),
5.04 (d, J = 6.0 Hz, 1H), 5.57 (d, J = 6.0 Hz, 1H), 6.95–7.02 (m, 2H),
7.16 (d, J = 8.0 Hz, 2H), 7.20–7.28 (m, 2H), 7.53 (d, J = 8.0 Hz, 2H);
13C NMR (100 MHz, CDCl3) d 19.9, 21.4, 28.2, 48.2, 81.4, 104.3,
116.1, 119.9, 124.4, 126.8, 128.9, 129.1, 129.6, 139.2, 142.6,
A
white solid (27.2 mg, 65%); mp 148–149 °C; 1H NMR
(300 MHz, CDCl3, TMS) d 1.26 (t, J = 7.2 Hz, 3H), 2.43 (s, 3H),
4.00–4.15 (m, 2H), 5.42 (d, J = 6.0 Hz, 1H), 5.62 (d, J = 6.0 Hz, 1H),
6.96 (t, J = 7.8 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 7.24–7.28 (m, 2H),
7.76 (d, J = 9.0 Hz, 2H), 8.19 (d, J = 9.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 14.2, 20.0, 48.6, 60.9, 102.8, 116.5, 119.0,
150.7, 162.2, 165.7; IR (neat)
m 3357, 2924, 2853, 1664, 1588,
1488, 1363, 1150, 1031, 988, 777, 660 cmꢁ1; MS (ESI) m/e 438
123.7, 124.8, 129.5, 147.7, 149.5, 150.7, 163.8, 166.4; IR (neat)
m
(M+Na); HRMS (ESI) for C22H25NNaO5S (M+Na): 438.1346; found:
3260, 2985, 2928, 1710, 1637, 1608, 1529, 1488, 1461, 1348,
438.1350. ½a 2D0
¼ þ12:0 (c 0.45, CHCl3) (65% ee); Chiralcel IC, hex-
ꢂ
1221, 1161, 1092, 989, 762, 746 cmꢁ1; MS (ESI) m/e 441 (M+Na);
ane/iPrOH = 80:20,
0.7 mL/min,
214 nm,
tmajor = 20.13 min,
HRMS (ESI) for
C
19H18N2NaO7S (M+Na): 441.0727; found:
tminor = 23.73 min.
441.0742. ½a 2D0
¼ ꢁ9 (c 0.20, CHCl3) (43% ee); Chiralcel IC, hex-
ꢂ
ane/iPrOH = 70:30,
0.7 mL/min,
214 nm,
tmajor = 21.13 min,
4.7.13. Isopropyl 2-methyl-4-((4-methylphenylsulfonamido)-
tminor = 23.08 min.
methyl)-4H-chromene-3-carboxylate 3ad
A
white solid (33.9 mg, 80%); mp 157–159 °C; 1H NMR
4.7.9. Ethyl 4-(4-bromophenylsulfonamido)-2-methyl-4H-
(400 MHz, CDCl3, TMS) d 1.24 (d, J = 6.4 Hz, 3H), 1.28 (d,
chromene-3-carboxylate 3ia
J = 6.4 Hz, 3H), 2.36 (s, 3H), 2.38 (s, 3H), 4.97–5.03 (m, 2H), 5.58
(d, J = 6.4 Hz, 1H), 6.96–7.04 (m, 2H), 7.16 (d, J = 7.6 Hz, 2H),
7.21–7.28 (m, 3H), 7.51 (d, J = 7.6 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d 19.9, 21.4, 21.8, 21.9, 48.1, 68.4, 103.2, 116.2, 119.7,
124.6, 126.8, 129.0, 129.1, 129.6, 139.2, 142.7, 150.7, 163.0,
A
white solid (31.1 mg, 69%); mp 151–153 °C; 1H NMR
(400 MHz, CDCl3, TMS) d 1.25 (t, J = 7.2 Hz, 3H), 2.40 (s, 3H), 2.39
(s, 3H), 3.93–4.01 (m, 1H), 4.08–4.16 (m, 1H), 5.28 (s, 1H), 5.58
(s, 1H), 6.99–7.05 (m, 2H), 7.23–7.30 (m, 3H), 7.47–7,53(m, 4H);
13C NMR (100 MHz, CDCl3) d 14.2, 19.9, 48.2, 60.7, 102.9, 116.3,
119.4, 124.8, 126.8, 128.3, 129.3, 129.6, 131.7, 141.2, 150.6,
166.0; IR (neat)
m 3272, 2926, 1708, 1637, 1587, 1489, 1461,
1381, 1343, 1291, 1262, 1159, 1106, 1063, 814, 760, 664 cmꢁ1
;
163.4, 166.4; IR (neat)
m
2988, 2891, 1709, 1637, 1587, 1576,
MS (ESI) m/e 424 (M+Na); HRMS (ESI) for C21H23NO5SNa (M+Na):
1488, 1275, 1260, 1109, 750 cmꢁ1; MS (ESI) m/e 473 (M+Na);
424.1189; found: 424.1189. ½a D20
¼ þ24:6 (c 0.70, CHCl3) (70%
ꢂ
HRMS (ESI) for C21H26N3OS (M+Na): 473.9981; found: 473.9988.
ee); Chiralcel IC, hexane/iPrOH = 80:20, 0.7 mL/min, 214 nm,
½
a 2D0
ꢂ
¼ þ2:8 (c 0.40, CHCl3) (61% ee); Chiralcel OJ-H, hex-
tmajor = 30.43 min, tminor = 42.33 min.
ane/iPrOH = 80:20,
0.7 mL/min,
214 nm,
tmajor = 22.28 min,
tminor = 32.73 min.
4.7.14. Isopropyl 6-Cl-2-methyl-4-((4-methylphenylsulfon-
amido)methyl)-4H-chromene-3-carboxylate 3bd
4.7.10. Ethyl 2-methyl-4-(2,4,6-triisopropylphenylsulfonamido)-
A
white solid (36.5 mg, 80%); mp 135–137 °C; 1H NMR
4H-chromene-3-carboxylate 3ja
(400 MHz, CDCl3, TMS) d 1.26 (d, J = 6.0 Hz, 3H), 1.29 (d,
A
white solid (24.9 mg, 50%); mp 155–158 °C; 1H NMR
J = 6.0 Hz, 3H), 2.39 (s, 3H), 2.39 (s, 3H), 5.02 (sept, J = 6.0 Hz,
1H), 5.24 (d, J = 5.6 Hz, 1H), 5.45 (d, J = 5.6 Hz, 1H), 6.96 (d,
J = 8.4 Hz, 1H), 7.00 (br s, 1H), 7.12–7.18 (m, 3H), 7.47 (d,
J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 19.8, 21.4, 21.8, 21.9,
47.8, 68.6, 103.2, 117.6, 120.7, 126.6, 129.1, 129.18, 129.23,
(400 MHz, CDCl3, TMS)
d 1.13 (d, J = 6.4 Hz, 6H), 1.18 (t,
J = 7.2 Hz, 3H), 1.24 (d, J = 7.6 Hz, 12H), 2.45 (s, 3H), 2.88 (dsept,
J = 7.2, 14.4 Hz, 1H), 3.74–3.82 (m, 1H), 4.01–4.11 (m, 3H), 4.70
(d, J = 7.6 Hz, 1H), 5.70 (d, J = 7.6 Hz, 1H), 6.87 (t, J = 7.2 Hz, 1H),
7.00 (d, J = 8.0 Hz, 1H), 7.07 (s, 2H), 7.15–7.26 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 14.2, 19.6, 23.6, 23.7, 24.4, 24.7, 29.6, 34.1,
47.7, 60.4, 104.1, 116.2, 120.6, 123.3, 128.8, 129.3, 135.5, 149.2,
150.4, 152.1, 162.7, 166.3; IR (neat)
1630, 1487, 1462, 1363, 1217, 1145, 1064, 986, 777, 659 cmꢁ1
MS (ESI) m/e 522 (M+H); HRMS (ESI) for C28H37NNaO5S (M+Na):
139.0, 143.0, 149.3, 162.9, 165.8; IR (neat)
m 3207, 2924, 2877,
1654, 1633, 1479, 1373, 1328, 1278, 1236, 1151, 1088, 885,
763 cmꢁ1; MS (ESI) m/e 458 (M+Na); HRMS (ESI) for C21H22NO5SCl-
m
3285, 2958, 2867, 1706,
Na (M+Na): 458.0799; found: 458.0809. ½a D20
¼ þ39 (c 0.30, CHCl3)
ꢂ
;
(67% ee); Chiralcel OD-H, hexane/iPrOH = 80:20, 0.7 mL/min,
214 nm, tmajor = 7.82 min, tminor = 9.19 min.

C.-K. Pei, M. Shi / Tetrahedron: Asymmetry 22 (2011) 1239–1248
1247
4.7.15. Isopropyl 6-bromo-2-methyl-4-((4-methylphenylsulfon-
amido)methyl)-4H-chromene-3-carboxylate 3cd
white solid (36.1 mg, 72%); mp 155–157 °C; 1H NMR
(400 MHz, CDCl3, TMS) 1.26 (d, J = 6.4 Hz, 3H), 1.29 (d,
4.7.19. Isopropyl 6-methoxy-2-methyl-4-((4-methylphenyl-
sulfonamido)methyl)-4H-chromene-3-carboxylate 3gd
A
A
white solid (34.1 mg, 75%); mp 157–159 °C; 1H NMR
d
(300 MHz, CDCl3, TMS) d 1.25 (d, J = 6.0 Hz, 3H), 1.27 (d,
J = 6.4 Hz, 3H), 2.39 (s, 3H), 2.40 (s, 3H), 5.02 (sept, J = 6.4 Hz,
1H), 5.34 (br s, 1H), 5.44 (d, J = 6.0 Hz, 1H), 6.89 (d, J = 8.8 Hz,
1H), 7.11 (d, J = 1.6 Hz, 1H), 7.17 (d, J = 7.6 Hz, 2H), 7.25 (d,
J = 8.8 Hz, 1H), 7.46 (d, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 19.8, 21.5, 21.8, 21.9, 47.7, 68.6, 103.3, 116.6, 118.0, 121.1,
126.6, 129.3, 131.9, 132.1, 138.9, 143.0, 149.8, 162.9, 165.8; IR
J = 6.0 Hz, 3H), 2.37 (s, 3H), 2.37 (s, 3H), 3.61 (s, 3H), 5.01 (sept,
J = 6.0 Hz, 1H), 5.09 (d, J = 6.0 Hz, 1H), 5.54 (d, J = 6.0 Hz, 1H),
6.65 (d, J = 3.0 Hz, 1H), 6.77 (dd, J = 3.0 Hz, 9.0 Hz, 1H), 6.96 (d,
J = 9.0 Hz, 1H), 7.16 (d, J = 7.8 Hz, 2H), 7.49 (d, J = 7.8 Hz, 2H); 13C
NMR (100 MHz, CDCl3) d 19.9, 21.3, 21.8, 21.9, 48.6, 55.3, 68.3,
102.4, 112.0, 116.4, 117.2, 119.9, 126.7, 129.0, 139.4, 142.6,
(neat)
m
3672, 2972, 2901, 1709, 1652, 1633, 1602, 1376, 1328,
144.9, 156.1, 163.1, 166.2; IR (neat)
m 3288, 2924, 2877, 1658,
1234, 1066, 907, 777 cmꢁ1; MS (ESI) m/e 502 (M+Na); HRMS
1494, 1374, 1340, 1289, 1224, 1204, 1155, 1073, 811, 762 cmꢁ1
;
(ESI) for C21H22BrNNaO5S (M+Na): 502.0294; found: 502.0309.
MS (ESI) m/e 454 (M+Na); HRMS (ESI) for C22H25NO6SNa (M+Na):
½
a 2D0
ꢂ
¼ þ20:8 (c 0.35, CHCl3) (76% ee); Chiralcel OD-H, hex-
454.1295; found: 454.1311. ½a D20
¼ þ17:4 (c 0.50, CHCl3) (64%
ꢂ
ane/iPrOH = 80:20,
0.7 mL/min,
214 nm,
tmajor = 8.58 min,
ee); Chiralcel OD-H, hexane/iPrOH = 95:5, 0.7 mL/min, 214 nm,
tminor = 10.33 min.
tmajor = 30.49 min, tminor = 38.12 min.
4.7.20. Isopropyl 2,8-dimethyl-4-(4-methylphenylsulfon-
4.7.16. Isopropyl 6,8-dichloro-2-methyl-4-(4-methylphenyl-
amido)-4H-chromene-3-carboxylate 3kd
sulfonamido)-4H-chromene-3-carboxylate 3dd
white solid (35.0 mg, 80%); mp 124–126 °C; 1H NMR
A
yellow solid (13.3 mg, 27%); mp 145–147 °C; 1H NMR
A
(300 MHz, CDCl3, TMS)
d 1.24 (d, J = 6.6 Hz, 3H), 1.26 (d,
(400 MHz, CDCl3, TMS)
d 1.26 (d, J = 6.4 Hz, 3H), 1.29 (d,
J = 6.6 Hz, 3H), 2.30 (s, 3H), 2.38 (s, 3H), 2.39 (s, 3H), 4.95–5.02
(m, 2H), 5.58 (d, J = 4.5 Hz, 1H), 6.87 (t, J = 7.5 Hz, 1H), 7.05–7.10
(m, 2H), 7.16 (d, J = 7.8 Hz, 2H), 7.52 (d, J = 7.8 Hz, 2H); 13C NMR
(75 MHz, CDCl3) d 15.6, 19.9, 21.5, 21.9, 22.0, 48.4, 68.4, 103.5,
119.6, 124.1, 125.5, 126.9, 127.1, 129.2, 130.3, 139.3, 142.7,
J = 6.4 Hz, 3H), 2.40 (s, 3H), 2.44 (s, 3H), 5.03 (sept, J = 6.4 Hz,
1H), 5.13 (d, J = 6.0 Hz, 1H), 5.47 (d, J = 6.0 Hz, 1H), 6.99 (d,
J = 2.4 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 2.4 Hz, 1H),
7.50 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 19.6, 21.4,
21.8, 21.9, 47.8, 68.9, 103.8, 122.1, 122.3, 126.8, 127.7, 129.0,
149.2, 163.0, 166.1; IR (neat)
m 3312, 2954, 2919, 1689, 1648,
129.3, 129.4, 138.8, 143.2, 145.6, 162.7, 165.4; IR (neat)
m 3005,
1593, 1531, 1465, 1382, 1283, 1242, 1089, 763, 660 cmꢁ1; MS
2926, 1683, 1580, 1364, 1275, 1257, 1158, 980, 750, 658 cmꢁ1
;
(ESI) m/e 438 (M+Na); HRMS (ESI) for C22H25NNaO5S (M+Na):
MS (ESI) m/e 492 (M+Na); HRMS (ESI) for C21H21NO5SCl2Na
438.1346; found: 438.1349. ½a D20
¼ þ11:0 (c 0.30, CHCl3) (87%
ꢂ
(M+Na): 492.0410; found: 492.0427. ½a D20
¼ þ9:6 (c 0.50, CHCl3)
ꢂ
ee); Chiralcel IC, hexane/iPrOH = 80:20, 1.0 mL/min, 220 nm,
(38% ee); Chiralcel IC, hexane/iPrOH = 70:30, 0.5 mL/min, 214 nm,
tmajor = 22.28 min, tminor = 33.38 min.
tmajor = 19.21 min, tminor = 25.54 min.
4.7.21. Isopropyl 6,8-di-tert-butyl-2-methyl-4-(4-methyl-
phenylsulfonamido)-4H-chromene-3-carboxylate 3ld
4.7.17. Isopropyl 6,8-dibromo-2-methyl-4-(4-methylphenyl-
sulfonamido)-4H-chromene-3-carboxylate 3ed
A
white solid (34.8 mg, 65%); mp 128–130 °C; 1H NMR
A
white solid (12.2 mg, 21%); mp 155–157 °C; 1H NMR
(400 MHz, CDCl3, TMS) d 1.18 (s, 9H), 1.28 (d, J = 6.0 Hz, 3H), 1.30
(d, J = 6.0 Hz, 3H), 1.42 (s, 9H), 2.35 (s, 3H), 2.45 (s, 3H), 4.85 (d,
J = 6.4 Hz, 1H), 5.06 (sept, J = 6.0 Hz, 1H), 5.58 (d, J = 6.4 Hz, 1H),
7.06 (d, J = 2.4 Hz, 1H), 7.13 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 2.4 Hz,
1H), 7.51 (d, J = 8.0 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 14.2,
19.7, 21.4, 21.8, 22.0, 30.0, 31.2, 34.4, 34.9, 48.9, 68.3, 103.7,
119.5, 123.6, 124.0, 126.7, 129.1, 136.5, 139.4, 142.5, 146.7,
(300 MHz, CDCl3, TMS)
d 1.27 (d, J = 6.0 Hz, 3H), 1.29 (d,
J = 6.0 Hz, 3H), 2.41 (s, 3H), 2.45 (s, 3H), 5.02–5.10 (m, 2H), 5.47
(d, J = 6.0 Hz, 1H), 7.14 (d, J = 2.1 Hz, 1H), 7.20 (d, J = 8.1 Hz, 2H),
7.48 (d, J = 8.1 Hz, 2H), 7.54 (d, J = 2.1 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 19.6, 21.5, 21.78, 21.85, 47.8, 68.9, 104.0,
111.1, 116.5, 122.4, 126.7, 129.3, 131.3, 134.9, 138.7, 143.2,
147.0, 162.8, 165.3; IR (neat)
m 3290, 3005, 1682, 1571, 1459,
162.9, 166.0; IR (neat)
m 3277, 2931, 2962, 2926, 1708, 1664,
1365, 1275, 1258, 1203, 1157, 1073, 1026, 979, 749, 657 cmꢁ1
;
1640, 1589, 1460, 1364, 1240, 1201, 1159, 1070, 760, 739,
MS (ESI) m/e 579 (M+Na); HRMS (ESI) for C21H21NNaBr2O5S
663 cmꢁ1; MS (ESI) m/e 536 (M+Na); HRMS (ESI) for C29H39NNaO5S
(M+Na): 579.9399; found: 579.9425. ½a D20
¼ þ6:4 (c 0.35, CHCl3)
ꢂ
(M+Na): 536.2441; found: 536.2461. ½a D20
¼ þ50:6 (c 0.35, CHCl3)
ꢂ
(21% ee); Chiralcel IC, hexane/iPrOH = 80:20, 0.7 mL/min, 214 nm,
(72% ee); Chiralcel AD-H, hexane/iPrOH = 90:10, 0.8 mL/min,
tmajor = 19.83 min, tminor = 28.38 min.
230 nm, tmajor = 6.18 min, tminor = 14.73 min.
4.7.18. Isopropyl 8-methoxy-2-methyl-4-(4-methylphenyl-
4.7.22. Isopropyl 2-methyl-4-(4-nitrophenylsulfonamido)-4H-
sulfonamido)-4H-chromene-3-carboxylate 3fd
chromene-3-carboxylate 3hd
white solid (35.9 mg, 79%); mp 157–159 °C; 1H NMR
A
white solid (29.8 mg, 69%); mp 152–155 °C; 1H NMR
A
(400 MHz, CDCl3, TMS)
d 1.24 (d, J = 6.0 Hz, 3H), 1.28 (d,
(400 MHz, CDCl3, TMS)
d 1.23 (d, J = 6.0 Hz, 3H), 1.28 (d,
J = 6.0 Hz, 3H), 2.21 (s, 3H), 2.38 (s, 3H), 3.81 (s, 3H), 4.98 (sept,
J = 6.0 Hz, 1H), 5.27 (d, J = 7.2 Hz, 1H), 5.65 (d, J = 7.2 Hz, 1H),
6.79 (d, J = 7.6 Hz, 1H), 6.89–6.96 (m, 2H), 7.18 (d, J = 8.0 Hz, 2H),
7.60 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 19.4, 21.4,
21.7, 21.8, 47.7, 55.9, 68.4, 103.4, 110.8, 120.8, 121.3, 124.3,
J = 6.0 Hz, 3H), 2.42 (s, 3H), 5.00 (sept, J = 6.0 Hz, 1H), 5.32 (d,
J = 4.2 Hz, 1H), 5.61 (d, J = 4.2 Hz, 1H), 6.93 (t, J = 8.4 Hz, 1H), 7.07
(d, J = 8.4 Hz, 1H), 7.21–7.26 (m, 2H), 7.75 (d, J = 8.8 Hz, 2H), 8.18
(d, J = 8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 20.1, 21.9, 48.7,
68.7, 103.2, 116.5, 118.9, 123.7, 124.7, 128.1, 129.50, 129.52,
126.8, 129.1, 139.2, 140.3, 142.6, 147.2, 162.5, 165.9; IR (neat)
m
147.7, 149.5, 150.8, 163.4, 166.0; IR (neat)
m 3279, 2988, 1657,
3298, 2921, 1704, 1589, 1332, 1276, 1210, 1156, 1092, 1015,
1527, 1373, 1341, 1277, 1240, 1199, 1154, 1087, 1015, 764,
764, 748, 660 cmꢁ1; MS (ESI) m/e 454 (M+Na); HRMS (ESI) for
748 cmꢁ1
;
MS (ESI) m/e 455 (M+Na); HRMS (ESI) for
C22H25NNaO6S (M+Na): 454.1295; found: 454.1314. ½a D20
¼ þ22:0
ꢂ
C
20H20N2NaO7S (M+Na): 455.0883; found: 455.0890. ½a D20
¼ ꢁ3:0
ꢂ
(c 0.20, CHCl3) (76% ee); Chiralcel OJ-H, hexane/iPrOH = 80:20,
0.7 mL/min, 214 nm, tmajor = 20.09 min, tminor = 29.13 min.
(c 0.30, CHCl3) (65% ee); Chiralcel AD-H, hexane/iPrOH = 70:30,
0.6 mL/min, 214 nm, tmajor = 31.21 min, tminor = 52.54 min.

1248
C.-K. Pei, M. Shi / Tetrahedron: Asymmetry 22 (2011) 1239–1248
2. Hepworth, J. In Comprehensive Heterocyclic Chemistry; Katrizky, A. R., Rees, C.
W., Eds.; Pergamon: Oxford, 1984; Vol. 3, pp 737–883.
4.7.23. Isopropyl 4-(4-bromophenylsulfonamido)-2-methyl-4H-
chromene-3-carboxylate 3id
3. (a) Kaye, P. T.; Musa, M. A.; Nocanda, X. W.; Robinson, R. S. Org. Biomol. Chem.
2003, 1, 1133–1138; (b) Kaye, P. T.; Musa, M. A. Synthesis 2003, 531–534; (c)
Kaye, P. T.; Nocanda, X. W. J. Chem. Soc., Perkin Trans. 1 2002, 1318–1323; (d)
Kaye, P. T.; Musa, M. A. Synthesis 2002, 2701–2706; (e) Kaye, P. T.; Nocanda, X.
W. Synthesis 2001, 2389–2392; (f) Kaye, P. T.; Nocanda, X. W. J. Chem. Soc.,
Perkin Trans. I 2000, 1331–1332; (g) Familoni, O. B.; Kaye, P. T.; Klaas, P. J. Chem.
Commun. 1998, 2563–2564; (h) Robinson, R. S.; Kaye, P. T. Synth. Commun.
1996, 26, 2085–2097; (i) Lesch, B.; Bräse, S. Angew. Chem., Int. Ed. 2004, 43,
115–118; (j) Yamaguchi, S.; Saitoh, T.; Kamiumezawa, M.; Enomoto, H.;
Kawase, Y. J. Heterocycl. Chem. 1992, 29, 755–758; (k) Kawase, Y.; Yamaguchi,
S.; Horita, H.; Takeno, J.; Kameyama, H. Bull. Chem. Soc. Jpn. 1982, 55, 1153–
1155; (l) Lesch, B.; Toräng, J.; Vanderheiden, S.; Bräse, S. Adv. Synth. Catal. 2005,
347, 555–562; (m) Lee, K. Y.; Kim, J. M.; Kim, J. N. Bull. Korean Chem. Soc. 2003,
24, 17–18; (n) Shi, Y.-L.; Shi, M. Org. Biomol. Chem. 2005, 3, 1620–1621; (o) Qi,
M.-J.; Shi, M. Tetrahedron 2007, 63, 10415–10424; (p) Nising, C.; Bräse, S. Chem.
Soc. Rev. 2008, 37, 1218–1228.
4. For reactions of allenoates with N-tosylated imines, see: (a) Xu, Z.; Lu, X.
Tetrahedron Lett. 1997, 38, 3461–3464; (b) Xu, Z.; Lu, X. J. Org. Chem.
1998, 63, 5031–5041; (c) Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34,
535–544; (d) Zhu, X.-F.; Lan, J.; Kwon, O. J. Am. Chem. Soc. 2003, 125,
4716–4717; (e) Zhao, G.-L.; Huang, J.-W.; Shi, M. Org. Lett. 2003, 5, 4737–
4739; (f) Zhu, X.-F.; Henry, C. E.; Kwon, O. J. Am. Chem. Soc. 2007, 129,
6722–6723; (g) Moreno-Clavijo, E.; Carmona, A. T.; Reissig, H.-U.; Moreno-
Vargas, A. J.; Alvarez, E.; Robina, I. Org. Lett. 2009, 11, 4778–4781; (h) Zhu,
X.-F.; Henry, C. E.; Kwon, O. Tetrahedron 2005, 61, 6276–6282; (i) Zhao,
G.-L.; Shi, M. J. Org. Chem. 2005, 70, 9975–9984.
5. For reactions of allenoates with aldehydes catalyzed by phosphine Lewis base,
see: (a) Zhu, X.-F.; Henry, C. E.; Wang, J.; Dudding, T.; Kwon, O. Org. Lett. 2005,
7, 1387–1390; (b) Zhu, X.-F.; Schaffner, A.-P.; Li, R. C.; Kwon, O. Org. Lett. 2005,
7, 2977–2980; (c) Castellano, S.; Fiji, H. D. G.; Kinderman, S. S.; Watanabe, M.;
de Leon, P.; Tamanoi, F.; Kwon, O. J. Am. Chem. Soc. 2007, 129, 5843–5845; (d)
Tran, Y. S.; Kwon, O. J. Am. Chem. Soc. 2007, 129, 12632–12633; (e) Lu, Z.; Zheng,
S.; Zhang, X.; Lu, X. Org. Lett. 2008, 10, 3267–3270; (f) Henry, C. E.; Kwon, O.
Org. Lett. 2007, 9, 3069–3072; (g) Cowen, B. J.; Miller, S. J. Chem. Soc. Rev. 2009,
38, 3102–3116; (h) Garnier, J.-M.; Liu, F. Org. Biomol. Chem. 2009, 7, 1272–
1275; (i) Xu, S.; Zhou, L.; Zeng, S.; Ma, R.; Wang, Z.; He, Z. Org. Lett. 2009, 11,
3498–3501; (j) He, Z.; Tang, X.; He, Z. Phosphorus, Sulfur Silicon Relat. Elem.
2008, 183, 1518–1525; (k) Song, M.; Montgomery, J. Tetrahedron 2005, 62, 457–
460; (l) Creech, G. S.; Kwon, O. Org. Lett. 2008, 10, 429–432; (m) Yu, X.; Lu, X.
Org. Lett. 2009, 11, 4366–4369.
A
white solid (34.2 mg, 72%); mp 156–158 °C; 1H NMR
(400 MHz, CDCl3, TMS)
d 1.25 (d, J = 6.4 Hz, 3H), 1.27 (d,
J = 6.4 Hz, 3H), 2.39 (s, 3H), 5.00 (sept, J = 6.4 Hz, 1H), 5.24 (d,
J = 4.2 Hz, 1H), 5.57 (d, J = 4.2 Hz, 1H), 6.98 (t, J = 8.0 Hz, 1H), 7.03
(d, J = 8.0 Hz, 1H), 7.24 (d, J = 7.2 Hz, 2H), 7.44–7.50 (m, 4H); 13C
NMR (100 MHz, CDCl3) d 20.0, 21.87, 21.91, 48.3, 68.6, 103.2,
116.3, 119.2, 124.6, 126.8, 128.4, 129.2, 129.6, 131.7, 141.2,
150.7, 163.1, 166.1; IR (neat)
m 3240, 2984, 1774, 1660. 1588,
1373, 1335, 1241, 1147, 1068, 1016, 988, 757 cmꢁ1; MS (ESI) m/e
488 (M+Na); HRMS (ESI) for C20H20NNaBrO5S (M+Na): 488.0138;
found: 488.0156. ½a D20
¼ þ7:0 (c 0.30, CHCl3) (64% ee); Chiralcel
ꢂ
IC, hexane/iPrOH = 70:30, 0.6 mL/min, 214 nm, tmajor = 15.04 min,
tminor = 16.63 min.
4.7.24. Isopropyl 2-methyl-4-(2,4,6-triisopropylphenylsulfon-
amido)-4H-chromene-3-carboxylate 3jd
A
white solid (35.9 mg, 70%); mp 159–162 °C 1H NMR
(400 MHz, CDCl3, TMS) d 1.07 (d, J = 6.8 Hz, 6H), 1.22–1.28 (m,
18H), 2.45 (s, 3H), 2.86 (dsept, J = 2.8 Hz, 6.8 Hz, 1H), 3.96–4.02
(m, 2H), 4.68 (d, J = 7.2 Hz, 1H), 5.02 (dsept, J = 6.4, 12.4 Hz, 1H),
5.69 (d, J = 7.2 Hz, 1H), 6.77 (t, J = 7.6 Hz, 1H), 6.91–6.93 (m, 1H),
6.98 (d, J = 7.6 Hz, 1H), 7.03 (s, 2H), 7.12–7.16 (m, 1H); 13C NMR
(100 MHz, CDCl3) d 19.7, 21.7, 21.9, 23.7, 23.8, 24.2, 24.9, 34.1,
47.9, 68.5, 104.6, 116.2, 120.4, 123.3, 124.3, 128.7, 129.0, 135.7,
149.1, 150.6, 152.1, 162.4, 165.9; IR (neat)
m 3310, 2971, 2925,
1699, 1632, 1585, 1487, 1461, 1381, 1258, 1065, 880, 777,
658 cmꢁ1; MS (ESI) m/e 536 (M+Na); HRMS (ESI) for C29H39NNaO5S
(M+Na): 536.2441; found: 536.2454. ½a D20
¼ ꢁ9 (c 0.20, CHCl3)
ꢂ
(55% ee); Chiralcel AD-H, hexane/iPrOH = 70:30, 0.6 mL/min,
254 nm, 6.46 min, tminor = 12.13 min.
6. For reactions of allenic esters and ketones with salicyl N-tosylimines or
aldehydes, see: (a) Shi, Y.-L.; Shi, M. Org. Lett. 2005, 7, 3057–3060; (b) Zhao, G.-
L.; Shi, M. Org. Biomol. Chem. 2005, 3, 3686–3694; (c) Zhao, G.-L.; Shi, Y.-L.; Shi,
M. Org. Lett. 2005, 7, 4527–4530; (d) Dai, L.-Z.; Shi, Y.-L.; Zhao, G.-L.; Shi, M.
Chem. Eur. J. 2007, 13, 3701–3706; (e) Shi, M.; Dai, L.-Z.; Shi, Y.-L.; Zhao, G.-L.
Adv. Synth. Catal. 2006, 348, 967–972; (f) Denis, J.-B.; Masson, G.; Retailleau, P.;
Zhu, J. Angew. Chem., Int. Ed. 2011, 50, 5356–5360.
7. (a) Abermil, N.; Masson, G.; Zhu, J. J. Am. Chem. Soc. 2008, 130, 12596–12597;
(b) Song, J.; Wang, Y.; Deng, L. J. Am. Chem. Soc. 2006, 128, 6048–6049.
8. Pei, C.-K.; Zhang, X.-C.; Shi, M. Eur. J. Org. Chem. 2011, doi:10.1002/
ejoc.201100501.
9. (a) Corrao, S. L.; Macielag, M. J.; Turchi J. Org. Chem. 1990, 55, 4484–4487; (b)
Yokoyama, M.; Menjo, Y.; Watanabe, M.; Togo, H. Synthesis 1994, 1467–1470.
10. The crystal data of compound 3cd have been deposited in the CCDC with
number 814064. Empirical Formula: C21H22BrNO5S; Formula Weight: 480.37;
Crystal Color, Habit: colorless; Crystal Dimensions: 0.50 ꢃ 0.08 ꢃ 0.05 mm;
Crystal System: Orthorhombic; Lattice Type: Primitive; Lattice Parameters:
Acknowledgments
Financial support from the Shanghai Municipal Committee of
Science and Technology (08dj1400100-2), the National Basic Re-
search Program of China (973)-2010CB833302, the Fundamental
Research Funds for the Central Universities and the National Natu-
ral Science Foundation of China (21072206, 20472096, 20902019,
20872162, 20672127, 20821002, 20732008 and 20702059) and
Professor Jie Sun for performing X-ray diffraction are greatly
acknowledged.
References
a = 5.645(2) Å, b = 15.486(6) Å, c = 24.252(8) Å,
V = 2120.2(13) Å3; Space group: P2(1)2(1)2(1); Z = 4; Dcalcd = 1.505 g/cm3;
F(0 0 0) = 984; Final R indices [I > 2 (I)]: R1 = 0.0459; wR2 = 0.1142.
a = 90°, b = 90°, c = 90°,
1. (a) Schweizer, E. E.; Meeder-Nycz, O. In Chromenes, Chromanes, Chromones;
Ellis, G. P., Ed.; Wiley-Interscience: New York, 1977; pp 11–139; (b) Bowers, W.
S.; Ohta, T.; Cleere, J. S.; Marsella, P. A. Science 1976, 193, 542.
r