Asymmetric diels-alder reactions of sulfonyl-functionalized α,β-unsaturated ketones with cyclopentadiene catalyzed by chiral lewis acid

Article abstract of DOI:10.1055/s-0028-1083167

Asymmetric Diels-Alder reactions of (E)-1-substituted sulfonyl-3-penten-2- ones with cyclopentadiene catalyzed by a chiral titanium reagent were investigated. The enantioselectivity was studied with different substituents in the position of sulfonyl moiet

Full text of DOI:10.1055/s-0028-1083167

PAPER
3383
Asymmetric Diels–Alder Reactions of Sulfonyl-Functionalized a,b-
Unsaturated Ketones with Cyclopentadiene Catalyzed by Chiral Lewis Acid
R
eactions of Sulfonyl-
F
e
unctionaliz
n
ed
a
,
b
-Unsaturated
P
K
etones
w
ith
e
Cyclopenta
i
diene ,* Yu-Guang Wang, Yong-Jiang Wang, Li Sun
College of Chemical Engineering and Materials, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R. of China
Fax +86(571)88320629; E-mail: peiwen58@zjut.edu.cn
Received 7 May 2008; revised 14 July 2008
conformation in the position of the a,b-unsaturated ketone
Abstract: Asymmetric Diels–Alder reactions of (E)-1-substituted
moiety in the transition state of the reaction of 4-phenyl-
sulfonyl-3-penten- 2-ones with cyclopentadiene catalyzed by a
chiral titanium reagent were investigated. The enantioselectivity
was studied with different substituents in the position of sulfonyl
1-phenylsulfonyl-3-buten-2-ones with cyclopentadiene.4
To our delight, we have also obtained crystals of (5R,6S)-
moiety. 6-Methyl-5-(substituted-sulfonylacetyl)bicyclo[2.2.1]hept- 6-methyl-5-(phenylsulfonylacetyl)-bicyclo[2.2.1]hept-2-
ene (4a) with >99% ee.5 Herein, we wish to discuss the
2-enes (4) were prepared in high yield with high optical purity. The
absolute configuration of the cycloadducts was determined by an al-
ternative synthetic route to compound 4, which was prepared by an
substituted sulfonyl-3-alken-2-ones 1, and the hetero-
asymmetric Diels–Alder reaction of the acyloxazolidinone 6 with
asymmetric Diels–Alder reaction mechanism of (E)-1-
Diels–Alder reaction of same substrate 1 as hetero 1,3-
cyclopentadiene, followed by nucleophilic addition of substituted
dienes in a chiral titanium reagent. We also wish to sum-
marize our recent results on the Diels–Alder reactions of
(E)-1-substituted sulfonyl-3-alken-2-ones 1 catalyzed by
a chiral titanium reagent (Scheme 1).
sulfonylmethyl lithium to the product. Crystals of (5R,6S)-6-meth-
yl-5-(phenylsulfonylacetyl)bicyclo-[2.2.1]hept-2-ene (4a) with
>99% ee was prepared and studied. A mechanism of asymmetric re-
action of sulfonyl-functionalized a,b-unsaturated ketone with cy-
clopentadiene is presented.
The asymmetric Diels–Alder reaction of (E)-1-phenylsul-
fonyl-3-penten-2-one (1a) with cyclopentadiene was first
examined as a model reaction using chiral catalyst 2c.
(5R,6S)-6-Methyl-5-(phenylsulfonylacetyl)bicyclo[2.2.1]-
hept-2-ene (4a) was obtained in high yield and with high
optical purity (>99% ee). The colorless crystals obtained
were studied by X-ray crystallography, and the structure
is shown in Figure 1.
Key words: sulfonyl unsaturated ketone, Diels–Alder reaction,
chiral Lewis acid, asymmetric catalyst, crystal, mechanism
The Diels–Alder reaction has long been recognized as one
of the most important methods for constructing cyclohex-
ene derivatives.1 Our interest has focused on the utiliza-
tion of sulfonyl-functionalized a,b-unsaturated ketones as
prochiral electrophilic substrates in catalyzed asymmetric
carbon–carbon bond formations. We have reported that
(E)-1-phenylsulfonyl-3-alken-2-ones (1) as sulfonyl-
functionalized chelating enones, work effectively as het-
ero 1,3-dienes in chiral Lewis acid catalyzed hetero
Diels–Alder reactions with vinyl ethers. In the presence of
a chiral titanium catalyst 2, high enantioselectivities were
achieved and 4-substituted (2R,4R)- or (2R,4S)-2-iso-
propoxy-6-phenylsulfonyl-3,4-dihydro-2H-pyrans (3) were
produced in high yield, with the exclusive endo-selectivi- Figure 1
ties.2 In the presence of a chiral titanium catalyst 2, 6-sub-
stituted-5-(phenylsulfonylacetyl)bicyclo[2.2.1]hept-2-ene
Chiral titanium catalysts 2 were prepared in situ according
was also obtained by ordinary asymmetric Diels–Alder
reaction of (E)-1-substituted sulfonyl-3-alken-2-ones 1 as
chelating dienophiles with dienes in high yields and with
the excellent enantio-control.3 However, the reaction
mechanism of the asymmetric Diels–Alder reaction of
(E)-1-substituted sulfonyl-3-alken-2-ones 1 was not dis-
cussed because no crystals of the cycloadduct were avail-
able. We recently prepared crystals of (5R,6R)-6-phenyl-
5-(phenylsulfonylacetyl)bicyclo[2.2.1]hept-2-ene with
>99% ee and found the reaction proceeded with (S)-cis
to the literature procedure from TiBr2(i-PrO)2.6 In the
presence of 4Å molecular sieves, 1.1 equivalents of cata-
lyst 2 was added to a dichloromethane solution of 1.0
equivalent of enone 1 at either –78 °C or room tempera-
ture. The mixture was stirred for 30 minutes then excess
cyclopentadiene was added. Workup of the reaction mix-
ture afforded mainly the endo-cycloadduct together with
a small amount of the exo-cycloadduct (>99:1 ratio) in
high yield. The two isomers could easily be separated by
silica gel chromatography; the enantiomeric purities of
cycloadducts 4 were determined by chiral HPLC analysis
and chiral capillary GLC analysis after its conversion into
5-acetyl-6-methyl-bicyclo[2.2.1]hept-2-ene (5) by reduc-
SYNTHESIS 2008, No. 21, pp 3383–3388
x
x.
x
x
.
2
0
0
8
Advanced online publication: 16.10.2008
DOI: 10.1055/s-0028-1083167; Art ID: F09908SS
© Georg Thieme Verlag Stuttgart · New York

3384
W. Pei et al.
PAPER
Oi-Pr
O
R
i-PrO
O
R
i-PrO
SO2Ph
SO2Ph
+
as hetero 1, 3-diene
3
(2R,4R)
>97% ee
O
Ar
Ar
Br
Br
SO2R
O
O
O
Ti
Ar = a, Ph; b, 3,5-xylyl; c, 1-Naph
O
Ar
1
Ar
R: a, Ph; b, Me; c, Tol
chiral catalyst 2
+
as dienophile
COCH2SO2R
COCH2SO2R
(5R,6S) >99% ee
4
Scheme 1
O
O
SO2R
+
SO2R
+
chiral
catalyst 2
chiral
catalyst 2
COCH2SO2R
COCH2SO2R
COCH2SO2R
PhSO2CH2Li
COCH2SO2R
1
1
4
4
R: a, Ph; b, Me; c, Tol
R: a, Ph; b, Me; c, Tol
chiral catalyst 2
Ar
Ar
chiral catalyst 2
Br
Br
O
+
O
O
O
O
Ar
Ar
Ti
Br
Br
O
O
Ar
O
O
COMe
Ti
COMe
Ar
N
O
5
O
O
Ar
chiral
catalyst 2
Ar: a, Ph; b, 3,5-xylyl; c, 1-Naph
Ar
C
N
7
6
O
O
Scheme 2
Ar: a, Ph; b, 3,5-xylyl; c, 1-Naph
Scheme 3
tive desulfonylation with tributyltin hydride in the pres-
ence of AIBN, based on a literature method (Scheme 2).7
complexes are involved in the transition-state. We envis-
aged that the shielding substituents (Ar) of the chiral
ligands or the substituent on the sulfonyl moiety might
play important roles in the chiral induction step. Thus, we
investigated the double asymmetric Diels–Alder reaction
of 1-(R)-p-tolylsulfinyl-3-penten-2-one with cyclopenta-
diene under the above reaction conditions in order to ex-
amine the role of the sulfonyl moiety. When ZnI2 was
used as Lewis acid catalyst, the corresponding cycload-
duct was obtained in high yield and with 64% de (Table 2,
The absolute configurations of the endo-cycloadduct were
confirmed on the basis of their chiral HPLC analysis using
authentic samples of 4 prepared by the sulfonylmethyla-
tion of 3-(6-substituted-bicycle[2.2.1]hept-2-ene-5-car-
bonyl)-1,3-oxazolidin-2-ones (7), which are known
Diels–Alder cycloadducts of a,b-unsaturated 2-oxazolidi-
nones 6 (Scheme 3).6 The results were shown in Table 1.
The above asymmetric Diels–Alder results suggest that
the diastereomeric substrate and/or Lewis acid catalyst
Table 1 Asymmetric Diels–Alder Reactions
Entry
Compd
Catalyst
Temp ( °C) Time (h)
Product
4a
Yield (%)a Endo/Exob ee (%)c
Abs. config.c
5S,6R
1
2
3
4
5
6
1a
1a
1b
1c
6
2b
2c
2c
2c
2a
–
–78
45
5
90
92
91
90
75
89
97:3
99:1
99:1
99:1
97:3
97:3
76
>99
>99
>99
72
r.t.
4a
5R,6S
–78
44
5
4b
5R,6S
r.t.
4c
5R,6S
–78
20
18
7
5S,6R
7
–78 to r.t.
4a
72
5S,6R
a Isolated yield.
b Determined by chiral HPLC analysis.
c Determined by chiral HPLC analysis using authentic samples.
Synthesis 2008, No. 21, 3383–3388 © Thieme Stuttgart · New York

PAPER
Reactions of Sulfonyl-Functionalized a,b-Unsaturated Ketones with Cyclopentadiene
3385
entry 1). When the chiral catalyst 2a–c was used, the dia- For the Diels–Alder reaction of 1-(R)-p-tolylsulfinyl-3-
stereoselectivity of cycloadduct was improved (Table 2, penten-2-one with cyclopentadiene, we calculated the sta-
entries 2, 3 and 4). When the opposite chirality catalyst bility of possible transition-states in half-chair or boat
2a(S)–2c(S) was used, the diastereoselectivity of cycload- conformations with (S)-cis or (S)-trans conformations at
duct formation was lowered (Table 2, entry 5, 6, 7). Fur- the a,b-unsaturated ketone moiety using molecular orbital
thermore, the use of catalyst 2b(S), resulted in the methods. The results indicated that the half-chair transi-
formation of a cycloadduct with opposite absolute config- tion-state with (S)-cis conformation at the a,b-unsaturated
uration. In order to determine the absolute configuration ketone moiety was more stable. It is therefore likely that
of cycloadduct, the cycloadduct was first oxidized to the the Diels–Alder reaction of 1-(R)-p-tolylsulfinyl-3-pent-
corresponding sulfonyl derivative 4c with H2O2 and en-2-one with cyclopentadiene proceeds through a half-
(NH4)6Mo7O24 in methanol. The absolute configuration chair transition-state with (S)-cis conformation to give the
was confirmed by comparison with the sulfonylmethyled cycloadduct 4d (Figure 2).
products (Scheme 4).
O
O
S
+
Tol
chiral catalyst 2
COCH2SOTol
COCH2SO2Tol
COCH2SOTol
1d
4d
H2O2, (NH4)6MoO24
4c
chiral catalyst 2
Ar
Ar
(5S,6R)
Br
Br
4d COCH2SOTol
O
O
O
Ti
O
Ar
TolSO2CH2Li
Ar
O
O
Ar: a, Ph; b, 3,5-xylyl; c, 1-Naph
O
N
O
C
N
chiral catalyst 2
O
O
7
6
(5S,6R)
Scheme 4
*
H
L
H
H
H
H
H
Br
Br
Br
Br
Mtl
H
O
Zn
>
Zn
O
O
H
H
S
O
*
L
Tol
S
O
S
O
COCH2SOTol
Ph
Ph
4d
s-trans, half chair
H.F. = –207.4628 kJ/mol
s-cis, half chair
H.F. = –216.1772 kJ/mol
(5S,6R)
C(β)-si-face
(MOPAC 6.0/PM3)
Figure 2
Table 2 Asymmetric Diels–Alder Reactions of 1-(R)-p-Tolylsulfinyl-3-penten-2-one with Cyclopentadiene
Entry
Catalyst
ZnI2
2a
Temp ( °C)
–78→r.t.
–78
Time (h)
16
Yield (%)a
endo/exob
97:3
de (%)c
64
Abs. config.c
5S,6R
1
2
3
4
5
6
7
90
62
25
92
51
19
36
90
93:7
74
5S,6R
2b
–78
45
99:1
90
5S,6R
2c
–78
45
99:1
88
5S,6R
2a(S)
2b(S)
2c(S)
–78
90
93:7
44
5S,6R
–78
48
93:7
2
5R,6S
–78
12
92:8
78
5S,6R
a Isolated yield of the.
b Determined by chiral HPLC analysis.
c For the endo-mer, determined by chiral HPLC analysis using authentic samples.
Synthesis 2008, No. 21, 3383–3388 © Thieme Stuttgart · New York

3386
W. Pei et al.
PAPER
H
O
O
H
O
O
H
H
I
H
H
I
I
I
H
H
S
Zn
O
O
O
Zn
H
Zn
O
O
I
>
I
O
S
Ph
S
Ph
I
Zn
S
H
H
Ph
O
Ph
H
I
O
s-trans, boat conformation
H.F. = –148.2471kJ/mol (MOPAC 6.0/PM3)
s-cis, boat conformation
H.F. = –152.5566 kJ/mol
Figure 3
In the asymmetric Diels–Alder reactions of sulfonylfunc- nyl-3-alken-2-one (1a) takes place on the C(b)-si face of
tionalized a,b-unsaturated ketones, the most stable transi- the C=C double-bond with (S)-cis conformation of the
tion-state conformation was also calculated by the isopropoxyl vinyl ether, and affords the (2R,4R)-cycload-
molecular orbital method and found to be the boat-confor- duct with 97% ee using the chiral catalyst 2a. The
mation with (S)-cis orientation of the a,b-unsaturated ke- (5R,6S)-cycloadduct was obtained with >99% ee in the
tone moiety (Figure 3).
presence of chiral catalyst 2c through the asymmetric
Diels–Alder reaction of (E)-1-phenylsulfonyl-3-alken-2-
one (1a) on the C(b)-re face of the C=C double-bond with
(S)-trans conformation of the cyclopentadiene.
According to the calculated result, the transition-state of
the asymmetric hetero Diels–Alder reaction of (E)-1-phe-
nylsulfonyl-3-alken-2-ones 1 (as hetero 1,3-dienes) with
vinyl ethers, should proceed through a boat-conformation
with (S)-cis orientation of the a,b-unsaturated ketone moi-
ety. In agreement with this expectation, highly enantiose-
lective formation of 4-substituted (2R,4R)-2-isopropoxy-
6-phenylsulfonyl-3,4-dihydro-2H-pyrans 3, was observed
(Scheme 5).
Melting points were determined on a WR-52 melting point appara-
tus and are uncorrected. IR spectra were taken with a Bruker Vector
1
22 spectrometer. H NMR (400 MHz) and 13C NMR(100 MHz)
spectra were recorded on a JEOL GSX-270 or a Bruker 400 spec-
trometer as CDCl3 or DMSO-d6 solutions; chemical shifts (d) are
given in ppm and referenced to TMS as an internal standard. Mass
spectra were measured with a HP 5998B mass spectrometer (EI).
Elemental analyses were performed on a Carlo Erba 1106 and
Finnigan 1120 CHN analyzer. Optical purity was measured with a
Shimadazu chiral HPLC and chiral GLC.
Similarly, the transition-state of the asymmetric Diels–
Alder reaction of (E)-1-phenylsulfonyl-3-alken-2-ones 1,
as the dienophile with cyclopentadiene, catalyzed by
chiral catalyst, proceeds through a boat-conformation
with (S)-trans configuration of the a,b-unsaturated ketone
moiety; (5R,6S)-6-methyl-5-(phenylsulfonylacetyl)bicyc-
lo[2.2.1]hept-2-ene was obtained in high enantioselectiv-
ity due to steric effects (Scheme 6).
Preparation of (E)-1-Methylsulfonyl-3-penten-2-one (1a); Gen-
eral Procedure
1-Phenylsulfonyl-4-hydroxy-pentan-2-one (2.82 g, 11.6 mmol) and
PTSA (0.2 g, 1.0 mmol) were refluxed in benzene for 12 h. The sol-
vent was removed and the residue was subjected to column chroma-
tography (n-hexane–EtOAc, 2:1) to give 1a.
In conclusion, the results presented here indicate that the
hetero Diels–Alder cycloaddition of (E)-1-phenylsulfo-
Yield: 2.03 g (78%); colorless needles; mp 73–75 °C.
Ph
Ph
H
H
O
Br
Ti
O
Br
Ti
O
O
H
H
O
H
H
O
O
i-PrO
O
O
O
O
O
SO2Ph
O
S
O
S
Br
H
Br
Ph
Ph
O
H
R1O
(2R,4R) >97% ee
C(β)-si-face
3
Scheme 5
Ar
H
H
O
Br
O
H
Ti
O
O
H
O
Ar
S
O
COCH2SO2Ph
(5R,6S) >99% ee
Br
O
C(β)-re-face
Scheme 6
Synthesis 2008, No. 21, 3383–3388 © Thieme Stuttgart · New York

PAPER
Reactions of Sulfonyl-Functionalized a,b-Unsaturated Ketones with Cyclopentadiene
3387
IR (KBr): 2985, 1690, 1450, 1380, 1300, 1150, 1075, 975, 770, 710,
690 cm–1.
1H NMR (CDCl3): d = 1.95 (dd, J5–4 = 7.0 Hz, J5–3 = 1.5 Hz, 3 H),
4.25 (s, 2 H), 6.31 (dq, J3–4 = 15.8 Hz, J5–3 = 1.5 Hz, 1 H), 6.97 (dq,
J4–3 = 15.8 Hz, J4–5 = 7.0 Hz, 1 H), 7.54–7.71 (m, 3 H), 7.87–7.90
(m, 2 H).
13C NMR (CDCl3): d = 18.64, 65.25, 128.42, 129.27, 130.99,
134.24, 138.69, 147.91, 186.86.
MS (EI, 70 eV): m/z (%) = 224 (8) [M+], 160 (28), 77 (39), 69 (100),
41 (21).
in CH2Cl2 (5 mL) and the mixture was cooled to –78 °C for 30 min.
A solution of the enone 1a (224 mg, 1 mmol) in CH2Cl2 (2 mL) was
added to the mixture. Stirring was continued for 30 min then cyclo-
pentadiene (0.5 mL, 5 mmol) was added. The mixture was stirred
for 45 h then the resulting mixture was quenched with sat. aq
NaHCO3 (15 mL) and extracted with CH2Cl2 (3 × 25 mL). The
combined extracts were dried (MgSO4) and evaporated in vacuo.
The crude product was purified by chromatography on silica gel
(hexane–EtOAc, 10:1) to give 4a (261 mg, 90%) as the endo-iso-
mer. Other reactions were performed under the reaction conditions
shown in Table 1.
Anal. Calcd for C11H12O3S: C, 58.91; H, 5.39. Found: C, 59.27; H,
5.41.
(5R,6S)-6-Methyl-5-(phenylsulfonylacetyl)bicyclo[2.2.1]hept-2-
ene (4a)
White solid; mp 101–102 °C; [a]25D +85.0 (c 1.33, CHCl3).
(E)-1-Methylsulfonyl-3-penten-2-one (1b); General Procedure
A solution of 1-methylsulfonyl-3-penten-2-ol (3.95 g, 24 mmol) in
acetone (20 mL) was cooled to –15 °C, and Jones reagent [CrO3
(0.8 g, 8 mmol) and H2SO4 (6.4 N, 4.9 mL)] was added dropwise.
The mixture was stirred for 6 h then i-PrOH (10 mL) was added to
quench the reaction. The mixture was extracted with CH2Cl2 (3 × 20
mL), dried over MgSO4 and the solvent was removed. The residue
was subjected to column chromatography (n-hexane–EtOAc, 1:1)
to give 1b.
IR (KBr): 2900, 2450, 2300, 2000, 1690, 1640, 1450, 1320, 1250,
1150, 1070, 900 cm–1.
1H NMR (CDCl3): d = 1.16 (d, J = 7.0 Hz, 3 H), 1.47 (ddd, J = 8.8,
3.7, 1.8 Hz, 1 H), 1.62 (d, J = 8.8 Hz, 1 H), 1.80–1.89 (m, 1 H), 2.48
(s, 1 H), 2.79 (t, J = 3.8 Hz, 1 H), 3.18 (s, 1 H), 4.09 (d, J = 13.6 Hz,
1 H), 4.28 (d, J = 13.6 Hz, 1 H), 5.78 (dd, J = 5.9, 2.9 Hz, 1 H), 6.21
(dd, J = 5.9, 3.3 Hz, 1 H), 7.51–7.71 (m, 3 H), 7.86–7.92 (m, 2 H).
13C NMR (CDCl3): d = 20.62, 35.88, 46.37, 46.44, 49.67, 62.10,
65.70, 128.40, 129.25, 131.85, 134.18, 138.92, 139.09, 198.50.
Yield: 3.0 g (78%); colorless prisms; mp 59–60 °C.
MS (EI, 70eV): m/z (%) = 290 (2) [M+], 225 (100), 141 (21), 77
(34), 66 (87).
IR (KBr): 2950, 2500, 1650, 1452, 1370, 1285, 1200, 1150, 1120,
1085, 950, 900, 760, 720 cm–1.
1H NMR (CDCl3): d = 1.95 (dd, J5–4 = 7.0 Hz, J5–3 = 1.5 Hz, 3 H),
3.06 (s, 3 H), 4.17 (s, 2 H), 6.28 (dq, J4–3 = 15.8 Hz, J4–5 = 7.0 Hz,
1 H), 7.12 (dq, J3–4 = 15.8 Hz, J5–3 = 1.5 Hz, 1 H).
Anal. Calcd for C16H18O3S: C, 66.18; H, 6.25. Found: C, 66.51; H,
6.23.
13C NMR (CDCl3): d = 18.67, 41.45, 62.56, 131.33, 148.67, 188.24.
MS (EI, 70 eV): m/z (%) = 162 (10) [M+], 83 (41), 69 (100), 41 (39),
(5R,6S)-6-Methyl-5-(methylsulfonylacetyl)bicyclo[2.2.1]hept-2-
ene (4b)
White solid; mp 99–100 °C; [a]25D +76.9 (c 0.67, CHCl3).
39 (25).
IR (KBr): 2950, 2300, 1700, 1380, 1300, 1120, 980, 900, 710 cm–1.
Anal. Calcd for C6H10O3S: C, 44.44; H, 6.17. Found: C, 44.61; H,
6.25.
1H NMR (CDCl3): d = 1.19 (d, J = 7.0 Hz, 3 H), 1.52 (ddd, J = 8.8,
3.3, 1.8 Hz, 1 H), 1.55 (d, J = 8.8 Hz, 1 H), 1.88–1.99 (m, 1 H), 2.53
(s, 1 H), 2.75 (dd, J = 4.4, 3.1 Hz, 1 H), 3.05 (s, 3 H), 3.21 (s, 1 H),
3.98 (d, J = 13.8 Hz, 1 H), 4.10 (d, J = 13.8 Hz, 1 H), 5.91 (dd,
J = 5.9, 2.9 Hz, 1 H), 6.28 (dd, J = 5.9, 3.3 Hz, 1 H), 7.51–7.71 (m,
3 H).
(R)-(E)-1-p-Tolylsulfinyl-3-penten-2-one (1d); General Proce-
dure
Under a positive pressure of nitrogen, to a solution of the 1-meth-
anesulfinyl-4-methyl-benzene (23 mL, 8 mmol) in anhydrous THF
(40 mL) at –30 °C was added, dropwise, freshly-prepared LDA [di-
isopropylamine (2.24 mL, 16 mmol) and n-BuLi (9.6 mL, 16 mmol)
in anhydrous THF at –78 °C]. The mixture was stirred for 4 h at
0 °C and then added to but-2-enoic acid methyl ester (1.27 mL, 12
mmol). The reaction was stirred at 0 °C for 3 h and then quenched
with sat NH4Cl (15 mL). The mixture was extracted with CH2Cl2
(3 × 20 mL), dried and the solvent was removed. The residue was
subjected to column chromatography (n-hexane–EtOAc, 1:1) to
give 1d.
13C NMR (CDCl3): d = 20.66, 35.85, 41.72, 46.16, 46.42, 49.11,
62.57, 63.60, 132.06, 139.17, 200.02.
MS (EI, 70 eV): m/z (%) = 230 (20) [M+ + 2], 229 (100) [M+ + 1],
228 (19) [M+], 122 (26), 115 (19), 106 (28).
Anal. Calcd for C11H16O3S: C, 57.89; H, 7.02. Found: C, 58.05; H,
6.95.
(5R,6S)-6-Methyl-5-(p-tolylsulfonylacetyl)bicyclo[2.2.1]hept-2-
ene (4c)
Yield: 1.1 g (65%); colorless oil; [a]25D +239.6 (c 1.93, CHCl3).
White solid; mp 90–91 °C; [a]25D +86.5 (c 0.91, CHCl3).
IR (KBr): 2985, 1690, 1620, 1450, 1380, 1300, 1150, 1075, 975,
770, 710, 690 cm–1.
IR (KBr): 2950, 1700, 1450, 1370, 1275, 1140, 800, 710 cm–1.
1H NMR (CDCl3): d = 1.19 (d, J = 7.0 Hz, 3 H), 1.45 (ddd, J = 8.8,
3.7, 1.8 Hz, 1 H), 1.62 (d, J = 8.8 Hz, 1 H), 1.94 (m, 1 H), 2.45 (s,
3 H), 2.47 (s, 1 H), 2.80 (dd, J = 4.8, 3.3 Hz, 1 H), 3.18 (s, 1 H),
4.11 (d, J = 13.6 Hz, 1 H), 4.26 (d, J = 13.6 Hz, 1 H), 5.78 (dd,
J = 5.4, 2.9 Hz, 1 H), 6.21 (dd, J = 5.4, 3.3 Hz, 1 H), 7.28–7.37 (m,
2 H), 7.74–7.78 (m, 2 H).
13C NMR (CDCl3): d = 20.66, 21.57, 35.85, 46.23, 46.29, 48.98,
62.07, 65.90, 128.24 129.74, 131.75, 138.88, 136.06, 145.17,
198.72.
1H NMR (CDCl3): d = 1.90 (dd, J5–4 = 7.0 Hz, J5–3 = 1.5 Hz, 3 H),
2.38 (s, 3 H), 3.88 (d, Jgem = 13.6 Hz, 1 H), 4.21 (d, Jgem = 13.6 Hz,
1 H), 6.13 (dq, J4–3 = 15.8 Hz, J4–5 = 7.0 Hz, 1 H), 6.97 (dq, J3–4
15.8 Hz, J5–3 = 1.5 Hz, 1 H), 7.5–7.7 (m, 2 H), 7.8–7.9 (m, 2 H).
=
13C NMR (CDCl3): d = 18.29, 21.13, 66.07, 123.89, 129.67, 131.72,
141.78, 146.76, 186.89.
Asymmetric Diels–Alder Reaction; Typical Procedure
As a typical example, the reaction of 1a with cyclopentadiene in the
presence of chiral catalyst was conducted as follows: Under a nitro-
gen atmosphere, to a suspension of 4Å MS (200 mg) in CH2Cl2 (5
mL), was added a solution of the chiral titanium catalyst (0.1 mmol)
MS (EI, 70 eV): m/z (%) = 304 (2) [M+], 239 (82), 155 (27), 91 (84),
79 (22), 69 (37), 66 (100).
Synthesis 2008, No. 21, 3383–3388 © Thieme Stuttgart · New York

3388
W. Pei et al.
PAPER
Anal. Calcd for C17H20O3S: C, 67.11; H, 6.58. Found: C, 66.55; H,
6.62.
orated in vacuo. The crude product was purified by chromatography
on silica gel (hexane–EtOAc, 10:1) to give 4 (61 mg, 80%).
(5R,6S)-6-Methyl-5-[(R)-tolylsulfinylacetyl]bicyclo[2.2.1]hept-
2-ene (4d)
Oxidation of 4d; General Procedure
To a solution of cycloadduct 4d (55 mg, 0.2 mmol) in MeOH (10
mL), was added (NH4)6Mo7O24 (100 mg, 0.08 mmol) and the mix-
ture was cooled to 0 °C. A solution of H2O2 (30%, 10 mL, 0.15
mmol) was added dropwise and the mixture was stirred at r.t. for 5
h. The resulting mixture was extracted with CH2Cl2 (3 × 25 mL)
and the combined extracts were dried (MgSO4) and evaporated in
vacuo. The crude product was purified by chromatography on silica
gel (hexane–EtOAc, 10:1) to give 4c (36 mg, 60%).
White solid; mp 75–76 °C; [a]25D +87.2 (c 0.88, CHCl3).
IR (KBr): 2980, 1710, 1500, 1450, 1390, 1050, 830, 750, 690 cm–1.
1H NMR (CDCl3): d = 1.14 (d, J = 7.0 Hz, 3 H), 1.44 (ddd, J = 8.8,
3.7, 1.8 Hz, 1 H), 1.58 (d, J = 8.8 Hz, 1 H), 1.85–1.95 (m, 1 H), 2.42
(s, 3 H), 2.46 (s, 1 H), 2.48 (dd, J = 4.8, 3.3 Hz, 1 H), 3.65 (s, 1 H),
3.66 (d, J = 14.0 Hz, 1 H), 4.04 (d, J = 14.0 Hz, 1 H), 5.67 (dd,
J = 5.5, 2.9 Hz, 1 H), 6.21 (dd, J = 5.5, 3.3 Hz, 1 H), 7.30–7.60 (m,
4 H).
References
13C NMR (CDCl3): d = 20.86, 21.47, 35.65, 46.12, 46.28, 49.01,
62.45, 68.32, 124.24, 124.67, 130.09, 131.96, 139.06, 140.17,
202.33.
MS (EI, 70eV): m/z (%) = 288 (9) [M+], 139 (100), 91 (21), 79 (25),
69 (39), 66 (36).
(1) (a) Evans, D. A.; Chapman, K. T.; Bisaha, J. J. Am. Chem.
Soc. 1988, 110, 1238. (b) Kagan, H. B.; Riant, O. Chem.
Rev. 1992, 92, 1007. (c) Takao, K. I.; Munakata, R.;
Tadano, K. Chem. Rev. 2005, 105, 4779.
(2) (a) Wada, E.; Yasuoka, H.; Pei, W.; Chin, U.; Kanemasa, S.
Engineering Sciences Reports, Kyushu University 1995, 17,
353. (b) Wada, E.; Pei, W.; Yasuoka, H.; Chin, U.;
Kanemasa, S. Tetrahedron 1996, 52, 1205.
(3) (a) Wada, E.; Pei, W.; Kanemasa, S. Chem. Lett. 1994,
2345. (b) Pei, W.; Wada, E.; Kanemasa, S. Chin. Chem. Lett.
1997, 8, 935. (c) Pei, W. Chem. J. Chin. Univ. 1998, 19,
402. (d) Pei, W.; Deng, Q.; Wang, H. B.; Sun, L. Chin. J.
Org. Chem. 2006, 26, 727.
Anal. Calcd for C17H20O2S: C, 70.80; H, 6.94. Found: C, 70.90; H,
6.97.
Desulfonylation of 4; General Procedure
Under a nitrogen atmosphere, a solution of compound 1a (75 mg,
0.25 mmol), tri-n-butylstannane (0.35 mL, 1.3 mmol) and azobis-
isobutyronitrile (AIBN; 90 mg, 0.55 mmol) in toluene (5 mL) was
refluxed for 3 h. The resulting mixture was evaporated in vacuo and
purified by chromatography on silica gel (hexane–EtOAc, 10:1) to
give 5 (32 mg, 83%).
(4) Pei, W.; Shao, Y. S.; Sun, L. Acta Crystallogr., Sect. E 2004,
60, 374.
(5) Pei, W.; Wang, Y. J.; Sun, M. Z.; Xiong, X. B.; Yu, C. Q.
Acta Crystallogr., Sect. E: Struct. Rep. Online 2007, 63,
2142.
(6) Narasaka, K.; Iwasawa, N.; Inoue, M.; Yamada, T.;
Nakashima, M.; Sugimori, J. J. Am. Chem. Soc. 1989, 111,
5340.
Sulfonylmethylation of 7; General Procedure
Under a nitrogen atmosphere, to a solution of methyl phenyl sulfone
(80 mg, 0.51 mmol) in THF (2 mL), was added n-BuLi (1.6 M in
hexane, 0.53 mmol) and the mixture was stirred at r.t. for 2 h. A so-
lution of 7 (50 mg, 0.23 mmol) in THF (2 mL) was added and the
mixture was stirred at r.t. for 18 h. The resulting mixture was
quenched with sat. aq NH4Cl (15 mL) and extracted with CH2Cl2
(3 × 25 mL). The combined extracts were dried (MgSO4) and evap-
(7) Smith, A. B.; Hale, K. J.; Mccauley, J. P. Tetrahedron Lett.
1989, 30, 5579.
Synthesis 2008, No. 21, 3383–3388 © Thieme Stuttgart · New York