Lewis base effects in the Baylis-Hillman reaction of arenecarbaldehydes and N-arylidene-4-methylbenzenesulfonamides with α,β-unsaturated cyclic ketones

Article abstract of DOI:10.1002/1099-0690(200211)2002:21<3666::AID-EJOC3666>3.0.CO;2-9

In investigations into the Baylis-Hillman reaction between arenecarbaldehydes and 2-cyclohexen-1-one or 2-cyclopenten-1-one, we found that the reaction is very complicated, because the Lewis bases, solvents, the substrates, and the ring-size of the α,β-un

Full text of DOI:10.1002/1099-0690(200211)2002:21<3666::AID-EJOC3666>3.0.CO;2-9

FULL PAPER
Lewis Base Effects in the Baylis؊Hillman Reaction of Arenecarbaldehydes and
N-Arylidene-4-methylbenzenesulfonamides with α,β-Unsaturated Cyclic Ketones
Min Shi,*[a] Yong-Mei Xu,[a] Gui-Ling Zhao,[a] and Xiao-Feng Wu[a]
Keywords: Aldehydes / Amides / BaylisϪHillman reaction / Ketones / Lewis bases
In investigations into the Baylis−Hillman reaction between
abnormal Baylis−Hillman adducts 3-aryl-2-(4-tolylsulfonyl)-
arenecarbaldehydes and 2-cyclohexen-1-one or 2-cyclo- 2-azabicyclo[2.2.2]octan-5-ones 5 were formed at the same
penten-1-one, we found that the reaction is very complic-
ated, because the Lewis bases, solvents, the substrates, and
the ring-size of the α,β-unsaturated cyclic ketone can all sig-
time. In addition, in reactions between N-arylidene-4-
methylbenzenesulfonamides and 2-cyclohepten-1-one or 2-
cycloocten-1-one, the reactions were very sluggish in the
nificantly affect the Baylis−Hillman reaction rate and even presence of a range of Lewis bases, and the abnormal
the reaction product. In particular, the abnormal adducts 3
were formed along with the normal Baylis−Hillman adducts
2 on treatment of arenecarbaldehydes and 2-cyclopenten-1-
one under Baylis−Hillman reaction conditions in the pres-
ence of PBu3 as a Lewis base. On the other hand, in
Baylis−Hillman reactions between N-benzylidene-4-methyl-
Baylis−Hillman adducts 7 or 9 − derived from aldol condensa-
tions − were obtained in moderate yields together with the
normal Baylis−Hillman adduct 4. When Baylis−Hillman reac-
tion conditions were applied to N-arylidene-4-methylben-
zenesulfonamides and 2-cycloocten-1-one in methanol, prod-
ucts 10 − derived from Michael additions of methanol to 9 −
benzenesulfonamides and 2-cyclohexen-1-one or 2-cyclo- were formed as the major products, along with traces of 9. In
penten-1-one, we found that the reaction could be greatly
accelerated in the presence of catalytic amounts of DMAP to
give the normal Baylis−Hillman adducts 4 or 6 in good or
general, the ring-size of the α,β-unsaturated cyclic ketone
can significantly affect the reaction products and rates, the
Baylis−Hillman reaction and the aldol condensation reaction
excellent yields. Moreover, application of Baylis−Hillman re- taking place at the same time for 2-cyclohexen-1-one or 2-
action conditions to N-arylidene-4-methylbenzenesulfonam- cyclohepten-1-one. For large-sized α,β-unsaturated cyclic
ide and 2-cyclopenten-1-one in the presence of PBu3 as a ketones such as 2-cycloocten-1-one, only aldol condensation
Lewis base provided the normal Baylis−Hillman adducts 6 in
very high yields within 5 h. In the presence of PBu3 or DBU
reactions occurred. The substituent effects in all α,β-unsatur-
ated cyclic ketone substrates were also examined.
as a Lewis base for reactions between N-arylidene-4-methyl- ( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
benzenesulfonamides and 2-cyclohexen-1-one, however, the
2002)
Introduction
ously reported in a short communication, if the arenecarb-
aldehyde components are replaced with N-arylidene-4-
methylbenzenesulfonamides (imines), BaylisϪHillman reac-
tions between these species and 2-cyclohexen-1-one or 2-
cyclopenten-1-one can be greatly accelerated in the presence
of catalytic amounts of the Lewis bases DMAP or PBu3.[4f]
In the presence in particular of PBu3 or DBU as Lewis ba-
ses, however, unexpected abnormal BaylisϪHillman ad-
ducts 5 were also formed on treatment of N-arylidene-4-
methylbenzenesulfonamides (imines) and 2-cyclohexen-1-
one under the same BaylisϪHillman reaction conditions.[4f]
Therefore, in order to understand BaylisϪHillman reaction
behavior between arenecarbaldehydes or N-arylidene-4-
methylbenzenesulfonamides (imines) and α,β-unsaturated
cyclic ketones comprehensively,[5] we intensely studied the
BaylisϪHillman reaction behavior of arenecarbaldehydes
and imines with α,β-unsaturated cyclic ketones and found
many unusual results. Since BaylisϪHillman reactions be-
tween imines and α,β-unsaturated cyclic ketones have not
so far been systematically investigated, except in our short
communication, we wish here to report full details of the
The BaylisϪHillman reaction has recently made great
progress,[1] and now includes a catalytic asymmetric ver-
sion,[2] since Baylis and Hillman first reported the reaction
between acetaldehyde and ethyl acrylate or acrylonitrile in
the presence of catalytic amounts of strong Lewis bases
such as 1,4-diazabicyclo[2.2.2]octane (DABCO) in 1972.[3]
During our own investigations into this very simple and
useful reaction, we found that BaylisϪHillman reactions
between many arenecarbaldehydes and α,β-unsaturated cyc-
lic ketones were very sluggish under the traditional
BaylisϪHillman reaction conditions, or even in the pres-
ence of TiCl4 (1.4 equiv. as a Lewis acid) and catalytic
amounts of amine, SMe2, or phosphane (0.2 equiv.) as
Lewis bases at Ϫ37 °C.[4] Additionally, as we have previ-
[a]
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China
Fax: (internat.) ϩ 86-21/64166128
E-mail: mshi@pub.sioc.ac.cn
3666
 2002 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/02/1121Ϫ3666 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2002, 3666Ϫ3679

Lewis Base Effects in the BaylisϪHillman Reaction
FULL PAPER
reaction behavior between arenecarbaldehydes or imines 1a being obtained in 75% yield after 15 d at room temper-
and α,β-unsaturated cyclic ketones under BaylisϪHillman ature (Table 1, Entries 20 and 21), and (2) with TiCl4 (1.4
conditions. In this full paper, we have significantly equiv.) as a Lewis acid in dichloromethane at Ϫ37 °C, 1a
expanded the scope and defined the limitations of the being obtained in 78% yield within 1 d (Table 1, Entry 25).
BaylisϪHillman reaction with α,β-unsaturated cyclic ke- The combination of TiCl4 (1.4 equiv.) with Lewis base (0.2
tones as Michael acceptors. Moreover, we also disclose in equiv.) did not significantly improve the yield of 1a (Table 1,
this full paper that the ring-sizes of α,β-unsaturated cyclic Entries 26 and 27). However, as can be seen from Scheme 2
ketones can drastically affect the reaction products and re- and Table 2, we elucidated that the two best reaction sys-
action rates.
tems can only promote BaylisϪHillman reactions between
arenecarbaldehydes with strongly electron-withdrawing
groups (such as nitrobenzaldehyde) and 2-cyclohexen-1-one
(Table 2, Entries 1, 2, 5, and 6). For other arenecarbal-
dehydes, no reaction occurred (Table 2, Entries 3, 4, 7,
and 8).
Results and Discussion
1) Application of Baylis؊Hillman Reaction Conditions to
Arenecarbaldehydes and 2-Cyclohexen-1-one or 2-Cyclo-
penten-1-one
We also examined the application of BaylisϪHillman
conditions to reactions between p-nitrobenzaldehyde and 2-
cyclopenten-1-one,
either
under
the
traditional
As shown in Scheme 1 and Table 1, we first systematically
investigated various conditions for the BaylisϪHillman re-
action between p-nitrobenzaldehyde and 2-cyclohexen-1-
one. The best reaction conditions are: (1) with 4-dimethyl-
aminopyridine (DMAP) or 4-pyrrolidinopyridine as a
Lewis base in dichloromethane, the BaylisϪHillman adduct
BaylisϪHillman conditions or in the presence of TiCl4 (1.4
equiv.) as a Lewis acid and catalytic amounts of amine,
SMe2, or phosphane (0.2 equiv.) as a Lewis base. Treatment
Scheme 1
Scheme 2
Table 1. The reactions between arenecarbaldehyde and 2-cyclohexene-1-one under various reaction conditions
Entry
Promoter[a]
Solvent
Time [d]
Temp. [°C]
Yields (%)[b]
1
2
3
4
5
6
7
8
DBU
DBU
DBU
DABCO
DABCO
DABCO
DABCO/-proline
DABCO/morpholine
DMAP/-proline
DMAP/Yb(OTf)3
DMAP/-proline
DMAP
CH2Cl2
DMF
MeOH
CH2Cl2
DMF
MeOH
ClCH2CH2Cl
ClCH2CH2Cl
CH2Cl2
CH2Cl2
DMF
0.5
0.5
0.17
10
7
6
5
5
3
3
2
2
5
5
2
5
5
5
4
15
15
4
4
7
1
1
0.2
15
15
15
15
15
15
70
70
15
15
15
15
70
15
15
15
15
50
15
15
15
15
15
15
Ϫ37
Ϫ37
Ϫ37
8
many products
26
trace
15
10
many products
no reaction
trace
trace
10
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
THF
ClCH2CH2Cl
THF
5
DMAP
trace
36
15
30
42
trace
41
75
75
5
15
trace
78
58
65
DMAP/Binol
DMAP/MS4A
DMAP/MgO
DMAPLiCl
DMAP
DMAP
DMAP
4-pyrrolidinophyridine
PBu3
PBu3/Binol
PBu3/MS4A
CH2Cl2
CH2Cl2
CH2Cl2
DMF
CH2Cl2
CH2Cl2
CH2Cl2
THF
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
[c]
TiCl4
TiCl4/DBU[d]
BBr3/Me2S[e]
[a]
[b]
[c]
[e]
10 mol % of Lewis base.
Isolated yields. 1.4 equiv. of TiCl4.[d] 1.4 equiv. of TiCl4 and 0.2 equiv. of DBU. 1.4 equiv. of BBr3
and 0.2 equiv. of Me2S.
Eur. J. Org. Chem. 2002, 3666Ϫ3679
3667

M. Shi, Y.-M. Xu, G.-L. Zhao, X.-F. Wu
FULL PAPER
dehyde and 2-cyclopenten-1-one under BaylisϪHillman re-
action conditions produced the normal BaylisϪHillman ad-
ducts 2e or 2f as the sole products (Table 4, Entries 4 and
5). The crystal structure of the major isomer of syn-3b was
determined by X-ray analysis (Figure 1). The syn/anti ratios
obtained are based on the 1H NMR spectroscopic data. We
believe that compounds 3 are derived from aldol condensa-
tion reactions between the BaylisϪHillman adducts 2 and
the arenecarbaldehydes in the presence of the Lewis base
PBu3.
Table 2. Reactions between arenecarbaldehydes and 2-cyclohexene-
1-one under various reaction conditions
Entry
Ar
Promoter
Yields (%)[a]
1
2
3
4
5
6
7
8
m-NO2C6H4
o-NO2C6H4
p-ClC6H4
C6H5
m-NO2C6H4
o-NO2C6H4
p-ClC6H4
C6H5
DMAP
DMAP
DMAP
DMAP
TiCl4/DBU (Ϫ37 °C)
TiCl4/DBU (Ϫ37 °C)
TiCl4/DBU (Ϫ37 °C)
TiCl4/DBU (Ϫ37 °C)
70
70
no reaction
no reaction
55
49
no reaction
no reaction
Table 4. Reactions between arenecarbaldehydes and 2-cyclopen-
tene-1-one in the presence of PBu3
[a]
Isolated yields.
Entry
Ar
Time
[h]
Yield (%)[a]
2
3 (syn/anti)
1
2
3
4
5
C6H5
24
5
7
24
8
59
69
79
84
75
24 (65:35)
13 (68:32)
11 (70:30)
0
0
p-ClC6H4
p-ClC6H4
p-EtC6H4
p-MeOC6H4
[a]
Isolated yields.
Scheme 3
of p-nitrobenzaldehyde and 2-cyclopenten-1-one in the
presence of DMAP as a Lewis base resulted in only traces
of the corresponding BaylisϪHillman adduct 2a (Scheme 3,
Entry 2). In the presence of PBu3 as a Lewis base, 2a could
be obtained in 53% yield in THF, but only together with the
formation of another, abnormal, BaylisϪHillman reaction
product 3a (syn and anti mixture) (Table 3, Entry 1). The
TiCl4 and Lewis base reaction system gave 2a in 40% yield
(Table 3, Entry 3). We also examined BaylisϪHillman reac-
tions between other arenecarbaldehydes and 2-cyclopenten-
1-one under the same conditions but in the presence of
PBu3 as a Lewis base (Scheme 4). The substituents on the
phenyl ring of arenecarbaldehydes do not impair this reac-
tion; treatment of p-ethylbenzaldehyde or p-methoxybenzal-
Figure 1. The crystal structure of syn-3b
These results clearly showed that BaylisϪHillman reac-
tion behavior of arenecarbaldehydes and α,β-unsaturated
cyclic ketones is very complicated, since the Lewis bases,
the solvents, the substrates, and the ring-sizes of the α,β-
unsaturated cyclic ketones can all significantly affect the
BaylisϪHillman reaction rates and even the reaction prod-
ucts.
Table 3. Reactions between arenecarbaldehydes and 2-cyclopenten-
1-ene under various reaction conditions
Entry Promoter
Solvent Time Yield (%)[a]
2) Application of Baylis؊Hillman Reaction Conditions to
N-Benzylidene-4-methylbenzenesulfonamides and
2-Cyclohexen-1-one or 2-Cyclopenten-1-one
[h]
2
3 (syn/anti)
1
2
3
PBu3
DMAP
THF
CH2Cl2 24
15
53
trace
40
26 (60:40)
The substituents on the phenyl ring can significantly af-
fect the reaction products and rates of BaylisϪHillman re-
actions between arenecarbaldehydes and α,β-unsaturated
cyclic ketones. We therefore attempted to use N-arylidene-
4-methylbenzenesulfonamides in place of arenecarbal-
dehydes, as the very strongly electron-withdrawing sulfonyl
groups (ϪSO2Ar) should reduce the influence of the sub-
stituents on the phenyl ring on the BaylisϪHillman reaction
rates. At first, promoters for the reaction between N-(4-
chlorobenzylidene)-4-methylbenzenesulfonamide[6] and 2-
cyclohexen-1-one were examined systematically (Scheme 5,
Table 5). We found that the solvents, the reaction temper-
TiCl4/DBU (Ϫ37 °C) CH2Cl2 36
[a]
Isolated yields.
Scheme 4
3668
Eur. J. Org. Chem. 2002, 3666Ϫ3679

Lewis Base Effects in the BaylisϪHillman Reaction
FULL PAPER
atures, and the Lewis bases played very important roles for
this reaction. In the presence of 20 mol % of DMAP as a
Lewis base, for example, the reaction proceeded very well
in methanol at 40 °C to give the normal BaylisϪHillman
adduct 4 in good yield (Table 5, Entry 9), although this
Lewis base was unable to promote the same reaction in
DMF (Table 5, Entry 5). With 20 mol % of PPh3 or dppe as
Lewis bases, no reactions occurred (Table 5, Entries 1Ϫ3).
However, in the presence of PBu3 or DBU as a Lewis base
in MeOH at 40 °C, an unexpected adduct 5 (endo/exo mix-
ture; abnormal BaylisϪHillman adduct) was obtained
along with 4 (Scheme 5, Table 5, Entries 8 and 11Ϫ12).
Similar results were obtained for other N-arylidene-4-
methylbenzenesulfonamides under the optimized reaction
conditions in MeOH in the presence of PBu3, PhPMe2,
Ph2PMe, or DBU as Lewis bases (Scheme 6); the results are
summarized in Table 6. The substituents on the phenyl ring
of the N-arylidene-4-methylbenzenesulfonamide indeed do
not significantly affect the reaction products and rates. We
believe that 5 is produced stepwise through an aldol con-
densation reaction of the enolate derived from 2-cyclo-
Scheme 6
Table 6. BaylisϪHillman reactions between N-(benzylidene)-4-
methylbenzenesulfonamide (1.0 equiv.) and 2-cyclohexen-1-one in
the presence of Lewis base (20 mol %)
Entry Ar
Lewis base Time Yields (%)[a]
[h]
4a endo-5 exo-5
1
2
3
4
5
6
7
8
C6H5
C6H5
C6H5
C6H5
p-EtC6H4
p-MeOC6H4 PBu3
p-FC6H4
p-NO2C6H4
DBU
PBu3
PhPMe2
Ph2PMe
DBU
3
24
5
24
3
24
26
24
40 12
16 16
14 18
20
22
29
33
18
23
22
25
Table 5. BaylisϪHillman reactions between N-(4-chlorobenzylid-
ene)-4-methylbenzenesulfonamide (1.0 equiv.) and 2-cyclohexen-1-
one (1.0 equiv.) in the presence of Lewis base (20 mol %)
9
20
32 10
25 25
20 19
15 10
Entry Lewis base
Solvent Time Temp. Yields (%)[a]
[h]
[ °C] 4a
endo-5a exo-5a
PBu3
PBu3
1
2
3
4
5
6
7
8
PPh3
PPh3/BINOL THF
dppe/BINOL THF
PBu3
DMAP
DBU
DABCO
PBu3
DMAP
DMAP
DBU
MeOH 24
20
40
20
40
20
20
20
40
40
20
40
0
0
0
0
0
0
0
0
0
0
0
0
0
22
0
[a]
Isolated yields.
48
72
DMF 48
DMF 36
DMF 24
MeOH 36
MeOH 24
MeOH 24
MeOH 24
CH2Cl2 24
MeOH 24
trace 0
0
0
30
20
65
41
32
40
0
0
0
15
0
0
10
10
hexen-1-one in the presence of Lewis base to the imine and
an intramolecular conjugated addition (Michael addition)
of the anion formed to the α,β-unsaturated cyclic ketone
moiety. The structures of 4 and 5 were determined by spec-
troscopic data, and the crystal structure of isomer exo-5d
was established by X-ray analysis (Figure 2).
9
10
11
12
0
18
20
DBU
Meanwhile, we also examined reactions between other N-
arylidene-4-methylbenzenesulfonamides and 2-cyclohexen-
1-one in the presence of DMAP as a Lewis base (Scheme 7).
[a]
Isolated yields.
Scheme 5
Eur. J. Org. Chem. 2002, 3666Ϫ3679
Figure 2. The crystal structure of exo-5d
3669

M. Shi, Y.-M. Xu, G.-L. Zhao, X.-F. Wu
FULL PAPER
Table 8. BaylisϪHillman reactions between N-(benzylidene)-4-
methylbenzenesulfonamide (1.0 equiv.) and 2-cyclopenten-1-one
(1.0 equiv.) in the presence of the Lewis bases DMAP or PBu3
(20 mol %)
Entry
R
Lewis base
Time
[h]
Yields (%)[a]
6
1
2
3
4
5
6
7
8
C6H5
C6H5
C6H5
DMAP
PBu3
Ph2PMe
DMAP
PBu3
PBu3
PhPMe2
PBu3
PBu3
DMAP
PBu3
DMAP
PBu3
24
5
27
24
6
6
4
6
5
24
5
24
5
75
70
67
82
85
87
99
90
99
54
83
80
90
Scheme 7
p-EtC6H4
p-EtC6H4
p-MeOC6H4
p-MeOC6H4
p-Me2NC6H4
p-ClC6H4
p-ClC6H4
p-BrC6H4
p-NO2C6H4
p-NO2C6H4
Table 7. BaylisϪHillman reactions between N-(benzylidene)-4-
methylbenzenesulfonamide (1.0 equiv.) and 2-cyclohexen-1-one in
the presence of the Lewis base DMAP (20 mol %)
Entry
Ar
Time
[h]
Yield (%)[a]
4
9
10
11
12
13
1
2
3
4
5
C6H5
24
24
36
24
24
50
40
30
60
52
p-EtC6H4
p-MeOC6H4
p-FC6H4
p-NO2C6H4
[a]
Isolated yields.
[a]
formed along with the normal BaylisϪHillman adducts 8
(Scheme 9), the results for several imines substrates being
summarized in Table 9. The crystal structure of the major
Isolated yields.
Only the normal BaylisϪHillman products 4 were formed,
in moderate yields. The results are elucidated in Table 7.
For reactions between N-arylidene-4-methylbenzenesul-
fonamides and 2-cyclopenten-1-one, on the other hand, we
were delighted to find that the normal BaylisϪHillman
products 6 could be exclusively obtained in the presence of
DMAP, PhPMe2, Ph2PMe, or PBu3 as Lewis bases under
the same reaction conditions, although PPh3 or DABCO
had no activity for this reaction (Scheme 8, Table 8). No
abnormal adducts were formed, and the BaylisϪHillman
adducts 6 were obtained in very high yields. This may be
due to the aldol condensation reaction being difficult for
small cyclic ketones in the presence of Lewis bases. The
reaction rates are much faster than those for 2-cyclohexen-
1-one under similar conditions. Especially with PhPMe2 or
PBu3 as a Lewis base, yields of products 6 can reach 90%
within 5 h at room temperature, the reactions in some cases
proceeding quantitatively. This result also suggests that the
ring-size of α,β-unsaturated cyclic ketones can significantly
affect the reaction products and rates. Meanwhile, the sub-
stituents on the phenyl ring also do not affect the reaction
products and rates.
Scheme 9
Table 9. BaylisϪHillman reactions between N-(benzylidene)-4-
methylbenzenesulfonamide (1.0 equiv.) and 2-cyclohepten-1-one
(1.0 equiv.) in the presence of the Lewis bases DMAP or PBu3
(20 mol %)
Entry R
Lewis base Solvent Time Yields (%)[a]
[h]
7 (endo/exo) 8
1
2
3
4
5
6
C6H5
C6H5
p-ClC6H4
p-ClC6H4
p-MeOC6H4 DBU
p-MeOC6H4 PBu3
DMAP
PBu3
PBu3
MeOH 48
14 (41:59)
Ϫ
Ϫ
22 (22:78)
21 (35:65)
Ϫ
27
Ϫ
Ϫ
9
trace
Ϫ
THF
THF
5
5
Scheme 8
DBU
MeOH 48
MeOH 48
We found that reactions between imines and 2-cyclo-
hepten-1-one[7] are in general sluggish under various condi-
tions. The abnormal BaylisϪHillman adducts 7 were
THF
6
[a]
Isolated yields.
3670
Eur. J. Org. Chem. 2002, 3666Ϫ3679

Lewis Base Effects in the BaylisϪHillman Reaction
FULL PAPER
isomer exo-7a was determined by X-ray analysis (Figure 3).
1
The endo/exo ratios obtained are based on the H NMR
spectroscopic data. It is very clear that the abnormal
BaylisϪHillman adducts 7 derive from aldol condensation
reactions, followed by intramolecular Michael addition, as
in the case of the formation of 5 shown in Scheme 5.
Scheme 10
Table 10. BaylisϪHillman reactions between N-(benzylidene)-4-
methylbenzenesulfonamide (1.0 equiv.) and 2-cycloocten-1-one (1.0
equiv.) in the presence of the Lewis bases DMAP or PBu3 (20
mol %)
Yields (%)[a]
9 (syn/anti)
Figure 3. The crystal structure of exo-7a
Entry
R
Lewis base
Time
[h]
10
For reactions between imines and 2-cycloocten-1-one,[8]
however, we surprisingly found that, although none of the
BaylisϪHillman adducts 11 were formed at all and the reac-
tions were sluggish, the abnormal BaylisϪHillman adducts
9 (syn and anti mixtures) were formed exclusively in THF
in the presence of DMAP or PBu3 as Lewis bases
(Scheme 10). Obviously, compounds 9 are derived from al-
dol reactions between imines and 2-cycloocten-1-one in the
presence of a Lewis base. In addition, when the reactions
were carried out in methanol, the products 10, derived from
Michael addition of methanol to 9, became the major prod-
ucts along with traces of 9 (Scheme 10). The results for sev-
eral imine substrates are summarized in Table 10. The struc-
tures of 9 and 10 were established by spectroscopic data
and microanalysis, while the X-ray crystal structures of the
major isomers of 9 and 10 are shown in Figures 4 and 5.
The syn/anti ratios obtained are based on 1H NMR spectro-
scopic data.
1
2
3
4
5
6
C6H5
C6H5
p-ClC6H4
p-ClC6H4
p-MeOC6H4
p-MeOC6H4
DMAP
PBu3
PBu3
DMAP
DMAP
PBu3
48
48
48
48
48
48
Ϫ
45
Ϫ
Ϫ
51
44
Ϫ
42 (35:65)
30 (40:60)
Ϫ
Ϫ
49 (41:59)
[a]
Isolated yields.
These results suggest that, for medium-sized α,β-unsatur-
ated cyclic ketones such as 2-cyclohexen-1-one or 2-cyclo-
hepten-1-one, the aldol condensation reaction in general
takes place along with the BaylisϪHillman reaction. For
the larger 2-cycloocten-1-one, however, the aldol condensa-
tion reaction occurred exclusively, rather than the
BaylisϪHillman reaction. This is because the Lewis bases
used for BaylisϪHillman reactions, such as DMAP,
DABCO, PBu3, or DBU, are also organic bases used for
aldol condensation reactions in organic chemistry. Thus,
Figure 4. The crystal structure of 9b
both the BaylisϪHillman reaction and aldol condensation Lewis base, and so the BaylisϪHillman reaction takes place
can take place at the same time for the α,β-unsaturated cyc- exclusively. For medium-sized α,β-unsaturated cyclic ke-
lic ketone. For 2-cyclopenten-1-one (a small α,β-unsatur- tones such as 2-cyclohexen-1-one or 2-cyclohepten-1-one,
ated cyclic ketone), abstraction of the α-H by the organic both the BaylisϪHillman reaction and aldol condensation
base is difficult. The organic base thus plays a role only as occur at the same time.
Eur. J. Org. Chem. 2002, 3666Ϫ3679
3671

M. Shi, Y.-M. Xu, G.-L. Zhao, X.-F. Wu
FULL PAPER
Figure 5. The crystal structure of 10c
Additionally, we also found a very interesting result in tions between 9 and the imines, followed by the elimination
the application of BaylisϪHillman reaction conditions to of TsNHϪ. Scheme 12 elucidates a plausible reaction mech-
imines and 2-cycloocten-1-one in the presence of DBU as a anism for the formation of 12 (Scheme 12). Attack of the
Lewis base. The abnormal BaylisϪHillman reaction prod- allyl enolate anion to tosylimine gives the adduct A, in
ucts 12 were formed in moderate yields, each as a single which the α-carbonyl hydrogen atom, particularly acidic be-
(anti) stereoisomer (Scheme 11). The structures of 12 were cause of double activation (carbonyl ϩ double bond), can
established by spectroscopic data and X-ray analysis (Fig- be selectively abstracted by DBU. This results in the elim-
ure 6). We believe that products 12 derive from aldol reac- ination of TsNHϪ, a good leaving group because of the
stabilization of the negative charge by the sulfonyl group,
giving product 12.
Scheme 11
Scheme 12
Conclusion
In this full paper, we have clearly elucidated that the ap-
plication of BaylisϪHillman reaction conditions to arene-
carbaldehydes or tosylimines and α,β-unsaturated cyclic ke-
tones is very complicated, since the Lewis bases, the solv-
Figure 6. The crystal structure of 12b
ents, the substrates, and the ring-sizes of α,β-unsaturated
3672
Eur. J. Org. Chem. 2002, 3666Ϫ3679

Lewis Base Effects in the BaylisϪHillman Reaction
FULL PAPER
2-[Hydroxy(3-nitrophenyl)methyl]cyclohex-2-enone (1c): Colorless
oil; 87 mg, 70%. IR (CHCl3): ν˜ ϭ 1666 cmϪ1 (CϭO). 1H NMR
(CDCl3, TMS, 300 MHz): δ ϭ 2.01Ϫ2.05 (m, 2 H, CH2),
2.43Ϫ2.47 (m, 4 H, CH2), 3.75 (d, J ϭ 5.9 Hz, 1 H, OH), 5.60 (d,
J ϭ 5.9 Hz, 1 H, CH), 6.90 (t, J ϭ 4.2 Hz, 1 H, ϭCH), 7.51 (t,
J ϭ 7.9 Hz, 1 H, Ar), 7.75 (d, J ϭ 8.2 Hz, 1 H, Ar), 8.10 (d, J ϭ
8.2 Hz, 1 H, Ar), 8.22 (s, 1 H, Ar) ppm. MS (EI): m/z (%) ϭ 248
(8.15) [Mϩ], 230 (100) [Mϩ Ϫ 18]. C13H13NO4: calcd. C 63.15, H
5.30, N 5.67; found C 63.05, H 5.24, N 5.67.
cyclic ketones can all significantly affect the BaylisϪ
Hillman reaction rates and even products. However, it is
clear that aldol condensation reactions can take place along
with the BaylisϪHillman reactions, to give abnormal
BaylisϪHillman adducts such as 3, 5, 7 and 9, 10 and 12 in
each case. Efforts are currently underway both to obtain
mechanistic insights regarding the Lewis bases used in these
BaylisϪHillman reactions of arenecarbaldehydes or N-aryl-
idene-4-methylbenzenesulfonamides (imines) with α,β-un-
saturated cyclic ketones and to determine the scope and
limitations of this type of BaylisϪHillman reaction.
Typical Reaction Procedure for the Tributylphosphane-Catalyzed
Baylis؊Hillman Reaction between 2-Cyclopenten-1-one and 4-Nitro-
benzaldehyde: 2-Cyclopenten-1-one (42 µL, 0.5 mmol) was added
at room temperature to a solution of 4-nitrobenzaldehyde (113 mg,
0.75 mmol) and tributylphosphane (24 µL, 0.1 mmol) in THF
(1.0 mL). After the mixture had been stirred for 5 h at room tem-
perature, the solvent was removed under reduced pressure and the
residue was purified by flash chromatography (SiO2; EtOAc/petro-
leum ether, 1:2) to yield 2a (62 mg, 53%) and 3a (50 mg, 26%) as
yellow solids which were recrystallized from acetone/n-hexane (1:6).
Experimental Section
General Remarks: Unless otherwise stated, all reactions were car-
ried out under argon. All solvents were purified by distillation. Tri-
butylphosphane were obtained from Tokyo Chemical Industries
(Tokyo Kasei Co. Ltd.) and used without purification. All N-tosyl-
imines were prepared according to the literature. Infrared spectra
2-[Hydroxy(4-nitrophenyl)methyl]cyclopent-2-enone (2a): Pale yel-
low solid; m.p. 135Ϫ137 °C; 62 mg, 53%. IR (CHCl3): ν˜ ϭ 1692
1
were measured with a PerkinϪElmer 983 spectrometer. H NMR
1
cmϪ1 (CϭO). H NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.36Ϫ2.39
spectra were recorded with a 300 MHz spectrometer in CDCl3 with
tetramethylsilane as the internal standard. Mass spectra were re-
corded with an HP-5989 instrument and HRMS was performed
with a Finnigan MAϩ mass spectrometer. Satisfactory CHN mic-
roanalyses were obtained with a CarloϪErba 1106 analyzer for
solid products. For oily products, HRMS was used to analyze the
elemental composition since we do not have a diffusion pump (high
pressure) suitable to distill oily products. Melting points were ob-
tained by means of a micro melting point apparatus and are uncor-
rected.
(m, 2 H, CH2), 2.50Ϫ2.54 (m, 2 H, CH2), 3.63 (d, J ϭ 4.3 Hz, 1
H, OH), 5.68 (s, 1 H, CH), 7.31 (t, J ϭ 1.1 Hz, 1 H, ϭCH), 7.47
(d, J ϭ 8.6 Hz, 2 H, Ar), 8.10 (d, J ϭ 8.6 Hz, 2 H, Ar) ppm. MS
(EI): m/z (%) ϭ 233 (100) [Mϩ], 216 (73.62) [Mϩ Ϫ 17].
C12H11NO4: calcd. C 61.80, H 4.72, N 6.00; found C 61.92, H 4.74,
N 6.22.
syn-2,5-Bis[hydroxy(4-nitrophenyl)methyl]cyclopent-2-enone
(3a):
Pale yellow solid; m.p. 82Ϫ83 °C. IR (CHCl3): ν˜ ϭ 1696 cmϪ1 (Cϭ
1
O). H NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.34Ϫ2.36 (m, 1 H,),
2.46Ϫ2.48 (m, 1 H,), 2.67Ϫ2.68 (m, 1 H), 2.80Ϫ2.82 (m, 1 H),
3.32Ϫ3.34 (m, 1 H), 5.53Ϫ5.55 (m, 1 H, CH), 5.71Ϫ5.72 (m, 1 H,
CH), 7.44 (t, J ϭ 1.4 Hz, 1 H, ϭCH), 7.56 (d, J ϭ 8.7 Hz, 2 H,
Ar), 7.60 (d, J ϭ 8.7 Hz, 2 H, Ar), 8.22 (d, J ϭ 8.7 Hz, 2 H, Ar),
8.25 (d, J ϭ 8.7 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 233 (100)
[Mϩ Ϫ 151], 216 (43.83) [Mϩ Ϫ 168].C19H116N2O7·H2O: calcd. C
56.43, H 4.99, N 6.99; found C 57.05, H 4.74, N 7.11.
Typical Reaction Procedure for the DMAP-Catalyzed
Baylis؊Hillman Reaction between 2-Cyclohexen-1-one and 4-Nitro-
benzenaldehyde: 2-Cyclohexen-1-one (48 µL, 0.5 mmol) was added
at room temperature to a solution of p-nitrobenzenaldehyde
(76 mg, 0.5 mmol) and DMAP (6 mg, 0.05 mmol) in CH2Cl2
(0.5 mL). After the mixture had been stirred for 15 d, the solvent
was removed under reduced pressure and the residue was purified
by flash chromatography (SiO2; EtOAc/petroleum ether, 1:2) to
yield 1a (93 mg, 75%) as a yellow solid, which was recrystallized
from acetone/n-hexane (1:4).
anti-2,5-Bis[hydroxy(4-nitrophenyl)methyl]cyclopent-2-enone (3a):
Pale yellow solid; m.p. 82Ϫ83 °C. IR (CHCl3): ν˜ ϭ 1696 cmϪ1 (Cϭ
1
O). H NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.41Ϫ2.44 (m, 1 H,),
2.45Ϫ2.47 (m, 1 H,), 2.74Ϫ2.75 (m, 1 H), 2.81Ϫ2.84 (m, 1 H),
3.35Ϫ3.37 (m, 1 H), 5.55Ϫ5.56 (m, 1 H, CH), 5.68Ϫ5.70 (m, 1 H,
CH), 7.38 (t, J ϭ 1.4 Hz, 1 H, ϭCH), 7.57 (d, J ϭ 8.7 Hz, 2 H,
Ar), 7.62 (d, J ϭ 8.7 Hz, 2 H, Ar), 8.23 (d, J ϭ 8.7 Hz, 2 H, Ar),
8.26 (d, J ϭ 8.7 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 233 (100)
[Mϩ Ϫ 151], 216 (43.83) [Mϩ Ϫ 168]. C19H116N2O7·H2O: calcd. C
56.43, H 4.99, N 6.99; found C 57.05, H 4.74, N 7.11.
2-[Hydroxy(4-nitrophenyl)methyl]cyclohex-2-enone (1a): Yellow
solid; 93 mg, 75%; m.p. 88Ϫ89 °C. IR (CHCl3): ν˜ ϭ 1666 cmϪ1
(CϭO). H NMR (CDCl3, TMS, 300 MHz): δ ϭ 1.97Ϫ2.05 (m, 2
H, CH2), 2.41Ϫ2.48 (m, 4 H, CH2), 3.57 (d, J ϭ 6.0 Hz, 1 H, OH),
5.60 (d, J ϭ 6.0 Hz, 1 H, CH), 6.82 (t, J ϭ 4.1 Hz, 1 H, ϭCH),
7.55 (d, J ϭ 8.7 Hz, 2 H, Ar), 8.20 (d, J ϭ 8.7 Hz, 2 H, Ar) ppm.
MS (EI): m/z (%) ϭ 247 (3.39) [Mϩ], 230 (100) [Mϩ Ϫ 17].
C13H13NO4: calcd. C 63.15, H 5.30, N 5.67; found C 63.23, H 5.36,
N 5.65.
1
The total yield of syn-3a and anti-3a was 50 mg, 26%.
2-[Hydroxy(phenyl)methyl]cyclopent-2-enone (2b): Colorless liquid;
56 mg, 59%. IR (CHCl3): ν˜ ϭ 1692 cmϪ1 (CϭO). 1H NMR
2-[Hydroxy(2-nitrophenyl)methyl]cyclohex-2-enone (1b): Yellow
solid; 86 mg, 70%; m.p. 124Ϫ125 °C. IR (CHCl3): ν˜ ϭ 1658 cmϪ1
(CϭO). H NMR (CDCl3, TMS, 300 MHz): δ ϭ 1.96Ϫ2.04 (m, 2
H, CH2), 2.35Ϫ2.40 (m, 2 H, CH2), 2.46Ϫ2.50 (m, 2 H, CH2), 3.67
(d, J ϭ 4.9 Hz, 1 H, OH), 6.18 (d, J ϭ 4.9 Hz, 1 H, CH), 6.62 (t,
J ϭ 4.1 Hz, 1 H, ϭCH), 7.45 (dd, J ϭ 7.5, 7.9 Hz, 1 H, Ar), 7.66
(dd, J ϭ 7.5, 8.1 Hz, 1 H, Ar), 7.82 (d, J ϭ 7.9 Hz, 1 H, Ar), 7.94
(d, J ϭ 8.1 Hz, 1 H, Ar) ppm. MS (EI): m/z (%) ϭ 248 (3.23) [Mϩ],
(CDCl3, TMS, 300 MHz):
δ ϭ 2.42Ϫ2.45 (m, 2 H, CH2),
1
2.56Ϫ2.58 (m, 2 H, CH2), 3.52 (s, 1 H, br, OH), 5.54 (s, 1 H, CH),
7.26(t, J ϭ 1.1 Hz, 1 H, ϭCH), 7.27Ϫ7.56 (m, 5 H) ppm. MS (EI):
m/z (%) ϭ 188 (87.72) [M], 269 (2.66) [Mϩ ϩ 2], 170 (8.25) [Mϩ Ϫ
18], 128 (100) [Mϩ Ϫ 60]. HRMS: calcd. for C12H12O2 188.0837;
found 188.0830.
230 (31.18) [Mϩ Ϫ 18]. C13H13NO4: calcd. C 63.15, H 5.30, N 5.67; syn-2,5-Bis[hydroxy(phenyl)methyl]cyclopent-2-enone (3b): Pale yel-
found C 62.97, H 5.10, N 5.41.
low solid; m.p. 138Ϫ139 °C. IR (CHCl3): ν˜ ϭ 1680 cmϪ1 (Cϭ
Eur. J. Org. Chem. 2002, 3666Ϫ3679
3673

M. Shi, Y.-M. Xu, G.-L. Zhao, X.-F. Wu
FULL PAPER
O). H NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.40Ϫ2.42(m, 1 H,), Ϫ 18], 205 (44.07) [Mϩ Ϫ 158, . HRMS: calcd. for C19H15Cl2O2
2.66Ϫ2.67 (m, 1 H, CH), 2.68 (s, 1 H, br, OH), 2.78Ϫ2.79 (m, 1 [Mϩ ϩ 1 Ϫ H2O) 345.0449; found 345.0446.
H), 3.49 (s, 1 H, br, OH), 5.40Ϫ5.41 (m, 1 H, CH), 5.58Ϫ5.59 (m,
1
anti-2,5-Bis[(4-chlorophenyl)(hydroxy)methyl]cyclopent-2-enone
1 H, CH), 7.34 (t, J ϭ 1.4 Hz, 1 H, ϭCH), 7.34Ϫ7.42 (m, 10 H,
(3d): Colorless, viscous liquid. IR (CHCl3): ν˜ ϭ 1688 cmϪ1 (Cϭ
Ar) ppm. MS (EI): m/z (%) ϭ 276 (32.24) [Mϩ Ϫ 18], 259 (100)
1
O). H NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.39Ϫ2.40 (m, 1 H,
[Mϩ Ϫ 35]. C19H18O3: calcd. C 77.55, H 6.12; found C 77.58, H
CH), 2.48Ϫ2.51 (m, 1 H, CH), 2.66Ϫ2.70 (m, 1 H, CH), 2.76Ϫ2.79
6.08.
(m, 1 H, CH), 3.27Ϫ3.28 (m, 1 H, CH), 5.31Ϫ5.34 (m, 1 H, CH),
anti-2,5-Bis[hydroxy(phenyl)methyl]cyclopent-2-enone (3b): Pale yel-
low solid; m.p. 138Ϫ139 °C. IR (CHCl3): ν˜ ϭ 1680 cmϪ1 (CϭO).
1H NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.34Ϫ2.36 (m, 1 H, CH),
2.70 (s, 1 H, br, OH), 2.76Ϫ2.77 (m, 1 H, CH), 2.79Ϫ2.80 (m, 1
H), 3.38 (s, 1 H, br, OH), 5.41Ϫ5.42 (m, 1 H, CH), 5.59Ϫ5.60 (m,
1 H, CH), 7.32 (t, J ϭ 1.4 Hz, 1 H, ϭCH), 7.27Ϫ7.36 (m, 10 H,
Ar) ppm. MS (EI): m/z (%) ϭ 276 (32.24) [Mϩ Ϫ 18], 259 (100)
[Mϩ Ϫ 35]. C19H18O3: calcd. C 77.55, H 6.12; found C 77.58, H
6.08.
5.51Ϫ5.53 (m, 1 H, CH), 7.35 (t, J ϭ 1.4 Hz, 1 H, ϭCH),
7.30Ϫ7.38 (m, 8 H, Ar) ppm. MS (EI): m/z (%) ϭ 345 (5.51) [Mϩ
Ϫ 18], 205 (44.07) [Mϩ Ϫ 158]. HRMS: calcd. for C19H15Cl2O2
[Mϩ ϩ 1 Ϫ H2O) 345.0449; found 345.0446.
The total yield of syn-3d and anti-3d was 19 mg, 11%.
2-[(4-Ethylphenyl)(hydroxy)methyl]cyclopent-2-enone (2e): Colorless
1
liquid; 81 mg, 75%. IR (CHCl3): ν˜ ϭ 1690 cmϪ1 (CϭO). H NMR
(CDCl3, TMS, 300 MHz): δ ϭ 1.21 (t, J ϭ 7.6 Hz, 3 H, CH3),
2.41Ϫ2.44 (m, 2 H, CH2), 2.55Ϫ2.58 (m, 2 H, CH2), 2.61 (q, J ϭ
7.6 Hz, 2 H, CH2), 3.30Ϫ3.70 (s, 1 H, br, OH), 5.51 (s, 1 H, CH),
7.16 (d, J ϭ 8.0 Hz, 2 H, Ar), 7.26Ϫ7.30 (m, 2 H), 7.31 (t, J ϭ
1.1 Hz, 1 H, ϭCH) ppm. MS (EI): m/z ϭ 216 (5.50) [Mϩ], 199 (100
)[Mϩ Ϫ 17]. C14H16O2: calcd. C 77.75, H 7.46; found C 77.49,
H 7.34.
The total yield of syn-3b and anti-3b was 35 mg, 24%.
2-[(4-Bromophenyl)(hydroxy)methyl]cyclopent-2-enone (2c): Color-
less liquid; 92 mg, 69%. IR (CHCl3): ν˜ ϭ 1688 cmϪ1 (CϭO). 1H
NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.40Ϫ2.45 (m, 2 H, CH2),
2.57Ϫ2.58 (m, 2 H, CH2), 3.78 (s, 1 H, br, OH), 5.47 (s, 1 H, CH),
7.23Ϫ7.27 (m, 2 H), 7.28 (t, J ϭ 1.1 Hz, 1 H, ϭCH), 7.43 (d, J ϭ
8.5 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 267 (2.57) [M], 269
(2.66) [Mϩ ϩ 2], 249 (100) [Mϩ Ϫ 18], 251 (96.13) [Mϩ Ϫ 16].
C12H11BrO2: calcd. C 53.96, H 4.15; found C 54.27, H 4.58.
2-[Hydroxy(4-methoxyphenyl)methyl]cyclopent-2-enone (2f): Color-
less liquid; 92 mg, 84%. IR (CHCl3): ν˜ ϭ 1689 cmϪ1 (CϭO). 1H
NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.38Ϫ2.42 (m, 2 H, CH2),
2.53Ϫ2.56 (m, 2 H, CH2), 3.70 (s, 1 H, br, OH), 3.79 (s, 3 H, CH3),
5.45 (s, 1 H, CH), 6.84 (d, J ϭ 8.7 Hz, 2 H, Ar), 7.24Ϫ7.31 (m, 2
H), 7.32 (t, J ϭ 1.1 Hz, 1 H, ϭCH) ppm. MS (EI): m/z (%) ϭ 218
(34.89) [Mϩ], 201 (100) [Mϩ Ϫ 17]. HRMS: calcd. for C13H14O3:
calcd. 218.0943; found 218.0933.
syn-2,5-Bis[(4-bromophenyl)(hydroxy)methyl]cyclopent-2-enone (3c):
Pale yellow solid; m.p. 150Ϫ152 °C. IR (CHCl3): ν˜ ϭ 1687 cmϪ1
1
(CϭO). H NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.37Ϫ2.40 (m, 1
H), 2.58 Ϫ2.61 (m, 1 H), 2.71Ϫ2.74 (m, 1 H), 3.28 (s, 1 H, br, OH),
3.76 (s, 1 H, br, OH), 5.34 (d, J ϭ 2.4 Hz, 1 H, CH), 5.49Ϫ5.50
(m, 1 H, CH), 7.17Ϫ7.24 (m, 4 H, Ar), 7.34 (t, J ϭ 1.4 Hz, 1 H, ϭ
CH), 7.42Ϫ7.48 (m, 4 H, Ar) ppm. MS (EI): m/z (%) ϭ 452 (0.43)
[M], 266 (30.72) [Mϩ Ϫ 186]. C19H16Br2O3: calcd. C 50.47, H 3.57;
found C 50.62, H 3.41.
Typical Reaction Procedure for the Tributylphosphane-Catalyzed
Baylis؊Hillman Reaction between 2-Cyclohexen-1-one and N-(4-
Ethylbenzylidene)-4-methylbenzenesulfonylamide: 2-Cyclohexen-1-
one (48 µL, 0.5 mmol) was added at 40 °C to a solution of N-(4-
ethylbenzylidene)-4-methylbenzenesulfonylamide
(144 mg,
anti-2,5-Bis[(4-bromophenyl)(hydroxy)methyl]cyclopent-2-enone
(3c): Pale yellow solid; m.p. 150Ϫ152 °C. IR (CHCl3): ν˜ ϭ 1687
0.5 mmol) and tributylphosphane (25 µL, 0.1 mmol) in CH3OH
(0.5 mL). After the mixture had been stirred for 24 h, the solvent
was removed under reduced pressure and the residue was purified
by flash chromatography (SiO2; EtOAc/petroleum ether, 1:5) to
yield 4c (58 mg, 31.3%), endo-5c (11 mg, 5.74%), and exo-5c
(33 mg, 17.2%) as colorless solids, which were recrystallized from
acetone/n-hexane (1:3).
1
cmϪ1 (CϭO). H NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.27Ϫ2.33
(m, 1 H), 2.65Ϫ2.67 (m, 1 H), 2.75Ϫ2.78 (m, 1 H), 2.91 (s, 1 H,
br, OH), 3.52 (s, 1 H, br, OH), 5.29 (d, J ϭ 2.4 Hz, 1 H, CH),
5.50Ϫ5.51 (m, 1 H, CH), 7.19Ϫ7.26 (m, 4 H, Ar), 7.31 (t, J ϭ
1.4 Hz, 1 H, ϭCH), 7.44Ϫ7.49 (m, 4 H, Ar) ppm. MS (EI): m/z
(%) ϭ 452 (0.43) [Mϩ], 266 (30.72) [Mϩ Ϫ 186]. C19H16Br2O3:
calcd. C 50.47, H 3.57; found C 50.62, H 3.41.
N-[(4-Chlorophenyl)(6-oxocyclohex-1-enyl)methyl]-4-methylbenzene-
sulfonamide (4a): Colorless solid; m.p. 135Ϫ136 °C; 39 mg, 20%.
IR (CHCl3): ν˜ ϭ 1667 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.62Ϫ2.32 (m, 6 H, CH2), 2.39 (s, 3 H, Me), 5.09
(d, J ϭ 9.6 Hz, 1 H, NH), 6.18 (d, J ϭ 9.6 Hz, 1 H, CH), 6.80 (t,
J ϭ 4.1 Hz, 1 H, ϭCH), 7.10 (d, J ϭ 8.7 Hz, 2 H, Ar), 7.15 (2 H,
J ϭ 8.7 Hz, Ar), 7.21 (d, J ϭ 8.2 Hz, 2 H, Ar), 7.60 (d, J ϭ 8.2 Hz,
2 H, Ar) ppm. MS (EI): m/z (%) ϭ 294 (1.59) [Mϩ Ϫ 96], 234 (100)
[Mϩ Ϫ 156]. C20H20ClNO3S: calcd. C 61.61, H 5.17, N 3.59; found
C 61.54, H 5.18, N 3.71.
The total yield of syn-3c and anti-3c was 30 mg, 13%.
2-[(4-Chlorophenyl)(hydroxy)methyl]cyclopent-2-enone (2d): Color-
less liquid; 88 mg, 79%. IR (CHCl3): ν˜ ϭ 1690 cmϪ1 (CϭO). 1H
NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.45Ϫ2.49 (m, 2 H, CH2),
2.58Ϫ2.63 (m, 2 H, CH2), 3.50 (d, J ϭ 4.3 Hz, 1 H, OH), 5.55 (d,
J ϭ 4.3 Hz, 1 H, CH), 7.25 (t, J ϭ 1.1 Hz, 1 H, ϭCH), 7.31Ϫ7.40
(m, 4 H, Ar) ppm. MS (EI): m/z (%) ϭ 222 (40.11) [Mϩ], 205
(75.61) [Mϩ Ϫ 17]. C12H11ClO2: calcd. C 64.72, H 4.94; found C
64.55, H 5.18.
endo-3-(4-Chlorophenyl)-2-(4-tolylsulfonyl)-2-azabicyclo[2.2.2]-
syn-2,5-Bis[(4-chlorophenyl)(hydroxy)methyl]cyclopent-2-enone (3d): octan-5-one (5a): Colorless solid; m.p. 158Ϫ159 °C; 29 mg, 15%.
1
Colorless, viscous liquid. IR (CHCl3): ν˜ ϭ 1688 cmϪ1 (CϭO). H
IR (CHCl3): ν˜ ϭ 1727 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.23Ϫ2.48 (m, 7 H, CH2), 2.43 (s, 3 H, Me), 4.46
NMR (CDCl3, TMS, 300 MHz): δ ϭ 2.40Ϫ2.41 (m, 1 H),
2.59Ϫ2.60 (m, 1 H, CH), 2.61Ϫ2.63 (m, 1 H, CH), 2.73Ϫ2.75 (m, (d, J ϭ 2.4 Hz, 1 H, CH), 5.06 (d, J ϭ 2.0 Hz, 1 H, CH), 7.30 (m,
1 H, CH), 3.37Ϫ3.39 (m, 1 H, CH), 5.36Ϫ5.38 (m, 1 H, CH), 6 H, Ar), 7.62 (2 H, J ϭ 8.3 Hz, Ar) ppm. MS (EI): m/z (%) ϭ
5.52Ϫ5.54 (m, 1 H, CH), 7.35 (t, J ϭ 1.4 Hz, 1 H, ϭCH), 389(16.15) [Mϩ Ϫ 1], 234 (100) [Mϩ Ϫ 156]. C20H20ClNO3S: calcd.
7.28Ϫ7.33 (m, 8 H, Ar) ppm. MS (EI): m/z (%) ϭ 345 (5.51) [Mϩ
C 61.61, H 5.17, N 3.59; found C 61.74, H 5.20, N 3.38.
Eur. J. Org. Chem. 2002, 3666Ϫ3679
3674

Lewis Base Effects in the BaylisϪHillman Reaction
exo-3-(4-Chlorophenyl)-2-(4-toluylsulfonyl)-2-azabicyclo[2.2.2]- J ϭ 2.5 Hz, 1 H, CH), 4.98 (d, J ϭ 2.5 Hz, 1 H, CH), 7.03 (d, J ϭ
FULL PAPER
octan5-one (5a): Colorless solid; m.p. 201Ϫ202 °C; 43 mg, 22%. IR
8.3 Hz, 2 H, Ar), 7.09 (2 H, J ϭ 8.2 Hz, Ar), 7.20 (d, J ϭ 8.3 Hz,
2 H, Ar), 7.60 (d, J ϭ 8.2 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ
(CHCl3): ν˜ ϭ 1728 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.55Ϫ2.75 (m, 7 H, CH2), 2.42 (s, 3 H, Me), 4.53 383 (1.26) [Mϩ Ϫ 1], 228 (100) [Mϩ Ϫ 155]. C22H25NO3S: calcd.
(s, 1 H, CH), 4.97 (d, J ϭ 2.5 Hz, 1 H, CH), 7.05 (d, J ϭ 8.5 Hz,
2 H, Ar), 7.18 (d, J ϭ 8.5 Hz, 2 H, Ar), 7.22 (d, J ϭ 8.2 Hz, 2 H,
Ar), 7.61 (2 H, J ϭ 8.2 Hz, Ar) ppm. MS (EI): m/z (%) ϭ 389
(16.15) [Mϩ Ϫ 1], 234 (100) [Mϩ Ϫ 156]. C20H20ClNO3S: calcd. C
61.61, H 5.17, N 3.59; found C 61.45, H 5.23, N 3.58.
C 68.90 H, 6.57 N, 3.65; found C 69.15 H, 6.64 N, 3.60.
N-[(4-Methoxyphenyl)(6-oxocyclohex-1-enyl)methyl]-4-methylben-
zenesulfonamide (4d): Colorless solid; m.p. 113Ϫ115 °C; 48 mg,
25%. IR (CHCl3): ν˜ ϭ 1666 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.65Ϫ2.35 (m, 6 H, CH2), 2.41 (s, 3 H, Me), 3.73
(s, 3 H, Me), 5.05 (d, J ϭ 9.2 Hz, 1 H, NH), 5.86 (d, J ϭ 9.2 Hz,
1 H, CH), 6.76 (d, J ϭ 8.7 Hz, 2 H, Ar), 6.81 (t, J ϭ 4.1 Hz, 1
4-Methyl-N-[(6-oxocyclohex-1-enyl)(phenyl)methyl]benzene-
sulfonamide (4b): Colorless solid; m.p. 148Ϫ149 °C; 29 mg, 16%.
IR (CHCl3): ν˜ ϭ 1670 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS, H, ϭCH), 7.09 (d, J ϭ 8.7 Hz, 2 H, Ar), 7.25 (d, J ϭ 8.2 Hz, 2 H,
300 MHz): δ ϭ 1.67Ϫ2.31 (m, 6 H, CH2), 2.41 (s, 3 H, Me), 5.10 Ar), 7.63 (d, J ϭ 8.2 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 278
(d, J ϭ 9.5 Hz, 1 H, NH), 5.93 (d, J ϭ 9.5 Hz, 1 H, CH), 6.82 (t,
(1.84) [Mϩ Ϫ 107], 230 (100) [Mϩ Ϫ 155]. C21H23NO4S: calcd. C
J ϭ 4.1 Hz, 1 H, ϭCH), 7.20 (m, 7 H, Ar), 7.64 (d, J ϭ 8.2 Hz, 2 65.43, H 6.01, N 3.63; found C 65.31, H 6.09, N 3.52.
H, Ar) ppm. MS (EI): m/z (%) ϭ 278 (1.84) [Mϩ Ϫ 77], 200 (100)
endo-3-(4-Methoxyphenyl)-2-(4-toluylsulfonyl)-2-azabicyclo[2.2.2]-
[Mϩ Ϫ 155]. C20H21NO3S: calcd. C 67.58, H 5.95, N 3.94; found
octan-5-one (5d): Colorless solid; m.p. 174Ϫ175 °C; 48 mg, 25%.
C 67.02, H 5.83, N 3.80.
IR (CHCl3): ν˜ ϭ 1724 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
endo-3-Phenyl-2-(4-toluylsulfonyl)-2-azabicyclo[2.2.2]octan-5-one 300 MHz): δ ϭ 1.22Ϫ2.46 (m, 7 H, CH2), 2.44 (s, 3 H, Me), 3.73
(5b): Colorless solid; m.p. 182Ϫ183 °C; 29 mg, 16%. IR (CHCl3):
(s, 3 H, Me), 4.44 (d, J ϭ 2.2 Hz, 1 H, CH), 5.05 (d, J ϭ 1.8 Hz,
1
ν˜ ϭ 1726 cmϪ1 (CϭO). H NMR (CDCl3, TMS, 300 MHz): δ ϭ 1 H, CH), 6.85 (d, J ϭ 8.5 Hz, 2 H, Ar), 7.21 (d, J ϭ 8.5 Hz, 2 H,
1.56Ϫ2.53 (m, 7 H, CH2), 2.42 (s, 3 H, Me), 4.47 (s, 1 H, CH), Ar), 7.24 (d, J ϭ 8.2 Hz, 2 H, Ar), 7.62 (d, J ϭ 8.2 Hz, 2 H, Ar)
5.11 (d, J ϭ 1.8 Hz, 1 H, CH), 7.25Ϫ7.36 (m, 7 H, Ar), 7.63 (d,
ppm. MS (EI): m/z ϭ 385 (25.63) [Mϩ], 230 (88.03) [Mϩ Ϫ 155].
J ϭ 8.2 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 355 (10.61) [M] C21H23NO4S: calcd. C 65.43, H 6.01, N 3.63; found C 64.92, H
200 (100) [Mϩ Ϫ 155]. C20H21NO3S: calcd. C 67.58, H 5.95, N
6.18, N 3.49.
3.94; found C 67.63, H 5.93, N 3.89.
exo-3-(4-Methoxyphenyl)-2-(4-tolylsulfonyl)-2-azabicyclo[2.2.2]-
exo-3-Phenyl-2-(4-toluylsulfonyl)-2-azabicyclo[2.2.2]octan-5-one
octan-5-one (5d): Colorless solid: m.p. 197Ϫ198 °C; 44 mg, 23%.
Ϫ1
IR (CHCl3): ν ϭ 1731 cm (CϭO). 1H NMR (CDCl3, TMS,
˜
(5b): Colorless solid; m.p. 188Ϫ189 °C; 39 mg, 22%. IR (CHCl3):
1
ν˜ ϭ 1734 cmϪ1 (CϭO). H NMR (CDCl3, TMS, 300 MHz): δ ϭ 300 MHz): δ ϭ 1.48Ϫ2.75 (m, 7 H, CH2), 2.38 (s, 3 H, Me), 3.73
1.56Ϫ2.80 (m, 7 H, CH2), 2.42 (s, 3 H, Me), 4.54 (s, 1 H, CH), (s, 3 H, Me), 4.50 (s, 1 H, CH), 4.94 (d, J ϭ 2.4 Hz, 1 H, CH),
5.01 (d, J ϭ 2.5 Hz, 1 H, CH), 7.09Ϫ7.26 (m, 7 H, Ar), 7.61 (d,
J ϭ 8.2 Hz, 2 H, Ar) ppm. MS (EI): m/z ϭ 355 (2.15) [Mϩ], 200
6.72 (d, J ϭ 8.7 Hz, 2 H, Ar), 7.00 (d, J ϭ 8.7 Hz, 2 H, Ar), 7.20
(d, J ϭ 8.2 Hz, 2 H, Ar), 7.58 (d, J ϭ 8.2 Hz, 2 H, Ar) ppm.
(100) [Mϩ Ϫ 155]. C20H21NO3S: calcd. C 67.58, H 5.95, N 3.94; MS (EI): m/z (%) ϭ 385 (26.36) [Mϩ], 230 (78.47) [Mϩ Ϫ 155].
found C 67.41, H 5.88, N 3.84.
C21H23NO4S: calcd. C 65.43, H 6.01, N 3.63; found C 64.73, H
5.93, N 3.53.
N-[(4-Ethylphenyl)(6-oxocyclohex-1-enyl)methyl]-4-methylbenzene-
sulfonamide (4c): Colorless solid; m.p. 111Ϫ112 °C; 61 mg, 32%.
N-[(4-Fluorophenyl)(6-oxocyclohex-1-enyl)methyl]-4-methylbenzene-
IR (CHCl3): ν˜ ϭ 1730 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS, sulfonamide (4e): Colorless solid; m.p. 132Ϫ133 °C; 37 mg, 20%.
300 MHz): δ ϭ 1.17 (t, J ϭ 7.6 Hz, 3 H, Me), 1.79Ϫ2.30 (m, 6 H, IR (CHCl3): ν˜ ϭ 1652 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
CH2), 2.40 (s, 3 H, Me), 2.55 (q, J ϭ 7.6 Hz, 2 H, CH2), 5.09 (d,
J ϭ 9.3 Hz, 1 H, NH), 6.01 (d, J ϭ 9.3 Hz, 1 H, CH), 6.81 (t, J ϭ
300 MHz): δ ϭ 1.67Ϫ2.36 (m, 6 H, CH2), 2.43 (s, 3 H, Me), 5.07
(d, J ϭ 9.5 Hz, 1 H, NH), 5.95 (d, J ϭ 9.5 Hz, 1 H, CH), 6.81 (t,
4.1 Hz, 1 H, ϭCH), 7.04 (d, J ϭ 8.2 Hz, 2 H, Ar), 7.09 (2 H, J ϭ J ϭ 4.1 Hz, 1 H, ϭCH), 6.92 (d, J ϭ 8.6 Hz, 2 H, Ar), 7.17 (d,
8.2 Hz, Ar), 7.22 (d, J ϭ 8.2 Hz, 2 H, Ar), 7.63 (d, J ϭ 8.2 Hz, 2 J ϭ 8.6 Hz, 2 H, Ar), 7.27 (d, J ϭ 8.2 Hz, 2 H, Ar), 7.64 (d, J ϭ
H, Ar) ppm. MS (EI): m/z (%) ϭ 383 (1.00) [Mϩ Ϫ 1], 228 (100) 8.2 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 278 (1.59) [Mϩ Ϫ 95],
[Mϩ Ϫ 155]. C22H25NO3S: calcd. C 68.90, H 6.57, N 3.65; found
218 (100) [Mϩ Ϫ 155. C20H20FNO3S: calcd. C 64.32, H 5.40, N
C 68.89, H 6.50, N 3.66.
3.75; found C 64.42, H 5.37, N 3.59.
endo-3-(4-Ethylphenyl)-2-(4-toluylsulfonyl)-2-azabicyclo[2.2.2]octan- endo-3-(4-Fluorophenyl)-2-(4-tolylsulfonyl)-2-azabicyclo[2.2.2]octan-
5-one (5c): Colorless solid; m.p. 140Ϫ142 °C; 19 mg, 10%. IR 5-one (5e): Colorless solid; m.p. 163Ϫ164 °C; 35 mg, 19%. IR
(CHCl3): ν˜ ϭ 1723 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
(CHCl3): ν˜ ϭ 1728 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.24 (t, J ϭ 7.6 Hz, 3 H, Me), 1.44Ϫ2.50 (m, 7 H, 300 MHz): δ ϭ 1.42Ϫ2.47 (m, 7 H, CH2), 2.44 (s, 3 H, Me), 4.46
CH2), 2.42 (s, 3 H, Me), 2.63 (q, J ϭ 7.6 Hz, 2 H, CH2), 4.47 (s, 1 (s, 1 H, CH), 5.07 (s, 1 H, CH), 7.04 (d, J ϭ 8.6 Hz, 2 H, Ar), 7.25
H, CH), 5.07 (s, 1 H, CH), 7.16 (d, J ϭ 8.2 Hz, 2 H, Ar), 7.24 (2 (d, J ϭ 8.2 Hz, 2 H, Ar), 7.32 (d, J ϭ 8.6 Hz, 2 H, Ar), 7.62 (d,
H, J ϭ 8.2 Hz, Ar), 7.27 (d, J ϭ 8.3 Hz, 2 H, Ar), 7.63 (d, J ϭ J ϭ 8.2 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 373 (5.98) [Mϩ],
8.3 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 383 (4.15) [Mϩ Ϫ 1],
228 (100) [Mϩ Ϫ 155]. C22H25NO3S: calcd. C 68.90, H 6.57, N
3.65; found C 68.82, H 6.60, N 3.45.
218 (100) [Mϩ Ϫ 155]. C20H20FNO3S: calcd. C 64.32, H 5.40, N
3.75; found C 64.55, H 5.21, N 3.57.
exo-3-(4-Fluorophenyl)-2-(4-tolylsulfonyl)-2-azabicyclo[2.2.2]octan-
exo-3-(4-Ethylphenyl)-2-(4-toluylsulfonyl)-2-azabicyclo[2.2.2]octan- 5-one (5e): Colorless solid; m.p. 186Ϫ187 °C; 41 mg, 22%. IR
5-one (5c): Colorless solid; m.p. 171Ϫ172 °C; 34 mg, 18%. IR (CHCl3): ν˜ ϭ 1726 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
(CHCl3): ν˜ ϭ 1730 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.40Ϫ2.75 (m, 7 H, CH2), 2.40 (s, 3 H, Me), 4.51
300 MHz): δ ϭ 1.18 (1 H, J ϭ 7.6 Hz, Me), 1.43Ϫ2.79 (m, 7 H, (d, J ϭ 2.4 Hz, 1 H, CH), 4.97 (1 H,d, J ϭ 2.4 Hz, CH), 6.92 (d,
CH2), 2.39 (s, 3 H, Me), 2.56 (q, J ϭ 7.6 Hz, 2 H, CH2), 4.53 (d,
Eur. J. Org. Chem. 2002, 3666Ϫ3679
J ϭ 8.6 Hz, 2 H, Ar), 7.08 (d, J ϭ 8.6 Hz, 2 H, Ar), 7.22 (d, J ϭ
3675

M. Shi, Y.-M. Xu, G.-L. Zhao, X.-F. Wu
FULL PAPER
8.2 Hz, 2 H, Ar), 7.60 (d, J ϭ 8.2 Hz, 2 H, Ar) ppm. MS (EI):
(0.82) [Mϩ Ϫ 81], 214 (100) [Mϩ Ϫ 155]. C21H23NO3S: calcd. C
m/z (%) ϭ 373 (1.27) [Mϩ], 218 (100) [Mϩ Ϫ 155]. C20H20FNO3S: 68.27, H 6.27, N 3.79; found C 67.82, H 6.21, N 3.71.
calcd. C 64.32, H 5.40, N 3.75; found C 64.15, H 5.53, N 3.64.
N-[(4-Methoxyphenyl)(5-oxocyclopent-1-enyl)methyl]-4-methyl-
benzenesulfonamide (6c): Colorless solid; m.p. 118Ϫ120 °C; 162 mg,
87%. IR (CHCl3): ν˜ ϭ 1684 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 2.13Ϫ2.45 (m, 4 H, CH2), 2.35 (s, 3 H, Me), 3.73
(s, 3 H, CH3), 5.20 (d, J ϭ 8.4 Hz, 1 H, NH), 5.92 (d, J ϭ 8.4 Hz,
1 H, CH), 6.72 (d, J ϭ 8.6 Hz, 2 H, Ar), 7.05 (d, J ϭ 8.6 Hz, 2 H,
Ar), 7.19 (2 H, J ϭ 8.2 Hz, Ar), 7.35 (t, J ϭ 2.6 Hz, 1 H, ϭCH),
7.59 (d, J ϭ 8.2 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 371 (0.39)
[Mϩ], 216 (100) [Mϩ Ϫ 155]. C20H22NO4S: calcd. C 64.67, H 5.70,
N 3.77; found C 64.60, H 5.60, N 3.53.
4-Methyl-N-[(4-nitrophenyl)(6-oxocyclohex-1-enyl)methyl]benzene-
sulfonamide (4f): Colorless solid; m.p. 183Ϫ185 °C; 30 mg, 15%. IR
(CHCl3): ν˜ ϭ 1647 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.69Ϫ2.35 (m, 6 H, CH2), 2.43 (s, 3 H, Me), 5.16
(d, J ϭ 9.8 Hz, 1 H, NH), 6.10 (d, J ϭ 9.8 Hz, 1 H, CH), 6.86 (t,
J ϭ 4.1 Hz, 1 H, ϭCH), 7.27 (d, J ϭ 7.4 Hz, 2 H, Ar), 7.42 (2 H,
J ϭ 8.6 Hz, Ar), 7.64 (d, J ϭ 7.4 Hz, 2 H, Ar), 8.10 (d, J ϭ 8.6 Hz,
2 H, Ar) ppm. MS (EI): m/z (%) ϭ 278 (1.59) [Mϩ Ϫ 122], 245
(100) [Mϩ Ϫ 155]. C20H20N2O5S: calcd. C 59.99, H 5.03, N 7.00;
found C 59.99, H 4.96, N 6.76.
N-{[4-(Dimethylamino)phenyl](5-oxocyclopent-1-enyl)methyl}-4-
methylbenzenesulfonamide (6d): Yellow solid; m.p. 175Ϫ176 °C;
173 mg, 90%. IR (CHCl3): ν˜ ϭ 1676 cmϪ1 (CϭO). 1H NMR
(CDCl3, TMS, 300 MHz): δ ϭ 2.12Ϫ2.46 (m, 4 H, CH2), 2.36 (s,
3 H, Me), 2.88 (s, 6 H, CH3), 5.14 (d, J ϭ 8.1 Hz, 1 H, NH), 5.79
(d, J ϭ 8.1 Hz, 1 H, CH), 6.53 (d, J ϭ 8.8 Hz, 2 H, Ar), 6.97 (d,
J ϭ 8.8 Hz, 2 H, Ar), 7.19 (2 H, J ϭ 8.2 Hz, Ar), 7.33 (t, J ϭ
2.6 Hz, 1 H, ϭCH), 7.59 (d, J ϭ 8.2 Hz, 2 H, Ar) ppm. MS (EI):
m/z (%) ϭ 384 (33.88) [Mϩ], 229 (100) [Mϩ Ϫ 155]. C21H24N2O3S:
calcd. C 65.60, H 6.29, N 7.29; found C 65.51, H 6.24, N 7.14.
endo-3-(4-Nitrophenyl)-2-(4-tolylsulfonyl)-2-azabicyclo[2.2.2]octan-
5-one (5f): Colorless solid; m.p. 191Ϫ193 °C; 20 mg, 10%. IR
(CHCl3): ν˜ ϭ 1728 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.48Ϫ2.54 (m, 7 H, CH2), 2.45 (s, 3 H, Me), 4.48
(d, J ϭ 2.4 Hz, 1 H, CH), 5.14 (d, J ϭ 2.0 Hz, 1 H, CH), 7.28 (d,
J ϭ 8.2 Hz, 2 H, Ar), 7.55 (d, J ϭ 8.7 Hz, 2 H, Ar), 7.64 (2 H, J ϭ
8.2 Hz, Ar), 8.24 (d, J ϭ 8.7 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ
400 (5.13) [Mϩ], 245 (100) [Mϩ Ϫ 155]. C20H20N2O5S: calcd. C
59.99, H 5.03, N 7.00; found C 59.97, H 4.96, N 7.04.
N-[(4-Chlorophenyl)(5-oxocyclopent-1-enyl)methyl]-4-methylben-
zenesulfonamide (6e): Colorless solid; m.p. 190Ϫ192 °C; 186 mg,
99%. IR (CHCl3): ν˜ ϭ 1675 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 2.14Ϫ2.53 (m, 4 H, CH2), 2.36 (s, 3 H, Me), 5.28
(d, J ϭ 8.6 Hz, 1 H, NH), 6.08 (d, J ϭ 8.6 Hz, 1 H, CH), 7.14 (d,
J ϭ 8.6 Hz, 2 H, Ar), 7.21 (d, J ϭ 8.3 Hz, 2 H, Ar), 7.22 (2 H, J ϭ
8.6 Hz, Ar), 7.37 (t, J ϭ 2.6 Hz, 1 H, ϭCH), 7.61 (d, J ϭ 8.3 Hz,
2 H, Ar) ppm. MS (EI): m/z (%) ϭ 294 (0.60) [Mϩ Ϫ 81], 220 (100)
[Mϩ Ϫ 155]. C19H18ClNO3S: calcd. C 60.71, H 4.83, N 3.73; found
C 60.54, H 4.84, N 3.42.
exo-3-(4-Nitrophenyl)-2-(4-tolylsulfonyl)-2-azabicyclo[2.2.2]octan-5-
one (5f): Colorless solid; m.p. 221Ϫ222 °C; 50 mg, 25%. IR
(CHCl3): ν˜ ϭ 1730 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.23Ϫ2.48 (m, 7 H, CH2), 2.43 (s, 3 H, Me), 4.46
(d, J ϭ 2.4 Hz, 1 H, CH), 5.06 (d, J ϭ 2.0 Hz, 1 H, CH) 7.26 (d,
J ϭ 8.2 Hz, 2 H, Ar), 7.32 (d, J ϭ 8.7 Hz, 2 H, Ar), 7.63 (2 H, J ϭ
8.2 Hz, Ar), 8.11 (d, J ϭ 8.7 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ
400 (3.09) [Mϩ], 245 (100) [Mϩ Ϫ 155]. C20H20N2O5S: calcd. C
59.99, H 5.03, N 7.00; found C 59.95, H 5.13, N 7.11.
Typical Reaction Procedure for the Tributylphosphane-Catalyzed
Baylis؊Hillman Reaction between 2-Cyclopenten-1-one and N-(4-
Ethylphenylsulfonyl)benzaldimine: 2-Cyclopenten-1-one (42 µL,
0.5 mmol) was added at room temperature to a solution of N-(4-
ethylphenylsulfonyl)benzaldimine (144 mg, 0.5 mmol) and tributyl-
phosphane (24 µL, 0.1 mmol) in THF (1.0 mL). After the mixture
had been stirred for 5 h at room temperature, the solvent was re-
moved under reduced pressure and the residue was purified by flash
chromatography (SiO2; EtOAc/petroleum ether, 1:2) to yield 6b
(157 mg, 85%) as a colorless solid, which was recrystallized from
acetone/n-hexane (1:5).
N-[(4-Bromophenyl)(5-oxocyclopent-1-enyl)methyl]-4-methylben-
zenesulfonamide (6f): Colorless solid; m.p. 198Ϫ201 °C; 174 mg,
83%. IR (CHCl3): ν˜ ϭ 1676 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 2.12Ϫ2.48 (m, 4 H, CH2), 2.36 (s, 3 H, Me), 5.21
(d, J ϭ 8.6 Hz, 1 H, NH), 6.04 (d, J ϭ 8.6 Hz, 1 H, CH), 7.02 (d,
J ϭ 8.4 Hz, 2 H, Ar), 7.18 (d, J ϭ 8.3 Hz, 2 H, Ar), 7.30 (2 H, J ϭ
8.4 Hz, Ar), 7.31 (t, J ϭ 2.6 Hz, 1 H, ϭCH), 7.57 (d, J ϭ 8.3 Hz,
2 H, Ar) ppm. MS (EI): m/z (%) ϭ 266 (93.12) [Mϩ Ϫ 153], 264
(100) [Mϩ Ϫ 155]. C19H18BrNO3S: calcd. C 54.29, H 4.32, N 3.33;
found C 54.18, H 4.38, N 3.08.
4-Methyl-N-[(4-nitrophenyl)(5-oxocyclopent-1-enyl)methyl]benzene-
sulfonamide (6g): Pale yellow solid; m.p. 187Ϫ188 °C; 174 mg, 90%.
IR (CHCl3): ν˜ ϭ 1676 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 2.17Ϫ2.56 (m, 4 H, CH2), 2.43 (s, 3 H, Me), 5.42
(d, J ϭ 8.8 Hz, 1 H, NH), 6.27 (d, J ϭ 8.8 Hz, 1 H, CH), 7.25 (d,
J ϭ 8.2 Hz, 2 H, Ar), 7.40 (d, J ϭ 6.8 Hz, 2 H, Ar), 7.43 (t, J ϭ
2.6 Hz, 1 H, ϭCH), 7.64 (2 H, J ϭ 8.2 Hz, Ar), 8.10 (d, J ϭ 6.8 Hz,
2 H, Ar) ppm. MS (EI): m/z (%) ϭ 305 (0.73) [Mϩ Ϫ 81], 231 (100)
[Mϩ Ϫ 155]. C19H18N2O5S: calcd. C 59.06, H 4.70, N 7.25; found
C 59.30, H 4.85, N 7.25.
4-Methyl-N-[(5-oxo-cyclopent-1-enyl)(phenyl)methyl]benzenesulfon-
amide (6a): Colorless solid; m.p. 124Ϫ125 °C; 19 mg, 70%. IR
(CHCl3): ν˜ ϭ 1689 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 2.09Ϫ2.49 (m, 4 H, CH2), 2.35 (s, 3 H, Me), 5.27
(d, J ϭ 8.5 Hz, 1 H, NH), 6.02 (d, J ϭ 8.5 Hz, 1 H, CH), 7.15-
7.26 (m, 7 H, Ar), 7.35 (t, J ϭ 2.6 Hz, 1 H, ϭCH), 7.62 (2 H, J ϭ
8.2 Hz, Ar) ppm. MS (EI): m/z (%) ϭ 341 (0.03) [Mϩ], 186 (100)
[Mϩ Ϫ 155] C19H19NO3S: calcd. C 66.84, H 5.61, N 4.10; found C
66.51, H 5.69, N 3.86.
N-[(4-Ethylphenyl)(5-oxocyclopent-1-enyl)methyl]-4-methylbenzene-
sulfonamide (6b): Colorless solid; m.p. 110Ϫ111 °C; 157 mg, 85%.
IR (CHCl3): ν˜ ϭ 1676 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.17 (t, J ϭ 7.6 Hz, 3 H, Me), 2.15Ϫ2.47 (m, 4 H,
CH2), 2.35 (s, 3 H, Me), 2.57 (q, J ϭ 7.6 Hz, 2 H, CH2), 5.24 (d,
J ϭ 8.5 Hz, 1 H, NH), 6.01 (d, J ϭ 8.5 Hz, 1 H, CH), 7.04 (m, 4
H, Ar), 7.19 (2 H, J ϭ 8.2 Hz, Ar), 7.35 (t, J ϭ 2.6 Hz, 1 H, ϭ
CH), 7.59 (d, J ϭ 8.2 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 288
Typical Reaction Procedure for the Tributylphosphane-Catalyzed
Baylis؊Hillman Reaction between 2-Cyclohepten-1-one and N-(4-
Methylphenylsulfonyl)araldimine: The reaction was carried out in
the same manner as those described above, but the scale was: imine
(1.0 mmol), 2-cyclohepten-1-one (1.0 mmol), PBu3 (0.2 mmol).
exo-7-Phenyl-6-(4-tolylsulfonyl)-6-azabicyclo[3,2,2]nonan-8-one
(7a): White solid; m.p. 65Ϫ66 °C; 30 mg, 8%. IR (neat): ν˜ ϭ 1723
3676
Eur. J. Org. Chem. 2002, 3666Ϫ3679

Lewis Base Effects in the BaylisϪHillman Reaction
(CϭO), 1157 cmϪ1 1H NMR (CDCl3, TMS, 300 MHz): δ ϭ
FULL PAPER
6.06 (d, J ϭ 9.7 Hz, 1 H, CH), 6.48 (t, J ϭ 7.6 Hz, 1 H, ϭCH),
.
1.34Ϫ2.14 (m, 6 H, CH2), 2.51 (s, 3 H, CH3), 2.51Ϫ2.56 (m, 1 H), 6.91Ϫ7.01 (m, 2 H, Ar), 7.05Ϫ7.18 (m, 5 H, Ar), 7.39Ϫ7.42 (m, 1
2.71Ϫ2.83 (m, 2 H), 4.61 (m, 1 H), 4.97 (1H m), 7.37Ϫ7.42 (m, 2 H, Ar), 7.59Ϫ7.61 (m, 1 H, Ar) ppm. MS (EI): m/z (%) ϭ 369
H, Ar), 7.46Ϫ7.48 (m, 5 H, Ar), 7.67Ϫ7.70 (m, 2 H, Ar) ppm. MS
(79.71) [Mϩ Ϫ 155], 91 (100) [PhMeϩ]. C21H23NO3S: calcd. C
(EI): m/z (%) ϭ 327 (16.25) [Mϩ Ϫ 42], 250 (52.67) [Mϩ Ϫ 119], 68.26, H 6.27, N 3.79; found C 67.75, H 6.33, N 3.66.
91 (100) [PhMeϩ]. C21H23NO3S: calcd. C 68.26, H 6.27, N 3.79;
found C 67.71, H 6.30, N 3.64.
anti-4-Methyl-N-[(2-oxocyclooct-3-enyl)(phenyl)methyl]benzene-
sulfonamide (9a): White solid; m.p. 175Ϫ178 °C; 105 mg, 27%. IR
(neat): ν˜ ϭ 1662 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS, 300 MHz):
endo-7-Phenyl-6-(4-tolylsulfonyl)-6-azabicyclo[3,2,2]nonan-8-one
δ ϭ 1.23Ϫ1.88 (m, 6 H, CH2), 1.90Ϫ2.05 (m, 1 H), 2.30 (s, 3 H,
CH3), 2.59Ϫ2.67 (m, 1 H), 3.34Ϫ3.41 (m, 1 H, CH), 4.53Ϫ4.58 (m,
1 H, CH), 5.89 (d, J ϭ 12.2 Hz, 1 H, NH), 6.27Ϫ6.36 (1H, m, ϭ
CH), 6.44 (d, J ϭ 8.6 Hz, 1 H, ϭCH), 6.90Ϫ6.94 (m, 2 H, Ar),
6.95Ϫ7.08 (m, 5 H, Ar), 7.43Ϫ7.49 (m, 2 H, Ar) ppm. MS (EI):
(7a): White solid; m.p. 65Ϫ66 °C; 22 mg, 6%. IR (neat): ν˜ ϭ 1723
(CϭO), 1157 cmϪ1 1H NMR (CDCl3, TMS, 300 MHz): δ ϭ
.
1.77Ϫ2.32 (m, 6 H), 2.32 (s, 3 H, CH3), 2.43Ϫ2.51 (m, 1 H),
2.76Ϫ2.82 (m, 2 H), 4.70 (d, J ϭ 4.3 Hz, 1 H, CH), 5.26 (d, J ϭ
1.8 Hz, 1 H, CH), 6.94Ϫ6.97 (m, 2 H, Ar), 7.07Ϫ7.13 (m, 5 H,
Ar), 7.39Ϫ7.41 (m, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 327 (16.25)
m/z (%)
ϭ Ϫ
260 (30.26) [Mϩ 155], 91 (100) [PhMeϩ].
[Mϩ
Ϫ Ϫ
42], 250 (52.67) [Mϩ 119], 91 (100) [PhMeϩ].
C22H25NO3S: calcd. C 68.90, H 6.53, N 3.66; found C 68.69, H
6.81, N 3.56.
C21H23NO3S: calcd. C 68.26, H 6.27, N 3.79; found C 67.71, H
6.30, N 3.64.
syn-4-Methyl-N-[(2-oxocyclooct-3-enyl)(phenyl)methyl]ben-
zenesulfonamide (9a): White solid; m.p. 175Ϫ178 °C; 56 mg, 15%.
IR (neat): ν˜ ϭ 1662 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.23Ϫ1.90 (m, 6 H, CH2), 1.90Ϫ2.07 (m, 1 H), 2.33
(s, 3 H, CH3), 2.67Ϫ2.75 (m, 1 H), 3.30Ϫ3.34 (m, 1 H, CH),
4.46Ϫ4.53 (m, 1 H, CH), 5.36 (d, J ϭ 7.9 Hz, 1 H, NH), 5.64 (d,
J ϭ 12.8 Hz, 1 H, ϭCH), 6.16Ϫ6.21 (m, 1 H, ϭCH), 7.02Ϫ7.08
(m, 2 H, Ar), 7.30Ϫ7.32 (m, 5 H, Ar), 7.81Ϫ7.84 (m, 2 H, Ar) ppm.
MS (EI): m/z (%) ϭ 260 (30.26) [Mϩ Ϫ 155], 91 (100) [PhMeϩ].
C22H25NO3S: calcd. C 68.90, H 6.53, N 3.66; found C 68.69, H
6.81, N 3.56.
exo-7-(4-Chlorophenyl)-6-(4-tolylsulfonyl)-6-azabicyclo[3.2.2]nonan-
8-one (7b): White solid; m.p. 162Ϫ166 °C; 70 mg, 17%. IR (neat):
1
ν˜ ϭ 1723 cmϪ1 (CϭO). H NMR (CDCl3, TMS, 300 MHz): δ ϭ
1.26Ϫ2.15 (m, 6 H, CH2), 2.39 (s, 3 H, CH3), 2.45Ϫ2.53 (m, 1 H),
2.72Ϫ2.81 (m, 2 H, CH2), 4.56 (m, 1 H, CH), 4.93 (d, J ϭ 4.4 Hz,
1 H), 7.23Ϫ7.27 (m, 2 H, Ar), 7.31Ϫ7.42 (m, 4 H, Ar), 7.67Ϫ7.69
(m, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 403 (1.42) [Mϩ], 250 (100)
[Mϩ Ϫ 153], 91 (61.99) [PhMeϩ]. C21H22ClNO3S: calcd. C 62.44,
H 5.49, N 3.47; found C 62.40, H 5.86, N 3.29.
endo-7-(4-Chlorophenyl)-6-(4-tolylsulfonyl)-6-azabicyclo[3.2.2]-
nonan-8-one (7b): White solid; m.p. 162Ϫ166 °C; 20 mg, 5%. IR
(neat): ν˜ ϭ 1723 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS, 300 MHz):
δ ϭ 1.78Ϫ2.15 (m, 6 H, CH2), 2.39 (s, 3 H, CH3), 2.45Ϫ2.53 (m,
1 H), 2.73Ϫ2.80 (m, 2 H, CH2), 4.72Ϫ4.73 (m, 1 H, CH), 5.23 (d,
J ϭ 1.3 Hz, 1 H), 6.90Ϫ6.93 (m, 2 H, Ar), 7.07Ϫ7.15 (m, 4 H, Ar),
7.42Ϫ7.45 (m, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 403 (1.42) [Mϩ],
250 (100) [Mϩ Ϫ 153], 91 (61.99) [PhMeϩ]. C21H22ClNO3S: calcd.
C 62.44, H 5.49, N 3.47; found C 62.40, H 5.86, N 3.29.
anti-N-[(4-Chlorophenyl)(2-oxocyclooct-3-enyl)methyl]-4-methyl-
benzenesulfonamide (9b): White solid; m.p. 150Ϫ153 °C; 75 mg,
1
18%. IR (neat): ν˜ ϭ 1659 cmϪ1 (CϭO). H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.23Ϫ1.72 (m, 6 H, CH2), 1.87Ϫ2.05 (m, 1 H), 2.34
(s, 3 H, CH3), 2.64Ϫ2.73 (m, 1 H), 3.51Ϫ3.54 (m, 1 H, CH),
4.34Ϫ4.39 (m, 1 H, CH), 5.91 (d, J ϭ 12.2 Hz, 1 H, ϭCH),
6.31Ϫ6.40 (1H, m, ϭCH), 6.56 (d, J ϭ 8.6 Hz, 1 H, NH),
6.84Ϫ6.99 (m, 2 H, Ar), 7.01Ϫ7.13 (m, 4 H, Ar), 7.44Ϫ7.48 (m, 2
H, Ar) ppm. MS (EI): m/z (%) ϭ 418 (1.14) [Mϩ], 294 (100) [Mϩ
Ϫ 124], 91 (42.82) [PhMeϩ]. C22H24ClNO3S: calcd. C 63.22, H
5.79, N 3.35; found C 63.24, H 5.93, N 3.12.
exo-7-(4-Methoxyphenyl)-6-(4-tolylsulfonyl)-6-azabicyclo[3.2.2]-
nonan-8-one (7c): Light yellow solid: m.p. 173Ϫ174 °C; 54 mg, 13%.
IR (neat): ν˜ ϭ 1723 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.26Ϫ1.99 (m, 6 H, CH2), 2.44 (s, 3 H, CH3),
2.50Ϫ2.51 (m, 1 H), 2.68Ϫ2.76 (m, 2 H, CH2), 3.82 (s, 3 H, OCH3),
4.59Ϫ4.61 (m, 1 H, CH), 4.92 (d, J ϭ 4.2 Hz, 1 H), 7.09Ϫ7.12 (m,
2 H, Ar), 7.26Ϫ7.35 (m, 4 H, Ar), 7.66Ϫ7.69 (m, 2 H, Ar) ppm.
MS (EI): m/z (%) ϭ 399 (19.20) [Mϩ], 244 (86.24) [Mϩ Ϫ 155], 91
(100) [PhMeϩ]. C22H25NO4S·1/10CH2Cl2: calcd. C 65.13, H 6.24,
N 3.44; found C 65.17, H 6.53, N 3.25.
syn-N-[(4-Chlorophenyl)(2-oxocyclooct-3-enyl)methyl]-4-methyl-
benzenesulfonamide (9b): White solid; m.p. 150Ϫ153 °C; 50 mg,
1
12%. IR (neat): ν˜ ϭ 1659 cmϪ1 (CϭO). H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.23Ϫ1.72 (m, 6 H, CH2), 1.87Ϫ2.05 (m, 1 H), 2.36
(s, 3 H, CH3), 2.64Ϫ2.73 (m, 1 H), 3.34Ϫ3.41 (m, 1 H, CH),
4.43Ϫ4.47 (m, 1 H, CH), 5.95 (d, J ϭ 12.2 Hz, 1 H, ϭCH),
6.50Ϫ6.53 (1 H, m, ϭCH), 6.56 (d, J ϭ 8.6 Hz, 1 H, NH),
6.84Ϫ6.99 (m, 2 H, Ar), 7.01Ϫ7.13 (m, 4 H, Ar), 7.44Ϫ7.48 (m, 2
H, Ar) ppm. MS (EI): m/z (%) ϭ 418 (1.14) [Mϩ], 294 (100) [Mϩ
Ϫ 124], 91 (42.82) [PhMeϩ]. C22H24ClNO3S: calcd. C 63.22, H
5.79, N 3.35; found C 63.24, H 5.93, N 3.12.
endo-7-(4-Methoxyphenyl)-6-(4-tolylsulfonyl)-6-azabicyclo[3.2.2]-
nonan-8-one (7c): Light yellow solid: m.p. 173Ϫ174 °C; 30 mg, 7%.
IR (neat): ν˜ ϭ 1723 cmϪ1 (CϭO). 1H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.79Ϫ2.14 (m, 6 H, CH2), 2.36 (s, 3 H, CH3),
2.50Ϫ2.53 (m, 1 H), 2.74Ϫ2.82 (m, 2 H, CH2), 3.74 (s, 3 H, OCH3),
4.68Ϫ4.69 (m, 1 H,CH), 5.22 (d, J ϭ 1.3 Hz, 1 H), 6.62Ϫ6.66 (m,
2 H, Ar), 6.87Ϫ6.94 (m, 4 H, Ar), 7.39Ϫ7.41 (m, 2 H, Ar) ppm.
MS (EI): m/z (%) ϭ 399 (19.20) [Mϩ], 244 (86.24) [Mϩ Ϫ 155, 91
(100) [PhMeϩ]. C22H25NO4S·1/10CH2Cl2: calcd. C 65.13, H 6.24,
N 3.44; found C 65.17, H 6.53, N 3.25.
anti-N-[(4-Methoxyphenyl)(2-oxocyclooct-3-enyl)methyl]-4-methyl-
benzenesulfonamide (9c): White solid: m.p. 135Ϫ138 °C; 120 mg,
1
29%. IR (neat): ν˜ ϭ 1656 cmϪ1 (CϭO). H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.41Ϫ1.64 (m, 6 H, CH2), 1.89Ϫ1.98 (m, 1 H), 2.34
(s, 3 H, CH3), 2.64Ϫ2.67 (m, 1 H), 3.34Ϫ3.38 (m, 1 H, CH), 3.72
(s, 3 H, OCH3), 4.39Ϫ4.43 (m, 1 H, CH), 5.90 (d, J ϭ 12.8 Hz, 1
H, ϭCH), 6.27Ϫ6.37 (1H, m, ϭCH), 6.27Ϫ6.37 (m, 1 H, NH),
4-Methyl-N-[(7-oxocyclohept-1-enyl)(phenyl)methyl]benzenesulfon- 6.58Ϫ6.60 (m, 2 H, Ar), 6.87Ϫ6.91 (m, 2 H, Ar), 6.91Ϫ7.05 (m, 2
amide (8a): White solid; m.p. 109Ϫ110 °C; 100 mg, 27%. IR (neat): H, Ar), 7.43Ϫ7.46 (m, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 376
ν˜ ϭ 1660 cmϪ1 (CϭO). H NMR (CDCl3, TMS, 300 MHz): δ ϭ (8.09) [Mϩ Ϫ 37], 290 (100) [Mϩ Ϫ 123], 91 (95.10) [PhMeϩ].
1.26Ϫ2.04 (m, 6 H, CH2), 2.11Ϫ2.31 (m, 2 H, CH2), 2.33 (s, 3 H, C23H27NO4S: calcd. C 66.80, H 6.58, N 3.39; found C 65.33, H
1
CH3), 2.95Ϫ3.17 (m, 1 H, CH2), 5.06 (d, J ϭ 9.4 Hz, 1 H, NH), 6.72, N 3.44.
Eur. J. Org. Chem. 2002, 3666Ϫ3679
3677

M. Shi, Y.-M. Xu, G.-L. Zhao, X.-F. Wu
FULL PAPER
Table 11. Crystal data of syn-3b, exo-5d, exo-7a, 9b, 10c and 12b ((AUTHOR: If 9b is orthorhombic, β is by definition 90° [not 90(2)°];
please check! Is 12b really monoclinic or is it orthorhombic; how significant is the β value? Please check!))
syn-3b
exo-5d
exo-7a
9b
10c
12b
Empirical formula
Formula mass
Temperature [K]
Crystal system
Lattice type
C19H18O3
294.13
293(2)
triclinic
primitive
C21H23O4NS
385.48
293(2)
orthorhombic
primitive
C21H21O3NS
367.45
293(2)
monoclinic
primitive
C22H24ClO3NS
417.93
293(2)
orthorhombic
primitive
C23H28ClO4NS
449.98
293(2)
triclinic
primitive
C29H27Cl2O3NS
540.48
293(2)
monoclinic
primitive
Unit cell dimensions
˚
a [A]
12.0362(9)
12.4221(8)
14.2841(10)
65.6880
89.3970
65.9370
7.935(3)
10.593(3)
22.562(2)
90
90
90
1896(1)
Pna21
4
1.350
816.00
11.8564811)
6.4710(6)
12.2722(11)
90
94.886(2)
90
938.14(15)
Pna2(1)
2
7.7059(10)
11.4103(14)
24.388(3)
90
90
90
2144.3(5)
Pna2(1)
4
1.295
880.00
11.8173(19)
12.932(2)
15.095(3)
85.122(3)
89.983
12.642(2)
6.7653(10)
31.543(5)
90
90
90
2697.8(7)
P21/c
4
1.221
1128.00
˚
b [A]
˚
c [A]
α [°]
β [°]
γ [°]
89.923
3
˚
V [A ]
1745.1(2)
2298.6(6)
¯
¯
Space group
Ze
P1
P1
3
2
Dcalcd. [g/cm3]
F(000)
1.273
704.00
1.301
388.00
1.300
952
syn-N-[(4-Methoxyphenyl)(2-oxocyclooct-3-enyl)methyl]-4-methyl- CH), 5.32 (d, J ϭ 8.4 Hz, 1 H, NH), 6.58Ϫ6.64 (m, 2 H, Ar),
benzenesulfonamide (9c): White solid: m.p. 135Ϫ138 °C; 82 mg, 6.76Ϫ6.91 (m, 2 H, Ar), 7.04Ϫ7.10 (m, 2 H, Ar), 7.44Ϫ7.49 (m, 2
20%. IR (neat): ν˜ ϭ 1656 cmϪ1 (CϭO). H NMR (CDCl3, TMS, H, Ar) ppm. MS (EI): m/z (%) ϭ 290 (100) [Mϩ Ϫ 155], 91 (75.76)
300 MHz): δ ϭ 1.41Ϫ1.75 (m, 6 H, CH2), 1.89Ϫ1.98 (m, 1 H), 2.29
[PhMeϩ]. C24H31NO5S: calcd. C 64.69, H 7.01, N 3.14; found C
1
(s, 3 H, CH3), 2.54Ϫ2.69 (m, 1 H), 3.31Ϫ3.40 (m, 1 H, CH), 3.66 64.72, H 7.04, N 3.05.
(s, 3 H, OCH3), 4.47Ϫ4.53 (m, 1 H, CH), 5.68 (d, J ϭ 12.8 Hz, 1
N-[(3-Benzylidene-2-oxocyclooct-4-enyl)(phenyl)methyl]-4-methyl-
benzenesulfonamide (12a): m.p. 208Ϫ210 °C; 188 mg, 40%. IR
(KBr): ν˜ ϭ 1674 (CϭO), 1584, 1215 cmϪ1 1H NMR (CDCl3,
H, ϭCH), 6.19Ϫ6.27 (m, 1 H, ϭCH), 6.27Ϫ6.37 (m, 1 H, NH),
6.83Ϫ6.87 (m, 2 H, Ar), 7.05Ϫ7.10 (m, 2 H, Ar), 7.30Ϫ7.33 (m, 2
H, Ar), 7.81Ϫ7.84 (m, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 376
(8.09) [Mϩ Ϫ 37], 290 (100) [Mϩ Ϫ 123], 91 (95.10) [PhMeϩ].
C23H27NO4S: calcd. C 66.80, H 6.58, N 3.39; found C 65.33, H
6.72, N 3.44.
.
TMS, 300 MHz): δ ϭ 1.30Ϫ1.45 (m, 1 H, CH2), 1.80Ϫ2.0 (m, 3
H, CH2), 2.12Ϫ2.42 (m, 2 H, CH2), 2.33 (s, 3 H, CH3), 3.42 (t, J ϭ
11.4 Hz, 1 H, CH), 4.37 (t, J ϭ 9.1 Hz, 1 H, CH), 5.05 (d, J ϭ
9.1 Hz, 1 H, CH), 5.85Ϫ6.0 (m, 1 H, ϭCH), 6.07 (s, 1 H, ϭCH),
6.10 (d, J ϭ 9.1 Hz, 1 H, NH), 6.79 (d, J ϭ 8.6 Hz, 2 H, Ar),
6.98Ϫ7.12 (m, 6 H, Ar), 7.20Ϫ7.30 (m, 4 H, Ar), 7.48 (d, J ϭ
8.6 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 454 [Mϩ Ϫ 17].
C29H29NO3S: calcd. C 73.86, H 6.20, N 2.97; found C 73.72, H
6.24, N 2.88.
N-[(4-Methoxy-2-oxocyclooctyl)(phenyl)methyl]-4-methylbenzene-
sulfonamide (10a): Colorless, oily compound; 22 mg, 6%; 187 mg,
1
45%. IR (neat): ν˜ ϭ 1698 cmϪ1 (CϭO). H NMR (CDCl3, TMS,
300 MHz): δ ϭ 1.27Ϫ1.94 (m, 8 H, CH2), 2.34Ϫ2.51 (m, 2 H,
CH2), 2.36 (s, 3 H, CH3), 2.79Ϫ2.80(m, 1 H, CH), 3.29 (s, 3 H,
OCH3), 3.55Ϫ3.56 (m, 1 H, CH), 4.39Ϫ4.44 (m, 1 H, CH), 6.18
(d, J ϭ 8.6 Hz, 1 H, NH), 7.01Ϫ7.16 (m, 7 H, Ar), 7.46Ϫ7.49 (m,
2 H, Ar) ppm. MS (EI): m/z (%) ϭ 260 (100) [Mϩ Ϫ 155], 155
(43.69) [Mϩ Ϫ 260], 91 (53.18) [PhMeϩ]. HRMS: calcd. for
C16H21NO2 [Mϩ Ϫ 156] 259.1572; found 259.1603.
N-[(3-Chlorobenzylidene-2-oxocyclooct-4-enyl](4-chlorophenyl)-
methyl]-4-methylbenzenesulfonamide (12b): M.p. 204Ϫ206 °C;
184 mg, 34%. IR (KBr): ν˜ ϭ 1674 (CϭO), 1496, 1216 cmϪ1 1H
.
NMR (CDCl3, 300 MHz, TMS): δ ϭ 1.30Ϫ1.45 (m, 1 H, CH2),
1.72Ϫ2.0 (m, 3 H, CH2), 2.12Ϫ2.42 (m, 2 H, CH2), 2.37 (s, 3 H,
CH3), 3.41 (t, J ϭ 11.4 Hz, 1 H, CH), 4.37 (t, J ϭ 9.1 Hz, 1 H,
CH), 5.29 (d, J ϭ 9.1 Hz, 1 H, CH), 5.85Ϫ6.0 (m, 1 H, ϭCH),
6.02 (s, 1 H, ϭCH), 6.10 (d, J ϭ 9.1 Hz, 1 H, NH), 6.79 (d, J ϭ
8.6 Hz, 2 H, Ar), 6.98Ϫ7.12 (m, 6 H, Ar), 7.20Ϫ7.30 (m, 4 H, Ar),
7.48 (d, J ϭ 8.6 Hz, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 384 [Mϩ
Ϫ 156]. C29H27Cl2NO3S: calcd. C 64.44, H 5.04, N 2.59; found C
64.42, H 4.99, N 2.52.
N-[(4-Chlorophenyl)(4-methoxy-2-oxocyclooctyl)methyl]-4-methyl-
benzenesulfonamide (10b): Colorless solid; m.p. 136Ϫ140 °C;
230 mg, 51%. IR (neat): ν˜ ϭ 1698 cmϪ1 (CϭO). 1H NMR (CDCl3,
TMS, 300 MHz): δ ϭ 1.33Ϫ1.93 (m, 8 H, CH2), 2.20Ϫ2.46 (m, 2
H), 2.35 (s, 3 H, CH3), 2.68Ϫ2.76 (m, 1 H, CH), 3.28 (s, 3 H,
OCH3), 3.49Ϫ3.57 (m, 1 H, CH), 4.34Ϫ4.39 (m, 1 H, CH), 5.96
(d, J ϭ 7.9 Hz, 1 H, NH), 6.92Ϫ6.95 (m, 2 H, Ar), 7.08Ϫ7.12 (m,
4 H, Ar), 7.43Ϫ7.46 (m, 2 H, Ar) ppm. MS (EI): m/z (%) ϭ 433
(0.21) [Mϩ Ϫ 15], 294 (35.86) [Mϩ Ϫ 155], 91 (100) [PhMeϩ].
C23H28ClNO4S: calcd. C 61.39, H 6.27, N 3.11; found C 61.06, H
6.42, N 3.26.
X-ray Crystal Data: Diffractometer: Rigaku AFC7R. syn-3b: R,
Rw: 0.0762, 0.2311; CCDC-176795. exo-5d: R, Rw: 0.062, 0.063;
CCDC-165558. exo-7a: R, Rw: 0.0459, 0.0763; CCDC-175594. 9b:
R, Rw: 0.0561, 0.1263; CCDC-175595. 10c: R, Rw: 0.0467, 0.0566;
CCDC-193516. 12b: R, Rw: 0.0442, 0.0516; CCDC-175596. The
CCDC numbers refer to the supplementary crystallographic
N-[(4-Methoxy-2-oxocyclooctyl)(4-methoxyphenyl)methyl]-4-
methylbenzenesulfonamide (10c): Light yellow solid; m.p. 65Ϫ67 °C;
196 mg, 44%. IR (neat): ν˜ ϭ 1702 cmϪ1 (CϭO). 1H NMR (CDCl3,
TMS, 300 MHz): δ ϭ 1.24Ϫ1.83 (m, 8 H, CH2), 2.02Ϫ2.32 (m, 2 data for this paper. These data can be obtained free of
H), 2.36 (s, 3 H, CH3), 2.68 (m, 1 H, CH), 3.26 (s, 3 H, OCH3), charge at www.ccdc.cam.ac.uk/conts/retrieving.html or from the
3.39Ϫ3.42 (m, 1 H, CH), 3.73 (s, 3 H, OCH3) 4.36Ϫ4.42 (m, 1 H, Cambridge Crystallographic Data Centre, 12 Union Road, Cam-
3678
Eur. J. Org. Chem. 2002, 3666Ϫ3679

Lewis Base Effects in the BaylisϪHillman Reaction
FULL PAPER
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of China for financial support (20025206). We also thank the Inoue
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Received April 19, 2002
[O02216]
Eur. J. Org. Chem. 2002, 3666Ϫ3679
3679