Highly Efficient aza-Baylis-Hillman Reaction of N-Tosylated Imines with MVK, Acrolein, and Phenyl Acrylate or α-Naphthyl Acrylate: Lewis Base Effects and A Convenient Method to Synthesize α,β-Unsaturated β-Amino Carbonyl Compounds

Article abstract of DOI:10.1021/jo035103p

This paper describes several highly efficient aza-Baylis-Hillman reactions of N-tosylated imines with MVK, acrolein, and phenyl acrylate or α-naphthyl acrylate in the presence of a Lewis base. In most cases, the reaction can be completed within 1 h using

Full text of DOI:10.1021/jo035103p

High ly Efficien t a za -Ba ylis-Hillm a n Rea ction of N-Tosyla ted
Im in es w ith MVK, Acr olein , a n d P h en yl Acr yla te or r-Na p h th yl
Acr yla te: Lew is Ba se Effects a n d A Con ven ien t Meth od to
Syn th esize r,â-Un sa tu r a ted â-Am in o Ca r bon yl Com p ou n d s
Yong-Mei Xu and Min Shi*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
mshi@pub.sioc.ac.cn
Received J uly 29, 2003
This paper describes several highly efficient aza-Baylis-Hillman reactions of N-tosylated imines
with MVK, acrolein, and phenyl acrylate or R-naphthyl acrylate in the presence of a Lewis base.
In most cases, the reaction can be completed within 1 h using the appropriate Lewis base catalyst.
An efficient method to synthesize â-amino ketones, aldehydes and esters in high yields and short
reaction time has been developed.
In tr od u ction
electron-donating groups such as Et or MeO on the
benzene ring, with some Michael acceptors such as
methyl vinyl ketone (MVK) or methyl acrylate, either the
reactions were sluggish or no reactions occurred under
the traditional Baylis-Hillman reaction conditions. How-
ever, our previous investigations disclosed that, using
N-tosylated imines to replace arylaldehydes, the aza-
Baylis-Hillman reaction can be accelerated to some
extent to provide â-amino carbonyl compounds in higher
yields compared with their arylaldehydes in the presence
of nitrogen or phosphine Lewis base catalyst (Scheme
1).6,7
According to the generally accepted mechanism of the
Baylis-Hillman reaction,1,2 we attempted to vary the
structures of the Michael acceptors and nucleophilic
Lewis base catalysts in order to allow the ammonium or
phosphonium enolates to be formed more easily. By this
protocol, the zwitterionic ammonium or phosphonium
The Baylis-Hillman reaction, notorious for its poor
reaction rate, is an important carbon-carbon bond-
forming process that affords densely functionalized prod-
ucts. This reaction is generally catalyzed by Lewis bases
such as tertiary amines or phosphines [DABCO (1,4-
diazabicyclic[2,2,2]octane) or triphenylphosphine (PPh3)].1
A plausible mechanism for this reaction was previously
proposed in which the addition of ammonium or phos-
phonium enolate to an electrophile is believed to be the
rate-determining step.2 Efforts to accelerate the reaction
rate have been explored, including chemical methods3
and physical techniques.4 During our own investigations
on this very simple and useful reaction,5 we found that
in the reaction of arylaldehydes, especially having the
(1) (a) Baylis, A. B.; Hillman, M. E. D. Ger. Offen. 1972, 2,155,113;
Chem. Abstr. 1972, 77, 34174q; Hillman, M. E. D.; Baylis, A. B. U.S.
Patent, 1973, 3, 743, 669. (b) Morita, K.; Suzuki, Z.; Hirose, H. Bull.
Chem. Soc. J pn. 1968, 41, 2815-2819. For reviews, see: (c) Basavaiah,
D.; Rao, P. D.; Hyma, R. S. Tetrahedron 1996, 52, 8001-8062. (d)
Drewes, S. E.; Roo, G. H. P. Tetrahedron 1988, 44, 4653-4670. (e)
Ciganek, E. Org. React. 1997, 51, 201-350. (f) Langer, P. Angew.
Chem., Int. Ed. 2000, 39, 3049-3052. (g) Basavaiah, D.; Rao, A. J .;
Satyanarayana, T. Chem. Rev. 2003, 103, 811-892.
(2) Hill, J . S.; Issacs, N. S. J . Phys. Org. Chem. 1990, 44, 285-292.
(3) (a) Rafel, S.; Leahy, J . W. J . Org. Chem. 1997, 62, 1521-1522.
(b) Aggarwal, V. K.; Tarver, G. J .; McCague, R. Chem. Commun. 1996,
2713-2714. (c) Aggarwal, V. K.; Mereu, A.; Tarver, G. J .; McCague,
R. J . Org. Chem. 1998, 63, 7183-7189. (d) Aggarwal, V. K.; Dean, D.
K.; Mereu, A.; Williams, R. J . Org. Chem. 2002, 67, 510-514. (e)
Aggarwal, V. K.; Mereu, A. Chem. Commun. 1999, 2311-2312. (f)
Hayase, T.; Shibata, T.; Soai, K.; Wakatsuki, Y. Chem. Commun. 1998,
1271-1272. (g) Barrett, A. G. M.; Cook, A. S.; Kamimura, A. Chem.
Commun. 1998, 2533-2534. (h) Kawamura, M.; Kobayashi, S. Tetra-
hedron Lett. 1999, 40, 1539-1542. (i) Basavaiah, D.; Kumaraguruba-
ran, N. Tetrahedron Lett. 2001, 42, 477-479. (j) Lee, W. D.; Yang, K.
S.; Chen, K. Chem. Commun. 2001, 1612-1613. (k) Yu, C. Z.; Liu, B.;
Hu, L. Q. J . Org. Chem. 2001, 66, 5413-5418. (l) Li, G.-G.; Wei, H.-
X.; Gao, J .-J .; Caputo, T. D. Tetrahedron Lett. 2000, 41, 1-3. (m) Li,
G.-G.; Gao, J .-J .; Wei, H.-X.; Enright, M. Org. Lett. 2000, 2, 617-619
and references therein. (n) Iwamura, T.; Fujita, M.; Kawakita, T.;
Kinoshita, S.; Watanabe, S.-I.; Kataoka, T. Tetrahedron 2001, 57,
8455-8461 and references therein.
(4) (a) J enner, G. High-Pressure Res. 1999, 16, 243-252. (b) Kun,
M. K.; Mukherjee, S. B.; Balu, N.; Padmakumar, R.; Bhat, S. V. Synlett
1994, 444-446. (c) Roos, G. H. P.; Padmakumar, R. Synth. Commun.
1993, 23, 1261-1266. (d) Isaacs, N. S. Tetrahedron 1991, 47, 8463-
8497.
(5) (a) Shi, M.; J iang, J .-K.; Feng, Y.-S. Org. Lett. 2000, 2, 2397-
2400. (b) Shi, M.; Feng, Y.-S. J . Org. Chem. 2001, 66, 406-411. (c)
Shi, M.; Li, C.-Q.; J iang, J .-K. Chem. Commun. 2001, 833-834.
(6) (a) Shi, M.; Xu, Y.-M. Chem. Commun. 2001, 1876-1877. (b) Shi,
M.; Xu, Y.-M. Eur. J . Org. Chem. 2002, 696-701. (c) Shi, M.; Xu, Y.-
M.; Zhao, G.-L.; Wu, X.-F. Eur. J . Org. Chem. 2002, 3666-3679. (d)
Shi, M.; Zhao, G.-L. Tetrahedron Lett. 2002, 43, 4499-4502. (e) Shi,
M.; Xu, Y.-M. J . Org. Chem. 2003, 68, 4784-4790. (f) Shi, M.; Xu, Y.
M. Angew. Chem., Int. Ed. 2002, 41, 4507-4510. (g) Shi, M.; Chen, L.
H. Chem. Commun. 2003, 1310-1311.
(7) The following reports relate to the aza-Baylis-Hillman reaction
of methyl acrylate with sulfonated imines. Please see: (a) Perlmutter,
P.; Teo, C. C. Tetrahedron Lett. 1984, 25, 5951-5952. (b) Takagi, M.;
Yamamoto, K. Tetrahedron 1991, 47, 8869-8871. (c) Campi, E. M.;
Holmes, A.; Perlmutter, P.; Teo, C. C. Aust. J . Chem. 1995, 48, 1535-
1540. The following reports relate to the aza-Baylis-Hillman reaction
of MVK with imine generated in situ. Please see: (c) Bertenshow, S.;
Kahn, M. Tetrahedron Lett. 1989, 30, 2731-2734. (d) Balan, D.;
Adolfsson, H. J . Org. Chem. 2002, 67, 2329-2334 and references
therein.
10.1021/jo035103p CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/16/2003
J . Org. Chem. 2004, 69, 417-425
417

Xu and Shi
TABLE 2. a za -Ba ylis-Hillm a n Rea ction of N-Tosyla ted
Im in es 1 (0.5 equ iv) w ith Meth yl Vin yl Keton e 2a (1.0
equ iv)
SCHEME 1
TABLE 1. a za -Ba ylis-Hillm a n Rea ction of
N-Ben zylid en e-4-m eth ylben zen esu lfon a m id e 1a (0.5
equ iv) w ith MVK 2a (1.0 equ iv) in th e P r esen ce of
Va r iou s Lew is Ba ses
entry
R1
time (min) product yield (%) of 3a
1
2
3
4
5
6
p-ClC6H4 (1b)
m-FC6H4 (1c)
p-MeC6H4 (1d )
p-NO2C6H4 (1e)
p-CH3OC6H4 (1f)
2,3-Cl2C6H3 (1g)
30
30
45
30
50
35
3b
3c
3d
3e
3f
77
78
88
67
87
63
3g
a
Yield of isolated product.
entry
catalyst (10 mol %)
time (h)
yield (%) of 3a a
1
2
3
4
5
6
7
8
9
DMAP
DABCO
PPh3
22
22
24
2
0.75
2
9
48
48
30
45
72
b
80
b
65
c
c
base in THF.8 For example, treatment of N-benzylidene-
4-methylbenzenesulfonamide 1a with MVK in the pres-
ence of PPh2Me (10 mol %) provided the desired product
3a in 80% yield within 45 min under the same conditions
(entry 5 in Table 1). At higher reaction temperature (>30
°C), the polymerization of MVK was observed and the
aza-Baylis-Hillman adduct 3a was formed in lower yield.
The use of stronger Lewis bases such as PBu3 or PhPMe2
gave the pyrrolidine derivatives without the formation
of the corresponding normal aza-Baylis-Hillman adduct
3 (entries 4 and 6 in Table 1).6b Using PtBu3 or P(o-Tol)3
as a Lewis base, no reaction occurred under the same
conditions because the sterically bulky tert-butyl or o-tolyl
group around the phosphine atom diminished the nu-
cleophilicity of the tertiary phosphine and therefore
reduced its catalytic ability as a Lewis base to initiate
the aza-Baylis-Hillman reaction (entries 8 and 9 in
Table 1). Thus, PPh2Me is the best Lewis base for this
version of aza-Baylis-Hillman reaction.
We then examined the aza-Baylis-Hillman reaction
of other N-tosylated aromatic imines (0.5 equiv) with
MVK 2a (1.0 equiv) under the optimized conditions. The
results are summarized in Table 2. As can be seen from
Table 2, similar results were observed, and the aza-
Baylis-Hillman adducts 3 were obtained in very high
yields. The substituents on the benzene ring of N-
tosylated aromatic imines have little effect on the reac-
tion rate. Specifically, when N-(4-methoxybenzylidene)-
4-methylbenzenesulfonamide 1f was used as the substrate,
this version of the aza-Baylis-Hillman reaction can be
finished within 50 min in 87% yield as well (entry 5 in
Table 2).
PBu3
Ph2PMe
PhPMe2
dppe
PBut
3
P(o-Tol)3
Yields of isolated product. Other products were obtained.6b
a
b
c No reaction occurred.
enolate species, generated from the Michael addition of
a nucleophilic Lewis base to an R,â-unsaturated enone,
can be maintained in higher concentration in the reaction
solution, which may shift the equilibrium forward to
accomplish the nucleophilic attack of the formed enolate
species to the electrophile, giving the Baylis-Hillman
adduct. As a result, the reaction rate can be accelerated.
Herein we wish to report several highly efficient aza-
Baylis-Hillman reactions of N-tosylated imines 1 with
R,â-unsaturated aldehydes, ketones, and esters 2 in the
presence of appropriate Lewis base catalysts to give â′-
amino-R,â-unsaturated carbonyl compounds in good yields.
Most of these aza-Baylis-Hillman reactions can be
accomplished within 1 h.
Resu lts a n d Discu ssion
During our careful investigations, we found that this
type of aza-Baylis-Hillman reaction is extremely sensi-
tive to temperatures, solvents, and Lewis base catalysts.
First, we examined the reaction of N-benzylidene-4-
methylbenzenesulfonamide 1a (R1 ) Ph) (0.5 equiv) with
methyl vinyl ketone (MVK) 2a (R2 ) Me) (1.0 equiv)
under various reaction conditions. A variety of Lewis base
catalysts (10 mol %) were examined, and the results are
summarized in Table 1. The use of tertiary amines such
as 4-N,N-(dimethylamino)pyridine (DMAP) or DABCO as
a Lewis base gave the corresponding aza-Baylis-Hillman
adduct 3a in 30% or 45% yield, respectively, after 22 h
at room temperature (20 °C) (entries 1 and 2 in Table
1). Tertiary phosphines can more efficiently catalyze this
reaction. For example, Lewis base Ph3P gave the normal
aza-Baylis-Hillman adduct 3a in 72% yield after 24 h
(entry 3 in Table 1). The use of 1,2-bis(diphenylphos-
phino)ethane (dppe) as a Lewis base afforded a similar
result (entry 7 in Table 1). A significant rate acceleration
was observed when PPh2Me was employed as a Lewis
This result stimulated us to seek out other versions of
fast aza-Baylis-Hillman reactions using other Michael
acceptors. Therefore, we selected the more active Michael
acceptor acrolein 2b (R2 ) H) as the substrate. After
screening of various Lewis base catalysts as the proce-
dures shown in Table 1, we found that the aza-Baylis-
Hillman reactions of N-benzylidene-4-methylbenzene-
sulfonamide 1a (0.5 equiv) with acrolein 2b (1.0 equiv)
in THF in the presence of DABCO (10 mol %) at room
temperature gave the corresponding aza-Baylis-Hillman
adduct 4a in 80% yield within 50 min. To further
determine the feasibility of this catalytic system, various
(8) The solvent effect has been examined throughout this report.
THF is the best choice of solvent for various Lewis base catalysts.
418 J . Org. Chem., Vol. 69, No. 2, 2004

aza-Baylis-Hillman Reaction of N-Tosylated Imines
TABLE 3. a za -Ba ylis-Hillm a n Rea ction of N-Tosyla ted
Im in es 1 (0.5 equ iv) w ith Acr olein 2b (10 equ iv)
TABLE 4. a za -Ba ylis-Hillm a n Rea ction of
N-Ben zylid en e-4-m eth ylben zen esu lfon a m id e 1a (0.5
equ iv) w ith Meth yl Acr yla te 2c (1.0 equ iv)
entry
R1
time (min) product yield (%) of 4b
entry
catalyst
temp (°C)
time (h)
yield (%)a
1
2
3
4
5
6
7
8
9
C6H5 (1a )
50
25
4a
4b
4c
4d
4e
4f
80
83
82
43
77
82
88
89
91
p-ClC6H4 (1b)
p-CH3C6H4 (1d )
p-NO2C6H4 (1e)
p-CH3OC6H4 (1f)
m-ClC6H4 (1h )
p-BrC6H4 (1i)
p-FC6H4 (1j)
1
2
3
4
5
6
7
8c
Ph3P
rt
40
40
rt
rt
rt
24
40
48
24
10
6
Ph3Pb
120
30
180
20
Ph3P
DABCO
PBu3
PPh2Me
PPhMe2
DABCO
63
25
30
90
4g
4h
4i
62
43
73
rt
rt
4
15
p-EtC6H4 (1k )
a
a
b
i
Isolated yields. The reaction was carried out in PrOH. c N-
(4-Chlorobenzylidene)-4-methylbenzenesulfonamide 1b was used,
and the product was 5b.
All reactions were conducted using 2:1 molar ratio of acrolein
b
and N-tosylimine in THF at room temperature. Isolated yields
based on the imine.
N-tosylated imines 1 were also examined under the
optimal conditions. Most of the N-tosylated imines 1 gave
the desired adducts in good to excellent yields within a
short reaction time, although the substituents on the
benzene ring of 1 have some effects on the reaction rate.
This is because, as can be seen from Table 3, when the
benzene ring of the N-tosylated imines 1 has electron-
withdrawing groups, the reactions can be finished within
30 min (entries 2, 4, 6-8 in Table 3). On the other hand,
the reaction time has to be prolonged to 2 or 3 h if the
electron-donating substituents are present on the ben-
zene ring of 1 (entries 1, 3, 5, 9 in Table 3). In the aza-
Baylis-Hillman reaction of 1e, which has the strongest
electron-withdrawing nitro group on the benzene ring,
with 2b, we found that 1e decomposed rapidly and the
corresponding aza-Baylis-Hillman adduct 4d was ob-
tained in 43% yield along with many unidentified prod-
ucts under the same conditions (Table 1, entry 4). In
addition, it should be emphasized here that in this type
of aza-Baylis-Hillman reaction, the reaction furnished
complicated products and none of the corresponding
normal aza-Baylis-Hillman adduct 4 was formed if using
PPh3, PBu3, or PPh2Me as a Lewis base promoter.
Furthermore, we also attempted the aza-Baylis-Hill-
man reaction of N-benzylidene-4-methylbenzenesulfona-
mide 1a with various acrylates. This was done because
we also want to find a version of an efficient aza-Baylis-
Hillman reaction to prepare â-amino esters. First, we
used methyl acrylate 2c (R2) OMe) (1.0 equiv) as the
Michael acceptor to react with N-benzylidene-4-methyl-
benzenesulfonamide 1a (0.5 equiv) in the presence of
various Lewis base catalysts (10 mol %). The results are
presented in Table 4. In the aza-Baylis-Hillman reaction
of N-benzylidene-4-methylbenzenesulfonamide 1a with
methyl acrylate 2c, the tertiary phosphine Lewis base
catalyst PPh3 did not give the corresponding aza-Baylis-
Hillman adduct 5a , although the solvent was changed
and the reaction temperature was raised (entries 1-3 in
Table 4). Tributylphosphine also showed no catalytic
activity for this aza-Baylis-Hillman reaction (entry 5 in
Table 4). Using tertiary nitrogen Lewis base DABCO as
a catalyst, the corresponding aza-Baylis-Hillman adduct
5a was obtained in 63% yield after 24 h (entry 4 in Table
4). Introducing an electron-withdrawing group such as
Cl on the benzene ring of N-tosylated imine 1 slightly
improved the reaction rate in the presence of DABCO
but did not significantly affect the outcome of this aza-
Baylis-Hillman reaction (Table 4, entry 8). Using PPh2-
Me or PhPMe2 as the catalyst, the reaction was some-
what accelerated to give 5a in 62% yield after 6 h or in
43% after 4 h, respectively (entries 6 and 7 in Table 4).
However, the achieved yields and reaction rates are still
not satisfactory enough.
Previously, Chen and co-workers reported that, using
phenyl acrylate 2d (R2 ) OPh) or R-naphthyl acrylate
2e [R2 ) O(R-Nap)] as a Michael acceptor, the Baylis-
Hillman reaction with aldehydes can be significantly
accelerated in the presence of DABCO (30 mol %).3j
Encouraged by this result, we exchanged methyl acrylate
with more reactive phenyl acrylate 2d as a Michael
acceptor (1.0 equiv) for the above aza-Baylis-Hillman
reaction with 1a (0.5 equiv). We delightfully found that
in the presence of PPh2Me (10 mol %) or DABCO (30 mol
%) the desired aza-Baylis-Hillman adduct 6a was ob-
tained in 94% yield in THF after 30 min or in 81% yield
in MeCN after 40 min, respectively (entries 1 and 2 in
Table 5). The phosphine Lewis base PPh2Me is also more
effective than DABCO in the aza-Baylis-Hillman reac-
tion of N-(4-chlorobenzylidene)-4-methylbenzenesulfona-
mide 1b (0.5 equiv) or N-(4-methoxybenzylidene)-4-
methylbenzenesulfonamide 1f (0.5 equiv) with phenyl
acrylate 2d (1.0 equiv) (entries 3, 4 and 8, 9 in Table 5).
The results are summarized in Table 5. Similar results
were obtained for other N-tosylated imines 1 using PPh2-
Me (10 mol %) as a catalyst under the optimal reaction
conditions. Using R-naphthyl acrylate 2e as a Michael
acceptor under the same conditions, the corresponding
aza-Baylis-Hillman adducts 6k -m were also obtained
in good yields within 30 min (Scheme 2). The aza-Baylis-
Hillman reaction was accelerated dramatically using
phenyl acrylate 2d or R-naphthyl acrylate 2e as a
Michael acceptor, and most of the corresponding aza-
Baylis-Hillman adducts 6 were obtained in good to
excellent yields within 1 h (Table 5 and Scheme 2).
The effect of Lewis bases in the aza-Baylis-Hillman
reaction has been throughout studied in this Article. If
the catalytic activities of the employed Lewis base
catalysts and the reactivities of Michael acceptors match,
the Baylis-Hillman reaction can proceed very well to
J . Org. Chem, Vol. 69, No. 2, 2004 419

Xu and Shi
TABLE 5. a za -Ba ylis-Hillm a n Rea ction of N-Tosyla ted
Im in es 1 (0.5 equ iv) w ith P h en yl Acr yla te 2d (1.0 equ iv)
SCHEME 3
entry
R1
time (min) product yield (%) of 6a
1
2
3
4
5
6
7
8
C6H5 (1a )
C6H5 (1a )
30
40
25
25
40
45
15
30
100
30
35
25
60
6a
6a
6b
6b
6c
6d
6e
6f
6f
6g
6h
6i
94
81b
90
84b
90
88
71
96
57b
74
92
90
84
p-ClC6H4 (1b)
p-ClC6H4 (1b)
m-FC6H4 (1c)
p-MeC6H4 (1d )
p-NO2C6H4 (1e)
p-CH3OC6H4 (1f)
p-CH3OC6H4 (1f)
2,3-Cl2C6H3 (1g)
p-EtC6H4 (1k )
m-CH3C6H4 (1l)
2-furyl (1m )
SCHEME 4
9
10
11
12
13
6j
a
b
Isolated yield. Using DABCO (30 mol %) as a catalyst in
CH3CN.
SCHEME 2
reduced by LiAlH4 to give the corresponding γ-amino
alcohol 7 in 89% yield. The amino alcohol 7 was trans-
formed to the Boc-protected amino alcohol 8 by reaction
with di-tert-butyl dicarbonate [(Boc)2O] and DMAP in
dichloromethane in 99% yield. Treatment of the obtained
amino alcohol 8 with Mg/MeOH resulted in the selective
removal of the N-tosyl substituent,9 and the Boc-
protected amino alcohol 9 was isolated in 82% yield.
Thus, the N-tosyl group has been changed to the syn-
thetically more useful Boc group because the Boc protect-
ing group can be easily removed by various methods
(Scheme 3).
In 2002, Tewari and co-workers reported a convenient
synthesis of C-nucleoside 11 analogues by cyclic amida-
tion of 10 catalyzed by DBU, tert-butylammonium bro-
mide (TBAB), and 4 Å molecular sieves (Scheme 4).10 We
intended to convert, under similar conditions, the aza-
Baylis-Hillman adducts 5 and 6 derived by reaction of
N-tosylated imines with acrylates to â-lactams, which are
more important synthetic intermediates in organic chem-
istry. However, under the reported reaction conditions,
we found that the aza-Baylis-Hillman adducts 5b and
6a were stereoselectively transformed to the correspond-
ing methyl (2E)-3-(4-chlorophenyl)-2-[(toluene-4-sulfony-
lamino)methyl]acrylate 12 and phenyl (2E)-3-phenyl-2-
[(toluene-4-sulfonylamino)methyl]acrylate 13 in good
yields.11 The structure of 12 was determined by X-ray
diffraction (Figure 1).12 On the basis of further investiga-
give the corresponding aza-Baylis-Hillman adducts in
high yields and with a short reaction time (30-60 min).
Moreover, the results obtained in the aza-Baylis-Hill-
man reaction of methyl vinyl ketone, acrolein, phenyl
acrylate, and R-naphthyl acrylate with N-tosylated imi-
nes 1 suggest that when the Michael acceptor is more
reactive (e.g., acrolein), less nucleophilic Lewis base
should be selected as a catalyst (e.g., DABCO). For the
less reactive Michael acceptor such as MVK, phenyl
acrylate, or R-naphthyl acrylate, the aza-Baylis-Hillman
adducts can also be obtained in higher yields within a
short reaction time if a stronger nucleophilic Lewis base
(e.g., PPh2Me) is employed as a catalyst. In general, PPh2-
Me accelerates the reaction rate more efficiently than
DABCO in the aza-Baylis-Hillman reaction (Table 1,
Table 4, entries 1, 2 and 3, 4 and 8, 9 in Table 5).
On the other hand, in the aza-Baylis-Hillman reaction
of aliphatic N-tosylated imines with MVK, acrolein, or
phenyl acrylate, under similar reaction conditions, none
of the corresponding normal aza-Baylis-Hillman adduct
was formed and the reaction usually gave complicated
products.
If the N-tosyl group of these aza-Baylis-Hillman
adducts (â′-amino-R,â-unsaturated aldehydes, ketones,
and esters) could be easily removed, the synthetic utility
of these amino adducts could be expanded. However, the
N-tosyl group is usually very difficult to be removed. In
Scheme 3, we presented the further potential synthetic
application of this adduct by a preparation of γ-amino
alcohol via reduction of the aza-Baylis-Hillman adduct
and removal of the N-tosyl group. The aza-Baylis-
Hillman adduct 4c derived from the aza-Baylis-Hillman
reaction of N-tosylated imine with acrolein was first
(9) J uhl, K.; Gathergood. N.; J φrgenson, A. K. Angew. Chem., Int.
Ed. 2001, 40, 2995-2997.
(10) Tewari, N.; Mishra, R. C.; Tiwari, V. K.; Tripathi, R. P. Synlett
2002, 11, 1779-1782.
(11) The reaction of the Baylis-Hillman acetate with amines of
N-sulfonated amines in the presence of K2CO3 has been previously
reported. See: (a) Kim, J . N.; Kim, H. S.; Gong, J . H.; Chung, Y. M.
Tetrahedron Lett. 2001, 42, 8341-8344. (b) Chung, Y. M.; Lee, H. J .;
Hwang, S. S.; Kim, J . N. Bull. Korean Chem. Soc. 2001, 22, 799-805.
(c) Kim, J . N.; Chung, Y. M.; Im, Y. J . Tetrahedron Lett. 2002, 43,
6209-6212.
420 J . Org. Chem., Vol. 69, No. 2, 2004

aza-Baylis-Hillman Reaction of N-Tosylated Imines
of these aza-Baylis-Hillman adducts have been disclosed
in this paper. Therefore, a highly efficient synthetic
method to prepare R-methylene-â-amino carbonyl com-
pounds in good to excellent yields has been established.
We believe that the pronounced acceleration of the rate
in these reactions further extends the aza-Baylis-Hill-
man reaction into a viable transformation and allows the
Baylis-Hillman reaction to be qualified as one of the
efficient synthetic reactions. Further studies on applica-
tions of these aza-Baylis-Hillman reaction products are
underway.
Exp er im en ta l Section
All of the N-tosylated imines were prepared according to
the literature.13 The spectroscopic data for compounds 3a -g
shown in Tables 1 and 2 have been reported in our previous
paper.6b
Typ ica l Rea ction P r oced u r e for P P h 2Me (Meth yl-
d ip h en ylp h osp h in e)-Ca ta lyzed a za -Ba ylis-Hillm a n Re-
a ction of Meth yl Vin yl Keton e w ith N-Ben zylid en e-4-
m eth ylben zen esu lfon a m id e. To a solution of N-benzylidene-
4-methylbenzsulfonamide 1a (129 mg, 0.5 mmol) and PPh2Me
(9 µL, 0.05 mmol) in THF (1.0 mL) at room temperature was
added methyl vinyl ketone 2a (70 µL, 1.0 mmol), and the
reaction mixture was further stirred at room temperature. The
reaction was monitored by a TLC plate. When the N-tosylated
imine disappeared, the solvent was removed under reduced
pressure, and the residue was purified by a flash column
chromatography (SiO2, EtOAc/petroleum ether ) 1:5) to yield
3a (132 mg, 80%) as a colorless solid.
F IGURE 1. ORTEP drawing of 12.
tions, we found that this reaction can also be carried out
by only using a catalytic amount of DBU (0.3 equiv)
(Scheme 5). This transformation can provide a convenient
method to the preparation of quinoline derivatives.11
Typ ica l Rea ction P r oced u r e for DABCO-Ca ta lyzed
a za -Ba ylis-Hillm a n Rea ction of Acr olein w ith N-Ben z-
ylid en e-4-m eth ylben zen esu lfon a m id e. To a solution of
N-benzylidene-4-methylbenzsulfonamide 1a (129 mg, 0.5 mmol)
and DABCO (6 mg, 0.05 mmol) in THF (1.0 mL) at room
temperature was added acrolein 2b (67 µL, 1.0 mmol), and
the reaction mixture was further stirred at room temperature.
The reaction was monitored by a TLC plate. When the
N-tosylated imine disappeared, the solvent was removed under
reduced pressure, and the residue was purified by a flash
column chromatography (SiO2, EtOAc/petroleum ether ) 1:5)
to yield 4a (126 mg, 80%) as a colorless solid.
N-(2-F or m yl-1-p h en yla llyl)-4-m eth yl Ben zen esu lfon a -
m id e (4a ). A colorless solid: mp 107-108 °C; IR (CHCl3) ν
1690 cm-1 (CdO); 1H NMR (CDCl3, TMS, 300 MHz) δ 2.46
(3H, s, Me), 5.26 (1H, d, J ) 8.1 Hz), 5.49 (1H, d, J ) 8.1 Hz),
6.12 (1H, s), 6.54 (1H, s), 7.06-7.09 (2H, m, Ar), 7.19-7.22
(3H, m, Ar), 7.25 (2H, d, J ) 8.7 Hz, Ar), 7.66 (2H, d, J ) 8.7
Con clu sion
Usually the Baylis-Hillman reaction, which possesses
the two most important requirements, atom economy and
generation of functional groups, is a slow reaction requir-
ing a few days to a few weeks for completion depending
upon the reactivities of both activated alkene and elec-
trophile.1 In this paper, we have found several highly
efficient aza-Baylis-Hillman reactions by the appropri-
ate combination of Michael acceptors and Lewis base
promoters. Most of these aza-Baylis-Hillman reactions
of N-tosylated imines with R,â-unsaturated enones re-
ported can be accomplished within 1 h. These presented,
to the best our knowledge, are the best rate acceleration
systems in the aza-Baylis-Hillman reactions under mild
reaction conditions. Moreover, several transformations
SCHEME 5. Tr a n sfor m a tion of a za -Ba ylis-Hillm a n Ad d u cts 5 a n d 6
J . Org. Chem, Vol. 69, No. 2, 2004 421

Xu and Shi
Hz, Ar), 9.39 (1H, s); 13C NMR (CDCl3, 75.4 MHz) δ 21.5, 56.7,
126.7, 127.2, 127.9, 128.6, 129.5, 135.9, 137.1, 138.0, 143.5,
148.0, 192.8; MS (EI) m/e 314 (M+ - 1, 4.05), 91 (PhMe+, 100).
Anal. Calcd for C17H17NO3S requires C, 64.76; H, 5.39; N, 4.44.
Found: C, 64.77; H, 5.53; N, 4.33.
ClNO3S requires C, 58.37; H, 4.61; N, 4.00. Found: C, 58.45;
H, 4.51; N, 4.13.
N-[2-F or m yl-1-(4-b r om op h en yl)a llyl]-4-m et h yl Ben -
zen esu lfon a m id e (4g). A colorless solid (172 mg, 88%): mp
106-107 °C; IR (CHCl3) ν 1690 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 2.45 (3H, s, Me), 5.25 (1H, d, J ) 8.3 Hz),
5.56 (1H, d, J ) 8.3 Hz), 6.14 (1H, s), 6.53 (1H, s), 7.00 (2H, d,
J ) 8.4 Hz, Ar), 7.27 (2H, d, J ) 8.5 Hz, Ar), 7.36 (2H, d, J )
8.4 Hz, Ar), 7.65 (2H, d, J ) 8.5 Hz, Ar), 9.40 (1H, s); 13C NMR
(CDCl3, 75.4 MHz) δ 21.5, 56.0, 121.9, 127.1, 128.5, 129.6,
131.6, 136.1, 136.9, 137.1, 143.7, 147.6, 192.7; MS (EI) m/e 339
N-[2-F or m yl-1-(4-ch lor op h en yl)a llyl]-4-m et h yl Ben -
zen esu lfon a m id e (4b). A colorless solid (144 mg, 83%): mp
101-102 °C; IR (CHCl3) ν 1691 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 2.46 (3H, s, Me), 5.26 (1H, d, J ) 8.6 Hz),
5.62 (1H, d, J ) 8.6 Hz), 6.12 (1H, s), 6.52 (1H, s), 7.04 (2H, d,
J ) 8.4 Hz, Ar), 7.19 (2H, d, J ) 8.4 Hz, Ar), 7.25 (2H, d, J )
8.6 Hz, Ar), 7.64 (2H, d, J ) 8.6 Hz, Ar), 9.38 (1H, s); 13C NMR
(CDCl3, 75.4 MHz) δ 21.4, 56.2, 127.1, 128.1, 128.7, 129.5,
133.8, 136.0, 136.5, 137.0, 143.7, 147.6, 192.7; MS (EI) m/e 294
(M+ - 55, 3.39), 337 (M+ - 57, 3.15). Anal. Calcd for C17H16
-
BrNO3S requires C, 51.79; H, 4.09; N, 3.55. Found: C, 51.90;
H, 4.27; N, 3.48.
(M+ - 55, 15.60), 194 (M+ - 155, 100). Anal. Calcd for C17H16
-
N-[2-F or m yl-1-(4-flu or op h en yl)a llyl]-4-m et h yl Ben -
zen esu lfon a m id e (4h ). A colorless solid (148 mg, 89%): mp
135-136 °C; IR (CHCl3) ν 1690 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 2.42 (3H, s, Me), 5.26 (1H, d, J ) 7.8 Hz),
5.61 (1H, d, J ) 7.8 Hz), 6.12 (1H, s), 6.52 (1H, s), 6.90 (2H,
dd, J ) 8.4, 8.3 Hz, Ar), 7.07 (2H, dd, J ) 8.3, 5.8 Hz, Ar),
7.25 (2H, d, J ) 8.4 Hz, Ar), 7.64 (2H, d, J ) 8.4 Hz, Ar), 9.38
(1H, s); 13C NMR (CDCl3, 75.4 MHz) δ 21.4, 55.6, 115.3 (d,
ClNO3S requires C, 58.37; H, 4.61; N, 4.01. Found: C, 58.57;
H, 4.84; N, 3.90.
N-[2-F or m yl-1-(4-m et h ylp h en yl)a llyl]-4-m et h yl Ben -
zen esu lfon a m id e (4c). A colorless solid (135 mg, 82%): mp
108-109 °C; IR (CHCl3) ν 1691 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 2.26 (3H, s, Me), 2.41 (3H, s, Me), 5.22 (1H,
d, J ) 8.0 Hz), 5.45 (1H, d, J ) 8.0 Hz), 6.10 (1H, s), 6.53 (1H,
s), 6.93 (2H, d, J ) 8.2 Hz, Ar), 7.01 (2H, d, J ) 8.2 Hz, Ar),
7.23 (2H, d, J ) 8.4 Hz, Ar), 7.64 (2H, d, J ) 8.4 Hz, Ar), 9.41
(1H, s). 13C NMR (CDCl3, 75.4 MHz) δ 21.0, 21.5, 56.6, 126.6,
127.3, 129.3, 129.5, 135.1, 135.8, 137.1, 137.8, 143.5, 148.2,
192.9; MS (EI) m/e 274 (M+ - 55, 7.41), 174 (M+ - 155, 100).
Anal. Calcd for C18H19NO3S requires C, 65.65; H, 5.78; N, 4.26.
Found: C, 65.80; H, 5.50; N, 4.09.
J C-F ) 21.2 Hz), 127.0, 128.4, 128.5, 129.4, 133.8 (d, J C-F
)
2.5 Hz), 136.3 (d, J C-F ) 79.5 Hz), 143.6, 147.8, 162.0 (d, J C-F
) 242.5 Hz), 192.7; MS (EI) m/e 278 (M+ - 55, 4.51), 178 (M+
- 155, 82.25). Anal. Calcd for C17H16FNO3S requires C, 61.25;
H, 4.84; N, 4.20. Found: C, 61.36; H, 5.05; N, 4.12.
N-[2-F or m yl-1-(4-et h ylp h en yl)a llyl]-4-m et h yl
Ben -
zen esu lfon a m id e (4i). A colorless solid (156 mg, 91%): mp
N-[2-F or m yl-1-(4-n it r op h en yl)a llyl]-4-m et h yl
Ben -
1
90-92 °C; IR (CHCl3) ν 1689 cm-1 (CdO); H NMR (CDCl3,
zen esu lfon a m id e (4d ). A colorless solid (77 mg, 43%): mp
144-145 °C; IR (CHCl3) ν 1692 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 2.40 (3H, s, Me), 5.39 (1H, d, J ) 8.7 Hz),
6.14 (1H, s), 6.19 (1H, d, J ) 8.7 Hz), 6.52 (1H, s), 7.21 (2H, d,
J ) 7.8 Hz, Ar), 7.31 (2H, d, J ) 8.4 Hz, Ar), 7.63 (2H, d, J )
8.4 Hz, Ar), 8.02 (2H, d, J ) 7.8 Hz, Ar), 9.35 (1H, s); 13C NMR
(CDCl3, 75.4 MHz) δ 21.5, 56.1, 123.6, 127.0, 127.7, 129.6,
136.8, 136.9, 144.0, 145.3, 146.8, 147.2, 192.5; MS (EI) m/e 205
(M+ - 155, 4.62), 130 (M+ - 230, 20.82), 91 (M+ - 269, 100).
Anal. Calcd for C17H16N2O5S requires C, 56.66; H, 4.47; N, 7.77.
Found: C, 56.60; H, 4.39; N, 7.72.
TMS, 300 MHz) δ 1.18 (3H, t, J ) 7.6 Hz, Me), 2.42 (3H, s,
Me), 2.56 (2H, q, J ) 7.6 Hz, CH2), 5.25 (1H, d, J ) 8.3 Hz),
5.51 (1H, d, J ) 8.3 Hz), 6.11 (1H, s), 6.56 (1H, s), 6.97 (2H, d,
J ) 8.2 Hz, Ar), 7.01 (2H, d, J ) 8.2 Hz, Ar), 7.24 (2H, d, J )
8.4 Hz, Ar), 7.65 (2H, d, J ) 8.4 Hz, Ar), 9.40 (1H, s); 13C NMR
(CDCl3, 75.4 MHz) δ 15.4, 21.5, 28.3, 56.6, 126.6, 127.2, 128.1,
129.5, 135.2, 135.8, 135.8, 137.0, 143.5, 144.1, 148.0, 193.0;
MS (EI) m/e 288 (M+ - 55, 8.23), 188 (M+ - 155, 100). Anal.
Calcd for C19H21BNO3S requires C, 66.45; H, 6.16; N, 4.08.
Found: C, 66.54; H, 6.34; N, 3.89.
N-[2-F or m yl-1-(4-m eth oxyp h en yl)a llyl]-4-m eth yl Ben -
zen esu lfon a m id e (4e). A colorless solid (132 mg, 77%): mp
120-122 °C; IR (CHCl3) ν 1689 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 2.44 (3H, s, Me), 3.76 (3H, s, Me), 5.22 (1H,
d, J ) 7.8 Hz), 5.37 (1H, d, J ) 7.8 Hz), 6.12 (1H, s), 6.57 (1H,
s), 6.75 (2H, d, J ) 8.8 Hz, Ar), 6.98 (2H, d, J ) 8.8 Hz, Ar),
7.27 (2H, d, J ) 8.5 Hz, Ar), 7.66 (2H, d, J ) 8.5 Hz, Ar), 9.41
(1H, s); 13C NMR (CDCl3, 75.4 MHz) δ 21.5, 55.2, 56.3, 114.0,
127.3, 128.0, 129.5, 130.1, 135.7, 137.1, 143.5, 148.2, 159.2,
193.0; MS (EI) m/e 290 (M+ - 55, 7.64), 190 (M+ - 155, 100).
Anal. Calcd for C18H19NO4S requires C, 62.59; H, 5.54; N, 4.06.
Found: C, 62.80; H, 5.71; N, 3.97.
Typ ica l Rea ction P r oced u r e for P P h 2Me (Meth yl-
d ip h en ylp h osp h in e)-Ca ta lyzed a za -Ba ylis-Hillm a n Re-
a ction of Meth yl Acr yla te w ith N-Ben zylid en e-4-m eth -
ylben zen e Su lfon a m id e. To a solution of N-benzylidene-4-
methylbenzenesulfonamide 1a (129 mg, 0.5 mmol) and
methyldiphenylphosphine (9 µL, 0.05 mmol) in THF (1.0 mL)
at room temperature was added methyl acrylate (89 mg, 0.60
mmol), and the reaction mixture was further stirred at room
temperature. The reaction was monitored by TLC plate. When
the N-tosylated imine disappeared, the solvent was removed
under reduced pressure, and the residue was purified by a
flash column chromatography (SiO2, EtOAc/petroleum ether
) 1:5) to yield 5a (108 mg, 63%) as a colorless solid.
N-[2-F or m yl-1-(3-ch lor op h en yl)a llyl]-4-m et h yl Ben -
zen esu lfon a m id e (4f). A colorless solid (142 mg, 82%): mp
112-114 °C; IR (CHCl3) ν 1691 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 2.49 (3H, s, Me), 5.32 (1H, d, J ) 8.1 Hz),
5.65 (1H, d, J ) 8.1 Hz), 6.20 (1H, s), 6.57 (1H, s), 7.06-7.09
(2H, m, Ar), 7.22-7.25 (2H, m, Ar), 7.32 (2H, d, J ) 8.7 Hz,
Ar), 7.70 (2H, d, J ) 8.7 Hz, Ar), 9.45 (1H, s); 13C NMR (CDCl3,
75.4 MHz) δ 21.5, 56.5, 124.8, 126.9, 127.2, 128.1, 129.6, 129.9,
134.5, 136.3, 137.0, 140.0, 143.8, 147.4, 192.7; MS (EI) m/e 294
Meth yl 2-[P h en yl-(tolu en e-4-su lfon yla m in o)m eth yl]-
a cr yla te (5a ). This is an known compound:7c a colorless oil,
IR (CHCl3) ν 1708 cm-1 (CdO), 1633 cm-1 (CdC); 1H NMR
(CDCl3, TMS, 300 MHz) δ 2.40 (3H, s, Me), 3.60 (3H, s, Me),
5.29 (1H, d, J ) 9.2 Hz, NH), 5.65 (1H, d, J ) 9.2 Hz), 5.83
(1H, s), 6.22 (1H, s), 7.13 (2H, m, Ar), 7.21 (3H, m, Ar), 7.67
(2H, d, J ) 8.6 Hz, Ar); MS (EI) m/e 314 (M+ - 31, 1.94), 190
(M+ - 155, 100.00), 155 (SO2PhMe+, 67.94); HRMS calcd for
(M+ - 56, 4.34), 194 (M+ - 156, 100). Anal. Calcd for C17H16
-
C
17H16NO3S requires 314.0859 (M+ - OCH3), found 314.0890.
Meth yl 2-[(4-Ch lor op h en yl)-(tolu en e-4-su lfon yla m i-
(12) The X-ray data of 12 has been deposited in CCDC with number
215232. Empirical formula: C18H18NO4SCl. Formula weight: 379.84.
Crystal color, habit: colorless, prismatic. Crystal dimensions: 0.456
× 0.226 × 0.203 mm3. Crystal system: triclinic. Lattice type: primitive.
Lattice parameters: a ) 7.679(4) Å, b ) 8.422(5) Å, c ) 14.216(8) Å,
R ) 97.700(10)°, â ) 91.157(10)°, γ ) 90.604(9)°, V ) 910.8(8) Å3. Space
group: P-1. Z value ) 2; Dcalc ) 1.385 g/cm3; F000 ) 396; µ(Mo KR) )
1.98 cm-1. Diffractometer: Rigaku AFC7R. Residuals: R, Rw: 0.0942,
0.2726.
n o)m eth yl]a cr yla te (5b). This is an known compound:7c
a
colorless solid, mp 105-106 °C; IR (CHCl3) ν 1713 cm-1
1
(CdO); H NMR (CDCl3, TMS, 300 MHz) δ 2.42 (3H, s, Me),
3.62 (3H, s, Me), 5.27 (1H, d, J ) 9.2 Hz, NH), 5.76 (1H, d, J
) 9.2 Hz, CH), 5.80 (1H, s), 6.21 (1H, s), 7.09 (2H, d, J ) 8.6
Hz, Ar), 7.19 (2H, d, J ) 8.6 Hz, Ar), 7.23 (2H, d, J ) 8.6 Hz,
Ar), 7.65 (2H, d, J ) 8.6 Hz, Ar); MS (EI) m/e 348 (M+ - 31,
2.52), 225 (M+ - 155, 100), 91 (PhMe+, 13.95). Anal. Calcd for
(13) Love, B. E.; Raje, P. S. Synlett 1994, 493.
422 J . Org. Chem., Vol. 69, No. 2, 2004

aza-Baylis-Hillman Reaction of N-Tosylated Imines
18H18ClNO4S requires C, 56.99; H, 4.78; N, 3.69%; Found C,
C
126.1, 127.0, 129.3, 129.6, 130.3, 137.0, 137.4, 143.8, 145.6,
147.1, 149.8, 163.3; MS (EI): m/e 359 (M+ - 93, 9.48), 155
(M+ - 297, 38.73). Anal. Calcd for C23H20N2O6S requires C,
61.05; H, 4.45; N, 6.19%, Found: C, 61.06; H, 4.51; N, 6.05.
57.21; H, 4.62; N, 3.60.
Typ ica l Rea ction P r oced u r e for P P h 2Me (Meth yl-
d ip h en ylp h osp h in e)-Ca ta lyzed a za -Ba ylis-Hillm a n Re-
a ction of P h en yl Acr yla te w ith N-Ben zylid en e-4-m eth -
ylben zen e Su lfon a m id e. To a solution of N-benzylidene-4-
methylbenzenesulfonamide 1a (129 mg, 0.5 mmol) and
methyldiphenylphosphine (9 µL, 0.05 mmol) in THF (1.0 mL)
at room temperature was added phenyl acrylate (89 mg, 0.60
mmol), and the reaction mixture was further stirred at room
temperature. The reaction was monitored by TLC plate. When
the N-tosylated imine disappeared, the solvent was removed
under reduced pressure, and the residue was purified by a
flash column chromatography (SiO2, EtOAc/petroleum ether
) 1:5) to yield 6a (192 mg, 94%) as a colorless solid.
P h en yl 2-[(4-Meth oxyp h en yl)-(tolu en e-4-su lfon yla m i-
n o)m eth yl]a cr yla te (6f). A colorless solid (209 mg, 96%): mp
1
95-96 °C; IR (CHCl3) ν 1731 cm-1 (CdO); H NMR (CDCl3,
TMS, 300 MHz) δ 2.42 (3H, s, Me), 3.88 (3H, s, Me), 5.35 (1H,
d, J ) 8.8 Hz), 5.46 (1H, d, J ) 8.8 Hz), 6.08 (1H, s), 6.49 (1H,
s), 6.76 (2H, d, J ) 8.8 Hz, Ar), 6.87 (2H, d, J ) 7.3 Hz. Ar),
7.07 (2H, d, J ) 8.8 Hz, Ar), 7.18-7.35 (5H, m, Ar), 7.71 (2H,
d, J ) 7.3 Hz, Ar); 13C NMR (CDCl3, 75.4 MHz) δ 21.5, 55.2,
58.4, 114.0, 121.3, 126.0, 127.2, 127.8, 128.8, 129.3, 129.5,
130.4, 137.4, 138.6, 143.5, 150.1, 159.2, 163.9; MS (EI) m/e 345
(M+ - 92, 11.07), 281 (M+ - 156, 4.18). Anal. Calcd for C24H23
-
NO5S requires C, 65.90; H, 5.26; N, 3.20. Found: C, 65.80; H,
5.36; N, 3.22.
P h en yl 2-[P h en yl-(tolu en e-4-su lfon yla m in o)m eth yl]-
a cr yla te (6a ). A colorless solid: mp 107-108 °C; IR (CHCl3)
1
ν 1650 cm-1 (CdO); H NMR (CDCl3, TMS, 300 MHz) δ 2.40
P h en yl 2-[(2,3-Dich lor oph en yl)-(tolu en e-4-su lfon ylam i-
n o)m eth yl]a cr yla te (6g). A viscous liquid (176 mg, 74%): IR
(CHCl3) ν 1735 cm-1 (CdO); 1H NMR (CDCl3, TMS, 300 MHz)
δ 2.36 (3H, s, Me), 5.72 (1H, d, J ) 8.7 Hz), 5.88 (1H, d, J )
8.7 Hz), 6.13 (1H, s), 6.59 (1H, s), 6.94 (2H, d, J ) 7.8 Hz, Ar),
7.08 (1H, dd, J ) 8.2, 7.8 Hz, Ar), 7.16-7.38 (7H, m, Ar), 7.65
(2H, d, J ) 8.2 Hz, Ar); 13C NMR (CDCl3, 75.4 MHz) δ 21.3,
55.6, 121.2, 125.9, 127.0, 127.2, 129.2, 129.3, 129.7, 130.3,
131.2, 133.2, 136.7, 137.5, 137.5, 138.1, 143.5, 150.0, 163.6;
MS (EI) m/e 382 (M+ - 94, 35.43), 155 (TolSO2+, 90.16); HRMS
Calcd for C23H19Cl2NO4S requires 475.0412. Found: 475.0405.
(3H, s, Me), 5.46 (1H, d, J ) 8.4 Hz), 5.76 (1H, s), 5.91 (1H, d,
J ) 8.4 Hz), 6.13 (1H, s), 7.19-7.25 (7H, m, Ar), 7.36-7.42
(2H, m, Ar), 7.50-7.56 (3H, m, Ar), 7.72 (2H, d, J ) 8.7 Hz,
Ar); 13C NMR (CDCl3, 75.4 MHz) δ 21.5, 58.8, 121.3, 126.0,
126.6, 127.2, 127.9, 128.6, 129.1, 129.3, 129.5, 137.5, 138.4,
138.6, 143.4, 150.1, 163.8; MS (EI) m/e 276 (M+ - 131, 5.94),
252 (M+ - 155 100). Anal. Calcd for C23H21NO4S requires C,
67.81; H, 5.16; N, 3.44. Found: C, 67.83; H, 5.37; N, 3.48.
P h en yl 2-[(4-Ch lor oph en yl)-(tolu en e-4-su lfon ylam in o)-
m eth yl]a cr yla te (6b). A colorless solid (199 mg, 90%): mp
108-110 °C; IR (CHCl3) ν 1729 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 2.42 (3H, s, Me), 5.38 (1H, d, J ) 9.1 Hz),
5.71 (1H, d, J ) 9.1 Hz), 6.04 (1H, s), 6.49 (1H, s), 6.88 (2H, d,
J ) 8.8 Hz, Ar), 7.12 (2H, d, J ) 8.8 Hz, Ar), 7.20-7.36 (7H,
m, Ar), 7.68 (2H, d, J ) 8.5 Hz, Ar); 13C NMR (CDCl3, 75.4
MHz) δ 21.5, 58.3, 121.2, 126.1, 127.1, 128.0, 128.7, 129.4,
129.5, 129.6, 133.7, 137.0, 137.3, 138.2, 143.6, 150.0, 163.7;
MS (EI) m/e 441 (M+ - 1, 3.55), 155 (TolSO2+ - 1, 100). Anal.
Calcd for C23H20ClNO4S requires C, 62.66; H, 4.54; N, 3.17.
Found: C, 62.66; H, 4.61; N, 3.04.
P h en yl 2-[(4-Eth ylp h en yl)-(tolu en e-4-su lfon yla m in o)-
m eth yl]a cr yla te (6h ). A colorless solid (200 mg, 92%): mp
1
77-79 °C; IR (CHCl3) ν 1732 cm-1 (CdO); H NMR (CDCl3,
TMS, 300 MHz) δ 1.18 (3H, t, J ) 7.7 Hz, CH3), 2.42 (3H, s,
Me), 2.58 (2H, q, J ) 7.8 Hz, CH2), 5.37 (1H, d, J ) 8.7 Hz),
5.49 (1H, d, J ) 8.7 Hz), 6.08 (1H, s), 6.50 (1H, s), 6.87 (2H, d,
J ) 8.7 Hz, Ar), 7.03-7.13 (4H, m, Ar), 7.19-7.34 (5H, m, Ar),
7.70 (2H, d, J ) 8.2 Hz, Ar); 13C NMR (CDCl3, 75.4 MHz) δ
15.8, 21.8, 28.7, 58.9, 121.6, 126.3, 126.9, 127.5, 128.4, 129.2,
129.6, 129.8, 135.9, 137.7, 139.0, 143.7, 144.3, 150.4, 164.2;
MS (EI) m/e 343 (M+ - 92, 45.03), 155 (TolSO2+, 34.93). Anal.
Calcd for C25H25NO4S requires C, 68.97; H, 5.75; N, 3.22.
Found: C, 68.97; H, 5.94; N, 3.20.
P h en yl 2-[(3-Flu or op h en yl)-(tolu en e-4-su lfon yla m in o)-
m eth yl]a cr yla te (6c). A colorless solid (192 mg, 90%): mp
107-109 °C; IR (CHCl3) ν 1733 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 2.39 (3H, s, Me), 5.39 (1H, d, J ) 8.7 Hz),
5.71 (1H, d, J ) 8.7 Hz), 6.04 (1H, s), 6.50 (1H, s), 6.89-7.00
(5H, m, Ar), 7.19-7.36 (6H, m, Ar), 7.70 (2H, d, J ) 8.2 Hz,
P h en yl 2-[(3-Meth ylph en yl)-(tolu en e-4-su lfon ylam in o)-
m eth yl]a cr yla te (6i). A colorless solid (190 mg, 90%): mp
1
82-84 °C; IR (CHCl3) ν 1732 cm-1 (CdO); H NMR (CDCl3,
Ar); 13C NMR (CDCl3, 75.4 MHz) δ 21.5, 58.4, 113.7 (d, J C-F
)
TMS, 300 MHz) δ 2.25 (3H, s, Me), 2.43 (3H, s, Me), 5.37 (1H,
d, J ) 9.0 Hz), 5.49 (1H, d, J ) 9.0 Hz), 6.10 (1H, s), 6.51 (1H,
s), 6.85-6.90 (3H, m, Ar), 6.94 (1H, d, J ) 6.5 Hz, Ar), 7.04
(1H, d, J ) 6.5 Hz, Ar), 7.12-7.36 (6H, m, Ar), 7.71 (2H, d, J
) 8.1 Hz, Ar); 13C NMR (CDCl3, 75.4 MHz) δ 21.6, 21.8, 59.0,
121.6, 123.9, 126.3, 127.5, 127.7, 128.8, 128.9, 129.0, 129.2,
129.6, 129.8, 137.7, 138.6, 139.2, 143.7, 150.4, 164.2; MS (EI)
m/e 328 (M+ - 94, 72.34), 157 (TolSO2+ + 2, 100). Anal. Calcd
for C24H23NO4S requires C, 68.39; H, 5.50; N, 3.32. Found: C,
68.15; H, 5.68; N, 3.42.
0.3 Hz), 114.8 (d, J C-F ) 0.3 Hz), 121.2, 122.1 (d, J C-F ) 0.04
Hz), 126.1, 127.1, 129.5 (d, J C-F ) 0.2 Hz), 129.7, 130.2 (d,
J C-F ) 0.1 Hz), 137.3, 138.0, 140.9, 141.0, 143.7, 150.0, 162.7
(d, J C-F ) 3.3 Hz), 163.6; MS (EI) m/e 332 (M+ - 93, 42.44),
+
155 (TolSO2 - 1, 83.82). Anal. Calcd for C23H20FNO4S
requires C, 64.94; H, 4.71; N, 3.29. Found: C, 64.96; H, 5.10;
N, 3.24.
P h en yl 2-[(4-Meth ylph en yl)-(tolu en e-4-su lfon ylam in o)-
m eth yl]a cr yla te (6d ). A colorless solid (186 mg, 88%): mp
1
93-94 °C; IR (CHCl3) ν 1730 cm-1 (CdO); H NMR (CDCl3,
P h en yl 2-[Fu r an -2-yl-(tolu en e-4-su lfon ylam in o)m eth yl]-
a cr yla te (6j). A colorless solid (166 mg, 84%): mp 120-122
°C; IR (CHCl3) ν 1732 cm-1 (CdO); 1H NMR (CDCl3, TMS, 300
MHz) δ 2.41 (3H, s, Me), 5.50 (1H, d, J ) 9.1 Hz), 5.65 (1H, d,
J ) 9.1 Hz), 6.05 (1H, s), 6.10-6.16 (2H, m, Ar), 6.50 (1H, s),
6.95 (2H, d, J ) 8.2 Hz, Ar), 7.18-7.39 (6H, m, Ar), 7.72 (2H,
d, J ) 8.2 Hz, Ar); 13C NMR (CDCl3, 75.4 MHz) δ 21.8, 53.5,
107.9, 110.9, 121.6, 126.3, 127.4, 129.7, 129.8, 130.1, 137.0,
137.6, 142.6, 143.8, 150.4, 151.1, 163.9; MS (EI) m/e 304 (M+
TMS, 300 MHz) δ 2.32 (3H, s, Me), 2.44 (3H, s, Me), 5.38 (1H,
d, J ) 8.7 Hz), 5.54 (1H, d, J ) 8.7 Hz), 6.11 (1H, s), 6.52 (1H,
s), 6.89 (2H, d, J ) 7.5 Hz, Ar), 7.04-7.07 (4H, m, Ar), 7.22-
7.37 (5H, m, Ar), 7.73 (2H, d, J ) 8.4 Hz, Ar); 13C NMR (CDCl3,
75.4 MHz) δ 21.3, 21.8, 58.7, 121.6, 126.2, 126.9, 127.5, 129.1,
129.6, 129.6, 129.8, 135.8, 137.8, 137.9, 139.1, 143.7, 150.5,
164.2; MS (EI) m/e 328 (M+ - 94, 34.25), 157 (TolSO2 + 2,
+
100). Anal. Calcd for C24H23NO4S requires C, 68.39; H, 5.50;
N, 3.32. Found: C, 68.41; H, 5.58; N, 3.10.
- 93, 61.06), 242 (M+ - 155, 74.69). Anal. Calcd for C21H19
-
NO5S requires C, 63.48; H, 4.79; N, 3.53. Found: C, 63.28; H,
4.88; N, 3.45.
P h en yl 2-[(4-Nitr op h en yl)-(tolu en e-4-su lfon yla m in o)-
m eth yl]a cr yla te (6e). A colorless solid (148 mg, 71%): mp
122-124 °C; IR (KCl) ν 1730.4 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 2.42 (3H, s, Me), 5.48 (1H, d, J ) 9.1 Hz),
5.87 (1H, d, J ) 9.1 Hz), 6.06 (1H, s), 6.53 (1H, s), 6.87-6.90
(2H, m, Ar), 7.23-7.37 (5H, m, Ar), 7.43 (2H, d, J ) 8.7 Hz,
Ar), 7.70 (2H, d, J ) 8.7 Hz, Ar), 8.12 (2H, dd, J ) 8.7, 2.0 Hz,
Ar); 13C NMR (CDCl3, 75.4 MHz) δ 21.3, 58.2, 121.0, 123.5,
r-Naph th yl2-[P h en yl-(tolu en e-4-su lfon ylam in o)m eth yl]-
a cr yla te (6k ). A colorless solid: mp 152-154 °C; IR (CHCl3)
1
ν 1735 cm-1 (CdO); H NMR (CDCl3, TMS, 300 MHz) δ 2.43
(3H, s, Me), 5.52 (1H, d, J ) 8.8 Hz), 5.54 (1H, d, J ) 8.8 Hz),
6.18 (1H, s), 6.66 (1H, s), 7.03 (1H, d, J ) 7.6 Hz, Ar), 7.19-
7.46 (9H, m, Ar), 7.71 (2H, d, J ) 9.1 Hz, Ar), 7.75 (2H, d, J
J . Org. Chem, Vol. 69, No. 2, 2004 423

Xu and Shi
) 8.5 Hz, Ar), 7.82 (1H, J ) 8.5 Hz, Ar); 13C NMR (CDCl3,
75.4 MHz) δ 21.5, 59.0, 117.9, 120.8, 125.2, 126.3, 126.4, 126.5,
126.6, 127.2, 127.8, 127.9, 128.0, 128.8, 129.4, 129.6, 134.5,
137.4, 138.3, 138.4, 143.6, 146.0, 164.0; MS (EI) m/e 457 (M+,
4.91), 314 (M+ - 143, 7.80). Anal. Calcd for C27H23NO4S
requires C, 70.88; H, 5.07; N, 3.06. Found: C, 71.14; H, 5.41;
N, 3.04.
pressure, and the residue was subject to a flash column
chromatography (SiO2, EtOAc/petroleum ether ) 1:10) to give
the compound 8 (85 mg, 99%) as a viscous liquid.
ter t-Bu tyl [1-(4-F lu or op h en yl)-2-(h yd r oxym eth yl)a llyl-
(tolu en e-4-su lfon il)]ca r ba m a te (8). A viscous liquid: IR
(CHCl3) ν 2892, 2934 cm-1, 1740 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 1.28 (9H, s, Me), 1.53 (1H, s, br, OH), 2.45
(3H, s, Me), 4.63 (2H, s), 5.15 (1H, d, J ) 1.8 Hz), 5.52 (1H, d,
J ) 1.8 Hz), 6.31 (1H, s), 7.06 (2H, dd, J ) 9.0, 8.7 Hz, Ar),
7.29 (2H, d, J ) 8.7 Hz, Ar), 7.41 (2H, dd, J ) 8.7, 5.4 Hz, Ar),
7.70 (2H, d, J ) 8.7 Hz, Ar); 13C NMR (CDCl3, 75.4 MHz) δ
21.5, 27.7, 61.7, 67.5, 82.3, 84.8, 115.1 (d, J C-F ) 21.5 Hz),
118.0, 128.6 (d, J C-F ) 62.6 Hz), 130.6 (d, J C-F ) 8.1 Hz), 133.1,
136.7, 140.9, 144.2, 150.5, 153.1, 162.1 (d, J C-F ) 247.2 Hz);
MS (EI) m/e 423 (M+ - 15, 16.14), 224 (M+ - 213, 100.00).
Anal. Calcd for C22H28FNO5S requires C, 60.39; H, 6.45; N,
3.20. Found: C, 60.38; H, 6.60; N, 3.20.
r-Na p h t h yl 2-[(4-Ch lor op h en yl)-(t olu en e-4-su lfon yl-
a m in o)m eth yl]a cr yla te (6l). A colorless solid: mp 180-181
°C; IR (CHCl3) ν 1731 cm-1 (CdO); 1H NMR (CDCl3, TMS, 300
MHz) δ 2.44 (3H, s, Me), 5.47 (1H, d, J ) 8.8 Hz), 5.66 (1H, d,
J ) 8.8 Hz), 6.14 (1H, s), 6.66 (1H, s), 7.05 (1H, d, J ) 8.5 Hz,
Ar), 7.19 (2H, d, J ) 8.5 Hz, Ar), 7.24-7.51 (9H, m, Ar), 7.73
(2H, d, J ) 8.5 Hz, Ar), 7.85 (1H, J ) 8.5 Hz, Ar); 13C NMR
(CDCl3, 75.4 MHz) δ 21.6, 58.6, 117.9, 120.6, 125.2, 126.3,
126.4, 126.5, 126.6, 127.2, 128.0, 128.9, 129.6, 129.7, 134.0,
134.6, 137.0, 137.4, 138.1, 143.7, 143.8, 145.9, 163.9; MS (EI)
m/e 491 (M+, 1.52), 348 (M+ - 143, 2.84). Anal. Calcd for
Detosyla tion of ter t-Bu tyl [1-(4-F lu or op h en yl)-2-(h y-
dr oxym eth yl)allyl(tolu en e-4-su lfon il)]car bam ate (8). Com-
pound 8 (85 mg, 0.194 mmol) was transferred to an oven-dried
flask under argon atmosphere. Then, this reaction vessel was
charged with 1.5 mL of dry MeOH, followed by the addition
of Mg (24 mg, 5 equiv). The reaction mixture was sonicated
for 45 min and then was poured into 1.0 M HCl. The organic
compound was extracted with ether (3 × 15 mL). The organic
phase was washed with saturated NaHCO3 and brine and
dried over anhydrous MgSO4. The solvent was removed under
reduced pressure, and the residue was subject to a flash
column chromatography (SiO2, EtOAc/petroleum ether ) 1:6)
to give compound 9 (48 mg, 82%) as a colorless solid.
C
27H22ClNO4S requires C, 65.91; H, 4.51; N, 2.85. Found: C,
65.83; H, 4.74; N, 2.59.
r-Na p h th yl 2-[(4-Meth oxyp h en yl)-(tolu en e-4-su lfon yl-
a m in o)m eth yl]a cr yla te (6m ). A colorless solid: mp 152-
154 °C; IR (CHCl3) ν 1735 cm-1 (CdO); 1H NMR (CDCl3, TMS,
300 MHz) δ 2.43 (3H, s, Me), 3.78 (3H, s, Me), 5.44 (2H, s),
6.18 (1H, s), 6.65 (1H, s), 6.81 (2H, d, J ) 8.8 Hz, Ar), 7.04
(1H, d, J ) 8.5 Hz, Ar), 7.13 (2H, d, J ) 8.8 Hz, Ar), 7.21-
7.49 (6H, m, Ar), 7.71 (1H, d, J ) 8.5 Hz, Ar), 7.74 (2H, d, J
) 8.2 Hz, Ar), 7.83 (1H, J ) 8.5 Hz, Ar); 13C NMR (CDCl3,
75.4 MHz) δ 21.6, 55.3, 58.5, 114.2, 117.9, 120.9, 125.2, 126.3,
126.4, 126.5, 126.6, 127.3, 128.0, 128.9, 129.6, 130.5, 134.5,
137.5, 138.7, 143.5, 143.6, 146.0, 159.4, 164.1; MS (EI) m/e 487
(M+, 0.39), 344 (M+ - 143, 4.68). Anal. Calcd for C28H25NO5S
requires C, 68.98; H, 5.17; N, 2.87. Found: C, 68.92; H, 5.36;
N, 2.72.
ter t-Bu tyl [1-(4-F lu or op h en yl)-2-h yd r oxym eth yla llyl]-
ca r ba m a te (9). A colorless solid: mp 98-99 °C; IR (CHCl3) ν
3447 cm-1 (OH), 1738, 1712 cm-1 (CdO); 1H NMR (CDCl3,
TMS, 300 MHz) δ 1.47 (9H, s), 4.48 (2H, s), 5.08-5.16 (1H,
br, s), 5.25 (1H, s), 5.32-5.41 (1H, br, s), 5.37 (1H, s), 7.04
(2H, dd, J ) 8.7, 9.0 Hz, Ar), 7.26-7.30 (2H, m, Ar); 13C NMR
(CDCl3, 75.4 MHz) δ 27.7 (3C), 28.3, 67.1, 82.3, 115.5, 115.5
(d, J C-F ) 21.4 Hz), 128.7 (d, J C-F ) 8.2 Hz), 135.4, 153.1,
154.8, 162.2 (d, J C-F ) 246.1 Hz); MS (EI) m/e 224 (M+ - 57,
28.16), 207 (M+ - 74, 74.22); HRMS calcd for C11H11FNO3
requires 224.0723, found 224.0706.
Red u ction of Com p ou n d 4c w ith LiAlH4. Compound 4c
(166 mg, 0.5 mmol) was placed in
a flask under argon
atmosphere. THF (3.0 mL) was added into the solution, and
then LiAlH4 (38 mg, 1.0 mmol) was added into the reaction
mixture at 0 °C. The reaction mixture was further stirred at
room temperature. The reaction was monitored by TLC plate.
After 4 h, compound 4c was consumed completely, and the
reaction was quenched by addition of saturated NH4Cl aqueous
solution at 0 °C. The reaction mixture was extracted with CH2-
Cl2 three times. The organic phases were combined and dried
over anhydrous MgSO4. The solvent was removed under
reduced pressure, and the residue was subject to a flash
column chromatography (SiO2, EtOAc/petroleum ether ) 1:2)
to give the compound 7 (148 mg, 89%) as a colorless solid.
Typ ica l Rea ction P r oced u r e of th e Syn th esis of Com -
p ou n d 12. A mixture of compound 5b (114 mg, 0.3 mmol) and
DBU (16 µL, 0.1 mmol) in anhydrous toluene (5 mL) was
refluxed for 2 h. The solvent was evaporated under reduced
pressure, and the residue was chromatographed over a SiO2
flash column using a gradient of petroleum/ethyl acetate (5:1)
as eluent to give the compound 12 (84 mg, 74%). The compound
13 was similarly synthesized from the compound 6a .
N-[1-(4-F lu or op h en yl)-2-h yd r oxym eth yl-a llyl]-4-m eth -
ylben zen esu lfon a m id e (7). A colorless solid: mp 78-80 °C;
IR (CHCl3) ν 3278 cm-1 (OH), 1603 cm-1 (CdC); 1H NMR
(CDCl3, TMS, 300 MHz) δ 2.41 (3H, s, Me), 2.02-2.07 (1H,
br, OH), 3.95 (1H, dd, J ) 9.9, 5.7 Hz), 4.08 (1H, dd, J ) 9.9,
5.7 Hz), 4.97 (1H, s), 5.07 (1H, d, J ) 7.8 Hz), 5.15 (1H, s),
5.78 (1H, d, J ) 7.8 Hz), 6.91 (2H, dd, J ) 8.7, 8.1 Hz, Ar),
7.11 (2H, dd, J ) 8.7, 5.4 Hz, Ar), 7.23 (2H, d, J ) 8.4 Hz, Ar),
7.64 (2H, d, J ) 8.4 Hz, Ar), 9.38 (1H, s); 13C NMR (CDCl3,
75.4 MHz) δ 21.7, 59.7, 64.1, 115.4, 115.5 (1C, J C-F ) 21.4
Meth yl (2E)-3-(4-Ch lor op h en yl)-2-[(tolu en e-4-su lfon yl-
a m in o)m eth yl]a cr yla te (12). A colorless solid: mp 118-119
°C; IR (CHCl3) ν 1706 cm-1 (CdO), 1633 cm-1 (CdC); 1H NMR
(CDCl3, TMS, 300 MHz) δ 2.44 (3H, s, Me), 3.77 (3H, s, Me),
3.89 (2H, d, J ) 6.0 Hz), 5.16 (1H, t, J ) 6.0 Hz), 7.29 (2H, d,
J ) 8.4 Hz, Ar), 7.33 (2H, d, J ) 8.7 Hz, Ar), 7.36 (1H, s, d
CH), 7.39 (2H, d, J ) 8.7 Hz, Ar), 7.68 (2H, d, J ) 8.4 Hz, Ar);
13C NMR (CDCl3, 75.4 MHz) δ 21.5, 40.4, 52.4, 126.9, 127.2,
129.0, 129.6, 130.8, 132.2, 135.5, 136.2, 142.1, 143.6, 167.4;
MS (EI) m/e 379 (M+ - 1, 0.24), 224 (M+ - 155, 100.00). Anal.
Calcd for C18H18ClNO4S requires C, 56.91; H, 4.78; N, 3.69.
Found: C, 56.90; H, 4.75; N, 3.63.
Hz), 127.4, 129.0 (1C, J C-F ) 8.4 Hz), 129.7, 134.6 (1C, J C-F
)
3.6 Hz), 137.4, 143.7, 146.8, 162.7 (1C, J C-F ) 246.8 Hz); MS
(EI) m/e 317 (M+ - 18, 0.75), 278 (M+ - 157, 30.61). Anal.
Calcd for C17H18FNO3S requires C, 60.88; H, 5.41; N, 4.18.
Found: C, 61.21; H, 5.54; N, 4.07.
P h en yl (2E)-3-P h en yl-2-[(t olu en e-4-su lfon yla m in o)-
m eth yl]a cr yla te (13). A colorless solid (79 mg, 65%): mp 95-
Boc-P r otection of Com p ou n d 7. Compound 7 (68 mg,
0.20 mmol) was placed in a flask under argon atmosphere.
Solvent CH2Cl2 (2.0 mL) was added into the reaction vessel,
and then DMAP (4.5 mg, 0.04 mmol, 0.2 equiv) and di-tert-
butyl dicarbonate (87 mg, 0.4 mmol, 2 equiv) were added into
the reaction mixture at room temperature. The reaction
mixture was further stirred at room temperature. The reaction
was monitored by TLC plate. After 2 h, the substrate was
consumed completely. The solvent was removed under reduced
1
96 °C; IR (CHCl3) ν 1713 cm-1 (CdO), 1633 cm-1 (CdC); H
NMR (CDCl3, TMS, 300 MHz) δ 2.42 (3H, s, Me), 4.06 (2H, d,
J ) 6.9 Hz), 5.23 (1H, t, J ) 6.9 Hz), 7.06 (2H, d, J ) 7.2 Hz),
7.26 (2H, d, J ) 8.4 Hz, Ar), 7.25-7.31 (1H, m, Ar), 7.40-7.52
(7H, m, Ar), 7.68 (2H, d, J ) 8.4 Hz, Ar), 8.03 (1H, s); 13C NMR
(CDCl3, 75.4 MHz) δ 21.5, 40.7, 121.4, 125.8, 126.1, 127.2,
128.8, 129.5, 129.7, 129.7, 129.9, 133.6, 136.2, 143.5, 145.1,
150.4, 166.0; MS (EI) m/e 408 (M+ + 1, 1.57), 143 (M+ - 264,
424 J . Org. Chem., Vol. 69, No. 2, 2004

aza-Baylis-Hillman Reaction of N-Tosylated Imines
100.00). Anal. Calcd for C23H21NO4S requires C, 67.81; H, 5.16;
N, 3.44. Found: C, 68.02; H, 5.03; N, 3.31.
China for financial support (20025206, 203900502, and
20272069).
Su p p or tin g In for m a tion Ava ila ble: X-ray diffraction
data of 12. This material is available free of charge via the
Internet at http://pubs.acs.org.
Ack n ow led gm en t. We thank the State Key Project
of Basic Research (Project 973) (no. G2000048007),
Shanghai Municipal Committee of Science and Technol-
ogy, and the National Natural Science Foundation of
J O035103P
J . Org. Chem, Vol. 69, No. 2, 2004 425