Sequential aza-Baylis-Hillman/ring closing metathesis/aromatization as a novel route for the synthesis of substituted pyrroles

Article abstract of DOI:10.1021/jo048519r

A new route to diverse 2-substituted-3-methoxycarbonyl pyrroles has been developed. Diverse SES protected α-methylene β-aminoesters were obtained by a 3-component aza-Baylis-Hillman reaction. Diversity arose from the aryl aldehydes which can be used in th

Full text of DOI:10.1021/jo048519r

Sequential aza-Baylis-Hillman/Ring Closing Metathesis/
Aromatization as a Novel Route for the Synthesis of Substituted
Pyrroles
Vale´rie Declerck, Patrice Ribie`re, Jean Martinez, and Fre´de´ric Lamaty*
Laboratoire des Aminoacides, Peptides et Prote´ines (LAPP), CNRS-Universite´s Montpellier 1 et 2,
Place Euge`ne Bataillon, 34095 Montpellier Cedex 5, France
frederic@univ-montp2.fr
Received August 24, 2004
A new route to diverse 2-substituted-3-methoxycarbonyl pyrroles has been developed. Diverse SES
protected R-methylene â-aminoesters were obtained by a 3-component aza-Baylis-Hillman reaction.
Diversity arose from the aryl aldehydes which can be used in this reaction. N-Alkylation with allyl
bromide under mild conditions provided the corresponding dienes. These substituted dienes were
cyclized by ring closing metathesis at room temperature or under microwave-activation with Grubbs-
type II catalyst to yield SES-protected pyrroline intermediates. The final pyrroles were obtained
by base-promoted dehydrodesulfinylation/aromatization. The scope of each of these reactions was
explored.
Introduction
found in biomolecules6a,b such as porphyrins and cyto-
chromes. It serves also as a building block for the
preparation of polymeric and supramolecular structures
which have applications in nonlinear optics.6c,d
The 2-trimethylsilyethylsulfonyl (or SES) group is a
valuable protecting group of amines in organic synthesis.1
It is mainly used to protect an amine as a sulfonamide
and promote Mitsunobu or base-activated alkylation.
This group can be cleaved usually by fluoride-promoted
â-elimination. A less usual pathway to remove the SES
group is to perform a base-promoted dehydrodesulfin-
ylation, which consists of abstracting a proton in the
R-position to the nitrogen of the sulfonamide. This process
is favored in the case of unsaturated cyclic compounds
when an aromatization to the final product is possible.
It has been described in the literature mostly with the
tosyl2 or related protecting groups2d,3 and more rarely
with the SES group3k,4 (eq 1).
Results and Discussion
As described in the retrosynthetic scheme (Scheme 1),
the pyrrole ring can be obtained after dehydrodesulfin-
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1995, 51, 8585-8598. (r) Davis, F. A.; Liang, C.-H.; Liu, H. J. Org.
Chem. 1997, 62, 3796-3797. (s) Meng, Q.; Thibblin, A. J. Am. Chem.
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As part of our ongoing project on the synthesis of
heterocyclic structures by ring closing metathesis
(RCM),4b,5 we report herein a new strategy for the
preparation of 2,3-disubstituted pyrroles using the de-
hydrodesulfinylation as the aromatization step of pyrro-
lines formed by RCM. The pyrrole6 ring is an important
scaffold in pharmaceutical and material chemistry. It is
* Address correspondence to this author. Fax: +33 (0) 4-67-14-48-
66.
(1) (a) Weinreb, S. M.; Ralbovsky, J. L. In Handbook of Reagents
for Organic Synthesis, Activating Agents and Protecting Groups;
Pearson, A. J., Roush, W. J., Eds.; Wiley: Chichester, UK, 1999; pp
425-427. (b) In Protective Groups in Organic Synthesis, 3rd ed.;
Greene, T. W., Wuts, P. G. M., Eds.; Wiley: New York, 1999; p 612.
(c) Kocienski, P. J. In Protecting Groups; Enders, D., Noyori, R., Trost,
B. M., Eds.; Thieme: New York, 2000; pp 215-216.
10.1021/jo048519r CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/03/2004
8372
J. Org. Chem. 2004, 69, 8372-8381

Synthesis of Substituted Pyrroles
SCHEME 1
ylation/aromatization of
a SES-protected pyrroline
TABLE 1.
formed via RCM of an appropriate linear precursor.
This precursor can result from the alkylation of an
unsaturated â-aminoester synthesized by the aza-
Baylis-Hillman reaction. Recently we have presented
the synthesis of an ester-substituted pyrroline via RCM.5b
To increase the diversity of this class of molecules7 as
well as the pyrrole derivatives obtained by aromatization,
we needed to prepare more diverse R-methylene-â-
aminoesters which can be obtained via the aza-Baylis-
Hillman reaction.
The 3-component aza version of the Baylis-Hillman
reaction is an attractive method for the synthesis of
â-aminoesters. This reaction has been performed with the
tosyl group (R3 ) tosyl) as the protecting and activating
group of ammonia.8 With the purpose of synthesizing
â-aminoesters bearing more easily cleavable protecting
groups, we decided to investigate the SES group for
protection (eq 2).9
a
yield of 5 (%)
conditions Ag conditions Bg
yield
(%)
yield yield of yielda of yielda of
(%)
R4 t (h)
t (h)
6 (%)
7 (%)
8 (%)
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
24
96
48
24
72
72
73
46
64
75
36
42
10
72
6
86
67
90
98
98
97
c
98
95
92
c
80
83
b
c
c
6
6
79
86
60
86
70
66
86
73
61
60
71
99
99
98
98
97
98
99
99
98
97
e
95
90
90
98
92
96
95
94
5f
81
81
66
72
78
88
81
81
d
c
48
38
72
72
14
10
14
6
c
c
d
d
d
d
d
10f
6
a After purification by column chromatography. b Aromatization
occurred along with transesterification of the side chain with
t-BuOH. c Not performed. d Slow reaction at room temperature and
degradation of the aldehyde upon heating. e Degradation observed.
f Conversion evaluated by 1H NMR. g Conditions A: SESNH2 (1
equiv), ArCHO (1 equiv), methyl acrylate (1.1 equiv), 3-HQD (0.15
equiv), Ti-(OiPr)4 (0.02 equiv), i-PrOH, MS 4 Å, 70 °C. Conditions
B: SESNH2 (1 equiv), ArCHO (5 equiv), methyl acrylate (5 equiv),
DABCO (0.5 equiv), i-PrOH, 70 °C.
First, the conditions by Balan et al.8b for Ts-NH2 were
tested with use of SES-NH2, benzaldehyde, and methyl
acrylate in the presence of a Lewis acid (Ti(Oi-Pr4)),
3-HQD as a base, and molecular sieves. When the
reaction was performed at room temperature conversion
was slow and selectivity between formation of the â-ami-
noester and the â-hydroxyester was moderate. Increasing
the reaction temperature to 70 °C resulted in complete
conversion after 24 h and better selectivity. Reaction of
SES-NH2 was slower than that with Ts-NH2 (8 h in the
same reaction conditions). We applied these reaction
conditions to the synthesis of six aminoesters (5a-f).
However, we realized that in some cases, the reaction
time and conditions were not satisfactory. With some
aldehydes, the reaction was too slow and incomplete after
24 h. Heating the reaction mixture resulted in the
degradation of the reactants. Consequently we also
performed the reactions in different conditions (DABCO
in i-PrOH) in the presence of an excess of benzaldehyde
and methyl acrylate to drive the reaction to completion.
Concomitant formation of the corresponding hydroxyester
was not avoided. The aminoesters were obtained pure
after column chromatography. Results are presented in
Table 1.
The various â-aminoesters obtained from the aza-
Baylis-Hillman reaction (5a-n) were reacted with allyl
bromide in the presence of K2CO3 in DMF5b to yield the
corresponding dienes in most cases, except for 5d, which
yielded a complex mixture, and 5o, which was degraded
in these reaction conditions. 6a-c and 6e-n were
obtained in almost quantitative yields.
Ring closing metathesis is a powerful method for the
construction of cyclic structures.10 In the past few years,
it has been widely applied to the synthesis of hetero-
(3) (a) Mertes, M. P.; Borne, R. F.; Hare, L. E. J. Org. Chem. 1968,
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2316.
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Lambeth, R. H. Synthesis 2004, 918-922. (b) Dhawan, R.; Arndtsen,
B. A. J. Am. Chem. Soc. 2004, 126, 468-469 (c) Venkatraman, S.;
Kumar, R.; Sankar, J.; Chandrashekar, T. K.; Sendhil, K.; Vijayan,
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(7) During the course of our study, a similar approach for the
synthesis of pyrrolines was published: Balan, D.; Adolfsson, H.
Tetrahedron Lett. 2004, 45, 3089-3092.
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(b) Balan, D.; Adolfsson, H. J. Org. Chem. 2002, 67, 2329-34. (c) Balan,
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J. Comb. Chem. 2004, 6, 464-467.
J. Org. Chem, Vol. 69, No. 24, 2004 8373

Declerck et al.
FIGURE 1. R4 substituents.
TABLE 2. Yielda of Products Obtained at the SES
Cleavage/Aromatization Step of 7a
yield (%)
7a pyrrole 8a isomer 9
entry
conditions
1
2
3
4
5
6
n-Bu4NF, THF, rt
CsF, DMF, 80 °C, 2 h
DBU, THF, rt, 24 h
K2CO3, DMF, 80 °C, 24 h
DBU, THF, reflux, 16 h
t-BuOK, DMF, rt, 2 h
0
0
0
0
0
0
21
41
0
0
0
26
24
0
0
FIGURE 2. Grubbs-type II catalyst.
64
83
0
cycles.11 Recently the availability of more reactive cata-
lysts such as Grubbs-type II catalyst (Figure 2) has
opened the path to more demanding processes such as
substituent bearing olefins. Among these substituents,
carboxymethyl has not been fully exploited so far4b,5b,12
while its importance as a functional group is widely
recognized.
The dienes 6a-c and 6e-n were submitted to RCM
reaction conditions (Grubbs-type II catalyst, 5 mol % in
CH2Cl2) to yield the corresponding cyclic structures 7 (eq
3). Yields are generally excellent (Table 1) except in the
a Yields were determined by 1H NMR with CH2Br2 as an
internal standard.
with the ruthenium catalyst, unfavorable for the cycliza-
tion reaction. While the cylizations of 6a-c and 6e-l
were complete within 12 h at room temperature, they
could be conveniently accelerated by microwave activa-
tion.5a,7,12d,14 Under these conditions (100 °C, CH2Cl2),
completion of the cyclization was reached within 5 min.
The next step was the cleavage of the SES group and
aromatization (eq 4). Results of the different reaction
conditions are summarized in Table 2.
cases of 6m and 6n which gave a low conversion to 7m
and 7n, respectively. This may result from a complex-
ation of the arylic side chain (alkyne13 or nitro group)
The method described in the literature for this type of
substrate4a (eq 4) yielded only a small amount of the
expected product 8a (entry 1). Using a different fluoride
source4b (entry 2) resulted in a moderate yield. Stronger
bases were then employed. DBU in THF at room
temperature2x (entry 3) and K2CO3 in DMF at 80 °C3k
(entry 4) resulted in the isomerization of pyrroline 7a
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8374 J. Org. Chem., Vol. 69, No. 24, 2004

Synthesis of Substituted Pyrroles
Methyl 2-(Phenyl(2-(trimethylsilyl)ethylsulfonamido)-
methyl)acrylate (5a): Conditions A. The crude product was
purified by silica gel chromatography (Et2O/hexane ) 3/7) to
yield 519 mg (73%) of the title compound as a white solid.
Conditions B. The crude product was purified by silica gel
chromatography (Et2O/hexane ) 3/7) to yield 614 mg (86%) of
the title compound as a white solid.
Mp 91.6-92.2 °C; IR 3368 (m), 2955 (m), 1719 (s), 1335 (s)
cm-1; 1H NMR (CDCl3, Me4Si) δ -0.01 (s, 9H), 0.80-1.05 (m,
2H), 2.75-2.95 (m, 2H), 3.73 (s, 3H), 5.45 (d, 1H, J3 ) 9.3 Hz),
5.53 (d, 1H, J3 ) 9.3 Hz), 6.02 (s, 1H), 6.43 (d, 1H, J4 ) 0.6
Hz), 7.25-7.45 (m, 5H); 13C NMR (CDCl3, Me4Si) δ -1.6, 10.9,
50.4, 52.6, 59.5, 127.0, 128.0, 128.4, 129.2, 139.6, 140.2, 166.3;
ESIMS m/z 174.8 (M - SESNH2 + H)+, 356.0 (M + H)+, 378.1
(M + Na)+, 710.9 (2M + H)+, 733.1 (2M + Na)+; FAB+ m/z
175 (M - SESNH2 + H)+, 356 (M + H)+; HRMS calcd for
C16H26NO4SSi 356.1352, found 356.1316.
into 9 without cleavage of the SES group and aromati-
zation. DBU in refluxing THF3e (entry 5) provided better
yields of 8a. Best results were obtained with t-BuOK in
DMF at room temperature2w,y (entry 6). In this case, 83%
of the expected pyrrole 8a was obtained within 2 h via
elimination/aromatization. This result could be applied
to all the SES protected pyrroline 7a,b and 7e-l to
provide the corresponding pyrroles 8a,b and 8e-l in high
yields. In the case of 7c transesterification of the methyl
ester of the side chain to the t-Bu ester occurred.
Conclusion
In conclusion, an efficient regiocontrolled synthesis of
2-substituted-3-methoxycarbonyl pyrroles was developed.
Ten different pyrroles were obtained in an overall high
yield and high purity, starting from highly diverse
R-methylene â-aminoesters. Further development of this
chemistry is underway in our laboratory.
Methyl 2-((3,5-Dimethoxyphenyl)(2-(trimethylsilyl)-
ethylsulfonamido)methyl)acrylate (5b): Conditions A.
The crude product was purified by silica gel chromatography
(Et2O/hexane ) 4/6) to yield 383 mg (46%) of the title
compound as a white solid.
Conditions B. The crude product was purified by silica gel
chromatography (Et2O/hexane ) 4/6) to yield 557 mg (67%) of
the title compound as a white solid.
Experimental Section
General Remarks.9 Microwave-assisted reactions were
performed with a Personal Chemistry Emrys Optimizer or
with a CEM Explorer monomode system.
Mp 91.4-95.5 °C; IR 3383 (m), 2963 (m), 1719 (s), 1334 (s)
cm-1; 1H NMR (CDCl3, Me4Si) δ -0.01 (s, 9H), 0.85-1.05 (m,
2H), 2.80-2.95 (m, 2H), 3.74 (s, 3H), 3.79 (s, 6H), 5.36 (d, 1H,
J3 ) 9.3 Hz), 5.55 (d, 1H, J3 ) 9.3 Hz), 5.99 (s, 1H), 6.35-6.40
(m, 1H), 6.41 (d, 1H, J4 ) 0.4 Hz), 6.50-6.55 (m, 2H); 13C NMR
(CDCl3, Me4Si) δ -1.7, 10.9, 50.4, 52.6, 55.8, 59.5, 99.9, 105.2,
128.1, 139.9, 142.0, 161.4, 166.3; ESIMS m/z 235.2 (M -
SESNH2 + H)+, 416.2 (M + H)+, 831.3 (2M + H)+, 853.4 (2M
+ Na)+; FAB+ m/z 235 (M - SESNH2 + H)+, 415 (M - e-)+;
HRMS calcd for C18H29NO6SSi 415.1485, found 415.1480.
Methyl 4-(2-(Methoxycarbonyl)-1-(2-(trimethylsilyl)-
ethylsulfonamido)allyl)benzoate (5c): Conditions A. The
crude product was purified by silica gel chromatography (Et2O/
hexane ) 4/6) to yield 530 mg (64%) of the title compound as
a white solid.
2-(Trimethylsilyl)ethanesulfonamide (2). Phosphorus
pentachloride (7.7 g, 36.7 mmol) was added portionwise to a
suspension of sodium 2-(trimethylsilyl)ethanesulfonate (5 g,
24.5 mmol) in 100 mL of CH2Cl2. The reaction mixture was
stirred at room temperature for 30 min. The organic phase
was washed three times with saturated NaHCO3, dried over
MgSO4, filtered, and evaporated. The residue was dissolved
in 100 mL of CH2Cl2, and gaseous NH3 was bubbled through
the solution for 15 min at -10 °C. The mixture was stirred at
room temperature overnight, then filtered over Celite and
evaporated. The residue was dissolved with AcOEt and washed
with water and brine. The organic layer was dried over MgSO4,
filtered, and evaporated to yield 2.95 g (67%) of the title
compound.15
Conditions B. The crude product was purified by silica gel
chromatography (Et2O/hexane ) 4/6) to yield 747 mg (90%) of
the title compound as a white solid.
1H NMR (CDCl3, Me4Si) δ 0.08 (s, 9H), 1.05-1.15 (m, 2H),
3.00-3.10 (m, 2H), 4.97 (large s, 2H); 13C NMR (CDCl3, Me4-
Si) δ -1.6, 11.2, 52.0.
Mp 103.7-108.5 °C; IR 3406 (m), 2950 (m), 1719 (s), 1332
(s) cm-1 1H NMR (CDCl3, Me4Si) δ 0.00 (s, 9H), 0.75-1.10
;
General Procedure for the Synthesis of â-Aminoesters
5: Conditions A. To a mixture8b of 2-(trimethylsilylethane)-
sulfonamide 2 (363 mg, 2 mmol), 3-hydroxyquinuclidine (38
mg, 0.30 mmol), and molecular sieves (4 Å, 400 mg, 200 mg/
mmol substrate) in 1 mL of 2-propanol was added aldehyde 3
(2 mmol), methyl acrylate (186 mg, 2.2 mmol), and Ti(OiPr)4
(12 mg, 0.04 mmol). The reaction mixture was stirred for the
indicated time at 70 °C and filtered over Celite. The Celite
was rinsed three times with 2-propanol. The solvent was
evaporated and the residue was diluted with AcOEt, neutral-
ized with aq KHSO4 (1%), and washed with saturated NaHCO3
and brine. The organic layer was dried over MgSO4, filtered,
and evaporated. Silica gel chromatography (Et2O/hexane)
yielded â-aminoester 5.
Conditions B. To a solution of 2-(trimethylsilylethane)-
sulfonamide 2 (363 mg, 2 mmol) and DABCO (112 mg, 1 mmol)
in 1 mL of 2-propanol was added aldehyde 3 (10 mmol) and
methyl acrylate (861 mg, 10 mmol). The reaction mixture was
stirred for the indicated time at 70 °C, evaporated, diluted with
AcOEt, neutralized with aq KHSO4 (1%), and washed with
saturated NaHCO3 and brine. The organic layer was dried over
MgSO4, filtered, and evaporated. Silica gel chromatography
(Et2O/hexane) yielded â-aminoester 5.
(m, 2H), 2.85-3.00 (m, 2H), 3.72 (s, 3H), 3.93 (s, 3H), 5.48 (d,
1H, J3 ) 9.7 Hz), 5.71 (d, 1H, J3 ) 9.7 Hz), 6.03 (s, 1H), 6.46
(s, 1H), 7.46 (d, 2H, J3 ) 8.5 Hz), 8.03 (d, 2H, J3 ) 8.5 Hz); 13
C
NMR (CDCl3, Me4Si) δ -1.6, 10.9, 50.6, 52.6, 52.7, 59.5, 126.8,
128.9, 130.2, 130.4, 139.5, 144.6, 166.1, 167.0; ESIMS m/z
414.1 (M + H)+, 827.5 (2M + H)+, 849.3 (2M + Na)+; FAB+
m/z 233 (M - SESNH2 + H)+, 414 (M + H)+; HRMS calcd for
C18H28NO6SSi 414.1407, found 414.1435.
Methyl 2-(Pyridin-3-yl(2-(trimethylsilyl)ethylsulfon-
amido)methyl)acrylate (5d): Conditions A. The crude
product was purified by silica gel chromatography (Et2O/
hexane ) 4/6 + 1% Et3N) to yield 535 mg (75%) of the title
compound as a white solid.
Mp 129.2-129.8 °C; IR 3418 (m), 2950 (m), 1716 (s), 1331
(s) cm-1 1H NMR (CDCl3, Me4Si) δ 0.02 (s, 9H), 0.85-1.20
;
(m, 2H), 2.80-3.05 (m, 2H), 3.75 (s, 3H), 5.48 (d, 1H, J3 ) 9.5
Hz), 5.70 (d, 1H, J3 ) 9.5 Hz), 6.07 (s, 1H), 6.49 (d, 1H, J4 )
0.4 Hz), 7.32 (dd, 1H, J3 ) 8.0 Hz, J3 ) 4.8 Hz), 7.79 (dt, 1H,
J3 ) 8.0 Hz, J4 ) 1.7 Hz), 8.57 (dd, 1H, J3 ) 4.8 Hz, J4 ) 1.2
Hz), 8.61 (d, 1H, J4 ) 1.9 Hz); 13C NMR (CDCl3, Me4Si) δ -1.6,
10.9, 50.7, 52.8, 58.0, 123.9, 129.2, 134.6, 135.3, 139.2, 148.5,
149.6, 166.0; ESIMS m/z 357.1 (M + H)+, 713.3 (2M + H)+;
FAB+ m/z 357 (M + H)+, 379 (M + Na)+; HRMS calcd for
C17H27N2O4SSi 357.1304, found 357.1301.
(15) (a) Stien, D.; Anderson, G. T.; Chase, C. E.; Koh, Y.-H.; Weinreb,
S. M. J. Am. Chem. Soc. 1999, 121, 9574-9579. (b) Parker, L. L.;
Gowans, N. D.; Jones, S. W.; Robins, D. J. Tetrahedron 2003, 59,
10165-10171.
Methyl 2-((3-Fluorophenyl)(2-(trimethylsilyl)ethylsul-
fonamido)methyl)acrylate (5e): Conditions A. The crude
product was purified by silica gel chromatography (Et2O/
J. Org. Chem, Vol. 69, No. 24, 2004 8375

Declerck et al.
hexane ) 3/7) to yield 269 mg (36%) of the title compound as
Mp 92.0-93.4 °C; IR 3383 (m), 2953 (m), 1715 (s), 1334 (s)
cm-1; 1H NMR (CDCl3, Me4Si) δ -0.01 (s, 9H), 0.85-1.00 (m,
2H), 2.32 (s, 6H), 2.80-2.95 (m, 2H), 3.74 (s, 3H), 5.36 (d, 1H,
J3 ) 9.3 Hz), 5.42 (d, 1H, J3 ) 9.3 Hz), 6.02 (s, 1H), 6.42 (d,
1H, J4 ) 0.6 Hz), 6.94 (s, 1H), 6.97 (s, 2H); 13C NMR (CDCl3,
Me4Si) δ -1.7, 10.9, 21.8, 50.3, 52.6, 59.4, 124.7, 127.8, 130.1,
138.8, 139.4, 140.2, 166.3; ESIMS m/z 203.3 (M - SESNH2 +
H)+, 384.3 (M + H)+, 767.3 (2M + H)+; FAB+ m/z 203 (M -
SESNH2 + H)+, 384 (M + H)+, 406 (M + Na)+; HRMS calcd
for C18H30NO4SSi 384.1665, found 384.1670.
Methyl 2-((2,3-Methylenedioxyphenyl)(2-(trimethyl-
silyl)ethylsulfonamido)methyl)acrylate (5j): Conditions
B. The crude product was purified by silica gel chromatography
(Et2O/hexane ) 4/6) to yield 526 mg (66%) of the title
compound as a white solid.
a white solid.
Conditions B. The crude product was purified by silica gel
chromatography (Et2O/hexane ) 3/7) to yield 592 mg (79%) of
the title compound as a white solid.
Mp 68.1-69.1 °C; IR 3370 (m), 2958 (m), 1714 (s), 1334 (s),
1
1093 (m) cm-1; H NMR (CDCl3, Me4Si) δ 0.01 (s, 9H), 0.80-
1.10 (m, 2H), 2.80-3.00 (m, 2H), 3.75 (s, 3H), 5.43 (d, 1H, J3
) 9.5 Hz), 5.62 (d, 1H, J3 ) 9.5 Hz), 6.02 (s, 1H), 6.45 (s, 1H),
6.95-7.25 (m, 3H), 7.30-7.45 (m, 1H); 13C NMR (CDCl3, Me4-
Si) δ -1.7, 10.9, 50.6, 52.7, 59.2 (d, J4 ) 1.5 Hz), 114.0 (d, J2
) 22.6 Hz), 115.3 (d, J2 ) 21.1 Hz), 122.5 (d, J4 ) 2.8 Hz),
128.7, 130.7 (d, J3 ) 8.5 Hz), 139.6, 142.3 (d, J3 ) 6.8 Hz),
163.3 (d, J1 ) 246.9 Hz), 166.1; ESIMS m/z 374.1 (M + H)+,
747.2 (2M + H)+; FAB+ m/z 193 (M - SESNH2 + H)+, 374 (M
+ H)+, 396 (M + Na)+; HRMS calcd for C16H25FNO4SSi
374.1258, found 374.1273.
Mp 93.0-94.8 °C; IR 3375 (m), 2955 (m), 1725 (s), 1339 (s)
cm-1; 1H NMR (CDCl3, Me4Si) δ -0.02 (s, 9H), 0.75-1.05 (m,
2H), 2.75-3.05 (m, 2H), 3.76 (s, 3H), 5.52 (d, 1H, J3 ) 9.8 Hz),
5.57 (d, 1H, J3 ) 9.8 Hz), 5.99 (s, 1H), 6.01 (s, 1H), 6.38 (s,
1H), 6.75-6.95 (m, 3H); 13C NMR (CDCl3, Me4Si) δ -1.7, 10.8,
50.2, 52.6, 54.8, 101.6, 108.9, 120.9, 121.5, 122.5, 127.4, 139.2,
144.9, 148.0, 166.2; ESIMS m/z 219.2 (M - SESNH2 + H)+,
400.0 (M + H)+, 799.2 (2M + H)+, 821.2 (2M + Na)+; FAB+
m/z 219 (M - SESNH2 + H)+, 399 (M - e-)+, 422 (M + Na)+;
HRMS calcd for C17H25NO6SSi 399.1172, found 399.1164.
Methyl 2-((4-Chlorophenyl)(2-(trimethylsilyl)ethylsul-
fonamido)methyl)acrylate (5k): Conditions B. The crude
product was purified by silica gel chromatography (Et2O/
hexane ) 3/7) to yield 670 mg (86%) of the title compound as
a white solid.
Methyl 2-((2-Bromophenyl)(2-(trimethylsilyl)ethylsul-
fonamido)methyl)acrylate (5f): Conditions A. The crude
product was purified by silica gel chromatography (Et2O/
hexane ) 3/7) to yield 367 mg (42%) of the title compound as
a white solid.
Conditions B. The crude product was purified by silica gel
chromatography (Et2O/hexane ) 3/7) to yield 759 mg (86%) of
the title compound as a white solid.
Mp 104.4-105.3 °C; IR 3378 (m), 2955 (m), 1726 (s), 1336
(s) cm-1 1H NMR (CDCl3, Me4Si) δ 0.00 (s, 9H), 0.80-1.00
;
(m, 2H), 2.85-3.10 (m, 2H), 3.75 (s, 3H), 5.32 (d, 1H, J3 ) 8.9
Hz), 5.88 (d, 1H, J3 ) 8.9 Hz), 6.03 (d, 1H, J4 ) 1.5 Hz), 6.46
(s, 1H), 7.20 (td, 1H, J3 ) 7.7 Hz, J4 ) 1.7 Hz), 7.37 (td, 1H, J3
) 7.7 Hz, J4 ) 1.3 Hz), 7.55 (dd, 1H, J3 ) 7.8 Hz, J4 ) 1.7
Hz), 7.60 (dd, 1H, J3 ) 7.8 Hz, J4 ) 1.3 Hz); 13C NMR (CDCl3,
Me4Si) δ -1.6, 10.9, 50.4, 52.6, 58.0, 123.7, 128.3, 128.9, 129.3,
130.0, 133.9, 138.9, 139.3, 166.3; ESIMS m/z 434.0/436.0 (M
+ H)+, 867.1/869.1/871.1 (2M + H)+; FAB+ m/z 253/255 (M -
SESNH2 + H)+, 434/436 (M + H)+, 456/458 (M + Na)+; HRMS
calcd for C16H25BrNO4SSi 434.0457, found 434.0442.
Mp 106.4-107.1 °C; IR 3425 (m), 1713 (s), 1335 (s) cm-1
;
1H NMR (CDCl3, Me4Si) δ 0.02 (s, 9H), 0.80-1.10 (m, 2H),
2.80-3.00 (m, 2H), 3.74 (s, 3H), 5.41 (d, 1H, J3 ) 9.3 Hz), 5.54
(d, 1H, J3 ) 9.3 Hz), 6.01 (s, 1H), 6.44 (s, 1H), 7.34 (s, 4H); 13
C
NMR (CDCl3, Me4Si) δ -1.6, 10.9, 50.6, 52.7, 59.2, 128.3, 128.5,
129.3, 134.3, 138.1, 139.7, 166.1; ESIMS m/z 208.8 (M -
SESNH2 + H)+, 390.1 (M + H)+, 412.0 (M + Na)+, 779.0 (2M
+ H)+, 801.1 (2M + Na)+; FAB+ m/z 209 (M - SESNH2
+
Methyl 2-(Naphthalen-2-yl(2-(trimethylsilyl)ethylsul-
fonamido)methyl)acrylate (5g): Conditions B. The crude
product was purified by silica gel chromatography (Et2O/
hexane ) 3/7) to yield 487 mg (60%) of the title compound as
a white solid.
H)+, 390 (M + H)+, 412 (M + Na)+; HRMS calcd for C16H25-
ClNO4SSi 390.0962, found 390.0974.
Methyl 2-((2-Iodophenyl)(2-(trimethylsilyl)ethylsul-
fonamido)methyl)acrylate (5l): Conditions B. The crude
product was purified by silica gel chromatography (Et2O/
hexane ) 3/7) to yield 707 mg (73%) of the title compound as
a white solid.
Mp 110.7-112.0 °C; IR 3388 (m), 2963 (m), 1715 (s), 1333
1
(s) cm-1; H NMR (CDCl3, Me4Si) δ -0.07 (s, 9H), 0.85-1.00
(m, 2H), 2.80-2.95 (m, 2H), 3.72 (s, 3H), 5.63 (d, 1H, J3 ) 9.3
Hz), 5.70 (d, 1H, J3 ) 9.3 Hz), 6.09 (s, 1H), 6.48 (s, 1H), 7.45-
7.55 (m, 3H), 7.75-7.95 (m, 4H); 13C NMR (CDCl3, Me4Si) δ
-1.7, 10.9, 50.5, 52.6, 59.6, 124.9, 126.0, 126.8, 126.9, 128.0,
128.1, 128.5, 129.1, 133.3, 133.6, 136.9, 140.1, 166.3; ESIMS
m/z 225.1 (M - SESNH2 + H)+, 405.9 (M + H)+; FAB+ m/z
225 (M - SESNH2 + H)+, 405 (M + H)+; HRMS calcd for
C20H27NO4SSi 405.1430, found 405.1431.
Methyl 2-(m-Tolyl(2-(trimethylsilyl)ethylsulfonamido)-
methyl)acrylate (5h): Conditions B. The crude product was
purified by silica gel chromatography (Et2O/hexane ) 3/7) to
yield 633 mg (86%) of the title compound as a white solid.
Mp 60.7-62.4 °C; IR 3425 (m), 2955 (m), 1720 (s), 1328 (s)
cm-1; 1H NMR (CDCl3, Me4Si) δ -0.01 (s, 9H), 0.80-1.00 (m,
2H), 2.36 (s, 3H), 2.75-2.95 (m, 2H), 3.73 (s, 3H), 5.41 (d, 1H,
J3 ) 9.3 Hz), 5.54 (d, 1H, J3 ) 9.3 Hz), 6.02 (s, 1H), 6.42 (s,
1H), 7.05-7.35 (m, 4H); 13C NMR (CDCl3, Me4Si) δ -1.7, 10.9,
21.9, 50.4, 52.6, 59.4, 124.0, 127.7, 127.8, 129.1, 129.2, 138.9,
139.5, 140.2, 166.3; ESIMS m/z 189.1 (M - SESNH2 + H)+,
370.1 (M + H)+, 739.3 (2M + H)+, 761.2 (2M + Na)+; FAB+
m/z 189 (M - SESNH2 + H)+, 370 (M + H)+, 392 (M + Na)+;
HRMS calcd for C17H28NO4SSi 370.1508, found 370.1548.
Methyl 2-((3,5-Dimethylphenyl)(2-(trimethylsilyl)eth-
ylsulfonamido)methyl)acrylate (5i): Conditions B. The
crude product was purified by silica gel chromatography (Et2O/
hexane ) 3/7) to yield 537 mg (70%) of the title compound as
a white solid.
Mp 127.4-128.6 °C; IR 3383 (m), 2953 (m), 1723 (s), 1346
(s) cm-1 1H NMR (CDCl3, Me4Si) δ 0.01 (s, 9H), 0.80-1.05
;
(m, 2H), 2.85-3.15 (m, 2H), 3.77 (s, 3H), 5.21 (d, 1H, J3 ) 8.7
Hz), 5.78 (d, 1H, J3 ) 8.7 Hz), 6.02 (d, 1H, J4 ) 0.9 Hz), 6.47
(s, 1H), 7.03 (ddd, 1H, J3 ) 8.0 Hz, J3 ) 7.2 Hz, J4 ) 1.9 Hz),
7.40 (ddd, 1H, J3 ) 7.8 Hz, J3 ) 7.2 Hz, J4 ) 1.3 Hz), 7.51 (dd,
1H, J3 ) 7.8 Hz, J4 ) 1.9 Hz), 7.90 (dd, 1H, J3 ) 7.9 Hz, J4 )
1.2 Hz); 13C NMR (CDCl3, Me4Si) δ -1.5, 10.9, 50.6, 52.6, 62.3,
99.8, 128.7, 129.0, 129.2, 130.2, 139.6, 140.7, 142.0, 166.3;
ESIMS m/z 300.9 (M - SESNH2 + H)+, 482.1 (M + H)+; FAB+
m/z 301 (M - SESNH2 + H)+, 482 (M + H)+, 504 (M + Na)+;
HRMS calcd for C16H25INO4SSi 482.0318, found 482.0311.
Methyl 2-((2-(Trimethylsilyl)ethylsulfonamido)(4-(2-
(trimethylsilyl)ethynyl)phenyl)methyl)acrylate (5m):
Conditions B. The crude product was purified by silica gel
chromatography (Et2O/hexane ) 3/7) to yield 551 mg (61%) of
the title compound as a white solid.
Mp 90.2-91.4 °C; IR 3380 (m), 2955 (m), 2158 (m), 1719
(s), 1334 (s) cm-1; 1H NMR (CDCl3, Me4Si) δ 0.02 (s, 9H), 0.26
(s, 9H), 0.75-1.10 (m, 2H), 2.80-3.00 (m, 2H), 3.72 (s, 3H),
5.42 (d, 1H, J3 ) 9.5 Hz), 5.53 (d, 1H, J3 ) 9.5 Hz), 6.01 (s,
1H), 6.43 (s, 1H), 7.31 (d, 2H, J3 ) 8.5 Hz), 7.46 (d, 2H, J3 )
8.5 Hz); 13C NMR (CDCl3, Me4Si) δ -1.6, 0.3, 10.9, 50.6, 52.6,
59.4, 95.3, 104.8, 123.3, 126.8, 128.5, 132.7, 139.7, 139.8, 166.1;
ESIMS m/z 271.3 (M - SESNH2 + H)+, 452.0 (M + H)+; FAB+
m/z 271 (M - SESNH2 + H)+, 452 (M + H)+, 474 (M + Na)+;
HRMS calcd for C21H34NO4SSi 452.1747, found 452.1755.
8376 J. Org. Chem., Vol. 69, No. 24, 2004

Synthesis of Substituted Pyrroles
Methyl 2-((4-Nitrophenyl)(2-(trimethylsilyl)ethylsul-
fonamido)methyl)acrylate (5n): Conditions B. The crude
product was purified by silica gel chromatography (Et2O/
hexane ) 4/6) to yield 481 mg (60%) of the title compound as
a white solid.
Mp 104.9-113.7 °C; IR 3368 (m), 2958 (m), 1715 (s), 1526
(s), 1354 (s), 1339 (s) cm-1; 1H NMR (CDCl3, Me4Si) δ 0.03 (s,
9H), 0.75-1.15 (m, 2H), 2.85-3.05 (m, 2H), 3.75 (s, 3H), 5.51
(d, 1H, J3 ) 9.8 Hz), 5.77 (d, 1H, J3 ) 9.8 Hz), 6.07 (s, 1H),
6.51 (s, 1H), 7.59 (d, 2H, J3 ) 8.8 Hz), 8.22 (d, 2H, J3 ) 8.8
Hz); 13C NMR (CDCl3, Me4Si) δ -1.6, 11.0, 50.8, 52.9, 59.4,
124.3, 127.8, 129.6, 139.1, 146.9, 147.9, 165.9; ESIMS m/z
801.2 (2M + H)+, 823.3 (2M + Na)+; FAB+ m/z 401 (M + H)+,
423 (M + Na)+; HRMS calcd for C16H25N2O6SSi 401.1203,
found 401.1187.
IR 2955 (m), 1719 (s), 1329 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.05 (s, 9H), 0.95-1.15 (m, 2H), 2.80-3.10 (m, 2H), 3.73
(s, 3H), 3.85-4.00 (m, 5H), 4.95-5.15 (m, 2H), 5.25-5.50 (m,
1H), 5.85 (d, 1H, J4 ) 1.7 Hz), 6.14 (s, 1H), 6.62 (d, 1H, J4 )
1.1 Hz), 7.40 (d, 2H, J3 ) 8.2 Hz), 8.05 (d, 2H, J3 ) 8.4 Hz);
13C NMR (CDCl3, Me4Si) δ -1.6, 10.7, 49.1, 51.2, 52.6, 52.7,
62.0, 119.3, 128.9, 129.8, 130.2, 130.3, 134.4, 139.7, 143.6,
166.6, 167.0; ESIMS m/z 454.2 (M + H)+, 476.2 (M + Na)+,
907.6 (2M + H)+; FAB+ m/z 454 (M + H)+, 476 (M + Na)+;
HRMS calcd for C21H32NO6SSi 454.1720, found 454.1720.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(3-fluorophenyl)methyl)acrylate (6e). Alkylation of
the â-aminoester 5e yielded 102 mg (99%) of the title com-
pound as a pale yellow oil.
IR 2893 (m), 1725 (s), 1331 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.05 (s, 9H), 0.95-1.15 (m, 2H), 2.80-3.10 (m, 2H), 3.74
(s, 3H), 3.80-4.10 (m, 2H), 4.95-5.15 (m, 2H), 5.25-5.55 (m,
1H), 5.88 (d, 1H, J4 ) 1.7 Hz), 6.09 (s, 1H), 6.60 (d, 1H, J4 )
1.1 Hz), 6.95-7.15 (m, 3H), 7.25-7.45 (m, 1H); 13C NMR
(CDCl3, Me4Si) δ -1.6, 10.7, 49.1, 51.2, 52.7, 61.7 (d, J4 ) 1.4
Hz), 115.5 (d, J2 ) 21.2 Hz), 116.0 (d, J2 ) 22.2 Hz), 119.2,
124.5 (d, J4 ) 2.8 Hz), 129.6, 130.6 (d, J3 ) 8.5 Hz), 134.5,
139.8, 141.0 (d, J3 ) 6.7 Hz), 163.3 (d, J1 ) 246.9 Hz), 166.6;
ESIMS m/z 414.2 (M + H)+, 436.2 (M + Na)+; FAB+ m/z 414
(M + H)+, 436 (M + Na)+; HRMS calcd for C19H29FNO4SSi
414.1571, found 414.1620.
Methyl 2-(Furan-2-yl(2-(trimethylsilyl)ethylsulfon-
amido)methyl)acrylate (5o): Conditions B. The crude
product was purified by silica gel chromatography (Et2O/
hexane ) 3/7) to yield 489 mg (71%) of the title compound as
a yellow oil.
IR 3370 (m), 2955 (m), 1723 (s), 1335 (s) cm-1 1H NMR
;
(CDCl3, Me4Si) δ 0.02 (s, 9H), 0.80-1.05 (m, 2H), 2.80-3.00
(m, 2H), 3.77 (s, 3H), 5.49 (d, 1H, J3 ) 9.5 Hz), 5.57 (d, 1H, J3
) 9.5 Hz), 6.00 (s, 1H), 6.27 (d, 1H, J3 ) 3.3 Hz), 6.34 (dd, 1H,
J3 ) 3.2 Hz, J3 ) 1.9 Hz), 6.42 (s, 1H), 7.37 (dd, 1H, J3 ) 1.9
Hz, J4 ) 1.0 Hz); 13C NMR (CDCl3, Me4Si) δ -1.6, 10.8, 50.4,
52.7, 53.58, 108.0, 111.2, 128.6, 138.2, 142.9, 152.3, 166.1;
ESIMS m/z 346.1 (M + H)+, 691.3 (2M + H)+, 713.3 (2M +
Na)+; FAB+ m/z 165 (M - SESNH2 + H)+, 346 (M + H)+, 368
(M + Na)+; HRMS calcd for C14H24NO5SSi 346.1144, found
346.1149.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(2-bromophenyl)methyl)acrylate (6f). Alkylation of
the â-aminoester 5f yielded 117 mg (99%) of the title compound
as a pale yellow oil.
IR 2950 (m), 1716 (s), 1333 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.03 (s, 9H), 0.95-1.15 (m, 2H), 2.80-3.05 (m, 2H), 3.72
(s, 3H), 4.08 (dd, 2H, J3 ) 6.5 Hz, J4 ) 1.1 Hz), 5.00-5.20 (m,
2H), 5.35-5.60 (m, 1H), 5.88 (d, 1H, J4 ) 1.5 Hz), 6.21 (d, 1H
J4 ) 0.8 Hz), 6.60 (d, 1H, ) 0.8 Hz), 7.20 (ddd, 1H, J4 ) 2.0
Hz, J3 ) 7.2 Hz, J3 ) 7.8 Hz), 7.33 (ddd, 1H, J4 ) 1.3 Hz, J3
) 7.2 Hz, J3 ) 7.8 Hz), 7.42 (dd, 1H, J4 ) 2.0 Hz, J3 ) 7.8
Hz), 7.61 (dd, 1H, J4 ) 1.3 Hz, J3 ) 7.8 Hz); 13C NMR (CDCl3,
Me4Si) δ -1.6, 10.5, 50.5, 51.4, 52.6, 62.6, 119.0, 125.0, 128.0,
129.8, 130.0, 130.8, 133.8, 134.7, 137.9, 139.4, 166.4; ESIMS
m/z 474.4/476.4 (M + H)+; FAB+ m/z 474/476 (M + H)+; HRMS
calcd for C19H29BrNO4SSi 474.0770, found 474.0749.
General Procedure for the Alkylation of â-Ami-
noesters 6. To a mixture5a of â-aminoester 5 (0.25 mmol) and
K2CO3 (345 mg, 2.5 mmol) in 3.5 mL of DMF was added allyl
bromide (121 mg, 1 mmol). The mixture was stirred at room
temperature for 6 h, then filtered and diluted with AcOEt. The
organic layer was successively washed with water and brine,
dried over MgSO4, filtered, and evaporated, to yield the
corresponding N-allyl-â-aminoester 6.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(phenyl)methyl)acrylate (6a). Alkylation of the
â-aminoester 5a yielded 97 mg (98%) of the title compound as
a pale yellow oil.
IR 2953 (m), 1720 (s), 1328 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.04 (s, 9H), 0.95-1.15 (m, 2H), 2.75-3.05 (m, 2H), 3.70
(s, 3H), 3.93 (d, 2H, J3 ) 6.5 Hz), 4.95-5.15 (m, 2H), 5.20-
5.45 (m, 1H), 5.91 (dd, 1H, J2 ) 0.6 Hz, J4 ) 1.7 Hz), 6.09 (s,
1H), 6.58 (dd, 1H, J2 ) 0.6 Hz, J4 ) 1.3 Hz), 7.25-7.45 (m,
5H); 13C NMR (CDCl3, Me4Si) δ -1.6, 10.7, 49.1, 51.1, 52.5,
62.4, 118.9, 128.5, 128.8, 129.0, 129.1, 134.7, 138.1, 140.3,
166.8; ESIMS m/z 396.1 (M + H)+, 791.7 (2M + H)+, 813.3
(2M + Na)+; FAB+ m/z 396 (M + H)+, 418 (M + Na)+; HRMS
calcd for C19H30NO4SSi 396.1665, found 356.1675.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(naphthalen-2-yl)methyl)acrylate (6g). Alkylation
of the â-aminoester 5g yielded 109 mg (98%) of the title
compound as a pale yellow oil.
IR 2953 (m), 1723 (s), 1333 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.03 (s, 9H), 1.00-1.15 (m, 2H), 2.80-3.10 (m, 2H), 3.71
(s, 3H), 4.00 (dd, 2H, J4 ) 5.8 Hz, J3 ) 5.9 Hz), 4.90-5.15 (m,
2H), 5.20-5.45 (m, 1H), 5.95 (d, 1H, J4 ) 1.1 Hz), 6.27 (s, 1H),
6.64 (s, 1H), 7.40-7.60 (m, 3H), 7.70-7.90 (m, 4H); 13C NMR
(CDCl3, Me4Si) δ -1.6, 10.7, 49.0, 51.2, 52.6, 62.5, 119.1, 126.9,
127.0, 127.9, 128.0, 128.6, 128.9, 129.0, 133.3, 133.6, 134.7,
135.6, 140.3, 166.9; ESIMS m/z 446.4 (M + H)+, 468.4 (M +
Na)+; FAB+ m/z 446 (M + H)+, 468 (M + Na)+; HRMS calcd
for C23H32NO4SSi 446.1821, found 446.1814.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(3,5-dimethoxyphenyl)methyl)acrylate (6b). Alky-
lation of the â-aminoester 5b yielded 112 mg (98%) of the title
compound as a pale yellow oil.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(m-tolyl)methyl)acrylate (6h). Alkylation of the
â-aminoester 5h yielded 100 mg (98%) of the title compound
as a pale yellow oil.
IR 2950 (m), 1719 (s), 1330 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.04 (s, 9H), 0.95-1.15 (m, 2H), 2.85-3.05 (m, 2H), 3.73
(s, 3H), 3.79 (s, 6H), 3.93 (d, 2H, J3 ) 6.7 Hz), 4.95-5.15 (m,
2H), 5.25-5.50 (m, 1H), 5.89 (d, 1H, J4 ) 1.3 Hz), 6.03 (s, 1H),
6.41 (t, 1H, J3 ) 2.2 Hz), 6.46 (t, 2H, J3 ) 2.2 Hz), 6.55 (d, 1H,
J4 ) 0.7 Hz); 13C NMR (CDCl3, Me4Si) δ -1.6, 10.7, 49.0, 51.0,
52.6, 55.7, 60.3, 100.2, 107.2, 118.9, 128.8, 134.9, 140.2, 140.5,
161.4, 166.8; ESIMS m/z 456.2 (M + H)+, 478.3 (M + Na)+,
911.5 (2M + H)+; FAB+ m/z 455 (M - e-)+, 478 (M + Na)+;
HRMS calcd for C21H33NO6SSi 455.1798, found 455.1815.
IR 2953 (m), 1719 (s), 1325 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.04 (s, 9H), 0.95-1.15 (m, 2H), 2.37 (s, 3H), 2.75-3.05
(m, 2H), 3.70 (s, 3H), 3.92 (d, 2H, J3 ) 6.4 Hz), 4.95-5.15 (m,
2H), 5.15-5.40 (m, 1H), 5.90 (dd, 1H, J2 ) 0.4 Hz, J4 ) 1.3
Hz), 6.05 (s, 1H), 6.56 (dd, 1H, J2 ) 0.4 Hz, J4 ) 1.3 Hz), 7.05-
7.30 (m, 4H); 13C NMR (CDCl3, Me4Si) δ -1.6, 10.7, 21.9, 49.0,
51.0, 52.5, 62.4, 118.9, 126.0, 128.6, 129.0, 129.3, 129.8, 134.8,
137.9, 138.8, 140.3, 166.9; ESIMS m/z 410.2 (M + H)+, 432.2
(M + Na)+, 841.3 (2M + Na)+; FAB+ m/z 410 (M + H)+, 432
(M + Na)+; HRMS calcd for C20H32NO4SSi 410.1821, found
410.1841.
Methyl 4-(1-(N-Allyl-2-(trimethylsilyl)ethan-3-ylsul-
fonamido)-2-(methoxycarbonyl)allyl)benzoate (6c). Alky-
lation of the â-aminoester 5c yielded 110 mg (97%) of the title
compound as a pale yellow oil.
J. Org. Chem, Vol. 69, No. 24, 2004 8377

Declerck et al.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(3,5-dimethylphenyl)methyl)acrylate (6i). Alkyla-
tion of the â-aminoester 5i yielded 103 mg (97%) of the title
compound as a pale yellow oil.
the â-aminoester 5n yielded 107 mg (97%) of the title com-
pound as a pale yellow oil.
1
IR 2950 (m), 1723 (s), 1528 (s), 1350 (s), 1335 (s) cm-1; H
NMR (CDCl3, Me4Si) δ 0.06 (s, 9H), 0.90-1.10 (m, 2H), 2.85-
3.10 (m, 2H), 3.79 (s, 3H), 3.93 (d, 1H, J3 ) 7.0 Hz), 4.00 (d,
1H, J3 ) 5.7 Hz), 5.00-5.20 (m, 2H), 5.35-5.60 (m, 1H), 5.80
(d, 1H, J4 ) 1.5 Hz), 6.19 (s, 1H), 6.67 (d, 1H, J4 ) 0.9 Hz),
7.51 (d, 2H, J3 ) 8.7 Hz), 8.23 (d, 2H, J3 ) 8.7 Hz); 13C NMR
(CDCl3, Me4Si) δ -1.6, 10.6, 49.3, 51.3, 52.9, 61.6, 119.7, 124.2,
129.6, 131.0, 134.2, 139.2, 146.3, 147.8, 166.5; ESIMS m/z
396.3 (M + H)+, 791.7 (2M + H)+; FAB+ m/z 441 (M + H)+,
463 (M + Na)+; HRMS calcd for C19H29N2O6SSi 441.1516,
found 441.1517.
IR 2953 (m), 1721 (s), 1331 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.04 (s, 9H), 0.95-1.15 (m, 2H), 2.32 (s, 6H), 2.75-3.05
(m, 2H), 3.70 (s, 3H), 3.91 (d, 2H, J3 ) 6.1 Hz), 4.95-5.15 (m,
2H), 5.15-5.40 (m, 1H), 5.90 (dd, 1H, J2 ) 0.6 Hz, J4 ) 1.7
Hz), 6.01 (s, 1H), 6.54 (dd, 1H, J2 ) 0.5 Hz, J4 ) 1.3 Hz), 6.91
(s, 2H), 6.95 (s, 1H); 13C NMR (CDCl3, Me4Si) δ -1.6, 10.7,
21.8, 48.9, 51.0, 52.5, 62.4, 118.8, 126.8, 128.4, 130.2, 134.9,
137.8, 138.6, 140.5, 166.9; ESIMS m/z 424.3 (M + H)+; FAB+
m/z 424 (M + H)+, 446 (M + Na)+; HRMS calcd for C21H34-
NO4SSi 424.1978, found 424.2021.
General Procedure for the Synthesis of 2,5-Dihydro-
pyrrole Derivatives 7: Thermal Conditions. Cl2(PCy3)-
(IMes)RudCHPh (8 mg, 0.01 mmol) was added to a solution12a
of N-allyl-â-aminoester 6 (0.20 mmol) in 20 mL of CH2Cl2, and
the mixture was stirred overnight at room temperature. Then
35 µL of DMSO (50 equiv/Ru) was added and the mixture was
stirred for 24 h. The solution was evaporated. Silica gel
chromatography (Et2O/hexane) yielded the corresponding 2,5-
dihydropyrrole 7.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(2,3-methylenedioxyphenyl)methyl)acrylate (6j).
Alkylation of the â-aminoester 5j yielded 108 mg (98%) of the
title compound as a pale yellow oil.
IR 2938 (m), 1720 (s), 1329 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.05 (s, 9H), 0.95-1.20 (m, 2H), 2.80-3.15 (m, 2H), 3.70
(s, 3H), 3.89 (dd, 1H, J2 ) 5.8 Hz, J3 ) 16.0 Hz), 4.05 (dd, 1H,
J2 ) 7.2 Hz, J3 ) 16.0 Hz), 4.95-5.15 (m, 2H), 5.20-5.45 (m,
1H), 5.95-6.00 (m, 3H), 6.10 (s, 1), 6.55 (d, 1H, J4 ) 1.5 Hz),
6.70-6.90 (m, 3H); 13C NMR (CDCl3, Me4Si) δ -1.6, 10.4, 49.0,
50.8, 52.5, 57.4, 101.3, 109.2, 118.9, 120.1, 121.9, 122.4, 128.3,
134.6, 139.1, 145.8, 147.8, 166.5; ESIMS m/z 440.1 (M + H)+,
462.4 (M + Na)+; FAB+ m/z 440 (M + H)+, 444 (M + Na)+;
HRMS calcd for C20H30NO6SSi 440.1563, found 440.1534.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(4-chlorophenyl)methyl)acrylate (6k). Alkylation
of the â-aminoester 5k yielded 106 mg (99%) of the title
compound as a pale yellow oil.
Microwave Irradiation. A solution14a of Cl2(PCy3)(IMes)-
RudCHPh in CH2Cl2 (0.5 mM, 0.5 mL) was added to N-allyl-
â-aminoester 6 (0.005 mmol), and the mixture was irradiated
by microwave 5 min at 100 °C. Filtration through a plug of
silica yielded the corresponding 2,5-dihydropyrrole 7.
Methyl 2-Phenyl-1-(2-(trimethylsilyl)ethylsulfonyl)-
2,5-dihydro-1H-pyrrole-3-carboxylate (7a): Thermal Con-
ditions. The crude product was purified by silica gel chroma-
tography (Et2O/hexane ) 3/7) to yield 72 mg (98%) of the title
compound4a as a white solid.
IR 2948 (m), 1718 (s), 1329 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.05 (s, 9H), 0.95-1.10 (m, 2H), 2.75-3.05 (m, 2H), 3.73
(s, 3H), 3.80-4.05 (m, 2H), 5.00-5.15 (m, 2H), 5.25-5.55 (m,
1H), 5.88 (d, 1H, J4 ) 1.5 Hz), 6.05 (s, 1H), 6.59 (d, 1H, J4 )
0.9 Hz), 7.25 (d, 2H, J3 ) 8.4 Hz), 7.35 (d, 2H, J3 ) 8.7 Hz);
13C NMR (CDCl3, Me4Si) δ -1.6, 10.7, 49.1, 51.2, 52.7, 61.7,
119.3, 129.3, 129.4, 130.3, 134.4, 134.8, 136.8, 139.8, 166.7;
ESIMS m/z 430.2 (M + H)+, 452.0 (M + Na)+; FAB+ m/z 430
(M + H)+, 452 (M + Na)+; HRMS calcd for C19H28ClNO4SSi
430.1275, found 430.1266
Microwave Irradiation. Cyclization of the compound 6a
yielded 1.8 mg (98%) of the title compound.
Mp 95.6-97.0 °C dec; IR 2950 (m), 1729 (s), 1340 (s), 1335
1
(s) cm-1; H NMR (CDCl3, Me4Si) δ -0.15 (s, 9H), 0.55-0.95
(m, 2H), 2.20-2.50 (m, 2H), 3.65 (s, 3H), 4.41 (ddd, 1H, J2 )
17.1 Hz, J3 ) 6.2 Hz, J4 ) 2.0 Hz), 4.79 (dt, 1H, J2 ) 17.1 Hz,
J3 ) 2.6 Hz), 5.84 (ddd, 1H, J4 ) 6.1 Hz, J4 ) 2.6 Hz, J4 ) 1.7
Hz), 6.95 (dt, 1H, J3 ) 2.2 Hz, J4 ) 1.8 Hz), 7.30-7.45 (m,
5H); 13C NMR (CDCl3, Me4Si) δ -1.8, 10.3, 50.3, 52.3, 55.9,
68.8, 128.2, 129.0, 129.1, 135.8, 136.5, 140.0, 162.7; ESIMS
m/z 368.0 (M + H)+, 390.2 (M + Na)+, 735.3 (2M + H)+, 757.1
(2M + Na)+; FAB+ m/z 368 (M + H)+; HRMS calcd for C17H26-
NO4SSi 368.1352, found 368.1349.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(2-iodophenyl)methyl)acrylate (6l). Alkylation of
the â-aminoester 5l yielded 129 mg (99%) of the title compound
as a pale yellow oil.
Methyl 2-(3,5-Dimethoxyphenyl)-1-(2-(trimethylsilyl)-
ethylsulfonyl)-2,5-dihydro-1H-pyrrole-3-carboxylate
(7b): Thermal Conditions. The crude product was purified
by silica gel chromatography (Et2O/hexane ) 4/6) to yield 82
mg (95%) of the title compound as a white solid.
IR 2950 (m), 1723 (s), 1331 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.04 (s, 9H), 1.00-1.15 (m, 2H), 2.90-3.05 (m, 2H), 3.74
(s, 3H), 4.10 (d, 2H, J3 ) 6.7 Hz), 5.00-5.20 (m, 2H), 5.35-
5.60 (m, 1H), 5.83 (d, 1H, J4 ) 1.5 Hz), 6.08 (s, 1H), 6.61 (d,
1H, J4 ) 0.7 Hz), 6.95-7.10 (m, 1H), 7.30-7.45 (m, 2H), 7.85-
7.95 (m, 1H); 13C NMR (CDCl3, Me4Si) δ -1.5, 10.5, 50.6, 51.5,
52.6, 67.1, 101.2, 118.9, 128.8, 130.1, 130.3, 130.3, 134.8, 139.5,
140.7, 141.2, 166.4; ESIMS m/z 522.3 (M + H)+, 544.4 (M +
Na)+; FAB+ m/z 522 (M + H)+, 544 (M + Na)+; HRMS calcd
for C19H29INO4SSi 522.0631, found 522.0655.
Microwave Irradiation. Cyclization of the compound 6b
yielded 2.0 mg (92%) of the title compound.
Mp 101.0-105.0 °C dec; IR 2950 (m), 1729 (s), 1344 (s) cm-1
;
1H NMR (CDCl3, Me4Si) δ -0.12 (s, 9H), 0.60-1.00 (m, 2H),
2.25-2.60 (m, 2H), 3.67 (s, 3H), 3.80 (s, 6H), 4.39 (ddd, 1H, J2
) 17.1 Hz, J3 ) 6.1 Hz, J4 ) 2.0 Hz), 4.77 (dt, 1H, J2 ) 17.1
Hz, J3 ) 2.6 Hz), 5.76 (ddd, 1H, J4 ) 6.1 Hz, J4 ) 2.4 Hz, J4
) 1.7 Hz), 6.41 (t, 1H, J3 ) 2.2 Hz), 6.51 (d, 2H), 6.93 (q, 1H,
J3 ) 2.0 Hz, J4 ) 1.8 Hz); 13C NMR (CDCl3, Me4Si) δ -1.9,
10.5, 50.4, 52.3, 55.7, 56.0, 68.7, 100.4, 106.4, 135.6, 136.6,
142.3, 161.4, 162.7; ESIMS m/z 428.1 (M + H)+, 450.2 (M +
Na)+; FAB+ m/z 427 (M + e-)+, 428 (M + H)+; HRMS calcd
for C19H30NO6SSi 428.1563, found 428.1582.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(4-(2-(trimethylsilyl)ethynyl)phenyl)methyl)-
acrylate (6m). Alkylation of the â-aminoester 5m yielded 120
mg (98%) of the title compound as a pale yellow oil.
IR 2953 (m), 1723 (s), 1334 (s) cm-1; 1H NMR (CDCl3, Me4-
Si) δ 0.05 (s, 9H), 0.27 (s, 9H), 0.95-1.10 (m, 2H), 2.80-3.05
(m, 2H), 3.69 (s, 3H), 3.90 (d, 2H, J3 ) 6.3 Hz), 4.95-5.15 (m,
2H), 5.20-5.45 (m, 1H), 5.87 (d, 1H, J4 ) 1.5 Hz), 6.06 (s, 1H),
6.58 (d, 1H, J4 ) 1.1 Hz), 7.25 (d, 1H, J3 ) 8.4 Hz), 7.47 (d,
1H, J3 ) 8.4 Hz); 13C NMR (CDCl3, Me4Si) δ -2.0, -0.1, 10.3,
48.6, 50.8, 52.2, 61.8, 95.1, 104.4, 118.8, 123.0, 128.4, 128.7,
132.3, 134.1, 138.2, 139.5, 166.3; ESIMS m/z 492.4 (M + H)+;
FAB+ m/z 492 (M + H)+, 514 (M + Na)+; HRMS calcd for
C24H38NO4SSi2 492.2060, found 492.2047.
Methyl 2-(4-(Methoxycarbonyl)phenyl)-1-(2-(trimeth-
ylsilyl)ethylsulfonyl)-2,5-dihydro-1H-pyrrole-3-carboxy-
late (7c): Thermal Conditions. The crude product was
purified by silica gel chromatography (Et2O/hexane ) 4/6) to
yield 78 mg (92%) of the title compound as a white solid.
Microwave Irradiation. Cyclization of the compound 6c
yielded 2.0 mg (92%) of the title compound.
Methyl 2-((N-Allyl-2-(trimethylsilyl)ethan-3-ylsulfon-
amido)(4-nitrophenyl)methyl)acrylate (6n). Alkylation of
Mp 106.4-107.4 °C; IR 2950 (m), 1731 (s), 1348 (s) cm-1
1H NMR (CDCl3, Me4Si) δ -0.15 (s, 9H), 0.55-0.95 (m, 2H),
;
8378 J. Org. Chem., Vol. 69, No. 24, 2004

Synthesis of Substituted Pyrroles
2.25-2.60 (m, 2H), 3.65 (s, 3H), 3.93 (s, 3H), 4.44 (ddd, 1H, J2
) 17.1 Hz, J3 ) 6.1 Hz, J4 ) 1.9 Hz), 4.80 (dt, 1H, J2 ) 17.1
Hz, J3 ) 2.6 Hz), 5.90 (ddd, 1H, J4 ) 6.1 Hz, J4 ) 2.6 Hz, J4
) 1.9 Hz), 6.98 (q, 1H, J3 ) 2.0 Hz), 7.46 (ddd, 2H, J3 ) 8.5
J3 ) 2.6 Hz), 5.79 (ddd, 1H, J4 ) 6.1 Hz, J4 ) 2.6 Hz, J4 ) 1.7
Hz), 6.94 (dt, 1H, J3 ) 2.2 Hz, J4 ) 1.9 Hz), 7.05-7.35 (m,
4H); 13C NMR (CDCl3, Me4Si) δ -1.8, 10.3, 21.8, 50.2, 52.3,
55.9, 68.8, 125.3, 128.8, 129.0, 129.8, 135.8, 136.9, 138.7, 139.9,
162.76; ESIMS m/z 382.1 (M + H)+, 404.1 (M + Na)+, 763.4
(2M + H)+; FAB+ m/z 382 (M + H)+, 404 (M + Na)+; HRMS
calcd for C18H28NO4SSi 382.1508, found 382.1505.
Hz, J4 ) 1.9 Hz), 8.06 (ddd, 2H, J3 ) 8.5 Hz, J4 ) 1.9 Hz); 13
C
NMR (CDCl3, Me4Si) δ -1.8, 10.3, 50.2, 52.4, 52.6, 56.1, 68.5,
128.2, 130.4, 130.8, 135.4, 137.1, 145.2, 162.5, 166.9; ESIMS
m/z 426.2 (M + H)+, 851.2 (2M + H)+, 873.3 (2M + Na)+; FAB+
m/z 426 (M + H)+, 448 (M + Na)+; HRMS calcd for C19H28-
NO6SSi 426.1407, found 426.1403.
Methyl 2-(3,5-Dimethylphenyl)-1-(2-(trimethylsilyl)-
ethylsulfonyl)-2,5-dihydro-1H-pyrrole-3-carboxylate
(7i): Thermal Conditions. The crude product was purified
by silica gel chromatography (Et2O/hexane ) 3/7) to yield 73
mg (92%) of the title compound as a white solid.
Methyl 2-(3-Fluorophenyl)-1-(2-(trimethylsilyl)ethyl-
sulfonyl)-2,5-dihydro-1H-pyrrole-3-carboxylate
(7e):
Thermal Conditions. The crude product was purified by
silica gel chromatography (Et2O/hexane ) 3/7) to yield 73 mg
(95%) of the title compound as a white solid.
1
Mp 96.0-97.2 °C; IR 2950 (m), 1731 (s), 1344 (s) cm-1; H
NMR (CDCl3, Me4Si) δ -0.15 (s, 9H), 0.55-0.95 (m, 2H), 2.20-
2.50 (m, 2H), 2.32 (s, 6H), 3.67 (s, 3H), 4.40 (ddd, 1H, J2
)
Mp 80.1-80.7 °C dec; IR 2950 (m), 1731 (s), 1346 (s) cm-1
;
17.1 Hz, J3 ) 6.1 Hz, J4 ) 2.0 Hz), 4.77 (dt, 1H, J2 ) 17.1 Hz,
J3 ) 2.6 Hz), 5.75 (ddd, 1H, J4 ) 6.1 Hz, J4 ) 2.4 Hz, J4 ) 1.7
Hz), 6.90-7.00 (m, 4H); 13C NMR (CDCl3, Me4Si) δ -1.9, 10.2,
21.7, 50.2, 52.3, 55.8, 68.7, 125.9, 130.7, 135.9, 136.3, 138.6,
139.8, 162.8; ESIMS m/z 396.1 (M + H)+, 418.1 (M + Na)+;
791.4 (2M + H)+, 813.2 (2M + Na)+; FAB+ m/z 396 (M + H)+,
418 (M + Na)+; HRMS calcd for C19H30NO4SSi 396.1665, found
396.1651.
1H NMR (CDCl3, Me4Si) δ -0.12 (s, 9H), 0.60-0.95 (m, 2H),
2.25-2.60 (m, 2H), 3.66 (s, 3H), 4.42 (ddd, 1H, J2 ) 2.0 Hz, J3
) 6.1 Hz, J4 ) 17.1 Hz), 4.78 (dt, 1H, J2 ) 2.6 Hz, J4 ) 17.1
Hz), 5.85 (m, 1H), 6.90-7.10 (m, 3H), 7.15-7.25 (m, 1H), 7.30-
7.45 (m, 1H); 13C NMR (CDCl3, Me4Si) δ -1.8, 10.3, 50.3, 52.4,
56.0, 68.3 (d, J4 ) 1.6 Hz), 114.9 (d, J2 ) 22.0 Hz), 116.0 (d, J2
) 21.2 Hz), 124.1 (d, J4 ) 2.8 Hz), 130.7 (d, J3 ) 7.8 Hz), 135.4,
136.9, 142.8 (d, J3 ) 6.1 Hz), 162.6, 163.3 (d, J1 ) 247.5 Hz);
ESIMS m/z 386.1 (M + H)+, 771.2 (2M + H)+, 793.2 (2M +
Na)+; FAB+ m/z 386 (M + H)+, 408 (M + Na)+, 771 (2M +
H)+, 793 (2M + Na)+; HRMS calcd for C17H25FNO4SSi 386.1258,
found 386.1234.
Methyl 2-(2,3-Methylenedioxyphenyl)-1-(2-(trimethyl-
silyl)ethylsulfonyl)-2,5-dihydro-1H-pyrrole-3-carboxy-
late (7j): Thermal Conditions. The crude product was
purified by silica gel chromatography (Et2O/hexane ) 4/6) to
yield 79 mg (96%) of the title compound as a white solid.
Methyl 2-(2-Bromophenyl)-1-(2-(trimethylsilyl)ethyl-
sulfonyl)-2,5-dihydro-1H-pyrrole-3-carboxylate (7f): Ther-
mal Conditions. The crude product was purified by silica gel
chromatography (Et2O/hexane ) 3/7) to yield 80 mg (90%) of
the title compound as a white solid.
Mp 123.5-124.6 °C dec; IR 2953 (m), 1729 (s), 1356 (s) cm-1
;
1H NMR (CDCl3, Me4Si) δ -0.10 (s, 9H), 0.65-1.00 (m, 2H),
2.40-2.70 (m, 2H), 3.68 (s, 3H), 4.44 (ddd, 1H, J2 ) 16.7 Hz,
J3 ) 6.1 Hz, J4 ) 1.9 Hz), 4.76 (dt, 1H, J2 ) 16.7 Hz, J3 ) 2.4
Hz), 5.84 (ddd, 1H, J4 ) 6.1 Hz, J4 ) 2.4 Hz, J4 ) 1.7 Hz),
5.98 (s, 2H), 6.75-6.95 (m, 4H); 13C NMR (CDCl3, Me4Si) δ
-1.8, 10.2, 50.0, 52.3, 56.0, 64.7, 101.5, 109.1, 121.2, 122.2,
122.4, 133.8, 137.3, 145.6, 148.2, 162.7; ESIMS m/z 412.0 (M
+ H)+, 450.1 (M + K)+, 823.2 (2M + H)+, 845.1 (2M + Na)+;
FAB+ m/z 411 (M + e-)+, 434 (M + Na)+; HRMS calcd for
C18H25NO4SSi 411.1172, found 411.1180.
Microwave Irradiation. Cyclization of compound 6f yielded
2.0 mg (90%) of the title compound.
Mp 88.7-90.1 °C dec; IR 2950 (m), 1728 (s), 1340 (s) cm-1
;
1H NMR (CDCl3, Me4Si) δ -0.11 (s, 9H), 0.65-1.00 (m, 2H),
2.35-2.70 (m, 2H), 3.66 (s, 3H), 4.47 (ddd, 1H, J2 ) 17.1 Hz,
J3 ) 6.3 Hz, J4 ) 2.0 Hz), 4.83 (dt, 1H, J2 ) 17.1 Hz, J3 ) 2.8
Hz), 6.31 (ddd, 1H, J4 ) 6.3 Hz, J4 ) 2.8 Hz, J4 ) 2.0 Hz),
6.95 (q, 1H, J3 ) 2.0 Hz), 7.10-7.40 (m, 3H), 7.55-7.65 (m,
1H); 13C NMR (CDCl3, Me4Si) δ -2.2, 9.8, 49.7, 51.9, 55.9, 67.9,
123.6, 127.8, 129.8, 130.4, 133.7, 134.7, 136.8, 138.7, 162.0;
ESIMS m/z 445.9/447.9 (M + H)+; FAB+ m/z 446/448 (M +
H)+; HRMS calcd for C17H25BrNO4SSi 446.0457, found 446.0427.
Methyl 2-(Naphthalen-2-yl)-1-(2-(trimethylsilyl)ethyl-
sulfonyl)-2,5-dihydro-1H-pyrrole-3-carboxylate (7g): Ther-
mal Conditions. The crude product was purified by silica gel
chromatography (Et2O/hexane ) 3/7) to yield 75 mg (90%) of
the title compound as a white solid.
Methyl 2-(4-Chlorophenyl)-1-(2-(trimethylsilyl)ethyl-
sulfonyl)-2,5-dihydro-1H-pyrrole-3-carboxylate
(7k):
Thermal Conditions. The crude product was purified by
silica gel chromatography (Et2O/hexane ) 3/7) to yield 77 mg
(95%) of the title compound4a as a white solid.
Microwave Irradiation. Cyclization of the compound 6k
yielded 1.5 mg (95%) of the title compound.
Mp 86.1-87.4 °C dec; IR 2950 (m), 1733 (s), 1346 (s) cm-1
;
1H NMR (CDCl3, Me4Si) δ -0.11 (s, 9H), 0.55-0.95 (m, 2H),
2.25-2.60 (m, 2H), 3.66 (s, 3H), 4.40 (ddd, 1H, J2 ) 17.1 Hz,
J3 ) 6.1 Hz, J4 ) 2.0 Hz), 4.77 (dt, 1H, J2 ) 17.1 Hz, J3 ) 2.6
Hz), 5.83 (ddd, 1H, J4 ) 6.1 Hz, J4 ) 2.6 Hz, J4 ) 1.7 Hz),
Microwave Irradiation. Cyclization of compound 6g
yielded 1.9 mg (89%) of the title compound.
6.96 (dt, 1H, J3 ) 2.2 Hz, J4 ) 1.9 Hz), 7.35-7.40 (m, 4H); 13
C
Mp 123.1-124.3 °C; IR 2950 (m), 1728 (s), 1339 (s) cm-1
;
1H NMR (CDCl3, Me4Si) δ -0.37 (s, 9H), 0.50-0.85 (m, 2H),
2.10-2.45 (m, 2H), 3.62 (s, 3H), 4.49 (ddd, 1H, J2 ) 17.1 Hz,
J3 ) 6.3 Hz, J4 ) 2.0 Hz), 4.84 (dt, 1H, J2 ) 17.1 Hz, J3 ) 2.6
Hz), 6.02 (ddd, 1H, J4 ) 6.1 Hz, J4 ) 2.6 Hz, J4 ) 1.7 Hz),
7.02 (dt, 1H, J3 ) 2.0 Hz, J4 ) 1.8 Hz), 7.35-7.60 (m, 3H),
7.75-7.95 (m, 4H); 13C NMR (CDCl3, Me4Si) δ -2.1, 10.2, 50.3,
52.3, 56.0, 69.0, 125.1, 126.9, 127.9, 128.1, 128.6, 129.1, 133.6,
133.8, 135.7, 136.7, 137.1, 162.7; ESIMS m/z 418.2 (M + H)+,
440.0 (M + Na)+; FAB+ m/z 417 (M - e-)+, 440 (M + Na)+;
HRMS calcd for C21H27NO4SSi 417.1430, found 417.1421.
Methyl 2-m-Tolyl-1-(2-(trimethylsilyl)ethylsulfonyl)-
2,5-dihydro-1H-pyrrole-3-carboxylate (7h): Thermal Con-
ditions. The crude product was purified by silica gel chroma-
tography (Et2O/hexane ) 3/7) to yield 75 mg (98%) of the title
compound as a white solid.
NMR (CDCl3, Me4Si) δ -1.8, 10.3, 50.3, 52.4, 55.9, 68.2, 129.35,
129.6, 134.9, 135.4, 136.8, 138.8, 162.5; ESIMS m/z 402.0 (M
+ H)+; FAB+ m/z 402 (M + H)+, 424 (M + Na)+; HRMS calcd
for C17H25ClNO4SSi 402.0962, found 402.0955.
Methyl 2-(2-Iodophenyl)-1-(2-(trimethylsilyl)ethylsul-
fonyl)-2,5-dihydro-1H-pyrrole-3-carboxylate (7l): Ther-
mal Conditions. The crude product was purified by silica gel
chromatography (Et2O/hexane ) 3/7) to yield 93 mg (94%) of
the title compound as a white solid.
Mp 134.1-134.7 °C dec; IR 2948 (m), 1729 (s), 1341 (s) cm-1
;
1H NMR (CDCl3, Me4Si) δ -0.11 (s, 9H), 0.65-1.00 (m, 2H),
2.35-2.70 (m, 2H), 3.66 (s, 3H), 4.50 (ddd, 1H, J2 ) 17.3 Hz,
J3 ) 6.3 Hz, J4 ) 2.0 Hz), 4.82 (dt, 1H, J2 ) 17.3 Hz, J3 ) 2.6
Hz), 6.21 (ddd, 1H, J4 ) 6.1 Hz, J4 ) 2.8 Hz, J4 ) 2.0 Hz),
6.90-7.10 (m, 2H), 7.20-7.45 (m, 2H), 7.85-7.95 (m, 1H); 13
C
1
Mp 85.0-87.2 °C; IR 2945 (m), 1731 (s), 1344 (s) cm-1; H
NMR (CDCl3, Me4Si) δ -2.8, 9.1, 49.0, 51.2, 55.3, 71.3, 98.6,
127.9, 128.6, 129.3, 134.6, 136.0, 139.6, 141.7, 161.3; ESIMS
m/z 494.0 (M + H)+, 987.0 (2M + H)+; FAB+ m/z 494 (M +
H)+; HRMS calcd for C17H25INO4SSi 494.0318, found 494.0307.
NMR (CDCl3, Me4Si) δ -0.15 (s, 9H), 0.55-0.95 (m, 2H), 2.20-
2.50 (m, 2H), 2.37 (s, 3H), 3.66 (s, 3H), 4.41 (ddd, 1H, J2
)
17.1 Hz, J3 ) 6.3 Hz, J4 ) 2.0 Hz), 4.78 (dt, 1H, J2 ) 17.1 Hz,
J. Org. Chem, Vol. 69, No. 24, 2004 8379

Declerck et al.
General Procedure for the Synthesis of Pyrroles 8. To
a stirred solution2y of 2,5-dihydropyrrole 7 (0.10 mmol) in 2
mL of DMF was added t-BuOK (37 mg, 0.50 mmol). The
mixture was stirred at room temperature for 2 h, then 15 mL
of AcOEt was added and the mixture was neutralized with aq
KHSO4 (1%) and washed with saturated NaHCO3, water, and
brine. The organic layer was dried over MgSO4, filtered, and
evaporated. Silica gel chromatography (Et2O/hexane) yielded
the pyrrole 8.
Methyl 2-Phenyl-1H-pyrrole-3-carboxylate (8a). The
crude product was purified by silica gel chromatography (Et2O/
hexane ) 2/8) to yield 16 mg (80%) of the title compound4a as
a white solid.
FAB+ m/z 280/282 (M + H)+; HRMS calcd for C12H11BrNO2
279.9973, found 279.9960.
Methyl 2-(Naphthalen-2-yl)-1H-pyrrole-3-carboxylate
(8g). The crude product was purified by silica gel chromatog-
raphy (Et2O/hexane ) 2/8) to yield 17 mg (66%) of the title
compound as a white solid.
Mp 110.6-112.3 °C dec; IR 3463 (m), 2928 (m), 1694 (s),
1284 (s) cm-1; 1H NMR (acetone-d6, Me4Si) δ 3.62 (s, 3H), 6.62
(t, 1H, J3 ) 2.8 Hz), 6.87 (t, 1H, J3 ) 2.8 Hz), 7.40-7.50 (m,
2H), 7.70-7.90 (m, 4H), 8.05-8.15 (m, 1H); 10.80 (large s, 1H);
13C NMR (acetone-d6, Me4Si) δ 50.9, 112.8, 119.4, 127.1, 127.1,
127.9, 128.3, 128.4, 128.5, 129.0, 131.0, 133.8, 134.0, 137.5,
165.7; ESIMS m/z 252.0 (M + H)+, 503.5 (2M + H)+; FAB+
m/z 251 (M - e-)+, 252 (M + H)+; HRMS calcd for C16H13NO2
251.0946, found 251.0958.
Methyl 2-m-Tolyl-1H-pyrrole-3-carboxylate (8h). The
crude product was purified by silica gel chromatography (Et2O/
hexane ) 2/8) to yield 15 mg (72%) of the title compound as a
white solid.
Mp 90.0-91.4 °C dec; IR 3463 (m), 2943 (m), 1694 (s), 1290
1
(s) cm-1; H NMR (acetone-d6, Me4Si) δ 3.57 (s, 3H), 6.54 (t,
1H, J3 ) 2.8 Hz), 6.78 (t, 1H, J3 ) 2.8 Hz), 7.20-7.35 (m, 3H),
7.50-7.60 (m, 2H), 10.61 (large s, 1H); 13C NMR (acetone-d6,
Me4Si) δ 50.8, 112.4, 112.6, 119.0, 128.5, 128.7, 129.9, 133.4,
137.6, 165.6; ESIMS m/z 202.1 (M + H)+; FAB+ m/z 201 (M
- e-)+, 202 (M + H)+; HRMS calcd for C12H11NO2 201.0790,
found 201.0779.
Methyl 2-(3,5-Dimethoxyphenyl)-1H-pyrrole-3-carbox-
ylate (8b). The crude product was purified by silica gel
chromatography (Et2O/hexane ) 3/7) to yield 22 mg (83%) of
the title compound as a white solid.
Mp 120.9-124.0 °C dec; IR 3380 (m), 2930 (m), 1704 (s),
1306 (s) cm-1; 1H NMR (acetone-d6, Me4Si) δ 3.63 (s, 3H), 3.74
(s, 6H), 6.40 (t, 1H, J3 ) 2.3 Hz), 6.57 (t, 1H, J3 ) 2.8 Hz),
6.80 (t, 1H, J3 ) 2.8 Hz), 6.83 (d, 2H, J3 ) 2.3 Hz), 10.65 (large
s, 1H); 13C NMR (acetone-d6, Me4Si) δ 52.7, 57.4, 102.6, 109.6,
114.4, 114.7, 120.7, 136.7, 139.0, 163.1, 167.4; ESIMS m/z
262.1 (M + H)+; FAB+ m/z 261 (M - e-)+, 262 (M + H)+;
HRMS calcd for C14H15NO4 261.1001, found 261.1030.
Methyl 2-(4-(Methoxycarbonyl)phenyl)-1H-pyrrole-3-
carboxylate (8c). The crude product was purified by silica
gel chromatography (Et2O/hexane ) 3/7) to yield the title
compound along with the product of transesterification 8c′ (8c/
8c′ ) 1/3).
Mp 71.1-72.1 °C dec; IR 3458 (m), 2950 (m), 1693 (s), 1293
1
(s) cm-1; H NMR (acetone-d6, Me4Si) δ 2.25 (s, 3H), 3.58 (s,
3H), 6.53 (t, 1H, J3 ) 2.8 Hz), 6.77 (t, 1H, J3 ) 2.8 Hz), 7.00-
7.25 (m, 2H), 7.30-7.40 (m, 2H), 10.59 (large s, 1H); 13C NMR
(acetone-d6, Me4Si) δ 21.4, 50.8, 112.4, 112.6, 118.9, 127.0,
128.6, 129.2, 130.4, 133.3, 137.8, 138.0, 165.6; ESIMS m/z
216.2 (M + H)+; FAB+ m/z 215 (M - e-)+, 216 (M + H)+;
HRMS calcd for C13H13NO2 215.0946, found 215.0951.
Methyl 2-(3,5-Dimethylphenyl)-1H-pyrrole-3-carboxy-
late (8i). The crude product was purified by silica gel chro-
matography (Et2O/hexane ) 2/8) to yield 18 mg (78%) of the
title compound as a white solid.
Mp 124.8-126.2 °C dec; IR 3463 (m), 2943 (m), 1693 (s),
1303 (s) cm-1; 1H NMR (acetone-d6, Me4Si) δ 2.17 (s, 6H), 3.54
(s, 3H), 6.48 (t, 1H, J3 ) 2.8 Hz), 6.71 (t, 1H, J3 ) 2.8 Hz),
6.80-6.90 (m, 1H), 7.10-7.20 (m, 2H), 10.49 (large s, 1H); 13
C
NMR (acetone-d6, Me4Si) δ 18.9, 48.3, 109.9, 110.2, 116.3,
125.3, 127.6, 130.9, 135.5, 163.2; ESIMS m/z 230.2 (M + H)+;
FAB+ m/z 229 (M - e-)+, 230 (M + H)+; HRMS calcd for
C14H15NO2 229.1103, found 229.1096.
Methyl 2-(2,3-Methylenedioxyphenyl)-1H-pyrrole-3-
carboxylate (8j). The crude product was purified by silica
gel chromatography (Et2O/hexane ) 3/7) to yield 22 mg (88%)
of the title compound as a white solid.
8c: 1H NMR (acetone-d6, Me4Si) δ 3.63 (s, 3H), 3.83 (s, 3H),
6.55-6.65 (m, 1H), 6.85-6.90 (m, 1H), 7.70-7.80 (m, 2H),
7.90-8.00 (m, 2H), 10.85 (large s, 1H).
Methyl 2-(4-(tert-Butyloxycarbonyl)phenyl)-1H-pyrrole-
Mp 101.9-104.7 °C dec; IR 3455 (m), 2968 (m), 1730 (s),
1295 (s) cm-1; 1H NMR (acetone-d6, Me4Si) δ 3.62 (s, 3H), 5.93
(s, 2H), 6.57 (t, 1H, J3 ) 2.8 Hz), 6.75-6.85 (m, 2H), 6.85 (t,
1H, J3 ) 2.8 Hz), 7.10-7.20 (m, 1H), 10.61 (large s, 1H); 13C
NMR (acetone-d6, Me4Si) δ 50.9, 101.7, 108.6, 112.2, 114.1,
115.8, 119.3, 121.9, 123.8, 131.3, 145.8, 148.3, 165.5; ESIMS
m/z 246.0 (M + H)+; FAB+ m/z 245 (M - e-)+, 246 (M + H)+;
HRMS calcd for C13H11NO4 245.0688, found 245.0678.
Methyl 2-(4-Chlorophenyl)-1H-pyrrole-3-carboxylate
(8k). The crude product was purified by silica gel chromatog-
raphy (Et2O/hexane ) 2/8) to yield 19 mg (81%) of the title
compound4a as a white solid.
Mp 113.3-114.5 °C dec; IR 3380 (m), 2948 (m), 1695 (s),
1286 (s) cm-1; 1H NMR (acetone-d6, Me4Si) δ 3.62 (s, 3H), 6.58
(t, 1H, J3 ) 2.8 Hz), 6.84 (t, 1H, J3 ) 2.8 Hz), 7.30-7.40 (m,
2H), 7.55-7.65 (m, 2H), 10.75 (large s, 1H); 13C NMR (acetone-
d6, Me4Si) δ 50.9, 112.8, 112.9, 119.4, 128.7, 131.5, 132.1, 133.9,
136.1, 165.5; ESIMS m/z 236.3 (M + H)+; FAB+ m/z 235 (M
- e-)+, 236 (M + H)+; HRMS calcd for C12H10ClNO2 235.0400,
found 235.0383.
Methyl 2-(2-Iodophenyl)-1H-pyrrole-3-carboxylate (8l).
The crude product was purified by silica gel chromatography
(Et2O/hexane ) 2/8) to yield 27 mg (81%) of the title compound
as a white solid.
Mp 140.4-144.8 °C dec; IR 3465 (m), 2950 (m), 1711 (s),
1275 (s) cm-1; 1H NMR (acetone-d6, Me4Si) δ 3.47 (s, 3H), 6.51
(t, 1H, J3 ) 2.8 Hz), 6.79 (t, 1H, J3 ) 2.8 Hz), 7.05 (ddd, 1H,
J3 ) 7.9 Hz, J3 ) 7.3 Hz, J4 ) 1.9 Hz), 7.26 (dd, 1H, J3 ) 7.6
Hz, J4 ) 1.9 Hz), 7.34 (ddd, 1H, J3 ) 7.6 Hz, J3 ) 7.3 Hz, J4
1
3-carboxylate (8c′). H NMR (acetone-d6, Me4Si) δ 1.53 (s,
9H), 3.63 (s, 3H), 6.55-6.65 (m, 1H), 6.85-6.90 (m, 1H), 7.65-
7.75 (m, 2H), 7.85-7.95 (m, 2H), 10.85 (large s, 1H).
Methyl 2-(3-Fluorophenyl)-1H-pyrrole-3-carboxylate
(8e). The crude product was purified by silica gel chromatog-
raphy (Et2O/hexane ) 2/8) to yield 18 mg (81%) of the title
compound as a white solid.
Mp 106.9-108.3 °C dec; IR 3460 (m), 2945 (m), 1719 (s),
1296 (s) cm-1; 1H NMR (acetone-d6, Me4Si) δ 3.64 (s, 3H), 6.59
(t, 1H, J3 ) 2.8 Hz), 6.85 (t, 1H, J3 ) 2.8 Hz), 7.00-7.10 (m,
1H), 7.30-7.50 (m, 4H), 10.88 (large s, 1H); 13C NMR (acetone-
d6, Me4Si) δ 51.0, 112.9, 113.0, 115.1 (d, J2 ) 21.1 Hz), 116.7
(d, J2 ) 23.4 Hz), 119.5, 125.6 (d, J4 ) 3.0 Hz), 130.5 (d, J3 )
9.1 Hz), 135.4 (d, J3 ) 9.1 Hz), 135.9, 163.2 (d, J1 ) 243.0 Hz),
165.5; ESIMS m/z 220.1 (M + H)+; FAB+ m/z 219 (M - e-)+,
220 (M + H)+; HRMS calcd for C12H11FNO2 220.0774, found
220.0784.
Methyl 2-(2-Bromophenyl)-1H-pyrrole-3-carboxylate
(8f). The crude product was purified by silica gel chromatog-
raphy (Et2O/hexane ) 2/8) to yield 23 mg (81%) of the title
compound as a white solid.
Mp 145.8-147.4 °C dec; IR 3458 (m), 2948 (m), 1693 (s),
1290 (s) cm-1; 1H NMR (acetone-d6, Me4Si) δ 3.48 (s, 3H), 6.52
(t, 1H, J3 ) 2.8 Hz), 6.81 (t, 1H, J3 ) 2.8 Hz), 7.15-7.35 (m,
3H), 7.55-7.60 (m, 1H), 10.57 (large s, 1H); 13C NMR (acetone-
d6, Me4Si) δ 50.7, 111.0, 114.4, 118.9, 125.1, 127.7, 130.7, 133.2,
133.5, 135.5, 135.9, 165.1; ESIMS m/z 280.2/282.1 (M + H)+;
8380 J. Org. Chem., Vol. 69, No. 24, 2004

Synthesis of Substituted Pyrroles
) 1.2 Hz), 7.83 (dd, 1H, J3 ) 7.9 Hz, J4 ) 1.2 Hz), 10.50 (large
s, 1H); 13C NMR (acetone-d6, Me4Si) δ 50.7, 101.1, 110.9, 114.1,
118.7, 128.4, 130.63, 132.4, 139.1, 139.5, 139.9, 165.0; ESIMS
m/z 328.1 (M + H)+; FAB+ m/z 328 (M + H)+; HRMS calcd
for C12H11INO2 327.9835, found 327.9863.
from Biotage (Personal Chemistry) and CEM for the
microwave-activated experiments is acknowledged.
Supporting Information Available: 1H NMR spectra of
compounds 5a-o, 6a-c, 6e-n, 7a-c, 7e-l, 8a,b, 8c,c′, and
8e-l. This material is available free of charge via the Internet
at http://pubs.acs.org.
Acknowledgment. We thank the CNRS and the
MENRT for financial support. The technical support
JO048519R
J. Org. Chem, Vol. 69, No. 24, 2004 8381