Synthesis of substituted 3-iodopyrroles by cycloisomerization of propargylic aziridines with iodine

Article abstract of DOI:10.1016/j.tet.2011.03.015

The electrophilic cyclizations of N-substituted propargylic aziridines are described. 3-Iodopyrroles having a variety of substituents at the 2- and 3-positions were synthesized by reacting propargylic aziridines with iodine. Whereas N-tosyl-substituted su

Full text of DOI:10.1016/j.tet.2011.03.015

Tetrahedron 67 (2011) 3194e3200
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Synthesis of substituted 3-iodopyrroles by cycloisomerization of propargylic
aziridines with iodine
*
Masahiro Yoshida , Salina Easmin, Mohammad Al-Amin, Yuuki Hirai, Kozo Shishido
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The electrophilic cyclizations of N-substituted propargylic aziridines are described. 3-Iodopyrroles hav-
ing a variety of substituents at the 2- and 3-positions were synthesized by reacting propargylic aziridines
with iodine. Whereas N-tosyl-substituted substrates require a platinum catalyst to promote the reaction,
the iodine-promoted cycloisomerizations proceed when N-benzyl-substituted substrates are employed.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 2 February 2011
Received in revised form 4 March 2011
Accepted 7 March 2011
Available online 12 March 2011
1. Introduction
aziridination of the N-sulfonylimines with sulfonium propargylides
(Scheme 2).4b,8 Thus, when the imines 1aef, having a variety of
Substituted pyrroles are used extensively in heterocyclic chem-
istry as key structural subunits in biologically active molecules and
in compounds for industrial purposes.1 They are also widely utilized
as synthetic intermediates in organic synthesis for further structural
elaboration.2 Consequently, considerable effort has been devoted to
the development of an efficient methodology for the synthesis of
pyrroles.3 Transition metal-catalyzed cycloisomerization of prop-
argylic aziridines is one such methodology, in which a variety of 2,5-
disubstituted pyrroles is obtained with gold4 or platinum5 catalysts.
During the course of our study of platinum-catalyzed cyclo-
isomerization of propargylic oxiranes, it was found that 3-iodofur-
ans could be synthesized in the presence of NIS as an electrophile
(Scheme 1).5,6 We anticipated that a similar reaction would proceed
if propargylic aziridines were employed as the substrate. We report
herein the synthesis of 3-iodopyrroles by cycloisomerization of
propargylic aziridines with iodine, in which various 2,5-di-
substituted 3-iodopyrroles were synthesized with high efficiency.7
substituents, were treated with the propargylic dimethylsulfonium
salts 2aec and Cs2CO3 at rt, the corresponding cis-propargylic
aziridines 3aeh were selectively produced in moderate to good
yields.
Scheme 2. Synthesis of N-tosyl-substituted propargylic aziridines 3.
The initial reactions for the synthesis of substituted pyrroles
were attempted using the diphenyl-substituted propargylic azir-
idine 3a (Table 1). When 3a was subjected to the reaction with NIS
and 10 mol % of PtCl2 in dioxane/H2O (2/1) at 100 ꢀC following our
procedure for the synthesis of 3-iodofuran,5,6 only decomposition
of the substrate was observed (entry 1). However, the desired 3-
iodopyrrole 4a was produced in 35% yield using iodine as the
electrophile (entry 2). After experimenting with various solvents
and temperatures (entries 3e8), we found that the yield of 4a could
be increased to 92% when the reaction was carried out in MeCN/
H2O (10/1) at 80 ꢀC (entry 8).
Scheme 1. Synthesis of 3-iodofuran by cycloisomerization of propargylic oxiranes.
2. Results and discussion
N-Tosyl-substituted propargylic aziridines, the initial substrates
for the cycloisomerization reaction, were easily prepared by ylide
Having identified a useful set of reaction conditions, we next
conducted a study of the substrate scope (Table 2). Propargylic
aziridine 3b having a cyclohexyl group on the aziridine ring
* Corresponding author. Tel./fax: þ81 88 6337294; e-mail address: yoshida@
ph.tokushima-u.ac.jp (M. Yoshida).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.015

M. Yoshida et al. / Tetrahedron 67 (2011) 3194e3200
3195
Table 1
successfully reacted with iodine in the presence of the platinum
catalyst to produce the 3-iodopyrrole 4b in 95% yield (entry 1).
When the reactions of the substrates 3c, 3d, and 3e containing an
alkyl group were carried out, the corresponding products 4c, 4d, and
4ewere obtained in moderateyields (entries 2e4). The reaction of 3f
having a 2-bromophenyl group also afforded the pyrrole 4f without
anyproblems (entry5). Thecorresponding product 4g was produced
from the reaction of 3g with a hexyl group on the alkynyl moiety;
however, the yield was decreased (entry 6). When the TMS-
substituted substrate 3h was subjected to the reaction, the desily-
lated product 4h was obtained in only moderate yield (entry 7).
Platinum-catalyzed iodocyclizations of 3a
Ts
N
Ts
N
electrophile
10 mol % PtCl2
Ph
Ph
solvent
Ph
I
Ph
3a
4a
Entry
Electrophile
Solvent
Temp (ꢀC)
Yield (%)
1
2
3
4
5
6
7
8
NIS
I2
I2
I2
I2
I2
I2
I2
Dioxane/H2O (2/1)
Dioxane/H2O (2/1)
PhCN/H2O (2/1)
MeCN/H2O (2/1)
MeCN/H2O (2/1)
MeCN/H2O (2/1)
MeCN/H2O (5/1)
MeCN/H2O (10/1)
100
100
100
100
80
60
80
80
Decomp.
35
48
50
55
48
60
92
A
plausible mechanism for the platinum-catalyzed cyclo-
isomerization of 3 is shown in Scheme 3. Recently, Pale reported
results of mechanistic studies on the metal-catalyzed cyclo-
isomerization of propargylic oxiranes to furans in the presence of
alcohol, in which the epoxide ring opening product with a hydroxyl
group was identified as the reaction intermediate.9 We concluded
that a similar process can be expected to occur using our aqueous
reaction conditions. Thus, the platinum catalyst activates the sub-
strate 3 by coordination to the aziridine nitrogen, which promotes
the aziridine ring opening by water as shown in 5. The resulting
sulfonamide nitrogen in 6 attacks the distal position of the alkyne
to form the cyclized intermediate 7. Aromatization by elimination
of water followed by iodo-demetalation with iodine produces the
iodopyrrole 4.
Table 2
Reactions with various propargylic aziridines 3beha
Entry
Substrate
Product
Yield (%)
Ts
N
Ts
N
Cy
Pr
Ph
1
95
Cy
Pr
I
I
I
I
4b
3b
Ph
Ph
Ph
Ph
Ts
N
Ts
N
Ph
4c
2
3
4
5
6
64
65
85
66
3c
Ts
N
Ts
N
Bu
Ph
4d
Bu
3d
Scheme 3.
Ts
N
Ts
N
i
We next examined the reactions using N-benzyl-substituted
propargylic aziridines.5 In our initial attempt, we used trans-
propargylic aziridine 8a under platinum-catalyzed iodocyclization
conditions. When 8a was treated with 10 mol % of PtCl2 and 2 equiv
NIS in dioxane/H2O (2/1) at 100 ꢀC for 60 min, the desired 3-
iodopyrrole 9a was produced in 22% yield along with the non-io-
dinated pyrrole 10 as the inseparable major product10 in 49% yield
(Scheme 4). Several attempts under various platinum-catalyzed
conditions resulted in similar results. For this reason, it was thought
Pr
2-BrPh
Ph
Ph
4e
i
Pr
3e
Ts
N
Ts
N
Ph
4f
2-BrPh
I
3f
Ph
Ts
Ts
N
N
Hex
4g
25
45
Ph
Ph
3g
I
Hex
Ts
N
Ts
N
Ph
7
I
3h
4h
TMS
a
All reactions were carried out in the presence of 2 equiv iodine and 10 mol %
PtCl2 MeCN/H2O (10/1) at 80 ꢀC for 10 min.
Scheme 4.

3196
M. Yoshida et al. / Tetrahedron 67 (2011) 3194e3200
that proto-demetalation of the pyrrolyl-platinum intermediate 11
occurred prior to iodo-demetalation in the case of the N-benzyl-
substituted propargylic aziridines 8a.
Table 4
Reactions with various propargylic aziridines 8beja
We next turned our attention to the electrophilic activation of
propargylic aziridines,11 in which a similar process could take place
in the reaction of 8a with iodine (Table 3). When 8a was treated
with 2 equiv of iodine and 2 equiv of NaHCO3 in THF at rt,11r no
reaction occurred (entry 1). However, the desired product 9a was
obtained in 43% yield under reflux conditions in THF (entry 2). The
yield was improved to 64% when the reaction was carried out in
dioxane at 100 ꢀC (entry 3), but the non-iodinated pyrrole 10 was
isolated as a by-product in 28% yield. For this reason, it was
expected that the hydrogen iodide produced in the reaction would
catalyze the cycloisomerization of 8a to the non-iodinated pyrrole
10.12 When 5 equiv of NaHCO3 was used to neutralize the hydrogen
iodide, the iodopyrrole 9a was successfully obtained in 90% yield as
the sole product (entry 4).
Entry
Substrate
Product
Yield (%)
Bn
N
Bn
N
Cy
Cy
Ph
1
90
Cy
Cy
I
9b
8b
Ph
Bn
Bn
N
Bn
N
Bn
9c
2
3
79
86
8c
I
Table 3
Bn
Bn
N
Iodocyclizations of 8a in the presence of iodine
N
Cy
Bn
N
Bn
N
Bn
N
Cy
Cy
Pr
I2
Pr
Cy
+
8d
9d
I
NaHCO3, solvent
10–90 min
Cy
I
Pr
Bn
N
9a
10
Bn
N
8a
Cy
( )3
Temp (ꢀC)
Yields (%)
OTBDPS
4
5
86
76
Entry
Solvent
NaHCO3 (equiv)
Cy
9a
10
9e
OTBDPS
I
8e
( )3
1
2
3
4
THF
THF
Dioxane
Dioxane
2
2
2
5
rt
N.R.
43
64
Reflux
100
100
d
28
d
Bn
N
Bn
N
90
( )3
OH
Cy
Cy
OH
( )3
9f
I
8f
The electrophilic cyclizations of the substituted propargylic
aziridines 8bej under the optimized conditions are summarized in
Table 4. When the reactions of the substrates 8bee containing,
respectively, a phenyl, benzyl, allyl, and siloxypropyl group at the
alkynyl position were carried out, the corresponding products
9bee were obtained in good yields (entries 1e4). The propargylic
aziridine 8f having a free hydroxyl group was uneventfully trans-
formed to the 3-iodopyrrole 9f in 76% yield (entry 5). The substrates
8g and 8h, which contain butyl and tert-butyl groups on the azir-
idine ring, were successfully transformed to the 3-iodopyrroles 9g
and 9h in 94% and 95% yield, respectively (entries 6 and 7). The
reactions of the phenyl- and 2-naphthyl-substituted substrates 8i
and 8j also proceeded to afford the corresponding products 9i and
9j in 95% and 68% yield, respectively (entries 8 and 9).
A plausible mechanism for the iodine-promoted cyclization of
the N-benzyl-substituted propargylic aziridines 8 is shown in
Scheme 5. Coordination of the propargylic triple bond to an iodine
cation forms the cyclic iodonium ion 12. Subsequent attack of the
aziridine nitrogen on the iodonium ion produces the cyclized cat-
ionic intermediate 13, which undergoes aromatization by elimi-
nation of the proton leading to the 3-iodopyrrole 9.13
Further functionalization of the resulting products provides
a broad insight into the 3-iodo-substitued pyrroles (Scheme 6). When
the MiyauraeSuzuki coupling reaction of 4b with 4-methox-
yphenylboronic acid was carried out, the 4-methoxyphenyl group
was introduced to give 14 in 76% yield. The Sonogashira coupling
reaction of 4b with phenylacetylene also afforded the coupled prod-
uct 15 in 70% yield. The iodopyrrole 9a likewise underwent the
Negishi coupling with 3-methoxyphenylzinc chloride to produce the
corresponding product 16 in 83% yield.
Bn
N
Bn
N
Bu
Pr
9g
6
7
8
94
95
95
68
Bu
8g
I
I
I
Pr
Pr
Pr
Pr
Bn
N
Bn
N
t
Bu
Ph
Pr
t
Bu
8h
9h
Bn
N
Bn
N
Pr
9i
Ph
8i
Bn
N
Bn
N
Nap
Pr
9b
Nap
I
9j
8j
a
All reactions were carried out in the presence of 2 equiv iodine and 5 equiv
NaHCO3 in dioxane at 100 ꢀC for 10 min.
b
Nap¼2-naphthyl.

M. Yoshida et al. / Tetrahedron 67 (2011) 3194e3200
3197
4.2. General procedure for the synthesis of N-tosyl-
substituted propargylic aziridines 3.8 Reaction of 1f with 2a
(Scheme 2)
To a stirred solution of N-sulfonyl imine 1f (250 mg, 0.972 mmol)
in CH2Cl2 (10 mL) were gradually added propargylic dime-
thylsulfonium salt 2a (329 mg, 0.972 mmol) and Cs2CO3 (317 mg,
0.972 mmol). The reaction mixture was stirred for 1.5 h at rt. The
reaction mixture was filtered through a pad of silica gel to remove
the inorganic salt. Concentration at reduced pressure gave the res-
idue, which was chromatographed on silica gel using hexane/AcOEt
(80/20) as the eluent to give the propargylic aziridine 3f (234 mg,
53%) as a yellow oil.
Scheme 5.
4.2.1. 2-Butyl-3-phenylethynyl-1-(toluene-4-sulfonyl)aziridine (3d).
Yield: 32%; colorless oil; IR (neat): 3029, 2956, 2871, 2230, 2360,1597,
1492, 1444, 1330 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d 7.87 (2H, d,
J¼8.0 Hz), 7.40e7.35 (4H, m), 7.32e7.26 (3H, m), 3.58 (1H, d,
J¼6.8 Hz), 2.95 (1H, q, J¼6.8 Hz), 2.45 (3H, s), 1.74e1.59 (4H, m),
1.32e1.29 (2H, m), 0.84 (3H, t, J¼7.2 Hz); 13C NMR (100 MHz, CDCl3):
144.8,134.8,131.9,129.7,128.8,128.2,128.0,121.9, 82.1, 45.3, 34.4, 28.7,
27.9, 22.2, 21.7, 13.9; HRMS (ESI): m/z calcd for C21H23NNaO2S
(MþþNa): 376.1347; found 376.1347.
4.2.2. 2-(2-Bromo-phenyl)-3-phenylethynyl-1-(toluene-4-sulfo-
nyl)aziridine (3f). Yield: 53%; yellow oil; IR (neat): 3024, 2924,
2233, 1597, 1569, 1492, 1442, 1380 cmꢁ1 1H NMR (400 MHz,
;
CDCl3):
d
7.94 (2H, d, J¼8.0 Hz), 7.55 (1H, d, J¼8.0 Hz), 7.38e7.32
(3H, m), 7.26e7.15 (5H, m), 7.08e7.06 (2H, m), 4.29 (1H, d,
J¼6.8 Hz), 3.94 (1H, d, J¼6.8 Hz), 2.44 (3H, s); 13C NMR (100 MHz,
CDCl3): d 145.0, 134.0, 132.0, 131.9, 131.6, 129.8, 129.7, 129.3, 128.6,
127.9, 127.9, 126.9, 123.2, 121.3, 84.4, 81.1, 46.8, 36.1, 21.5; HRMS
(ESI): m/z calcd for C23H18BrNNaO2S (MþþNa): 474.0139; found
474.0136.
4.2.3. 2-Oct-1-ynyl-3-phenyl-1-(toluene-4-sulfonyl)aziridine (3g).
Yield: 73%; colorless oil; IR (neat) 3061, 2931, 2859, 2248,
1598 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
7.88 (2H, d, J¼8.3 Hz),
7.34e7.27 (7H, m), 3.94 (1H, d, J¼6.9 Hz), 3.63 (1H, dt, J¼6.9 and
1.7 Hz), 2.43 (3H, s), 2.00 (2H, td, J¼6.8 and 1.7 Hz), 1.31e1.10 (8H,
m), 0.84 (3H, t, J¼7.2 Hz); 13C NMR (400 MHz, CDCl3):
d 144.8,134.8,
132.3, 129.8, 128.6, 128.3, 127.9, 127.8, 86.8, 72.2, 46.2, 36.3, 31.2,
28.2, 28.0, 22.5, 21.7, 18.6, 14.0; HRMS (ESI) m/z calcd for
C23H27NNaO2S (MþþNa): 404.1660; found 404.1654.
Scheme 6.
4.3. General procedure for the synthesis of N-tosyl-
substituted 3-iodopyrroles 4. Reaction of 3b (entry 1 in
Table 2)
3. Conclusion
In conclusion, we have developed a methodology for the syn-
thesis of 3-iodopyrroles by an electrophilic cyclization of the N-
substituted propargylic aziridines. Whereas N-tosyl-substituted
substrates require a platinum catalyst to promote the reaction, the
iodine-promoted cycloisomerizations proceed when N-benzyl-
substituted substrates are employed. The reactions afford a variety
of substituted 3-iodopyrroles, and the process is an efficient and
convenient protocol for the preparation of these derivatives.
To a stirred solution of propargylic aziridine 3b (32.0 mg,
0.084 mmol) in CH3CN/H2O (10/1) were gradually added iodine
(42.8 mg, 0.168 mmol) and PtCl2 (2.2 mg, 8.4 mmol) at rt. After the
stirring was continued for 25 min at 80 ꢀC, the reaction mixture was
cooled to rt and diluted with minimum amount of Et2O. The solu-
tion was then dried over MgSO4 and filtered through a small
amount of silica gel. Concentration at reduced pressure gave the
residue, which was chromatographed on silica gel using hexane/
AcOEt (92/8) as the eluent to give the 3-iodopyrrole 4b (34.0 mg,
95%) as a colorless oil.
4. Experimental
4.1. General
4.3.1. 3-Iodo-2,5-diphenyl-1-(toluene-4-sulfonyl)-1H-pyrrole
Materials were obtained from commercial suppliers and used
without further purification except when otherwise noted. Sol-
vents were dried and distilled according to standard protocol.
Propargylic aziridines 3aec,e,h,4b,8 and 8aej5 were prepared
according to the procedures described in the literature.
(4a). Yield: 92%; colorless oil; IR (neat): 3060, 3029, 2924, 1597,
1487,1444,1376 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
7.47e7.37 (10H,
m), 7.09 (2H, d, J¼8.0 Hz), 7.04 (2H, d, J¼8.0 Hz), 6.38 (1H, s), 2.38
(3H, s); 13C NMR (100 MHz, CDCl3):
144.8,140.8,139.6,135.0,132.2,
131.5,129.9,129.6,129.6,129.1,128.8,128.7,128.4,128.3,127.9,127.6,
d

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M. Yoshida et al. / Tetrahedron 67 (2011) 3194e3200
127.6, 127.5, 127.4, 127.1, 123.7, 74.8, 21.6; HRMS (ESI): m/z calcd for
C23H18INNaO2S (MþþNa): 522.0001; found 522.0002.
128.8, 127.6, 127.4, 127.3, 121.9, 65.5, 21.6; HRMS (ESI) m/z calcd for
C
17H14INNaO2S (MþþNa): 445.9688; found 445.9678.
4.3.2. 5-Cyclohexyl-3-iodo-2-phenyl-1-(toluene-4-sulfonyl)-1H-pyr-
4.4. General procedure for the synthesis of N-benzyl-
role (4b). Yield: 95%; IR (neat): 3061, 3029, 2926, 2852, 1597, 1477,
substituted 3-iodopyrroles 9. Reaction of 8a (entry 4 in Table 3)
1446, 1371 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d 7.38e7.29 (4H, m),
7.25e7.22 (2H, m), 7.16e7.12 (3H, m), 6.20 (1H, s), 3.28 (1H, tt, J¼2.8
To a stirred solution of propargylic aziridine 8a (200 mg,
and 11.2 Hz), 2.38 (3H, s), 2.07 (2H, d, J¼11.2 Hz), 1.84e1.73 (3H, m),
0.711 mmol) in dioxane (20.0 mL) were gradually added iodine
(361 mg, 1.42 mmol) and NaHCO3 (299 mg, 3.56 mmol) at rt. After
stirring for 10 min at 100 ꢀC, the reaction mixture was cooled to rt and
the excess I2 was removed by washing with a saturated aqueous so-
lution of Na2S2O3 (30.0 mL). The aqueous solution was then extracted
withEt2O(3ꢂ25 mL)andthecombinedorganiclayersweredriedover
MgSO4. Concentration at reduced pressure gave the residue, which
was purified by flash chromatography using hexane/AcOEt (98/2) as
the eluent to give the 3-iodopyrrole 9a (261 mg, 90%) as a colorless oil.
1.48e1.18(5H, m); 13C NMR (100 MHz, CDCl3):
d 146.2, 144.6, 137.1,
136.5, 132.4, 131.9, 129.5, 128.4, 127.3, 126.5, 117.6, 73.8, 37.6, 34.6,
26.7, 26.2, 21.6; HRMS (ESI): m/z calcd for C23H24INNaO2S (MþþNa):
528.0470; found 528.0475.
4.3.3. 3-Iodo-2-phenyl-5-propyl-1-(toluene-4-sulfonyl)-1H-pyrrole
(4c). Yield: 64%; colorless oil; IR (neat): 3029, 2962, 2930, 2873,
1729, 1597, 1494, 1444, 1375 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
d
7.40e7.29 (3H, m), 7.26 (3H, d, J¼8.0 Hz), 7.17e7.12 (3H, m), 6.19
(1H, s), 2.91 (2H, t, J¼7.2 Hz), 2.39 (3H, s), 1.75 (2H, sext, J¼7.2 Hz),
4.4.1. 1-Benzyl-5-cyclohexyl-3-iodo-2-propyl-1H-pyrrole
1.03 (3H, t, J¼7.2 Hz); 13C NMR (100 MHz, CDCl3):
d
144.7,139.9,137.1,
(9a). Yield: 90%; colorless oil; IR (neat): 3087, 3063, 3028, 2927,
136.3,132.2,132.0,130.5,129.5,128.5,127.3,127.2,126.7,126.4,119.0,
73.2, 31.2, 22.5, 21.6, 14.0; HRMS (ESI): m/z calcd for C20H20INNaO2S
(MþþNa): 488.0157; found 488.0162.
2851, 1605, 1545, 1496, 1453, 1415, 1373 cmꢁ1 1H NMR (400 MHz,
;
CDCl3):
d
7.30e7.21 (3H, m), 6.84 (2H, d, J¼7.6 Hz), 6.02 (1H, s), 5.08
(2H, s), 2.44 (2H, t, J¼7.6 Hz), 2.28 (1H, tt, J¼10.8 and 3.2 Hz),
1.78e1.64 (5H, m),1.41e1.18 (7H, m), 0.86 (3H, t, J¼7.2 Hz); 13C NMR
4.3.4. 5-Butyl-3-iodo-2-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrole
(100 MHz, CDCl3): d 140.5, 138.6, 133.2, 128.7, 127.1, 125.4, 110.5,
(4d). Yield:65%;colorlessoil;IR(neat):3029, 2956, 2928, 2870,2360,
61.6, 47.4, 35.8, 33.9, 28.9, 26.5, 26.0, 23.2, 13.9; HRMS (ESI): m/z
1597, 1444, 1376 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d 7.40e7.31 (3H,
calcd for C20H26NNaI (MþþNa): 430.1008; found 430.1010.
m), 7.27e7.25 (2H, m), 7.17e7.12 (4H, m), 6.19 (1H, s), 2.93 (2H, t,
J¼7.2 Hz), 2.40 (3H, s), 1.69 (2H, quint, J¼7.2 Hz), 1.45 (2H,
sext, J¼7.2 Hz), 0.97 (3H, t, J¼7.2 Hz); 13C NMR (100 MHz, CDCl3):
4.4.2. 1-Benzyl-5-cyclohexyl-3-iodo-2-phenyl-1H-pyrrole
(9b). Yield: 90%; white solid; mp: 102.5e102.7 ꢀC; IR (neat): 3062,
d
144.7,140.1,137.1,136.4,132.3,132.0, 130.5, 129.5, 129.3,128.5,127.3,
3028, 2926, 2850, 1637, 1509, 1496, 1449, 1353 cmꢁ1 1H NMR
;
127.2, 126.7, 126.4, 118.9, 73.2, 31.3, 28.9, 22.5, 21.6, 13.9; HRMS (ESI):
(400 MHz, CDCl3):
d
7.32e7.16 (8H, m), 6.79 (2H, d, J¼7.2 Hz), 6.19
m/z calcd for C21H22INNaO2S (MþþNa): 502.0314; found 502.0312.
(1H, s), 5.03 (2H, s), 2.32 (1H, tt, J¼11.2 and 3.2 Hz), 1.80e1.64 (5H,
m), 1.39e1.27 (2H, m), 1.25e1.15 (3H, m); 13C NMR (100 MHz,
4.3.5. 3-Iodo-5-isopropyl-2-phenyl-1-(toluene-4-sulfonyl)-1H-pyr-
CDCl3): d 141.7, 138.8, 134.7, 132.5, 131.0, 128.5, 128.0, 127.8, 127.0,
role (4e). Yield: 85%; colorless oil; IR (neat): 2969, 2360, 1597, 1559,
125.5, 112.0, 62.6, 48.4, 36.0, 34.0, 26.6, 25.9; HRMS (ESI): m/z calcd
1523, 1444, 1378 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d 7.39e7.29 (3H,
for C23H25NI (MþþH): 442.1032; found 442.1031.
m), 7.23 (3H, d, J¼8.0 Hz), 7.15 (3H, d, J¼8.0 Hz), 6.23 (1H, s), 3.65
(1H, sext, J¼6.8 Hz), 2.39 (3H, s), 1.30 (6H, d, J¼6.8 Hz); 13C NMR
4.4.3. 1,2-Dibenzyl-5-cyclohexyl-3-iodo-1H-pyrrole (9c). Yield: 79%;
(100 MHz, CDCl3):
d
147.2, 144.6, 137.5, 136.4, 132.3, 131.9, 129.5,
colorless oil; IR (neat): 3061, 3027, 2925, 2850, 1603, 1546, 1495,
128.5,127.3,126.5,117.5, 73.8, 27.9, 23.8, 21.6; HRMS (ESI): m/z calcd
1454, 1417, 1354 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d 7.28e7.14 (6H,
for C20H20INNaO2S (MþþNa): 488.0157; found 488.0157.
m), 7.03 (2H, d, J¼7.2 Hz), 6.76 (2H, d, J¼7.6 Hz), 6.09 (1H, s), 4.88
(2H, s), 3.82 (2H, s), 2.30 (1H, tt, J¼11.6 and 2.8 Hz), 1.77e1.64 (5H,
m), 1.36e1.25 (2H, m), 1.24e1.19 (3H, m); 13C NMR (100 MHz,
4.3.6. 5-(2-Bromo-phenyl)-3-iodo-2-phenyl-1-(toluene-4-sulfonyl)-
1H-pyrrole (4f). Yield: 66%; colorless oil; IR (neat): 3028, 2924,
CDCl3): d 141.4, 139.0, 138.2, 131.4, 128.6, 128.4, 127.9, 127.1, 126.1,
1596, 1561, 1478, 1456, 1379 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
125.4, 110.5, 63.7, 47.5, 35.8, 33.9, 32.8, 26.5, 25.9; HRMS (ESI): m/z
d
7.66 (1H, d, J¼8.0 Hz), 7.46e7.36 (4H, m), 7.30e7.27 (4H, m), 7.10
calcd for C24H26NNaI (MþþNa): 478.1008; found 478.1010.
(4H, s), 6.46 (1H, s), 2.38 (3H, s); 13C NMR (100 MHz, CDCl3):
d
144.9,
138.2, 137.1, 135.5, 133.8, 132.6, 132.6, 131.4, 129.9, 129.3, 128.8,
127.4, 127.4, 126.5, 125.1, 123.3, 73.2, 21.6; HRMS (ESI): m/z calcd for
C23H17BrINNaO2S (MþþNa): 599.9106; found 599.9111.
4.4.4. 2-Allyl-1-benzyl-5-cyclohexyl-3-iodo-1H-pyrrole (9d). Yield:
86%; colorless oil; IR (neat): 3063, 3028, 2926, 2851, 1637, 1605,
1496, 1452, 1417, 1354 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
7.30e7.21 (3H, m), 6.83 (2H, d, J¼7.6 Hz), 6.04 (1H, s), 5.71 (1H,
4.3.7. 2-Hexyl-3-iodo-5-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrole
ddt, J¼17.2, 10.0 and 6.0 Hz), 5.07 (2H, s), 4.96 (1H, dd, J¼10.0 and
1.6 Hz), 4.89 (1H, dd, J¼17.2 and 1.6 Hz), 3.22 (2H, d, J¼6.0 Hz), 2.33
(1H, tt, J¼11.2 and 3.2 Hz), 1.79e1.64 (5H, m), 1.35e1.17 (5H, m); 13C
(4g). Yield: 25%; yellow oil; IR (neat) 3061, 2926, 2856, 1597 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d 7.36e7.21 (7H, m), 7.13 (2H, d,
J¼8.1 Hz), 6.17 (1H, s), 2.98 (2H, t, J¼7.6 Hz), 2.37 (3H, s), 1.70 (2H,
NMR (100 MHz, CDCl3): d 141.1,138.4, 135.1, 130.1, 128.7, 127.1, 125.4,
quint, J¼7.6 Hz), 1.43e1.33 (6H, m), 0.92 (3H, t, J¼7.2 Hz); 13C NMR
115.5, 110.5, 62.4, 47.3, 35.8, 33.9, 31.4, 26.5, 26.0; HRMS (ESI): m/z
(400 MHz, CDCl3):
d 144.7, 139.8, 138.8, 136.1, 132.2, 130.6, 129.5,
calcd for C20H25NaI (MþþH): 406.1032; found 406.1033.
128.2, 127.3, 126.6, 122.2, 72.8, 31.6, 30.5, 30.1, 29.1, 22.7, 21.6, 14.1;
HRMS (ESI) m/z calcd for C23H26INNaO2S (MþþNa): 530.0627;
found 530.0627.
4.4.5. 1-Benzyl-2-[3-(tert-butyl-diphenyl-silanyloxy)-propyl]-5-cy-
clohexyl-3-iodo-1H-pyrrole (9e). Yield: 86%; colorless oil; IR (neat):
3069, 3029, 2998, 2927, 2855, 1605, 1589, 1547, 1496, 1472, 1452,
4.3.8. 4-Iodo-2-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrole
1428, 1390 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d 7.61 (4H, d,
(4h). Yield: 45%; brown solid; mp: 109.1e113.6 ꢀC; IR (neat) 3144,
J¼6.8 Hz), 7.42e7.32 (6H, m), 7.27e7.20 (3H, m), 6.78 (2H, d,
J¼6.8 Hz), 6.02 (1H, s), 5.08 (2H, s), 3.60 (2H, t, J¼7.2 Hz), 2.59 (2H, t,
J¼7.6 Hz), 2.28 (1H, tt, J¼10.8 and 3.2 Hz), 1.77e1.71 (4H, m),
1.63e1.55 (4H, m), 1.30e1.18 (4H, m), 1.02 (9H, s); 13C NMR
3066, 2917, 1596 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d 7.52 (1H, d,
J¼1.7 Hz), 7.39e7.09 (9H, m), 6.20 (1H, d, J¼1.7 Hz), 2.36 (3H, s); 13C
NMR (400 MHz, CDCl3):
d 145.2, 137.2, 135.1, 131.0, 130.0, 129.5,

M. Yoshida et al. / Tetrahedron 67 (2011) 3194e3200
3199
(100 MHz, CDCl3):
d
140.5, 138.6, 135.5, 133.8, 132.8, 129.5, 128.6,
15) as the eluent to give the coupled product 14 (22.0 mg, 76%) as
127.5, 127.1, 125.4, 110.5, 63.2, 61.3, 47.3, 35.8, 33.9, 32.7, 26.8, 26.5,
26.0, 23.5, 19.1; HRMS (ESI): m/z calcd for C36H45NOSiI (MþþH):
662.2315; found 662.2315.
a colorless oil; IR (neat) 3045, 2928, 2852, 1613, 1513 cmꢁ1; 1H NMR
(400 MHz, CDCl3): d 7.30e7.19 (5H, m), 7.13e7.07 (4H, m), 6.89 (2H,
d, J¼8.7 Hz), 6.64 (2H, d, J¼8.7 Hz), 6.24 (1H, s), 3.70 (3H, s), 3.34
(1H, tt, J¼11.2 and 2.9 Hz), 2.35 (3H, s), 2.14e2.18 (2H, m), 1.85e1.75
4.4.6. 3-(1-Benzyl-5-cyclohexyl-3-iodo-1H-pyrrol-2-yl)propan-1-ol
(3H, m), 1.52e1.19 (5H, m); 13C NMR (400 MHz, CDCl3):
d 158.0,
(9f). Yield: 76%; colorless oil; IR (neat): 3413, 3088, 3064, 2929,
144.9, 144.1, 137.2, 132.4, 132.2, 131.3, 129.3, 129.1, 127.8, 127.4, 127.0,
126.9, 126.4, 113.4, 111.7, 55.1, 37.7, 34.8, 26.8, 26.4, 21.6; HRMS (ESI)
m/z calcd for C30H31NNaO3S (MþþNa) 508.1922; found 508.1920.
2854, 1605, 1586, 1546, 1497, 1452, 1417, 1374 cmꢁ1 1H NMR
;
(400 MHz, CDCl3):
d
7.31e7.22 (3H, m), 6.84 (2H, d, J¼7.6 Hz), 6.03
(1H, s), 5.12 (2H, s), 3.56 (2H, t, J¼6.0 Hz), 2.59 (2H, t, J¼7.6 Hz), 2.31
(1H, tt, J¼11.6 and 3.2 Hz), 1.79e1.71 (4H, m), 1.66e1.55 (3H, m),
4.6. 5-Cyclohexyl-2-phenyl-3-phenylethynyl-1-(toluene-4-
sulfonyl)-1H-pyrrole (15)
1.32e1.17 (6H, m); 13C NMR (100 MHz, CDCl3):
d 140.9, 138.5, 132.2,
128.7, 127.2, 125.4, 110.6, 61.9, 61.8, 47.4, 35.9, 33.9, 32.5, 26.5, 25.9,
23.1; HRMS (ESI): m/z calcd for C20H26NONaI (MþþNa): 446.0957;
found 446.0961.
To a stirred solution of 3-iodopyrrole 4b (57.3 mg, 0.113 mmol)
in Et3N (3.8 mL) were added phenylacetylene (46.2 mg,
0.452 mmol), PdCl2(PPh3)2 (7.9 mg, 0.011 mmol), and CuI (4.3 mg,
0.023 mmol) at rt. After the stirring was continued for 14 h at 60 ꢀC,
the reaction mixture was diluted with saturated aqueous solution
of NH4Cl and extracted with AcOEt. The combined extracts were
washed with brine and the organic layer was dried over MgSO4.
Concentration at reduced pressure gave the residue, which was
chromatographed on silica gel using hexane/AcOEt (90/10) as the
eluent to give the coupled product 15 (38.0 mg, 70%) as a brown
solid. Mp: 146.4e148.3 ꢀC; IR (neat) 3061, 3032, 2928, 2853, 2213,
4.4.7. 1-Benzyl-5-butyl-3-iodo-2-propyl-1H-pyrrole
94%; colorless oil; IR (neat): 3063, 3029, 2956, 2929, 2870, 1600,
1551, 1497, 1454, 1432, 1414, 1378, 1354 cmꢁ1 1H NMR (400 MHz,
CDCl3):
(9g). Yield:
;
d
7.30e7.21 (3H, m), 6.85 (2H, d, J¼7.6 Hz), 6.02 (1H, s), 5.06
(2H, s), 2.48 (2H, t, J¼7.6 Hz), 2.36 (2H, t, J¼7.6 Hz), 1.56e1.47 (2H,
m), 1.42e1.26 (4H, m), 0.92e0.82 (6H, m); 13C NMR (100 MHz,
CDCl3): d 138.3, 134.7, 133.6, 128.7, 127.1, 125.4, 112.1, 61.1, 47.5, 30.5,
28.9, 26.1, 23.3, 22.3, 13.8, 13.8; HRMS (ESI): m/z calcd for
C18H24NNaI (MþþNa): 404.0851; found 404.0851.
1597 cmꢁ1
; d 7.44e7.35 (6H, m),
1H NMR (400 MHz, CDCl3):
7.24e7.13 (8H, m), 6.19 (1H, s) 3.27 (1H, tt, J¼11.5 and 2.8 Hz), 2.37
(3H, s), 2.07e2.11 (2H, m), 1.85e1.75 (3H, m), 1.51e1.18 (5H, m); 13C
4.4.8. 1-Benzyl-5-tert-butyl-3-iodo-2-propyl-1H-pyrrole
(9h). Yield: 95%; colorless oil; IR (neat): 3063, 3028, 2961, 2927,
NMR (400 MHz, CDCl3):
d 145.6, 144.6, 140.5, 136.2, 131.6, 131.2,
2870, 1605, 1567, 1497, 1466, 1454, 1397, 1364 cmꢁ1 1H NMR
;
131.2, 129.4, 128.2, 128.2, 127.9, 127.1, 126.4, 123.4, 113.5, 110.4, 91.3,
83.8, 37.8, 34.5, 26.7, 26.3, 21.6; HRMS (ESI) m/z calcd for
C31H29NNaO2S (MþþNa) 502.1817; found 502.1815.
(400 MHz, CDCl3):
d
7.29e7.19 (3H, m), 6.78 (2H, d, J¼7.2 Hz), 6.07
(1H, s), 5.31 (2H, s), 2.32 (2H, t, J¼7.6 Hz), 1.36 (2H, sext, J¼7.6 Hz),
1.24 (9H, s), 0.85 (3H, t, J¼7.6 Hz); 13C NMR (100 MHz, CDCl3):
d
142.6, 139.1, 135.5, 128.5, 126.9, 125.3, 111.8, 61.4, 49.2, 32.2, 30.8,
4.7. 1-Benzyl-5-cyclohexyl-3-(3-methoxy-phenyl)-2-propyl-
1H-pyrrole (16)
29.6, 28.9, 23.0, 13.9; HRMS (ESI): m/z calcd for C18H24NNaI
(MþþNa): 404.0851; found 404.0855.
To a stirred solution of 3-methoxybromobenzene (0.06 mL,
0.442 mmol) in THF (1.0 mL) was added dropwise tert-butyllithium
(0.70 mL of a 1.32 M solution in pentane, 0.884 mmol) at ꢁ78 ꢀC.
Stirring was continued for 0.2 h at the same temperature, and an-
hydrous ZnCl2 (60 mg, 0.442 mmol) was added to the reaction
mixture and then the cold bath was removed. Whilst warming, 3-
iodopyrrole 9a (30.0 mg, 0.074 mmol) and Pd(PPh3)4 (8 mg,
0.007 mmol) were added to the reaction mixture, which was then
stirred at rt for 0.5 h. The resulting mixture was filtered through
a small amount of flash silica. Concentration at reduced pressure
gave the residue, which was chromatographed on silica gel with
hexane/AcOEt (98/2) as eluent to give the coupled product 16
(23.7 mg, 83%) as a yellow oil; IR (neat): 3062, 3028, 2927, 2852,
1605, 1515, 1495, 1453, 1411, 1353 cmꢁ1; 1H NMR (400 MHz, CDCl3):
4.4.9. 1-Benzyl-3-iodo-5-phenyl-2-propyl-1H-pyrrole
(9i). Yield:
95%; colorless oil; IR (neat): 3062, 3028, 2958, 2957, 2929, 2869,
1603,1496,1453,1401,1384,1356 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
7.29e7.22 (8H, m), 6.87 (2H, d, J¼7.2 Hz), 6.35 (1H, s), 5.16 (2H, s),
2.48 (2H, t, J¼7.6 Hz),1.45 (2H, sext, J¼7.6 Hz), 0.90 (3H, t, J¼7.6 Hz);
13C NMR (100 MHz, CDCl3):
138.6, 136.0, 135.6, 132.6, 128.9, 128.7,
d
128.3, 127.2, 127.1, 125.5, 115.3, 62.9, 48.4, 29.1, 23.0, 14.0; HRMS
(ESI): m/z calcd for C20H21NI (MþþH): 402.0719; found 402.0719.
4.4.10. 1-Benzyl-3-iodo-5-naphthalen-2-yl-2-propyl-1H-pyrrole
(9j). Yield: 68%; yellow oil; IR (neat): 3057, 3029, 2961, 2928, 2872,
1630, 1603, 1497, 1454, 1414, 1379, 1357 cmꢁ1 1H NMR (400 MHz,
;
CDCl3):
d 7.81e7.74 (2H, m), 7.68e7.65 (2H, m), 7.46e7.41 (2H, m),
7.39 (1H, d, J¼7.6 Hz), 7.29e7.23 (3H, m), 6.91 (2H, d, J¼7.6 Hz), 6.46
d
7.31e7.21 (4H, m), 7.02e6.97 (2H, m), 6.89 (2H, d, J¼7.6 Hz), 6.74
(1H, s), 5.23 (2H, s), 2.53 (2H, t, J¼7.6 Hz), 1.49 (2H, sext, J¼7.6 Hz),
0.93 (3H, t, J¼7.6 Hz); 13C NMR (100 MHz, CDCl3):
d 138.6, 136.0,
(1H, d, J¼7.6 Hz), 6.09 (1H, s), 5.10 (2H, s), 3.83 (3H, s), 2.53e2.57
(2H, m), 2.30e2.36 (1H, m), 1.83e1.65 (5H, m), 1.53e1.21 (7H, m),
132.4, 128.7, 127.9, 127.9, 127.5, 127.5, 127.2, 127.0, 126.2, 126.0,
125.5, 115.8, 63.1, 48.6, 29.1, 23.0, 14.0; HRMS (ESI): m/z calcd for
C24H22NNaI (MþþNa): 474.0695; found 474.0696.
0.86 (3H, t, J¼7.2 Hz); 13C NMR (100 MHz, CDCl3):
d 159.5, 139.3,
139.2, 138.6, 129.0, 128.8, 128.6, 126.9, 125.5, 121.0, 120.3, 113.1,
110.6, 103.9, 55.1, 46.6, 35.8, 34.1, 27.4, 26.7, 26.1, 24.2, 14.2; HRMS
(ESI): m/z calcd for C27H34NO (MþþH): 388.2640; found 388.2644.
4.5. 5-Cyclohexyl-3-(4-methoxyphenyl)-2-phenyl-1-(toluene-
4-sulfonyl)-1H-pyrrole (14)
Acknowledgements
To a stirred solution of 3-iodopyrrole 4b (30.0 mg, 0.059 mmol)
in toluene/MeOH (1/1, 2.0 mL) were added 4-methoxyphenylbor-
onic acid (18.0 mg, 0.118 mmol), Pd(PPh3)4 (6.8 mg, 5.9 mmol), and
Na2CO3 (18.8 mg, 0.177 mmol) at rt. After the stirring was contin-
ued for 60 min at 60 ꢀC, the reaction mixture was filtered through
a pad of Celite. Concentration at reduced pressure gave the residue,
which was chromatographed on silica gel using hexane/AcOEt (85/
This study was supported in part by a Grant-in-Aid for the En-
couragement of Young Scientists (B) from the Japan Society for the
Promotion of Science (JSPS), the Takeda Science Foundation, the
Uehara Memorial Foundation, and the Program for the Promotion
of Basic and Applied Research for Innovations in the Bio-oriented
Industry (BRAIN).

3200
M. Yoshida et al. / Tetrahedron 67 (2011) 3194e3200
9. Blanc, A.; Tenbrink, K.; Weibel, J.-M.; Pale, P. J. Org. Chem. 2009, 74, 5342.
Supplementary data
10. The structure of 10 was determined by comparison of the spectral data with
our authentic sample, see Ref. 5.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.03.015. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
11. For selected examples, see: (a) Flynn, B. L.; Verdier-Pinard, P.; Hamel, E. Org.
Lett. 2001, 3, 651; (b) Huang, Q.; Hunter, J. A.; Larock, R. C. Org. Lett. 2001, 3,
2973; (c) Yue, D.; Larock, R. C. J. Org. Chem. 2002, 67, 1905; (d) Huang, Q.;
Hunter, J. A.; Larock, R. C. J. Org. Chem. 2002, 67, 3437; (e) Arcadi, A.; Cacchi, S.;
Giuseppe, S. D.; Fabrizi, G.; Marinelli, F. Org. Lett. 2002, 4, 2409; (f) Yao, T.;
Larock, R. C. J. Org. Chem. 2003, 68, 5936; (g) Hessian, K. O.; Flynn, B. L. Org. Lett.
2003, 5, 4377; (h) Peng, A. Y.; Ding, Y. X. Org. Lett. 2004, 6, 1119; (i) Yao, T.;
Campo, M. A.; Larock, R. C. Org. Lett. 2004, 6, 2677; (j) Yue, D.; Della, C. N.;
Larock, R. C. Org. Lett. 2004, 6, 1581; (k) Yao, T.; Larock, R. C. J. Org. Chem. 2005,
70, 1432; (l) Barluenga, J.; Trincado, M.; Marco-Arias, M.; Ballesteros, A.; Rubio,
E.; Gonzalez, J. M. Chem. Commun. 2005, 2008; (m) Sniady, A.; Wheeler, K. A.;
Dembinski, R. Org. Lett. 2005, 7, 1769; (n) Liu, Y.-H.; Song, F.-J.; Cong, L. Q. J. Org.
Chem. 2005, 70, 6999; (o) Yue, D.; Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70,
10292; (p) Bi, H.-P.; Guo, L.-N.; Duan, X.-H.; Gou, F.-R.; Huang, S.-H.; Liu, X.-Y.;
Liang, Y.-M. Org. Lett. 2007, 9, 397; (q) Fischer, D.; Tomeba, H.; Pahadi, N. K.;
Patil, N. T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2007, 46, 4764; (r) Xie, Y.-X.; Liu,
References and notes
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Bellina, F.; Rossi, R. Tetrahedron 2006, 62, 7213.
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ARKIVOC 2007, 121; (d) Schmuck, C.; Rupprecht, D. Synthesis 2007, 3095; (e)
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X.-Y.; Wu, L.-Y.; Han, Y.; Zhao, L
ˇ .-B.; Fan, M.-J.; Liang, Y.-M. Eur. J. Org. Chem.
2008, 1013; (s) Cherry, K.; Duchene, A.; Thibonnet, J.; Parrain, J.-L.; Anselmi, E.;
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4. (a) Davies, P. W.; Martin, N. Org. Lett. 2009, 11, 2293; (b) Chen, D.-D.; Hou, X.-L.;
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12. It is known that Brønsted acid-catalyzed cycloisomerization of propargylic
oxiranes occurs; see Ref. 5 and 6.
5. Yoshida, M.; Al-Amin, M.; Shishido, K. Synthesis 2009, 2454.
6. Yoshida, M.; Al-Amin, M.; Matsuda, K.; Shishido, K. Tetrahedron Lett. 2008, 49,
5021.
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13. As another mechanism, the reaction was triggered by N-iodination and sub-
sequent SN20 ring opening of propargylic aziridine with the iodide ion. Then the
resulting allene could be activated by additional iodine to form the dihy-
dropyrrole, which would be converted to the 3-iodopyrrole by the aromati-
zation along with the regeneration of iodine.
8. Li, A.-H.; Zhou, Y.-G.; Dai, L.-X.; Hou, X.-L.; Xia, L.-J.; Lin, L. J. Org. Chem. 1998, 63,
4338.