Syntheses of substituted furans and pyrroles by platinum-catalyzed cyclizations of propargylic oxiranes and aziridines in aqueous media

Article abstract of DOI:10.1055/s-0029-1216867

The reactions of propargylic oxiranes and aziridines with a platinum catalyst in aqueous media are described. Furans having a variety of substituents were conveniently synthesized by the platinum-catalyzed reaction of propargylic oxiranes. The reaction in the presence of N-iodosuccinimide afforded the 3-iodo-substituted furan, which was further functionalized to tetrasubstituted furans with high efficiency. Propargylic aziridines were also reacted with the platinum catalyst to produce the corresponding substituted pyrroles in good yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1216867

2454
FEATURE ARTICLE
Syntheses of Substituted Furans and Pyrroles by Platinum-Catalyzed
Cyclizations of Propargylic Oxiranes and Aziridines in Aqueous Media
S
ynthese
s
of Substitute
a
dFurans
a
s
nd Pyrrole
a
s
hiro Yoshida,* Mohammad Al-Amin, Kozo Shishido
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan
Fax +81(88)6337294; E-mail: yoshida@ph.tokushima-u.ac.jp
Received 11 May 2009; revised 21 May 2009
R1
R2
X
R1
Abstract: The reactions of propargylic oxiranes and aziridines with
a platinum catalyst in aqueous media are described. Furans having
a variety of substituents were conveniently synthesized by the plat-
X
cat. Pt(II)
R2
aqueous conditions
R3
R3
inum-catalyzed reaction of propargylic oxiranes. The reaction in the
presence of N-iodosuccinimide afforded the 3-iodo-substituted fu-
ran, which was further functionalized to tetrasubstituted furans with
high efficiency. Propargylic aziridines were also reacted with the
platinum catalyst to produce the corresponding substituted pyrroles
in good yields.
1 X = O
3 X = NBn
2 X = O
4 X = NBn
Scheme 1
Key words: alkyne, epoxide, furan, platinum, pyrrole
yields by employing 3-chloroperbenzoic acid under basic
conditions.
The initial attempts at the synthesis of substituted furans
were carried out using phenyl-substituted propargylic ox-
irane 1a. Treatment of 1a with 10 mol% of platinum(II)
chloride in dioxane at 100 °C for 180 minutes gave tet-
rahydrobenzofuran 2a in 90% yield (Table 2, entry 1).
Further efforts revealed that the presence of water en-
hanced the reactivity (entries 2 and 3). Thus, the reaction
in dioxane–water (2:1) was complete within 10 minutes to
afford the product 2a in 96% yield (entry 3). The yields of
2a decreased as the temperature was lowered (entries 4–
6). The reaction also proceeded in a mixture of various
aqueous solvents to give 2a in good yields (entries 7–11).
The reactivity was maintained even in the presence of 5
mol% platinum catalyst (entry 12), but with 2 mol% of
catalyst, the production of 2a decreased (entry 13). The
Brønsted acid catalyzed reaction in the presence of hydro-
chloric acid also proceeded, but the yield was very low
(entry 14). Treatment of 1a with 10 mol% gold(III) chlo-
ride in acetonitrile at room temperature in accordance
with Hashmi’s procedure4h gave 2a in 21% yield (entry
15).
Substituted furans and pyrroles are an important class of
heteroaromatic molecules that are components in a variety
of biologically active natural products and industrially
useful compounds.1 They are also extensively utilized as
synthetic intermediates for acyclic, carbocyclic, and het-
erocyclic compounds in organic synthesis.2 For these rea-
sons, considerable effort has been devoted toward finding
efficient syntheses of substituted furans and pyrroles.3
Among them, cycloisomerization of propargylic oxiranes
is one of the most useful methodologies for the synthesis
of substituted furans.4 It has been reported that a variety of
reagents activate the process that leads to the correspond-
ing substituted furans. For example, Hashmi reported the
gold-catalyzed cycloisomerization of propargylic ox-
iranes to furans.4h The reaction allows the synthesis of
substituted furans under mild conditions, but the reaction
examples were limited to only 2,4-disubstituted furans
and the chemical yields were moderate to low. During the
course of our studies on the reaction of propargylic ox-
iranes with a transition metal catalyst,5 we focused on the
reactivity of a platinum(II) catalyst.6 We report herein full
details of a platinum-catalyzed reaction of propargylic ox-
iranes, in which various substituted furans can be conve-
niently synthesized in aqueous media with high
efficiency.7 The application of this reaction to propargylic
aziridines for the synthesis of substituted pyrroles is also
described (Scheme 1).
Table 3 shows our attempts using various substituted pro-
pargylic oxiranes 1b–k. The reaction of 1b, having a butyl
group at the alkynyl position, with platinum(II) chloride
yielded tetrahydrobenzofuran 2b in 83% yield (entry 1).
The benzyl- and siloxyethyl-substituted propargylic ox-
iranes 1c and 1d were transformed into the corresponding
products 2c and 2d, each in 92% yield (entries 2 and 3).
Furthermore, the propargylic oxirane with a free hydroxy
group, 1e, was uneventfully converted into 2e in 79%
yield (entry 4). The reaction of 1f containing a 2-vinylphe-
nyl group also afforded furan 2f without any problems due
to the vinyl group (entry 5). When cyclopentyl-substituted
substrate 1g was subjected to the reaction, 5,6-dihydrocy-
clopentafuran 2g was obtained in 34% yield (entry 6). The
low yield can be attributed to the difficulties encountered
in constructing the strained 5,6-dihydro-4H-cyclopen-
Propargylic oxiranes 1 for platinum-catalyzed cyclization
were easily prepared by the epoxidation of the corre-
sponding enynes (Table 1). Thus, enynes 5a–k having a
variety of substituents were converted into the corre-
sponding propargylic oxiranes 1a–k in moderate to good
SYNTHESIS 2009, No. 14, pp 2454–2466
x
x.
x
x
.
2
0
0
9
Advanced online publication: 26.06.2009
DOI: 10.1055/s-0029-1216867; Art ID: Z09409SS
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Syntheses of Substituted Furans and Pyrroles
2455
ta[b]furan ring system. The reactions of substrates 1h and
1i, which contain seven- and eight-membered rings, suc-
cessfully afforded the corresponding furans 2h and 2i in
92% and 89% yields, respectively (entries 7 and 8). Reac-
tion of acyclic propargylic oxirane 1j gave 2,4-disubstitut-
ed furan 2j in 90% yield (entry 9).8 Similarly, the 2,5-
disubstituted furan 2k was obtained in yields of 82% and
83% from the reactions of trans-1k and cis-1k (entries 10
and 11).
R1
O
O
PtX2
R2
R1
R2
(X = Cl or OH)
R3
R3
PtX2
1
6
H
R2
R1
O
R2
R1
O
– H+
– X–
R3
R3
PtX
PtX
A plausible mechanism for the reaction of propargylic ox-
iranes 1 is shown in Scheme 2. The platinum catalyst ac-
tivates the C≡C bond in the substrate 1 by coordination as
shown in 6. The epoxide oxygen attacks the distal position
of the alkyne to form the cyclized intermediate 7. Aroma-
tization by elimination of the proton followed by proto-
demetalation from the resulting furyl–platinum species 8
produces the furan 2. As to the cause of the increased re-
activity under aqueous conditions, it is presumed that the
platinum hydroxide complex, which would enhance the
reactivity of the proto-demetalation from the intermediate
8, exists as an active species in the aqueous media.9
7
8
R2
R1
O
H2O
– PtX2
R3
2
Scheme 2
Biographical Sketches
Masahiro Yoshida was University of Toronto as a Japan, Tohoku District, in
born in Aichi prefecture, Ja- postdoctoral fellow during 2003, and a FUJIFILM
pan in 1974. He received his 2001–2002, he was appoint- Award in Synthetic Organic
B.S. in 1996 from the To- ed as a Research Associate Chemistry, Japan, in 2005.
hoku University under the at Tohoku University in At present, his research is
direction of Emeritus Pro- 2002. In 2005, he moved to focused on the development
fessor Keiichiro Fukumoto the Graduate School of of new catalytic reactions
and his Ph.D. in 2001 from Pharmaceutical Sciences, using transition metal com-
Tohoku University under University of Tokushima, as plexes and their application
the direction of Emeritus an Associate Professor. His to the synthesis of natural
Professor Masataka Ihara. awards include an Encour- products.
After he joined Professor aging Award from The
Mark Lautens’ group at the Pharmaceutical Society of
Mohammad Al-Amin was rently carrying out his Ph.D. search interests include the
born in Chandpur, Bang- studies in the group of Pro- development of synthetic
ladesh in 1979. He received fessor Yoshida and Profes- methods for heteroaromatic
his B.S. in 2003, and M.S. sor Shishido at the Graduate compounds based on transi-
degree in 2005 from Jahan- School of Pharmaceutical tion-metal-catalyzed reac-
girnagar University under Sciences, University of tions.
the supervision of Professor Tokushima, as a MEXT
Md. Rabiul Islam. He is cur- scholarship student. His re-
Kozo Shishido was born in he joined the late Professor sor in 1989. In 1994, he rose
Miyagi prefecture, Japan in A. I. Scott’s group at Texas to the rank of Full Professor
1946, and received his B.S. A&M University and then at University of Tokushima,
in 1970 and Ph.D. in 1976 Professor M. E. Jung’s where he is currently
from Tohoku University un- group at the University of Professor of the Graduate
der the direction of the late California, Los Angeles as a School of Pharmaceutical
Professor Tetsuji Kametani. postdoctoral fellow from Sciences. His research inter-
After he was appointed as 1978–1980. He then moved est is in the area of total
an Assistant Professor at to the University of Tokush- synthesis of biologically
Tohoku University in 1972, ima as an Associate Profes- significant molecules.
Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York

2456
M. Yoshida et al.
FEATURE ARTICLE
Table 1 Synthesis of Propargylic Oxiranes 1a–k
R4
R3
R4
R3
O
m-CPBA
R1
R1
NaHCO3, CH2Cl2
r.t.
R2
5a–k
R2
1a–k
Entry
Substrate
R1
R2
R3
H
R4
Product
Yield (%)
1
2
5a
5b
5c
5d
5e
5f
(CH2)4
Ph
1a
1b
1c
1d
1e
1f
69
82
65
71
79
43
52
67
86
64
(CH2)4
(CH2)4
(CH2)4
(CH2)4
(CH2)4
(CH2)3
(CH2)5
(CH2)6
H
Bu
3
H
Bn
4
H
(CH2)2OTBDPS
5
H
(CH2)2OH
6
H
2-H2C=CHC6H4
7
5g
5h
5i
H
Ph
1g
1h
1i
8
H
Ph
9
H
Ph
10
11
5j
H
Me
H
H
(CH2)3OH
Ph
1j
(E)-5k
(Z)-5k
Ph/H
H/Ph
trans-1k
cis-1k
34
39
Information on the reaction mechanism was gained when creased to 69% when the reaction was carried out in ace-
the reaction was conducted in deuterium oxide tonitrile–water (2:1) (entry 5). The product 9 was obtained
(Scheme 3). In this case, 97% of deuterium was incorpo- even in the absence of platinum catalyst, but the yield de-
rated at the 3-position on the furan ring to give 2a-D in creased to 22% (entry 6). This result indicates that the re-
89% yield. No reaction occurred when the isolated furan action also proceeds via iodonium intermediate 10
2a was subjected to the same reaction condition. These re- (Scheme 4), but the pathway involving the furyl–platinum
sults support the hypothesis that the reaction proceeds via species 8 is preferred in this reaction.11
the formation of the furyl–platinum intermediate 8.
The presence of the iodo functional group on the furan
ring provided an opportunity for further functionalization
(Scheme 5). The 4-methoxyphenyl group was introduced
to give 11a in 98% yield using the Miyaura–Suzuki cou-
pling reaction of 9 with 4-methoxyphenylboronic acid.
Compound 9 also underwent Sonogashira and Stille cou-
pling reactions with phenylacetylene and tributyl(vi-
nyl)tin to produce the corresponding 3-alkynyl- and 3-
vinyl-substituted furans 11b and 11c in 93% and 52%
yields, respectively. Heck reaction of 9 with methyl acry-
late also proceeded to afford 11d in 98% yield.
Ph
O
O
Ph
PtCl2 (10 mol%)
dioxane–D2O (2:1)
100 °C, 10 min
D
1a
2a-D 89%
97% deuterized
O
Ph
PtCl2 (10 mol%)
no reaction
dioxane–D2O (2:1)
100 °C, 1 h
2a
O
Ph
Scheme 3
1a
9
I+
To further highlight the potential of this process, we tried
to trap the furyl–platinum species with electrophilic io-
dine prior to protonation (Table 4).10 When propargylic
oxirane 1a was treated with N-iodosuccinimide in the
presence of platinum(II) chloride in dioxane–water (2:1),
3-iodotetrahydrobenzofuran 9 was produced in 63% yield
(entry 1). Examination of the reaction in various aqueous
solvents (entries 2–5) revealed that the yield of 9 in-
10
Scheme 4
We next turned our attention to the synthesis of substitut-
ed pyrroles. Although many examples of cyclizations of
propargylic oxiranes to furans have been reported, there
are few focusing on the conversion of propargylic aziri-
Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York

FEATURE ARTICLE
Syntheses of Substituted Furans and Pyrroles
2457
Table 3 Reactions with Various Propargylic Oxiranes 1b–ka
Table 2 Platinum-Catalyzed Cyclizations of 1a
Ph
Entry Substrate
Product
Yld.
(%)
O
O
Ph
PtCl2 (10 mol%)
Bu
O
O
O
O
Bu
Bn
2a
1a
1
83
92
Entry
1
Solvent
Temp (°C) Time (min) Yield (%)
2b
2c
2d
1b
dioxane
100
100
100
80
180
10
10
15
45
600
40
10
10
60
20
10
30
10
90
Bn
O
2
dioxane–H2O (1:2)
dioxane–H2O (2:1)
dioxane–H2O (2:1)
dioxane–H2O (2:1)
dioxane–H2O (2:1)
MeCN–H2O (2:1)
THF–H2O (2:1)
DMF–H2O (2:1)
toluene–H2O (2:1)
DMSO–H2O (2:1)
dioxane–H2O (2:1)
dioxane–H2O (2:1)
dioxane–H2O (2:1)
MeCN
87
2
3
96
1c
4
95
OTBDPS
OTBDPS
O
5
60
61
3
92
79
6
25
27
7
100
100
100
100
100
100
100
100
25
76
1d
8
86
OH
O
OH
O
9
87
4
10
11
12a
13b
14c
15d
91
2e
1e
83
94
O
O
5
73
34
10
2f
1f
36 h
21 (29)e
Ph
O
Ph
O
a 5 mol% of PtCl2 was used.
b 2 mol% of PtCl2 was used.
c 10 mol% HCl was used.
d 10 mol% AuCl3 was used.
6
34
92
2g
2h
1g
e The yield in parenthesis is based on recovered starting material.
Ph
O
O
Ph
7
dines into pyrroles.12,13 We expected that our platinum-
catalyzed conditions could be applied to the synthesis of
substituted pyrroles and, therefore, attempted the reaction
of propargylic aziridines. The substrates 3a–k for the cy-
clization reactions were synthesized as follows
(Scheme 6). According to Chemla’s procedure,14 the reac-
tion of the imine 12a with the allenylzinc reagent 13a
gave the corresponding trimethylsilyl-substituted propar-
gylic aziridine, which was subjected to the reaction with
potassium carbonate in methanol to afford the desilylated
compound 3g. Various substituents at the terminal posi-
tion of alkyne 3g were introduced to give 3a and 3c–e by
reactions with butyllithium and alkyl bromides 14a and
14c–e. The phenyl-substituted propargylic aziridine 3b
was obtained directly by the reaction of imine 12a with al-
lenylzinc reagent 13b. Compound 3f containing a free hy-
droxy group was obtained in 98% yield from the reaction
of 3e with tetrabutylammonium fluoride. The propargylic
aziridines 3h–k, which have a substituent on the aziridine
ring, were also prepared from the corresponding imines
12h–k in three steps.
1h
Ph
O
O
Ph
8
89
90
2i
1i
O
O
OH
OH
9
1j
2j
Ph
O
Ph
Ph
Ph
O
10
82
83
Ph
2k
trans-1k
Ph
O
Ph
Ph
O
11
2k
cis-1k
a PtCl2 (10 mol%), dioxane–H2O (2:1), 100 °C, 10 min.
Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York

2458
M. Yoshida et al.
FEATURE ARTICLE
1)
Cl
TMS
ZnBr
Table 4 Platinum-Catalyzed Cyclizations of 1a in the Presence of
N-Iodosuccinimide
·
H
13a
Bn
H
Bn
Ph
O
N
O
O
Ph
+
THF, –78 °C
N
Ph
NIS, PtCl2 (10 mol%)
solvent, 100 °C
Cy
R
Cy
2) K2CO3, MeOH, r.t.
2 steps 95%
I
12a
3g
9
2a
1a
Bn
Entry Solvent
Time (min) Yield (%)
BuLi; RBr 14
N
9
2a
–
Cy
HMPA, THF, –78 °C
1
2
3
4
5
6a
dioxane–H2O (1:2)
10
60
10
10
10
10
63
44
40
56
69
22
14a R = Pr
14c R = Bn
14d R = allyl
14e R = -(CH2)3OTBDPS
3a R = Pr 80%
3c R = Bn 72%
3d R = allyl 81%
CH2Cl2–H2O (2:1)
DMF–H2O (2:1)
DMSO–H2O (2:1)
MeCN–H2O (2:1)
MeCN–H2O (2:1)
–
3e R = -(CH2)3OTBDPS 52%
23
31
–
Cl
Ph
·
Bn
Bn
Ph
N
H
ZnBr
13b
N
Cy
Cy
H
THF, –78 °C
28% (59% brsm)
–
a Reaction was carried out in the absence of PtCl2.
3b
12a
Bn
Bn
( )
( )
3 OH
3
OTBDPS
TBAF
N
N
Cy
THF, r.t., 98%
Cy
O
Ph
3e
3f
O
(HO)2B
OMe
Ph
Pd(PPh3)4 (10 mol%)
K2CO3, toluene–EtOH
80 °C, 7 h
1)
Cl
TMS
I
·
OMe
H
ZnBr
13a
Bn
H
Bn
9
11a 98%
N
THF, –78 °C
N
O
R
Ph
R
2) K2CO3, MeOH, r.t.
3) BuLi; propyl bromide (14a)
HMPA, THF, –78 °C
Ph
9
PdCl2(PPh3)2 (10 mol%)
CuI (10 mol%), Et3N
MeCN, 50 °C, 24 h
3h R = Bu 3 steps 80%
3i R = t-Bu 3 steps 61%
3j R = Ph 3 steps 77%
12h R = Bu
12i R = t-Bu
12j R = Ph
Ph
11b 93%
3k R = 2-naphthyl 3 steps 85%
12k R = 2-naphthyl
O
Ph
SnBu3
Scheme 6
9
Pd(PPh3)4 (10 mol%)
LiCl, THF, 50 °C, 15 h
creased to 38% when platinum(II) chloride and dichlo-
ro(p-cymene)ruthenium(II) dimer were used (entries 3
and 4). The Brønsted acid catalyzed reaction in the pres-
ence of hydrochloric acid also proceeded, but the yield
was only 18% (entry 5). These results suggest that the
platinum catalyst is the most suitable in the conversion of
the propargylic aziridine into the pyrrole.
11c 52%
O
Ph
CO2Me
9
Pd(OAc)2 (5 mol%)
Ph3P (20 mol%), Et3N
DMF, 80 °C, 2 h
CO2Me
11d 98%
The reactions of various substituted propargylic aziridines
3b–k are summarized in Table 6. When substrates 3b–e
having respectively a phenyl, benzyl, allyl, and 3-siloxy-
propyl group at the alkynyl position were subjected to the
platinum-catalyzed reaction, the corresponding products
4b–e were produced in good yields (entries 1–4). The pro-
pargylic aziridine containing a free hydroxy group, 3f,
was uneventfully transformed into pyrrole 4f in 70% yield
(entry 5). The monosubstituted pyrrole 4g was obtained
by the reaction of the unsubstituted substrate 3g, but the
yield decreased to 38% (entry 6). The reactions of sub-
strates 3h and 3i, which contain butyl and tert-butyl
Scheme 5
Attempts to synthesize substituted pyrroles were per-
formed using 3a (Table 5). When 3a was treated with 10
mol% of platinum(II) chloride in dioxane–water (2:1) at
100 °C for 120 minutes, the desired 2,5-disubstituted pyr-
role 4a was produced in 77% yield (entry 1). To compare
the effects of the catalyst in this reaction, catalyst screen-
ing using other transition metals was carried out (entries
2–5). Gold(III) chloride catalyzed the reaction of 3a to
produce 4a in 51% yield (entry 2). The yields of 4a de-
Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York

FEATURE ARTICLE
Syntheses of Substituted Furans and Pyrroles
2459
Table 5 Platinum-Catalyzed Cyclizations of 3a
Table 6 Reactions with Various Propargylic Aziridines 3b–ka
Bn
N
Entry Substrate
Product
Yield
(%)
Bn
catalyst (10 mol%)
Cy
N
dioxane–H2O (2:1)
100 °C
Cy
Bn
Bn
Ph
Bn
3a
4a
N
N
Cy
Ph
Bn
1
79
68
65
72
70
38
81
Cy
Entry
Catalyst
Time (min) Yield (%)
3b
4b
1
2
3
4
5
PtCl2
120
77
51
38
38
18
Bn
N
Bn
N
Cy
AuCl3
45
20
2
Cy
PdCl2
3c
4c
[(p-cymene)RuCl2]2
240
60
Bn
N
Bn
Bn
Bn
Bn
N
N
N
N
Cy
3
4
5
6
7
HCl
Cy
3d
4d
groups on the aziridine ring, successfully afforded pyr-
roles 4h and 4i in 81% and 71% yields, respectively (en-
tries 7 and 8). The phenyl- and 2-naphthyl-substituted
substrates 3j and 3k were also converted into the corre-
sponding products 4j and 4k in 72% and 48% yields, re-
spectively (entries 9 and 10).
Bn
N
( )
3
OTBDPS
Cy
( )
3
OTBDPS
Cy
3e
4e
Bn
N
( )
3
OH
Cy
( )
A plausible mechanism for the reaction of propargylic
aziridines 3 is shown in Scheme 7. Coordination of plati-
num to the C≡C bond as in 15 followed by attack of the
aziridine nitrogen on the alkyne produces the cyclized in-
termediate 16. Aromatization by elimination of the proton
forms the pyrrolyl–platinum species 17, which further un-
dergoes proto-demetalation to afford pyrrole 4.
3
OH
Cy
3f
4f
Bn
N
Cy
Cy
3g
4g
Bn
Bn
N
N
( )
3
Bn
Bn
R1
N
( )3
N
PtX2
R2
R1
3h
R2
4h
(X = Cl or OH)
R3
15
R3
Bn
N
Bn
PtX2
N
3
8
71
Bn
Bn
H
R2
R1
N
R2
R1
4i
N
3i
Bn
– H+
– X–
Bn
R3
PtX
N
Ph
R3
N
PtX
9
72
48
17
Ph
16
3j
4j
Bn
Bn
R2
R1
N
Bn
H2O
N
10b
N
Nap
– PtX2
Nap
R3
3k
4
4k
a PtCl2 (10 mol%), dioxane–H2O (2:1), 100 °C, 1–2 h.
b Nap = 2-naphthyl.
Scheme 7
In conclusion, we have developed a methodology for the
synthesis of substituted furans and pyrroles using a plati-
num catalyst. The reactions afforded a variety of substitut-
ed furans and pyrroles under aqueous conditions and the
process provided an efficient and convenient protocol for
the preparation of these derivatives. Efforts to extend the
scope of these reactions and their subsequent application
to the syntheses of natural products are currently in
progress.
All nonaqueous reactions were carried out under a positive atmo-
sphere of argon in dried glassware unless otherwise indicated. Ma-
terials were obtained from commercial suppliers and used without
further purification except when otherwise noted. Solvents were
dried and distilled according to standard protocol. The phrase ‘resi-
Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York

2460
M. Yoshida et al.
FEATURE ARTICLE
due upon workup’ refers to the residue obtained when the organic
layer was separated and dried (anhyd MgSO4) and the solvent was
evaporated under reduced pressure. Enynes 5a–k were prepared ac-
cording to the procedures described in the literature.5c,15
2-Phenyl-4,5,6,7-tetrahydrobenzofuran (2a); Typical Proce-
dure
To a stirred soln of 1a (30.0 mg, 0.151 mmol) in dioxane–H2O (2:1)
was added PtCl2 (4.0 mg, 0.015 mmol) at r.t. The mixture was
stirred at 100 °C for 10 min and then cooled to r.t. and diluted with
the minimum amount of Et2O. The soln was then dried (MgSO4)
and filtered through a small amount of silica gel. Concentration at
reduced pressure gave the residue, which was chromatographed
(silica gel, pentane–Et2O, 97:3) to give 2a (28.8 mg, 96%) as a col-
orless oil.
1-(Phenylethynyl)-7-oxabicyclo[4.1.0]heptane (1a); Typical
Procedure
To a stirred soln of enyne 5a (1.50 g, 8.2 mmol) in CH2Cl2 (60 mL)
was added m-CPBA (2.83 g, 16.4 mmol) at r.t.; stirring was contin-
ued at r.t. for 2 h. The mixture was diluted with sat. aq NaHCO3 (30
mL) and extracted with EtOAc (3 ꢀ 40 mL). The combined extracts
were washed with brine (2 ꢀ 40 mL). After filtration of the mixture
using a small amount of basic alumina, the residue upon workup
was chromatographed (silica gel, hexane–EtOAc, 95:5) to give 1a
(1.12 g, 69%) as a colorless oil.
IR (neat): 3079, 3058, 2926, 2849, 1634, 1603, 1549, 1486, 1443
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.61 (d, J = 7.6 Hz, 2 H), 7.39–
7.29 (m, 2 H), 7.19 (t, J = 7.2 Hz, 1 H), 6.47 (s, 1 H), 2.66 (t, J = 6.0
Hz, 2 H), 2.45 (t, J = 6.0 Hz, 2 H), 1.89–1.86 (m, 2 H), 1.85–1.83
(m, 2 H).
The spectral data of 1a–c and 1g–k were in complete agreement
with that reported in the literature.4h,5c,11,16,17
13C NMR (100 MHz, CDCl3): d = 151.53, 150.75, 131.38, 128.51,
126.49, 123.19, 118.94, 105.97, 23.25, 23.10, 23.04, 22.10.
1-[4-(tert-Butyldiphenylsiloxy)but-1-ynyl]-7-oxabicy-
clo[4.1.0]heptane (1d)
Colorless oil; yield: 71%.
HRMS (ESI): m/z [M + Na]+ calcd for C14H14ONa: 221.0942;
found: 221.0936.
IR (neat): 3069, 3028, 2926, 2855, 2197, 1598, 1496, 1475, 1450,
1428, 1389 cm–1.
2-Butyl-4,5,6,7-tetrahydrobenzofuran (2b)
Colorless oil; yield: 83%.
1H NMR (400 MHz, CDCl3): d = 7.69–7.67 (m, 4 H), 7.45–7.36 (m,
6 H), 3.75 (t, J = 6.8 Hz, 2 H), 3.26 (s, 1 H), 2.47 (t, J = 7.2 Hz, 2
H), 2.21–2.06 (m, 1 H), 1.98–1.86 (m, 3 H), 1.40–1.34 (m, 1 H),
1.31–1.18 (m, 3 H), 1.05 (s, 9 H).
IR (neat): 3097, 2928, 2852, 1686, 1644, 1573, 1458, 1445 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.77 (s, 1 H), 2.55 (q, J = 6.8 Hz,
4 H), 2.39–2.35 (m, 2 H), 1.83–1.76 (m, 2 H), 1.73–1.67 (m, 2 H),
1.63–1.54 (m, 2 H), 1.42–1.33 (m, 2 H), 0.94–0.91 (t, J = 7.6 Hz, 3
H).
13C NMR (100 MHz, CDCl3): d = 135.51, 133.50, 129.64, 127.64,
81.76, 79.81, 62.18, 59.93, 50.39, 29.91, 26.72, 24.12, 22.82, 19.42,
19.16, 18.91.
13C NMR (100 MHz, CDCl3): d = 154.17, 148.60, 117.09, 105.41,
30.43, 27.85, 23.25, 23.22, 23.12, 22.34, 22.15, 13.83.
HRMS (ESI): m/z [M + H]+ calcd for C26H33O2Si: 405.2250; found:
405.2246.
HRMS (ESI): m/z [M + Na]+ calcd for C12H18ONa: 201.1255;
found: 201.1253.
4-(7-Oxabicyclo[4.1.0]hept-1-yl)but-3-yn-1-ol (1e)
Colorless oil; yield: 79%.
2-Benzyl-4,5,6,7-tetrahydrobenzofuran (2c)
Colorless oil; yield: 92%.
IR (neat): 3312, 3064, 3031, 2927, 2852, 2185, 1385 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.71 (t, J = 6.4 Hz, 2 H), 3.31 (t,
J = 2.4 Hz, 1 H), 2.48 (t, J = 6.4 Hz, 2 H), 2.17–2.10 (m, 1 H), 2.01–
1.88 (m, 3 H), 1.84 (s, 1 H), 1.45–1.33 (m, 2 H), 1.33–1.17 (m, 2 H).
IR (neat): 3087, 3062, 3029, 2926, 2850, 1642, 1604, 1569, 1496,
1454 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.31–7.19 (m, 5 H), 5.77 (s, 1 H),
3.90 (s, 2 H), 2.53 (t, J = 6.0 Hz, 2 H), 2.36–2.32 (m, 2 H), 1.81–
1.76 (m, 2 H), 1.71–1.65 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 82.08, 79.58, 60.61, 60.06, 50.47,
29.73, 23.94, 22.88, 19.25, 18.71.
13C NMR (100 MHz, CDCl3): d = 152.17, 149.56, 138.57, 128.75,
128.42, 126.32, 117.34, 107.11, 34.70, 29.69, 23.17, 23.13, 22.10.
HRMS (ESI): m/z [M + H]+ calcd for C10H15O2: 167.1072; found:
167.1077.
HRMS (ESI): m/z [M + H]+ calcd for C15H17O: 213.1279; found:
213.1283.
1-[(2-Vinylphenyl)ethynyl]-7-oxabicyclo[4.1.0]heptane (1f)
Colorless oil; yield: 43%.
2-[2-(tert-Butyldiphenylsiloxy)ethyl]-4,5,6,7-tetrahydrobenzo-
furan (2d)
Colorless oil; yield: 92%.
IR (neat): 3098, 3061, 2939, 2860, 2230, 1626, 1477, 1447, 1384,
1347 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.57 (d, J = 8.0 Hz, 1 H), 7.43–
7.41 (m, 1 H), 7.29–7.26 (m, 2 H), 6.26–6.15 (m, 1 H), 5.80 (d,
J = 17.6 Hz, 1 H), 5.35 (d, J = 11.6 Hz, 1 H), 3.46 (t, J = 2.4 Hz, 1
H), 2.29–2.24 (m, 1 H), 2.16–2.09 (m, 1 H), 1.99–1.95 (m, 2 H),
1.50–1.26 (m, 4 H).
IR (neat): 3084, 3062, 3021, 2936, 2852, 1638, 1604, 1569, 1496,
1454, 1358 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.64–7.62 (m, 4 H), 7.41–7.34 (m,
6 H), 5.83 (s, 1 H), 3.87 (t, J = 7.2 Hz, 2 H), 2.85 (t, J = 7.2 Hz, 2
H), 2.51 (t, J = 6.4 Hz, 2 H), 2.35 (t, J = 6.4 Hz, 2 H), 1.83–1.77 (m,
2 H), 1.70–1.66 (m, 2 H), 1.03 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 139.24, 134.68, 132.72, 128.60,
127.37, 124.50, 121.00, 115.64, 94.27, 80.35, 60.40, 50.75, 29.83,
24.20, 19.46, 18.89.
13C NMR (100 MHz, CDCl3): d = 150.62, 148.95, 135.55, 133.86,
129.65, 129.52, 127.71, 127.57, 117.26, 107.12, 62.78, 31.79,
26.79, 23.24, 23.10, 22.12, 19.18, 1.02.
HRMS (ESI): m/z [M + H]+ calcd for C16H17O: 225.1279; found:
225.1284.
HRMS (ESI): m/z [M + H]+ calcd for C26H33O2Si: 405.2250; found:
405.2254.
Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York

FEATURE ARTICLE
Syntheses of Substituted Furans and Pyrroles
2461
2-(4,5,6,7-Tetrahydrobenzofuran-2-yl)ethanol (2e)
Colorless oil; yield: 79%.
13C NMR (100 MHz, CDCl3): d = 151.71, 150.46, 131.35, 128.50,
126.36, 123.09, 120.53, 108.10, 28.87, 27.39, 26.10, 26.07, 25.29,
23.83.
IR (neat): 3058, 3022, 2929, 2837, 1632, 1605, 1569, 1497, 1453
cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C16H18ONa: 249.1255;
found: 249.1260.
1H NMR (400 MHz, CDCl3): d = 5.91 (s, 1 H), 3.84 (t, J = 6.4 Hz,
2 H), 2.84 (t, J = 6.4 Hz, 2 H), 2.54 (t, J = 6.0 Hz, 2 H), 2.39–2.36
(m, 2 H), 1.84–1.74 (m, 2 H), 1.71–1.60 (m, 3 H).
3-(4-Methylfuran-2-yl)propan-1-ol (2j)
Colorless oil; yield: 90%.
13C NMR (100 MHz, CDCl3): d = 150.20, 149.60, 117.34, 107.46,
61.16, 31.67, 23.10, 23.07, 23.02.
IR (neat): 3373, 2927, 2850, 1617, 1551, 1446, 1384 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.06 (s, 1 H), 5.88 (s, 1 H), 3.68
(t, J = 6.0 Hz, 2 H), 2.68 (t, J = 7.2 Hz, 2 H), 1.98 (s, 3 H), 1.93–
1.85 (m, 2 H).
HRMS (ESI): m/z [M + Na]+ calcd for C10H14O2Na: 189.0891;
found: 189.0895.
2-(2-Vinylphenyl)-4,5,6,7-tetrahydrobenzofuran (2f)
Colorless oil; yield: 73%.
13C NMR (100 MHz, CDCl3): d = 155.53, 137.45, 120.46, 107.87,
62.02, 30.94, 24.34, 9.72.
IR (neat): 3073, 3059, 2928, 2850, 1625, 1598, 1541, 1478, 1442
cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C8H12O2Na: 163.0735;
found: 163.0747.
1H NMR (400 MHz, CDCl3): d = 7.63 (d, J = 7.6 Hz, 1 H), 7.51 (d,
J = 7.6 Hz, 1 H), 7.31–7.22 (m, 2 H), 7.11 (dd, J = 17.2, 10.8 Hz, 1
H), 6.32 (s, 1 H), 5.66 (dd, J = 17.2, 1.2 Hz, 1 H), 5.29 (dd, J = 10.8,
1.2 Hz, 1 H), 2.67 (t, J = 6.0 Hz, 2 H), 2.47 (t, J = 6.0 Hz, 2 H),
1.90–1.85 (m, 2 H), 1.79–1.73 (m, 2 H).
2,5-Diphenylfuran (2k)
White solid; yield: 82% (trans-1k) and 83% (cis-1k).
IR (neat): 3056, 3036, 1670, 1609, 1598, 1539, 1488, 1479, 1468,
1448 cm–1.
13C NMR (100 MHz, CDCl3): d = 150.88, 150.07, 136.76, 135.06,
129.77, 127.62, 127.00, 126.89, 118.86, 115.21, 111.25, 23.27,
23.13, 23.08, 22.15.
1H NMR (400 MHz, CDCl3): d = 7.80–7.70 (m, 4 H), 7.43–7.36 (m,
4 H), 7.34–7.20 (m, 2 H), 6.74 (s, 2 H).
13C NMR (100 MHz, CDCl3): d = 153.35, 130.77, 128.70, 127.32,
123.71, 107.21.
HRMS (ESI): m/z [M + Na]+ calcd for C16H16ONa: 247.1099;
found: 247.1095.
HRMS (ESI): m/z [M + Na]+ calcd for C16H12ONa: 243.0786;
found: 243.0784.
2-Phenyl-5,6-dihydro-4H-cyclopenta[b]furan (2g)
Colorless oil; yield: 34%.
3-Deuterio-2-phenyl-4,5,6,7-tetrahydrobenzofuran (2a-D)
To a stirred soln of 1a (30.0 mg, 0.151 mmol) in dioxane–D2O (2:1)
was added PtCl2 (4.0 mg, 0.015 mmol) at r.t. The mixture was
stirred at 100 °C for 10 min and then cooled to r.t. and diluted with
the minimum amount of Et2O. The soln was dried (MgSO4) and fil-
tered through a small amount of silica gel. Concentration at reduced
pressure gave the residue, which was chromatographed (silica gel,
pentane–Et2O, 95:5) to give the deuterated furan 2a-D (26.74 mg,
89%, 97% deuterized) as a colorless oil.
IR (neat): 3059, 3034, 2924, 2857, 1627, 1601, 1539, 1483, 1447
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.61 (t, J = 7.6 Hz, 2 H), 7.34 (t,
J = 7.6 Hz, 2 H), 7.20 (t, J = 7.6 Hz, 1 H), 6.52 (s, 1 H), 2.78–2.74
(m, 2 H), 2.60–2.57 (m, 2 H), 2.50–2.43 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 133.42, 128.65, 128.57, 127.58,
126.57, 123.06, 103.58, 29.69, 27.73, 24.79.
HRMS (ESI): m/z [M + Na]+ calcd for C13H12ONa: 207.0786;
found: 207.0792.
IR (neat): 3078, 3058, 2929, 2850, 1669, 1604, 1542, 1484, 1444,
1408 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.60 (d, J = 7.6 Hz, 2 H), 7.33 (t,
J = 7.6 Hz, 2 H), 7.19 (t, J = 7.2 Hz, 1 H), 2.66 (t, J = 6.0 Hz, 2 H),
2.45 (t, J = 6.0 Hz, 2 H), 1.89–1.83 (m, 2 H), 1.77–1.71 (m, 2 H).
2-Phenyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]furan (2h)
Colorless oil; yield: 92%.
IR (neat): 3079, 3056, 2927, 2850, 1638, 1609, 1594, 1532, 1486,
1448 cm–1.
13C–NMR (100 MHz, CDCl3): d = 151.51, 150.79, 131.41, 128.53,
126.52, 123.22, 118.89, 105.99, 23.28, 23.12, 23.07, 22.11.
1H NMR (400 MHz, CDCl3): d = 7.60–7.57 (m, 2 H), 7.35–7.28 (m,
2 H), 7.20–7.16 (m, 1 H), 6.42 (s, 1 H), 2.83 (t, J = 6.0 Hz, 2 H),
2.50 (t, J = 5.6 Hz, 2 H), 1.80–1.70 (m, 6 H).
HRMS (ESI): m/z [M + Na]+ calcd for C14 H132HONa: 222.1005;
1
found: 222.1006.
13C NMR (100 MHz, CDCl3): d = 153.31, 149.75, 131.28, 128.51,
126.41, 123.14, 122.91, 108.69, 30.77, 29.01, 28.68, 26.60, 26.21.
3-Iodo-2-phenyl-4,5,6,7-tetrahydrobenzofuran (9)
To a stirred soln of 1a (30.0 mg, 0.151 mmol) in MeCN–H2O (2:1)
was added PtCl2 (4.0 mg, 0.015 mmol) and NIS (40.8 mg, 0.181
mmol) at r.t. The mixture was stirred at 100 °C for 10 min and then
it was cooled to r.t. and diluted with the minimum amount of Et2O.
The soln was then dried (MgSO4) and filtered through a small
amount of silica gel. Concentration at reduced pressure gave the res-
idue, which was chromatographed (silica gel, hexane–EtOAc, 97:3)
to give the iodofuran 9 (33.9 mg, 69%) as a colorless oil.
HRMS (ESI): m/z [M + Na]+ calcd for C15H16ONa: 235.1099;
found: 235.1099.
2-Phenyl-4,5,6,7,8,9-hexahydrocycloocta[b]furan (2i)
Colorless oil; yield: 89%.
IR (neat): 3080, 3056, 2927, 2845, 1624, 1607, 1542, 1485, 1454,
1352 cm–1.
IR (neat): 3078, 3057, 2929, 2847, 1628, 1603, 1542, 1484, 1443,
1400 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.62–7.59 (m, 2 H), 7.35–7.31 (m,
2 H), 7.20–7.16 (m, 1 H), 6.42 (s, 1 H), 2.83 (t, J = 6.0 Hz, 2 H),
2.57 (t, J = 6.0 Hz, 2 H), 1.79–1.75 (m, 2 H), 1.71–1.67 (m, 2 H),
1.53–1.50 (m, 4 H).
1H NMR (400 MHz, CDCl3): d = 7.96 (d, J = 7.2 Hz, 2 H), 7.39 (t,
J = 7.2 Hz, 2 H), 7.28 (t, J = 7.2 Hz, 1 H), 2.64 (t, J = 6.0 Hz, 2 H),
2.31 (t, J = 6.0 Hz, 2 H), 1.89–1.83 (m, 2 H), 1.77–1.71 (m, 2 H).
Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York

2462
M. Yoshida et al.
FEATURE ARTICLE
13C NMR (100 MHz, CDCl3): d = 151.23, 148.98, 130.82, 128.27,
127.46, 125.80, 123.23, 66.55, 23.28, 23.26, 23.17, 22.88.
1H NMR (400 MHz, CDCl3): d = 7.59 (t, J = 7.2 Hz, 2 H), 7.41–7.37
(m, 2 H), 7.32–7.25 (m, 1 H), 6.82 (dd, J = 17.6, 11.2 Hz, 1 H), 5.50
(dd, J = 17.6, 1.6 Hz, 1 H), 5.23 (dd, J = 11.2, 1.6 Hz, 1 H), 2.67–
2.60 (m, 4 H), 1.89–1.84 (m, 2 H), 1.82–1.76 (m, 2 H).
HRMS (ESI): m/z [M + Na]+ calcd for C14H13IONa: 346.9909;
found: 346.9905.
13C NMR (100 MHz, CDCl3): d = 150.72, 148.79, 131.60, 128.72,
128.48, 128.43, 128.23, 127.06, 126.60, 119.34, 117.70, 114.97,
22.29, 23.20, 22.78, 22.60.
3-(4-Methoxyphenyl)-2-phenyl-4,5,6,7-tetrahydrobenzofuran
(11a)
To a stirred soln of iodofuran 9 (30.0 mg, 0.093 mmol) in toluene–
EtOH (3:1) was added 4-methoxyphenylboronic acid (42.2 mg,
0.278 mmol), Pd(PPh3)4 (10.7 mg, 0.009 mmol), and K2CO3 (38.4
mg, 0.278 mmol) at r.t. The mixture was stirred at 80 °C for 7 h and
then it was cooled to r.t. and then filtered through a pad of Celite.
Concentration at reduced pressure gave the residue, which was
chromatographed (silica gel, hexane–EtOAc, 97:3) to give 11a
(27.5 mg, 98%) as a yellow oil.
HRMS (ESI): m/z [M + Na]+ calcd for C16H16ONa: 247.1099;
found: 247.1094.
Methyl 3-(2-Phenyl-4,5,6,7-tetrahydrobenzofuran-3-yl)acry-
late (11d)
To a stirred soln of iodofuran 9 (30.0 mg, 0.093 mmol) in DMF (1.5
mL) was added methyl acrylate (16.7 mL, 0.186 mmol), Pd(OAc)2
(2.0 mg, 0.009 mmol), Ph3P (2.4 mg, 0.009 mmol) ,and Et3N (38.8
mL, 0.279 mmol) at r.t. The mixture was stirred at 80 °C for 2.5 h,
the mixture was diluted with brine (10 mL) and extracted with
EtOAc (3 ꢀ 15 mL). The combined extracts were washed with brine
(20 mL) and dried (MgSO4). Concentration at reduced pressure
gave the residue, which was chromatographed (silica gel, hexane–
EtOAc, 97:3) to give 11d (25.6 mg, 98%) as a gray solid.
IR (neat): 3064, 3019, 2932, 2846, 1600, 1561, 1511, 1485, 1442,
1384 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.46–7.39 (m, 2 H), 7.32–7.20 (m,
4 H), 7.14 (t, J = 7.6 Hz, 1 H), 6.93–6.88 (m, 2 H), 3.84 (s, 3 H),
2.69 (t, J = 6.4 Hz, 2 H), 2.34 (t, J = 6.4 Hz, 2 H), 1.91–1.82 (m, 2
H), 1.77–1.71 (m, 2 H).
IR (neat): 3094, 3066, 2945, 2849, 1720, 1636, 1624, 1547, 1480,
1461, 1433, 1348 cm–1.
13C NMR (100 MHz, CDCl3): d = 158.60, 150.09, 146.34, 131.73,
130.52, 128.19, 126.63, 126.45, 125.41, 122.00, 119.61, 114.17,
114.03, 55.31, 55.18, 23.30, 23.07, 22.96, 21.38.
1H NMR (400 MHz, CDCl3): d = 7.85 (d, J = 16.0 Hz, 1 H), 7.58 (t,
J = 7.6 Hz, 2 H), 7.44 (t, J = 7.6 Hz, 2 H), 7.35 (t, J = 7.2 Hz, 1 H),
6.23 (d, J = 16.0 Hz, 1 H), 3.76 (s, 3 H), 2.67–2.62 (m, 4 H), 1.89–
1.79 (m, 4 H).
HRMS (ESI): m/z [M + Na]+ calcd for C21H20O2Na: 327.1361;
found: 327.1366.
2-Phenyl-3-(phenylethynyl)-4,5,6,7-tetrahydrobenzofuran
(11b)
13C NMR (100 MHz, CDCl3): d = 167.90, 153.54, 151.64, 137.08,
130.52, 128.71, 128.21, 127.36, 117.43, 117.28, 117.23, 51.48,
23.14, 22.95, 22.81, 22.36.
To a stirred soln of iodofuran 9 (30.0 mg, 0.093 mmol) in Et3N–
MeCN (4:1) was added PdCl2(PPh3)2 (3.3 mg, 0.005 mmol) and CuI
(2.0 mg, 0.009 mmol) at r.t. Phenylacetylene (48.1 mL, 0.372 mmol)
was then added to the stirred soln over 10 min at the same tempera-
ture. The mixture was stirred at r.t. for 25 h and it was quenched
with aq sat. NH4Cl and extracted with EtOAc (3 ꢀ 10 mL). The
combined extracts were washed with brine (20 mL) and dried
(MgSO4). Concentration at reduced pressure gave the residue,
which was chromatographed (silica gel, hexane–EtOAc, 99:1) to
give 11b (25.6 mg, 93%) as a white solid.
HRMS (ESI): m/z [M + H]+ calcd for C18H19O3: 283.1334; found:
283.1331.
(2R*,3R*)-1-Benzyl-2-cyclohexyl-3-ethynylaziridine (3g)
To a stirred soln of (3-chloroprop-1-ynyl)trimethylsilane (500 mg,
3.41 mmol) in THF (10.0 mL) was added ZnBr2 (1.54 g, 6.82 mmol)
at –78 °C. A freshly prepared soln of 1.0 M LDA in THF (6.82 mL,
6.82 mmol) was slowly added dropwise to the resulting white sus-
pension and stirring was continued at the same temperature for 1 h
to produce allenylzinc compound 13a. N-Benzylimine 12a (686
mg, 3.41 mmol) in THF (4.0 mL) was then added dropwise to the
resulting soln of 13a at –78 °C. The temperature was slowly al-
lowed to rise to r.t. and the mixture was stirred for a further 8 h at
this temperature. The mixture was quenched with aq sat. NH4Cl and
extracted with Et2O (3 ꢀ 20 mL). The combined organic extracts
were washed with H2O (2 ꢀ 20 mL) and brine (20 mL) and dried
(MgSO4). Concentration at reduced pressure gave the residue,
which was purified by flash chromatography, (hexane–EtOAc,
97:3) to give 1-benzyl-2-cyclohexyl-3-[(trimethylsilyl)ethyn-
yl]aziridine as a yellow oil. To a stirred soln of 1-benzyl-2-cyclo-
hexyl-3-[(trimethylsilyl)ethynyl]aziridine (600 mg, 1.93 mmol) in
MeOH (18 mL) was added K2CO3 (532 mg, 3.85 mmol) at r.t., and
stirring was continued for 0.5 h at this temperature. The mixture was
then poured into H2O–Et2O (1:1) and extracted with Et2O (3 ꢀ 25
mL). The combined organic extracts were washed with brine
(2 ꢀ 20 mL) and dried (MgSO4). The solvent was evaporated at re-
duced pressure and the residue was chromatographed (silica gel,
hexane–EtOAc, 92:8) to give 3g (458 mg, 95% 2 steps) as a color-
less oil.
IR (neat): 3060, 3020, 2934, 2852, 2210, 1638, 1600, 1552, 1498,
1484, 1444, 1351 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.08 (d, J = 7.6 Hz, 2 H), 7.53 (dd,
J = 7.6, 1.2 Hz, 2 H), 7.42–7.32 (m, 5 H), 7.26 (t, J = 7.6 Hz, 1 H),
2.64 (t, J = 6.0 Hz, 2 H), 2.53 (t, J = 6.0 Hz, 2 H), 1.91–1.85 (m, 2
H), 1.81–1.76 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 152.55, 150.22, 131.36, 130.98,
128.46, 128.36, 128.03, 127.30, 124.36, 123.76, 120.96, 103.53,
95.26, 82.53, 23.08, 22.93, 22.70, 20.91.
HRMS (ESI): m/z [M + Na]+ calcd for C22H18ONa: 321.1255;
found: 321.1252.
2-Phenyl-3-vinyl-4,5,6,7-tetrahydrobenzofuran (11c)
To a stirred soln of iodofuran 9 (35.5 mg, 0.110 mmol) in THF (2.0
mL) was added Pd(PPh3)4 (12.7 mg, 0.011 mmol), LiCl (14.0 mg,
0.330 mmol), and tributyl(vinyl)tin (64 mL, 0.220 mmol) at r.t. The
mixture was stirred at 50 °C for 15 h and it was cooled to r.t. and
then filtered through a pad of Celite. Concentration at reduced pres-
sure gave the residue, which was chromatographed (silica gel, hex-
ane–EtOAc–Et3N, 98.5:1:0.5) to give the coupled product 11c (12.8
mg, 52%) as a pale yellow oil.
IR (neat): 3295, 3086, 3062, 3029, 2922, 2850, 2114, 1603, 1495,
1450, 1416, 1383, 1354 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.39–7.37 (m, 2 H), 7.35–7.33 (m,
2 H), 7.28–7.24 (m, 1 H), 3.90 (d, J = 13.2 Hz, 1 H), 3.48 (d,
J = 13.2 Hz, 1 H), 2.41 (dd, J = 3.2, 2.0 Hz, 1 H), 2.22 (d, J = 2.0
IR (neat): 3096, 3066, 3029, 2940, 2848, 1636, 1604, 1597, 1480,
1461, 1431, 1354 cm–1.
Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York

FEATURE ARTICLE
Syntheses of Substituted Furans and Pyrroles
2463
Hz, 1 H), 1.71–1.68 (m, 2 H), 1.60–1.51 (m, 4 H), 1.15–0.86 (m, 6
H).
(2R*,3R*)-1-Benzyl-2-cyclohexyl-3-(3-phenylprop-1-ynyl)aziri-
dine (3c)
Following the typical procedure for 3a using 3g with BnBr (14c)
gave 3c as a colorless oil; yield: 72%.
13C NMR (100 MHz, CDCl3): d = 139.02, 128.56, 128.09, 126.86,
80.48, 71.59, 58.53, 53.17, 40.60, 30.56, 30.30, 29.75, 26.10, 25.58,
25.44.
IR (neat): 3062, 3029, 2925, 2850, 2195, 1644, 1603, 1495, 1451,
1419, 1354 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C17H21NNa: 262.1572;
found: 262.1576.
1H NMR (400 MHz, CDCl3): d = 7.37–7.35 (m, 2 H), 7.33–7.28 (m,
5 H), 7.27–7.22 (m, 3 H), 3.87 (d, J = 13.2 Hz, 1 H), 3.64 (d, J = 2.0
Hz, 2 H), 3.53 (d, J = 13.6 Hz, 1 H), 2.47 (dt, J = 3.2, 2.0 Hz, 1 H),
1.72–1.70 (m, 2 H), 1.59–1.54 (m, 3 H), 1.51 (dd, J = 7.2, 3.2 Hz, 1
H), 1.30–1.26 (m, 2 H), 1.24–1.02 (m, 4 H).
(2R*,3R*)-1-Benzyl-2-cyclohexyl-3-(pent-1-ynyl)aziridine (3a);
Typical Procedure
To a stirred soln of 3g (250 mg, 1.04 mmol) in THF (2.0 mL) was
added dropwise 2.6 M BuLi in hexane (1.2 mL, 3.13 mmol) at –78
°C. The mixture was stirred for 1 h and then a soln of PrBr (14a,
0.30 mL, 3.12 mmol) and HMPA (0.40 mL, 3.12 mmol) in THF (1.0
mL) was added dropwise to the stirred soln at the same temperature
of the mixture was allowed gradually rise to r.t. The mixture was
stirred at r.t. for 3 h and then it was quenched with aq sat. NH4Cl and
extracted with Et2O (3 ꢀ 10 mL). The combined organic extracts
were washed with brine (2 ꢀ 15 mL) and dried (MgSO4). The sol-
vent was evaporated at reduced pressure and the residue was chro-
matographed (silica gel, hexane–EtOAc, 94:6) to give 3a (235 mg,
80%) as a colorless oil.
13C NMR (100 MHz, CDCl3): d = 139.31, 136.68, 128.70, 128.53,
128.23, 127.82, 126.92, 126.56, 81.50, 78.67, 58.51, 53.37, 40.75,
31.67, 30.54, 30.01, 26.27, 25.74, 25.59, 25.26.
HRMS (ESI): m/z [M + Na]+ calcd for C24H27NNa: 352.2041;
found: 352.2041.
(2R*,3R*)-1-Benzyl-2-cyclohexyl-3-(pent-4-en-1-ynyl)aziridine
(3d)
Following the typical procedure for 3a using 3g with allyl bromide
(14d) gave 3d as a colorless oil; yield: 81%.
IR (neat): 3086, 3062, 3029, 2924, 2850, 2195, 1642, 1605, 1496,
1450, 1418, 1354 cm–1.
IR (neat): 3086, 3062, 3028, 2924, 2850, 2230, 1603, 1495, 1450,
1380 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.39–7.37 (m, 2 H), 7.35–7.30 (m,
2 H), 7.28–7.23 (m, 1 H), 5.86–5.76 (m, 1 H), 5.31–5.27 (m, 1 H),
5.12–5.09 (m, 1 H), 3.89 (d, J = 13.2 Hz, 1 H), 3.48 (d, J = 13.2 Hz,
1 H), 3.03–3.00 (m, 2 H), 2.44–2.43 (m, 1 H), 1.71–1.68 (m, 2 H),
1.60–1.55 (m, 3 H), 1.50–1.47 (m, 1 H), 1.15–1.04 (m, 4 H), 0.90–
0.86 (m, 2 H).
1H NMR (400 MHz, CDCl3): d = 7.38 (d, J = 6.8 Hz, 2 H), 7.34–
7.30 (m, 2 H), 7.26–7.23 (m, 1 H), 3.86 (d, J = 13.2 Hz, 1 H), 3.47
(d, J = 13.2 Hz, 1 H), 2.41–2.39 (m, 1 H), 2.22–2.18 (m, 2 H), 1.70–
1.67 (m, 2 H), 1.60–1.43 (m, 8 H), 1.14–1.07 (m, 4 H), 0.96 (t,
J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 139.61, 128.74, 128.18, 126.85,
83.98, 76.57, 58.54, 53.29, 40.90, 31.71, 30.54, 29.30, 26.28, 25.77,
25.61, 22.20, 20.84, 13.44.
13C NMR (100 MHz, CDCl3): d = 139.48, 132.48, 128.71, 128.26,
126.90, 116.07, 80.40, 78.97, 58.66, 53.33, 40.90, 31.56, 30.53,
29.98, 26.26, 25.75, 25.59, 23.19.
HRMS (ESI): m/z [M + Na]+ calcd for C20H27NNa: 304.2041;
found: 304.2042.
HRMS (ESI): m/z [M + Na]+ calcd for C20H25NNa: 302.1885;
found: 302.1880.
(2R*,3R*)-1-Benzyl-2-cyclohexyl-3-(phenylethynyl)aziridine
(3b)
(2R*,3R*)-1-Benzyl-3-[3-(tert-butyldiphenylsiloxy)propyl]-2-
cyclohexylaziridine (3e)
To a stirred soln of (3-chloroprop-1-ynyl)benzene (300 mg, 1.99
mmol) in THF (8.0 mL) was added ZnBr2 (896 mg, 3.98 mmol) at
–78 °C. A freshly prepared soln of 1.0 M LDA in THF (3.98 mL,
3.98 mmol) was slowly added dropwise to the resulting white sus-
pension and the stirring was continued for 1 h at this temperature to
produce allenylzinc compound 13b. N-Benzylimine 12a (400 mg,
1.99 mmol) in THF (3.0 mL) was then added dropwise to the result-
ing soln of 13b at –78 °C. The temperature was slowly allowed to
rise to r.t. and stirring was continued at this temperature for 8 h. The
mixture was quenched with aq sat. NH4Cl and extracted with Et2O
(3 ꢀ 20 mL). The combined organic extracts were washed with H2O
(2 ꢀ 20 mL) and brine (20 mL) and dried (MgSO4). Concentration
at reduced pressure gave the residue, which was purified by flash
chromatography (hexane–EtOAc, 95:5), to give 3b (176 mg, 28%)
as a yellow oil.
Following the typical procedure for 3a using 3g with (3-bromopro-
poxy)-tert-butyldiphenylsilane (14e) gave 3e as a colorless oil;
yield: 52%.
IR (neat): 3069, 3029, 2927, 2854, 2196, 1589, 1496, 1471, 1450,
1428, 1389, 1359 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.67–7.64 (m, 4 H), 7.43–7.20 (m,
11 H), 3.79 (d, J = 13.2 Hz, 1 H), 3.72 (t, J = 6.4 Hz, 2 H), 3.40 (d,
J = 13.2 Hz, 1 H), 2.39–2.36 (m, 3 H), 1.76–1.67 (m, 4 H), 1.60–
1.54 (m, 3 H), 1.30–1.24 (m, 3 H), 1.14–1.07 (m, 2 H), 1.04 (s, 9 H),
0.89 (t, J = 6.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 139.57, 135.54, 133.84, 129.57,
128.74, 128.18, 127.62, 126.85, 83.59, 77.31, 62.42, 58.59, 53.28,
40.93, 31.70, 31.67, 30.58, 30.03, 26.83, 25.79, 25.64, 22.64, 19.23,
14.10.
IR (neat): 3064, 3028, 2924, 2849, 2219, 1597, 1490, 1449, 1353
cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C36H45NOSiNa: 558.3168;
found: 558.3162.
1H NMR (400 MHz, CDCl3): d = 7.42–7.39 (m, 4 H), 7.35–7.24 (m,
6 H), 3.95 (d, J = 13.2 Hz, 1 H), 3.58 (d, J = 13.2 Hz, 1 H), 2.61 (d,
J = 3.2 Hz, 1 H), 1.76–1.58 (m, 6 H), 1.26–0.89 (m, 6 H).
(2R*,3R*)-5-(1-Benzyl-3-cyclohexylaziridin-2-yl)pent-4-yn-1-ol
(3f)
13C–NMR (100 MHz, CDCl3): d = 139.32, 131.60, 128.75, 128.23,
128.04, 126.96, 122.96, 86.43, 83.48, 58.88, 53.93, 40.89, 31.67,
30.53, 29.97, 26.24, 25.73, 25.59.
To a stirred soln of 3e (70.0 mg, 0.131 mmol) in THF (3.0 mL) was
added 1.0 M TBAF in THF (0.5 mL, 0.524 mmol) at 0 °C, and stir-
ring was continued at r.t. for 1.5 h. The mixture was poured into aq
sat. NH4Cl, and extracted with EtOAc (3 ꢀ 10 mL). The combined
organic extracts were washed with brine (2 ꢀ 15 mL) and dried
(MgSO4). The solvent was evaporated under reduced pressure and
HRMS (ESI): m/z [M + Na]+ calcd for C23H25NNa: 338.1885;
found: 338.1884.
Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York

2464
M. Yoshida et al.
FEATURE ARTICLE
the residue was chromatographed (silica gel, hexane–EtOAc,
65:35) to give 3f (38.1 mg, 98%) as a colorless oil.
(2R*,3R*)-1-Benzyl-2-(2-naphthyl)-3-(pent-1-ynyl)aziridine
(3k)
Following the typical procedure for 3a using imine 12k gave 3k in
3 steps as a colorless oil; yield: 85% (3 steps).
IR (neat): 3310, 3064, 3031, 2926, 2851, 2242, 1604, 1497, 1450,
1352 cm–1.
IR (neat): 3061, 3028, 2963, 2932, 2872, 2239, 1603, 1509, 1497,
1454, 1380, 1357 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.38–7.23 (m, 5 H), 3.84 (d,
J = 13.2 Hz, 1 H), 3.66 (t, J = 6.4 Hz, 2 H), 3.49 (d, J = 13.2 Hz, 1
H), 2.40 (d, J = 2.4 Hz, 1 H), 2.35–2.31 (m, 2 H), 1.93 (br s, 1 H),
1.75–1.67 (m, 4 H), 1.60–1.53 (m, 3 H), 1.47–1.43 (m, 1 H), 1.18–
1.04 (m, 4 H), 0.94–0.83 (m, 2 H).
1H NMR (400 MHz, CDCl3): d = 7.76–7.72 (m, 4 H), 7.45–7.33 (m,
5 H), 7.28–7.15 (m, 3 H), 4.12 (d, J = 14.4 Hz, 1 H), 3.87 (d,
J = 14.4 Hz, 1 H), 2.82 (d, J = 2.4 Hz, 1 H), 2.74 (d, J = 2.4 Hz, 1
H), 2.23 (t, J = 6.8 Hz, 2 H), 1.60–1.51 (m, 2 H), 1.00 (t, J = 7.2 Hz,
3 H).
13C NMR (100 MHz, CDCl3): d = 139.43, 128.62, 128.20, 126.90,
83.26, 76.69, 61.42, 58.51, 53.31, 40.84, 31.62, 31.37, 30.53, 29.97,
26.25, 25.72, 25.58, 15.39.
13C NMR (100 MHz, CDCl3): d = 139.37, 136.26, 133.24, 132.80,
128.24, 127.99, 127.97, 127.61, 126.75, 126.00, 125.49, 124.93,
124.14, 84.98, 75.65, 56.91, 49.64, 37.11, 22.13, 20.85, 13.48.
HRMS (ESI): m/z [M + Na]+ calcd for C20H27NONa: 320.1990;
found: 320.1992.
HRMS (ESI): m/z [M + Na]+ calcd for C24H23NNa: 348.1728;
found: 348.1722.
(2R*,3R*)-1-Benzyl-2-butyl-3-(pent-1-ynyl)aziridine (3h)
Following the typical procedure for 3a using imine 12h gave 3h in
3 steps as a colorless oil; yield: 80% (3 steps).
1-Benzyl-2-cyclohexyl-5-propyl-1H-pyrrole (4a); Typical Pro-
cedure
IR (neat): 3062, 3028, 2959, 2931, 2870, 2162, 1604, 1495, 1454,
1379, 1353 cm–1.
To a stirred soln of 3a (40.0 mg, 0.142 mmol) in dioxane–H2O (2:1)
was added PtCl2 (3.78 mg, 0.014 mmol) at r.t. The mixture was
stirred at 100 °C for 2 h and then cooled to r.t. and diluted with the
minimum amount of Et2O. The soln was dried (MgSO4) and filtered
through a small amount of silica gel. Concentration at reduced pres-
sure gave the residue, which was chromatographed (silica gel, hex-
ane–EtOAc, 98:2) to give 4a (30.8 mg, 77%) as a yellow oil.
1H NMR (400 MHz, CDCl3): d = 7.39 (d, J = 7.2 Hz, 2 H), 7.33 (t,
J = 7.2 Hz, 2 H), 7.24 (t, J = 7.2 Hz, 1 H), 3.87 (d, J = 13.6 Hz, 1
H), 3.54 (d, J = 13.6 Hz, 1 H), 2.35 (s, 1 H), 2.22–2.18 (m, 2 H),
1.65–1.61 (m, 1 H), 1.57–1.48 (m, 2 H), 1.44–1.41 (m, 2 H), 1.37–
1.26 (m, 4 H), 0.97 (t, J = 7.6 Hz, 3 H), 0.90–0.83 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 139.63, 128.38, 128.13, 126.72,
84.05, 76.40, 58.15, 48.05, 32.63, 32.30, 29.06, 22.26, 22.14, 20.78,
13.86, 13.37.
IR (neat): 3061, 3026, 2928, 2851, 1605, 1495, 1450, 1426, 1376,
1352 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.30–7.20 (m, 3 H), 6.84 (d,
J = 7.2 Hz, 2 H), 5.91 (s, 2 H), 5.04 (s, 2 H), 2.37–2.31 (m, 2 H),
1.82–1.79 (m, 2 H), 1.71–1.60 (m, 3 H), 1.58–1.54 (m, 3 H), 1.36–
1.30 (m, 2 H), 1.23–1.19 (m, 3 H), 0.90 (t, J = 7.2 Hz, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C18H26N: 256.2065; found:
256.2065.
(2R*,3R*)-1-Benzyl-2-tert-butyl-3-(pent-1-ynyl)aziridine (3i)
Following the typical procedure for 3a using imine 12i gave 3i in 3
steps as a colorless oil; yield: 61% (3 steps).
13C NMR (100 MHz, CDCl3): d = 139.22, 138.82, 132.37, 128.59,
126.87, 125.52, 104.40, 102.35, 46.30, 35.85, 34.22, 28.70, 26.73,
26.13, 21.74, 14.11.
IR (neat): 3063, 3030, 2958, 2904, 2870, 2227, 1605, 1496, 1477,
1455, 1413, 1382, 1362 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C20H27NNa: 304.2041;
found: 304.2040.
1H NMR (400 MHz, CDCl3): d = 7.40 (d, J = 7.2 Hz, 2 H), 7.31 (t,
J = 7.2 Hz, 2 H), 7.23 (t, J = 7.2 Hz, 1 H), 3.91 (d, J = 13.2 Hz, 1
H), 3.68 (d, J = 13.2 Hz, 1 H), 2.45 (s, 1 H), 2.18 (t, J = 6.8 Hz, 2
H), 1.56–1.47 (m, 3 H), 0.96 (t, J = 7.6 Hz, 3 H), 0.75 (s, 9 H).
1-Benzyl-2-cyclohexyl-5-phenyl-1H-pyrrole (4b)
Yellow oil; yield: 79%.
IR (neat): 3066, 3028, 2927, 2850, 1602, 1508, 1496, 1450, 1388,
1359 cm–1.
13C NMR (100 MHz, CDCl3): d = 139.95, 128.78, 128.57, 126.77,
83.53, 76.81, 58.66, 57.47, 30.47, 28.30, 27.60, 22.24, 20.85, 13.56.
1H NMR (400 MHz, CDCl3): d = 7.29–7.21 (m, 8 H), 6.88 (d,
J = 7.2 Hz, 2 H), 6.26 (d, J = 3.6 Hz, 1 H), 6.08 (d, J = 3.6 Hz, 1 H),
5.18 (s, 2 H), 2.38–2.31 (m, 1 H), 1.84–1.65 (m, 5 H), 1.45–1.36 (m,
2 H), 1.28–1.17 (m, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C18H25NNa: 278.1885;
found: 278.1884.
(2R*,3R*)-1-Benzyl-2-(pent-1-ynyl)-3-phenylaziridine (3j)
Following the typical procedure for 3a using imine 12j gave 3j in 3
steps as a colorless oil; yield: 77% (3 steps).
13C NMR (100 MHz, CDCl3): d = 141.06, 139.57, 133.90, 133.80,
128.88, 128.58, 128.21, 126.89, 126.55, 125.56, 108.30, 104.20,
47.39, 36.04, 34.29, 26.73, 26.07.
IR (neat): 3061, 3029, 2962, 2931, 2870, 2241, 1602, 1495, 1453,
1383, 1353 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C23H25NNa: 338.1885;
found: 338.1882.
1H NMR (400 MHz, CDCl3): d = 7.33 (d, J = 6.8 Hz, 2 H), 7.32–
7.22 (m, 8 H), 4.06 (d, J = 14.0 Hz, 1 H), 3.83 (d, J = 14.0 Hz, 1 H),
2.67 (d, J = 2.8 Hz, 1 H), 2.65–2.63 (m, 1 H), 2.26–2.23 (m, 2 H),
1.60–1.51 (m, 2 H), 0.99 (t, J = 7.2 Hz, 3 H).
1,2-Dibenzyl-5-cyclohexyl-1H-pyrrole (4c)
Yellow oil; yield: 68%.
IR (neat): 3062, 3027, 2926, 2852, 1604, 1495, 1452, 1427, 1355
cm–1.
13C NMR (100 MHz, CDCl3): d = 139.42, 138.75, 128.23, 128.20,
128.03, 127.13, 126.73, 126.11, 84.83, 75.65, 57.88, 49.42, 36.91,
22.12, 20.84, 13.46.
1H NMR (400 MHz, CDCl3): d = 7.29–7.12 (m, 6 H), 7.08 (d,
J = 7.2 Hz, 2 H), 6.82 (d, J = 6.8 Hz, 2 H), 5.91 (d, J = 3.2 Hz, 1 H),
5.83 (d, J = 3.2 Hz, 1 H), 4.95 (s, 2 H), 3.73 (s, 2 H), 2.38–2.32 (m,
1 H), 1.82–1.64 (m, 5 H), 1.40–1.34 (m, 2 H), 1.31–1.19 (m, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C20H22N: 276.1752; found:
276.1750.
Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York

FEATURE ARTICLE
Syntheses of Substituted Furans and Pyrroles
2465
13C NMR (100 MHz, CDCl3): d = 139.68, 139.62, 139.61, 130.50,
128.62, 128.27, 126.93, 126.03, 125.57, 107.17, 102.47, 46.56,
35.89, 34.15, 33.20, 26.71, 26.12.
13C NMR (100 MHz, CDCl3): d = 139.72, 138.89, 128.63, 127.27,
126.36, 120.39, 107.15, 103.74, 50.00, 35.58, 34.00, 26.71, 26.10.
HRMS (ESI): m/z [M + Na]+ calcd for C17H21NNa: 262.1572;
found: 262.1570.
HRMS (ESI): m/z [M + Na]+ calcd for C24H27NNa: 352.2041;
found: 352.2044.
1-Benzyl-2-butyl-5-propyl-1H-pyrrole (4h)
Colorless oil; yield: 81%.
2-Allyl-1-benzyl-5-cyclohexyl-1H-pyrrole (4d)
Yellow oil; yield: 65%.
IR (neat): 3063, 3026, 2956, 2929, 2870, 1605, 1509, 1495, 1454,
1423, 1377, 1353 cm–1.
IR (neat): 3063, 3028, 2926, 2851, 1638, 1605, 1496, 1450, 1429,
1355 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.30–7.19 (m, 3 H), 6.85 (d,
J = 7.6 Hz, 2 H), 5.90 (s, 2 H), 5.02 (s, 2 H), 2.40 (q, J = 7.2 Hz, 4
H), 1.63–1.50 (m, 4 H), 1.37–1.27 (m, 2 H), 0.92 (t, J = 7.6 Hz, 3
H), 0.85 (t, J = 7.2 Hz, 3 H).
1H NMR (400 MHz, CDCl3): d = 7.30–7.20 (m, 3 H), 6.84 (d,
J = 7.2 Hz, 2 H), 5.92–5.82 (m, 3 H), 5.05–4.96 (m, 4 H), 3.15 (d,
J = 6.8 Hz, 2 H), 2.40–2.27 (m, 1 H), 1.81–1.65 (m, 5 H), 1.43–1.28
(m, 2 H), 1.25–1.14 (m, 3 H).
13C–NMR (100 MHz, CDCl3): d = 138.94, 132.86, 132.73, 128.61,
126.89, 125.53, 104.34, 104.29, 46.39, 30.88, 28.75, 26.26, 22.50,
21.98, 14.06, 13.86.
13C NMR (100 MHz, CDCl3): d = 139.53, 139.03, 135.88, 129.65,
128.64, 126.93, 125.53, 115.79, 105.74, 102.51, 46.35, 35.84,
34.14, 31.48, 26.70, 26.11.
HRMS (ESI): m/z [M + Na]+ calcd for C18H25NNa: 278.1885;
found: 278.1889.
HRMS (ESI): m/z [M + Na]+ calcd for C20H25NNa: 302.1885;
found: 302.1882.
1-Benzyl-2-tert-butyl-5-propyl-1H-pyrrole (4i)
Colorless oil; yield: 71%.
1-Benzyl-2-[3-(tert-butyldiphenylsiloxy)propyl]-5-cyclohexyl-
1H-pyrrole (4e)
Yellow oil; yield: 72%.
IR (neat): 3063, 3028, 2960, 2929, 2871, 1605, 1567, 1497, 1467,
1454, 1414, 1394, 1377 cm–1.
IR (neat): 3070, 3050, 2928, 2855, 1589, 1496, 1450, 1427, 1389,
1355 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.29–7.18 (m, 3 H), 6.79 (d,
J = 7.2 Hz, 2 H), 5.97 (d, J = 3.6 Hz, 1 H), 5.90 (d, J = 3.6 Hz, 1 H),
5.28 (s, 2 H), 2.25 (t, J = 7.6 Hz, 2 H), 1.64–1.56 (m, 2 H), 1.27 (s,
9 H), 0.89 (t, J = 7.2 Hz, 3 H).
1H NMR (400 MHz, CDCl3): d = 7.61–7.58 (m, 4 H), 7.40–7.31 (m,
6 H), 7.26–7.24 (m, 3 H), 6.82 (d, J = 7.6 Hz, 2 H), 5.91–5.87 (m, 2
H), 5.03 (s, 2 H), 3.65 (t, J = 7.6 Hz, 2 H), 2.47 (t, J = 7.6 Hz, 2 H),
2.38–2.33 (m, 1 H), 1.83–1.79 (m, 4 H), 1.72–1.64 (m, 2 H), 1.39–
1.19 (m, 6 H), 0.95 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 140.95, 139.65, 134.75, 128.46,
126.68, 125.41, 103.79, 103.67, 48.25, 31.07, 28.58, 21.40, 14.13.
HRMS (ESI): m/z [M + Na]+ calcd for C18H25NNa: 278.1885;
found: 278.1889.
13C NMR (100 MHz, CDCl3): d = 139.05, 138.96, 135.54, 133.97,
132.01, 129.48, 128.62, 127.56, 126.89, 125.52, 104.32, 102.35,
63.44, 46.32, 35.84, 34.20, 31.49, 29.69, 26.82, 26.73, 26.12, 22.94,
19.16.
1-Benzyl-2-phenyl-5-propyl-1H-pyrrole (4j)
Yellow oil; yield: 72%.
HRMS (ESI): m/z [M + Na]+ calcd for C36H45NOSiNa: 558.3168;
found: 558.3163.
IR (neat): 3062, 3028, 2958, 2928, 2870, 1602, 1509, 1495, 1452,
1411, 1384, 1355 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.34–7.21 (m, 8 H), 6.92 (d,
J = 7.6 Hz, 2 H), 6.27 (d, J = 3.6 Hz, 1 H), 6.09 (d, J = 3.6 Hz, 1 H),
5.16 (s, 2 H), 2.42 (t, J = 7.6 Hz, 2 H), 1.66 (sext, J = 7.6 Hz, 2 H),
0.96 (t, J = 7.6 Hz, 3 H).
3-(1-Benzyl-5-cyclohexyl-1H-pyrrol-2-yl)propan-1-ol (4f)
Colorless oil; yield: 70%.
IR (neat): 3365, 3094, 3063, 2927, 2852, 1605, 1496, 1450, 1427,
1354 cm–1.
13C–NMR (100 MHz, CDCl3): d = 139.20, 135.12, 134.40, 133.82,
128.74, 128.65, 128.28, 126.91, 126.61, 125.59, 108.04, 105.91,
47.46, 28.78, 21.70, 14.09.
1H NMR (400 MHz, CDCl3): d = 7.30–7.20 (m, 3 H), 6.84 (d,
J = 7.6 Hz, 2 H), 5.93 (d, J = 3.6 Hz, 1 H), 5.91 (d, J = 3.6 Hz, 1 H),
5.06 (s, 2 H), 3.62 (t, J = 6.4 Hz, 2 H), 2.48 (t, J = 7.6 Hz, 2 H),
2.39–2.32 (m, 1 H), 1.84–1.79 (m, 4 H), 1.77–1.65 (m, 3 H), 1.39–
1.17 (m, 6 H).
HRMS (ESI): m/z [M + H]+ calcd for C20H22N: 276.1752; found:
276.1747.
13C NMR (100 MHz, CDCl3): d = 139.25, 138.98, 131.39, 128.66,
126.99, 125.48, 104.61, 102.47, 62.50, 46.31, 35.81, 34.17, 31.38,
26.69, 26.09, 22.79.
1-Benzyl-2-(2-naphthyl)-5-propyl-1H-pyrrole (4k)
Yellow oil; yield: 48%.
IR (neat): 3057, 3017, 2960, 2928, 2872, 1630, 1603, 1497, 1454,
1414, 1379, 1357 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C20H27NONa: 320.1990;
found: 320.1996.
1H NMR (400 MHz, CDCl3): d = 7.79–7.64 (m, 5 H), 7.46–7.40 (m,
2 H), 7.32–7.23 (m, 3 H), 6.94 (d, J = 6.8 Hz, 2 H), 6.37 (d, J = 3.6
Hz, 1 H), 6.12 (d, J = 3.6 Hz, 1 H), 5.21 (s, 2 H), 2.45 (t, J = 7.2 Hz,
2 H), 1.66 (sext, J = 7.2 Hz, 2 H), 0.89 (t, J = 7.2 Hz, 3 H).
1-Benzyl-2-cyclohexyl-1H-pyrrole (4g)
Yellow oil; yield: 38%.
IR (neat): 3063, 3034, 2926, 2852, 1699, 1496, 1451, 1354 cm–1.
13C–NMR (100 MHz, CDCl3): d = 139.16, 135.53, 134.34, 133.31,
132.09, 131.14, 128.70, 127.90, 127.81, 127.52, 127.30, 126.97,
126.90, 126.06, 125.61, 125.58, 108.56, 106.10, 47.61, 31.58,
22.64, 14.12.
1H NMR (400 MHz, CDCl3): d = 7.33–7.23 (m, 3 H), 7.00 (d,
J = 7.2 Hz, 2 H), 6.56–6.54 (m, 1 H), 6.14 (t, J = 3.2 Hz, 1 H), 5.97–
5.95 (m, 1 H), 5.07 (s, 2 H), 2.45–2.39 (m, 1 H), 1.82–1.69 (m, 4 H),
1.44–1.21 (m, 6 H).
HRMS (ESI): m/z [M + Na]+ calcd for C24H23NNa: 348.1728;
found: 348.1724.
Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York

2466
M. Yoshida et al.
FEATURE ARTICLE
Tenbrink, K.; Weibel, J.-M.; Pale, P. J. Org. Chem. 2009,
74, 4360.
Acknowledgment
This study was supported in part by a Grant-in-Aid for the Encou-
ragement of Young Scientists (B) from the Japan Society for the
Promotion of Science (JSPS) and the Program for the Promotion of
Basic and Applied Research for Innovations in the Bio-oriented
Industry (BRAIN).
(5) (a) Yoshida, M.; Ueda, H.; Ihara, M. Tetrahedron Lett. 2005,
46, 6705. (b) Yoshida, M.; Morishita, Y.; Ihara, M.
Tetrahedron Lett. 2005, 46, 3669. (c) Yoshida, M.;
Hayashi, M.; Shishido, K. Org. Lett. 2007, 9, 1643.
(d) Yoshida, M.; Hayashi, M.; Matsuda, K.; Shishido, K.
Heterocycles 2009, 77, 193.
(6) (a) Zhang, L.; Sun, J.; Kozmin, S. A. Adv. Synth. Catal.
2006, 348, 2271. (b) Fürstner, A.; Davies, P. D. Angew.
Chem. Int. Ed. 2007, 46, 3410.
(7) One part of the results on our preliminary studies has been
published: Yoshida, M.; Al-Amin, M.; Matsuda, K.;
Shishido, K. Tetrahedron Lett. 2008, 49, 5021.
(8) Hashmi also reported the conversion of 1i using a gold
catalyst, in which the reaction was complete in 17 h
affording 2i in 80% yield; see ref 4h.
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Synthesis 2009, No. 14, 2454–2466 © Thieme Stuttgart · New York