Cu(I)-catalyzed reaction of diazo compounds with terminal alkynes: A direct synthesis of trisubstituted furans

Article abstract of DOI:10.1016/j.tet.2014.07.086

A method for the synthesis of tri-substituted furans has been developed based on Cu(I)-catalyzed reaction of terminal alkynes with β-keto α-diazoesters. This method for the synthesis of 2,3,5-trisubstituted furans is operationally simple and applicable to

Full text of DOI:10.1016/j.tet.2014.07.086

Tetrahedron 70 (2014) 6957e6962
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Tetrahedron
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Cu(I)-catalyzed reaction of diazo compounds with terminal alkynes:
a direct synthesis of trisubstituted furans
,
,
,b,
Mohammad Lokman Hossain a y, Fei Ye a y, Yan Zhang a, Jianbo Wang a
*
a Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and Molecular
Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China
b State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 June 2014
Received in revised form 17 July 2014
Accepted 24 July 2014
Available online 30 July 2014
A method for the synthesis of tri-substituted furans has been developed based on Cu(I)-catalyzed reaction
of terminal alkynes with -keto -diazoesters. This method for the synthesis of 2,3,5-trisubstituted furans
is operationally simple and applicable to wide substrate scope. Moreover, this synthesis employs cheap
Cu(MeCN)4PF6 as the catalyst and no additional ligand is needed. Similar reaction has also been applied to
ethyl (E)-2-diazo-3-(methoxyimino)butanoate for the synthesis of 2,3,5-trisubstituted N-methox-
ypyrroles with limited success.
b
a
Keywords:
Diazo compounds
Alkyne
Ó 2014 Elsevier Ltd. All rights reserved.
Furan synthesis
Copper catalyst
Pyrrole synthesis
1. Introduction
the other hand, employed Ru(II) complex as catalyst in furan
synthesis.8
Poly-substituted furans constitute an important class of five-
membered O-heterocycles and broadly found in many natural
products, pharmaceuticals and agrochemicals.1 Furans and their
derivatives are also very useful building blocks for organic syn-
thesis.2 For these reasons, over the past few decades, many chem-
ists have devoted their efforts to the development of novel and
efficient methods for the synthesis of mono-, di-, tri-, and poly-
substituted furans.3 Of various methods established over the
Through the literature survey it has been noticed that Cu(I)
complexes, as another popular catalysts in carbene transfer re-
actions,4,9 have much less explored for the furan synthesis. Recently,
Coleman and co-workers have reported a Cu(I)-catalyzed reaction
of a-diazoesters with internal alkynes to give tetra-substituted fu-
rans.10 We have recently studied the Cu(I)-catalyzed reaction of
terminal alkynes with donoreacceptor diazoacetates. The reaction
gives tri-substituted allenes as the major products, instead of furans
(Scheme 1).11 Similar results have also been observed by Fox and co-
years, the transition metal-catalyzed cycloaddition of
a-diazo-
carbonyl compounds with alkynes is considered as one of the most
versatile and direct approaches for the construction of poly-
substituted furans.4 Davies and Romines in 1988 reported the
Rh2(OAc)4-catalyzed reaction of b-keto a-diazoesters, which gives
2,3,5-trisubstituted furans.5 Similar Rh(II)-catalyzed reactions have
later reported by several other groups.6
In addition to the traditional Rh(II) catalysts, other transition
metal catalysts have also been explored for this type of trans-
formations. Very recently, Zhang and co-workers reported the use
of Co(II)eporphyrin complexes as catalysts for furan synthesis from
alkynes and a
-diazocarbonyl compounds.7 Lee and co-workers, on
* Corresponding author. Tel.: þ86 10 6275 7248; fax: þ86 10 6275 1708; e-mail
address: wangjb@pku.edu.cn (J. Wang).
y
Scheme 1. Cu(I)-catalyzed reaction of a-diazoesters and terminal alkynes.
MLH and FY contributed equally to this project.
http://dx.doi.org/10.1016/j.tet.2014.07.086
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

6958
M.L. Hossain et al. / Tetrahedron 70 (2014) 6957e6962
workers.12 On the other hand, Fu and Saurez in 2004 reported the
CuI-catalyzed cross-coupling of terminal alkynes with diazoester,
yielding 3-alkynoate derivatives and in some cases 2,3-allenoates as
minor products.13 These results indicate that the reaction pathway
for Cu(I)-catalyzed reaction of alkyne with diazo compounds is
largely affected by the catalyst system and the structure of the diazo
substrates.
reaction did not occur (entries 12 and 13). Phosphine ligand and
base additive were found not effective (entries 14 and 15). Finally,
control experiment indicated the reaction did not occur in the ab-
sence of Cu(I) catalyst (entry 16).
With the best reaction conditions in hand, we investigated the
scope of the reaction by screening a variety of terminal alkynes
(2aeo) with ethyl 2-diazo-3-oxobutanoate (1a). As shown in
Scheme 2, the reaction affords the corresponding furans (3aeo) in
moderate to good yields. Notably, the reaction was not significantly
affected by the substituents on the aromatic ring of terminal al-
kynes. Both electron-rich (2b, 2c, 2m) and electron-deficient aryl
substituted alkynes (2j, 2k, 2o) were compatible, and alkoxy, ace-
toxy, fluoro, chloro, bromo groups were tolerated in the reaction. In
addition, this approach also worked well with aliphatic alkynes (2d,
2f, 2g, 3i), affording the corresponding furans in higher yields. The
Although various methodologies have been reported for furan
synthesis based on transition metal-catalyzed reaction of a-diazo-
carbonyl compounds and alkynes, these methods still suffer from
one or more limitations such as lower yields, poor regioselectivity,
low efficiency, and complicated catalytic system, etc. In particular,
expensive metal catalysts such as Rh2(OAc)4 are used in most cases.
Therefore, it is highly desirable to further develop efficient and
simple strategy for substituted furans synthesis with cheap cata-
lysts. Herein we wish to report a Cu(MeCN)4PF6-catalyzed synthesis
reaction also worked well with 2-thiophenyl- and
b-naphthyl-
of 2,3,5-trisubstituted furan from
b-keto
a
-diazoesters with ter-
substituted alkynes (2e and 3n) (Scheme 2).
minal alkynes. The reaction proceeds with moderate to good yields
with excellent regioselectivity. Moreover, the reaction has also been
applied to ethyl (E)-2-diazo-3-(methoxyimino)butanoate for the
synthesis of 2,3,5-trisubstituted N-methoxypyrroles.
2. Results and discussion
Initially, we chose b-keto a-diazoester 1a and phenylacetylene
2a as model substrates and began our studies with copper catalysts
(Table 1). To our delight, Cu(MeCN)4PF6 led to the expected furan
product 3a with 40% yield at 80 ꢀC in toluene (entry 1). Raising the
reaction temperature to 90 ꢀC slightly improved the yield to 60%
(entry 2). Further investigation into solvent systems revealed that
DCE and dioxane resulted in diminished yield whereas reaction
failed to give the desired product in polar solvent MeCN (entries
3e5). With the preliminary results, we next evaluated a series of Cu
catalysts and among them, Cu(OTf)2, Cu(O2CCF3)2, CuI, Cu(OEt)2
showed less effective, giving 1,3-diynes as the major product (en-
tries 6e10). Then, the ratio of the substrates was examined and it
was found that the 1.2:1 ratio of 1a and 2a led to improved yield
(entry 11). Under this condition, further raising the reaction tem-
perature to 110 ꢀC resulted in diminished yield while at 40 ꢀC the
Table 1
Optimization of the reaction conditionsa
Entry
Cat. (20 mol %)
Solvent
1a/2a
T (ꢀC)
3a,a
%
1
2
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(OTf)2
Cu(O2CCF3)2
CuI
Cu(OAc)2
Toluene
Toluene
DCE
Dioxane
MeCN
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
80
90
90
90
90
90
90
90
90
90
90
110
40
90
90
40
60
45
20
0
37
46
Trace
0
Trace
77
40
0
20
3
4b
5
6
7
8
9
10
11
12
13
14
15
Cu(OEt)2
1:1
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6/(2-furyl)3P
Cu(MeCN)4PF6/K2CO3
(100 mol %)
None
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
Trace
aReaction conditions: a mixture of Cu catalyst (20 mol%), diazoester 1a (0.36
mmol), alkynes 2a-o (0.3 mmol) in 2 mL toluene was stirred at 90 oC for 2 h.
bIsolated yield by alumina column chromatographic purification.
16
Toluene
1.2:1
90
0
a
Reaction conditions: A mixture of Cu catalyst (20 mol %), 1a (0.36 mmol), 2a
(0.3 mmol) in 2 mL toluene was stirred at the indicated temperature for 2 h.
Scheme 2. Substrate scope of terminal alkynes.a
b
Isolated yield by alumina column chromatographic purification method.

M.L. Hossain et al. / Tetrahedron 70 (2014) 6957e6962
6959
Subsequently, the scope of
(Scheme 3). The reaction was examined for several
esters 4aef with 4-phenylbutylene 2f under the optimized reaction
conditions. In all the cases the reaction also worked smoothly, giving
the corresponding poly-substituted furans in moderate to good
yields with good functional group tolerance.
b
-keto
a
-diazoesters was studied
However, the yields are low in all the cases, presumably attributed
to the instability of ethyl (E)-2-diazo-3-(methoxyimino)butanoate
under the reaction conditions.
b
-keto -diazo-
a
We proposed plausible mechanism to account for the Cu-
catalyzed reaction of diazoester and terminal alkyne as shown in
Scheme 5. In path I, copper acetylide A is firstly formed from
phenylacetylene and Cu(I) catalyst, which reacts with diazoester to
generate copper-carbene species B. The alkynyl migratory insertion
of carbene species B to the carbenic carbon gives the intermediate
C, which then produces 2,3-allenoate E by the direct protonation.
The allene E may undergo cyclization to afford the furan product
under the Cu(I)-catalyzed reaction conditions. Alternatively, from
intermediate C intramolecular nucleophilic attack of the carbonyl
group to the triple bond produces the intermediate D, which later
undergoes a subsequent proton transfer to afford furan 3a with
simultaneous regeneration of the Cu(I) catalyst.
a
Reaction conditions: a mixture of Cu catalyst (20 mol%), diazoesters 4a-f
(0.36 mmol), alkyne 2f (0.3 mmol) in 2 mL toluene was stirred at 90 oC for 2
h. bIsolated yield by alumina column chromatographic purification.
Scheme 3. Substrate scope of b-keto a
-diazoesters.a
Encouraged by the above success, we then turned our attention
to apply this methodology to synthesize N-methoxypyrroles using
a
-diazoesters bearing C]N bond in the
b
position. Thus, we chose
-diazo-
ethyl (E)-2-diazo-3-(methoxyimino)butanoate 6 as the
a
ester partner and carried out the reaction with terminal alkynes
under the optimized reaction conditions. We were pleased to find
that under the same reaction conditions, a-diazooximes undergo
cyclization reaction with terminal alkynes (2a, b, e, j), giving
the corresponding N-methoxypyrroles (7a, b, e, j) (Scheme 4).
Scheme 5. Proposed reaction mechanism.
Alternatively, the reaction may also follow path II. In this case,
Cu-catalyzed cyclopropenation occurs to produce cyclopropene G.
Under the Cu(I) catalysis, the cyclopropene G undergoes ring-
opening rearrangement to generate Cu carbene intermediate J or
L.19 From J, the furan 3a is generated through cyclization of the Cu
carbene with the carbonyl oxygen, while from L, 2,3,4-trisubstituted
furan 3a0 is generated.15 In this study furan 3a0 was not observed,
which indicates path II may be less likely compared to path I.
However, rigorous investigations are needed to unambiguously
establish the reaction mechanism.
a
Reaction conditions: a mixture of Cu catalyst (20 mol%), α-diazooxime 6
(0.33 mmol), alkynes 2a, 2b, 2e, 2j (0.3 mmol) in 2 mL toluene was stirred at
90 oC for 2 h. bIsolated yield by silica gel column chromatographic purification.
Scheme 4. Synthesis of N-methoxypyrroles from a
-diazooxime and terminal alkynes.a

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M.L. Hossain et al. / Tetrahedron 70 (2014) 6957e6962
3. Summary
purified by alumina column chromatography (eluted with 100:1,
petroleum ether/EtOAc) to afford pure 3d as colorless oil (37 mg,
59%); 1H NMR (400 MHz, CDCl3)
In conclusion, we have explored the copper-catalyzed reaction of
d
6.22 (s, 1H), 4.26 (q, J¼7.2 Hz, 2H),
b-keto
a-diazoesterwithterminalalkynes, resultingintheformation
2.55 (t, J¼7.2 Hz, 2H) one peak was missed because of overlap, 2.53
of tri-substituted furans with good efficiency and selectivity. This
furan synthesis method use readily available starting materials and
in particular use cheap Cu(I) complex as the catalyst. The reaction is
highly efficient and shows wide substrate scope. It is thus expected
that this method may find applications in organic synthesis.
(br, 3H), 1.63e1.57 (m, 2H), 1.41e1.32 (m, 5H), 0.92 (t, J¼7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3)
d 164.4, 157.4, 154.3, 113.7, 105.3, 59.9,
29.9, 27.3, 22.1, 14.4, 13.8, 13.7.
4.2.5. Ethyl 2-methyl-5-(thiophen-2-yl) furan-3-carboxylate
(3e).17 Following the typical procedure described above, the crude
residue was purified by alumina column chromatography (eluted
with 60:1, petroleum ether/EtOAc) to afford pure 3e as white powder
4. Experimental section
4.1. General
(57 mg, 80%); 1H NMR (400 MHz, CDCl3)
d 7.46e7.45 (m, 1H),
7.35e7.33 (m, 1H), 7.29e7.26 (m, 1H), 6.70 (s, 1H), 4.31 (q, J¼7.2 Hz,
All reactions were performed under nitrogen atmosphere in
a 10 mL microwave tube. All solvents were dried before use. For
chromatographic purification, 200e300 mesh silica gel (Qingdao,
China) was employed. 1H NMR and 13C NMR spectra were recorded
on Varian 300 MHz and Brucker ARX 400 MHz spectrometer in
CDCl3 solution and the chemical shifts were reported in parts per
2H), 2.63 (s, 3H), 1.37 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
164.1, 158.0, 148.8, 131.7, 126.4, 124.4, 119.1, 115.0, 105.1, 60.2, 14.4,
13.8; IR (film, cmꢁ1) 2927, 1716, 1230, 1097, 1049, 856, 774, 672, 658;
EIMS (m/z, relative intensity): 236 (Mþ, 74), 207 (100), 191 (17), 163
(10), 121 (10), 111 (23); HRMS (ESI) calcd for C12H13O3S [(MþH)þ]:
237.0580, found: 237.0581.
million (d) relative to internal standard TMS (0 ppm). b-Keto a-
diazoesters were prepared according to the literature procedure.14
Unless otherwise noted, materials obtained from commercial sup-
pliers were used without further purifications.
4.2.6. Ethyl 2-methyl-5-phenethylfuran-3-carboxylate (3f). Following
the typical procedure described above, the crude residue was puri-
fied by alumina column chromatography (eluted with 60:1, petro-
leum ether/EtOAc) to afford pure 3f as a light yellow oil (64 mg, 83%);
4.2. Typical procedure for the copper-catalyzed cross-cou-
1H NMR (400 MHz, CDCl3)
d 7.30e7.24 (m, 2H), 7.22e7.17 (m, 3H),
pling of
b
-keto diazoester and terminal alkynes
6.24 (s, 1H), 4.26 (q, J¼7.2 Hz, 2H), 2.96e2.91 (m, 2H), 2.88e2.84 (m,
2H), 2.54 (s, 3H), 1.33 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
Under a nitrogen atmosphere, ethynylbenzene 2a (30.6 mg,
0.3 mmol) was added in a suspension of Cu(MeCN)4PF6 (22.3 mg,
0.05 mmol) and b-keto diazoester 1a (56.16 mg, 0.36 mmol) in tol-
d 164.3, 157.6, 153.1, 140.9, 128.4, 128.3, 126.1, 113.8, 105.9, 59.9, 34.1,
29.6, 14.3, 13.7; IR (film, cmꢁ1) 2924,1714,1230, 1209, 1080, 778, 699,
668; EIMS (m/z, relative intensity): 258 (Mþ, 19), 213 (11), 167 (100),
139 (18), 121 (28), 91.1 (14), 65.1 (6); HRMS (ESI) calcd for C16H19O3
[(MþH)þ]: 259.1329, found: 259.1329.
uene (2 mL). The solutionwas stirredat 90 ꢀC for 2 h and the progress
of the reaction was monitored by TLC. After completion of the re-
action, it was cooled down to room temperature and the reaction
solutionwas filtered through a short path of silica gel by using EtOAc
as eluent. The solvent was removed in vacuum to leave a crude
mixture, which was purified by alumina column chromatography
(eluted with 60:1, petroleum ether/EtOAc) to afford pure product 3a.
4.2.7. Ethyl 2-methyl-5-pentylfuran-3-carboxylate (3g).18 Following
the typical procedure described above, the crude residue was puri-
fied by alumina column chromatography (eluted with 100:1, petro-
leum ether/EtOAc) to afford pure 3g as colorless oil (53 mg, 79%); 1H
NMR (400 MHz, CDCl3)
2.56e2.54 (m, 2H), 2.53 (s, 3H), 1.35e1.32 (m, 9H), 0.90 (t, J¼7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3)
164.4,157.4,154.3,113.8,105.3,59.9,
d
6.22 (s, 1H), 4.26 (q, J¼7.1 Hz, 2H),
4.2.1. Ethyl2-methyl-5-phenylfuran-3-carboxylate(3a).15 Colorless oil
(53 mg, 77%); 1H NMR (400 MHz, CDCl3)
d
7.64 (d, J¼7.2 Hz, 2H), 7.38
d
(t, J¼7.6 Hz, 2H), 7.29e7.26 (m,1H), 6.88 (s,1H), 4.31 (q, J¼7.1 Hz, 2H),
31.2, 27.6, 27.4, 22.4, 14.4, 13.9, 13.7.
2.65 (s, 3H), 1.37 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 164.0,
158.6, 151.7, 130.0, 128.7, 127.6, 123.6, 115.4, 105.5, 60.2, 14.4, 13.9.
4.2.8. Ethyl 5-cyclohexenyl-2-methylfuran-3-carboxylate (3h).7 Following
the typical procedure described above, the crude residue was purified by
alumina column chromatography (eluted with 100:1, petroleum ether/
EtOAc) to afford pure 3h as yellow oil (57 mg, 81%); 1H NMR (400 MHz,
4.2.2. Ethyl 2-methyl-5-m-tolylfuran-3-carboxylate (3b).16 Following
the typical procedure described above, the crude residue was puri-
fied by alumina column chromatography (eluted with 60:1, petro-
leum ether/EtOAc) to afford pure 3b as colorless oil (49 mg, 67%); 1H
CDCl3)
d
6.36 (s, 1H), 6.28e6.26 (m, 1H), 4.28 (q, J¼7.1 Hz, 2H), 2.56 (s,
3H), 2.24e2.23 (m, 2H), 2.20e2.18 (m, 2H), 1.73e1.71 (m, 2H), 1.65e1.62
NMR (400 MHz, CDCl3)
d
7.46e7.43 (m, 2H), 7.27 (t, J¼7.6 Hz, 1H),
(m, 2H), 1.34 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 164.3, 157.7,
7.08 (d, J¼7.6 Hz, 1H), 6.89 (s, 1H), 4.31 (q, J¼7.1 Hz, 2H), 2.65 (s, 3H),
153.2, 126.5, 122.7, 114.5, 103.9, 60.0, 25.0, 24.6, 22.2, 22.1, 14.3, 13.8.
2.38 (s, 3H), 1.37 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 164.1,
158.5, 151.8, 138.3, 130.0, 128.6, 128.4, 124.2, 120.8, 115.2, 105.3, 60.2,
21.4, 14.4, 13.9.
4.2.9. Ethyl 5-tert-butyl-2-methylfuran-3-carboxylate (3i).15,16 Following
the typical procedure described above, the crude residue was purified by
alumina column chromatography (eluted with 60:1, petroleum ether/
EtOAc) to afford pure 3i as colorless oil (47 mg, 75%); 1H NMR (400 MHz,
4.2.3. Ethyl 5-(4-tert-butylphenyl)-2-methylfuran-3-carboxylate
(3c).17 Following the typical procedure above, the crude residue
was purified by alumina column chromatography (eluted with 60:1,
petroleum ether/EtOAc) to afford pure 3c as colorless oil (48 mg,
CDCl3)
d
6.19 (s, 1H), 4.27 (q, J¼7.1 Hz, 2H), 2.54 (s, 3H), 1.34 (t, J¼7.2 Hz,
3H), 1.25 (s, 9H); 13C NMR (100 MHz, CDCl3)
102.6, 59.9, 32.3, 28.8, 14.4, 13.7.
d 164.5, 162.1, 157.4, 113.5,
56%); 1H NMR (400 MHz, CDCl3)
d
7.57 (d, J¼8.8 Hz, 2H), 7.40 (d,
J¼8.4 Hz, 2H), 6.83 (s, 1H), 4.31 (q, J¼7.1 Hz, 2H), 2.64 (s, 3H), 1.37 (t,
4.2.10. Ethyl 5-(4-fluorophenyl)-2-methylfuran-3-carboxylate
(3j).17 Following the typical procedure described above, the crude
residue was purified by alumina column chromatography (eluted
with 60:1, petroleum ether/EtOAc) to afford pure 3j as colorless oil
J¼7.2 Hz, 3H), 1.33 (s, 9H); 13C NMR (100 MHz, CDCl3)
d 164.1, 158.3,
151.9, 150.7, 127.4, 125.6, 123.4, 115.3, 104.8, 60.1, 34.6, 31.2, 14.4, 13.9.
4.2.4. Ethyl 5-butyl-2-methylfuran-3-carboxylate (3d).15 Following
(51 mg, 68%); 1H NMR (400 MHz, CDCl3)
d
7.61e7.58 (m, 2H), 7.07 (t,
the typical procedure described above, the crude residue was
J¼8.8 Hz, 2H), 6.81 (s, 1H), 4.31 (q, J¼7.2 Hz, 2H), 2.64 (s, 3H), 1.37 (t,

M.L. Hossain et al. / Tetrahedron 70 (2014) 6957e6962
6961
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
163.9, 162.2 (d,
34.0, 29.6, 13.7; IR (film, cmꢁ1) 2926,1715, 1228,1205,1076, 777, 699;
EIMS (m/z, relative intensity): 270 (Mþ, 25), 213 (19), 179 (100), 161
(12), 133 (9), 121 (12), 105 (6), 91 (27), 65 (9); HRMS (ESI) calcd for
J¼246.0 Hz),158.5,150.8,126.4 (d, J¼3.0 Hz),125.4 (d, J¼8.0 Hz),115.8
(d, J¼21.0 Hz), 115.4, 105.1, 60.2, 14.3, 13.8.
C
17H19O3 [(MþH)þ]: 271.1329, found: 271.1330.
4.2.11. Ethyl 5-(4-chlorophenyl)-2-methylfuran-3-carboxylate
(3k).17 Following the typical procedure described above, the crude
residue was purified by alumina column chromatography (eluted
with 60:1, petroleum ether/EtOAc) to afford pure 3k as colorless oil
4.2.17. Ethyl 2-ethyl-5-phenethylfuran-3-carboxylate (5b). Following
the typical procedure described above, the crude residue was puri-
fied by alumina column chromatography (eluted with 60:1, petro-
leum ether/EtOAc) to afford pure 5b as colorless oil (61 mg, 75%); 1H
(44 mg, 55%); 1H NMR (400 MHz, CDCl3)
d
7.54 (d, J¼8.4 Hz, 2H), 7.33
(d, J¼8.4 Hz, 2H), 6.86 (s, 1H), 4.31 (q, J¼6.9 Hz, 2H), 2.63 (s, 3H), 1.37
NMR (400 MHz, CDCl3) d 7.29e7.26 (m, 2H), 7.21e7.16 (m, 3H), 6.24
(t, J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
163.8, 158.8, 150.6,
(s, 1H), 4.25 (q, J¼7.2 Hz, 2H), 2.97 (q, J¼7.5 Hz, 2H), 2.94e2.92 (m,
133.2, 128.9, 128.5, 124.8, 116.5, 105.9, 60.2, 14.3, 13.8.
2H), 2.89e2.85 (m, 2H), 1.32 (t, J¼7.2 Hz, 3H), 1.23 (t, J¼7.6 Hz, 3H);
13C NMR (100 MHz, CDCl3)
d 164.2, 162.6, 153.1, 140.9, 128.4, 128.3,
4.2.12. Ethyl 5-(4-bromophenyl)-2-methylfuran-3-carboxylate
(3l).17 Following the typical procedure described above, the crude
residue was purified by alumina column chromatography (eluted
126.1, 112.9, 105.9, 59.8, 34.1, 29.6, 21.1, 14.3, 12.4; IR (film, cmꢁ1
)
2978, 2931, 1713, 1580, 1209, 1087, 1042, 780, 699; EIMS (m/z, relative
intensity): 272 (Mþ,19), 227 (12),181 (100),153 (13),135 (29),107 (5),
91 (19), 65 (7); HRMS (ESI) calcd for C17H21O3 [(MþH)þ]: 273.1485,
found: 273.1483.
with 100:1, petroleum ether/EtOAc) to afford pure 3l as colorless oil
1
(60 mg, 65%); H NMR (400 MHz, CDCl3)
d 7.48 (s, 4H), 6.87 (s, 1H),
4.31 (q, J¼7.2 Hz, 2H), 2.63 (s, 3H), 1.36 (t, J¼7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3)
d
163.8, 158.8, 150.5, 131.8, 128.9,125.0,121.3,115.5,
4.2.18. tert-Butyl 2-methyl-5-phenethylfuran-3-carboxylate
(5c). Following the typical procedure described above, the crude
residue was purified by alumina column chromatography (eluted
with 60:1, petroleum ether/EtOAc) to afford pure 5c as light yellow
106.0, 60.2, 14.3, 13.8.
4.2.13. Ethyl 5-(4-methoxyphenyl)-2-methylfuran-3-carboxylate
(3m).17 Following the typical procedure described above, the crude
residue was purified by alumina column chromatography (eluted
with 60:1, petroleum ether/EtOAc) to afford pure 3m as light yellow
oil (57 mg, 66%); 1H NMR (400 MHz, CDCl3)
d
7.30e7.26 (m, 2H),
7.22e7.17 (m, 3H), 6.20 (s,1H), 2.94e2.90 (m, 2H), 2.86e2.82 (m, 2H),
2.51 (s, 3H), 1.53 (m, 9H); 13C NMR (100 MHz, CDCl3)
163.6, 156.9,
d
oil (57 mg, 73%); 1H NMR (400 MHz, CDCl3)
d
7.55 (d, J¼8.8 Hz, 2H),
152.8, 140.9, 128.4, 128.2, 126.1, 115.3, 106.2, 80.2, 34.2, 29.6, 28.3,
13.7; IR (film, cmꢁ1) 2927,1708,1367,1230,1170,1081, 779, 699; EIMS
(m/z, relative intensity): 286 (Mþ, 15), 230 (6), 213 (15), 195 (16), 139
(100), 121 (10), 91 (12), 79 (5); HRMS (ESI) calcd for C18H22NaO3
[(MþNa)þ]: 309.1461, found: 309.1468.
6.95 (d, J¼8.8 Hz, 2H), 6.74 (s, 1H), 4.30 (q, J¼7.1 Hz, 2H), 3.81 (s, 3H),
2.62 (s, 3H), 1.36 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 164.1,
159.1, 157.9, 151.7, 125.0, 123.0, 115.2, 114.1, 103.7, 60.0, 55.2, 14.3, 13.8.
4.2.14. Ethyl 5-(2-methoxynaphthalen-6-yl)-2-methylfuran-3-
carboxylate (3n). Following the typical procedure described above,
the crude residue was purified by alumina column chromatography
(eluted with 60:1, petroleum ether/EtOAc) to afford pure 3n as light
4.2.19. Ethyl 5-phenethyl-2-phenylfuran-3-carboxylate
(5d). Following the typical procedure described above, the crude
residue was purified by alumina column chromatography (eluted
with 60:1, petroleum ether/EtOAc) to afford pure 5d as light yellow
yellow oil (52 mg, 56%); 1H NMR (400 MHz, CDCl3)
d 7.67e7.75 (m,
4H), 7.16e7.14 (m, 2H), 7.10 (d, J¼2.0 Hz, 1H), 6.93 (s, 1H), 4.32 (q,
oil (52 mg, 54%); 1H NMR (400 MHz, CDCl3)
d
7.94 (d, J¼6.8 Hz, 2H),
J¼7.1 Hz, 2H), 3.91 (s, 3H), 2.68 (s, 3H), 1.38 (t, J¼7.0 Hz, 3H); 13C NMR
7.44e7.36 (m, 3H), 7.32e7.28 (m, 2H), 7.24e7.20 (m, 3H), 6.45 (s, 1H),
4.27 (q, J¼7.2 Hz, 2H), 3.04e2.95 (m, 4H), 1.31 (t, J¼7.2 Hz, 3H); 13C
(100 MHz, CDCl3)
d 164.1, 158.5, 151.9, 133.9, 130.9, 129.6, 128.8, 127.2,
125.3, 1225, 121.0, 119.3, 115.4, 105.8, 105.2, 60.2, 55.3, 14.4, 13.9; IR
(film, cmꢁ1) 2960, 2925,1729,1260,1074,1018, 799; EIMS (m/z, relative
intensity): 310 (Mþ, 100), 281 (63), 267 (8), 239 (10), 185 (7), 132 (5);
HRMS (ESI) calcd for C19H19O4 [(MþH)þ]: 311.1278, found: 311.1286.
NMR (100 MHz, CDCl3) d 163.7, 156.0, 154.2, 140.7, 130.0, 129.0, 128.4,
128.3, 128.2, 128.0, 126.2, 114.3, 108.5, 60.4, 34.1, 29.6, 14.2; IR (film,
cmꢁ1) 2960, 2925, 1718, 1210, 1092, 1073, 1038, 1024, 797, 763, 695;
EIMS (m/z, relative intensity): 320 (Mþ, 24), 275 (7), 229 (100), 201
(28), 128 (8), 105 (17), 91 (9), 77 (12); HRMS (ESI) calcd for C21H21O3
[(MþH)þ]: 321.1485, found: 321.1494.
4.2.15. Ethyl 5-(4-(methoxycarbonyl) phenyl)-2-methylfuran-3-
carboxylate (3o). Following the typical procedure described above,
the crude residue was purified by alumina column chromatography
(eluted with 60:1, petroleum ether/EtOAc) to afford pure 3o as light
4.2.20. Ethyl 2-benzyl-5-phenethylfuran-3-carboxylate
(5e). Following the typical procedure described above, the crude
residue was purified by alumina column chromatography (eluted
with 60:1, petroleum ether/EtOAc) to afford pure 5e as light yellow
yellow oil (45 mg, 52%); 1H NMR (400 MHz, CDCl3)
d 8.05 (d,
J¼8.4 Hz, 2H), 7.69 (d, J¼8.4 Hz, 2H), 7.02 (s, 1H), 4.32 (q, J¼7.2 Hz,
2H), 3.92 (s, 3H), 2.66 (s, 3H), 1.38 (t, J¼7.2 Hz, 3H); 13C NMR
oil (62 mg, 62%); 1H NMR (400 MHz, CDCl3)
d 7.29e7.18 (m, 8H),
(100 MHz, CDCl3)
d
166.6, 163.7, 159.6, 150.6, 132.4, 130.1, 129.5, 123.2,
7.12e7.11 (m, 2H), 6.26 (s,1H), 4.31 (br, 2H), 4.27 (q, J¼7.2 Hz, 2H) one
115.8, 107.8, 60.3, 52.3, 52.1, 14.3, 13.9; IR (film, cmꢁ1) 2957, 2925,
1720,1277, 1248, 1232,1096, 1044, 1016, 800, 770; EIMS (m/z, relative
intensity): 288 (Mþ, 71), 259 (100), 243 (14), 229 (14), 163 (9); HRMS
(ESI) calcd for C16H17O5 [(MþH)þ]: 289.1071, found: 289.1075.
peak was missed because of overlap, 2.93e2.89 (m, 2H), 2.88e2.84
(m, 2H), 1.32 (t, J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 164.0,
158.8, 154.0, 140.7, 137.8, 128.7, 128.5, 128.4, 128.3, 126.4, 126.1, 114.2,
105.2, 60.1, 34.0, 33.5, 29.6, 14.3; IR (film, cmꢁ1) 2960, 2924, 1713,
1260, 1078, 1063, 1018, 799, 698; EIMS (m/z, relative intensity): 334
(Mþ, 40), 305 (19), 289 (9), 243 (100), 214 (15), 197 (56), 167 (8), 152
(6), 141 (18), 115 (13), 105 (20), 91 (64), 65 (13); HRMS (ESI) calcd for
4.2.16. Allyl 2-methyl-5-phenethylfuran-3-carboxylate(5a). Following
the typical procedure described above, the crude residue was puri-
fied by alumina column chromatography (eluted with 60:1, petro-
leum ether/EtOAc) to afford pure 5a as colorless oil (70 mg, 86%); 1H
C
22H23O3 [(MþH)þ]: 335.1642, found: 335.1644.
NMR (400 MHz, CDCl3)
d
7.26e7.30 (m, 2H), 7.22e7.17 (m, 3H), 6.25
4.2.21. Cinnamyl 2-methyl-5-phenethylfuran-3-carboxylate
(5f). Following the typical procedure described above, the crude
residue was purified by alumina column chromatography (eluted
with 60:1, petroleum ether/EtOAc) to afford pure 5f as light yellow oil
(s, 1H), 6.03e5.94 (m, 1H), 5.35 (dd, J¼19.2, 1.2 Hz, 1H), 5.25 (dd,
J¼10.2, 1.6 Hz, 1H), 4.71 (dt, J¼5.6, 1.4 Hz, 2H), 2.95e2.91 (m, 2H),
2.88e2.84 (m, 2H), 2.55 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 163.8,
158.0, 153.2, 140.8, 132.5, 128.4, 128.2, 126.1, 117.8, 113.5, 105.9, 64.6,
(78 mg, 75%); 1H NMR (400 MHz, CDCl3)
d 7.40 (m, 2H), 7.34e7.30 (m,

6962
M.L. Hossain et al. / Tetrahedron 70 (2014) 6957e6962
3H), 7.28e7.25 (m, 2H), 7.20e7.17 (m, 3H), 6.68 (d, J¼16.0 Hz, 1H),
6.35 (dt, J¼15.6, 6.4 Hz, 1H), 6.27 (s, 1H), 4.87 (dd, J¼6.4, 0.8 Hz, 2H),
2.96e2.93 (m, 2H), 2.88e2.84 (m, 2H), 2.56 (s, 3H); 13C NMR
with 20:1, petroleum ether/EtOAc) to afford pure 7j as light yellow oil
(21 mg, 25%); 1H NMR (400 MHz, CDCl3)
7.63 (dd, J¼5.4, 8.6 Hz, 2H),
d
7.09 (t, J¼8.7 Hz, 2H), 6.59 (s, 1H), 4.29 (q, J¼7.1 Hz, 2H), 3.70 (s, 3H),
(100 MHz, CDCl3)
d
164.0, 158.8, 154.0, 140.7, 137.8, 128.7, 128.5, 128.4,
2.59 (s, 3H), 1.36 (t, J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 165.0,
128.3, 126.4, 126.1, 114.2, 108.2, 60.1, 34.0, 33.5, 29.6, 14.3; IR (film,
cmꢁ1) 2961, 2925, 1713, 1260, 1073, 1019, 798, 777, 694; EIMS (m/z,
relative intensity): 346 (Mþ, 11), 255 (28), 213 (63), 139 (20), 117
(100), 91 (27), 65 (5); HRMS (ESI) calcd for C23H22NaO3 [(MþNa)þ]:
369.1461, found: 369.1494.
132.3, 128.3, 128.2, 126.2, 115.7, 115.5, 107.9, 105.1, 65.6, 59.6, 14.5, 9.9;
IR (film, cmꢁ1); 2928, 1702, 1572, 1489, 1242, 1157, 1065, 810, 771;
EIMS (m/z, relative intensity): 277 (Mþ, 95), 262 (5), 248 (20), 232
(20), 218 (100), 200 (55), 188 (5), 172 (10), 122 (25), 52 (10); HRMS
(ESI) calcd for C15H17FNO3 [(MþH)þ]: 278.1187, found: 278.1190.
4.3. Typical procedure for the Cu(MeCN)4PF6-catalyzed cross-
coupling of (E)-2-diazo-3-(methoxyimino)butanoate 6 and
terminal alkynes
Acknowledgements
This project was supported by National Basic Research Program
of China (973 Program, No. 2012CB821600) and National Natural
Science Foundation of China (Grant 21332002, 21272010 and
21172005).
Under a nitrogen atmosphere, ethynylbenzene 2a (30.6 mg,
0.3 mmol) was added to a suspension of Cu(MeCN)4PF6 (22.3 mg,
0.05 mmol) and a-diazooximes 6 (61 mg, 0.33 mmol) in toluene
(2 mL). The solution was stirred at 90 ꢀC for 2 h and the progress of
the reaction was monitored by TLC. After completion of the re-
action, it was cooled down to room temperature and the reaction
solution was filtered through a short path of silica gel by using
EtOAc as eluent. The solvent was removed in vacuum to leave
a crude mixture, which was purified by silica column chromatog-
raphy (eluted with 20:1, petroleum ether/EtOAc) to afford pure
product 7a.
Supplementary data
Copies of 1H and/or 13C spectra for isolated products. Supple-
mentary data associated with this article can be found in the online
version, at http://dx.doi.org/10.1016/j.tet.2014.07.086.
References and notes
1. For reviews, see: (a) Hou, X. L.; Yang, Z.; Wong, H. N. C. In Progress in Hetero-
cyclic Chemistry; Gribble, G. W., Gilchrist, T. L., Eds.; Pergamon: Oxford, UK,
2003; Vol. 15, p 167; (b) Dean, F. M. In Advances in Heterocyclic Chemistry;
Katritzky, A. R., Ed.; Academic: New York, NY, 1983; Vol. 31, p 237; (c) Sargent,
M. V.; Dean, F. M. In Comprehensive Heterocyclic Chemistry; Bird, C. W.,
Cheeseman, G. W. H., Eds.; Pergamon: Oxford, UK, 1984; Vol. 3, p 599.
2. (a) Lipshutz, B. H. Chem. Rev. 1986, 86, 795; (b) Dean, F. M. In Advances in
Heterocyclic Chemistry; Katritzky, A. R., Ed.; Academic: New York, NY, 1982; Vol.
30, p 167; (c) Dean, F. M.; Sargent, M. V. In Comprehensive Heterocyclic Chem-
istry; Bird, C. W., Cheeseman, G. W. H., Eds.; Pergamon: New York, NY, 1984;
Vol. 4; Part 3, p 531.
3. For reviews on the synthesis of furan derivatives: (a) Hou, X. L.; Cheung, H. Y.;
Hon, T. Y.; Kwan, P. L.; Lo, T. H.; Tong, S. Y. T.; Wong, H. N. C. Tetrahedron 1998,
54, 1955; (b) Kirsch, S. F. Org. Biomol. Chem. 2006, 4, 2076; (c) Beay, B. A. Chem.
Soc. Rev. 1999, 28, 209; (d) Cacchi, S. J. Organomet. Chem. 1999, 576, 42; (e)
Brown, R. C. D. Angew. Chem., Int. Ed. 2005, 44, 850; (f) Benassi, R. In Compre-
hensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V.,
Eds.; Pergamon: Oxford, UK, 1996; Vol. 2, p 259; (g) Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, UK, 1991.
4.3.1. Ethyl 1-methoxy-2-methyl-5-phenyl-1H-pyrrole-3-carboxylate
(7a). Colorless oil (31 mg, 40%); 1H NMR (400 MHz, CDCl3)
d 7.67 (d,
J¼7.2 Hz, 2H), 7.39 (m, 2H), 7.28 (m, 1H), 6.65 (s, 1H), 4.29 (q, J¼7.1 Hz,
2H), 3.71 (s, 3H), 2.60 (s, 3H), 1.36 (t, J¼7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3)
d 165.0, 132.4, 130.4, 128.6, 127.05, 127.01, 126.4, 107.9, 105.2,
65.6, 59.5, 14.5, 9.8; IR (film, cmꢁ1); 2976, 1702, 1240, 1065, 971, 757,
695; EIMS (m/z, relative intensity): 259 (Mþ, 100), 244 (5), 30 (20), 214
(18), 200 (95), 182 (55), 154 (8), 104 (25), 77 (6), 55 (5); HRMS (ESI)
calcd for C15H18 NO3 [(MþH)þ]: 260.1281, found: 260.1279.
4.3.2. Ethyl 1-methoxy-2-methyl-5-(m-tolyl)-1H-pyrrole-3-
carboxylate (7b). Following the typical procedure described above,
the crude residue was purified by silica column chromatography
(eluted with 10:1, petroleum ether/EtOAc) to afford pure 7b as light
yellow oil (25 mg, 30%); 1H NMR (400 MHz, CDCl3)
d
7.49 (d, J¼7.6 Hz,
4. For reviews on a-diazocarbonyl compounds, see: (a) Doyle, M. P.; McKervey, M.
A.; Ye, T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds;
Wiley: New York, NY, 1998; (b) Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94, 1091;
(c) Zhang, Z.; Wang, J. Tetrahedron 2008, 64, 6577.
2H), 7.28 (m, 1H), 7.10 (d, J¼7.5 Hz, 1H), 6.63 (s, 1H), 4.29 (q, J¼7.1 Hz,
2H), 3.71 (s, 3H), 2.59 (s, 3H), 2.39 (s, 3H), 1.36 (t, J¼7.1 Hz, 3H); 13C
5. (a) Davies, H. M. L.; Romines, K. R. Tetrahedron 1988, 44, 3343; (b) Davies, H. M.
L.; Cantrell, W. R., Jr.; Romines, K. R.; Baum, J. S. Org. Synth., Coll. Vol. 1998, 9,
422; (c) Briones, J. F.; Davies, H. M. L. Tetrahedron 2011, 67, 4313.
6. (a) Kinder, F. R.; Padwa, A. Tetrahedron Lett. 1990, 31, 6835; (b) Padwa, A.;
Chiacchio, U.; Gareau, Y.; Kassir, J. M.; Krumpe, K. E.; Schoffstall, A. M. J. Org.
Chem. 1990, 55, 414; (c) Padwa, A.; Krumpe, K. E.; Gareau, Y.; Chiacchio, U. J. Org.
Chem.1991, 56, 2523; (d) Padwa, A.; Krumpe, K. E.; Kassir, J. M. J. Org. Chem.1992,
57, 4940; (e) Pirrung, M. C.; Zhang, J.; Morehead, A. T. Tetrahedron Lett. 1994, 35,
6229; (f) Pang, W.; Zhu, S.; Xin, Y.; Jiang, H.; Zhu, S. Tetrahedron 2010, 66, 1261.
7. Cui, X.; Xu, X.; Wojtas, L.; Kim, M. M.; Zhang, X. P. J. Am. Chem. Soc. 2012, 134,
19981.
8. Xia, L.; Lee, Y. R. Eur. J. Org. Chem. 2014, 3430.
9. For a recent review on copper-catalyzed reaction of diazo compounds, see:
Zhao, X.; Zhang, Y.; Wang, J. Chem. Commun. 2012, 10162.
10. Swenson, A. K.; Higgins, K. E.; Brewer, M. G.; Brennessel, W. W.; Coleman, M. G.
Org. Biomol. Chem. 2012, 10, 7483.
NMR (100 MHz, CDCl3) d 165.1, 138.2, 132.3, 130.3, 128.5, 127.8, 127.2,
123.5, 107.9, 105.2, 65.6, 59.5, 21.5, 14.5, 9.9; IR (film, cmꢁ1); 2974,
1703, 1608, 1440, 1253, 1217, 1066, 918, 768, 696; EIMS (m/z, relative
intensity): 273 (Mþ, 90), 258 (10), 244 (15), 228 (18), 214 (100), 196
(35), 168 (10), 128 (8), 118 (18); HRMS (ESI) calcd for C16H20NO3
[(MþH)þ]: 274.1438, found: 274.1439.
4.3.3. Ethyl 1-methoxy-2-methyl-5-(thiophen-3-yl)-1H-pyrrole-3-
carboxylate (7e). Following the typical procedure described above,
the crude residue was purified by silica column chromatography
(eluted with 30:1, petroleum ether/EtOAc) to afford pure 7e as yellow
oil (22 mg, 28%); 1H NMR (400 MHz, CDCl3)
d
7.56 (dd, J¼1.4, 2.7 Hz,
1H), 7.32e7.36 (m, 2H), 6.62 (s,1H), 4.29 (q, J¼7.1 Hz, 2H), 3.83 (s, 3H),
11. The structures of the products were originally assigned as furans, they were
later corrected as allenes, see (a) Zhou, L.; Ma, J.; Zhang, Y.; Wang, J. Tetrahedron
Lett. 2011, 52, 5484; (b) Zhou, L.; Ma, J.; Zhang, Y.; Wang, J. Tetrahedron Lett.
2013, 54, 2558.
2.59 (s, 3H), 1.36 (t, J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 165.0,
131.8,130.6,126.3,125.5,123.3,119.3,107.7,104.3, 65.5, 59.5,14.5, 9.8;
IR (film, cmꢁ1); 2987, 2901, 1702, 1440, 1237, 1066, 769; EIMS (m/z,
relative intensity): 265 (Mþ, 100), 234 (20), 220 (15), 206 (90), 188
(40), 160 (12), 110 (10); HRMS (ESI) calcd for C13H16NO3S [(MþH)þ]:
266.0845, found: 266.0848.
12. Hassink, M.; Liu, X.; Fox, J. M. Org. Lett. 2011, 13, 2388.
13. Suarez, A.; Fu, G. C. Angew. Chem., Int. Ed. 2004, 43, 3580.
14. Davies, J. R.; Kane, P. D.; Moody, C. J. Tetrahedron 2004, 60, 3967.
15. Ma, S.; Zhang, J. J. Am. Chem. Soc. 2003, 125, 12386.
16. Aoyama, T.; Nagaoka, T.; Takido, T.; Kodomari, M. Synthesis 2011, 4, 619.
17. He, C.; Guo, S.; Ke, J.; Hao, J.; Xu, H.; Chen, H.; Lei, A. J. Am. Chem. Soc. 2012,134, 5766.
18. Kretchmer, R. A.; Laitar, R. A. J. Org. Chem. 1978, 43, 4597.
19. For examples of transition-metal-catalyzed ring-opening rearrangement, see:
Li, C.; Zeng, Y.; Wang, J. Tetrahedron Lett. 2009, 50, 2956 and references cited
therein.
4.3.4. Ethyl
5-(4-fluorophenyl)-1-methoxy-2-methyl-1H-pyrrole-3-
carboxylate (7j). Following the typical procedure described above, the
crude residue was purified by silica column chromatography (eluted