Synthesis of 2-substituted furans by iron- and palladium-catalyzed coupling reactions

Article abstract of DOI:10.1055/s-0030-1259484

The synthesis of 2-substituted furans via palladium- and iron-catalyzed coupling utilizing 2-bromofuran is described. Whereas palladium-catalyzed Suzuki coupling effectively provided the corresponding aryl furans, little or no product was obtained by palladium-catalyzed coupling with various alkyl nucleophiles. Iron-catalyzed coupling proved effective for the synthesis of primary and secondary alkyl furans in modest yields and aryl furans in low yields. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1259484

PAPER
731
Synthesis of 2-Substituted Furans by Iron- and Palladium-Catalyzed Coupling
Reactions
S
J
ynthesis
a
of 2-Substi
mt uted Furans ie Haner, Kelsey Jack, Jaipal Nagireddy, Mohammed Abdul Raheem, Robin Durham, William Tam*
Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, Department of Chemistry, University of Guelph,
Guelph, ON, N1G 2W1, Canada
Fax +1(519)8244120 (ext. 52268); E-mail: wtam@uoguelph.ca
Received 1 October 2010; revised 12 January 2011
For example, when 7-oxabenzonorbornadiene (1) is treat-
Abstract: The synthesis of 2-substituted furans via palladium- and
ed with an alkyne in the presence of the ruthenium cata-
iron-catalyzed coupling utilizing 2-bromofuran is described.
Whereas palladium-catalyzed Suzuki coupling effectively provided
the corresponding aryl furans, little or no product was obtained by
lyst, [Cp*Ru(cod)Cl], a [2+2] cycloaddition is observed
3
and cyclobutene cycloadduct 2 is formed. When 1 is
palladium-catalyzed coupling with various alkyl nucleophiles. Iron- treated with the secondary propargylic alcohol 8 in the
catalyzed coupling proved effective for the synthesis of primary and presence of the neutral Ru catalyst, [Cp*Ru(cod)Cl], in
secondary alkyl furans in modest yields and aryl furans in low
methanol or using a cationic Ru catalyst (e.g., [Cp-
yields.
4
Ru(MeCN) ]PF ), isochromene 3 is formed. On the other
3
6
Key words: furan, cross-coupling, catalysis, palladium, iron
hand, if the same reaction between 1 and the secondary
propargylic alcohol 8 is carried out with [Cp*Ru(cod)Cl]
in tetrahydrofuran (THF), cyclopropane 4 is produced.5
Oxabicyclic alkenes are valuable synthetic intermediates More recently, we have observed that in the absence of an
because they can serve as a general template to create alkyne, [Cp*Ru(cod)Cl] catalyzes the isomerization of 16
1
highly substituted ring systems. For instance, asymmetric to the corresponding naphthalene oxide 5 or naphthol 6.
ring opening of these alkenes allows the formation of sev- We have also reported that asymmetric cationic rhodi-
2
eral stereocenters in a single step. We have recently in- um(I)-catalyzed cyclodimerization of 1 produces dimers 7
vestigated different modes of transition-metal-catalyzed in excellent enantioselectivity (up to 99% ee).7
reactions of oxabenzonorbornadiene (1), and found that,
depending on the reaction conditions, several products 2–
Because oxabenzonorbornadiene (1) is symmetrical, no
regiochemical information could be gained from the
above studies. To explore the regioselectivity of the above
7
could be obtained (Scheme 1).
R1
O
R2
H
2
H
O
O
Ru catalyst
R1 R2
3
O
H
O
H
7
Ru catalyst
MeOH
O
OEt
OH
Rh catalyst
O
O
Ru catalyst
silica
EtO
8
1
OH
THF
Ru catalyst
O
Ru catalyst
O
neutral
alumina
OEt
6
O
4
O
5
Scheme 1 Transition-metal-catalyzed reactions of oxabenzonorbornadiene (1)
SYNTHESIS 2011, No. 5, pp 0731–0738
x
x
.
x
x
.2
0
1
1
Advanced online publication: 31.01.2011
DOI: 10.1055/s-0030-1259484; Art ID: M06610SS
Georg Thieme Verlag Stuttgart · New York
©

7
32
J. Haner et al.
PAPER
reactions, we planned to synthesize C1-substituted oxa- Table 1 Pd-Catalyzed Suzuki Coupling Reactions of 2-Bromofuran
(
12)a
benzonorbornadiene 11 by the Diels–Alder reaction of
benzyne 9 and 2-substituted furans 10 (Scheme 2). Al-
though some 2-substituted furans are commercially avail-
able (such as R = Me, t-Bu, COOMe), these R groups are
limited to simple alkyl groups and carbonyl groups. In this
paper, we describe our efforts to synthesize 2-substituted
furans with R = alkyl, cycloalkyl, and aryl substituents by
Fe- and Pd-catalyzed cross-coupling reactions.
O
O
Br
Ar
Pd catalysta
+
ArB(OH)2
DMF–H2O, K2CO3
75–85 °C
1
2
10
Yield (%)b
Entry 10 Ar
Pd(OAc)2 PdCl (PPh ) Pd(PPh ) Pd/C
2 3 2 3 4
1
2
3
4
5
6
7
8
9
0
10a Ph
21
24
19
12
62
80
78
56
57
72
63
65
67
70
56
59
77
85
71
97
95
77
77
69
53
77
80
78
84
74
74
87
73
38
40
11
43
41
9
O
10b 4-MeC H
6
4
4
4
+
O
R
1
10c 3-MeC H
6
R
9
10
11
10d 2-MeC H
6
Scheme 2 Synthesis of C1-substituted oxabenzonorbornadiene 11
10e 4-MeOC H 36
6 4
10f 3-MeOC H 48
6
4
To begin our study, 2-bromofuran (12) was prepared ac-
cording to literature procedures. Initially, Suzuki cou-
pling reactions were investigated to synthesize the desired
-aryl furans 10a–n (Table 1). 2-Bromofuran (12) was re-
acted with various aryl boronic acids in the presence of
several palladium sources with a solvent system of N,N-
dimethylformamide (DMF) and water; potassium carbon-
8
10g 2-MeOC H 42
6
4
4
4
4
4
10h 4-ClC H
17
5
73
50
31
52
63
52
67
6
2
10i 3-ClC
H
6
1
10j 2-ClC H
3
6
ate was used as a base. Four commercially available Pd(0) 11 10k 4-EtC H
38
40
6
and Pd(II) catalysts were examined for all of the coupling
1
2
10l 4-AcC H
6 4
reactions, including Pd(OAc) , PdCl (PPh ) , Pd(PPh ) ,
2
2
3 2
3 4
and 5% Pd/C (Table 1). Low yields of less than 50% were
obtained in all cases when Pd(OAc) was used, whereas
PdCl (PPh ) and Pd(PPh ) functioned as effective cata-
lysts, with Pd(PPh ) providing slightly higher yields in
13 10m 4-biphenyl 32
2
1
4
10n 1-naphthyl 36
2
3 2
3 4
a
Reaction conditions: Pd catalyst (2 mol%), K CO (2.5 equiv),
3
4
2
3
most cases except for the coupling of 2-MeOC H , 3- DMF–H
O (2:1).
2
6
4
b
Isolated yield after column chromatography.
MeOC H , and 4-biphenyl groups (Table 1, entries 6, 7,
6
4
and 13). Use of Pd/C as a source of palladium is not com-
mon in Suzuki couplings reactions, however, good yields
tions of Grignard reagents, with alkenyl chlorides, bro-
mides and iodides as well as alkenyl phosphates all being
(
67–73%) were obtained for substrates with phenyl, 4-
used successfully.1
1c–e
In 2004, Fürstner extended
ClC H , and 1-naphthyl groups (Table 1, entries 1, 8, and
6
4
Cahiez’s conditions to include alkenyl triflates as success-
ful substrates in iron-catalyzed alkenylations of Grignard
reagents.1
1
4). Indeed, the highest yield for the coupling of phenyl
boronic acid (73%) was provided with Pd/C.
1f–m
Attempts to expand the scope of this Pd-catalyzed Suzuki
coupling reaction with 1° or 2° alkyl boronic acids were
unsuccessful and did not afford any coupling products.
Thus, this Pd-catalyzed Suzuki coupling reaction would
only allow the production of 2-substituted furans 10 with
We began our investigation by studying the reaction con-
ditions of this iron-catalyzed coupling reaction using 2-
bromofuran (12) and cyclohexylmagnesium chloride.
Various solvents, iron catalysts, reaction temperatures, re-
action time, and equivalency of Grignard reagent were in-
vestigated, and reaction conditions were optimized.
Amide, phosphoramide, and urea based solvents provided
the highest yields (Table 2, entries 1–8) whereas ether,
amine, or pyridine based solvents provided either low or
no yield (entries 9–12). The solvents DMPU and dimeth-
ylamine (DMA) provided the highest yield (60%) of cou-
pling product (entries 1 and 8).
9
R = aryl groups.
The limitations of the above palladium-catalyzed cou-
pling reactions lead us to explore alternative methods for
the synthesis of 2-substituted furans 10. In 1945, Kharasch
and co-workers reported the first iron-catalyzed alkenyla-
1
0a,b
tion of Grignard reagents.
Kochi and co-workers im-
proved the procedures and studied the mechanism of the
reaction in 1971; however, the yields of the reactions re-
mained low and were not convenient for preparative ap-
Of the iron catalysts screened (ligands are shown in
1
0c,11a,b
Figure 1), Fe(acac) provided the highest yield (Table 2,
plications.
More recently, since 1998, Cahiez
3
entry 1). The bulkier malonate-derived iron sources
reported that the use of N-methyl-2-pyrrolidinone (NMP)
or N,N¢-dimethylpropylene urea (DMPU) as a co-solvent
greatly improved the yields of iron-catalyzed alkenyla-
[
Fe(dbm) or Fe(dpm) ] furnished only 30 and 22%
3 3
yields, respectively (Table 2, entry 15 and 16). FeCl pro-
3
vided the second highest yield (40%), whereas the hydrate
Synthesis 2011, No. 5, 731–738 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Substituted Furans
733
Table 2 Optimization of Conditions for the Synthesis of 10
O
O
H
H
O
ClMg
N
N
Br
O
Fe catalyst
R
R
Fe
t-Bu
O
O
t-Bu
+
Cl
solvent, temp
R = Me (acac, acetoacetonato)
R = t-Bu (dpm, dipivaloylmethio)
R = Ph (dbm, dibenzoylmethio)
12
10
t-Bu
t-Bu
Entry Solvent
Fe catalyst Time Temp Yield
Fe(Salen)Cl
(
min) (°C)
(%)a
60
40
40
35
39
40
38
60
5
Figure 1
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
DMPU
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
120 –25
120 –25
120 –25
120 –25
120 –25
120 –25
120 –25
120 –25
120 –25
120 –25
120 –25
120 –25
120 –25
substituted furans 10o–w (Table 3, entries 1–9). For
smaller sized alkyl groups of less than five carbons, isola-
tion of the product proved to be non-trivial (see below).
Aryl groups could be coupled with 2-bromfuran, howev-
er, low yields were observed (4–26%; Table 3, entries 10–
18) with the lowest yields (4–6%) obtained for phenyl and
the 4-fluoro, 2-methyl, and 2-methoxy substituted aryl
groups (Table 3, entries 10, 13, 16, and 18). Higher yields
THF–DMPU (3:1)
NMP
THF–NMP (3:1)
DMEU–THF (3:1)b
THF + HMPA (1 equiv) Fe(acac)3
(
20–26%) were obtained for 4- and 3-methyl and methoxy
DMF
DMA
THF
Fe(acac)3
substituted aryl groups (Table 3, entries 11, 12, 14, and
15). Low yields (15%) of 2-benzylfuran 10w were ob-
tained (entry 9). No coupling product was obtained from
Fe(acac)3
Fe(acac)3
3
-chloro magnesium chloride, ethynyl phenyl magnesium
1
1
1
1
1
1
1
1
1
1
2
2
2
Et N
Fe(acac)3
Fe(acac)3
Fe(acac)3
FeCl3
17
3
3
TMEDA
pyridine
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
Table 3 Optimization of Conditions for the Synthesis of 10
O
O
0
Br
R
Fe(acac)3
+
RMgX
DMPU, –25 °C
40
0
1
2
10
FeF ·H O 120 –25
3
2
Yield (%)a
Entry
R
X
10
Fe(dpm)3
Fe(dbm)3
120 –25
120 –25
30
22
5
1
2
3
4
5
6
7
8
9
cyclopropyl
n-Bu
Br
Cl
Cl
Cl
Cl
Cl
Br
Cl
Cl
Br
Br
Br
Br
Br
Br
Br
Br
Br
10o
10p
10q
10r
10s
10t
35
39
55
51
44
56
46
40
15
5
Fe(Salen)Cl 120 –25
s-Bu
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
15 –25
30 –25
60 –25
6
cyclobutyl
cyclopentyl
cyclohexyl
cycloheptyl
dodecyl
Bn
41
45
35
55
120
0
10u
10v
10w
10a
10b
10c
10d
10e
10f
120 –40
a
GC yields with internal standard of benzophenone.
DMEU = dimethylethylene urea.
b
1
0
Ph
of FeF provided no coupling product (entries 13 and 14).
3
Low yields were also obtained for Fe(Salen)Cl (5%; 11
Table 2, entry 17). Reaction times of 15, 30, 60, and 120
4-MeC H
26
24
4
6
4
4
4
12
13
14
15
16
3-MeC H
6
minutes were screened, with 120 minutes showing the
highest yield (Table 2, entries 1, and 18–20). Prolonged
reaction times beyond 120 minutes did not improve the
yield further. Variation of reaction temperature (0, –25,
and –40 °C; entries 1, 21, and 22) showed that the highest
yield was obtained at –25 °C, with no reaction observed at
2-MeC H
6
4-MeOC H
22
24
6
6
4
4
4
3-MeOC H
6
2-MeOC H
10g
10m
10x
–
78 °C.
6
To expand of scope of this coupling reaction, other groups 17
were investigated. Primary and secondary alkyl Grignard
reagents, including small to medium-sized ring cycloalkyl
groups, provided moderate to low yields (35–55%) of 2-
4-biphenyl
4-FC H
20
6
1
8
6
4
a
Isolated yield after column chromatography.
Synthesis 2011, No. 5, 731–738 © Thieme Stuttgart · New York

7
34
J. Haner et al.
PAPER
chloride, or tert-butyl magnesium chloride and, thus, this 13C NMR spectra are reported in parts per million (ppm) from TMS
with the solvent as the internal standard (CDCl : d = 77.0 ppm). Un-
coupling methodology may not extend to halide-substitut-
ed aryl, sp-hybridized, or tertiary alkyl Grignard reagents.
Variation of the halide within the Grignard reagents from
chloride to bromide did not appear to offer significantly
different yields; coupled products where observed in both
cases in similar yields.
3
less stated otherwise, commercial reagents were used without puri-
fication. Solvents were purified by distillation under dry nitrogen:
THF and Et O from potassium/benzophenone; DME from CaH ;
2
2
DMPU, DMSO, TMEDA, and Et N from 4 Å molecular sieves.
3
The catalysts Fe(dpm) , Fe(dbm) , and Fe(Salen)Cl were prepared
3
3
1
1f,13
by literature procedures.
before use according to literature procedures before use.
All the Grignard reagents were titrated
1
4
In the iron-catalyzed coupling of 2-bromofuran (12) with
various alkyl and aryl Grignard reagents, low to moderate
yields of the desired coupling product were obtained. Ho-
Palladium-Catalyzed Suzuki Coupling (Table 1); General Pro-
cedure A
mocoupling of 2-bromofuran (12) was observed, and bi- To an oven-dried vial containing a stir bar inside an inert atmo-
furan 13 was detected in every reaction (Figure 2). This sphere (Ar) glove box, the Pd catalyst (0.02 equiv) was added. The
vial was then removed from the glove box. Anhydrous K CO (2.5
compound is likely formed as a result of magnesium–
halide exchange to provide a 2-furyl magnesium halide,
which could undergo further unwanted coupling with 2-
bromofuran. The dimer of the Grignard reagent 14 was
also observed in all cases. Both of these compounds some-
times co-elute during column chromatography and have
2
3
equiv) and boronic acid (1.2 equiv) were then added, followed by
DMF and H O (2:1, v/v, ~1 M) and quickly capped. The vial was
the heated to 75–85 °C for 18–20 h. The crude product was then pu-
rified by column chromatography with hexanes or EtOAc–hexanes
mixture.
2
1
1k
similar boiling points to the desired coupled product, thus, Iron-Catalyzed Coupling (Table 3); General Procedure B
An oven-dried, nitrogen-flushed flask equipped with a magnetic
isolation was non-trivial and often required quantification
by NMR analysis.
stirring bar and rubber septum was charged with Fe(acac) (24 mg,
3
2
0 mol%) and DMPU (2.5 mL). The flask was cooled to –25°C and
bromofuran (12; 36 mL, 4 mmol) was added. RMgX (16 mmol, 400
mol%) was then added dropwise over a period of 20 min to provide
a deep-purple to brown solution. The solution was then stirred for
O
O
R
R
2
.5 h then H O (2 mL) was added dropwise followed by saturated
2
1
3
14
NaHCO (5 mL) and extracted with Et O (3 × 10 mL). The extract
was dried over Na SO and concentrated either by rotary evapora-
tion or by fractional distillation (compounds 10o–r). The crude
products were then purified by silica gel column chromatography
3
2
Figure 2 Homocoupled products obtained from Fe-catalyzed cou-
2
4
pling
[
EtOAc–hexanes or Et O–pentane (compounds 10o–r)].
2
In conclusion, our efforts have led to the synthesis of 2-
aryl and 2-alkyl furans by palladium and iron-catalyzed 2-Phenylfuran (10a)
coupling methodologies. These furans are useful interme- Following general procedure A; yield: 62% (90.0 mg).
diates in the synthesis of C1-substituted Diels–Alder cy-
cloadducts by treatment with the appropriate dienophile.
Moderate to high yields were obtained for palladium-cat-
alyzed coupling reactions of 2-bromofuran (12) with aryl
boron acids with a variety of commercially available pal-
ladium sources. However, alkyl furans were not attainable
by this coupling methodology. In contrast, iron-catalyzed
coupling of 2-bromofuran (12) with Grignard reagents
Following general procedure B; yield: 5% (45 mg).
Colorless oil; R = 0.38 (hexanes).
f
–
1
IR (CH Cl ): 3054, 1608, 1507, 1477, 1265, 1023 cm .
2
2
1
H NMR (CDCl , 300 MHz): d = 6.45–6.57 (m, 1 H), 6.66 (d,
3
J = 3.4 Hz, 1 H), 7.26 (t, J = 7.2 Hz, 1 H), 7.39 (t, J = 7.8 Hz, 2 H),
7
.47–7.48 (m, 1 H), 7.69 (d, J = 7.8 Hz, 2 H).
1
3
C NMR (APT; CDCl , 75 MHz): d = 104.9 (CH), 111.6 (CH),
3
1
23.8 (CH), 127.3 (CH), 128.6 (CH), 130.9 (qC), 142.0 (CH), 154.0
(
primary and secondary) provided the corresponding 2-
(
qC).
alkyl furans in moderate yields. 2-Aryl furans were also
attainable by this coupling methodology, albeit in low
yields. The limitations of this reaction showed that tertiary
alkyl or alkynyl Grignard reagents were not amenable
coupling partners.
+
HRMS (EI): m/z [M ] calcd for C H O: 144.0575; found:
10
8
1
44.0579.
2
-(4-Methylphenyl)furan (10b)
Following general procedure A; yield: 97% (83.3 mg).
Following general procedure B; yield: 26% (257 mg).
All reactions were carried out in an atmosphere of dry nitrogen at
ambient temperature unless otherwise stated. Standard column
chromatography was performed on 230–400 mesh silica gel using
Colorless oil; R = 0.65 (EtOAc–hexanes, 30:70).
f
–
1
IR (CH Cl ): 3290, 1620, 1509, 1455, 1380, 1260, 1100, 1052 cm .
2
2
1
2
1
flash column chromatography techniques. Analytical thin-layer
chromatography (TLC) was performed on Merck precoated silica
gel 60 F254 plates. All glassware was either oven-dried (120 °C) or
flame-dried under an inert atmosphere of dry nitrogen. Infrared
spectra were recorded with a Bomem MB-100 FTIR spectropho-
H NMR (CDCl , 400 MHz): d = 2.24 (s, 3 H), 6.33 (m, 1 H), 6.47
3
(d, J = 3.2 Hz, 1 H), 7.07 (d, J = 8.0 Hz, 2 H), 7.32 (br s, 1 H), 7.46
(d, J = 8.0 Hz, 2 H).
1
3
C NMR (APT; CDCl , 100 MHz): d = 21.0 (CH ), 104.0 (CH),
3
3
1
1.4 (CH), 123.6 (CH), 128.1 (qC), 129.2 (CH), 136.9 (qC), 141.5
1
13
tometer. H and C NMR spectra were recorded with Bruker
Avance-300, 400, or 600 MHz spectrometers. Chemical shifts for
(
CH), 154.0 (qC).
1
+
H NMR spectra are reported in parts per million (ppm) from tet-
HRMS (EI): m/z [M ] calcd for C11H10O: 158.0732; found:
ramethylsilane (TMS), with the residual protium resonance as the
158.0735.
internal standard (chloroform: d = 7.26 ppm). Chemical shifts for
Synthesis 2011, No. 5, 731–738 © Thieme Stuttgart · New York

PAPER
-(3-Methylphenyl)furan (10c)
Synthesis of 2-Substituted Furans
735
2
Following general procedure B; yield: 6% (94 mg).
Following general procedure A; yield: 95% (119.6 mg).
Brown oil; R = 0.42 (EtOAc–hexanes, 10:90).
f
Following general procedure B; yield: 24% (26 mg).
–1
IR (CH Cl ): 3002, 2940, 2837, 1602, 1464, 1083 cm .
2
2
Colorless oil; R = 0.63 (EtOAc–hexanes, 30:70).
1
f
H NMR (CDCl , 300 MHz): d = 3.93 (s, 3 H), 6.48–6.50 (m, 1 H),
3
–
1
IR (CH Cl ): 3288, 1622, 1521, 1447, 1382, 1260, 1105, 1059 cm .
6.93–7.04 (m, 3 H), 7.20–7.27 (m, 1 H), 7.46 (d, J = 0.7 Hz, 1 H),
7.85 (dd, J = 7.7, 1.3 Hz, 1 H).
2
2
1
H NMR (CDCl , 400 MHz): d = 2.54 (s, 3 H), 6.61 (m, 1 H), 6.79
3
1
3
(
m, 1 H), 7.23 (d, J = 7.5 Hz, 1 H), 7.43 (td, J = 7.7, 1.5 Hz, 1 H),
C NMR (APT; CDCl , 75 MHz): d = 55.4 (CH ), 109.8 (CH),
3 3
7
.60 (br s, 1 H), 7.54–7.76 (m, 2 H).
111.0 (CH), 111.6 (CH), 119.9 (qC), 120.7 (CH), 126.0 (CH), 128.0
(CH), 141.1 (CH), 150.3 (qC), 155.3 (qC).
1
3
C NMR (APT; CDCl , 100 MHz): d = 21.4 (CH ), 104.7 (CH),
3
3
+
1
1
11.5 (CH), 120.9 (CH), 124.3 (CH), 128.0 (CH), 128.5 (CH),
30.7 (qC), 138.1 (qC), 141.8 (CH), 154.0 (qC).
HRMS (EI): m/z [M ] calcd for C H O : 174.0681; found:
174.0685.
1
1
10
2
+
HRMS (EI): m/z [M ] calcd for C H O: 158.0732; found:
1
1
10
2
-(4-Chlorophenyl)furan (10h)
1
58.0737.
Following general procedure A; yield: 77% (116.0 mg).
2
-(2-Methylphenyl)furan (10d)
White solid. R = 0.29 (hexanes).
f
Following general procedure A; yield: 77% (114.4 mg).
–1
IR (CH Cl ): 3054, 2987, 1487, 1422, 1265, 1093, 1020 cm .
2
2
Following general procedure B; yield: 4% (34 mg).
1
H NMR (CDCl , 300 MHz): d = 6.42–6.49 (m, 1 H, CH), 6.62 (d,
3
Colorless oil; R = 0.67 (EtOAc–hexanes, 30:70).
J = 2.9 Hz, 1 H), 7.33 (d, J = 8.5 Hz, 2 H), 7.45 (s, 1 H), 7.58 (d,
J = 8.5 Hz, 2 H).
f
–
1
IR (CH Cl ): 3034, 1617, 1510, 1479, 1266, 1043 cm .
2
2
13C NMR (APT; CDCl
25.0 (CH), 128.9 (CH), 129.4 (qC), 133.0 (qC), 142.3 (CH), 153.0
qC).
, 75 MHz): d = 105.4 (CH), 111.8 (CH),
1
3
H NMR (CDCl , 400 MHz): d = 2.37 (s, 3 H), 6.36 (dd, J = 3.4,
3
1
(
1
.8 Hz, 1 H), 6.43 (d, J = 3.4 Hz, 1 H), 7.06–7.15 (m, 3 H), 7.37 (d,
J = 1.6 Hz, 1 H), 7.59 (d, J = 7.7 Hz, 1 H).
+
1
3
HRMS (EI): m/z [M ] calcd for C10H ClO: 178.0185; found:
7
1
C NMR (APT; CDCl , 100 MHz): d = 21.8 (CH ), 108.4 (CH),
3
3
78.0188.
1
11.2 (CH), 125.9 (CH), 127.1 (CH), 127.4 (CH), 130.2 (qC), 131.0
(
CH), 134.5 (qC), 141.6 (CH), 153.5 (qC).
2
-(3-Chlorophenyl)furan (10i)
+
HRMS (EI): m/z [M ] calcd for C H O: 158.0732; found:
1
1
1
10
Following general procedure A; yield: 80% (119.0 mg).
58.0736.
Colorless oil; R = 0.29 (hexanes).
f
–
1
2
-(4-Methoxyphenyl)furan (10e)
IR (CH Cl ): 3371, 1603, 1582, 1282, 1013 cm .
2 2
Following general procedure A; yield: 77% (100.0 mg).
1
H NMR (CDCl , 300 MHz): d = 6.44 (dd, J = 3.42, 1.83 Hz, 1 H),
3
Following general procedure B; yield: 22% (267 mg).
6.63 (d, J = 3.4 Hz, 1 H), 7.15–7.38 (m, 2 H), 7.46 (d, J = 1.71 Hz,
H), 7.49–7.52 (m, 1 H), 7.64 (t, J = 1.77 Hz, 1 H).
1
White solid; R = 0.26 (EtOAc–hexanes, 5:95).
f
13C NMR (APT; CDCl
1
(qC), 142.5 (CH), 152.5 (qC).
, 75 MHz): d = 106.0 (CH), 111.7 (CH),
–
1
3
IR (CH Cl ): 2959, 2937, 1617, 1218, 1047 cm .
2
2
21.8 (CH), 123.8 (CH), 127.2 (CH), 130.0 (CH), 132.5 (qC), 134.7
1
H NMR (CDCl , 300 MHz): d = 3.82 (s, 3 H), 6.43 (dd, J = 3.4,
3
1
7
.7 Hz, 1 H), 6.51 (d, J = 2.8 Hz, 1 H), 6.91 (d, J = 8.8 Hz, 2 H),
.41 (d, J = 1.3 Hz, 1 H), 7.61–7.56 (m, 2 H).
+
HRMS (EI): m/z [M ] calcd for C H ClO: 178.0185; found:
1
1
0
7
78.0182.
1
3
C NMR (APT; CDCl , 75 MHz): d = 55.2 (CH ), 103.3 (CH),
3
3
1
11.5 (CH), 114.1 (CH), 124.0 (qC), 125.2 (CH), 141.3 (CH), 154.0
2
-(2-Chlorophenyl)furan (10j)
(
qC), 159.0 (qC).
Following general procedure A; yield: 78% (70.0 mg).
+
HRMS (EI): m/z [M ] calcd for C H O : 174.0681; found:
1
1
10
2
Colorless oil; R = 0.29 (hexanes).
f
1
74.0686.
–
1
IR (CH Cl ): 3065, 1599, 1499, 1470, 1031 cm .
2
2
1
2
-(3-Methoxyphenyl)furan (10f)
H NMR (CDCl , 300 MHz): d = 6.53 (dd, J = 3.5, 1.8 Hz, 1 H),
3
Following general procedure A; yield: 72% (126.0 mg).
7.14 (dd, J = 3.5, 0.6 Hz, 1 H), 7.19 (dd, J = 7.4, 1.7 Hz, 1 H), 7.31
td, J = 3.9, 1.4 Hz, 1 H), 7.44 (dd, J = 7.9, 1.2 Hz, 1 H), 7.51 (dd,
(
Following general procedure B; yield: 24% (310 mg).
J = 1.8, 0.6 Hz, 1 H), 7.87 (dd, J = 7.9, 1.7 Hz, 1 H).
13
Brown oil; R = 0.45 (EtOAc–hexanes, 5:95).
f
C NMR (APT; CDCl , 75 MHz): d = 110.9 (CH), 111.7 (CH),
3
–
1
IR (CH Cl ): 2938, 1605, 1504, 1290, 1226, 1038 cm .
2
2
126.9 (CH), 127.9 (CH), 128.0 (CH), 129.3 (CH), 130.1 (qC), 130.7
(qC), 142.1 (CH), 150.2 (qC).
1
H NMR (CDCl , 300 MHz): d = 3.77 (s, 3 H), 6.38 (dd, J = 3.4,
3
1
7
.8 Hz, 1 H), 6.56 (d, J = 3.4 Hz, 1 H), 6.71–6.75 (m, 1 H), 7.13–
.21 (m, 3 H), 7.37 (d, J = 1.7 Hz, 1 H).
+
HRMS (EI): m/z [M ] calcd for C H ClO: 178.0185; found:
1
1
0
7
78.0181.
1
3
C NMR (APT; CDCl , 75 MHz): d = 55.3 (CH ), 105.3 (CH),
3
3
2
-(4-Ethylphenyl)furan (10k)
1
1
09.2 (CH), 111.7 (CH), 113.2 (CH), 116.4 (CH), 129.8 (CH),
Following general procedure A; yield: 84% (96.0 mg).
32.2 (qC), 142.1 (CH), 153.8 (qC), 159.9 (qC).
+
Brown oil; R = 0.5 (EtOAc–hexanes, 5:95).
HRMS (EI): m/z [M ] calcd for C H O : 174.0681; found:
f
1
1
10
2
1
74.0679.
–1
IR (CH Cl ): 3023, 2965, 2931, 1516, 1457, 1157, 1007 cm .
2
2
1
H NMR (CDCl , 300 MHz): d = 1.24 (t, J = 7.6 Hz, 3 H), 2.65 (q,
3
2
-(2-Methoxyphenyl)furan (10g)
J = 7.6 Hz, 2 H), 6.44 (dd, J = 3.3, 1.8 Hz, 1 H), 6.58 (d, J = 3.3 Hz,
Following general procedure A; yield: 63% (110.0 mg).
Synthesis 2011, No. 5, 731–738 © Thieme Stuttgart · New York

7
36
J. Haner et al.
PAPER
HRMS (EI): m/z [M ] calcd for C H O: 108.0575; found: 108.0572.
+
1
H), 7.21 (d, J = 8.2 Hz, 2 H); 7.43 (d, J = 1.6 Hz, 1 H), 7.59 (d,
7
8
J = 8.2 Hz, 2 H).
1
3
2-nButylfuran (10p)
Following general procedure B; yield: 39% (45 mg).
C NMR (APT; CDCl , 75 MHz): d = 15.5 (CH ), 28.6 (CH ),
3
3
2
1
04.2 (CH), 111.5 (CH), 123.8 (CH), 128.1 (CH), 128.5 (qC), 141.6
(
CH), 143.5 (qC), 154.2 (qC).
Orange liquid; R = 0.59 (EtOAc–hexanes, 10:90).
f
+
1
HRMS (EI): m/z [M ] calcd for C H O: 172.0888; found:
H NMR (CDCl , 400 MHz): d = 0.82 (t, J = 12.1 Hz, 3 H), 1.22-
1
2
12
3
1
72.0886.
1.34 (m, 2 H), 1.51 (quint, J = 7.5 Hz, 2 H), 2.50 (t, J = 3.7 Hz,
2
H), 5.83 (dd, J = 0.8, 3.1 Hz, 1 H), 6.12 (dd, J = 1.8, 3 Hz, 1 H),
2
-(4-Acetylphenyl)furan (10l)
7.14 (d, J = 1.1 Hz, 1 H).
Following general procedure A; yield: 74% (110.0 mg).
13
C NMR (APT; CDCl , 100 MHz): d = 15.2 (CH ), 22.8 (CH ),
3
3
2
White solid; R = 0.24 (EtOAc–hexanes, 20:80).
28.1 (CH ), 30.0 (CH ), 104.2 (CH), 110.1 (CH), 140.6 (CH), 155.0
f
2 2
–
1
(qC).
All data were in good agreement with previously reported data.15
IR (CH Cl ): 1668, 1475, 1416, 1079, 1020 cm .
2
2
1
H NMR (CDCl , 300 MHz): d = 2.59 (s, 3 H), 6.46–6.54 (m, 1 H),
3
6
7
.78 (d, J = 3.3 Hz, 1 H), 7.51 (s, 1 H), 7.72 (d, J = 8.4 Hz, 2 H),
.95 (d, J = 8.4 Hz, 2 H).
2
-s-Butylfuran (10q)
Following general procedure B; yield: 55% (345 mg).
1
3
C NMR (APT; CDCl , 75 MHz): d = 26.5 (CH ), 107.5 (CH),
3
3
Orange liquid; R = 0.64 (EtOAc–hexanes, 10:90).
f
1
12.1 (CH), 123.5 (CH), 128.9 (CH), 134.9 (qC), 135.5 (qC), 143.3
–
1
(
CH), 152.8 (qC), 197.3 (CO).
IR (CH Cl ): 2967, 2870, 1539, 1457, 1378, 1111 cm .
2 2
+
1
HRMS (EI): m/z [M ] calcd for C H O : 186.0681; found:
H NMR (CDCl , 400 MHz): d = 0.81–0.86 (m, 3 H), 1.18 (d,
3
1
2
10
2
1
86.0687.
J = 7.0 Hz, 3 H), 1.21–1.37 (m, 2 H), 2.68 (q, J = 7.0 Hz, 1 H), 5.91
d, J = 3.3 Hz, 1 H), 6.20–6.22 (m, 1 H), 7.30–7.35 (m, 1 H).
(
2
-(4-Biphenyl)furan (10m)
13
C NMR (APT; CDCl , 100 MHz): d = 11.4 (CH ), 18.4 (CH ),
3
3
3
Following general procedure A; yield: 77% (170.0 mg).
2
8.5 (CH ), 38.2 (CH), 104.9 (CH), 109.7 (CH), 141.6 (CH), 160.5
2
Following general procedure B; yield: 20% (277 mg).
(C).
+
White solid; R = 0.33 (EtOAc–hexanes, 5:95).
HRMS (EI): m/z [M ] calcd for C H O: 124.0888; found:
f
8
12
–
1
124.0893.
IR (CH Cl ): 3054, 2987, 1600, 1478, 1265, 1158 cm .
2
2
1
H NMR (CDCl , 300 MHz): d = 6.42–6.40 (m, 1 H), 6.69 (d,
3
2-Cyclobutylfuran (10r)
Following general procedure B; yield: 51% (625 mg).
J = 3.3 Hz, 1 H), 7.32–7.37 (m, 1 H), 7.33–7.50 (m, 3 H), 7.62 (d,
J = 8.4 Hz, 4 H), 7.75 (d, J = 8.4 Hz, 2 H).
Orange liquid; R = 0.55 (EtOAc–hexanes, 10:90).
f
1
3
C NMR (APT; CDCl , 75 MHz): d = 105.1 (CH), 111.7 (CH),
3
–1
IR (CH Cl ): 2976, 2852, 2249, 1558, 1265, 1112 cm .
2
2
1
(
24.2 (CH), 126.9 (CH), 127.3 (CH), 128.8 (CH), 129.9 (qC), 140.0
1
qC), 140.6 (qC), 142.1 (CH), 153.8 (qC).
H NMR (CDCl , 400 MHz): d = 2.14–2.36 (m, 6 H), 3.50 (quint,
3
+
J = 8.4 Hz, 1 H), 5.99 (d, J = 3.1 Hz, 1 H), 6.27 (dd, J = 3.1, 1.9 Hz,
HRMS (EI): m/z [M ] calcd for C H O: 220.0888; found:
2
1
6
12
1
H), 7.29 (dd, J = 1.9, 0.8 Hz, 1 H).
20.0885.
1
3
C NMR (APT; CDCl , 100 MHz): d = 18.4 (CH ), 22.5 (CH ),
3
2
2
2
-(1-Naphthyl)furan (10n)
33.6 (CH), 104.9 (CH), 111.1 (CH), 140.7 (CH), 159.3 (qC).
Following general procedure A; yield: 87% (165.0 mg).
+
HRMS (EI): m/z [M ] calcd for C H O: 122.0732; found:
8
10
Colorless oil; R = 0.45 (EtOAc–hexanes, 10:90).
122.0735.
f
–
1
IR (CH Cl ): 3054, 2987, 1512, 1422, 1265, 1015 cm .
2
2
2
-Cyclopentylfuran (10s)
1
H NMR (CDCl , 300 MHz): d = 6.58 (dd, J = 3.3, 1.9 Hz, 1 H),
.71 (d, J = 3.3 Hz, 1 H), 7.40–7.56 (m, 3 H), 7.61 (d, J = 1.7 Hz,
H), 7.71 (dd, J = 7.2, 1.0 Hz, 1 H), 7.80–7.89 (m, 2 H), 8.37–8.41
3
Following general procedure B; yield: 44% (244 mg).
6
1
Colorless oil; R = 0.60 (EtOAc–hexanes, 10:90).
f
–
1
(
m, 1 H).
IR (neat): 3150, 3120, 2952, 1741, 1650, 1594, 1237, 1000 cm .
1
3
1
C NMR (APT; CDCl , 75 MHz): d = 109.2 (CH), 111.3 (CH),
H NMR (CDCl , 400 MHz): d = 1.43–1.92 (m, 6 H), 1.99–2.13 (m,
3
3
1
1
25.3 (CH), 125.6 (CH), 125.9 (CH), 126.2 (CH), 126.5 (CH),
28.5 (CH), 128.6 (CH), 128.7 (qC), 130.4 (qC), 134.0 (qC), 142.4
2 H), 3.12 (quint, J = 7.7 Hz, 1 H), 6.00 (d, J = 3.20 Hz, 1 H), 6.30
(m, 1 H), 7.33 (m, 1 H).
(
CH), 153.4 (qC).
13
C NMR (APT; CDCl , 100 MHz): d = 25.3 (CH ), 31.8 (CH ),
3
2
2
+
HRMS (EI): m/z [M ] calcd for C H O: 194.0732; found:
38.7 (CH), 103.1 (CH), 109.8 (CH), 140.6 (CH), 160.0 (qC).
1
4
10
1
94.0726.
+
HRMS (EI): m/z [M ] calcd for C H O: 136.0888; found:
9
12
1
36.0890.
2
-Cyclopropylfuran (10o)
Following general procedure B; yield: 35% (245 mg).
2
-Cyclohexylfuran (10t)
Light-red liquid; R = 0.61 (EtOAc–hexanes, 1:9).
Following general procedure B; yield: 56% (551 mg).
f
–
1
IR (neat): 3111, 3088. 1607, 1524, 1293, 1008 cm .
Colorless oil; R = 0.62 (EtOAc–hexanes, 10:90).
f
1
1
H NMR (CDCl , 400 MHz): d = 0.47–0.88 (m, 4 H), 2.64–2.71 (m,
H NMR (CDCl , 400 MHz): d = 1.20–1.41 (m, 6 H), 1.70–1.75 (m,
3
3
1
(
H), 5.88 (d, J = 3.1 Hz, 1 H), 6.20 (dd, J = 3.0, 2.0 Hz, 1 H), 7.17
1 H), 1.75–1.82 (m, 2 H), 1.99–2.05 (m, 2 H), 2.56–2.65 (m, 1 H),
5.93 (d, J = 3.2 Hz, 1 H), 6.27 (dd, J = 1.9, 3.2 Hz, 1 H), 7.29 (d,
J = 1.9 Hz, 1 H).
t, J = 1 Hz, 1 H).
1
3
C NMR (CDCl , 100 MHz): d = 8.6, 15.9, 104.6, 111.2, 141.6,
3
1
57.3.
Synthesis 2011, No. 5, 731–738 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Substituted Furans
737
1
3
+
C NMR (APT; CDCl , 100 MHz): d = 24.9 (CH ), 25.1 (CH ),
HRMS (EI): m/z [M ] calcd for C H FO: 162.0481; found:
162.0487.
3
2
2
10
7
3
0.51 (CH ), 36.3 (CH), 101.5 (CH), 108.9 (CH), 140.1 (CH), 160.0
2
(
qC).
All data were in good agreement with previously reported data.16
Acknowledgment
2
-Cycloheptylfuran (10u)
This work was supported by the Merck Frosst Centre for Therapeu-
tic Research, Natural Sciences and Engineering Research Council
of Canada (NSERC), and Boehringer Ingelheim (Canada) Ltd. J.H.
and R.D. thank the Ontario Government for providing postgraduate
scholarships (OGS).
Following general procedure B; yield: 46% (699 mg).
Colorless oil; R = 0.66 (EtOAc–hexanes, 10:90).
f
–
1
IR (neat): 2925, 2855, 1589, 1505, 1161, 1147, 1008 cm .
1
H NMR (CDCl , 400 MHz): d = 1.46–1.78 (m, 10 H), 1.96–2.05
m, 2 H), 2.80 (sept., J = 4.6 Hz, 1 H), 5.93 (dt J = 3.1, 0.8 Hz, 1 H),
3
(
References
6
.24 (dd, J = 3.1, 1.8 Hz, 1 H), 7.26 (dd, J = 1.8, 0.8 Hz, 1 H).
1
3
C NMR (APT; CDCl , 100 MHz): d = 22.4 (CH ), 28.4 (CH ),
(1) For reviews, see: (a) Rayabarapu, D. K.; Cheng, C.-H. Acc.
Chem. Res. 2007, 40, 971. (b) Lautens, M.; Fagnou, K.;
Heibert, S. Acc. Chem. Res. 2003, 36, 48.
3
2
2
3
(
3.2 (CH ), 39.2 (CH), 102.7 (CH), 109.8 (CH), 140.4 (CH), 161.8
2
qC).
(
2) For selected examples of ring opening reactions of 7-
oxabicyclo[2.2.1]heptenes, see: (a) Cho, Y.; Zunic, V.;
Senboku, H.; Olsen, M.; Lautens, M. J. Am. Chem. Soc.
+
HRMS (EI): m/z [M ] calcd for C H O: 164.1201; found:
1
1
1
16
64.1207.
2
006, 128, 6837. (b) Chen, C. L.; Martin, S. F. J. Org.
2
-Dodecylfuran (10v)
Chem. 2006, 71, 4810. (c) Wu, M.-S.; Jeganmohan, M.;
Cheng, C.-H. J. Org. Chem. 2005, 70, 9545. (d) Lautens,
M.; Hiebert, S. J. Am. Chem. Soc. 2004, 126, 1437.
Following general procedure B; yield: 40% (1.77 g).
White solid; R = 0.64 (EtOAc–hexanes, 10:90).
f
(
e) Leong, P.; Lautens, M. J. Org. Chem. 2004, 69, 2194.
IR: 4328, 4255, 3854, 3744, 2956, 2930, 2856, 2360, 2334, 1507,
–
1
(3) For selected examples of Ru-catalyzed [2+2] cycloadditions
of bicyclic alkenes and alkynes, see: (a) Villeneuve, K.;
Tam, W. Angew. Chem. Int. Ed. 2004, 43, 610. (b) Burton,
R. R.; Tam, W. Tetrahedron Lett. 2006, 47, 7185.
1
465, 1378, 1145, 1007 cm .
1
H NMR (CDCl , 400 MHz): d = 0.96 (t, J = 7.3 Hz, 3 H), 1.22–
.37 (m, 20 H), 2.65 (t, J = 8.3 Hz, 2 H), 6.46 (dd, J = 3.3, 2.1 Hz,
H), 6.57–6.58 (d, J = 3.3 Hz, 1 H), 7.41 (d, J = 1.0 Hz, 1 H).
3
1
1
(
c) Burton, R. R.; Tam, W. J. Org. Chem. 2007, 72, 7333.
1
3
C NMR (APT; CDCl , 100 MHz): d = 14.1 (CH ), 22.8 (CH ),
(d) Allen, A.; Villeneuve, K.; Cockburn, N.; Fatila, E.;
Riddell, N.; Tam, W. Eur. J. Org. Chem. 2008, 4178.
(4) (a) Villeneuve, K.; Tam, W. Eur. J. Org. Chem. 2006, 5499.
(b) Villeneuve, K.; Tam, W. Organometallics 2007, 26,
6082.
5) Villeneuve, K.; Tam, W. Organometallics 2006, 25, 843.
6) (a) Villeneuve, K.; Tam, W. J. Am. Chem. Soc. 2006, 128,
3
3
2
2
8.1 (CH ), 28.2 (CH ), 29.3 (CH ), 29.5 (CH ), 29.7 (CH ), 29.8
2 2 2 2 2
(
CH ), 29.8 (CH ), 29.8 (CH ), 29.9 (CH ), 32.1 (CH ), 33.9 (CH ),
2 2 2 2 2 2
1
04.5 (CH), 110.0 (CH), 140.6 (CH), 156.6 (qC).
+
HRMS (EI): m/z [M ] calcd for C H O: 236.2140; found:
1
6
28
(
(
2
36.2147.
3
514. (b) Ballantine, M.; Menard, M. L.; Tam, W. J. Org.
2
-Benzylfuran (10w)
Chem. 2009, 74, 7570.
Following general procedure B; yield: 15% (146 mg).
(
(
7) Allen, A.; Le Marquand, P.; Burton, R.; Villeneuve, K.;
Tam, W. J. Org. Chem. 2007, 72, 7849.
8) (a) Verkruijsse, H. D.; Keegstra, M. A.; Brandsma, L. Synth.
Commun. 1989, 19, 1047. (b) Keegstra, M. A.; Klomp, A.
J.; Brandsma, L. Synth. Commun. 1990, 20, 3371.
Colorless liquid; R = 0.67 (EtOAc–hexanes, 50:50).
f
IR: 3854, 3752, 3688, 3085, 3064, 3028, 2930, 2365, 2327, 1846,
1
–
1
653, 1496, 1472, 1455, 1377 cm .
1
H NMR (CDCl , 400 MHz): d = 3.19 (s, 2 H), 6.66 (dd, J = 3.4,
3
(c) Raheem, M.-A.; Nagireddy, J. R.; Durham, R.; Tam, W.
1
.8 Hz, 1 H), 6.83 (d, J = 3.4 Hz, 1 H), 7.44–7.48 (m, 3 H), 7.53–
.56 (m, 2 H).
Synth. Commun. 2010, 40, 2138.
7
(
9) Several primary and secondary 2-alkyl-substituted furans
have been prepared in 51–82% yield by the coupling of 2-
lithiated furan and the corresponding organoboranes, see:
Marinelli, E. R.; Levy, A. B. Tetrahedron Lett. 1979, 2313.
1
3
C NMR (APT; CDCl , 100 MHz): d = 37.9 (CH ), 105.0 (CH),
11.3 (CH), 125.9 (CH), 128.3 (CH), 128.4 (CH), 141.7 (CH),
41.7 (qC), 146.6 (qC).
3
2
1
1
+
(10) For early work on Fe-catalyzed alkenylations, see:
a) Kharasch, M. S.; Fuchs, C. F. J. Org. Chem. 1945, 10,
92. (b) Kharasch, M. S.; Lambert, F. L.; Urry, W. H. J. Org.
HRMS (EI): m/z [M ] calcd for C H FO: 158.0732; found:
1
0
7
(
2
1
58.0736.
Chem. 1945, 10, 298. (c) Tamura, M.; Kochi, J. K. J. Am.
Chem. Soc. 1971, 93, 1487.
11) For selected recent examples of Fe-catalyzed alkenylations,
see: (a) Molander, G. A.; Rahn, B. J.; Shubert, D. C.; Bonde,
S. E. Tetrahedron Lett. 1983, 24, 5449. (b) Czaplik, W. M.;
Mayer, M.; Cvengros, S.; Jacobi, A. ChemSusChem 2009, 2,
2
-(4-Fluorophenyl)furan (10x)
Following general procedure B; yield: 6% (72 mg).
(
Brown solid; R = 0.55 (EtOAc–hexanes, 20:80).
f
–
1
IR: 3744, 2960, 2361, 1560, 1507, 1499, 1233, 1155 cm .
1
H NMR (CDCl , 400 MHz): d = 6.50 (dd, J = 3.2, 1.8 Hz, 1 H),
3
3
(
2
96. (c) Cahiez, G.; Avedissian, H. Synthesis 1998, 1199.
d) Dohle, W.; Kopp, F.; Cahiez, G.; Knochel, P. Synlett
001, 1901. (e) Cahiez, G.; Habiak, V.; Duplais, C.;
6
7
.61 (d, J = 3.3 Hz, 1 H), 7.13–7.18 (m, 2 H), 7.50–7.53 (m, 2 H),
.67 (d, J = 3.4 Hz, 1 H).
1
3
C NMR (APT; CDCl , 100 MHz): d = 104.6 (CH), 111.6 (CH),
Moyeux, A. Angew. Chem. Int. Ed. 2007, 46, 4364.
(f) Fürstner, A.; Leitner, A.; Mendez, M.; Krause, H. J. Am.
Chem. Soc. 2002, 124, 13856. (g) Scheiper, B.;
3
1
15.6 (d, J = 21.5 Hz, CH), 125.4 (d, J = 8.0, CH), 128.5 (d, J = 8.1,
CH), 136.3 (d, J = 3.3 Hz, qC), 161.2 (qC), 163.6 (qC).
Bonnekessel, M.; Krause, H.; Fürstner, A. J. Org. Chem.
2004, 69, 3943. (h) Martin, R.; Fürstner, A. Angew. Chem.
Synthesis 2011, No. 5, 731–738 © Thieme Stuttgart · New York

7
38
J. Haner et al.
PAPER
(12) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43,
Int. Ed. 2004, 43, 3955. (i) Fürstner, A.; Martin, R. Chem.
Lett. 2005, 34, 624. (j) Fürstner, A.; Krause, H.; Lehmann,
C. W. Angew. Chem. Int. Ed. 2006, 45, 440. (k) Fürstner,
A.; Majima, K.; Martin, R.; Krause, H.; Kattnig, E.; Goddard,
R.; Lehmann, C. W. J. Am. Chem. Soc. 2008, 130, 1992.
l) Guerinot, A.; Reymond, S.; Cossy, J. Angew. Chem. Int.
Ed. 2007, 46, 6521. (m) Xu, X.; Cheng, D.; Pei, W. J. Org.
Chem. 2006, 71, 6637.
2923.
(13) Neumann, S. M.; Kochi, J. K. J. Org. Chem. 1975, 40, 599.
(14) Krasovskiy, A.; Knochel, P. Synthesis 2006, 890.
(15) Cohen, T.; Nolan, S. M. J. Org. Chem. 1981, 46, 2476.
(16) Eom, D. K.; Choi, S. J.; An, D. K. Heterocycles 2007, 71,
1141.
(
Synthesis 2011, No. 5, 731–738 © Thieme Stuttgart · New York