Synthesis of substituted acetylenic epoxides followed by indium-catalyzed rearrangement to 2,3,5-trisubstituted furans

Article abstract of DOI:10.1021/jo2001353

Syntheses of various aromatic and aliphatic 2,3,5-trisubstituted furans from acetylenic epoxides are described. These epoxides are directly prepared by nucleophilic ring closure of propargylic alkoxides generated by lithium acetylide addition to α-haloketones.

Full text of DOI:10.1021/jo2001353

NOTE
pubs.acs.org/joc
Synthesis of Substituted Acetylenic Epoxides Followed by
Indium-Catalyzed Rearrangement to 2,3,5-Trisubstituted Furans
Jun Yong Kang and Brian T. Connell*
Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, Texas 77842-3012, United States
S Supporting Information
b
ABSTRACT: Syntheses of various aromatic and aliphatic 2,3,5-
trisubstituted furans from acetylenic epoxides are described.
These epoxides are directly prepared by nucleophilic ring
closure of propargylic alkoxides generated by lithium acetylide
addition to R-haloketones.
he Feist-Benary synthesis is a classic method for accessing
furans, occcuring via a condensation reaction between R-
ketone intermediates,14 as well as by nucleophilic ring closure of
propargylic alcohols derived from R-haloketones and acetylides.15
We found the addition of lithium acetylides to R-bromoketones
to proceed very efficiently as summarized in Table 1. When lithium
phenyl acetylide 1a was treated with 2-bromopropiophenone (2a),
phenyl acetylenic R,β-epoxide 3a was obtained in quantitative yield
(Table 1, entry 1). Very good yields are also obtained when
β-substituted ketones were employed (Table 1, entries 2 and 3)
(89% and 85%, respectively). Treatment of aliphatic ketone 2d
with acetylide 1a also proceeded well, providing a 90% yield of
epoxide 3d. A somewhat lower yield (70%) of epoxide product 3e
was obtained when an acetylide containing an electron-withdraw-
ing substituent (1b) was utilized (Table 1, entry 5). When silyl-
protected acetylides 1c and 1d were treated with 2a, epoxides 3f
and 3g were obtained in 95% and 99% yields, respectively (Table 1,
entries 6 and 7). Aliphatic substituted acetylide 1e yielded 3h in
96% yield upon treatment with 2a.
The relative stereochemistry of the epoxides is consistent with
Felkin-Anh addition to the ketone, followed by SN2 displace-
ment of the bromide by the neighboring incipient alkoxide.16,17
Stereochemistry was determined by NOE analysis (see the
Supporting Information). It is worth noting that cyclization of
a conformationally restricted R-haloketone, 2-bromo-1-inda-
none, failed to occur. The required backside displacement of
the bromide by the neighboring alkoxide could not occur, as
nucleophilic attack from the less hindered side of the ketone
produces the unreactive syn-hydroxybromide (eq 1).
T
haloketones and β-dicarbonyl compounds.1 Furans are some of
the most-synthesized heterocyclic compounds due to their
versatile applications in organic synthesis and numerous appear-
ances in natural products.2 Since Feist disclosed his synthesis of
furans in 1902,1 many different synthetic methods toward furan
synthesis have been reported.
Recent works directly toward furans have featured transition
metal-catalyzed reactions and Lewis acid-mediated syntheses. For
example, palladium-catalyzed cyclization of acetylenic ketones
furnishes substituted furans,3 platinum-catalyzed cyclization of
propargylic oxiranes in aqueous media proceeds successfully to
give trisubstituted furans,4 gold-mediated transformations of alky-
nylepoxides to furans have been disclosed,5 and molybdenum-
catalyzed cyclization of propagylic oxiranes is well-known.6 Lewis
acid-mediated syntheses, including use of ZnCl2 for cycloisome-
rization of alkynyl ketones to furans7 and AgOTf-mediated iso-
merization of alkynylepoxides,8 have been reported.
However, transition metal-catalyzed syntheses of furans have
suffered from moderate yields for Pd(II)3 and Pt(II)4 and limited
substrate scope for Au(III)5 and Mo(V).6 Some Lewis acid-mediated
syntheses of furans exhibit poor functional group tolerance.8
We desired an efficient methodology employing mild and
atom-economical reaction conditions. Indium attracted our
attention both because it is a readily available Lewis acid and is
exceptionally stabile to water and air.9 Indium has been reported
to enable allylation of aldehydes as well as aldol and Mannich
reactions.9 In spite of its potential versatile utility, indium-
mediated rearrangements and isomerizations have been reported
in limited cases, such as the Ferrier rearrangement10 and the
Beckman rearrangement.11 Herein, we report a mild and efficient
furan synthesis under indium catalysis via rearrangement of
acetylenic R,β-epoxides that are prepared by treatment of
R-haloketones with lithium acetylides.
Table 2 summarizes our initial cycloisomerization studies.
Palladium,18 known for cyclization of acetylenic ketones to
furans, and platinum,4 known for cyclization of propargylic
oxiranes to furans, were employed under standard reaction
Acetylenic R,β-epoxides have been prepared by various meth-
ods, including Sonogashira cross-coupling12 of alkynes and vinyl
halides and subsequent epoxidation,13 a cascade reaction of
alkynyl halides and disubstituted phenones via R-brominated
Received: January 28, 2011
Published: March 09, 2011
r
2011 American Chemical Society
2379
dx.doi.org/10.1021/jo2001353 J. Org. Chem. 2011, 76, 2379–2383
|

The Journal of Organic Chemistry
NOTE
Table 1. Formation of Epoxides upon Treatment of r-Bro-
Table 3. Scope of the Cycloisomerization Reactiona
moketones with Lithium Acetylidesa
entry
3, R1
Ph
3, R2
3, R3
product
yield (%)b
1
2
3
4
5
6
7
Ph
Ph
Ph
n-Pr
Ph
Ph
Ph
Me
Bn
3a
3b
3c
3d
3e
3f
4a
4b
4c
4d
4e
4f
>99
84c
84c
95
90c
>99
>99
entry
1, R1
2, R2 2, R3
product yield (%)b
Ph
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
1a Ph
Me
Bn
2a 3a
>99
89c
85c
90c
70
Ph
i-Pr
Et
1a Ph
1a Ph
1a n-Pr
1b Ph
1c Ph
2b 3b
2c 3c
2d 3d
2a 3e
2a 3f
2a 3g
2a 3h
Ph
i-Pr
Et
CO2Et
Si(CH3)3
n-Pr
Me
Me
Me
CO2Et
Me
Me
Me
Me
3h
4h
a Reactions were performed with acetylenic R,β-epoxides 3 (0.17 mmol)
and InCl3 (0.0085 mmol) in 1 mL of toluene at 70 °C for 20 min then
quenched with water. b Isolated yield after column chromatography.
c Calculated yield accounting for inseparable impurities. (See the Sup-
porting Information for spectra and details of purity.)
Si(CH3)3
95
Si(CH2CH3)3 1d Ph
99
n-Pr 1e Ph
96
a Reactions were performed with lithium acetylides 1 (0.35 mmol) and
R-haloketones 2 (0.32 mmol) in 1 mL of THF at rt for 2 h and quenched
with sat. NaHCO3. b Isolated yield after column chromatography.
c Calculated yield accounting for inseparable impurities. (See the Sup-
porting Information for spectra and details of purity.)
Scheme 1. Proposed Mechanistic Cycle for Alkynyl Epoxide
Cycloisomerization
Table 2. Initial Cycloisomerization Resultsa
entry
catalyst
temp, °C
time
48 h
yield (%)b
1
2
3
4
5
6
7
8
Pd2(dba)3, PPh3
Pt[(C2H5)2S]2Cl2
AuCl3
100
100
100
100
100
70
16
90
48 h
48 h
48 h
20 min
20 min
1 h
70
CuI
21
InCl3
>99
>99
95
InCl3
clean reaction to provide the desired product 4a in quantitative
yield after 20 min at 70 °C (Table 3, entry 1). To test the effect of
the nature of the β-substituents on epoxides, benzyl and isopropyl
β-substituted epoxides (Table 3, entries 2 and 3) were tested with
the following reaction conditions: 70 °C, 20 min, toluene. Results
indicate that β-substituted epoxides work well, providing 84%
yield (Table 3, entries 2 and 3) and indicating that adverse steric
interactions appear to be minor in this reaction.
When epoxide 3d was treated with InCl3 (5 mol %) under
standard reaction conditions, the furan 4d was obtained in 95%
yield (Table 3, entry 4). We were also interested in examining the
utility of this method with different substitutents on the alkyne.
Treatment of alkynyl epoxide 3e, containing an electron-with-
drawing alkynyl ester, under the reaction conditions proceeded
well, providing a 90% yield of product 4e (Table 3, entry 5).
Trimethylsilyl-protected alkynyl epoxide 3f also showed quanti-
tative conversion to furan 4f. However, it should be noted that
the closely related triethylsilyl-protected alkynyl epoxide unex-
pectedly decomposed upon exposure to the standard reaction
conditions. Aliphatic alkynyl epoxide 3h also converted to furan
4h in quantitative yield (Table 3, entry 7).
InCl3
50
InCl3
40
1 h
10
a Reactions were performed with acetylenic R,β-epoxides (0.17 mmol)
3a and catalysts (0.0085 mmol) in 1 mL of toluene and quenched
with water. b Isolated yield.
conditions (100 °C, 48 h, toluene) but the results showed either
low yield (Pd) of products or the necessity for extended reaction
times (Pt) (Table 2, entries 1 and 2). Gold and copper catalysts
afforded low to moderate yield of the product (Table 2, entries 3
and 4).
Gratifyingly, InCl3-catalyzed cycloisomerization led to furan
4a in a quantitative yield in only 20 min (Table 2, entry 5).
Lowering the temperature to 70 °C maintained the excellent
results (Table 2, entry 6). However, when temperature was
lowered below 70 °C, the reaction slowed down (Table 2, entries
7 and 8). Toluene is the solvent of choice. Ethereal solvents,
including THF and 1,4-dioxane, led to either low yield of
products and/or decomposition.
With these reaction conditions in hand, we explored the scope
of this reaction with various epoxides and the results are summar-
ized in Table 3. The parent acetylenic R,β-epoxide 3a underwent
A proposed mechanistic cycle for the cycloisomerization is
shown in Scheme 1. Coordination of indium complex to the
2380
dx.doi.org/10.1021/jo2001353 |J. Org. Chem. 2011, 76, 2379–2383

The Journal of Organic Chemistry
NOTE
epoxide 3a is followed by opening of the epoxide to generate
zwitterion 5. An apparent 1,3-hydride shift19 then generates
intermediate benzylic cation/enolate 6, which undergoes nu-
cleophilic C-O bond formation and loss of InCl3, affording the
observed furan product 4a.
In summary, we have reported a mild, efficient, catalytic
cycloisomerization reaction that transforms acetylenic R,β-ep-
oxides to 2,3,5-trisubstituted furans by InCl3 catalysis. The
acetylenic R,β-epoxides are prepared by nucleophilic ring closure
of propargylic alcohol synthesized by coupling R-haloketones
with acetylides. This reaction sequence allows rapid access to
valuable, highly substituted furan derivatives.
34.0; HRMS (MALDI) calcd for C23H18O [M þ H]þ 311.1436, found
311.1442.
(2S,3R)-3-Isopropyl-2-phenyl-2-(phenylethynyl)oxirane (3c).
(Phenylethynyl)lithium 1a (0.35 mmol, 38 mg, 1.1 equiv) and halide 2c
(0.32 mmol, 77 mg, 1.0 equiv) were subjected to the reaction conditions
described in GP1. Flash column chromatography on SiO2 eluting with
hexanes:CH2Cl2 (1:1) provides a colorless oil (80 mg, 95%, ca. 90% pure
by 1H and 13C NMR). Rf 0.76 (hexanes:CH2Cl2 = 1:1); IR (film, cm-1
)
2226, 1320, 891, 755; 1H NMR (300 MHz, CDCl3) δ 7.60-7.56
(m, 2H), 7.52-7.47 (m, 2H), 7.45-7.31 (m, 6H), 3.27 (d, J = 8.3 Hz,
1H), 1.13 (app s, 4H), 0.82 (d, J = 6.7 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 135.9, 132.0, 128.7, 128.3, 128.1, 128.0, 126.9, 122.3, 89.1,
82.9, 73.0, 56.7, 26.8, 19.6, 17.9; HRMS (MALDI) calcd for C19H18O
[M þ H]þ 263.1436, found 263.1428.
’ EXPERIMENTAL SECTION
(2S,3R)-3-Ethyl-2-(phenylethynyl)-2-propyloxirane (3d).
(Phenylethynyl)lithium 1a (0.35 mmol, 38 mg, 1.1 equiv) and halide
2d (0.32 mmol, 62 mg, 1.0 equiv) were subjected to the reaction
conditions described in GP1 to afford a colorless oil (68 mg, >99%, ca.
90% pure by 1H and 13C NMR). Rf 0.61 (hexanes:CH2Cl2 = 1:1); IR
General Information. All reactions were carried out under an
argon atmosphere in oven-dried glassware with magnetic stirring. Dry
THF and toluene were obtained by a solvent purification system under
argon. All commercially obtained reagents were used as received.
Purification of reaction products was carried out by flash column
chromatography, using silica gel 60 (230-400 mesh). Analytical thin
layer chromatography was performed on 0.25 mm glass-backed silica gel
60-F plates. Visualization was accompanied with UV light and KMnO4
solution. Concentration in vacuo refers to the removal of volatile solvent
using a rotary evaporator attached to a dry diaphragm pump (10-15
mmHg) followed by pumping to a constant weight with an oil pump
(<300 mTorr). 1H NMR spectra are recorded at 300 or 500 MHz and
1
(film, cm-1) 2226, 1302, 909, 752; H NMR (300 MHz, CDCl3) δ
7.47-7.45 (m, 2H), 7.35-7.32 (m, 3H), 3.24 (t, J = 6.58 Hz, 1H),
1.47-1.62 (m, 6H), 1.15-1.01 (m, 6H); 13C NMR (75 MHz, CDCl3)
δ 131.9, 128.6, 128.2, 122.4, 89.1, 82.6, 66.5, 55.3, 33.7, 21.5, 19.2, 14.1,
10.5; HRMS (ESI) calcd for C15H18O [M þ H]þ 215.1436, found
215.1442.
Ethyl 3-((2S,3R)-3-Methyl-2-phenyloxiran-2-yl)propiolate
(3e). (3-Ethoxy-3-oxoprop-1-yn-1-yl)lithium 1b (0.35 mmol, 36 mg,
1.1 equiv) and halide 2a (0.32 mmol, 68 mg, 1.0 equiv) were subjected to
the reaction conditions described in GP1. Flash column chromatogra-
phy on SiO2 eluting with hexanes:CH2Cl2 (1:1) provides a colorless oil
(52 mg, 70%). Rf 0.64 (hexanes:CH2Cl2 = 2:1); IR (film, cm-1) 2235,
1708, 1220, 953, 870; 1H NMR (300 MHz, CDCl3) δ 7.45-7.33
(m, 5H), 4.22 (q, J = 7.2 Hz, 2H), 3.64 (q, J = 5.4 Hz, 1H), 1.28 (t, J = 6.9
Hz, 3H), 1.06 (d, J = 5.4 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 135.7,
132.1, 128.7, 128.3, 128.1, 128.0, 127.1, 122.2, 88.92, 82.9, 63.5, 56.2,
13.4; HRMS (ESI) calcd for C14H14O3 [M þ H]þ 231.1021, found
231.1013.
1
are recorded relative to CDCl3 (δ 7.26) or TMS (δ 0.00). H NMR
coupling constants (J) are reported in hertz (Hz) and multiplicities are
indicated as follows: s (singlet), bs (broad singlet), d (doublet), t
(triplet), m (multiplet). Proton-decoupled 13C NMR spectra are
recorded at 75 or 125 MHz and are reported relative to CDCl3 (δ 77).
General Procedure (GP1) for Synthesis of Oxiranes:
(2S,3R)-3-Methyl-2-phenyl-2-(phenylethynyl)oxirane (3a).
To a drum vial were added R-haloketone 2a (0.32 mmol, 68 mg, 1.0
equiv) and THF (1.0 mL). The vial was cooled to -78 °C and followed
by addition of (phenylethynyl)lithium 1a (0.35 mmol, 38 mg, 1.1 equiv),
which was prepared from phenyl acetylene (1.0 equiv) and n-BuLi (1.01
equiv) in THF at -78 °C. After complete addition of 1a, the reaction
mixture was warmed to room temperature and stirred for 2 h. The
reaction mixture was quenched by a saturated aqueous NaHCO3
solution (1.5 mL) and the layers were separated and the aqueous layer
was extracted with Et2O. The combined organic layers were washed with
brine, dried over MgSO4, filtered, and concentrated under reduced
pressure. Purification was accomplished by flash chromatography
to afford alkynyl oxiranes 3a as a colorless oil (75 mg, >99% yield).
Rf 0.6 (hexanes:CH2Cl2 = 1:1); IR (film, cm-1) 2229, 1317, 938, 867;
1H NMR (300 MHz, CDCl3) δ 7.59-7.57 (m, 2H), 7.51-7.49
(m, 2H), 7.48-7.41 (m, 2H), 7.39-7.33 (m, 4H), 3.74(q, J = 5.5 Hz,
1H), 1.14(d, J = 5.4 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 135.7,
132.1, 128.7, 128.3, 128.1, 128.0, 127.1, 122.2, 88.92, 82.9, 63.5, 56.2,
13.4; HRMS (ESI) calcd for C17H15O [M þ H]þ 235.1123, found
235.1131.
(2S,3R)-3-Benzyl-2-phenyl-2-(phenylethynyl)oxirane (3b).
(Phenylethynyl)lithium 1a (0.35 mmol, 38 mg, 1.1 equiv) and halide
2b (0.32 mmol, 92 mg, 1.0 equiv) were subjected to the reaction
conditions described in GP1. Flash column chromatography on SiO2
eluting with hexanes:CH2Cl2 (1:1) provides a colorless oil (96 mg, 99%,
ca. 90% pure by 1H and 13C NMR). Rf10.83 (hexanes:CH2Cl2 = 1:1); IR
(film, cm-1) 2226, 1317, 938, 879; H NMR (300 MHz, CDCl3) δ
7.71-7.67 (m, 2H), 7.55-7.26 (m, 11H), 7.26-7.13 (m, 2H), 3.88
(t, J = 6.3 Hz, 1H), 2.79 (dd, J = 14.8, 6.1 Hz, 1H), 2.63 (dd, J = 14.8, 6.4
Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 136.7, 135.5, 132.0, 128.9,
128.8, 128.7, 128.3, 128.3, 127.2, 126.7, 122.1, 88.6, 83.2, 67.5, 56.5,
Trimethyl(((2S,3R)-3-methyl-2-phenyloxiran-2-yl)ethynyl)-
silane (3f). ((Trimethylsilyl)ethynyl) lithium 1c (0.35 mmol, 36 mg,
1.1 equiv) and halide 2a (0.32 mmol, 68 mg, 1.0 equiv) were subjected to
the reaction conditions described in GP1. Flash column chromatogra-
phy on SiO2 eluting with hexanes:CH2Cl2 (1:1) provides a colorless oil
(70 mg, 95%). Rf 0.75 (hexanes:CH2Cl2 = 1:1); IR (film, cm-1) 2173,
1
1249, 938, 844; H NMR (300 MHz, CDCl3) δ 7.52-7.34 (m, 5H),
3.62 (q, J = 5.4 Hz, 1H), 1.07 (d, J = 5.4 Hz, 3H), 0.23 (s, 9H); 13C NMR
(75 MHz, CDCl3) δ 135.3, 128.0, 128.0, 127.1, 104.8, 88.1, 63.3, 55.9,
13.2, -0.12; HRMS (ESI) calcd for C14H18OSi [M þ H]þ 231.1205,
found 231.1213.
Triethyl(((2S,3R)-3-methyl-2-phenyloxiran-2-yl)ethynyl)-
silane (3g). ((Triethylsilyl)ethynyl) lithium 1d (0.35 mmol, 51 mg, 1.1
equiv) and halide 2a (0.32 mmol, 68 mg, 1.0 equiv) were subjected to
the reaction conditions described in GP1. Flash column chromatogra-
phy on SiO2 eluting with hexanes:CH2Cl2 (1:1) provides a colorless oil
(86 mg, 99%). Rf 0.70 (hexanes:CH2Cl2 = 1:1); IR (film, cm-1) 2170,
1
1240, 938, 864; H NMR (300 MHz, CDCl3) δ 7.52-7.33 (m, 5H),
3.62 (q, J = 5.4 Hz, 1H), 1.08 (d, J = 5.8 Hz, 3H), 1.03 (t, J = 8.3 Hz, 9H),
0.65 (q, J = 7.8 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 135.4, 128.0,
127.9, 127.1, 106.1, 85.8, 63.5, 56.0, 13.1, 7.5, 4.3; HRMS (ESI) calcd for
C17H24OSi [M þ H]þ 273.1675, found 273.1662.
(2S,3R)-3-Methyl-2-(pent-1-yn-1-yl)-2-phenyloxirane (3h).
Pent-1-yn-1-yllithium 1e (0.35 mmol, 26 mg, 1.1 equiv) and halide 2a
(0.32 mmol, 68 mg, 1.0 equiv) were subjected to the reaction conditions
described in GP1. Flash column chromatography on SiO2 eluting with
hexanes:CH2Cl2 (1:1) provides a colorless oil (61 mg, 96%). Rf 0.60
2381
dx.doi.org/10.1021/jo2001353 |J. Org. Chem. 2011, 76, 2379–2383

The Journal of Organic Chemistry
NOTE
(hexanes:CH2Cl2 = 1:1); IR (film, cm-1) 2238, 1448, 867, 752; H
NMR (300 MHz, CDCl3) δ 7.51-7.29 (m, 5H), 3.57(q, J = 5.4 Hz,
1H), 2.24(t, J = 7.1 Hz, 2H), 1.64-1.52 (m, 2H), 1.07 (d, J = 5.4 Hz,
3H), 1.01 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 136.2,
127.9, 127.8, 127.0, 83.9, 80.1, 63.1, 56.1, 21.9, 20.8, 13.6, 13.3; HRMS
(ESI) calcd for C14H16O [M þ H]þ 201.1279, found 201.1282.
(1R,2S)-2-Bromo-1-(phenylethynyl)-2,3-dihydro-1H-inden-
1-ol (S1). (Phenylethynyl)lithium 1a (0.35 mmol, 38 mg, 1.1 equiv)
and 2-bromoindanone (0.32 mmol, 68 mg, 1.0 equiv) were subjected to
the reaction conditions described in GP1 for 40 h to afford a colorless oil
(60 mg, 60%, ca. 90% by pure by 1H and 13C NMR). Rf 0.33 (hexanes:
Et2O = 5:1); IR (film, cm-1) 3521, 3052, 2228, 1338, 922, 869;
1H NMR (300 MHz, CDCl3) δ 7.77-7.73 (m, 1H), 7.52-7.44 (m, 2H),
7.42-7.29 (m, 6H), 4.84 (t, J = 7.3 Hz, 1H), 3.54-3.39 (m, 2H), 3.08
(s, 1H); 13C NMR (75 MHz, CDCl3) δ 142.1, 140.2, 132.0, 129.9,
128.9, 128.4, 127.9, 124.8, 124.6, 122.0, 88.0, 85.4, 76.1, 60.3, 39.7;
HRMS (MALDI) calcd for C17H13BrO [M þ Na]þ 335.0048, found
335.0037.
CDCl3) δ 152.6, 151.0, 131.4, 128.6, 126.6, 123.3, 120.5, 107.3, 26.9,
23.9, 19.6, 13.9, 13.5; HRMS (MALDI) calcd for C15H18O [M þ H]þ
215.1436, found 215.1444.
1
Ethyl 5-Methyl-4-phenylfuran-2-carboxylate (4e). Oxirane
3e (0.17 mmol, 40 mg 1.0 equiv) and InCl3 (0.0085 mmol, 1.9 mg, 0.05
equiv) were subjected to the reaction conditions described in GP2 to
afford a colorless oil (40 mg, ca. 90% pure by 1H and 13C NMR). Rf 0.15
(hexanes:CH2Cl2 = 1:1); IR (film, cm-1) 3061, 1720, 1619, 1187;
1H NMR (300 MHz, CDCl3) δ 7.43-7.38 (m, 5H), 6.26 (s, 1H), 4.31
(q, J = 7.0 Hz, 2H), 2.51 (s, 3H), 1.36 (t, J = 7.45 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 163.4, 130.0, 129.3, 128.8, 128.6, 114.1, 92.9, 61.8, 28.8,
24.4, 14.3; HRMS (ESI) calcd for C14H14O3 231.1021, found 231.1010.
Trimethyl(5-methyl-4-phenylfuran-2-yl)silane (4f). Oxirane
3f (0.17 mmol, 39 mg 1.0 equiv) and InCl3 (0.0085 mmo0l, 1.9 mg, 0.05
equiv) were subjected to the reaction conditions described in GP2 to
afford a colorless oil (39 mg, >99%). Rf 0.64 (hexanes:CH2Cl2 = 1:1); IR
(film, cm-1) 3061, 2176, 1909, 1249, 850; 1H NMR (300 MHz, CDCl3)
δ 7.48-7.34 (m, 5H), 4.60 (s, 1H), 2.24 (s, 3H), 0.26 (s, 9H); 13C NMR
(75 MHz, CDCl3) δ 202.7, 134.6, 128.9, 128.0, 127.9, 101.3, 92.5, 53.7,
25.9, 0.0; HRMS (ESI) calcd for C14H18OSi [M þ Na]þ 253.1025,
found 253.1014.
General Procedure (GP2) for Synthesis of Furans: 2-Meth-
yl-3,5-diphenylfuran (4a). A drum vial was charged with InCl3
(5 mol %, 0.0085 mmol, 0.05 equiv) in the drybox. To the vial was added
a THF (1 mL) solution of oxiranes 3a (0.17 mmol, 40 mg 1.0 equiv) and
the vial was then placed in a 70 °C oil bath for 20 min. After 20 min of
stirring at 70 °C the reaction mixture was cooled to room temperature
and quenched by addition of water. The layers were separated and the
aqueous layer was extracted with Et2O. The combined organic layers
were washed with brine, dried over MgSO4, filtered, and concentrated
under reduced pressure. Purification was accomplished by flash chro-
matography to afford furan as a colorless oil 4a (40 mg, >99% yield).
Rf 0.83 (hexanes:CH2Cl2 = 1:1); IR (film, cm-1) 3061, 1599, 1495,
1448, 1018; 1H NMR (300 MHz, CDCl3) δ 7.76-7.73 (m, 2H), 7.53-
7.42 (m, 6H), 7.38-7.27 (m, 2H), 6.85 (s, 1H), 2.58 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 151.6, 147.6, 134.1, 130.8, 128.7, 128.6, 127.5,
127.0, 126.5, 123.4, 123.0, 106.4, 13.2; HRMS (ESI) calcd for C17H14O
[M þ Na]þ:257.0942, found 257.0949.
2-Methyl-3-phenyl-5-propylfuran (4h). Oxirane 3h (0.17
mmol, 34 mg 1.0 equiv) and InCl3 (0.0085 mmol, 1.9 mg, 0.05 equiv)
were subjected to the reaction conditions described in GP2 to afford a
colorless oil (34 mg, >99%). Rf 0.88 (hexanes:CH2Cl2 = 1:1); IR
1
(film, cm-1) 3061, 1581, 1495, 1448; H NMR (300 MHz, CDCl3)
δ 7.48-7.26 (m, 5H), 6.18 (s, 1H), 2.62 (t, J = 7.24 Hz, 2H), 2.47
(s, 3H), 1.81-1.69 (m, 2H), 1.06 (t, J = 7.50 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 154.2, 145.8, 134.7, 128.6, 127.4, 126.1, 121.2,
106.3, 30.1, 21.5, 13.9, 13.1; HRMS (ESI) calcd for C14H16O [M þ H]þ
201.1279, found 201.1289.
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra of
S
b
2-Benzyl-3,5-diphenylfuran (4b). Oxirane 3b (0.17 mmol,
53 mg 1.0 equiv) and InCl3 (0.0085 mmol, 1.9 mg, 0.05 equiv) were
subjected to the reaction conditions described in GP2 to afford a colo-
rless oil (53 mg, ca. 85% pure by 1H and 13C NMR). Rf 0.56 (hexanes-
new compounds and stereochemical proofs. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
1
CH2Cl2 = 1:1); IR (film, cm-1) 3064, 1599, 1495, 1448; H NMR
Corresponding Author
*E-mail: connell@chem.tamu.edu.
(300 MHz, CDCl3) δ 7.78-7.73 (m, 2H), 7.52-7.27 (m, 13H), 6.89
(s, 1H), 4.27 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 152.5, 149.0, 138.6,
133.8, 130.8, 128.7, 128.7, 128.7, 128.4, 127.8, 127.3, 126.9, 126.5, 125.7,
123.7, 106.7, 33.0; HRMS (MALDI) calcd for C23H18O [M þ H]þ
311.1436, found 311.1422.
’ ACKNOWLEDGMENT
2-Isopropyl-3,5-diphenylfuran (4c). Oxirane 3c (0.17 mmol,
53 mg 1.0 equiv) and InCl3 (0.0085 mmol, 1.9 mg, 0.05 equiv) were
subjected to the reaction conditions described in GP2 to afford a
colorless oil (45 mg, ca. 85% pure by 1H and 13C NMR). Rf 0.72
(hexanes:CH2Cl2 = 1:1); IR (film, cm-1) 3058, 1593, 1495; 1H NMR
(300 MHz, CDCl3) δ 7.79-7.72 (m, 2H), 7.51-7.27 (m, 8H), 6.79
(s, 1H), 3.39-3.29 (m, 1H), 1.43 (d, J = 7.0 Hz, 6H); 13C NMR
(75 MHz, CDCl3) δ 156.0, 151.4, 134.4, 131.1, 128.7, 128.6, 128.1,
127.1, 126.6, 126.0, 123.5, 106.7, 26.7, 23.7, 21.9; HRMS (MALDI)
calcd for C19H18O [M þ H]þ 263.1436, found 263.1448.
The Robert A. Welch Foundation (A-1623) is acknowledged
for support of this research.
’ REFERENCES
(1) Feist, F. Ber. Dtsch. Chem. 1902, 35, 1537–1544.
(2) Meegan, M. J.; Donnelly, D. M. X. In Comprehensive Heterocyclic
Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: New York,
1984; Vol. 4, pp 657-712.
(3) Fukuda, Y.; Shiragami, H.; Utimoto, K.; Nozaki, H. J. Org. Chem.
1991, 56, 5816–5819.
(4) Yoshida, M.; Al-Amin, M.; Shishido, K. Synthesis 2009, 2454–2466.
(5) Hashmi, A. S. K.; Sinha, P. Adv. Synth. Catal. 2004, 346, 432–438.
(6) McDonald, F. E.; Schultz, C. C. J. Am. Chem. Soc. 1994,
116, 9363–9364.
(7) Sniady, A.; Durham, A.; Morreale, M. S.; Wheeler, K. A.;
Dembinski, R. Org. Lett. 2007, 9, 1175–1178.
(8) Blanc, A.; Tenbrink, K.; Weibel, J.-M.; Pale, P. J. Org. Chem.
2009, 74, 4360–4363.
(9) Loh, T.-P.; Chua, G.-L. Chem. Commun. 2006, 2739–2749.
2-Ethyl-5-phenyl-3-propylfuran (4d). Oxirane 3d (0.17 mmol,
36 mg 1.0 equiv) and InCl3 (0.0085 mmol, 1.9 mg, 0.05 equiv) were
subjected to the reaction conditions described in GP2. Flash column
chromatography on SiO2 eluting with hexanes:CH2Cl2 (20:1) provides
a colorless oil (35 mg, 95%). Rf 0.85 (hexanes:CH2Cl2 = 1:1); IR
(film, cm-1) 3061, 1599, 1486, 1456, 1024; 1H NMR (300 MHz,
CDCl3) δ 7.67-7.65 (m, 2H), 7.41-7.21 (m, 3H), 6.52 (s, 1H), 2.70
(q, J = 7.94 Hz, 2H), 2.39 (t, J = 7.58 Hz, 2H), 1.68-1.56 (m, 2H), 1.31
(t, J = 7.72 Hz, 3H), 1.00 (t, J = 7.42 Hz, 3H); 13C NMR (75 MHz,
2382
dx.doi.org/10.1021/jo2001353 |J. Org. Chem. 2011, 76, 2379–2383

The Journal of Organic Chemistry
NOTE
(10) Boga, S. B.; Kalpattu, K. B. Tetrahedron Lett. 2000, 41, 1271–1274.
(11) Barman, D. C.; Thakur, A. J.; Prajapati, D.; Sandhu, J. S. Chem.
Lett. 2000, 29, 1196–1197.
(12) Lemay, A. B.; Vulic, K. S.; Ogilvie, W. W. J. Org. Chem. 2006,
71, 3615–3618.
(13) Cao, G.-A.; Wang, Z.-X.; Tu, Y.; Shi, Y. Tetrahedron Lett. 1998,
39, 4425–4428.
(14) Trofimov, A.; Chernyak, N.; Gevorgyan, V. J. Am. Chem. Soc.
2008, 130, 13538–13539.
(15) (a) Russell, G. A.; Ros, F. J. Am. Chem. Soc. 1982, 104, 7349–7351.
(b) Russell, G. A.; Ros, F. J. Am. Chem. Soc. 1985, 107, 2506–2511.
(16) Anh, N. T. Top. Curr. Chem. 1980, 88, 146–161.
(17) Mengel, A.; Reiser, O. Chem. Rev. 1999, 99, 1191–1224.
(18) Sheng, H.; Lin, S.; Huang, Y. Synthesis 1987, 1022–1023.
(19) (a) Pasto, D. J.; Brophy, J. E. J. Org. Chem. 1991,
56, 4554–4556. (b) Eberle, M. K.; Kahle, G. G. J. Am. Chem. Soc.
1977, 99, 6038–6042.
2383
dx.doi.org/10.1021/jo2001353 |J. Org. Chem. 2011, 76, 2379–2383