Regioselective synthesis of highly functionalized furans through the RuII-catalyzed [3+2] cycloaddition of diazodicarbonyl compounds

Article abstract of DOI:10.1002/ejoc.201402067

A novel method for the Ru^II-catalyzed regioselective synthesis of highly functionalized furans from readily available cyclic and acyclic diazodicarbonyl compounds and terminal alkynes is described. The devised protocol offers a straightforward means to the construction of a variety of diverse furan derivatives through powerful cascade processes, including the formation of ruthenium carbenoid, cyclopropenation, ring-opening metathesis, and cyclization. Copyright

Full text of DOI:10.1002/ejoc.201402067

FULL PAPER
DOI: 10.1002/ejoc.201402067
Regioselective Synthesis of Highly Functionalized Furans Through the
RuII-Catalyzed [3+2] Cycloaddition of Diazodicarbonyl Compounds
Likai Xia[a] and Yong Rok Lee*[a]
Keywords: Synthetic methods / Cycloaddition / Oxygen heterocycles / Ruthenium / Diazo compounds / Alkynes
A novel method for the RuII-catalyzed regioselective synthe-
sis of highly functionalized furans from readily available
cyclic and acyclic diazodicarbonyl compounds and terminal
alkynes is described. The devised protocol offers a straight-
forward means to the construction of a variety of diverse
furan derivatives through powerful cascade processes, in-
cluding the formation of ruthenium carbenoid, cyclopropen-
ation, ring-opening metathesis, and cyclization.
hydrofurans.[12] As part of our ongoing studies on the tran-
sition-metal-catalyzed transformations of diazodicarbonyl
compounds to provide novel molecules, we became inter-
ested in the RuII-catalyzed cycloaddition of diazodicarbonyl
compounds to terminal alkynes. To the best of our knowl-
edge, the RuII-complex-catalyzed [3+2] cycloaddition of di-
azodicarbonyl compounds to alkynes has not been de-
scribed previously.
Introduction
Highly functionalized furans are among the most impor-
tant molecules found in biologically active natural products,
pharmaceuticals, and agrochemicals.[1] They have been
widely used as important scaffolds and as building blocks
for the construction of complex organic compounds and
materials.[2] Because of their importance, numerous meth-
ods for the synthesis of substituted furans have been devel-
oped based on intra-[3] and intermolecular cyclization reac-
tions.[4] Representative approaches include transition-metal-
catalyzed reactions, which have become powerful tools for
the preparation of a variety of furan derivatives:[5–9] Pd,[5]
Au,[6] Ag,[7] Cu,[8] and Ru[9] are widely used as metal cata-
lysts. The most direct and practical routes for the synthesis
of highly functionalized furans involve transition-metal-cat-
alyzed [3+2] cycloaddition reactions between diazo com-
pounds and acetylenes.[10] In particular, RhII-,[10a–10f]
CuI-,[10g] and CoII[10h]-catalyzed reactions between diazo-
dicarbonyl compounds and terminal alkynes have been suc-
cessfully conducted. Although a number of transition-
metal-catalyzed reactions between diazodicarbonyl com-
pounds and alkynes have been reported for the synthesis of
substituted furans, there still remains a need for novel and
improved synthetic routes for the preparation of highly
functionalized diverse furans with high chemo- and regio-
selectivities under mild conditions. We have reported on the
decomposition of cyclic diazodicarbonyl compounds with
various substrates as a powerful means for synthesizing
heterocycles and novel organic compounds.[11] Recently we
reported on RuII-catalyzed reactions between diazodicarb-
onyl compounds and olefins to afford multisubstituted di-
Thus, we provide herein examples of mild RuII-complex-
catalyzed cascade reactions between cyclic or acyclic diazo-
dicarbonyl compounds and various terminal alkynes for the
synthesis of diverse polyfunctionalized furan derivatives in
good to excellent yields and with high regioselectivity
(Scheme 1).
Scheme 1. RuII-catalyzed cycloaddition for the synthesis of furans
starting from diazodicarbonyl compounds.
Results and Discussion
First, the use of several promising transition-metal cata-
lysts were investigated for the synthesis of 6,7-dihydro-
benzofuran starting from commercially available 2-diazo-
5,5-dimethylcyclohexanedione (diazodimedone, 1a) and
phenylacetylene (2a) in toluene at 70 °C. The results are
presented in Table 1. Various palladium catalysts were ex-
amined for their ability to activate cyclic diazodicarbonyl
compound 1a. In the presence of 10 mol-% [Pd(PPh3)4] or
Pd(OAc)2, complex mixtures were formed and the desired
product was not isolated (entries 1 and 2). Using 5 mol-%
[Co(PPh3)3Cl], [Au{P(tBu)2(o-biphenyl)}Cl], or [Au{P(p-
F3CC6H4)3}Cl] as catalysts, the products were not formed
[a] School of Chemical Engineering, Yeungnam University,
214-1 Dae-dong, Gyeongsan, 712-749, Korea
E-mail: yrlee@yu.ac.kr
http://display.yu.ac.kr/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402067.
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Regioselective Synthesis of Highly Functionalized Furans
even after 24 h (entries 3–5). CuI and CuII catalysts were Table 2. Optimization of the reaction solvent for the synthesis of 3.
next tested. With 20 mol-% CuI, [Cu(PPh3)Cl], or Cu-
(OAc)2, the desired products were not observed (entries 6–
8). However, the use of 20 mol-% [Cu(acac)2] as catalyst
resulted in the formation of the desired compound 3 in 32%
yield (entry 9). Although the InCl3-catalyzed transforma-
tion of diazo compounds has been reported, it was unsuit-
able for this reaction (entry 10).[13] Importantly, when
5 mol-% [Ru(PPh3)3(5-C5H5)Cl], [Ru(PPh3)4Cl2], [Ru(p-
cymene)Cl2]2, or [Ru(PPh3)3Cl2] were used, the cyclic ad-
duct 3 was produced in good yields (60–88%, entries 11–
14) and no other regioisomer was isolated. The best yield
(88%) was obtained with 5 mol-% [Ru(PPh3)3Cl2]. Further-
more, when the loading of [Ru(PPh3)3Cl2] was reduced to
2 mol-%, the yield was not reduced (entry 15). In the case
of 10 mol-% RuO2, no product was observed (entry 16).
Table 1. Optimization of catalysts for the synthesis of 3.[a]
[a] Reaction conditions: 1a (1.0 mmol) and 2a (3.0 mmol) in the
presence of [Ru(PPh3)3Cl2] (2 mol-%) in solvent (2.0 mL) under ni-
trogen. [b] Isolated yields. [c] No reaction. [d] Complex reaction
mixture formed.
the corresponding cyclic 1,3-dicarbonyl compounds, as de-
scribed previously.[15] The reactions between 1a and 4-eth-
ynyltoluene (2b), 3-ethynyltoluene (2c), 1-ethynyl-4-pentyl-
benzene (2d), or 1-ethynyl-4-methoxy-2-methylbenzene
(2e), which possess an electron-donating group on the
benzene ring, in the presence of 2 mol-% [Ru(PPh3)3Cl2]
in toluene at 70 °C for 8–12 h gave the cycloadducts 4–7
in yields of 74–94% (entries 1–4). Treatment of 1a with 1-
ethynyl-3-fluorobenzene (2f) bearing an electron-with-
drawing group on the benzene ring in the presence of
2 mol-% [Ru(PPh3)3Cl2] in toluene at 70 °C for 12 h pro-
[a] Reaction conditions: 1a (1.0 mmol) and 2a (3.0 mmol) in the
vided the product 8 in 66% yield (entry 5). The reactions
presence of catalysts in toluene (2.0 mL) under nitrogen. [b] Iso-
between 1a and other acetylenes, such as 1-ethynylnaphth-
lated yields. [c] A complex reaction mixture was produced.
alene (2g), 6-methoxy-2-naphthylacetylene (2h), or 9-eth-
ynylphenanthrene (2i), afforded the products 9–11 in
Further reactions were investigated in the presence of yields of 84, 66, and 58%, respectively (entries 6–8). Using
2 mol-% [Ru(PPh3)3Cl2] in several solvents (Table 2). Inter- the aromatic heterocyclic compounds 3-ethynylthiophene
estingly, the reaction was favored by less polar solvents, (2j) and 2-ethynylpyridine (2k), compounds 12 and 13
such as n-hexane, benzene, dichloromethane, chlorobenz- bearing heterocyclic rings on the furanyl ring were pro-
ene, xylenes, or mesitylene. Reactions in polar aprotic sol- duced in yields of 79 and 67%, respectively (entries 9 and
vents, such as DMSO or DMF, either gave no product or 10). In the case of 5-ethynyl-1-methyl-1H-imidazole (2l),
complex mixtures. Of the solvents screened, none produced the reaction did not give any product, possibly due to the
a higher yield than toluene (88%). Polar protic solvents, deactivation of [Ru(PPh3)3Cl2] by the formation of a RuII–
such as methanol and water, were not tested because the imidazole complex (entry 11). Additional reactions be-
formation of insertion products under these conditions is tween 2-diazocyclohexane-1,3-dione (1b), 2-diazo-5-meth-
well known.[14]
ylcyclohexane-1,3-dione (1c), or 2-diazo-5-isopropylcyclo-
After optimizing the reaction conditions, additional re- hexane-1,3-dione (1d) and various terminal acetylenes
actions were attempted between a variety of cyclic diazodi- were also attempted, and compounds 15–27 were pro-
carbonyl compounds and acetylenes in the presence of duced in yields of 63–88% with excellent regioselectivity
2 mol-% [Ru(PPh3)3Cl2] in toluene at 70 °C. The results (entries 12–24). The reactions between 5-aryl-substituted
are summarized in Table 3. The cyclic and acyclic diazodi- cyclic 2-diazo-1,3-diketones (1e and 1f) and various ter-
carbonyl compounds 1b–1k were readily prepared by the minal acetylenes were also successful and gave the corre-
transfer of the diazo moiety from tosyl or mesyl azide and sponding products 28–33 in yields of 54–75% (entries 25–
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30). When 5-furyl-substituted 1g was used, compounds membered ring, and phenylacetylene provided the desired
34–36 bearing a furyl ring on the cyclohexenone ring were compound 37 in a yield of 77% (entry 34). Thus, these
produced in yields of 70–72% (entries 31–33). The reac- reactions provide a rapid route to the synthesis of a variety
tion between diazodicarbonyl 1h, which contains a five- of arylfurans with excellent regioselectivity.
Table 3. Synthesis of 2-arylfurans starting from various cyclic diazodicarbonyl compounds and alkynes.[a]
[a] Reaction conditions: cyclic diazodicarbonyl compound (1.0 mmol) and alkyne (3.0 mmol) in toluene (2.0 mL) in the presence of
[Ru(PPh3)3Cl2] (2 mol-%) under nitrogen. [b] Isolated yields.
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Regioselective Synthesis of Highly Functionalized Furans
To extend the utility of these cycloadditions, additional pounds were readily separated by column chromatography
reactions between cyclic diazodicarbonyl compounds and and assigned on the basis of their spectroscopic data. In the
electron-deficient alkynes, namely ethyl propiolate (2m), 1H NMR spectrum of 46, the cyclopropene ring exhibits a
methyl propiolate (2n), or 3-butyn-2-one (2o), were next in- proton signal at δ = 6.92 ppm, whereas the proton on the
vestigated under the optimized reaction conditions. The re- furanyl ring of 47 produced a peak at δ = 6.76 ppm. Simi-
sults are summarized in Table 4. The reactions between 1a larly, the reaction between 1j and 2a provided cyclopropene
and 2m, 2n, or 2o in the presence of 2 mol-% [Ru(PPh3)3- 48 (10%) and furan 49 (29%), whereas that between 1k and
Cl2] in toluene at 70 °C for 4–6 h afforded 2-carbonyl-sub- 2a afforded compounds 50 (7%) and 51 (25%).
stituted furans 38, 39, and 40 in yields of 55, 54, and 48%,
Our results show that the reactions of acyclic diazodi-
respectively (entries 1–3). Similarly, treatment of 1b or 1e carbonyl compounds 1i–1k with phenylacetylene gave fur-
with the conjugated alkynes 2m–2o gave cycloadducts 41– ans in somewhat low yields when compared with those of
45 in yields of 42–52% (entries 4–8). Interestingly, in these cyclic diazodicarbonyl compounds. This is probably due to
cases, potential regioisomers produced by RhII-catalyzed re- the low thermal stability of the acyclic diazodicarbonyl
actions were not formed.[16]
compounds.[17,18]
To investigate the usefulness of this methodology, the re-
The chemo- and regioselectivity of the [Ru(PPh3)3Cl2]-
actions between acyclic diazodicarbonyl compounds 1i–1k catalyzed reactions of cyclic diazodicarbonyl compounds
and phenylacetylene (2a) were attempted under the opti- were next examined (Scheme 2). First, the chemoselectivity
mized reaction conditions (Table 5). The reaction between of the reaction of 1a with terminal acetylene and styrene
1i and 2a in the presence of 2 mol-% [Ru(PPh3)3Cl2] in tolu- was probed by conducting an intermolecular competition
ene at 70 °C for 12 h gave both cyclopropene 46 and furan reaction [Scheme 2, Equation (1)]. The reaction of 1a with
47 in yields of 10 and 31%, respectively. The two com- phenylacetylene (2a) and styrene (2p) showed a 12:1 prefer-
Table 4. Synthesis of substituted furans starting from various cyclic diazodicarbonyl compounds and conjugated alkynes in the presence
of [Ru(PPh3)3Cl2].[a]
[a] Reaction conditions: cyclic diazodicarbonyl compound (1.0 mmol) and alkyne (3.0 mmol) in toluene (2.0 mL) in the presence of
[Ru(PPh3)3Cl2] (2 mol-%) under nitrogen. [b] Isolated yields.
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Table 5. Synthesis of substituted cyclopropenes and furans starting from acyclic diazodicarbonyl compounds and alkynes in the presence
of [Ru(PPh3)3Cl2].[a]
[a] Reaction conditions: acyclic diazodicarbonyl compound (1.0 mmol) and alkyne (3.0 mmol) in toluene (2.0 mL) in the presence of
[Ru(PPh3)3Cl2] (2 mol-%) under nitrogen. [b] Isolated yields.
Scheme 2. Chemoselectivity and regioselectivity of [Ru(PPh3)3Cl2]-catalyzed reactions.
ence for the formation of furan 3 in 84% yield, which is in quent ring-opening of intermediate II leads to the cyclo-
accord with the higher nucleophilicity of the active alkyne. propene 46 or ruthenium carbenoid III.[17a,23] A carbonyl
The reactions of various diazodicarbonyl compounds with oxygen atom in III attacks the metal carbenoid carbon to
2-methyl-1-buten-3-yne (2q) also showed high regioselectiv- produce furan 47 and regenerate the catalyst. In the pres-
ity [Scheme 2, Equation (2)]. For example, the reaction be- ence of the RuII catalyst, cyclopropene 46 probably un-
tween 1a and 2q provided 53 (45%) as the sole product. dergoes ring-opening cycloisomerization to afford the cor-
Similarly, the reactions between 1b or 1e and 2q gave com- responding furan 47 as a major component. When toluene
pounds 55 and 57 as the sole products in yields of 42 and solutions of cyclopropenes 46, 48, and 50 were heated at
38%, respectively.
70 °C for 12 h in the presence of 2 mol-% [Ru(PPh3)3Cl2],
We suggest a mechanism for the formation of cyclo- the corresponding furans 47, 49, and 51 were obtained in
propene 46 and furan 47 based on a comparison with re- yields of 76, 81, and 78%, respectively. Importantly, in the
ported RhII-[19] and RuII-catalyzed[20] reactions (Scheme 3). cases of cyclic diazodicarbonyl compounds, cyclopropene
Diazodicarbonyl compound 1a first reacts with 2 mol-% products were not isolated. Presumably, cyclopropene prod-
[Ru(PPh3)3Cl2] to give ruthenium carbenoid I with the loss ucts directly undergo ring-opening cycloisomerization to
of nitrogen. The coordination of I to phenylacetylene (2a) give the corresponding furans through the relatively facile
then leads to the formation of metallacyclobutene II[21] attack of the fixed carbonyl oxygen atoms on the cyclic
through the formation of a ruthenium π complex.[22] Subse- rings compared with acyclic substrates.
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Regioselective Synthesis of Highly Functionalized Furans
was extracted with ethyl acetate (EA; 3ϫ 15 mL). Evaporation of
the solvent and purification by column chromatography on silica
gel using hexane/ethyl acetate (6:1) as eluent gave the product.
6,6-Dimethyl-2-phenyl-6,7-dihydrobenzofuran-4(5H)-one (3):[24a–24g]
Yield 88%; white solid; TLC (1:4 EA/hexane): Rf = 0.45; m.p. 100–
101 °C. IR (KBr): ν = 2930 3059, 2957, 2874, 1676, 1455, 1219,
˜
1
1124, 762, 692 cm–1. H NMR (300 MHz, CDCl3): δ = 7.56 (d, J
= 7.2 Hz, 2 H, Ar), 7.30 (uneven t, J = 7.5, 7.2 Hz, 2 H, Ar), 7.20
(uneven t, J = 7.2, 6.6 Hz, 1 H, Ar), 6.80 (s, 1 H, furan), 2.73 (s, 2
H, CH2), 2.31 (s, 2 H, CH2), 1.08 (s, 6 H, 2 CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 193.78, 165.75, 154.48, 129.77, 128.72,
127.97, 123.83, 121.63, 100.69, 51.94, 37.39, 35.20, 28.57 ppm.
HRMS (EI+): calcd. for C16H16O2 240.1150; found 240.1152.
6,6-Dimethyl-2-(p-tolyl)-6,7-dihydrobenzofuran-4(5H)-one (4):[24b,24f]
Yield 85%; white solid; TLC (1:4 EA/hexane): Rf = 0.40; m.p. 123–
124 °C. IR (KBr): ν = 3045, 2956, 1675, 1445, 1220, 1123, 1025,
˜
811, 737 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.43 (d, J =
7.8 Hz, 2 H, Ar), 7.08 (d, J = 8.1 Hz, 2 H, Ar), 6.72 (s, 1 H, furan),
2.68 (s, 2 H, CH2), 2.28 (s, 2 H, CH2), 2.25 (s, 3 H, Ar-CH3), 1.05
(s, 6 H, 2 CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 193.79,
165.41, 154.58, 137.81, 129.32, 126.95, 123.68, 121.46, 99.80, 51.81,
37.22, 35.10, 28.48, 21.17 ppm. HRMS (EI+): calcd. for C17H18O2
254.1307; found 254.1305.
Scheme 3. Mechanistic pathway for the RuII-catalyzed cascade syn-
thesis of compounds 46 and 47.
Conclusions
We have developed a novel and efficient method for syn-
thesizing functionalized furans by the reaction of cyclic or
acyclic diazodicarbonyl compounds with terminal alkynes
in the presence of RuII complexes. Our results provide a
new strategy for the construction of polysubstituted furan
derivatives with high chemoselectivity and regioselectivity.
Further investigations of RuII-complex-catalyzed trans-
formations and functionalizations of diazodicarbonyl com-
pounds are underway in our laboratory.
6,6-Dimethyl-2-(m-tolyl)-6,7-dihydrobenzofuran-4(5H)-one
(5):
Yield 94%; white solid; TLC (1:6 EA/hexane): Rf = 0.42; m.p. 81–
82 °C. IR (KBr): ν = 3042, 2950, 2889, 1678, 1445, 1220, 1123,
˜
1
1033, 787, 692 cm–1. H NMR (300 MHz, CDCl3): δ = 7.36–7.33
(m, 2 H, Ar), 7.16 (t, J = 7.5 Hz, 1 H, Ar), 6.99 (d, J = 7.2 Hz, 1
H, Ar), 6.75 (s, 1 H, furan), 2.68 (s, 2 H, CH2), 2.27 (br. s, 5 H,
CH2, Ar-CH3), 1.05 (s, 6 H, 2 CH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 193.69, 165.56, 154.46, 138.22, 129.52, 128.69, 128.53,
124.28, 121.44, 120.89, 100.42, 51.77, 37.18, 35.06, 28.43,
21.31 ppm. HRMS (EI+): calcd. for C17H18O2 254.1307; found
254.1308.
Experimental Section
6,6-Dimethyl-2-(4-pentylphenyl)-6,7-dihydrobenzofuran-4(5H)-one
(6): Yield 74%; brown solid; TLC (1:4 EA/hexane): Rf = 0.43; m.p.
General Experimental Methods: All alkynes and catalysts were ob-
tained commercially from Sigma–Aldrich and used without further
purification. The starting acyclic and cyclic diazodiarbonyls 1a–1k
were prepared by transfer of the diazo moiety of tosyl or mesyl
azide to the corresponding acyclic and acyclic 1,3-dicarbonyl com-
pounds, as described previously.[15] Solvents were purified accord-
ing to standard methods. All experiments were carried out under
nitrogen and glassware was oven-dried prior to use.
96–97 °C. IR (KBr): ν = 3039, 2937, 1678, 1446, 1219, 1124, 1018,
˜
813, 736 cm–1 1H NMR (300 MHz, CDCl3): δ = 7.46 (d, J =
.
7.8 Hz, 2 H, thiophene), 7.10 (d, J = 7.8 Hz, 2 H, Ar), 6.73 (s, 1
H, furan), 2.69 (s, 2 H, CH2), 2.51 (dd, J = 7.8, 7.2 Hz, 2 H, Ar-
CH2CH2CH2CH2CH3), 2.29 (s, 2 H, CH2), 1.52 (dd, J = 6.9,
6.6 Hz, 2 H, Ar-CH2CH2CH2CH2CH3), 1.22 (br. s, 4 H, Ar-
CH2CH2CH2CH2CH3), 1.06 (s, 6 H, 2 CH3), 0.79 (t, J = 6.0 Hz, 3
H, Ar-CH2CH2CH2CH2CH3) ppm. 13C NMR (75 MHz, CDCl3):
δ = 193.82, 165.45, 154.66, 142.94, 128.70, 127.17, 123.73, 121.49,
99.83, 51.83, 37.27, 35.57, 35.14, 31.31, 30.91, 28.49, 22.41,
13.94 ppm. HRMS (EI+): calcd. for C21H26O2 310.1933; found
310.1936.
Merck precoated silica gel plates (Art. 5554) with a fluorescent
indicator were used for analytical TLC. Flash column chromatog-
raphy was performed on silica gel 9385 (Merck). 1H and 13C NMR
spectra were recorded at 25 °C with a Bruker Avance DPX
300 MHz or Varian VNS 300 MHz spectrometer in CDCl3. Chemi-
cal shifts are reported in ppm and referenced to TMS. IR spectra
were recorded with a Bio-Rad Excalibur Series FTS 3000 spectro-
photometer. Melting points were obtained with a Fisher-Johns
melting-point apparatus. HR-EI-MS was performed with a JMS-
700 spectrometer at the Korean Basic Science Institute (Daegu
Branch, South Korea).
2-(4-Methoxy-2-methylphenyl)-6,6-dimethyl-6,7-dihydrobenzofuran-
4(5H)-one (7): Yield 87%; yellow solid; TLC (1:6 EA/hexane): Rf
= 0.29; m.p. 114–115 °C. IR (KBr): ν = 3144, 2952, 1673, 1606,
˜
1490, 1449, 1292, 1246, 1221, 1130, 1049, 1009, 810, 733, 643 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.56 (d, J = 8.1 Hz, 1 H, Ar),
6.76–6.74 (m, 2 H, Ar), 6.61 (s, 1 H, furan), 3.77 (s, 3 H, Ar-OCH3),
2.75 (s, 2 H, CH2), 2.40 (s, 3 H, Ar-CH3), 2.35 (s, 2 H, CH2), 1.12
(s, 6 H, 2 CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.00,
164.93, 159.06, 153.80, 136.47, 128.26, 121.90, 121.30, 116.32,
111.32, 102.80, 55.05, 51.81, 37.17, 35.11, 28.50, 21.94 ppm.
HRMS (EI+): calcd. for C18H20O3 284.1412; found 284.1411.
General Procedure for the Synthesis of Furans: Tris(triphenyl-
phosphine)ruthenium(II) dichloride ([Ru(PPh3)3Cl2]; 0.02 mol,
2 mol-%) was added to a solution of a cyclic diazodicarbonyl com-
pound (1.0 mmol, 1 equiv.) and terminal alkyne (3.0 mmol,
3 equiv.) in toluene (2.0 mL) at room temperature. The reaction
mixture was stirred at 70 °C for the indicated time and then cooled
to room temperature. Water (15 mL) was added and the solution
2-(3-Fluorophenyl)-6,6-dimethyl-6,7-dihydrobenzofuran-4(5H)-one
(8): Yield 66%; white solid; TLC (1:6 EA/hexane): Rf = 0.43; m.p.
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93–94 °C. IR (KBr): ν = 3103, 2959, 2874, 1677, 1616, 1564, 1448, (d, J = 3.9 Hz, 1 H, pyridine), 7.63 (dd, J = 7.8, 7.5 Hz, 1 H,
˜
1
1274, 1223, 1182, 1126, 941, 858, 785, 686, 624, 523, 483 cm–1. H
pyridine), 7.56 (d, J = 8.1 Hz, 1 H, pyridine), 7.15–7.10 (m, 2 H,
NMR (300 MHz, CDCl3): δ = 7.36 (uneven t, J = 7.8, 5.4 Hz, 1
pyridine-H, furan-H), 2.78 (s, 2 H, CH2), 2.34 (s, 2 H, CH2), 1.09
H, Ar), 7.32 (s, 1 H, Ar), 7.30–7.27 (m, 1 H, Ar), 6.94 (t, J = (s, 6 H, 2 CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 193.56,
8.1 Hz, 1 H, Ar), 6.87 (s, 1 H, furan), 2.78 (s, 2 H, CH2), 2.37 (s, 166.75, 153.53, 149.60, 148.20, 136.61, 122.37, 121.60, 118.83,
2 H, CH2), 1.14 (s, 6 H, 2 CH3) ppm. 13C NMR (75 MHz, CDCl3): 104.29, 51.85, 37.32, 35.11, 28.43 ppm. HRMS (EI+): calcd. for
1
δ = 193.71, 166.07, 162.97 (d, JC,F = 243.9 Hz), 153.15 (d, JCF
=
C15H15NO2 241.1103; found 241.1107.
2-Phenyl-6,7-dihydrobenzofuran-4(5H)-one (15):[24a,24c,24h] Yield
85%; white solid; TLC (1:6 EA/hexane): Rf = 0.25; m.p. 133–
3
3
2.8 Hz), 131.74 (d, JC,F = 8.3 Hz), 130.38 (d, JC,F = 8.3 Hz),
4
2
121.62, 119.45 (d, JC,F = 2.8 Hz), 114.73 (d, JC,F = 20.9 Hz),
110.70 (d, 2JC,F = 23.6 Hz), 101.76, 51.87, 37.30, 35.20, 28.53 ppm.
HRMS (EI+): calcd. for C16H15FO2 258.1056; found 258.1056.
134 °C. IR (KBr): ν = 3098, 3057, 2946, 1669, 1445, 1355, 1136,
˜
1
851, 756, 698 cm–1. H NMR (300 MHz, CDCl3): δ = 7.56 (d, J =
6,6-Dimethyl-2-(1-naphthyl)-6,7-dihydrobenzofuran-4(5H)-one
(9):[24b] Yield 84%; red liquid; TLC (1:6 EA/hexane): Rf = 0.37. IR
7.5 Hz, 2 H, Ar), 7.31 (uneven t, J = 7.5, 6.9 Hz, 2 H, Ar), 7.21
(uneven t, J = 7.8, 6.9 Hz, 1 H, Ar), 6.80 (s, 1 H, furan), 2.85 (t,
J = 6.0 Hz, 2 H, CH2CH2CH2), 2.44 (dd, J = 6.6, 6.0 Hz, 2 H,
CH2CH2CH2), 2.16–2.08 (m, 2 H, CH2CH2CH2) ppm. 13C NMR
(75 MHz, CDCl3): δ = 194.50, 166.63, 154.07, 129.65, 128.69,
127.98, 123.82, 122.79, 100.73, 37.51, 23.33, 22.45 ppm. HRMS
(EI+): calcd. for C14H12O2 212.0837; found 212.0835.
(neat): ν = 3054, 2955, 2887, 1673, 1444, 1220, 1122, 1043, 967, 788,
˜
1
733 cm–1. H NMR (300 MHz, CDCl3): δ = 8.33 (d, J = 8.4 Hz, 1
H, Ar), 7.88 (d, J = 8.4 Hz, 1 H, Ar), 7.86 (d, J = 8.4 Hz, 1 H,
Ar), 7.74 (d, J = 7.2 Hz, 1 H, Ar), 7.52–7.48 (m, 3 H, Ar), 6.98 (s,
1 H, furan), 2.87 (s, 2 H, CH2), 2.45 (s, 2 H, CH2), 1.20 (s, 6 H, 2
CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.12, 166.11,
153.73, 133.82, 130.06, 129.19, 128.62, 127.33, 126.84, 126.35,
126.10, 125.20, 125.02, 121.49, 105.21, 52.02, 37.48, 35.32,
28.68 ppm. HRMS (EI+): calcd. for C20H18O2 290.1307; found
290.1305.
2-(3-Fluorophenyl)-6,7-dihydrobenzofuran-4(5H)-one (16): Yield
69%; brown solid; TLC (1:6 EA/hexane): Rf = 0.24; m.p. 89–90 °C.
IR (KBr): ν = 3075, 2948, 2891, 1675, 1607, 1443, 1261, 1229, 1167,
˜
1
1005, 861, 788, 725, 691, 599, 521, 462 cm–1. H NMR (300 MHz,
CDCl3): δ = 7.37 (dd, J = 7.5, 5.7 Hz, 1 H, Ar), 7.32–7.29 (m, 2
H, Ar), 6.95 (dd, J = 8.4, 7.8 Hz, 1 H, Ar), 6.87 (s, 1 H, furan),
2.92 (t, J = 6.0 Hz, 2 H, CH2CH2CH2), 2.50 (dd, J = 6.3, 6.0 Hz,
2-(6-Methoxy-2-naphthyl)-6,6-dimethyl-6,7-dihydrobenzofuran-
4(5H)-one (10): Yield 66%; brown solid; TLC (1:6 EA/hexane): Rf
= 0.23; m.p. 174–175 °C. IR (KBr): ν = 3056, 2952, 1672, 1620,
2 H, CH2CH2CH2), 2.22–2.16 (m, 2 H, CH2CH2CH2) ppm. 13C
˜
1453, 1393, 1262, 1213, 1032, 750 cm–1
.
1H NMR (300 MHz, NMR (75 MHz, CDCl3): δ = 194.35, 166.93, 162.98 (d, JC,F
=
=
=
1
3
3
CDCl3): δ = 7.80 (s, 1 H, Ar), 7.73–7.61 (m, 3 H, Ar), 7.13 (d, J = 244.0 Hz), 152.84, 131.69 (d, JCF = 8.8 Hz), 130.38 (d, JCF
4
2
7.8 Hz, 1 H, Ar), 7.07 (s, 1 H, Ar), 6.89 (s, 1 H, furan), 3.87 (s, 3
H, Ar-OCH3), 2.76 (s, 2 H, CH2), 2.36 (s, 2 H, CH2), 1.14 (s, 6 H,
8.3 Hz), 122.84, 119.51 (d, JCF = 2.7 Hz), 114.78 (d, JCF
2
21.5 Hz), 110.75 (d, JCF
= 23.6 Hz), 101.86, 37.51, 23.33,
2 CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 193.79, 165.67, 22.41 ppm. HRMS (EI+): calcd. for C14H11FO2 230.0743; found
157.89, 154.63, 134.00, 129.57, 128.58, 127.24, 124.93, 122.45, 230.0741.
122.26, 121.59, 119.33, 105.69, 100.31, 55.17, 51.82, 37.25, 35.13,
2-(1-Naphthyl)-6,7-dihydrobenzofuran-4(5H)-one (17): Yield 82%;
28.51 ppm. HRMS (EI+): calcd. for C21H20O3 320.1412; found
brown liquid; TLC (1:6 EA/hexane): R = 0.20. IR (neat): ν = 3052,
˜
f
320.1408.
2946, 2893, 1673, 1592, 1436, 1223, 1125, 1005, 977, 788, 732 cm–1.
6,6-Dimethyl-2-(9-phenanthryl)-6,7-dihydrobenzofuran-4(5H)-one 1H NMR (300 MHz, CDCl3): δ = 8.33 (d, J = 7.2 Hz, 1 H, Ar),
(11): Yield 58%; brown liquid; TLC (1:6 EA/hexane): Rf = 0.37.
IR (neat): ν = 3058, 2952, 2883, 1674, 1606, 1441, 1221, 1124, 1036,
7.87 (d, J = 7.8 Hz, 1 H, Ar), 7.84 (d, J = 8.4 Hz, 1 H, Ar), 7.72
(d, J = 7.2 Hz, 1 H, Ar), 7.56–7.46 (m, 3 H, Ar), 6.99 (s, 1 H,
˜
955, 900, 826, 740, 628 cm–1. 1H NMR (300 MHz, CDCl3): δ = furan), 2.97 (dd, J = 6.3, 6.0 Hz, 2 H, CH2CH2CH2), 2.55 (dd, J
8.70 (d, J = 7.8 Hz, 1 H, Ar), 8.62 (d, J = 8.1 Hz, 1 H, Ar), 8.36
(d, J = 7.8 Hz, 1 H, Ar), 7.98 (s, 1 H, Ar), 7.87 (d, J = 7.5 Hz, 1 CH2CH2CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.60,
H, Ar), 7.66–7.55 (m, 4 H, Ar), 7.03 (s, 1 H, furan), 2.82 (s, 2 H, 166.89, 153.31, 133.73, 130.01, 129.15, 128.54, 127.22, 126.78,
= 6.6, 6.3 Hz, 2 H, CH2CH2CH2), 2.26–2.18 (m, 2 H,
CH2), 2.43 (s, 2 H, CH2), 1.18 (s, 6 H, 2 CH3) ppm. 13C NMR 126.32, 126.04, 125.13, 124.94, 122.64, 105.25, 37.55, 23.39,
(75 MHz, CDCl3): δ = 193.92, 166.00, 153.51, 130.86, 130.54,
130.17, 128.89, 128.86, 127.59, 127.30, 126.89, 126.88, 126.72,
125.92, 125.66, 122.98, 122.40, 121.32, 105.47, 51.87, 37.28, 35.15,
28.54 ppm. HRMS (EI+): calcd. for C24H20O2 340.1463; found
340.1459.
22.49 ppm. HRMS (EI+): calcd. for C18H14O2 262.0994; found
262.0996.
6-Methyl-2-phenyl-6,7-dihydrobenzofuran-4(5H)-one
Yield 84%; white solid; TLC (1:6 EA/hexane): Rf = 0.37; m.p. 97–
98 °C. IR (KBr): ν = 3055, 2952, 2892, 1674, 1610, 1441, 1218,
(18):[24a,24i]
˜
6,6-Dimethyl-2-(3-thienyl)-6,7-dihydrobenzofuran-4(5H)-one (12): 1133, 1052, 1012, 914, 752, 695 cm–1. 1H NMR (300 MHz, CDCl3):
Yield 79%; brown solid; TLC (1:6 EA/hexane): Rf = 0.37; m.p.
102–103 °C. IR (KBr): ν = 3108, 2953, 2883, 1672, 1447, 1220,
δ = 7.62 (d, J = 8.1 Hz, 2 H, Ar), 7.36 (t, J = 7.2 Hz, 2 H, Ar),
7.26 (uneven t, J = 6.9, 6.6 Hz, 1 H, Ar), 6.85 (s, 1 H, furan), 3.02–
˜
1
1121, 1038, 852, 786 cm–1. H NMR (300 MHz, CDCl3): δ = 7.40 2.95 (m, 1 H, CH2CHCH2a), 2.61–2.43 (m, 3 H, CH2aCHCH2b),
(s, 1 H, thiophene), 7.26 (d, J = 4.8 Hz, 1 H, thiophene), 7.20 (d,
J = 4.8 Hz, 1 H, thiophene), 6.61 (s, 1 H, furan), 2.70 (s, 2 H, CH2),
2.30 (s, 2 H, CH2), 1.07 (s, 6 H, 2 CH3) ppm. 13C NMR (75 MHz,
2.28–2.19 (m, 1 H, CH2bCHCH2), 1.16 (d, J = 6.3 Hz, 3 H,
CHCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 193.93, 166.24,
165.24, 129.68, 128.66, 127.93, 123.79, 122.40, 100.68, 45.95, 31.36,
CDCl3): δ = 193.83, 165.28, 151.33, 131.31, 126.53, 124.39, 121.25, 30.62, 20.95 ppm. HRMS (EI+): calcd. for C15H14O2 226.0994;
119.74, 100.28, 51.84, 37.25, 35.17, 28.50 ppm. HRMS (EI+): calcd. found 226.0995.
for C14H14O2S 246.0715; found 246.0719.
6-Methyl-2-(4-pentylphenyl)-6,7-dihydrobenzofuran-4(5H)-one (19):
6,6-Dimethyl-2-(2-pyridyl)-6,7-dihydrobenzofuran-4(5H)-one (13): Yield 68%; brown solid; TLC (1:6 EA/hexane): Rf = 0.53; m.p. 86–
Yield 67%; brown solid; TLC (1:6 EA/hexane): Rf = 0.23; m.p.
128–129 °C. IR (KBr): ν = 3063, 2954, 2885, 1675, 1609, 1444,
87 °C. IR (KBr): ν = 3037, 2936, 2871, 1677, 1446, 1218, 1131,
˜
1
1046, 1012, 823, 736 cm–1. H NMR (300 MHz, CDCl3): δ = 7.52
˜
1218, 1130, 782, 625 cm–1. H NMR (300 MHz, CDCl3): δ = 8.54 (d, J = 7.8 Hz, 2 H, Ar), 7.16 (d, J = 7.8 Hz, 2 H, Ar), 6.78 (s, 1
1
3436
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3430–3442

Regioselective Synthesis of Highly Functionalized Furans
H, furan), 3.00–2.93 (m, 1 H, CH2CHCH2a), 2.60–2.39 (m, 5 H, 6-Isopropyl-2-(p-tolyl)-6,7-dihydrobenzofuran-4(5H)-one
(24):[24i]
CH2aCHCH2b, Ar-CH2CH2CH2CH2CH3), 2.26–2.17 (m, 1 H, Yield 88%; white solid; TLC (1:6 EA/hexane): Rf = 0.42; m.p. 92–
CH2bCHCH2), 1.59 (t, J = 6.9 Hz, 2 H, Ar-CH2CH2CH2CH2CH3), 93 °C. IR (KBr): ν = 2956, 2888, 1673, 1609, 1447, 1266, 1216,
˜
1.30 (br. s, 4 H, Ar-CH2CH2CH2CH2CH3), 1.14 (d, J = 6.3 Hz, 3 1132, 1009, 813, 734, 644, 504 cm–1. 1H NMR (300 MHz, CDCl3):
H, CHCH3), 0.87 (dd,
CH2CH2CH2CH2CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 6.76 (s, 1 H, furan), 2.96–2.89 (m, 1 H, CH2CHCH2a), 2.63–2.51
193.93, 165.94, 154.52, 142.95, 128.67, 127.18, 123.78, 122.36, (m, 2 H, CH2aCHCH2b), 2.33 (s, 3 H, Ar-CH3), 2.28–2.19 (m, 1 H,
J
=
6.6, 6.0 Hz,
3
H, Ar-
δ = 7.50 (d, J = 7.8 Hz, 2 H, Ar), 7.15 (d, J = 7.8 Hz, 2 H, Ar),
99.90, 45.93, 35.55, 31.34, 31.31, 30.97, 30.63, 22.39, 20.93, CH2bCHCH2), 2.11–2.06 (m, 1 H, CH2CHCH2), 1.73–1.62 (m, 1
13.89 ppm. HRMS (EI+): calcd. for C20H24O2 296.1776; found
296.1779.
H, CHCH3), 0.96 (d, J = 6.9 Hz, 6 H, 2 CHCH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 194.07, 166.41, 154.40, 137.72, 129.23,
126.91, 123.63, 122.30, 99.70, 41.82, 41.64, 31.77, 26.76, 21.05,
19.64, 19.36 ppm. HRMS (EI+): calcd. for C18H20O2 268.1463;
found 268.1462.
2-(4-Methoxy-2-methylphenyl)-6-methyl-6,7-dihydrobenzofuran-
4(5H)-one (20): Yield 66%; brown solid; TLC (1:6 EA/hexane): Rf
= 0.33; m.p. 75–76 °C. IR (KBr): ν = 3049, 2948, 1671, 1604, 1447,
˜
1246, 1223, 1136, 1048, 1009, 847, 813, 733, 639 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 7.53 (d, J = 8.7 Hz, 1 H, Ar), 6.75–6.73
(m, 2 H, Ar), 6.59 (s, 1 H, furan), 3.76 (s, 3 H, Ar-OCH3), 2.99–
6-Isopropyl-2-(4-methoxy-2-methylphenyl)-6,7-dihydrobenzofuran-
4(5H)-one (25): Yield 69%; brown liquid; TLC (1:6 EA/hexane): Rf
= 0.27. IR (neat): ν = 2955, 1673, 1605, 1489, 1451, 1294, 1245,
˜
2.92 (m, 1 H, CH2CHCH2a), 2.58–2.46 (m, 3 H, CH2aCHCH2b), 1224, 1138, 1049, 1006, 845, 811, 730, 643 cm–1
.
1H NMR
(300 MHz, CDCl3): δ = 7.56 (d, J = 8.1 Hz, 1 H, Ar), 6.77–6.75
J = 6.3 Hz, 3 H, CHCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = (m, 2 H, Ar), 6.60 (s, 1 H, furan), 3.78 (s, 3 H, Ar-OCH3), 2.99–
2.39 (s, 3 H, Ar-CH3), 2.26–2.17 (m, 1 H, CH2bCHCH2), 1.14 (d,
194.07, 165.43, 159.12, 153.68, 136.55, 128.34, 122.16, 121.90,
116.32, 111.30, 102.86, 55.02, 45.90, 31.26, 30.64, 21.81, 20.93 ppm.
HRMS (EI+): calcd. for C17H18O3 270.1256; found 270.1252.
2.92 (m, 1 H, CH2CHCH2a), 2.67–2.54 (m, 2 H, CH2aCHCH2b),
2.41 (s, 3 H, Ar-CH3), 2.32–2.22 (m, 1 H, CH2bCHCH2), 2.16–2.12
(m, 1 H, CH2CHCH2), 1.73–1.64 (m, 1 H, CHCH3), 0.97 (d, J =
6.6 Hz, 6 H, 2 CHCH3) ppm. 13C NMR (75 MHz, CDCl3): δ =
194.61, 166.14, 159.12, 153.78, 136.59, 128.36, 122.26, 121.95,
116.36, 111.33, 102.83, 55.10, 42.01, 41.77, 31.91, 26.85, 21.93,
19.79, 19.50 ppm. HRMS (EI+): calcd. for C19H22O3 298.1569;
found 298.1565.
2-(3-Fluorophenyl)-6-methyl-6,7-dihydrobenzofuran-4(5H)-one (21):
Yield 68%; brown solid; TLC (1:6 EA/hexane): Rf = 0.33; m.p.
117–118 °C. IR (KBr): ν = 3105, 2954, 2893, 1675, 1605, 1444,
˜
1269, 1218, 1145, 1055, 862, 787, 686, 615, 518, 485 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 7.36 (dd, J = 7.5, 4.2 Hz, 1 H, Ar), 7.19–
7.15 (m, 2 H, Ar), 6.81 (dd, J = 7.8, 7.5 Hz, 1 H, Ar), 6.73 (s, 1
2-(3-Fluorophenyl)-6-isopropyl-6,7-dihydrobenzofuran-4(5H)-one
H, furan), 2.91–2.84 (m, 1 H, CH2CHCH2a), 2.50–2.32 (m, 3 H, (26): Yield 81%; brown solid; TLC (1:6 EA/hexane): Rf = 0.38;
CH2aCHCH2b), 2.16–2.07 (m, 1 H, CH2bCHCH2), 1.05 (d, J =
m.p. 66–67 °C. IR (KBr): ν = 3074, 2959, 2887, 1677, 1607, 1449,
˜
6.3 Hz, 3 H, CHCH3) ppm. 13C NMR (75 MHz, CDCl3): δ =
1271, 1218, 1173, 1147, 1044, 941, 862, 787, 689, 522, 475 cm–1. 1H
1
4
193.80, 166.54, 162.88 (d, JCF = 244.4 Hz), 152.87 (d, JCF
=
NMR (300 MHz, CDCl3): δ = 7.27–7.16 (m, 3 H, Ar), 6.83 (t, J =
3
3
2.8 Hz), 131.64 (d, JCF = 8.3 Hz), 130.30 (d, JCF = 8.8 Hz), 8.1 Hz, 1 H, Ar), 6.73 (s, 1 H, furan), 2.89–2.82 (m, 1 H,
122.38, 119.40 (d, JCF = 2.7 Hz), 114.66 (d, JCF = 21.4 Hz),
4
2
CH2CHCH2a), 2.56–2.43 (m, 2 H, CH2aCHCH2b), 2.20–2.11 (m, 1
H, CH2bCHCH2), 2.03–1.99 (m, 1 H, CH2CHCH2), 1.65–1.54 (m,
1 H, CHCH3), 0.86 (d, J = 8.1 Hz, 6 H, 2 CHCH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 194.21, 167.18, 162.92 (d, JCF = 243.9 Hz),
152.98 (d, JCF = 3.3 Hz), 131.68 (d, JCF = 8.9 Hz), 130.34 (d, JCF
2
110.61 (d, JCF = 23.6 Hz), 101.72, 45.87, 31.27, 30.57, 20.91 ppm.
HRMS (EI+): calcd. for C15H13FO2 244.0900; found 244.0897.
2-(6-Methoxy-2-naphthyl)-6-methyl-6,7-dihydrobenzofuran-4(5H)-
one (22): Yield 80%; brown solid; TLC (1:6 EA/hexane): Rf = 0.23;
= 8.8 Hz), 122.47, 119.42 (d, JCF = 2.7 Hz), 114.70 (d, JCF
=
m.p. 197–198 °C. IR (KBr): ν = 3076, 2949, 1673, 1617, 1448, 1390,
˜
20.9 Hz), 110.65 (d, JCF = 23.6 Hz), 101.68, 41.90, 41.76, 31.87,
26.87, 19.75, 19.45 ppm. HRMS (EI+): calcd. for C17H17FO2
272.1213; found 272.1210.
1218, 1126, 1025, 881, 811 cm–1. 1H NMR (300 MHz, CDCl3): δ =
8.01 (s, 1 H, Ar), 7.74–7.63 (m, 3 H, Ar), 7.13 (d, J = 9.0 Hz, 1 H,
Ar), 7.09 (s, 1 H, Ar), 6.89 (s, 1 H, furan), 3.90 (s, 3 H, Ar-OCH3),
3.06–2.99 (m,
1
H, CH2CHCH2a), 2.64–2.45 (m,
3
H,
6-Isopropyl-2-(1-naphthyl)-6,7-dihydrobenzofuran-4(5H)-one (27):
Yield 80%; brown liquid; TLC (1:6 EA/hexane): Rf = 0.43. IR
CH2aCHCH2b), 2.30–2.21 (m, 1 H, CH2bCHCH2), 1.18 (d, J =
6.0 Hz, 3 H, CHCH3) ppm. 13C NMR (75 MHz, CDCl3): δ =
194.15, 166.30, 157.97, 154.58, 134.09, 129.66, 128.66, 127.32,
(neat): ν = 3053, 2956, 2887, 1673, 1597, 1445, 1220, 1128, 1036,
˜
970, 913, 789, 736 cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.33 (d,
125.00, 122.56, 122.40, 119.41, 105.77, 100.44, 55.28, 46.04, 31.47, J = 7.5 Hz, 1 H, Ar), 7.85 (d, J = 9.0 Hz, 1 H, Ar), 7.82 (d, J =
30.73, 21.08 ppm. HRMS (EI+): calcd. for C20H18O3 306.1256; 8.7 Hz, 1 H, Ar), 7.71 (d, J = 7.2 Hz, 1 H, Ar), 7.55–7.45 (m, 3 H,
found 306.1258.
Ar), 6.97 (s, 1 H, furan), 3.00–2.93 (m, 1 H, CH2CHCH2a), 2.66–
2.57 (m, 2 H, CH2aCHCH2b), 2.28 (dd, J = 15.9, 12.9 Hz, 1 H,
CH2bCHCH2), 2.14–2.09 (m, 1 H, CH2CHCH2), 1.72–1.62 (m, 1
H, CHCH3), 0.95 (d, J = 6.6 Hz, 6 H, 2 CHCH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 194.39, 167.09, 153.45, 133.65, 129.87,
129.02, 128.47, 127.14, 126.69, 126.16, 125.95, 125.05, 124.85,
122.21, 105.02, 41.85, 41.71, 31.80, 26.84, 19.68, 19.39 ppm.
HRMS (EI+): calcd. for C21H20O2 304.1463; found 304.1461.
6-Isopropyl-2-phenyl-6,7-dihydrobenzofuran-4(5H)-one
Yield 78%; yellow liquid; TLC (1:6 EA/hexane): Rf = 0.42. IR
(23):[24i]
(neat): ν = 3056, 2956, 2886, 1673, 1611, 1447, 1219, 1135, 1047,
˜
1008, 828, 754, 693 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.62
(d, J = 7.5 Hz, 2 H, Ar), 7.37 (dd, J = 7.8, 7.2 Hz, 2 H, Ar), 7.27
(dd, J = 7.2, 6.8 Hz, 1 H, Ar), 6.85 (s, 1 H, furan), 3.00–2.98 (m,
1 H, CH2CHCH2a), 2.66–2.54 (m, 2 H, CH2aCHCH2b), 2.27 (dd,
J = 15.9, 12.9 Hz, 1 H, CH2bCHCH2), 2.12–2.09 (m, 1 H, 6-Phenyl-2-(p-tolyl)-6,7-dihydrobenzofuran-4(5H)-one (28): Yield
CH2CHCH2), 1.73–1.66 (m, 1 H, CHCH3), 0.97 (d, J = 6.6 Hz, 6 78%; brown solid; TLC (1:6 EA/hexane): Rf = 0.43; m.p. 67–68 °C.
H, 2 CHCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.34,
IR (KBr): ν = 3032, 2941, 1738, 1674, 1498, 1445, 1216, 1133, 1028,
˜
166.86, 154.18, 129.57, 128.59, 127.85, 123.67, 122.34, 100.49,
814, 755, 700, 507 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.48 (d,
41.83, 41.66, 31.79, 26.79, 19.70, 19.39 ppm. HRMS (EI+): calcd. J = 7.8 Hz, 2 H, Ar), 7.28 (d, J = 6.3 Hz, 2 H, Ar), 7.24–7.12 (m,
for C17H18O2 254.1307; found 254.1304.
5 H, Ar), 6.79 (s, 1 H, furan), 3.54–3.49 (m, 1 H, CH2CHCH2),
Eur. J. Org. Chem. 2014, 3430–3442
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3437

L. Xia, Y. R. Lee
FULL PAPER
3.0–2.99 (m, 2 H, CH2CHCH2), 2.73–2.43 (m, 2 H, CH2CHCH2), 125.97, 125.79, 123.13, 122.56, 119.86, 119.55, 108.51, 107.14,
2.29 (s, 3 H, Ar-CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 101.13, 100.97, 45.29, 41.15, 31.69 ppm. HRMS (EI+): calcd. for
193.11, 165.50, 154.91, 142.40, 138.15, 129.46, 128.84, 128.62,
127.21, 126.75, 126.67, 123.90, 99.99, 44.87, 41.20, 31.21,
21.28 ppm. HRMS (EI+): calcd. for C21H18O2 302.1307; found
302.1308.
C29H20O4 432.1362; found 432.1366.
6-(Benzo[d][1,3]dioxol-5-yl)-2-(6-methoxy-2-naphthyl)-6,7-dihydro-
benzofuran-4(5H)-one (33): Yield 75%; brown solid; TLC (1:4 EA/
hexane): R = 0.30; m.p. 211–212 °C. IR (KBr): ν = 3027, 2905,
˜
f
1661, 1626, 1485, 1390, 1216, 1030, 923, 808, 599 cm–1. H NMR
1
2-(4-Pentylphenyl)-6-phenyl-6,7-dihydrobenzofuran-4(5H)-one (29):
Yield 72%; brown solid; TLC (1:6 EA/hexane): Rf = 0.46; m.p. 64–
(300 MHz, CDCl3): δ = 8.05 (s, 1 H, Ar), 7.76–7.66 (m, 3 H, Ar),
7.15 (d, J = 9.0 Hz, 1 H, Ar), 7.11 (s, 1 H, Ar), 6.94 (s, 1 H, Ar),
6.80–6.72 (m, 3 H, Ar-2H, furan-H), 5.95 (s, 2 H, OCH2O), 3.91
(s, 3 H, Ar-OCH3), 3.57–3.46 (m, 1 H, CH2CHCH2), 3.26–3.19 (m,
1 H, CH2CHCH2a), 3.10–3.01 (m, 1 H, CH2CHCH2b), 2.75–2.71
(m, 2 H, CH2CHCH2) ppm. 13C NMR (75 MHz, CDCl3): δ =
192.90, 165.61, 158.13, 155.06, 147.97, 146.65, 136.42, 134.25,
129.73, 128.73, 127.41, 124.96, 122.88, 122.62, 119.87, 119.50,
108.51, 107.16, 105.90, 101.13, 100.53, 55.33, 45.25, 41.08,
31.62 ppm. HRMS (EI+): calcd. for C26H20O5 412.1311; found
412.1308.
65 °C. IR (KBr): ν = 3033, 2931, 2863, 1739, 1677, 1605, 1495,
˜
1447, 1215, 1130, 1008, 817, 756, 699, 513 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 7.50 (d, J = 8.1 Hz, 2 H, Ar), 7.29 (d, J =
6.3 Hz, 2 H, Ar), 7.24–7.13 (m, 5 H, Ar), 6.80 (s, 1 H, furan), 3.58–
3.48 (m, 1 H, CH2CHCH2), 3.22–3.00 (m, 2 H, CH2CHCH2), 2.74–
2.71 (m, 2 H, CH2CHCH2), 2.54 (dd, J = 7.8, 7.5 Hz, 2 H, Ar-
CH2CH2CH2CH2CH3),
CH2CH2CH2CH2CH3),
1.59–1.49
1.25 (br.
(m,
s,
2
4
H,
H,
Ar-
Ar-
CH2CH2CH2CH2CH3), 0.82 (dd, J = 6.6, 5.1 Hz, 3 H, Ar-
CH2CH2CH2CH2CH3) ppm. 13C NMR (75 MHz, CDCl3): δ =
193.12, 165.52, 154.99, 143.27, 142.43, 128.86, 128.84, 127.22,
126.77, 126.69, 123.95, 122.72, 100.02, 44.90, 41.23, 35.69, 31.42,
31.23, 31.01, 22.51, 14.02 ppm. HRMS (EI+): calcd. for C25H26O2
358.1933; found 358.1930.
6-(2-Furyl)-2-phenyl-6,7-dihydrobenzofuran-4(5H)-one (34): Yield
72%; yellow liquid; TLC (1:6 EA/hexane): R = 0.40. IR (neat): ν
˜
f
= 3119, 3058, 2956, 2904, 1674, 1438, 1330, 1216, 1137, 1008, 920,
812, 743, 700, 605 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.70 (d,
J = 7.5 Hz, 2 H, Ar), 7.47–7.41 (m, 3 H, Ar), 7.37–7.30 (m, 1 H,
furan), 6.94 (s, 1 H, furan), 6.36 (br. s, 1 H, furan), 6.16 (d, J =
3.3 Hz, 1 H, furan), 3.79–3.70 (m, 1 H, CH2CHCH2), 3.43–3.53
(m, 1 H, CH2CHCH2a), 3.26–3.17 (m, 1 H, CH2CHCH2b), 2.97–
2.77 (m, 2 H, CH2CHCH2) ppm. 13C NMR (75 MHz, CDCl3): δ
= 192.37, 164.90, 155.41, 154.74, 141.70, 129.60, 128.77, 128.17,
123.96, 122.72, 110.18, 105.09, 100.77, 42.02, 34.36, 28.49 ppm.
HRMS (EI+): calcd. for C18H14O3 278.0943; found 278.0944.
2-(4-Methoxy-2-methylphenyl)-6-phenyl-6,7-dihydrobenzofuran-
4(5H)-one (30): Yield 63%; brown solid; TLC (1:6 EA/hexane): Rf
= 0.28; m.p. 84–85 °C. IR (KBr): ν = 3029, 2947, 2845, 1674, 1605,
˜
1493, 1449, 1292, 1246, 1221, 1131, 1049, 1009, 812, 750, 701 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.53 (d, J = 9.3 Hz, 1 H, Ar),
7.29 (d, J = 6.9 Hz, 2 H, Ar), 7.25–7.18 (m, 3 H, Ar), 6.74–6.72
(m, 2 H, Ar), 6.62 (s, 1 H), 3.75 (s, 3 H, Ar-OCH3), 3.59–3.48 (m,
1 H, CH2CHCH2), 3.21–3.00 (m, 2 H, CH2CHCH2), 2.74–2.71 (m,
2 H, CH2CHCH2), 2.39 (s, 3 H, Ar-CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 193.27, 165.04, 159.31, 154.16, 142.45,
136.80, 128.85, 128.55, 127.21, 126.76, 122.55, 121.92, 116.46,
111.47, 103.06, 55.22, 44.89, 41.27, 31.18, 22.02 ppm. HRMS (EI+):
calcd. for C22H20O3 332.1412; found 332.1416.
6-(2-Furyl)-2-(4-methoxy-2-methylphenyl)-6,7-dihydrobenzofuran-
4(5H)-one (35): Yield 71%; brown solid; TLC (1:6 EA/hexane): Rf
= 0.37; m.p. 140–141 °C. IR (KBr): ν = 3122, 2938, 2853, 1671,
˜
1604, 1495, 1448, 1294, 1244, 1207, 1137, 1051, 803, 741, 631 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.58 (d, J = 8.4 Hz, 1 H, Ar),
7.34 (br. s, 1 H, Ar), 6.79–6.77 (m, 2 H, Ar), 6.65 (s, 1 H, furan),
6.30 (br. s, 1 H, furan), 6.10 (d, J = 2.7 Hz, 1 H, furan), 3.81 (s, 3
H, Ar-OCH3), 3.73–3.64 (m, 1 H, CH2CHCH2), 3.36–3.28 (m, 1
H, CH2CHCH2a), 3.18–3.09 (m, 1 H, CH2CHCH2b), 2.91–2.71 (m,
2 H, CH2CHCH2), 2.43 (s, 3 H, Ar-CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 192.59, 164.19, 159.39, 155.56, 154.29,
141.69, 136.84, 128.61, 122.56, 121.91, 116.50, 110.19, 105.03,
103.04, 55.23, 42.07, 34.46, 28.48, 21.97 ppm. HRMS (EI+): calcd.
for C20H18O4 322.1205; found 322.1206.
6-(Benzo[d][1,3]dioxol-5-yl)-2-(3-fluorophenyl)-6,7-dihydrobenzo-
furan-4(5H)-one (31): Yield 71%; brown liquid; TLC (1:6 EA/hex-
ane): R = 0.23. IR (neat): ν = 3062, 2896, 1736, 1676, 1606, 1491,
˜
f
1444, 1240, 1139, 1036, 932, 862, 803, 732, 701, 600, 519, 446 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.40 (dd, J = 7.8, 6.9 Hz, 1 H,
Ar), 7.35–7.32 (m, 2 H, Ar), 6.98 (dd, J = 8.4, 7.8 Hz, 1 H, Ar),
6.92 (s, 1 H, Ar), 6.77–6.72 (m, 3 H, Ar-2H, furan-H), 5.95 (s, 2
H, OCH2O), 3.56–3.46 (m, 1 H), 3.25–3.00 (m, 2 H), 2.74–2.71 (m,
2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 192.66, 165.89, 162.96
(d, JCF = 243.9 Hz), 153.31 (d, JCF = 2.8 Hz), 147.88, 146.58,
136.14, 131.58 (d, JCF = 8.8 Hz), 130.34 (d, JCF = 8.8 Hz), 122.69,
119.77, 119.54 (d, JCF = 3.3 Hz), 114.89 (d, JCF = 21.5 Hz), 110.79
(d, JCF = 23.6 Hz), 108.42, 107.03, 101.83, 101.07, 45.08, 40.89,
31.43 ppm. HRMS (EI+): calcd. for C21H15FO4 350.0954; found
350.0958.
6-(2-Furyl)-2-(1-naphthyl)-6,7-dihydrobenzofuran-4(5H)-one
Yield 70%; brown liquid; TLC (1:6 EA/hexane): Rf = 0.36. IR
(36):
(neat): ν = 3123, 3054, 2960, 2907, 1677, 1590, 1442, 1220, 1131,
˜
1
1019, 790, 740 cm–1. H NMR (300 MHz, CDCl3): δ = 8.32 (d, J
= 8.7 Hz, 1 H, Ar), 7.89 (d, J = 6.9 Hz, 1 H, Ar), 7.87 (d, J =
8.1 Hz, 1 H, Ar), 7.74 (d, J = 6.6 Hz, 1 H, Ar), 7.54–7.48 (m, 3 H,
Ar), 7.37 (br. s, 1 H, furan), 7.00 (s, 1 H, furan), 6.32 (br. s, 1
H, furan), 6.14 (d, J = 3.0 Hz, 1 H, furan), 3.80–3.70 (m, 1 H,
CH2CHCH2), 3.44–3.37 (m, 1 H, CH2CHCH2a), 3.27–3.18 (m, 1
H, CH2CHCH2b), 2.98–2.77 (m, 2 H, CH2CHCH2) ppm. 13C
NMR (75 MHz, CDCl3): δ = 192.55, 165.23, 155.45, 154.03,
141.76, 133.85, 130.14, 129.37, 128.64, 127.17, 126.91, 126.51,
126.15, 125.19, 124.99, 122.61, 110.22, 105.31, 105.12, 42.13, 34.48,
28.62 ppm. HRMS (EI+): calcd. for C22H16O3 328.1099; found
328.1096.
6-(Benzo[d][1,3]dioxol-5-yl)-2-(9-phenanthryl)-6,7-dihydrobenzo-
furan-4(5H)-one (32): Yield 54%; brown liquid; TLC (1:4 EA/hex-
ane): R = 0.43. IR (neat): ν = 3058, 2956, 2895, 1737, 1674, 1495,
˜
f
1443, 1242, 1127, 1038, 935, 813, 740 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 8.75 (d, J = 8.1 Hz, 1 H, Ar), 8.67 (d, J = 8.1 Hz, 1
H, Ar), 8.35 (d, J = 7.5 Hz, 1 H, Ar), 8.01 (s, 1 H, Ar), 7.91 (d, J
= 7.2 Hz, 1 H, Ar), 7.72–7.58 (m, 4 H, Ar), 7.05 (s, 1 H, Ar), 6.81–
6.66 (m, 3 H, Ar-2H, furan-H), 5.96 (s, 2 H, OCH2O), 3.63–3.52
(m, 1 H, CH2CHCH2), 3.35–3.07 (m, 2 H, CH2CHCH2), 2.80–
2.77 (m, 2 H, CH2CHCH2) ppm. 13C NMR (75 MHz, CDCl3): δ
= 193.03, 166.01, 153.93, 147.95, 146.64, 136.33, 130.97, 130.69,
2-Phenyl-4H-indeno[1,2-b]furan-4-one (37):[10e] Yield 77%; red so-
lid; TLC (1:6 EA/hexane): Rf = 0.60; m.p. 153–154 °C. IR (KBr):
130.39, 129.05, 129.04, 127.96, 127.52, 127.07, 127.06, 126.89, ν = 3111, 3059, 2926, 1712, 1610, 1466, 1413, 1269, 1177, 909, 871,
˜
3438
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3430–3442

Regioselective Synthesis of Highly Functionalized Furans
755, 719 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.46 (d, J =
7.5 Hz, 2 H, Ar), 7.25–7.21 (m, 3 H, Ar), 7.15 (d, J = 7.2 Hz, 1 H,
Ar), 7.10 (dd, J = 8.4, 7.2 Hz, 1 H, Ar), 6.97 (dd, J = 7.5, 7.2 Hz,
1 H, Ar), 6.91 (d, J = 6.9 Hz, 1 H, Ar), 6.47 (s, 1 H, furan) ppm.
13C NMR (75 MHz, CDCl3): δ = 184.96, 174.07, 160.07, 138.10,
133.79, 132.82, 129.54, 128.83, 128.63, 128.08, 125.03, 123.55,
123.44, 116.82, 100.92 ppm. HRMS (EI+): calcd. for C17H10O2
246.0681; found 246.0681.
CDCl3): δ = 7.30 (s, 1 H, furan), 2.91 (dd, J = 6.3, 6.0 Hz, 2 H,
CH2CH2CH2), 2.48 (dd, J = 6.9, 6.0 Hz, 2 H, CH2CH2CH2), 2.39
(s, 3 H, COCH3), 2.20–2.12 (m, 2 H, CH2CH2CH2) ppm. 13C
NMR (75 MHz, CDCl3): δ = 193.69, 186.21, 170.07, 151.73,
122.42, 113.72, 37.48, 25.85, 23.45, 21.98 ppm. HRMS: calcd. for
C10H10O3 178.0630; found 178.0633.
Ethyl 4-Oxo-6-phenyl-4,5,6,7-tetrahydrobenzofuran-2-carboxylate
(44):[16] Yield 48%; yellow solid; TLC (1:6 EA/hexane): Rf = 0.40;
Ethyl 6,6-Dimethyl-4-oxo-4,5,6,7-tetrahydrobenzofuran-2-carboxyl-
m.p. 72–73 °C. IR (KBr): ν = 3030, 2982, 1725, 1687, 1592, 1544,
˜
ate (38):[16] Yield 55%; yellow liquid; TLC (1:6 EA/hexane): Rf =
1450, 1285, 1215, 1145, 1029, 857, 763, 700 cm–1. 1H NMR
0.40. IR (neat): ν = 3131, 2962, 1725, 1690, 1593, 1545, 1451, 1372,
(300 MHz, CDCl3): δ = 7.35 (s, 1 H, furan), 7.33–7.28 (m, 2 H,
˜
1285, 1220, 1152, 1027, 859, 762 cm–1. 1H NMR (300 MHz, Ar), 7.25–7.20 (m, 3 H, Ar), 4.31 (q, J = 7.2 Hz, 2 H, OCH2CH3),
CDCl3): δ = 7.33 (s, 1 H, furan), 4.32 (q, J = 7.2 Hz, 2 H, 3.57–3.47 (m, 1 H, CH2CHCH2), 3.45–3.01 (m, 2 H, CH2CHCH2),
OCH2CH3), 2.78 (s, 2 H, CH2), 2.36 (s, 2 H, CH2), 1.33 (t, J =
2.74 (d, J = 8.4 Hz, 2 H, CH2CHCH2), 1.31 (t, J = 7.2 Hz, 3 H,
7.2 Hz, 3 H, OCH2CH3), 1.10 (s, 6 H, 2 CH3) ppm. 13C NMR OCH2CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 192.27, 168.62,
(75 MHz, CDCl3): δ = 193.11, 168.75, 158.36, 144.94, 121.22,
113.60, 61.32, 51.90, 37.40, 35.11, 28.40, 14.20 ppm. HRMS: calcd.
for C13H16O4 236.1049; found 236.1046.
158.32, 145.05, 141.70, 128.93, 127.41, 126.66, 122.25, 113.65,
61.43, 44.91, 40.78, 31.24, 14.21 ppm. HRMS: calcd. for C17H16O4
284.1049; found 284.1050.
Methyl
oxylate (39):[16] Yield 54%; yellow liquid; TLC (1:6 EA/hexane): Rf
= 0.38. IR (neat): ν = 2958, 1730, 1687, 1593, 1545, 1447, 1288,
6,6-Dimethyl-4-oxo-4,5,6,7-tetrahydrobenzofuran-2-carb-
2-Acetyl-6-phenyl-6,7-dihydrobenzofuran-4(5H)-one (45):[16] Yield
42%; yellow solid; TLC (1:6 EA/hexane): Rf = 0.35; m.p. 134–
135 °C. IR (KBr): ν = 3125, 3060, 2956, 2917, 1680, 1585, 1531,
˜
˜
1219, 1150, 1032, 762 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.36 1449, 1363, 1277, 1217, 1137, 1031, 965, 852, 762, 736, 701,
(s, 1 H, furan), 3.89 (s, 3 H, OCH3), 2.80 (s, 2 H, CH2), 2.39 (s, 2
649 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.34 (s, 1 H, furan),
H, CH2), 1.13 (s, 6 H, 2 CH3) ppm. 13C NMR (75 MHz, CDCl3): 7.32–7.27 (m, 2 H, Ar), 7.23–7.19 (m, 3 H, Ar), 3.57–3.46 (m, 1 H,
δ = 193.18, 168.91, 158.83, 144.68, 121.32, 113.89, 52.28, 51.96, CH2CHCH2), 3.24–3.10 (m, 2 H, CH2CHCH2), 2.73 (d, J =
37.46, 35.18, 28.47 ppm. HRMS: calcd. for C12H14O4 222.0892;
found 222.0893.
8.4 Hz, 2 H, CH2CHCH2), 2.40 (s, 3 H, COCH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 192.35, 186.25, 152.19, 147.25, 141.54,
128.90, 127.40, 126.60, 122.32, 113.65, 44.84, 40.65, 31.20,
25.92 ppm. HRMS: calcd. for C16H14O3 254.0943; found 254.0943.
2-Acetyl-6,6-dimethyl-6,7-dihydrobenzofuran-4(5H)-one
Yield 48%; white solid; TLC (1:6 EA/hexane): Rf = 0.35; m.p. 80–
(40):[16]
81 °C. IR (KBr): ν = 3110, 2956, 1673, 1581, 1525, 1451, 1281, 1,1-Diacetyl-2-phenylcycloprop-2-ene (46): Yield 10%; yellow li-
˜
1222, 1134, 1085, 1038, 964 cm–1. H NMR (300 MHz, CDCl3): δ
= 7.34 (s, 1 H, furan), 2.78 (s, 2 H, CH2), 2.42 (s, 3 H, COCH3),
2.39 (s, 2 H, CH2), 1.11 (s, 6 H, 2 CH3) ppm. 13C NMR (75 MHz,
quid; TLC (1:6 EA/hexane): R = 0.25. IR (neat): ν = 3140, 3062,
1
˜
f
3003, 2925, 1765, 1689, 1610, 1489, 1418, 1358, 1262, 1210, 1025,
1
765, 699 cm–1. H NMR (300 MHz, CDCl3): δ = 7.46–7.43 (m, 2
CDCl3): δ = 193.28, 186.22, 169.38, 152.20, 121.36, 113.75, 51.88, H, Ar), 7.35–7.30 (m, 3 H, Ar), 6.92 (s, 1 H, cyclopropene), 2.11
37.40, 35.10, 28.41, 28.26, 26.80 ppm. HRMS (EI+): calcd. for
C12H14O3 206.0943; found 206.0941.
(s, 6 H, 2 COCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 207.18,
130.61, 129.95, 128.92, 123.63, 113.87, 96.95, 47.67, 28.31 ppm.
HRMS (EI+): calcd. for C13H12O2 200.0837; found 200.0839.
Ethyl 4-Oxo-4,5,6,7-tetrahydrobenzofuran-2-carboxylate (41):[16]
Yield 52%; white solid; TLC (1:6 EA/hexane): Rf = 0.35; m.p. 54–
3-Acetyl-2-methyl-5-phenylfuran (47):[10f,24c,24j] Yield 31%; yellow
55 °C. IR (KBr): ν = 3003, 2978, 2938, 1713, 1689, 1592, 1544, liquid; TLC (1:6 EA/hexane): R = 0.55. IR (neat): ν = 3059, 3004,
˜
˜
f
1441, 1372, 1306, 1208, 1187, 1148, 1018, 1001, 892 cm–1. 1H NMR
2923, 2854, 1673, 1609, 1555, 1489, 1406, 1358, 1235, 1159, 1071,
(300 MHz, CDCl3): δ = 7.35 (s, 1 H, furan), 4.34 (q, J = 7.2 Hz, 2 1026, 950, 762, 693, 632 cm–1. 1H NMR (300 MHz, CDCl3): δ =
H, OCH2CH3), 2.94 (dd, J = 6.3, 6.0 Hz, 2 H, CH2CH2CH2), 2.51 7.56 (d, J = 7.5 Hz, 2 H, Ar), 7.34–7.29 (m, 2 H, Ar), 7.20 (dd, J
(dd, J = 6.9, 6.0 Hz, 2 H, CH2CH2CH2), 2.23–2.14 (m, 2 H,
= 7.0, 6.0 Hz, 1 H, Ar), 6.76 (s, 1 H, furan), 2.58 (s, 3 H, COCH3),
CH2CH2CH2), 1.34 (t, J = 7.2 Hz, 3 H, OCH2CH3) ppm. 13C
2.37 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.15,
NMR (75 MHz, CDCl3): δ = 193.70, 169.56, 158.43, 144.63, 157.90, 151.61, 129.85, 128.72, 127.72, 123.62, 123.17, 105.03,
122.41, 113.77, 61.39, 37.61, 23.56, 22.17, 14.24 ppm. HRMS (EI+):
calcd. for C11H12O4 208.0736; found 208.0738.
29.13, 14.50 ppm. HRMS (EI+): calcd. for C13H12O2 200.0837;
found 200.0838.
Methyl 4-Oxo-4,5,6,7-tetrahydrobenzofuran-2-carboxylate (42):[16]
Methyl 1-Acetyl-2-phenylcycloprop-2-ene-1-carboxylate (48):[24k]
Yield 50%; white solid; TLC (1:6 EA/hexane): Rf = 0.30; m.p. 67–
Yield 10%; yellow liquid; TLC (1:6 EA/hexane): Rf = 0.22. IR
68 °C. IR (KBr): ν = 3130, 2954, 1728, 1687, 1591, 1545, 1438, (neat): ν = 3144, 3060, 3004, 2953, 2845, 1731, 1614, 1443, 1358,
˜
˜
1
1297, 1213, 1145, 1004, 763, 727 cm–1. 1H NMR (300 MHz, 1272, 1045, 979, 764, 702 cm–1. H NMR (300 MHz, CDCl3): δ =
CDCl3): δ = 7.34 (s, 1 H, furan), 3.87 (s, 3 H, OCH3), 2.93 (t, J = 7.43–7.40 (m, 2 H, Ar), 7.27–7.24 (m, 3 H, Ar), 6.82 (s, 1 H, furan),
6.3 Hz, 2 H, CH2CH2CH2), 2.51 (dd, J = 6.9, 6.0 Hz, 2 H, 3.52 (s, 3 H, CO2CH3), 2.05 (s, 3 H, COCH3) ppm. 13C NMR
CH2CH2CH2), 2.22–2.15 (m, 2 H, CH2CH2CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 205.58, 171.32, 130.30, 129.83, 128.63,
(75 MHz, CDCl3): δ = 193.68, 169.65, 158.78, 144.26, 122.40,
113.94, 52.24, 37.57, 23.51, 22.11 ppm. HRMS: calcd. for
C10H10O4 194.0579; found 194.0577.
123.55, 112.65, 95.99, 51.67, 40.13, 27.44 ppm. HRMS: calcd. for
C13H12O3 216.0786; found 216.0788.
Methyl 2-Methyl-5-phenylfuran-3-carboxylate (49):[24k] Yield 29%;
2-Acetyl-6,7-dihydrobenzofuran-4(5H)-one (43):[16] Yield 45%; yel-
low solid; TLC (1:6 EA/hexane): Rf = 0.28; m.p. 54–55 °C. IR
yellow liquid; TLC (1:6 EA/hexane): R = 0.60. IR (neat): ν = 3135,
˜
f
3065, 2951, 1854, 1719, 1611, 1444, 1237, 1098, 1046, 762,
(KBr): ν = 3123, 2956, 1647, 1583, 1531, 1450, 1359, 1300, 1215, 661 cm–1. H NMR (300 MHz, CDCl3): δ = 7.56 (d, J = 7.2 Hz, 2
1
˜
1141, 1081, 1006, 969, 732, 695, 625 cm–1. 1H NMR (300 MHz,
H, Ar), 7.30 (t, J = 7.5 Hz, 2 H, Ar), 7.19 (dd, J = 7.5, 7.2 Hz, 1
3439
Eur. J. Org. Chem. 2014, 3430–3442
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org

L. Xia, Y. R. Lee
FULL PAPER
H, Ar), 6.80 (s, 1 H, furan), 3.77 (s, 3 H, CO2CH3), 2.57 (s, 3 H,
Supporting Information (see footnote on the first page of this arti-
CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 164.48, 158.75, cle): 1H and 13C NMR spectra for compounds 3–13, 15–51, 53, 55,
151.77, 130.02, 128.71, 127.64, 123.62, 115.10, 105.39, 51.37,
13.87 ppm. HRMS: calcd. for C13H12O3 216.0786; found 216.0788.
and 57.
Allyl 1-Acetyl-2-phenylcycloprop-2-ene-1-carboxylate (50): Yield
Acknowledgments
7%; yellow liquid; TLC (1:6 EA/hexane): R = 0.23. IR (neat): ν =
˜
f
3141, 3077, 2944, 1729, 1650, 1447, 1417, 1361, 1233, 1097, 1041,
991, 934, 765, 698 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.51–
7.48 (m, 2 H, Ar), 7.36–7.33 (m, 3 H, Ar), 6.86 (s, 1 H, cyclopro-
pene), 5.88–5.71 (m, 1 H, OCH2CH=CH2), 5.20–5.06 (m, 2 H,
OCH2CH=CH2), 4.55–4.53 (m, 2 H, CH2, OCH2CH=CH2), 2.15
(s, 3 H, COCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 205.76,
170.77, 131.70, 130.52, 130.09, 128.82, 123.76, 117.86, 112.97,
95.99, 65.31, 40.51, 27.83 ppm. HRMS: calcd. for C15H14O3
242.0943; found 242.0944.
This research was supported by the Korean Ministry of Education,
Science, and Technology, Korean National Research Foundation
(NRF) (grant number 2012M3A7B4049675) through the Nano
Material Technology Development Program.
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Allyl 2-Methyl-5-phenylfuran-3-carboxylate (51): Yield 25%; yellow
liquid; TLC (1:6 EA/hexane): R = 0.58. IR (neat): ν = 3133, 3083,
˜
f
2931, 1717, 1610, 1410, 1232, 1094, 1042, 928, 762, 691, 662 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.56 (d, J = 7.5 Hz, 2 H, Ar),
7.31 (dd, J = 7.8, 7.2 Hz, 2 H, Ar), 7.19 (dd, J = 7.5, 7.2 Hz, 1 H,
Ar), 6.82 (s, 1 H, furan), 6.02–5.89 (m, 1 H, OCH2CH=CH2), 5.32
(dd, J = 17.4, 1.5 Hz, 1 H, OCH2CH=CH2a), 5.21 (dd, J = 10.5,
1.2 Hz, 1 H, OCH2CH=CH2b), 4.69 (d, J = 5.7 Hz, 2 H,
OCH2CH=CH2), 2.58 (s, 3 H, CH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 163.66, 158.90, 151.78, 132.37, 129.99, 128.70, 127.64,
123.63, 118.10, 115.08, 105.41, 64.86, 13.95 ppm. HRMS: calcd.
for C15H14O3 242.0943; found 242.0942.
6,6-Dimethyl-2-phenyl-1,2,3,6-tetrahydrobenzofuran-4(5H)-one
(52):[12] Yield 7%.
6,6-Dimethyl-2-(prop-1-en-2-yl)-6,7-dihydrobenzofuran-4(5H)-one
(53):[16] Yield 45%; yellow liquid; TLC (1:6 EA/hexane): Rf = 0.45.
IR (neat): ν = 3118, 2949, 2892, 1676, 1445, 1379, 1219, 1122, 1034,
˜
894, 820, 647 cm–1. 1H NMR (300 MHz, CDCl3): δ = 6.48 (s, 1 H,
furan), 5.49 (s, 1 H, CH2a=CCH3), 4.99 (s, 1 H, CH2b=CCH3), 2.73
(s, 2 H, CH2), 2.34 (s, 2 H, CH2), 1.97 (s, 3 H, CH2=CCH3), 1.12
(s, 6 H, 2 CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 193.94,
165.99, 155.46, 132.10, 121.25, 111.08, 102.10, 51.90, 37.37, 35.22,
25.59, 19.15 ppm. HRMS (EI+): calcd. for C13H16O2 204.1150;
found 204.1149.
2-(Prop-1-en-2-yl)-6,7-dihydrobenzofuran-4(5H)-one (55):[16] Yield
42%; yellow liquid; TLC (1:6 EA/hexane): R = 0.30. IR (neat): ν
˜
f
= 3118, 2948, 2887, 1675, 1447, 1365, 1215, 1182, 1132, 1004, 891,
1
820, 726, 695, 620 cm–1. H NMR (300 MHz, CDCl3): δ = 6.46 (s,
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2.85 (t, J = 6.3 Hz, 2 H, CH2CH2CH2), 2.45 (dd, J = 7.2, 6.0 Hz,
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6-Phenyl-2-(prop-1-en-2-yl)-6,7-dihydrobenzofuran-4(5H)-one (57):
Yield 38%; yellow liquid; TLC (1:6 EA/hexane): Rf = 0.40. IR
(neat): ν = 3056, 3031, 2943, 1735, 1673, 1447, 1218, 1128, 1033,
˜
946, 895, 811, 736, 701 cm–1. 1H NMR (300 MHz, CDCl3): δ =
7.28–7.26 (m, 2 H, Ar), 7.22–7.20 (m, 3 H, Ar), 6.47 (s, 1 H, furan),
5.46 (s, 1 H, CH2a=CCH3), 4.96 (s, 1 H, CH2b=CCH3), 3.48–3.43
(m, 1 H, CH2CHCH2), 3.11 (dd, J = 17.1, 5.1 Hz, 1 H,
CH2CHCH2a), 2.98 (dd, J = 17.1, 10.8 Hz, 1 H, CH2CHCH2b),
2.68 (d,
J = 8.4 Hz, 2 H, CH2CHCH2), 1.93 (s, 3 H,
CH2=CCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 192.93,
165.86, 155.60, 142.34, 131.96, 128.81, 127.17, 126.69, 122.32,
111.40, 102.10, 44.78, 41.11, 31.13, 19.11 ppm. HRMS: calcd. for
C17H16O2 252.1150; found 252.1154.
3440
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3430–3442

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Received: February 26, 2014
Published Online: April 17, 2014
3442
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