Bismuth(III) triflate-catalyzed synthesis of substituted 2-alkenylfurans

Article abstract of DOI:10.1021/jo5009993

A convergent synthesis of the title compounds is reported, which relies on a successive 2-fold S_N'-type substitution reaction at methoxy-substituted propargylic acetates. The furan C3-C4 bond is presumably established by silyl enol ether attack at a propargylic cation intermediate. The resulting α-methoxyallene is intramolecularly substituted, leading to cyclization by displacement of the methoxy group (O-C2 bond formation) and to simultaneous formation of the exocyclic alkene double bond. Despite the relatively mild conditions, the reactions were complete within 5 min.

Full text of DOI:10.1021/jo5009993

Note
pubs.acs.org/joc
Bismuth(III) Triflate-Catalyzed Synthesis of Substituted
2‑Alkenylfurans
Dominik Nitsch and Thorsten Bach*
Lehrstuhl fur Organische Chemie I and Catalysis Research Center (CRC), Technische Universitat Munchen, Lichtenbergstr. 4, 85747
̈
̈
̈
Garching, Germany
S
* Supporting Information
ABSTRACT: A convergent synthesis of the title compounds
is reported, which relies on a successive 2-fold SN′-type
substitution reaction at methoxy-substituted propargylic
acetates. The furan C3−C4 bond is presumably established
by silyl enol ether attack at a propargylic cation intermediate.
The resulting α-methoxyallene is intramolecularly substituted,
leading to cyclization by displacement of the methoxy group
(O−C2 bond formation) and to simultaneous formation of the exocyclic alkene double bond. Despite the relatively mild
conditions, the reactions were complete within 5 min.
ubstituted furans play an important role in organic
chemistry due to their presence in many naturally occurring
During our studies on SN1-type reactions of propargylic
carbocations14 we observed that, in contrast to its secondary
analogues, tertiary propargylic acetate 1 reacted with the silyl
enol ether 2-trimethylsilyloxy-3,3-dimethylbutene not to the
expected substitution product but to 2-alkenylfuran 2. Typical
reaction conditions included the use of 10 mol % bismuth(III)
trifluoromethanesulfonate [Bi(OTf)3]15 as the Lewis acid and
nitromethane as the solvent (Scheme 2) at room temperature.
Mechanistically, the reaction outcome was interpreted as an
SN1′ attack of the nucleophile at the distal γ-position of the
propargylic cation 3. Indeed, in a previous example14a the γ-
approach had been observed at a related secondary cation for a
S
compounds1 and pharmaceuticals.2 Furthermore, they repre-
sent useful building blocks in synthetic chemistry.3 The
remarkable utility of furans has led to a broad spectrum of
synthetic routes for the construction of their heterocyclic core
structure. Besides classical reactions like the Paal−Knorr4 and
the Feist−Benary5 furan synthesis, transition-metal catalysis
often plays an essential role in the formation of multiply
substituted furans.6 These approaches include not only
cycloisomerization-type reactions7 but also formal [4 + 1]8
and [3 + 2]9 cycloaddition reactions of alkyne- and allene-
containing compounds.
When searching more specifically for an access to 2-
alkenylfurans of general structure A (Scheme 1), three main
Scheme 2. Formation of Furan 2 from Propargylic Acetate 1
upon Attempted Bi(OTf)3-Catalyzed SN1-type Substitution
and Mechanistic Explanation Based on Intermediates 3 and
4
Scheme 1. General Structure A of the Title Compounds and
Disconnection into Starting Materials of General Structure B
and C
access strategies are found in the literature.10 Starting from
enyne-ketones or alcohols, an attack of the oxygen nucleophile
at the triple bond leads to 2-alkenylfurans with simultaneous
generation of the furan core.11 Alternatively, the double bond
can be installed at an existing furan ring, either by C−C bond
formation at the 2-position of the furan nucleus12 or by
olefination reactions.13 In this note, we describe an alternative
access to the title compounds that is based on an acid-catalyzed
domino reaction between propargylic acetates of general
structure B and silyl enol ethers C (Scheme 1).
Received: May 8, 2014
Published: June 19, 2014
© 2014 American Chemical Society
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Note
sterically encumbered silyl enol ether but it had not led to a
consecutive reaction. In the present case, it is likely that the
tertiary group adjacent to the α-position prevents the SN1-type
attack and guides the nucleophile to form allene intermediate 4.
Apparently, the Lewis acid is not only sufficiently strong to
initiate formation of cation 3 but also induces another SN1′
substitution, which leads to oxygen−carbon formation at the
central allene carbon atom upon displacement of the methoxy
group. Deprotonation at the resulting cationic intermediate
generates the observed product 2 (d.r. = 54/46). Further
evidence for the suggested mechanism was obtained by
isolation of the intermediate allene related to 4, if the respective
methyl- instead of the methoxy-substituted substrate was
employed under identical reaction conditions.
Regarding the bond set, the reaction is reminiscent of a
recently reported FeCl3-catalyzed substitution reaction of
secondary propargylic acetates with silyl enol ethers affording
the corresponding γ-alkynyl ketones.16 A subsequent acid-
catalyzed cyclization provided tri- and tetrasubstituted furans.
Nevertheless, high temperatures and strong Brønsted acids
limit the scope of possible substrates for this transformation. A
milder alternative was reported by the Kirsch group who used
AuCl(PPh3) for a cascade reaction including a propargyl-
Claisen rearrangement followed by an heterocyclyzation of
propargyl vinyl ethers.17 In neither of these reactions 2-
alkenylketones are formed, however, because the reactions are
terminated by addition to the triple bond.
under Bi(OTf)3-catalysis was relatively slow at −78 °C, it was
found to proceed rapidly (within 5 min) at 0 °C. TLC control
indicated complete conversion and work-up was performed
upon warming to room temperature. Under these conditions
the yield rose to 77% (Table 1, entry 1), and the reaction could
be performed with similar success on larger scale. Using the
optimized conditions other silyl enol ethers were employed as
nucleophiles and the multiply substituted furans 6b−6e (entries
2−6) were obtained in moderate to high yields (46−92%).
The synthesis of the propargylic acetates was straightforward
and commenced with the respective acetylene, i.e., with para-
methoxyphenylaceteylene in the case of acetate 5. Deprotona-
tion with butyl lithium at −78 °C delivered a suitable
nucleophile for attack at the respective α-methoxyketone. The
intermediate alcohol 7 was subsequently acylated with acetyl
chloride employing sodium hydride as the base (Scheme 3).
Attempts to take alcohol 7 directly into the furan synthesis
failed under a variety of conditions.
Scheme 3. Synthesis of Substrate 5 from para-
Methoxyphenylaceteylene via Alcohol 7
It seemed as if the observed furan formation could be general
as long as the respective propargylic acetates were tertiary and
would carry a methoxy group as leaving group in the adjacent
position. The reaction of substrate 5 with 2-trimethylsilyloxy-
3,3-dimethylbutene was studied more closely and indeed led to
the expected furan product 6a (Table 1). It turned out that the
To avoid the formation of olefin diastereoisomers, we tested
in further experiments only substrates with identical sub-
stituents R4 at the methoxy-substituted carbon atom. As for
acetate 5, the reaction sequence commenced with the
respective alkyne (Table 2) and went via the respective alcohol
8 to acetates 9. Gratifyingly, we noted that the furan formation
was also general regarding different substituents R, R3 and R4.
Furans 10 were isolated in yields of 51 to 92% with the lowest
yield recorded for the butyl-substituted propargyl acetate 9b
(entry 2). The latter result indicates that stabilization of the
intermediate propargylic cation plays an important role for the
outcome of the reaction. The synthesis of the isopropyl-
substituted acetate 9g (entry 7) turned out to be not possible
under standard acetylation conditions. Instead, the alcohol 8g
could in this specific case be directly converted to the desired
furan 10g in moderate yield (55%). While the furan forming
reactions with other substituents R4 = alkyl went smoothly
(entries 1−6), the reaction for the respective substrate 9h with
R4 = H did not produce a furan (entry 8). In this case, the silyl
enol ether attacked the substrate at the α-position (Scheme 2)
in a direct SN1 but not in an SN1′ reaction forming an
alkynylketone. The addition product was obtained in 71% yield.
Apparently, the γ-attack of the silyl enol ether requires
significant steric shielding at the α-position to occur.
Table 1. Bi(OTf)3-Catalyzed Reaction of Propargylic Acetate
5 with Various Silyl Enol Ethers to 2-(1,2-Dimethyl-1-
propenyl)furans 6
a
entry
R1
R2
product
yield [%]
1
2
3
4
t-Bu
H
H
6a
6b
6c
6d
6e
6f
77
69
92
63
86
46
Ph
− (CH2)4 −
− (CH2)3 −
Me
Me
b
5
Et
6
Ac
a
Reactions were performed in dry MeNO2 (c = 125 mM). After 5 min
at 0 °C the reaction mixture was warmed to ambient temperature.
b
The silyl enol ether was used as an E/Z mixture (E/Z = 20/80).
In summary, a new route for the synthesis of various 2-
alkenylfurans was established, which is based on a simultaneous
construction of the furan core and of the alkenyl side chain. It
requires readily available starting materials (propargylic
acetates, silyl enol ethers), which can be easily varied. The
reaction appears general for several substitution patterns at
both substrates and should allow for the construction of a
diverse array of 2-alkenylfurans.
reaction can be performed not only with Bi(OTf)3 as catalyst
(10 mol %) but also with other Lewis and Brønsted acids.
Yields, which were comparable to the yield with Bi(OTf)3
(67%), were recorded at identical catalyst loadings for InCl3
(63%), AgOTf (62%), Sc(OTf)3 (65%) and HOTf (61%) in
nitromethane as solvent at ambient temperature (for further
details see the Supporting Information). While the reaction
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The Journal of Organic Chemistry
Note
saturated NaCl-solution (5.0 mL/mmol), dried over Na2SO4, filtered
and concentrated. The crude product was purified by flash
chromatography on silica gel to afford the tertiary propargylic alcohols
7 and 8.
Table 2. Preparation of Various Propargylic Acetates 9 and
Their Bi(OTf)3-Catalyzed Reaction with 3-
Trimethylsilyloxy-3,3-dimethylbutene to Furans 10
To transform the alcohol to the corresponding acetates 5 and 9, a
solution of the alcohol (1.0 equiv) in DMF (1.0 mL/mmol alcohol)
was added to a suspension of NaH (60% in mineral oil, 10.0 equiv) in
dry DMF (0.5 mL/mmol NaH) at 0 °C. The mixture was warmed to
room temperature and stirred for additional 30 min before it was
cooled to 0 °C again. Acetyl chloride (10.0 equiv) was added within 30
min; the reaction was warmed to room temperature and was stirred for
60 min. Water (4 mL/mmol) was added to the reaction mixture, and
the mixture was saturated with NaCl. The aqueous layer was then
extracted with diethyl ether (4 × 4 mL/mmol). The combined organic
extracts were washed subsequently with water (4 mL/mmol) and an
aqueous saturated NaCl-solution (4 mL/mmol), dried over Na2SO4,
filtered and concentrated. The crude product was purified by flash
chromatography on silica gel to afford the tertiary propargylic acetate 5
and 9.
4-Methoxy-1-(4-methoxyphenyl)-3,4-dimethylpent-1-yn-3-ol (7).
Synthesized according to the general procedure, using 1-ethynyl-4-
methoxybenzene (1.32 g, 10.0 mmol, 1.0 equiv) in THF (20 mL), n-
BuLi (4.0 mL, 10.0 mmol, 1.0 equiv) and 3-methoxy-3-methylbutan-2-
one (1.16 g, 10.0 mmol, 1.0 equiv) in THF (5 mL). Work up and
purification by column chromatography (n-pentane/EtOAc: 5/1)
yielded product 7 (1.99 g, 80%) as a colorless oil: TLC Rf = 0.42
entry
yield
(8)
yield
(9)
yield
(10)
[%]
(#
a
code)
R
R3
R4
[%]
[%]
1 (a)
2 (b)
3 (c)
4 (d)
5 (e)
6 (f)
cyclopropyl
n-Bu
Me Me
Me Me
Me Me
Me Me
Me Me
74
72
77
89
87
64
54
71
63
77
58
51
1-cyclohexenyl
PhS
51
60
67
84
Ph
69
92
PMP
Me −(CH2)5−
i Pr Me
62
88
(P:EtOAc 5:1 [UV/CAM]); IR (ATR) v = 3448, 2979, 2939, 2833,
̃
b
2237, 1508, 1247, 1109, 1028, 832, 738 cm−1; MS (EI, 70 eV) m/z
7 (g)
8 (h)
PMP
―
93
55
c
1
(%) = 248 (6) [C15H20O3]+, 73 (100) [C4H9O]+; H NMR (500
PMP
Me
H
―
a
MHz, CDCl3, 300 K) δ [ppm] = 1.27 (s, 3H), 1.40 (s, 3H), 1.53 (s,
3H), 3.05 (s, 1H), 3.33 (s, 3H), 3.80 (s, 3H), 6.79−6.84 (m, 2H),
7.34−7.39 (m, 2H); 13C {1H} NMR (91 MHz, CDCl3, 300 K) δ
[ppm] = 19.4, 19.9, 24.7, 50.2, 55.3, 74.3, 79.5, 83.7, 90.5, 113.8, 115.2,
133.1, 159.4; HRMS (EI, 70 eV) (C15H20O3) calcd. 248.1407, found
248.1404.
The latin letter refers to the substitution pattern at the propargylic
substrate. The silyl enol ether in the furan forming reaction was used
as an E/Z mixture (E/Z = 20/80). Instead of the acetate, the free
alcohol 8g was used in the furan synthesis. No furan formation was
observed. The SN1 substitution product was formed in 71% yield.
b
c
4-Methoxy-1-(4-methoxyphenyl)-3,4-dimethylpent-1-yn-3-yl ac-
etate (5). Synthesized according to the general procedure, using
alcohol 7 (1.11 g, 4.47 mmol, 1.0 equiv) in DMF (4.5 mL), NaH (1.80
g, 45.0 mmol, 10.0 equiv) in DMF (22 mL) and acetyl chloride (3.2
mL, 3.5 g, 45.0 mmol, 10.0 equiv). Work up and purification by
column chromatography (n-pentane/EtOAc: 5/1) yielded product 5
(0.99 g, 76%) as a colorless oil: TLC Rf = 0.48 (P:EtOAc 5:1 [UV/
EXPERIMENTAL SECTION
■
General Methods. All reactions, sensitive to air or moisture, were
carried out in flame-dried glassware under positive pressure of argon
using standard Schlenk techniques. Flash chromatography was
performed on silica gel 60 (230−400 mesh) with the eluent mixtures
given for the corresponding procedures. Thin layer chromatography
(TLC) was performed on silica coated glass plates (silca gel 60 F 254).
Compounds were detected by UV (λ = 254 nm, 366 nm) and CAM
(cerium ammonium molybdate solution). Technical solvents (n-
pentane, ethyl acetate) employed for preparative column chromatog-
raphy were purified by distillation prior to use. Chemical shifts are
reported relative to the solvent (CHCl3 δ(1H) = 7.26 ppm, δ(13C) =
77.0 ppm) as reference. HRMS data were recorded by electron
ionization (EI) on a transmission quadrupole mass spectrometer.
Commercially available, anhydrous Bi(OTf)3 was handled in a
glovebox. All other chemicals were used as received from commercial
suppliers. The silyl nucleophiles were synthesized by following known
procedures: [(3,3-dimethylbut-1-en-2-yl)oxy]trimethylsilane,18
trimethyl[(1-phenylvinyl)oxy]silane,19 (cyclohex-1-en-1-yloxy)-
trimethylsilane,20 (cyclopent-1-en-1-yloxy)trimethylsilane,21 trimethyl-
(pent-2-en-3-yloxy)silane,19 4-[(trimethylsilyl)oxy]pent-3-en-2-one.22
3-Methoxy-3-methylbutan-2-one,23 2-methoxy-2,4-dimethylpentan-3-
one24 and 1-(1-methoxycyclohexyl)ethanone25 were prepared accord-
ing to literature procedures.
General Procedure for the Preparation of Tertiary Prop-
argylic Acetates 5 and 9. n-BuLi (1.0 equiv, 2.5 M in hexane) was
added to a solution of the corresponding alkyne (1.00 equiv) in dry
THF (c = 0.5 M) at −78 °C. The solution was stirred for 30 min and a
solution of the ketone (1.00 equiv) in THF (c = 2.0 M) was added.
After complete addition the reaction mixture was stirred for additional
30 min at −78 °C and was subsequently warmed to room temperature.
Water (2.5 mL/mmol) was added to the reaction mixture, and the
aqueous layer was then extracted with ethyl acetate (3 × 2.5 mL/
mmol). The combined organic extracts were washed with an aqueous
CAM]); IR (ATR) v = 2981, 2950, 2835, 2233, 1741, 1509, 1241,
̃
1126, 1085, 1030, 832 cm−1; MS (EI, 70 eV) m/z (%) = 290 (3)
[C17H22O4]+, 230 (19) [C15H18O2]+, 200 (35) [C14H16O2]+, 73 (100)
[C4H9O]+, 43 (98) [C2H3O]+; 1H NMR (360 MHz, CDCl3, 300 K) δ
[ppm] = 1.39 (s, 6H), 1.81 (s, 3H), 2.06 (s, 3H), 3.36 (s, 3H), 3.79 (s,
3H), 6.78−6.83 (m, 2H), 7.34−7.39 (m, 2H); 13C {1H} NMR (91
MHz, CDCl3, 300 K) δ [ppm] = 19.7, 20.4, 21.4, 22.2, 50.9, 55.3, 79.4,
81.0, 85.8, 87.2, 113.7, 114.9, 133.2, 159.6, 169.0; HRMS (EI, 70 eV)
(C17H22O4) calcd. 290.1513, found 290.1515.
1-Cyclopropyl-4-methoxy-3,4-dimethylpent-1-yn-3-ol (8a). Syn-
thesized according to the general procedure, using cyclopropylacety-
lene (664 mg, 10.0 mmol, 1.0 equiv) in THF (20 mL), n-BuLi (4.0
mL, 10.0 mmol, 1.0 equiv) and 3-methoxy-3-methylbutan-2-one (1.16
g, 10.0 mmol, 1.0 equiv) in THF (5 mL). Work up and purification by
column chromatography (n-pentane/EtOAc: 20/1) yielded product
8a (1.35 g, 74%) as a colorless oil: TLC Rf = 0.37 (P:EtOAc 10:1
[UV/CAM]); IR (ATR) v = 3446, 2980, 2943, 2831, 2243, 1363,
̃
1160, 1088, 905, 876, 814 cm−1; MS (EI, 70 eV) m/z (%) = 182 (1)
[C11H18O2]+, 167 (1) [C10H15O2]+, 109 (3) [C7H9O]+, 73 (100)
[C4H9O]+, 43 (21) [C2H3O]+; 1H NMR (500 MHz, CDCl3, 300 K) δ
[ppm] = 0.63−0.66 (m, 2H), 0.71−0.75 (m, 2H), 1.18 (s, 3H), 1.23
(tt, 3J = 8.3, 5.0 Hz, 1H), 1.29 (s, 3H), 1.39 (s, 3H), 2.85 (s, 1H), 3.27
(s, 3H); 13C {1H} NMR (91 MHz, CDCl3, 300 K) δ [ppm] = −0.5,
8.2, 19.3, 19.8, 24.9, 50.2, 73.8, 77.9, 79.4, 87.3. The compound was
too labile to obtain an EI-HRMS.
1-Cyclopropyl-4-methoxy-3,4-dimethylpent-1-yn-3-yl acetate
(9a). Synthesized according to the general procedure, using 8a (1.35
g, 7.40 mmol, 1.0 equiv) in DMF (7.5 mL), NaH (2.96 g, 74.0 mmol,
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Note
10.0 equiv) in DMF (40 mL) and acetyl chloride (5.3 mL, 5.8 g, 74.0
mmol, 10.0 equiv). Work up and purification by column
chromatography (n-pentane/EtOAc: 30/1) yielded product 9a (1.05
g, 63%) as a colorless oil: TLC Rf = 0.41 (P:EtOAc 10:1 [UV/CAM]);
3H), 1.34 (s, 3H), 1.53−1.63 (m, 4H), 1.73 (s, 3H), 2.03 (s, 3H),
2.04−2.13 (m, 4H), 3.33 (s, 3H), 6.07−6.11 (m, 1H); 13C {1H} NMR
(91 MHz, CDCl3, 300 K) δ [ppm] = 19.7, 20.4, 21.4, 21.5, 22.2, 22.2,
25.6, 29.0, 50.9, 79.4, 81.0, 85.8, 87.7, 120.2, 135.1, 168.9. The
compound was too labile to obtain an EI-HRMS.
4-Methoxy-3,4-dimethyl-1-(phenylthio)pent-1-yn-3-ol (8d). Syn-
thesized according to the general procedure, using ethynyl(phenyl)-
sulfane (1.07 g, 8.0 mmol, 1.0 equiv) in THF (16 mL), n-BuLi (3.2
mL, 8.0 mmol, 1.0 equiv) and 3-methoxy-3-methylbutan-2-one (929
mg, 8.0 mmol, 1.0 equiv) in THF (4 mL). Work up and purification by
column chromatography (n-pentane/EtOAc: 20/1) yielded product
8d (1.79 g, 89%) as a colorless oil: TLC Rf = 0.39 (P:EtOAc 9:1 [UV/
IR (ATR) v = 2981, 2949, 2829, 2237, 1741, 1364, 1234, 1128, 1071,
̃
1013, 885, 817 cm−1; MS (EI, 70 eV) m/z (%) = 224 (1)
[C13H20O3]+, 209 (1) [C12H17O3]+, 73 (100) [C4H9O]+, 43 (21)
[C2H3O]+; 1H NMR (500 MHz, CDCl33, 300 K) δ [ppm] = 0.64−0.68
(m, 2H), 0.72−0.76 (m, 2H), 1.26 (tt, J = 8.2, 5.1 Hz, 1H), 1.28 (s,
3H), 1.30 (s, 3H), 1.68 (s, 3H), 2.02 (s, 3H), 3.31 (s, 3H); 13C {1H}
NMR (91 MHz, CDCl3, 300 K) δ [ppm] = −0.4, 8.2, 8.3, 19.6, 20.5,
21.2, 22.3, 50.8, 74.3, 79.3, 80.9, 89.6, 169.0. The compound was too
labile to obtain an EI-HRMS.
CAM]); IR (ATR) v = 3432, 3052, 2979, 2948, 2833, 2318, 1715,
̃
1439, 1200, 1088, 1024, 740, 688 cm−1; MS (EI, 70 eV) m/z (%) =
250 (6) [C14H18O2S]+, 177 (100) [C10H9OS]+, 141 (34) [C8H13O2]+;
1H NMR (500 MHz, CDCl3, 300 K) δ [ppm] = 1.25 (s, 3H), 1.36 (s,
2-Methoxy-2,3-dimethylnon-4-yn-3-ol (8b). Synthesized according
to the general procedure, using 1-hexyne (822 mg, 10.0 mmol, 1.0
equiv) in THF (20 mL), n-BuLi (4.0 mL, 10.0 mmol, 1.0 equiv) and 3-
methoxy-3-methylbutan-2-one (1.16 g, 10.0 mmol, 1.0 equiv) in THF
(5 mL). Work up and purification by column chromatography (n-
pentane/EtOAc: 20/1) yielded product 8b (1.43 g, 72%) as a colorless
3H), 1.53 (s, 3H), 3.14 (s, 1H), 3.32 (s, 3H), 7.18−7.23 (m, 1H),
7.30−7.35 (m, 2H), 7.41−7.45 (m, 2H); 13C {1H} NMR (91 MHz,
CDCl3, 300 K) δ [ppm] = 18.7, 20.1, 24.4, 50.1, 70.0, 75.0, 79.6, 102.0,
125.9, 126.3, 129.1, 133.1; HRMS (EI, 70 eV) (C14H18O2S) calcd.
250.1022, found 250.1042.
4-Methoxy-3,4-dimethyl-1-(phenylthio)pent-1-yn-3-yl acetate
(9d). Synthesized according to the general procedure, using 8d (1.13
g, 4.50 mmol, 1.0 equiv) in DMF (4.5 mL), NaH (1.80 g, 45.0 mmol,
10.0 equiv) in DMF (23 mL) and acetyl chloride (3.2 mL, 3.5 g, 45.0
mmol, 10.0 equiv). Work up and purification by column
chromatography (n-pentane/EtOAc: 7/1) yielded product 9d (0.88
g, 67%) as a colorless oil: TLC Rf = 0.40 (P:EtOAc 9:1 [UV/CAM]);
oil: TLC R = 0.48 (P:EtOAc 10:1 [UV/CAM]); IR (ATR) v = 3465,
̃
f
2978, 2956, 2934, 2832, 2244, 1465, 1363, 1154, 1116, 1091, 904, 768,
739 cm−1; MS (EI, 70 eV) m/z (%) = 141 (1) [C8H13O2]+, 125 (3)
[C8H13O]+, 73 (100) [C4H9O]+, 43 (21) [C2H3O]+; H NMR (500
1
3
MHz, CDCl3, 300 K) δ [ppm] = 0.89 (t, J = 7.3 Hz, 3H), 1.20 (s,
3H), 1.31 (s, 3H), 1.35−1.41 (m, 2H), 1.41 (s, 3H), 1.44−1.51 (m,
3
2H), 2.19 (t, J = 7.0 Hz, 2H), 2.86 (s, 1H), 3.27 (s, 3H); 13C {1H}
NMR (91 MHz, CDCl3, 300 K) δ [ppm] = 13.6, 18.4, 19.4, 19.8, 21.9,
25.0, 30.8, 50.2, 73.9, 79.4, 82.8, 84.4; HRMS (EI, 70 eV) (C12H22O2)
calcd. 198.1614, found 198.1607.
2-Methoxy-2,3-dimethylnon-4-yn-3-yl acetate (9b). Synthesized
according to the general procedure, using 8b (1.43 g, 7.20 mmol, 1.0
equiv) in DMF (7.0 mL), NaH (2.88 g, 72.0 mmol, 10.0 equiv) in
DMF (40 mL) and acetyl chloride (5.1 mL, 5.7 g, 72.0 mmol, 10.0
equiv). Work up and purification by column chromatography (n-
pentane/EtOAc: 30/1) yielded product 9b (1.00 g, 58%) as a colorless
IR (ATR) v = 3062, 2981, 2949, 2837, 2177, 1741, 1365, 1240, 1126,
̃
1085, 789, 688 cm−1; MS (EI, 70 eV) m/z (%) = 292 (2)
[C16H20O3S]+, 73 (100) [C4H9O]+, 43 (22) [C2H3O]+; 1H NMR
(360 MHz, CDCl3, 300 K) δ [ppm] = 1.35 (s, 3H), 1.37 (s, 3H), 1.82
(s, 3H), 2.07 (s, 3H), 3.35 (s, 3H), 7.18−7.22 (m, 1H), 7.31−7.35 (m,
2H), 7.47−7.50 (m, 2H); 13C {1H} NMR (91 MHz, CDCl3, 300 K) δ
[ppm] = 19.8, 20.7, 21.1, 22.1, 50.7, 72.7, 79.3, 81.1, 98.5, 126.1, 126.3,
129.1, 133.1, 169.0; HRMS (EI, 70 eV) (C16H20O3S) calcd. 292.1128,
found 292.1137.
oil: TLC R = 0.54 (P:EtOAc 10:1 [UV/CAM]); IR (ATR) v = 2984,
̃
f
2935, 2837, 2243, 1744, 1365, 1231, 1128, 1086, 1012, 947, 840 cm−1;
MS (EI, 70 eV) m/z (%) = 73 (100) [C4H9O]+, 43 (16) [C2H3O]+;
4-Methoxy-3,4-dimethyl-1-phenylpent-1-yn-3-ol (8e). Synthe-
sized according to the general procedure, using phenylacetylene
(818 mg, 8.0 mmol, 1.0 equiv) in THF (16 mL), n-BuLi (3.2 mL, 8.0
mmol, 1.0 equiv) and 3-methoxy-3-methylbutan-2-one (929 mg, 8.0
mmol, 1.0 equiv) in THF (4 mL). Work up and purification by
column chromatography (n-pentane/EtOAc: 20/1) yielded product
8e (1.52 g, 87%) as a colorless oil: TLC Rf = 0.39 (P:EtOAc 9:1 [UV/
1H NMR (500 MHz, CDCl3, 300 K) δ [ppm] = 0.89 (t, J = 7.3 Hz,
3
3H), 1.31 (s, 3H), 1.32 (s, 3H), 1.36−1.43 (m, 2H), 1.45−1.52 (m,
2H), 1.70 (s, 3H), 2.02 (s, 3H), 2.21 (t, 3J = 7.0 Hz, 2H), 3.32 (s, 3H);
13C {1H} NMR (91 MHz, CDCl3, 300 K) δ [ppm] = 13.6, 18.5, 19.5,
20.5, 21.2, 21.9, 22.3, 30.6, 50.8, 79.3, 79.4, 80.9, 86.6, 169.0; HRMS
(EI, 70 eV) [(C12H22O2(M-Ac)] calcd. 198.1614, found 198.1607.
1-(Cyclohex-1-en-1-yl)-4-methoxy-3,4-dimethylpent-1-yn-3-ol
(8c). Synthesized according to the general procedure, using 1-
ethynylcyclohexene (533 mg, 5.0 mmol, 1.0 equiv) in THF (10
mL), n-BuLi (2.0 mL, 5.0 mmol, 1.0 equiv) and 3-methoxy-3-
methylbutan-2-one (518 mg, 5.0 mmol, 1.0 equiv) in THF (2.5 mL).
Work up and purification by column chromatography (n-pentane/
EtOAc: 20/1) yielded product 8c (853 mg, 77%) as a colorless oil:
CAM]); IR (ATR) v = 3447, 2980, 2942, 2831, 2230, 1364, 1121,
̃
1106, 1089, 755, 690 cm−1; MS (EI, 70 eV) m/z (%) = 218 (2)
1
[C14H18O2]+, 102 (78), 73 (100) [C4H9O]+; H NMR (360 MHz,
CDCl3, 300 K) δ [ppm] = 1.28 (s, 3H), 1.41 (s, 3H), 1.55 (s, 3H),
3.09 (s, 1H), 3.33 (s, 3H), 7.27−7.32 (m, 3H), 7.41−7.46 (m, 2H);
13C {1H} NMR (91 MHz, CDCl3, 300 K) δ [ppm] = 19.3, 19.9, 24.6,
50.2, 74.3, 79.5, 83.8, 92.0, 123.0, 128.1, 128.1, 131.6; HRMS (EI, 70
eV) (C14H18O2) calcd. 218.1301, found 218.1296.
4-Methoxy-3,4-dimethyl-1-phenylpent-1-yn-3-yl acetate (9e).
Synthesized according to the general procedure, using 8e (982 mg,
4.50 mmol, 1.0 equiv) in DMF (4.5 mL), NaH (1.80 g, 45.0 mmol,
10.0 equiv) in DMF (23 mL) and acetyl chloride (3.2 mL, 3.5 g, 45.0
mmol, 10.0 equiv). Work up and purification by column
chromatography (n-pentane/EtOAc: 20/1) yielded product 9e (804
mg, 69%) as a colorless oil: TLC Rf = 0.48 (P:EtOAc 9:1 [UV/
TLC R = 0.34 (P:EtOAc 10:1 [UV/CAM]); IR (ATR) v = 3404,
̃
f
2979, 2939, 2832, 2209, 1716, 1672, 1364, 1182, 1087 cm−1; MS (EI,
70 eV) m/z (%) = 222 (2) [C14H22O2]+, 73 (100) [C4H9O]+, 43 (76)
[C2H3O]+; H NMR (360 MHz, CDCl3, 300 K) δ [ppm] = 1.21 (s,
1
3H), 1.32 (s, 3H), 1.45 (s, 3H), 1.52−1.67 (m, 4H), 2.04−2.14 (m,
4H), 2.94 (s, 1H), 3.29 (s, 3H), 6.05−6.09 (m, 1H); 13C {1H} NMR
(91 MHz, CDCl3, 300 K) δ [ppm] = 19.4, 19.9, 21.5, 22.3, 24.7, 25.5,
29.2, 50.2, 74.1, 79.4, 85.6, 89.2, 120.3, 134.6; HRMS (EI, 70 eV)
(C14H22O2) calcd. 222.1614, found 222.1615.
1-(Cyclohex-1-en-1-yl)-4-methoxy-3,4-dimethylpent-1-yn-3-yl
acetate (9c). Synthesized according to the general procedure, using 8c
(694 mg, 3.07 mmol, 1.0 equiv) in DMF (3.0 mL), NaH (1.23 g, 30.7
mmol, 10.0 equiv) in DMF (15 mL) and acetyl chloride (2.2 mL, 2.4
g, 31.0 mmol, 10.0 equiv). Work up and purification by column
chromatography (n-pentane/EtOAc: 30/1) yielded product 9c (418
mg, 51%) as a colorless oil: TLC Rf = 0.44 (P:EtOAc 10:1 [UV/
CAM]); IR (ATR) v = 2981, 2949, 2826, 2240, 1741, 1365, 1233,
̃
1126, 1085, 756, 691 cm−1; MS (EI, 70 eV) m/z (%) = 260 (3)
[C16H20O3]+, 73 (100) [C4H9O]+, 43 (54) [C2H3O]+; 1H NMR (360
MHz, CDCl3, 300 K) δ [ppm] = 1.40 (s, 6H), 1.82 (s, 3H), 2.07 (s,
3H), 3.36 (s, 3H), 7.27−7.31 (m, 3H), 7.41−7.46 (m, 2H); 13C {1H}
NMR (91 MHz, CDCl3, 300 K) δ [ppm] = 19.7, 20.3, 21.3, 22.2, 50.9,
79.4, 80.9, 85.9, 88.6, 122.8, 128.1, 128.3, 131.8, 168.9; HRMS (EI, 70
eV) (C16H20O3) calcd. 260.1407, found 260.1412.
CAM]); IR (ATR) v = 2980, 2939, 2833, 2209, 1717, 1365, 1086
2-(1-Methoxycyclohexyl)-4-(4-methoxyphenyl)but-3-yn-2-ol (8f).
Synthesized according to the general procedure, using 1-ethynyl-4-
methoxybenzene (1.98 g, 15.0 mmol, 1.0 equiv) in THF (30 mL), n-
̃
cm−1; MS (EI, 70 eV) m/z (%) = 73 (100) [C4H9O]+, 43 (89)
1
[C2H3O]+; H NMR (500 MHz, CDCl3, 300 K) δ [ppm] = 1.33 (s,
6375
dx.doi.org/10.1021/jo5009993 | J. Org. Chem. 2014, 79, 6372−6379

The Journal of Organic Chemistry
Note
BuLi (6.0 mL, 15.0 mmol, 1.0 equiv) and 1-(1-methoxycyclohexyl)-
ethanone (2.34 g, 15.0 mmol, 1.0 equiv) in THF (7 mL). Work up and
purification by column chromatography (n-pentane/EtOAc: 20/1)
yielded product 8f (2.77 g, 64%) as a colorless oil: TLC Rf = 0.33
NMR (500 MHz, CDCl3, 300 K) δ [ppm] = 0.89 (d, 3J = 6.6 Hz, 6H),
4
3
1.32 (s, 9H), 1.86 (d, J = 1.5 Hz, 3H), 2.45 (dhept, J = 9.8, 6.6 Hz,
4
3
1H), 3.82 (s, 3H), 5.37 (dd, J = 1.5 Hz, J = 9.8 Hz, 1H), 6.10 (s,
1H), 6.85−6.90 (m, 2H), 7.30−7.35 (m, 2H); 13C {1H} NMR (91
MHz, CDCl3, 300 K) δ [ppm] = 14.5, 22.3, 23.0, 29.1, 32.5, 55.2,
103.7, 113.7, 121.4, 124.4, 127.1, 128.5, 140.7, 147.0, 158.1, 162.3.
5-(tert-Butyl)-3-(4-methoxyphenyl)-2-(3-methylbut-2-en-2-yl)-
furan (6a). Synthesized according to the general procedure, using 5
(72.6 mg, 250 μmol, 1.0 equiv), [(3,3-dimethylbut-1-en-2-yl)oxy]-
trimethylsilane (172 mg, 1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg,
25.0 μmol, 0.1 equiv) and nitromethane (2.0 mL). Purification by
column chromatography (n-pentane) yielded product 6a (57.4 mg,
77%) as a colorless oil: TLC Rf = 0.20 (Pentane [UV/CAM]); IR
(P:EtOAc 9:1 [UV/CAM]); IR (ATR) v = 3446, 2934, 2856, 2835,
̃
2230, 1605, 1508, 1245, 1071, 1031, 830, 795 cm−1; MS (EI, 70 eV)
1
m/z (%) = 288 (2) [C18H24O3]+, 113 (100) [C7H13O]+; H NMR
(360 MHz, CDCl3, 300 K) δ [ppm] = 1.36−1.73 (m, 8H), 1.54 (s,
3H), 1.80−1.89 (m, 1H), 2.25−2.33 (m, 1H), 2.81 (s, 1H), 3.56 (s,
3H), 3.80 (s, 3H), 6.81−6.85 (m, 2H), 7.32−7.36 (m, 2H); 13C {1H}
NMR (91 MHz, CDCl3, 300 K) δ [ppm] = 21.8, 22.1, 25.4, 25.6, 27.2,
30.8, 51.7, 55.3, 73.6, 79.4, 84.9, 91.7, 113.9, 115.0, 132.8, 159.6;
HRMS (EI, 70 eV) (C18H24O3) calcd. 288.1720, found 288.1721.
2-(1-Methoxycyclohexyl)-4-(4-methoxyphenyl)but-3-yn-2-yl ace-
tate (9f). Synthesized according to the general procedure, using 8f
(865 mg, 3.00 mmol, 1.0 equiv) in DMF (3 mL), NaH (1.20 g, 30.0
mmol, 10.0 equiv) in DMF (15 mL) and acetyl chloride (1.7 mL, 1.9
g, 24.0 mmol, 10.0 equiv). Work up and purification by column
chromatography (n-pentane/EtOAc: 20/1) yielded product 9f (615
mg, 62%) as a colorless oil: TLC Rf = 0.37 (P:EtOAc 9:1 [UV/
(ATR) v = 2964, 2931, 2906, 2835, 1509, 1246, 1176, 1130, 1036, 833,
̃
801 cm−1; MS (EI, 70 eV) m/z (%) = 298 (59) [C20H26O2]+, 283
1
(100) [C19H23O2]+, 44 (66); H NMR (500 MHz, CDCl3, 300 K) δ
[ppm] = 1.32 (s, 9H), 1.53 (s, 3H), 1.81 (s, 3H), 1.92 (s, 3H), 3.82 (s,
3H), 6.13 (s, 1H), 6.85−6.88 (m, 2H), 7.30−7.33 (m, 2H); 13C {1H}
NMR (91 MHz, CDCl3, 300 K) δ [ppm] = 17.8, 20.5, 22.3, 29.1, 32.6,
55.2, 103.0, 113.7, 120.4, 120.6, 127.4, 127.9, 134.1, 148.9, 157.8,
162.1; HRMS (EI, 70 eV) (C20H26O2) calcd. 298.1927, found
298.1925.
3-(4-Methoxyphenyl)-2-(3-methylbut-2-en-2-yl)-5-phenylfuran
(6b). Synthesized according to the general procedure, using 5 (72.6
mg, 250 μmol, 1.0 equiv), trimethyl[(1-phenylvinyl)oxy]silane (192
mg, 1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg, 25.0 μmol, 0.1 equiv)
and nitromethane (2.0 mL). Purification by column chromatography
(n-pentane) yielded product 6b (54.9 mg, 69%) as a colorless oil: TLC
CAM]); IR (ATR) v = 2935, 2861, 2840, 2233, 1743, 1509, 1240,
̃
1077, 831 cm−1; MS (EI, 70 eV) m/z (%) = 330 (1) [C20H26O4]+, 113
1
(86) [C7H13O]+, 85 (64), 43 (100) [C2H3O]+; H NMR (500 MHz,
CDCl3, 300 K) δ [ppm] = 1.13−1.28 (m, 2H), 1.39−1.56 (m, 3H),
1.67−1.77 (m, 3H), 1.79 (s, 3H), 1.84−1.90 (m, 1H), 2.05 (s, 3H),
2.21−2.27 (m, 1H), 3.47 (s, 3H), 3.80 (s, 3H), 6.80−6.83 (m, 2H),
7.34−7.37 (m, 2H); 13C {1H} NMR (91 MHz, CDCl3, 300 K) δ
[ppm] = 20.2, 21.8, 21.8, 22.3, 25.6, 26.9, 30.9, 51.7, 55.3, 79.9, 82.2,
86.5, 87.5, 113.8, 114.9, 133.1, 159.7, 168.5; HRMS (EI, 70 eV)
(C20H26O4) calcd. 330.1826, found 330.1829.
3-Isopropyl-4-methoxy-1-(4-methoxyphenyl)-4-methylpent-1-yn-
3-ol (8g). Synthesized according to the general procedure, using 1-
ethynyl-4-methoxybenzene (1.98 g, 15.0 mmol, 1.0 equiv) in THF (30
mL), n-BuLi (6.0 mL, 15.0 mmol, 1.0 equiv) and 2-methoxy-2,4-
dimethylpentan-3-one (2.16 g, 15.0 mmol, 1.0 equiv) in THF (7 mL).
Work up and purification by column chromatography (n-pentane/
EtOAc: 20/1) yielded product 8g (2.23 g, 54%) as a colorless oil: TLC
R = 0.78 (P:EtOAc 10:1 [UV/CAM]); IR (ATR) v = 3058, 3035,
̃
f
2970, 2930, 2836, 1607, 1508, 1246, 1176, 1034, 833, 760, 690 cm−1;
MS (EI, 70 eV) m/z (%) = 318 (8) [C22H22O2]+, 115 (100), 77 (40)
[C6H5]+; H NMR (360 MHz, CDCl3, 300 K) δ [ppm] = 1.57 (s,
1
3H), 1.85 (s, 3H), 2.01 (s, 3H), 3.84 (s, 3H), 6.85 (s, 1H), 6.90−6.94
(m, 2H), 7.23−7.28 (m, 1H), 7.37−7.42 (m, 4H), 7.70−7.74 (m, 2H);
13C {1H} NMR (91 MHz, CDCl3, 300 K) δ [ppm] = 17.9, 20.6, 22.5,
55.2, 106.1, 113.9, 120.1, 122.7, 123.5, 126.7, 127.0, 128.0, 128.6,
131.0, 135.0, 150.7, 151.6, 158.2; HRMS (EI, 70 eV) (C22H22O2)
calcd. 318.1614, found 318.1615.
R = 0.43 (P:EtOAc 9:1 [UV/CAM]); IR (ATR) v = 3520, 2963, 2837,
̃
f
2216, 1605, 1500, 1250, 1020 cm−1; MS (EI, 70 eV) m/z (%) = 276
(5) [C17H24O3]+, 203 (10) [C13H15O2]+, 73 (100) [C4H9O]+; 1H
NMR (360 MHz, CDCl3, 300 K) δ [ppm] = 1.11 (d, 3J = 6.7 Hz, 3H),
3-(4-Methoxyphenyl)-2-(3-methylbut-2-en-2-yl)-4,5,6,7-tetrahy-
drobenzofuran (6c). Synthesized according to the general procedure,
using 5 (72.6 mg, 250 μmol, 1.0 equiv), (cyclohex-1-en-1-yloxy)-
trimethylsilane (170 mg, 1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg,
25.0 μmol, 0.1 equiv) and nitromethane (2.0 mL). Purification by
column chromatography (n-pentane) yielded product 6c (68.2 mg,
92%) as a colorless oil: TLC Rf = 0.88 (P:EtOAc 10:1 [UV/CAM]);
3
3
1.13 (d, J = 6.7 Hz, 3H), 1.29 (s, 3H), 1.45 (s, 3H), 2.08 (hept, J =
6.7 Hz, 1H), 3.32 (s, 3H), 3.47 (s, 1H), 3.80 (s, 3H), 6.80−6.84 (m,
2H), 7.35−7.39 (m, 2H); 13C {1H} NMR (91 MHz, CDCl3, 300 K) δ
[ppm] = 18.9, 19.8, 20.0, 21.6, 34.6, 49.7, 55.3, 79.5, 80.2, 85.5, 88.7,
113.8, 115.4, 133.0, 159.4; HRMS (EI, 70 eV) (C17H24O3) calcd.
276.1720, found 276.1715.
IR (ATR) v = 2931, 2853, 1509, 1244, 1173, 1034, 834, 731 cm−1; MS
̃
(EI, 70 eV) m/z (%) = 296 (27) [C20H24O2]+, 281 (37) [C19H21O2]+,
1
84 (100); H NMR (360 MHz, CDCl3, 300 K) δ [ppm] = 1.44 (s,
General Procedure for the Synthesis of Substituted 2-
Alkenylfurans 2, 6 and 10. To a solution of the propargylic acetate
(250 μmol, 1.0 equiv), silyl enol ether (1.00 mmol, 4.0 equiv) and
nitromethane (c = 125 mM) in a flame-dried flask was added Bi(OTf)3
(25 μmol, 0.1 equiv) at 0 °C. After 5 min the reaction mixture was
warmed to room temperature. The solvent was removed under
reduced pressure, and the crude mixture was purified by flash column
chromatography to afford the substituted 2-alkenylfuran.
3H), 1.72−1.78 (m, 5H), 1.85−1.89 (m, 2H), 1.91 (s, 3H), 2.48 (tt, 3J
= 6.2, 2.0 Hz, 2H), 2.64 (tt, 3J = 6.4, 1.8 Hz, 2H), 3.82 (s, 3H), 6.86−
6.90 (m, 2H), 7.19−7.23 (m, 2H); 13C {1H} NMR (91 MHz, CDCl3,
300 K) δ [ppm] = 18.1, 20.5, 22.2, 22.4, 22.9, 23.3, 23.3, 55.1, 113.6,
116.8, 120.0, 120.8, 129.2, 127.1, 133.4, 148.9, 149.4, 157.8; HRMS
(EI, 70 eV) (C20H24O2) calcd. 296.1771, found 296.1767.
3-(4-Methoxyphenyl)-2-(3-methylbut-2-en-2-yl)-5,6-dihydro-4H-
cyclopenta[b]furan (6d). Synthesized according to the general
procedure, using 5 (72.6 mg, 250 μmol, 1.0 equiv), (cyclopent-1-en-
1-yloxy)trimethylsilane (156 mg, 1.00 mmol, 4.0 equiv), Bi(OTf)3
(16.4 mg, 25.0 μmol, 0.1 equiv) and nitromethane (2.0 mL).
Purification by column chromatography (n-pentane) yielded product
6d (44.5 mg, 63%) as a colorless oil: TLC Rf = 0.85 (P:EtOAc 10:1
5-(tert-Butyl)-3-(4-methoxyphenyl)-2-(4-methylpent-2-en-2-yl)-
furan (2). Synthesized according to the general procedure, using 1
(76.1 mg, 250 μmol, 1.0 equiv), [(3,3-dimethylbut-1-en-2-yl)oxy]-
trimethylsilane (172 mg, 1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg,
25.0 μmol, 0.1 equiv) and nitromethane (2.0 mL). Purification by
column chromatography (n-pentane) yielded product 2 (61.7 mg,
49%) as a colorless oil (d.r. = 54/46): TLC Rf = 0.81 (P:EtOAc 10:1
[CAM]); MS (EI, 70 eV) m/z (%) = 312 (80) [C21H28O2]+, 297
(100) [C20H25O2]+; Major diastereoisomer, 1H NMR (500 MHz,
CDCl3, 300 K) δ [ppm] = 0.96 (d, 3J = 6.6 Hz, 6H), 1.32 (s, 9H), 1.85
(d, 4J = 1.5 Hz, 3H), 2.63 (dhept, 3J = 9.8, 6.6 Hz, 1H), 3.83 (s, 3H),
[UV/CAM]); IR (ATR) v = 2955, 2931, 2853, 1708, 1598, 1509,
̃
1249, 1175, 1029, 832, 732 cm−1; MS (EI, 70 eV) m/z (%) = 282 (12)
1
[C19H22O2]+, 225 (52) [C15H13O2]+, 84 (100); H NMR (360 MHz,
CDCl3, 300 K) δ [ppm] = 1.50 (s, 3H), 1.78 (s, 3H), 1.94 (s, 3H),
3
3
2.48 (p, J = 6.9 Hz, 2H), 2.73 (t, J = 6.9 Hz, 4H), 3.81 (s, 3H),
6.84−6.88 (m, 2H), 7.28−7.33 (m, 2H); 13C {1H} NMR (91 MHz,
CDCl3, 300 K) δ [ppm] = 18.0, 20.5, 22.4, 24.5, 24.9, 27.7, 55.2, 113.8,
119.0, 121.0, 125.6, 127.1, 127.9, 134.3, 154.4, 157.4, 157.8; HRMS
(EI, 70 eV) (C19H22O2) calcd. 282.1614, found 282.1617.
4
3
5.61 (dd, J = 1.5 Hz, J = 9.8 Hz, 1H), 5.99 (s, 1H), 6.85−6.90 (m,
2H), 7.30−7.35 (m, 2H); 13C {1H} NMR (91 MHz, CDCl3, 300 K) δ
[ppm] = 14.5, 22.5, 27.3, 29.1, 32.5, 55.2, 105.8, 113.5, 120.6, 123.6,
1
127.9, 129.7, 136.6, 149.0, 158.1, 161.4; Minor diastereoisomer, H
6376
dx.doi.org/10.1021/jo5009993 | J. Org. Chem. 2014, 79, 6372−6379

The Journal of Organic Chemistry
Note
2-Ethyl-4-(4-methoxyphenyl)-3-methyl-5-(3-methylbut-2-en-2-
yl)furan (6e). Synthesized according to the general procedure, using 5
(72.6 mg, 250 μmol, 1.0 equiv), trimethyl(pent-2-en-3-yloxy)silane
(158 mg, 1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg, 25.0 μmol, 0.1
equiv) and nitromethane (2.0 mL). Purification by column
chromatography (n-pentane) yielded product 6e (61.1 mg, 86%) as
a colorless oil: TLC Rf = 0.88 (P:EtOAc 10:1 [UV/CAM]); IR (ATR)
chromatography (n-pentane) yielded product 10c (38.8 mg, 60%) as
a colorless oil: TLC R = 0.40 (P [UV/CAM]); IR (ATR) v = 2970,
̃
f
2926, 2856, 1716, 1448, 1374, 1089, 919 cm−1; MS (EI, 70 eV) m/z
(%) = 258 (41) [C18H26O]+, 243 (100) [C17H23O]+; H NMR (360
1
MHz, CDCl3, 300 K) δ [ppm] = 1.18 (t, 3J = 7.5 Hz, 3H), 1.59−1.67
(m, 7H), 1.77 (s, 3H), 1.87 (s, 3H), 1.88 (s, 3H), 2.05−2.15 (m, 4H),
2.55 (q, J = 7.5 Hz, 2H), 5.53−5.57 (m, 1H); 13C {1H} NMR (91
3
v = 2972, 2933, 2837, 1509, 1245, 1173, 1035, 909, 833, 781 cm−1; MS
̃
MHz, CDCl3, 300 K) δ [ppm] = 9.3, 13.1, 18.1, 19.6, 20.6, 22.3, 22.6,
23.3, 25.7, 28.5, 112.9, 120.9, 124.9, 126.1, 131.1, 132.7, 148.7, 150.0;
HRMS (EI, 70 eV) (C18H26O) calcd. 258.1978, found 258.1979.
2-Ethyl-3-methyl-5-(3-methylbut-2-en-2-yl)-4-(phenylthio)furan
(10d). Synthesized according to the general procedure, using 9d (73.1
mg, 250 μmol, 1.0 equiv), trimethyl(pent-2-en-3-yloxy)silane (158 mg,
1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg, 25.0 μmol, 0.1 equiv) and
nitromethane (2.0 mL). Purification by column chromatography (n-
pentane) yielded product 10d (60.2 mg, 84%) as a colorless oil: TLC
(EI, 70 eV) m/z (%) = 284 (84) [C19H24O2]+, 269 (100)
[C18H21O2]+, 44 (84); 1H NMR (500 MHz, CDCl3, 300 K) δ
[ppm] = 1.25 (t, 3J = 7.6 Hz, 3H), 1.44 (s, 3H), 1.72 (s, 3H), 1.84 (s,
3
3H), 1.95 (s, 3H), 2.64 (q, J = 7.6 Hz, 2H), 3.83 (s, 3H), 6.88−6.91
(m, 2H), 7.15−7.18 (m, 2H); 13C {1H} NMR (91 MHz, CDCl3, 300
K) δ [ppm] = 9.1, 13.1, 18.0, 19.6, 20.5, 22.4, 55.1, 113.0, 113.6, 119.9,
122.5, 127.3, 129.9, 133.2, 149.4, 150.6, 157.8; HRMS (EI, 70 eV)
(C19H24O2) calcd. 284.1771, found 284.1767.
R = 0.90 (P:EtOAc 9:1 [UV/CAM]); IR (ATR) v = 3059, 2978, 2923,
1-[4-(4-Methoxyphenyl)-2-methyl-5-(3-methylbut-2-en-2-yl)-
furan-3-yl]ethanone (6f). Synthesized according to the general
procedure, using 5 (72.6 mg, 250 μmol, 1.0 equiv), 4-[(trimethylsilyl)-
oxy]pent-3-en-2-one (172 mg, 1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4
mg, 25.0 μmol, 0.1 equiv) and nitromethane (2.0 mL). Purification by
column chromatography (n-pentane) yielded product 6f (34.3 mg,
46%) as a colorless oil: TLC Rf = 0.53 (P:EtOAc 10:1 [UV/CAM]);
̃
f
2877, 1667, 1440, 1084, 1023, 739, 689 cm−1; MS (EI, 70 eV) m/z
(%) = 286 (100) [C18H22OS]+, 271 (22) [C17H19OS]+, 209 (64)
[C12H17OS]+; 1H NMR (360 MHz, CDCl3, 300 K) δ [ppm] = 1.25 (t,
3J = 7.5 Hz, 3H), 1.69 (s, 3H), 1.80 (s, 3H), 1.82 (s, 3H), 1.93 (s, 3H),
2.64 (q, 3J = 7.5 Hz, 2H), 7.05−7.13 (m, 3H), 7.18−7.24 (m, 2H); 13
C
{1H} NMR (91 MHz, CDCl3, 300 K) δ [ppm] = 8.3, 13.0, 18.3, 19.9,
20.6, 22.8, 109.5, 116.6, 119.5, 124.6, 125.7, 128.6, 135.7, 138.2, 151.4,
157.5; HRMS (EI, 70 eV) (C18H22OS) calcd. 286.1386, found
286.1390.
IR (ATR) v = 2931, 2839, 1670, 1509, 1245, 1174, 1031, 951, 832
̃
cm−1; MS (EI, 70 eV) m/z (%) = 298 (94) [C19H22O3]+, 283 (100)
[C18H19O3]+; 1H NMR (360 MHz, CDCl3, 300 K) δ [ppm] = 1.40 (s,
3H), 1.67 (s, 3H), 1.77 (s, 3H), 1.99 (s, 3H), 2.53 (s, 3H), 3.82 (s,
3H), 6.86−6.90 (m, 2H), 7.09−7.13 (m, 2H); 13C {1H} NMR (91
MHz, CDCl3, 300 K) δ [ppm] = 14.3, 18.2, 20.3, 22.5, 30.8, 55.1,
113.7, 118.5, 120.8, 123.2, 126.1, 130.6, 135.4, 150.8, 156.0, 158.7,
196.7; HRMS (EI, 70 eV) (C19H22O3) calcd. 298.1563, found
298.1555.
2-Ethyl-3-methyl-5-(3-methylbut-2-en-2-yl)-4-phenylfuran (10e).
Synthesized according to the general procedure, using 9e (65.1 mg,
250 μmol, 1.0 equiv), trimethyl(pent-2-en-3-yloxy)silane (158 mg,
1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg, 25.0 μmol, 0.1 equiv) and
nitromethane (2.0 mL). Purification by column chromatography (n-
pentane) yielded product 8e (58.5 mg, 92%) as a colorless oil: TLC Rf
3-Cyclopropyl-5-ethyl-4-methyl-2-(3-methylbut-2-en-2-yl)furan
(10a). Synthesized according to the general procedure, using 9a (56.1
mg, 250 μmol, 1.0 equiv), trimethyl(pent-2-en-3-yloxy)silane (158 mg,
1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg, 25.0 μmol, 0.1 equiv) and
nitromethane (2.0 mL). Purification by column chromatography (n-
pentane) yielded product 10a (42.0 mg, 77%) as a colorless oil: TLC
= 0.93 (P:EtOAc 9:1 [UV/CAM]); IR (ATR) v = 3057, 3027, 2975,
̃
2933, 2877, 1762, 1715, 1682, 1445, 1071, 769, 699 cm−1; MS (EI, 70
1
eV) m/z (%) = 254 (80) [C18H22O]+, 239 (100) [C17H19O]+; H
NMR (360 MHz, CDCl3, 300 K) δ [ppm] = 1.26 (t, 3J = 7.5 Hz, 3H),
1.43 (s, 3H), 1.72 (s, 3H), 1.86 (s, 3H), 1.98 (s, 3H), 2.65 (q, 3J = 7.5
Hz, 2H), 7.20−7.27 (m, 3H), 7.32−7.36 (m, 2H); 13C {1H} NMR (91
MHz, CDCl3, 300 K) δ [ppm] = 9.1, 13.1, 18.1, 19.6, 20.5, 22.4, 112.9,
119.8, 123.0, 126.0, 128.1, 128.9, 133.3, 134.9, 149.8, 150.8; HRMS
(EI, 70 eV) (C18H22O) calcd. 254.1665, found 254.1665.
R = 0.40 (P [UV/CAM]); IR (ATR) v = 2979, 2935, 1760, 1716,
̃
f
1376, 1025, 933 cm−1; MS (EI, 70 eV) m/z (%) = 218 (5)
[C15H22O]+, 177 (20) [C12H17O]+, 69 (81) [C5H9]+, 43 (100), 41
(61) [C3H5]+; 1H NMR (360 MHz, CDCl3, 300 K) δ [ppm] = 0.34−
0.39 (m, 2H), 0.63−0.69 (m, 2H), 1.17 (t, 3J = 7.5 Hz, 3H), 1.36 (tt, 3J
= 8.4, 5.3 Hz, 1H), 1.70 (s, 3H), 1.81 (s, 3H), 1.88 (s, 3H), 1.94 (s,
3H), 2.53 (q, 3J = 7.5 Hz, 2H); 13C {1H} NMR (91 MHz, CDCl3, 300
K) δ [ppm] = 5.0, 6.1, 8.4, 13.1, 18.2, 19.5, 20.4, 22.7, 114.8, 120.4,
121.5, 132.9, 149.7, 150.1; HRMS (EI, 70 eV) (C15H22O) calcd.
218.1665, found 218.1669.
2-(1-Cyclohexylideneethyl)-5-ethyl-3-(4-methoxyphenyl)-4-meth-
ylfuran (10f). Synthesized according to the general procedure, using 9f
(82.6 mg, 250 μmol, 1.0 equiv), trimethyl(pent-2-en-3-yloxy)silane
(158 mg, 1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg, 25.0 μmol, 0.1
equiv) and nitromethane (2.0 mL). Purification by column
chromatography (n-pentane/EtOAc: 40/1) yielded product 8f (71.4
mg, 88%) as a colorless oil: TLC Rf = 0.77 (P:EtOAc 9:1 [UV/
CAM]); IR (ATR) v = 2931, 2845, 1509, 1246, 1173, 1032, 834 cm−1;
3-n-Butyl-5-ethyl-4-methyl-2-(3-methylbut-2-en-2-yl)furan (10b).
Synthesized according to the general procedure, using 9b (60.1 mg,
250 μmol, 1.0 equiv), trimethyl(pent-2-en-3-yloxy)silane (158 mg,
1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg, 25.0 μmol, 0.1 equiv) and
nitromethane (2.0 mL). Purification by column chromatography (n-
pentane) yielded product 10b (29.9 mg, 51%) as a colorless oil: TLC
̃
MS (EI, 70 eV) m/z (%) = 324 (42) [C22H28O2]+, 309 (23)
[C21H25O2]+, 135 (100); 1H NMR (500 MHz, CDCl3, 300 K) δ
[ppm] = 1.08−1.13 (m, 2H), 1.23 (t, 3J = 7.6 Hz, 3H), 1.39−1.45 (m,
2H), 1.46−1.51 (m, 2H), 1.85 (s, 3H), 1.86−1.89 (m, 2H), 1.93 (s,
3
3H), 2.17−2.22 (m, 2H), 2.62 (q, J = 7.6 Hz, 2H), 3.82 (s, 3H),
̃
6.86−6.90 (m, 2H), 7.14−7.18 (m, 2H); 13C {1H} NMR (91 MHz,
CDCl3, 300 K) δ [ppm] = 9.1, 13.0, 17.5, 19.6, 26.6, 27.3, 27.5, 30.5,
32.3, 55.2, 112.9, 113.6, 116.7, 122.3, 127.3, 130.1, 141.1, 149.4, 150.6,
158.0; HRMS (EI, 70 eV) (C22H28O2) calcd. 324.2084, found
324.2083.
R = 0.55 (P [UV/CAM]); IR (ATR) v = 2958, 2932, 2872, 1716,
f
1457, 1377, 1084, 936 cm−1; MS (EI, 70 eV) m/z (%) = 234 (63)
[C16H26O]+, 219 (69) [C15H23O]+, 205 (63) [C14H21O]+, 191 (67)
[C13H19O]+, 57 (93) [C4H9]+, 43 (100) [C3H7]+; 1H NMR (360
MHz, CDCl3, 300 K) δ [ppm] = 0.89 (t, 3J = 7.2 Hz, 3H), 1.17 (t, 3J =
7.5 Hz, 3H), 1.24−1.34 (m, 2H), 1.36−1.45 (m, 2H), 1.64 (s, 3H),
1.79 (s, 3H), 1.87 (s, 3H), 1.89 (s, 3H), 2.17−2.23 (m, 2H), 2.55 (q, 3J
= 7.6 Hz, 2H); 13C {1H} NMR (91 MHz, CDCl3, 300 K) δ [ppm] =
8.5, 13.1, 13.9, 18.5, 19.5, 20.3, 22.5, 22.6, 23.9, 31.7, 113.5, 120.3,
120.7, 133.0, 149.0, 150.1; HRMS (EI, 70 eV) (C16H26O) calcd.
234.1978, found 234.1975.
2-(2,4-Dimethylpent-2-en-3-yl)-5-ethyl-3-(4-methoxyphenyl)-4-
methylfuran (10g). Synthesized according to the general procedure,
using 9g (69.1 mg, 250 μmol, 1.0 equiv), trimethyl(pent-2-en-3-
yloxy)silane (158 mg, 1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg, 25.0
μmol, 0.1 equiv) and nitromethane (2.0 mL). Purification by column
chromatography (n-pentane/EtOAc: 40/1) yielded product 8g (43.0
mg, 55%) as a colorless oil: TLC Rf = 0.75 (P:EtOAc 9:1 [UV/
3-(Cyclohex-1-en-1-yl)-5-ethyl-4-methyl-2-(3-methylbut-2-en-2-
yl)furan (10c). Synthesized according to the general procedure, using
9c (66.1 mg, 250 μmol, 1.0 equiv), trimethyl(pent-2-en-3-yloxy)silane
(158 mg, 1.00 mmol, 4.0 equiv), Bi(OTf)3 (16.4 mg, 25.0 μmol, 0.1
equiv) and nitromethane (2.0 mL). Purification by column
CAM]); IR (ATR) v = 2964, 2932, 2871, 1509, 1245, 1172, 1035, 831
̃
cm−1; MS (EI, 70 eV) m/z (%) = 312 (30) [C21H28O2]+, 269 (36)
[C18H21O2]+, 173 (100); 1H NMR (500 MHz, CDCl3, 300 K) δ
3
3
[ppm] = 0.86 (d, J = 6.9 Hz, 6H), 1.22 (t, J = 7.6 Hz, 3H), 1.43 (s,
6377
dx.doi.org/10.1021/jo5009993 | J. Org. Chem. 2014, 79, 6372−6379

The Journal of Organic Chemistry
Note
3H), 1.74 (s, 3H), 1.93 (s, 3H), 2.61 (q, 3J = 7.6 Hz, 2H), 2.92 (hept,
3J = 6.9 Hz, 1H), 3.81 (s, 3H), 6.84−6.88 (m, 2H), 7.12−7.17 (m,
2H); 13C {1H} NMR (91 MHz, CDCl3, 300 K) δ [ppm] = 9.3, 13.1,
19.6, 19.7, 21.6, 23.1, 30.6, 55.1, 112.5, 113.4, 123.7, 127.7, 129.9,
130.9, 133.7, 147.3, 150.7, 157.8; HRMS (EI, 70 eV) (C21H28O2)
calcd. 312.2084, found 312.2090.
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ASSOCIATED CONTENT
■
S
* Supporting Information
1
Complete set of conditions for the reaction optimization, H
and 13C NMR spectra of compounds 2, 5, 6, 7, 8, 9 and 10.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: thorsten.bach@ch.tum.de.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
́ ́
J.; Riesgo, L.; Vicente, R.; Lopez, L. A.; Tomas, M. J. Am. Chem. Soc.
This work was supported by the Deutsche Forschungsgemein-
schaft (Ba 1372/12-2) and by the Fonds der Chemischen
2008, 130, 13528−13529. (k) Blanc, A.; Tenbrink, K.; Weibel, J.-M.;
Pale, P. J. Org. Chem. 2009, 74, 4360−4363. (l) Liu, F.; Yu, Y.; Zhang,
J. Angew. Chem., Int. Ed. 2009, 48, 5505−5508. (m) Barluenga, J.;
Industrie (Kekule
́
scholarship to D.N.).
́ ́
Riesgo, L.; Lopez, L. A.; Rubio, E.; Tomas, M. Angew. Chem., Int. Ed.
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