Easy access to acetal-spiroacetal-enol ethers by tandem dearomatization of a furan ring and acetalization

Article abstract of DOI:10.1055/s-0032-1316548

A range of structurally novel acetal-spiroacetal-enol ethers were readily synthesized from 3-[5-(methoxymethyl)-2-furyl]propionaldehydes by dearomatization to form carbocations that were trapped intramolecularly by the formyl group with subsequent acetalization. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1316548

PAPER
▌2567
paper
Easy Access to Acetal-Spiroacetal-Enol Ethers by Tandem Dearomatization of
a Furan Ring and Acetalization
Acetal-Spiroacetal-Enol Ethers
Biao-Lin Yin,* Jin-Qiang Lai, Li Huang, Xiao-Yu Zhang, Fang-Hua Ji
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, P. R. of China
Fax 0086(20)87113735; E-mail: blyin@scut.edu.cn
Received: 08.04.2012; Accepted after revision: 16.05.2012
As part of our continuing interest in the search for bioac-
Abstract: A range of structurally novel acetal-spiroacetal-enol
tive spiro compounds, we recently disclosed a general and
ethers were readily synthesized from 3-[5-(methoxymethyl)-2-fu-
concise method for preparing libraries of spiroacetals 3
ryl]propionaldehydes by dearomatization to form carbocations that
and spirooxindoles 4 from 2-(hydroxymethyl)furans 1
substituted in the 5-position with a side chain that contains
a nucleophilic hydroxy or aminoaryl group (Scheme 1).8,9
The key steps involve protonation of the 2-hydroxymethyl
group of 1 to form a carbocation at the 5-position of the
furan ring, with subsequent dearomatization and intramo-
lecular trapping of the carbocation in intermediate 2 by
the nucleophilic substituent. We hypothesized that by
changing the nucleophile used to trap the carbocation in 2,
it might be possible produce a series of useful and struc-
turally novel spiro compounds. For example, intramolec-
ular trapping of the carbocation in 2 by a formyl group
should give structurally novel acetal-spiroacetal-enol
ethers 5; this structural motif occurs in natural product 6
(Figure 1), which shows a high cytotoxicity to Jurkat T
and HL-60 cells.10 The strategy might also be useful in
constructing the natural enol ether-spiroacetal-enol ethers
7–10.10 Below, we describe the synthesis of the acetal-spi-
roacetal-enol ethers 5.
were trapped intramolecularly by the formyl group with subsequent
acetalization.
Key words: enols, ethers, heterocycles, furans, carbocations
Because it contains olefin, diene, enol ether, and 1,4-di-
carbonyl functional groups in masked forms that can be
revealed by disruption of the conjugated π-system, the
readily available furan ring is widely used in a range of
valuable synthetic intermediates.1 A number of methods
that have been developed for dearomatizing the furan ring
have been used extensively in the syntheses of many bio-
active molecules. For example, Diels–Alder reactions em-
ploying furans as dienes or, less frequently, as dienophiles
give rise to bicyclic or tricyclic skeletons.2 Birch reduc-
tion of the furan ring leads to 2,5-dihydrofurans.3 Oxida-
tion of furan derivatives produces 2,5-dialkoxy-2,5-
dihydrofurans,4 6-hydroxy-2H-pyran-3(6H)-ones,5 1,6-
dihydropyridin-3(2H)-ones,6 or butenolides.7 For these
reasons, the intensive exploration of the use of furans as
synthetic building blocks remains a highly desirable ob-
jective.
We began by converting the silyl ether 11 into the α-sub-
stituted 2-(hydroxymethyl)furans 13a–d in good yields by
sequential treatment with butyllithium and the appropriate
O
O
Unsat
3
ref. 8
H
Nu
HNu
R2
ref. 9
acid
Unsat
O
O
O
NR1
Ar
Unsat
OH
2
1
4
O
this work
O
OMe
O
5
Unsat
Scheme 1 Strategy for the synthesis of spiro compounds through dearomatization of the furan ring
SYNTHESIS 2012, 44, 2567–2574
Advanced online publication: 02.07.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1316548; Art ID: SS-2012-H0349-OP
© Georg Thieme Verlag Stuttgart · New York

2568
B.-L. Yin et al.
PAPER
OH
O
OMe
LA
OMe
model A:
H
H
O
O
Cl
H
H
H
O
O
H
O
Me
Me
OAc
O
6
7
O
H
OMe
H
O
O
trans-17a (disfavored)
O
O
S
O
O
MeS
O
Me
H
H
8
9
model B:
H
H
H
O
O
O
O
O
O
MeS
H
LA
H
MeO
H
OMe
10
Figure 1 Naturally occurring acetal-spiroacetal-enol ether 6 and other
enol ether-spiroacetal-enol ethers 7–10
cis-17a (favored)
Scheme 3 Observed Partial nuclear Overhauser effect in product 17a
and the associated stereochemical models
carbonyl compound (Scheme 2). The 2-furylcarbinols
13e–g were prepared through the reaction of the formyl
derivative 12 with the appropriate lithiated alkyne. Meth-
ylation of 13 followed by deprotection with tetrabutylam-
monium fluoride gave the corresponding γ-alcohols 15,
which underwent Swern oxidation to give the correspond-
ing aldehydes 16. Because aldehydes 16 were unstable,
they were used directly without further purification in the
subsequent cyclization step.
zinc(II) chloride, iron(II) chloride, or iron(III) chloride at
110 °C gave the desired product, but in very low yields
(entries 2–6). A slightly better yield was obtained when by
using p-toluenesulfonic acid as the catalyst (entry 9). The
highest yield of 64% was obtained by treatment of 16a
with p-toluenesulfonic acid in dichloromethane at room
temperature for 0.5 hours with a diastereoselectivity of
3:1 in favor of the cis-isomer.
Having prepared the aldehydes 16, we directed our efforts
at optimizing the conditions for the cyclization of alde-
hyde 16a as the substrate (Table 1). The use of a strong
Lewis acid (boron trifluoride etherate) in toluene gave a
complicated mixture (entry 1). Relatively weaker Lewis
acids, such as copper(II) sulfate, ytterbium(III) triflate,
The stereochemistry of product 17a was assigned on the
basis of nuclear Overhauser effect spectroscopic experi-
ments (Scheme 3). The cis-isomers showed nuclear Over-
hauser coupling between the proton of the phenyl ring and
the three protons of the methyl group (see Supporting In-
formation). To rationalize the observed stereoselectivi-
OH
BuLi, TMEDA, THF,
R1
O
–78 °C then R1COR2
O
NaH, MeI
R2
TBSO
13a R1 = H; R2 = Ph
H
13
TBSO
11
80%
83%
87%
80%
82%
81%
64%
13b R1 = H; R2 = 4-MeOC6H4
13c R1 = H; R2 = 1-naphthyl
13d R1 = Ph; R2 = Ph
R3
13e R1 = H; R2 = C CPr
O
2
13f R1 = H; R =
C
CPh
OHC
13g R1 = H; R2 = (C C)2Me
TBSO
12 (75%)
OMe
oxalyl chloride,
OMe
R1
R2
O
TEA, DMSO,
OMe
R1
R2
O
TBAF, THF
CH2Cl2, –78 °C
R1
R2
O
14 TBSO
OHC
15
HO
14a 95%
14b 90%
15a 95%
15b 94%
16a–g
15c 85% (two steps)
15d 91% (two steps)
15e 92%
14e 93%
14f 95%
14g 40%
15f 90%
15g 38%
Scheme 2 Synthesis of 3-(2-furyl)propionaldehydes 16
Synthesis 2012, 44, 2567–2574
© Georg Thieme Verlag Stuttgart · New York

PAPER
Acetal-Spiroacetal-Enol Ethers
2569
O
H
Table 1 Optimization of the Reaction Conditions for the Cyclization
O
OMe
MeO
R1
PTSA, CH2Cl2, r.t.
R1
O
H
O
O
O
OMe
R2
conditions
R2
MeO
16
O
17
O
Ph
Ph
16a
17a
O
O
OMe
OMe
O
OMe
Entrya Solvent
Catalyst
Temp Time Yield Cis/trans
O
O
O
(°C)
(h)
(%)b ratioc
Ph
4-MeOC6H4
1-naphthyl
17c
17b
(35%, 1.9:1)
17a
(64%, 3:1)
(81%, 3.5:1)
1
2
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
CH2Cl2
CH2Cl2
THF
BF3·OEt2 –78
CuSO4 110
Yb(OTf)3 110
5
0
–
2
17
–
O
OMe
O
OMe
Ph
O
OMe
Pr
3
2
trace
20
–
Ph
O
O
O
Ph
4
ZnCl2
FeCl2
FeCl3
PPTS
CSA
110
110
110
40
2
–
17d
(58%, 3.2:1)
17e
(37%, 4:1)
17f
(63%, 4.5:1)
5
2
25
–
6
2
trace
18
–
O
OMe
O
7
2
–
17g
8
40
2
trace
30
–
0%
9
PTSA
PTSA
PTSA
PTSA
PTSA
40
2
3:1
3:1
3:1
2.5:1
2.3:1
10
11
12
13
40
0.5
0.5
0.5
0.5
42
Scheme 4 Syntheses of spiro compounds 17. All the reactions were
performed on a 0.3-mmol scale. The isolated yields of the products
are shown. The diastereoselectivity ratios are based on 1H NMR spec-
troscopic studies.
r.t.
r.t.
r.t.
64
49
MeCN
18
a All reactions were performed on a 0.3-mmol scale.
b Isolated yields.
spectively, and none of the desired enol ether-spiroacetal-
enol ethers 18 were obtained. A plausible mechanism for
this reaction is shown in Scheme 5. Treatment of 17 with
trimethylsilyl triflate generates the carbocations 20, which
undergo deprotonation with the assistance of triethyl-
amine to give the intermediates 21. These subsequently
undergoes a 1,7-hydride shift to give the aldehydes 19.
c Determined by 1H NMR spectroscopy.
ties, we proposed the stereochemical models A and B.
Model B is favored as a result of the interaction of the
Lewis acid with the two oxygen atoms, which directs the
approaching methoxy group.
In summary, we succeeded in dearomatizing a carboca-
tion derived from furans with subsequent intramolecular
trapping by a formyl group and acetalization to give novel
acetal-spiroacetal-enol ethers and enals. This protocol ex-
pands the range of synthetic applications of furans as
building blocks and might be useful in the synthesis of
bioactive natural products. The synthesis of additional an-
alogues and the evaluation of their bioactivities are under
way and will be reported in due course.
We then examined the cyclization of a series of aldehydes
16 with various substituents (Scheme 4). Except for 16g,
the aldehydes were transformed into the corresponding
spiro compounds 17 in yields of 35–81% and moderate
diastereoselectivities (1.9:1 to 4.5:1). In the case of 17b
and 17e, low yields were obtained, possibly because of the
instability of these compounds under the reaction condi-
tions. The failure of 16g to provide the corresponding
cyclic product may be the result of polymerization of the
diyne functionality. It is noteworthy that in the cases of
17e and 17f, none of the usual isomerization8a,b,d of the
exo-cyclic double bond occurred, and the Z-isomers were
obtained exclusively under the conditions that we used.
IR spectra were recorded with PerkinElmer 983 or Shimadzu IR-
440 spectrometers. 1H and 13C NMR spectra were recorded with an
AMX-300, a DPX-300, a Gemini-2000, or an INOVA-600 spec-
trometer with TMS as the internal standard. Mass spectra were re-
corded on a PerkinElmer Mariner spectrometer (ESI) or on
HP5973N or HP5989A instruments. HRMS (EI or ESI) spectra
were obtained by using a Kratos Concept 1H or a Bruker Apex III
7.0 TESLA mass spectrometer. Optical rotations were measured
with a PerkinElmer 241 MC polarimeter. Elemental analyses were
carried out in a Heraeus CHN-O-Rapid elemental analyzer. Melting
points were determined on X-4 Mel-Temp apparatus and are uncor-
rected. Flash column chromatography was performed on silica gel
H (1040 μm) with PE–EtOAc or EtOAc–EtOH mixtures as eluents.
Encouraged by these results, we attempted to synthesize
the enol ether-spiroacetal-enol ethers 18 from aldehydes
16 (Scheme 5). Treatment of 16 with 1.2 equivalents of
trimethylsilyl triflate and 2.4 equivalents of triethylamine
in anhydrous dichloromethane unexpectedly gave the cor-
responding enals 19a and 19c in 48 and 52% yield, re-
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2567–2574

2570
B.-L. Yin et al.
PAPER
O
O
R2
O
H
18
MeO
TMSOTf, TEN
CH2Cl2, r.t.
O
R2
16
CHO
O
R2
19a 48%
19c 52%
possible mechanism:
O
H
H
O
H
O
H
TMSOTf
MeO
O
MeO
O
R2
O
R2
R2
NEt3
20
16
O
H
1,7-H shift
CHO
O
O
H
R2
R2
19
21
Scheme 5 The formation of 19 and a possible mechanism for this reaction
(5-{3-[tert-Butyl(dimethyl)siloxy]propyl}-2-furyl)methanols
13a–13d; General Procedure
(5-{3-[tert-Butyl(dimethyl)siloxy]propyl}-2-furyl)(1-naph-
thyl)methanol (13c)
A 2.5 M soln of BuLi in hexane (9.6 mL, 24 mmol) was added to a
mixture of silyl ether 11 (4.80 g, 20 mmol), TMEDA (3.6 mL), and
THF (30 mL) at –78 °C under argon, and the mixture was stirred at
0 °C for 0.5 h then cooled to –78 °C. A soln of R1COR2 (22 mmol)
in THF (18 mL) was added dropwise. When the addition was com-
pleted, the mixture was stirred at –78 °C for 2 h then allowed to
warm to r.t. and stirred overnight. H2O (15 mL) was added to
quench the reaction. The resulting mixture was extracted with
EtOAc (3 × 15 mL), and the combined organic layers were dried
(Na2SO4) and concentrated in vacuo. The residue was purified by
flash chromatography (silica gel, PE–EtOAc).
Colorless syrup; yield: 6.89 g (87%).
1H NMR (400 MHz, CDCl3): δ = 8.03–8.00 (m, 1 H), 7.89–7.83 (m,
2 H), 7.74–7.72 (m, 1 H), 7.53–7.46 (m, 3 H), 6.52 (s, 1 H), 5.89 (d,
J = 3.2 Hz, 1 H), 5.85 (d, J = 3.2 Hz, 1 H), 3.66 (t, J = 6.4 Hz, 2 H),
2.71 (t, J = 6.8 Hz, 2 H), 1.90–1.83 (m, 2 H), 0.92 (s, 9 H), 0.06 (s,
6 H).
13C NMR (101 MHz, CDCl3): δ = 156.2, 153.9, 136.5, 133.8, 130.7,
128.7, 128.6, 126.1, 125.6, 125.4, 124.2, 123.7, 108.8, 105.7, 67.5,
62.3, 31.0, 26.0, 24.5, 18.4, –5.3.
HRMS: m/z [M + H]+ calcd for C24H33O3Si: 397.2199; found:
397.2185.
(5-{3-[tert-Butyl(dimethyl)siloxy]propyl}-2-furyl)(phe-
nyl)methanol (13a)
(5-{3-[tert-Butyl(dimethyl)siloxy]propyl}-2-furyl)(diphe-
nyl)methanol (13d)
Colorless syrup; yield: 6.75 g (80%).
1H NMR (400 MHz, CDCl3): δ = 7.32–7.27 (m, 10 H), 5.91 (d,
J = 3.2 Hz, 1 H), 5.74 (d, J = 3.2 Hz, 1 H), 3.63 (t, J = 6.4 Hz, 2 H),
3.06 (s, 1 H), 2.67 (t, J = 7.6 Hz, 2 H), 1.86–1.79 (m, 2 H), 0.88 (s,
9 H), 0.03 (s, 6 H).
13C NMR (101 MHz, CDCl3): δ = 156.5, 144.8, 127.9, 127.5, 127.3,
110.5, 105.3, 78.0, 62.2, 31.0, 26.0, 24.5, 18.4, 0.0, –5.3.
HRMS (ESI): m/z [M + H]+ calcd for C26H35O3Si: 423.2355; found:
423.2367.
Colorless syrup; yield: 5.54 g (80%).
1H NMR (600 MHz, CDCl3): δ = 7.45–7.43 (m, 2 H), 7.38–7.36 (m,
2 H), 7.33–7.31 (m, 1 H), 5.95 (d, J = 3.0 Hz, 1 H), 5.91 (d, J = 3.0
Hz, 1 H), 5.77 (d, J = 4.2 Hz, 1 H), 3.65 (t, J = 6.0 Hz, 2 H), 2.68 (t,
J = 7.8 Hz, 2 H), 2.44 (d, J = 5.4 Hz, 1 H), 1.87–1.82 (m, 2 H), 0.91
(s, 9 H), 0.05 (s, 6 H).
13C NMR (150 MHz, CDCl3): δ = 156.3, 154.1, 141.0, 128.3, 127.9,
126.6, 108.2, 105.4, 70.1, 62.2, 30.9, 25.9, 24.4, 18.3, –5.3.
HRMS: m/z [M + H]+ calcd for C20H31O3Si: 347.2042; found:
347.2035.
(5-{3-[tert-Butyl(dimethyl)siloxy]propyl}-2-furyl)(4-methoxy-
phenyl)methanol (13b)
Alkynyl(5-{3-[tert-Butyl(dimethyl)siloxy]propyl}-2-furyl)meth-
anols 13e–g; General Procedure
Colorless syrup; yield: 6.24 g (83%).
A 2.5 M soln of BuLi in hexane (5 mL, 12.5 mmol) was added drop-
wise to a mixture of R3C≡CH (10 mmol), TMEDA (1.8 mL), and
anhyd THF (10 mL) at –78 °C under N2. The mixture was stirred at
–78 °C for 0.5 h then warmed to r.t. A soln of aldehyde 12 (10 mL)
in THF (15 mL) was added dropwise and the mixture was stirred for
3 h. The reaction was then quenched with H2O (15 mL) and the re-
sulting mixture was extracted with EtOAc (4 × 30 mL). The com-
bined organic layers were dried (Na2SO4) and concentrated in
vacuo. The residue was purified by flash chromatography (silica
gel, PE–EtOAc).
1H NMR (600 MHz, CDCl3): δ = 7.36 (d, J = 9.0 Hz, 2 H), 6.89 (d,
J = 9.0 Hz, 2 H), 5.94 (d, J = 3.0 Hz, 1 H), 5.90 (d, J = 3.0 Hz, 1 H),
5.72 (d, J = 1.8 Hz, 1 H), 3.81 (s, 3 H), 3.64 (t, J = 6.6 Hz, 2 H), 2.67
(t, J = 7.8 Hz, 2 H), 1.86–1.82 (m, 2 H), 0.90 (s, 9 H), 0.05 (s, 6 H).
13C NMR (150 MHz, CDCl3): δ = 159.3, 156.1, 154.4, 133.3, 127.9,
113.7, 108.0, 105.4, 69.8, 62.2, 55.2, 30.9, 25.9, 24.4, 18.3, –5.3.
HRMS: m/z [M + H]+ calcd for C21H33O4Si: 377.2148; Found:
377.2156.
Synthesis 2012, 44, 2567–2574
© Georg Thieme Verlag Stuttgart · New York

PAPER
Acetal-Spiroacetal-Enol Ethers
2571
1-(5-{3-[tert-Butyl(dimethyl)siloxy]propyl}-2-furyl)hex-2-yn-1-
ol (13e)
1H NMR (400 MHz, CDCl3): δ = 7.34 (d, J = 8.0 Hz, 2 H), 6.90 (d,
J = 8.0 Hz, 2 H), 5.94 (d, J = 2.8 Hz, 1 H), 5.89 (d, J = 2.8 Hz, 1 H),
5.17 (s, 1 H), 3.81 (s, 3 H), 3.64 (t, J = 6.0 Hz, 2 H), 3.35 (s, 3 H),
2.67 (t, J = 7.6 Hz, 2 H), 1.87–1.80 (m, 2 H), 0.89 (s, 9 H), 0.04 (s,
6 H).
13C NMR (101 MHz, CDCl3): δ = 159.3, 156.3, 152.7, 131.3, 128.5,
113.7, 109.1, 105.3, 78.8, 62.2, 56.6, 55.2, 30.9, 25.9, 24.5, 18.3,
–5.4.
Colorless syrup; yield: 2.76 g (82%).
1H NMR (400 MHz, CDCl3): δ = 6.31 (d, J = 3.2 Hz, 1 H), 5.92 (d,
J = 3.2 Hz, 1 H), 5.38 (s, 1 H), 3.64 (t, J = 6.0 Hz, 2 H), 2.67 (t,
J = 7.6 Hz, 2 H), 2.42 (br s, 1 H), 2.23 (dt, J = 7.2, 2.0 Hz, 2 H),
1.87–1.80 (m, 2 H), 1.60–1.51 (m, 2 H), 0.99 (t, J = 7.6 Hz, 3 H),
0.89 (s, 9 H), 0.04 (s, 6 H).
13C NMR (101 MHz, CDCl3): δ = 156.5, 151.9, 108.0, 105.5, 86.3,
77.8, 62.1, 58.3, 30.8, 25.9, 24.4, 21.8, 20.7, 18.2, 13.4, –5.4.
HRMS (ESI): m/z [M + H]+ calcd for C22H35O4Si: 391.2305; found:
391.2310.
HRMS (ESI): m/z [M + H]+ calcd for C19H33O3Si: 337.2199; found:
337.2188.
tert-Butyl{3-[5-(1-methoxyhex-2-yn-1-yl)-2-furyl]propoxy}di-
methylsilane (14e)
Syrup; yield: 3.26 g (93%).
1H NMR (400 MHz, CDCl3): δ = 6.37 (d, J = 2.8 Hz, 1 H), 5.94 (d,
J = 2.8 Hz, 1 H), 5.12 (s, 1 H), 3.64 (t, J = 6.0 Hz, 2 H), 3.37 (s, 3
H), 2.69 (t, J = 7.6 Hz, 2 H), 2.26 (dt, J = 7.2, 2.0 Hz, 2 H), 1.88–
1.81 (m, 2 H), 1.62–1.53 (m, 2 H), 1.01 (t, J = 7.6 Hz, 3 H), 0.89 (s,
9 H), 0.04 (s, 6 H).
1-(5-{3-[tert-Butyl(dimethyl)siloxy]propyl}-2-furyl)-3-phenyl-
prop-2-yn-1-ol (13f)
Colorless syrup; yield: 3.0 g (81%).
1H NMR (400 MHz, CDCl3): δ = 7.49–7.47 (m, 2 H), 7.33–7.30 (m,
3 H), 6.42 (d, J = 3.2 Hz, 1 H), 5.98 (d, J = 3.2 Hz, 1 H), 5.64 (d,
J = 4.0 Hz, 1 H), 3.67 (t, J = 6.0 Hz, 2 H), 2.72 (t, J = 7.6 Hz, 2 H),
1.91–1.85 (m, 2 H), 0.91 (s, 9 H), 0.06 (s, 6 H).
13C NMR (101 MHz, CDCl3): δ = 156.8, 149.9, 109.8, 105.5, 87.4,
13C NMR (101 MHz, CDCl3): δ = 156.8, 151.1, 131.7, 128.6, 128.2,
122.2, 108.5, 105.7, 86.5, 85.4, 62.1, 58.6, 30.8, 25.9, 24.4, 18.3,
–5.4.
HRMS (ESI): m/z [M + H]+ calcd for C22H31O3Si 371.2042; found:
371.2058.
75.4, 66.1, 62.1, 54.8, 30.9, 25.9, 24.5, 22.0, 20.7, 18.3, 13.5, –5.4.
HRMS (ESI): m/z [M + H]+ calcd for C20H35O3Si: 351.2355; found:
351.2348.
tert-Butyl{3-[5-(1-methoxy-3-phenylprop-2-yn-1-yl)-2-fu-
ryl]propoxy}dimethylsilane (14f)
Syrup; yield: 3.65 g (95%).
1-(5-{3-[tert-Butyl(dimethyl)siloxy]propyl}-2-furyl)hexa-2,4-
diyn-1-ol (13g)
Colorless syrup; yield: 2.12 g (64%).
1H NMR (600 MHz, CDCl3): δ = 6.33 (d, J = 2.4 Hz, 1 H), 5.94 (d,
J = 2.4 Hz, 1 H), 5.41 (s, 1 H), 3.64 (t, J = 6.0 Hz, 2 H), 2.67 (t,
J = 7.6 Hz, 2 H), 2.54 (br s, 1 H), 1.94 (s, 3 H), 1.87–1.80 (m, 2 H),
0.89 (s, 9 H), 0.04 (s, 6 H).
13C NMR (150 MHz, CDCl3): δ = 157.0, 150.4, 108.8, 105.8, 78.0,
72.0, 70.7, 63.7, 62.2, 58.5, 30.9, 26.0, 24.5, 18.3, 4.3, –5.3.
HRMS (ESI): m/z [M + H]+ calcd for C19H29O3S: 333.1886; found:
1H NMR (400 MHz, CDCl3): δ = 7.51–7.49 (m, 2 H), 7.34–7.31 (m,
3 H), 6.47 (d, J = 3.2 Hz, 1 H), 5.99 (d, J = 3.2 Hz, 1 H), 5.37 (s, 1
H), 3.66 (t, J = 6.0 Hz, 2 H), 3.47 (s, 3 H), 2.72 (t, J = 7.6 Hz, 2 H),
1.91–1.84 (m, 2 H), 0.90 (s, 9 H), 0.05 (s, 6 H).
13C NMR (101 MHz, CDCl3): δ = 157.1, 149.1, 131.8, 128.6, 128.3,
122.3, 110.2, 105.6, 86.6, 84.3, 66.5, 62.1, 55.1, 30.9, 25.9, 24.5,
18.3, –5.3.
HRMS (ESI): m/z [M + H]+ calcd for C23H33O3Si: 385.2199; found:
385.2206.
333.1895.
tert-Butyl{3-[5-(1-methoxyhexa-2,4-diyn-1-yl)-2-furyl]pro-
poxy}dimethylsilane (14g)
Syrup; yield: 1.38 g (40%).
(5-{3-[tert-Butyl(dimethyl)siloxy]propyl}-2-furyl)methyl Meth-
yl Ethers 14; General Procedure
1H NMR (600 MHz, CDCl3): δ = 6.39 (d, J = 2.7 Hz, 1 H), 5.95 (d,
J = 2.7 Hz, 1 H), 5.18 (s, 1 H), 3.64 (t, J = 6.0 Hz, 2 H), 3.38 (s, 3
H), 2.69 (t, J = 7.6 Hz, 2 H), 1.95 (s, 3 H), 1.88–1.81 (m, 2 H), 0.89
(s, 9 H), 0.04 (s, 6 H).
13C NMR (150 MHz, CDCl3): δ = 157.2, 148.4, 110.4, 105.6, 77.4,
71.7, 70.1, 66.3, 63.7, 62.1, 55.1, 30.8, 25.9, 24.5, 18.3, 4.3, –5.4.
60% NaH (0.72 g, 12 mmol) was added portionwise to a stirred soln
of alcohol 13 (10 mmol) in anhyd THF (30 mL) at 0 °C. The mixture
was warmed to r.t., stirred for 1 h, and treated by dropwise addition
of MeI (1.56 g, 11 mmol). The mixture was stirred for 1 h and then
the reaction was quenched with H2O (50 mL). The layers were sep-
arated and the aqueous layer was extracted with PE (3 × 20 mL).
The combined organic layers were washed with brine, dried
(Na2SO4), and concentrated in vacuo. The residue was purified by
flash chromatography (silica gel, PE–EtOAc).
HRMS (ESI): m/z [M + H]+ calcd for C20H31O3Si: 347.2042; found:
347.2053.
tert-Butyl(3-{5-[methoxy(phenyl)methyl]-2-furyl}propoxy)di-
methylsilane (14a)
3-[5-(Methoxymethyl)-2-furyl]propan-1-ols 15; General Proce-
dure
Syrup; yield: 3.42 g (95%).
TBAF (10.8 mmol, 1.1 equiv) was added to a stirred soln of silyl
ether 14 (9.9 mmol) in THF (30 mL), and the mixture was stirred at
r.t. until the substrate was consumed (TLC). H2O (50 mL) was then
added, the layers were separated, and the aqueous layer was extract-
ed with EtOAc (3 × 20 mL). The combined organic layers were
washed with brine, dried (Na2SO4), and concentrated in vacuo. The
residue was purified by flash chromatography (silica gel, PE–
EtOAc).
1H NMR (600 MHz, CDCl3): δ = 7.42–7.41 (m, 2 H), 7.37–7.35 (m,
2 H), 7.31–7.29 (m, 1 H), 5.97 (d, J = 3.6 Hz, 1 H), 5.92 (d, J = 3.6
Hz, 1 H), 5.21 (s, 1 H), 3.64 (t, J = 4.8 Hz, 2 H), 3.37 (s, 3 H), 2.70
(t, J = 7.2 Hz, 2 H), 1.89–1.85 (m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 156.0, 152.5, 138.9, 128.3, 127.8,
127.1, 109.4, 105.5, 78.9, 61.8, 56.7, 30.8, 24.3.
HRMS (ESI): m/z [M + H]+ calcd for C21H33O3Si: 361.2199; found:
361.2185.
3-{5-[Methoxy(phenyl)methyl]-2-furyl}propan-1-ol (15a)
Colorless syrup; yield: 2.31 g (95%).
1H NMR (600 MHz, CDCl3): δ = 7.42–7.41 (m, 2 H), 7.37–7.35 (m,
2 H), 7.31–7.29 (m, 1 H), 5.97 (d, J = 3.6 Hz, 1 H), 5.92 (d, J = 3.6
Hz, 1 H), 5.21 (s, 1 H), 3.64 (t, J = 4.8 Hz, 2 H), 3.37 (s, 3 H), 2.70
(t, J = 7.2 Hz, 2 H), 1.89–1.85 (m, 2 H).
tert-Butyl(3-{5-[methoxy(4-methoxyphenyl)methyl]-2-fu-
ryl}propoxy)dimethylsilane (14b)
Syrup; yield: 3.51 g (90%).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2567–2574

2572
B.-L. Yin et al.
PAPER
13C NMR (101 MHz, CDCl3): δ = 156.0, 152.5, 138.9, 128.3, 127.8,
127.1, 109.4, 105.5, 78.9, 61.8, 56.7, 30.8, 24.3.
HRMS (ESI): m/z [M + H]+ calcd for C15H19O3: 247.1334; found:
247.1345.
1H NMR (400 MHz, CDCl3): δ = 6.39 (d, J = 3.2 Hz, 1 H), 5.98 (d,
J = 3.2 Hz, 1 H), 5.18 (s, 1 H), 3.66 (q, J = 6.4 Hz, 2 H), 3.38 (s, 3
H), 2.72 (t, J = 7.2 Hz, 2 H), 1.96 (s, 3 H), 1.92–1.85 (m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 156.7, 148.5, 110.4, 105.8, 77.6,
71.7, 69.9, 66.2, 63.6, 61.8, 55.1, 30.7, 24.3, 4.2.
HRMS (ESI): m/z [M + H]+ calcd for C14H17O3: 233.1178; found:
233.1185.
3-{5-[Methoxy(4-methoxyphenyl)methyl]-2-furyl}propan-1-ol
(15b)
Colorless syrup; yield: 2.57 g (94%).
1H NMR (400 MHz, CDCl3): δ = 7.24 (d, J = 8.0 Hz, 2 H), 6.80 (d,
J = 8.0 Hz, 2 H), 5.85 (d, J = 2.8 Hz, 1 H), 5.82 (d, J = 2.8 Hz, 1 H),
5.07 (s, 1 H), 3.72 (s, 3 H), 3.56 (t, J = 6.0 Hz, 2 H), 3.25 (s, 3 H),
2.61 (t, J = 7.6 Hz, 2 H), 1.82–1.75 (m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 159.3, 155.8, 152.9, 131.1, 128.5,
113.7, 109.2, 105.5, 78.5, 62.0, 56.6, 55.2, 30.9, 24.4.
2-Alkylidene-7-methoxy-1,6-dioxaspiro[4.4]non-3-enes (17);
General Procedure
A mixture of DMSO (1.6 mL, 20 mmol) and anhyd CH2Cl2 was
added dropwise over 20 min to a stirred solution of oxalyl chloride
(0.7 mL, 7.3 mmol) in anhyd CH2Cl2 (30 mL) at –78 °C under N2.
The mixture was stirred at –78 °C for 0.5 h, and then a soln of 15
(5.1 mmol) in CH2Cl2 (12 mL) was added dropwise. The mixture
was stirred for 1 h at –78 °C then warmed to r.t. and stirred for a fur-
ther 1 h. H2O (50 mL) was added to quench the reaction and the lay-
ers were separated. The aqueous layer was extracted with CH2Cl2 (3
× 20 mL). The organic layers were combined, washed with brine,
dried (Na2SO4), and concentrated in vacuo. The crude aldehyde 16
was used in the next step without further purification.
HRMS (ESI): m/z [M + H]+ calcd for C16H21O4: 277.1440; found:
277.1448.
3-{5-[Methoxy(1-naphthyl)methyl]-2-furyl}propan-1-ol (15c)
Colorless syrup; yield: 2.49 g (85%).
1H NMR (400 MHz, CDCl3): δ = 8.06–8.04 (m, 1 H), 7.87–7.81 (m,
2 H), 7.70–7.68 (m, 1 H), 7.52–7.44 (m, 3 H), 5.93 (s, 1 H), 5.87 (s,
2 H), 3.62 (t, J = 6.4 Hz, 2 H), 3.45 (s, 3 H), 2.70 (t, J = 7.2 Hz, 2
H), 1.89–1.82 (m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 155.8, 152.5, 134.3, 133.9, 131.1,
128.7, 128.6, 126.0, 125.6, 125.4, 125.0, 123.8, 109.8, 105.9, 76.9,
62.0, 57.2, 30.9, 24.5.
A stirred soln of aldehyde 16 (0.3 mmol) in anhyd CH2Cl2 (2 mL)
was treated with PTSA (51 mg, 0.3 mmol), and the mixture was
stirred at r.t. until the starting material disappeared. The reaction
was quenched with sat. aq NaHCO3 (15 mL) and the layers were
separated. The aqueous layer was extracted with EtOAc (3 × 20
mL), and the organic layers were combined, washed with brine,
dried (Na2SO4), and concentrated in vacuo. The residue was puri-
fied by flash chromatography (silica gel, PE–EtOAc).
HRMS (ESI): m/z [M + H]+ calcd for C19H21O3: 297.1491; found:
297.1496.
cis-2-Benzylidene-7-methoxy-1,6-dioxaspiro[4.4]non-3-ene (cis-
3-{5-[Methoxy(diphenyl)methyl]-2-furyl}propan-1-ol (15d)
17a)
Colorless syrup; yield: 2.99 g (91%).
Colorless syrup; yield: 35 mg (48%).
1H NMR (600 MHz, CDCl3): δ = 7.39–7.38 (m, 4 H), 7.30–7.27 (m,
4 H), 7.25–7.23 (m, 2 H), 6.04 (d, J = 3.0 Hz, 1 H), 5.98 (d, J = 3.0
Hz, 1 H), 3.63 (t, J = 6.6 Hz, 2 H), 3.27 (s, 3 H), 2.71 (t, J = 7.2 Hz,
2 H), 1.87–1.83 (m, 2 H).
13C NMR (150 MHz, CDCl3): δ = 156.2, 153.9, 143.4, 127.8, 127.5,
127.1, 113.0, 105.5, 83.2, 61.9, 52.8, 31.1, 24.5.
1H NMR (600 MHz, CD3COCD3): δ = 7.50–7.48 (m, 2 H), 7.15–
7.13 (m, 2 H), 7.00–6.97 (m, 1 H), 6.36 (d, J = 5.4 Hz, 1 H), 6.05
(dd, J = 5.4, 0.6 Hz, 1 H), 5.35 (s, 1 H), 5.11 (d, J = 4.8 Hz, 1 H),
3.18 (s, 3 H), 2.27–2.23 (m, 1 H), 2.21–2.15 (m, 1 H), 1.97–1.94 (m,
1 H), 1.90–1.87 (m, 1 H).
13C NMR (150 MHz, CDCl3): δ = 155.7, 136.0, 131.9, 129.4, 128.2,
128.2, 125.8, 121.1, 106.0, 101.6, 55.3, 33.7, 31.4.
HRMS (ESI): m/z [M + H]+ calcd for C21H23O3: 323.1647; found:
323.1653.
HRMS (EI): m/z [M]+ calcd for C15H16O3: 244.1099; found:
244.1095.
3-[5-(1-Methoxyhex-2-yn-1-yl)-2-furyl]propan-1-ol (15e)
Colorless syrup; yield: 2.15 g (92%).
trans-2-Benzylidene-7-methoxy-1,6-dioxaspiro[4.4]non-3-ene
(trans-17a)
1H NMR (400 MHz, CDCl3): δ = 6.38 (d, J = 3.2 Hz, 1 H), 5.97 (d,
J = 3.2 Hz, 1 H), 5.12 (s, 1 H), 3.68 (t, J = 6.4 Hz, 2 H), 3.38 (s, 3
H), 2.73 (t, J = 7.6 Hz, 2 H), 2.27 (dt, J = 7.2, 2.0 Hz, 2 H), 1.93–
1.86 (m, 2 H), 1.63–1.54 (m, 2 H), 1.02 (t, J = 7.6 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 156.3, 150.0, 109.9, 105.7, 87.5,
75.3, 66.1, 61.9, 54.8, 30.9, 24.4, 21.9, 20.7, 13.4.
Colorless syrup; yield: 12 mg (16%).
1H NMR (600 MHz, CD3COCD3): δ = 7.56–7.54 (m, 2 H), 7.16–
7.14 (m, 2 H), 7.00–6.97 (m, 1 H), 6.35 (d, J = 5.4 Hz, 1 H), 6.05
(d, J = 5.4 Hz, 1 H), 5.35 (s, 1 H), 5.07–5.06 (m, 1 H), 3.24 (s, 3 H),
2.20–2.17 (m, 1 H), 2.15–2.08 (m, 2 H), 2.04–2.00 (m, 1 H).
HRMS (ESI): m/z [M + H]+ calcd for C14H21O3: 237.1491; found:
237.1485.
13C NMR (150 MHz, CD3COCD3): δ = 156.7, 136.6, 132.3, 128.8,
128.1, 128.1, 125.5, 121.1, 106.4, 100.7, 54.4, 34.2, 31.5.
HRMS (EI): m/z [M]+ calcd for C15H16O3: 244.1099; found:
244.1095.
3-[5-(1-Methoxy-3-phenylprop-2-yn-1-yl)-2-furyl]propan-1-ol
(15f)
Colorless syrup; yield: 2.41 g (90%).
7-Methoxy-2-(4-methoxybenzylidene)-1,6-dioxaspiro[4.4]non-
3-ene (17b)
Colorless syrup; yield: 18 mg (35%).
1H NMR (400 MHz, CDCl3): δ = 7.50–7.48 (m, 2 H), 7.33–7.32 (m,
3 H), 6.47 (d, J = 3.2 Hz, 1 H), 6.00 (d, J = 3.2 Hz, 1 H), 5.36 (s, 1
H), 3.67 (t, J = 6.4 Hz, 2 H), 3.46 (s, 3 H), 2.74 (t, J = 7.6 Hz, 2 H),
1.94–1.87 (m, 2 H), 1.84 (br s, 1 H).
13C NMR (101 MHz, CDCl3): δ = 156.6, 149.2, 131.8, 128.6, 128.2,
122.2, 110.2, 105.8, 86.6, 84.1, 66.4, 61.8, 55.0, 30.8, 24.4.
1H NMR (400 MHz, CD3COCD3): δ = 7.59 (d, J = 8.8 Hz, 0.35 H),
7.54 (d, J = 8.8 Hz, 0.65 H), 6.83 (d, J = 8.8 Hz, 0.35 H), 6.82 (d,
J = 8.8 Hz, 0.65 H), 6.39 (d, J = 5.6 Hz, 0.65 H), 6.36 (d, J = 5.6 Hz,
0.35 H), 6.03 (d, J = 5.6 Hz, 0.65 H), 6.03 (d, J = 5.6 Hz, 0.35 H),
5.37 (s, 0.65 H), 5.34 (s, 0.35 H), 5.18–5.11 (m, 1 H), 3.72 (s, 1.05
H), 3.71 (s, 1.05 H), 3.33 (s, 1.05 H), 3.26 (s, 1.95 H), 2.34–1.92 (m,
4 H).
HRMS (ESI): m/z [M + H]+ calcd for C17H19O3: 271.1334; found:
271.1345.
3-[5-(1-Methoxyhexa-2,4-diyn-1-yl)-2-furyl]propan-1-ol (15g)
Colorless oil; yield: 0.87 g (38%).
Synthesis 2012, 44, 2567–2574
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PAPER
Acetal-Spiroacetal-Enol Ethers
2573
13C NMR (101 MHz, CD3COCD3): δ = 158.8 (0.35 C), 158.8 (0.65
C), 156.1 (0.35 C), 155.7 (0.65 C), 132.4 (0.65 C), 132.0 (0.35 C),
130.3 (0.35 C), 130.3 (0.65 C), 130.2 (0.35 C), 130.1 (0.65 C),
130.0 (0.35 C), 129.7 (0.65 C), 122.0 (0.65 C), 121.8 (0.35 C),
114.6 (1 C), 107.2 (0.35 C), 106.6 (0.65 C), 101.5 (0.35 C), 101.4
(0.65 C), 69.4 (0.35 C), 55.6 (0.65 C), 55.4 (0.35 C), 55.2 (0.65 C),
35.3 (0.35 C), 34.5 (0.65 C), 32.5 (0.35 C), 32.1 (0.65 C).
13C NMR (150 MHz, CD3COCD3): δ = 166.7 (0.2 C), 164.5 (0.8 C),
136.5 (0.2 C), 135.7 (0.8 C), 128.0 (0.8 C), 125.4 (0.2 C), 121.3 (0.8
C), 121.1 (0.2 C), 107.6 (0.2 C), 106.7 (0.8 C), 94.9 (0.8 C), 92.0
(0.2 C), 81.4 (0.2 C), 80.9 (0.8 C), 77.2 (0.2 C), 77.2 (0.8 C), 55.5
(0.2 C), 55.1 (0.8 C), 34.7 (0.2 C), 34.0 (0.80 C), 32.2 (0.2 C), 31.9
(0.8 C), 23.1 (0.2 C), 23.1 (0.8 C), 22.2 (0.8 C), 22.0 (0.2 C), 13.7
(0.2 C), 13.7 (0.8 C).
HRMS (EI): m/z [M]+ calcd for C16H18O4: 274.1205; found:
HRMS (EI): m/z [M]+ calcd for C14H18O3: 234.1256. Found
274.1195.
234.1251.
cis-7-Methoxy-2-(1-naphthylmethylene)-1,6-dioxaspi-
ro[4.4]non-3-ene (cis-17c)
Colorless syrup; yield: 56 mg (63%).
cis-7-Methoxy-2-(3-phenylprop-2-yn-1-ylidene)-1,6-dioxaspi-
ro[4.4]non-3-ene (cis-17f)
Colorless syrup; yield: 41.5 mg (51.5%).
1H NMR (600 MHz, CD3COCD3): δ = 8.25–8.22 (m, 2 H), 7.88–
7.87 (m, 1 H), 7.73–7.71 (m, 1 H), 7.53–7.46 (m, 3 H), 6.67 (d,
J = 5.4 Hz, 1 H), 6.30 (s, 1 H), 6.24 (d, J = 5.4 Hz, 1 H), 5.24 (d,
J = 4.8 Hz, 1 H), 3.33 (s, 3 H), 2.38–2.31 (m, 2 H), 2.14–2.11 (m, 1
H), 2.03–2.00 (m, 1 H).
13C NMR (150 MHz, CD3COCD3): δ = 158.1, 134.8, 133.7, 132.9,
132.0, 130.3, 129.4, 127.0, 127.0, 126.5, 126.4, 126.2, 124.3, 122.2,
106.7, 96.8, 55.1, 34.4, 31.9.
1H NMR (600 MHz, CD3COCD3): δ = 7.45–7.44 (m, 2 H), 7.37–
7.30 (m, 3 H), 6.87 (d, J = 5.4 Hz, 1 H), 6.42 (dd, J = 5.4, 1.8 Hz, 1
H), 5.21 (d, J = 4.8 Hz, 1 H), 5.13 (d, J = 1.8 Hz, 1 H), 3.32 (s, 3 H),
2.34–2.23 (m, 2 H), 2.07–2.03 (m, 1 H), 2.01–1.97 (m, 1 H).
13C NMR (150 MHz, CD3COCD3): δ = 167.2, 138.1, 131.6, 129.2,
128.4, 125.9, 125.0, 121.6, 106.9, 92.0, 87.0, 80.8, 55.1, 33.9, 31.8.
HRMS (EI): m/z [M]+ calcd for C17H16O3: 268.1099; found:
268.1091
HRMS (EI): m/z [M]+ calcd for C19H18O3: 294.1256; found:
294.1251.
trans-7-Methoxy-2-(3-phenylprop-2-yn-1-ylidene)-1,6-dioxa-
spiro[4.4]non-3-ene (trans-17f)
Colorless syrup; yield: 9 mg (11.5%).
1H NMR (600 MHz, CD3COCD3): δ = 7.43–7.41 (m, 2 H), 7.37–
7.31 (m, 3 H), 6.51 (d, J = 5.4 Hz, 1 H), 6.32 (d, J = 5.4 Hz, 1 H),
5.23–5.23 (m, 1 H), 4.93 (s, 1 H), 3.32 (s, 3 H), 2.35–2.28 (m, 2 H),
2.09–2.08 (m, 1 H), 2.01–1.98 (m, 1 H).
13C NMR (150 MHz, CD3COCD3): δ = 165.6, 137.0, 131.8, 129.3,
128.6, 128.0, 125.1, 121.7, 106.9, 94.2, 86.8, 80.0, 55.1, 34.0, 31.9.
HRMS (EI): m/z [M]+ calcd for C17H16O3: 268.1099; found:
268.1091.
trans-7-Methoxy-2-(1-naphthylmethylene)-1,6-dioxaspi-
ro[4.4]non-3-ene (trans-17c)
Colorless syrup; yield: 16 mg (18%).
1H NMR (600 MHz, CD3COCD3): δ = 8.35–8.33 (m, 1 H), 8.24–
8.22 (m, 1 H), 7.87–7.86 (m, 1 H), 7.72–7.70 (m, 1 H), 7.52–7.46
(m, 3 H), 6.66 (d, J = 5.4 Hz, 1 H), 6.31 (s, 1 H), 6.25 (d, J = 5.4 Hz,
1 H), 5.21–5.20 (m, 1 H), 3.39 (s, 3 H), 2.35–2.31 (m, 1 H), 2.28–
2.23 (m, 2 H), 2.16–2.11 (m, 1 H).
13C NMR (150 MHz, CD3COCD3): δ = 158.6, 134.8, 133.4, 133.0,
132.0, 130.0, 129.5, 127.1, 127.0, 126.5, 126.5, 126.2, 124.3, 122.1,
107.4, 96.7, 55.4, 35.1, 32.4.
HRMS (EI): m/z [M]+ calcd for C19H18O3: 294.1256; found:
294.1251.
Acknowledgment
This work was support by the Fundamental Research Funds for the
Central Universities (2009ZM0241), the National Natural Science
Foundation of China (No. 21072062), and the Natural Science
Foundation of Guangdong Province, China (10351064101000000).
2-(Diphenylmethylene)-7-methoxy-1,6-dioxaspiro[4.4]non-3-
ene (17d)
Colorless syrup; yield: 56 mg (58%).
1H NMR (600 MHz, CD3COCD3): δ = 7.48–7.13 (m, 10 H), 6.25 (d,
J = 5.4 Hz, 0.24 H), 6.22 (d, J = 5.4, 0.76 H), 6.18 (d, J = 5.4 Hz,
0.76 H), 6.17 (d, J = 5.4 Hz, 0.24 H), 5.19–5.16 (m, 1 H), 2.31–2.71
(m, 4 H).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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13C NMR (150 MHz, CD3 COCD3): δ = 155.1 (0.76 C), 155.1 (0.24
C), 141.1 (0.24 C), 141.1 (0.76 C), 140.1 (0.76 C), 140.0 (0.24 C), References
134.4 (0.76 C), 134.0 (0.24 C), 131.9 (0.24 C), 131.9 (0.76 C),
(1) For reviews on the dearomatization of furan rings, see:
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(2) For selected recent examples of furan dearomatizations
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Z. Chem. Commun. (Cambridge) 2009, 662.
(3) (a) Gribble, G. W. In Comprehensive Organic Synthesis;
Vol. VIII; Trost, B. M.; Fleming, I., Eds.; Pergamon:
Oxford, 1991, 603. (b) Donohoe, T. J.; Garg, R.; Stevenson,
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T. J.; Calabrese, A. A.; Stevenson, C. A.; Ladduwahetty, T.
J. Chem. Soc., Perkin Trans. 1 2000, 3724.
130.3 (0.76 C), 130.3 (0.24 C), 129.1 (0.76 C), 128.5 (0.76 C),
128.4 (0.24 C), 128.2 (0.24 C), 128.0 (0.24 C), 127.7 (0.76 C),
126.8 (0.76 C), 126.8 (0.24 C), 121.1 (0.76 C), 121.1 (0.24 C),
114.8 (0.24 C), 114.8 (0.76 C), 107.2 (0.24 C), 106.5 (0.76 C), 55.3
(0.24 C), 55.1 (0.76 C), 35.0 (0.24 C), 34.2 (0.76 C), 32.4 (0.24 C),
32.0 (0.76 C).
HRMS (EI): m/z [M]+ calcd for C21H20O3: 320.1412; found:
320.1402.
2-Hex-2-yn-1-ylidene-7-methoxy-1,6-dioxaspiro[4.4]non-3-ene
(17e)
Colorless syrup; yield: 26 mg (37%).
1H NMR (600 MHz, CD3COCD3): δ = 6.66 (d, J = 5.4 Hz, 0.2 H),
6.41 (d, J = 5.4 Hz, 0.8 H), 6.30 (dd, J = 5.4, 1.8 Hz, 0.2 H), 6.19 (d,
J = 5.4 Hz, 0.8 H), 5.19–5.18 (m, 0.80 H), 5.15–5.14 (m, 0.20 H),
4.87–4.86 (m, 0.20 H), 4.65–4.64 (m, 0.8 H), 3.33 (s, 0.6 H), 3.30
(s, 2.4 H), 2.33–1.51 (m, 8 H), 0.99 (t, J = 7.2 Hz, 3 H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2567–2574

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