Novel conversions of furandiols and spiroacetal enol ethers into cyclopentenones: Implications of the isomerization mechanism of 2-furylcarbinols into cyclopentenones

Article abstract of DOI:10.1002/ejoc.200900129

Two acid-catalyzed conversions of furandiols 8 and its dehydration spiroacetalized products 9 into oxabicyclic cyclopentenones 10 in good to excellent yields are reported. To disclose the mechanism of these conversions, the fact that H₂O cataly

Full text of DOI:10.1002/ejoc.200900129

FULL PAPER
DOI: 10.1002/ejoc.200900129
Novel Conversions of Furandiols and Spiroacetal Enol Ethers into
Cyclopentenones: Implications of the Isomerization Mechanism of
2-Furylcarbinols into Cyclopentenones
Biao-Lin Yin,*[a] Yu-Lin Wu,[b] and Jin-Qiang Lai[a]
Keywords: Spiro compounds / Enols / Carbocycles / Isomerization
Two acid-catalyzed conversions of furandiols 8 and its dehy- presented, for which an intramolecular aldol reaction is the
dration spiroacetalized products 9 into oxabicyclic cyclopen- key step. On the basis of these results, we propose that these
tenones 10 in good to excellent yields are reported. To dis-
close the mechanism of these conversions, the fact that H2O
catalyzes the conversion of 9 into 10 is presented and inter-
mediates 9k and 20i have been structurally verified. In ad-
dition, two other related conversions of spiroacetal enol
ethers 11 and 14 derived from 8 into cyclopentenones are
conversions occur through an aldol condensation step in-
stead of electrocyclization of the 4π-electron system, which
was previously reported.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
ylcarbinols and predicted its pericyclic nature. However,
D’Auria provided evidence that intermediate 2 is an obvi-
ous mixture of trans and cis isomers when the R group is a
small alkyl group and proposed an alternative pathway.[5]
For this reaction, cis-2-alkyl(aryl)-3-hydroxycyclopent-4-en-
1-one formed through an alternative conrotatory electrocy-
clization could be isomerized to the more thermodynami-
cally stable trans isomer in acidic media or during purifica-
tion, complicating the interpretation of the stereochemical
outcome. Therefore, mechanistic studies on the isomeriza-
tion are still needed.
Introduction
The first acid-catalyzed isomerization reaction of 2-furyl-
carbinols into cyclopentenones was reported by Pianca-
telli[1] about 30 years ago, and since then significant re-
search effort has been focused on the reaction mechanism
and its applications in the synthesis of numerous biolo-
gically active natural products like prostanoids.[2] A brief
literature survey reveals that this isomerization involves two
steps. In the first step, 2-furylcarbinol 1 forms intermediate
2, which further rearranges into cyclopentenone
3
(Scheme 1). Usually this isomerization is catalyzed by a
protic acid such as formic acid, polyphosphoric acid, and
p-toluenesulfonic acid or by a Lewis acid such as zinc chlo-
ride in an aqueous system.[3] The mechanism of the isomer-
ization of 2-furylcarbinols into cyclopentenones has not yet
been fully studied. Piancatelli[1] once proposed that this
isomerization underwent a thermal conrotatory electro-
cyclic reaction of the 4π-electron system (Scheme 2). The
key step involves formation of carbocation 5. A water mole-
cule then attacks the 5-position of the furan ring to form
enol ether intermediate 6 (Z isomer). Prototropic shifts and
ring opening give intermediate 7, which cyclizes by a 4π-
electron thermal conrotatory electrocyclization. Subsequent
isomerization affords 3. Recently, Lera[4] studied the reac-
tion profile computationally with structurally simple 2-fur-
Scheme 1. Isomerization of 2-furylcarbinol into cyclopentenone.
Recently, we developed a concise and general synthetic
strategy to tonghaosu and its analogues 9, characterized by
a spiroacetal enol ether subunit, by an acid-catalyzed dehy-
dration–spiroacetalization reaction of corresponding furan-
diol 8 in an aprotic aromatic solvent such as toluene
(Scheme 3).[6] It is worth noting that when the unsaturated
part is an aromatic group, the Z isomer is produced exclu-
sively. However, when the unsaturated part is an alkenyl or
alkynyl group, the reaction gives rise to a mixture of Z and
E isomers in variable ratios. The conversion of intermediate
8 into tonghaosu analogs seems to involve the formation
of an enol ether carbocation like 6 in the acid-catalyzed
isomerization of 2-furylcarbinols and a subsequent intra-
molecular nucleophilic attack of the remaining hydroxy
[a] School of Chemistry and Chemical Engineering, South China
University of Technology,
Guangzhou, 510640, China
E-mail: blyin@scut.edu.cn
[b] State Key Laboratory of Bioorganic and Natural Products
Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Science,
Shanghai 20032, China
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B.-L. Yin, Y.-L. Wu, J.-Q. Lai
FULL PAPER
tion times (10b Ͻ 10g and 10h, 10d Ͻ 10i, 10e Ͻ 10j). By
using this protocol, a facile synthesis of thiophene-substi-
tuted oxabicyclic cyclopentenone 10f was accomplished in
83% yield from readily accessible 8f (Table 1, Entry 6).
Compound 10f is also a natural product named chrycorin
isolated from the same original plant Chrysanthemum as
natural product 9f by Tada and Chiba in 1984.[7] All the
spectroscopic data were in accordance with those reported
in the literature.
Table 1. Conversion of 8 into 10.
Scheme 2. Documented mechanism for the isomerization of 2-fur-
ylcarbinol.
group on the carbocation. To the best of our knowledge,
the conversion of these special 2-furylcarbinols into cyclo-
pentenones in the presence of an acid in an aqueous system
has not been reported so far. Meanwhile, this conversion
might shed some new light on the mechanism of 2-furylcar-
binol isomerization. We herein would like to detail the re-
sults.
Entry
2-Furylcarbinol
Reaction
time [h]
Products
(% yield[a]
)
1
2
3
4
5
6
7
8
9
8b
8c
8d
8e
8f
8g
8h
8i
5
4
3.5
6
4
6
6
5
8
3
10b (81)
10c (85)
10d (90)
10e (75)
10f (83)
10g (78)
10h (75)
10i (86)
10j (70)
10k (84)
8j
8k
10
[a] Isolated yields.
Scheme 3. General strategy to tonghaosu analogues 9.
During the course of the reaction, an intermediate was
found by TLC as a lower polarity spot than 10. This inter-
mediate was isolated and its structure was verified by NMR
spectroscopic analysis to be 9, which is the dehydration–
spiroacetalized product of 8. Accordingly, it is reasonable to
Results and Discussion
As can be seen from Table 1, all the 2-furylcarbinols were anticipate that spiroacetal enol ethers 9 could also undergo
converted into new compounds with a lower polarity than rearrangement into cyclopentenone 10 under the same reac-
8 in good to excellent yields when heated under reflux with tion conditions. As can be seen from Table 2, compounds 9
a catalytic amount of ZnCl2 in aqueous ethylene glycol di- indeed underwent isomerization into cyclopentenone 10 in
methyl ether. Spectroscopic data (IR, NMR, MS) showed yields comparable to those of 8. In addition, the reaction
that the molecular weight of these new compounds is time for 9 was shorter. On the basis of the above results, we
18 grams less than that of 8 and that they contain a ketone were interested in the mechanism of the two conversions
carbonyl group but no olefinic proton, which clearly sug- and envisioned that they might involve the same intermedi-
gests the formation of oxabicyclic cyclopentenones 10. The ate. In our previous study we reported a preliminary mecha-
nature of the substituent on the phenyl ring apparently in- nism of the isomerization of spiroacetal enol ether 9 into
fluenced the reaction yield and rate. Electron-donating cyclopentenone 10 by electrocyclization of a 4π-electron
groups on the phenyl ring led to better yields (10d Ͼ 10c Ͼ system.[8] However, according to this mechanism, 9 should
10b Ͼ 10e and 10i Ͼ 10h Ͼ 10j) and shorter reaction times isomerize into 10 under anhydrous acidic conditions. Sur-
(10d Ͻ 10c Ͻ 10b Ͻ 10e and 10i Ͻ 10h Ͻ 10j). Meanwhile, prisingly, after treatment of compound 9b with either ZnCl2
the side chain at the 5-position of the furan ring also as Lewis acid or p-TosOH as protic acid in refluxing anhy-
slightly influenced the reaction yield and rate. Relative to drous solvents such as DME or MeOH, the reaction system
substrates bearing a chain length of five carbon atoms or a was very complicated and compound 10b was not isolated.
heteroatom-containing carbon chain, molecules with a Interestingly, the addition of H2O (1 equiv.) into the anhy-
chain length of four carbon atoms gave higher yields (10b drous DME and ZnCl2 system was favorable and com-
Ͼ 10g and 10h, 10d Ͼ 10i, 10eϾ 10j) and had shorter reac- pound 10b was formed in 61% yield. The addition of larger
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Eur. J. Org. Chem. 2009, 2695–2699

Conversions of Furandiols and Spiroacetal Enol Ethers into Cyclopentenones
amounts of H2O resulted in shorter reaction times and
higher yields. In contrast, furandiol 8b, which produces one
equivalent of H2O in the presence of ZnCl2, can be con-
verted into 10b in 65% yield in refluxing anhydrous DME.
Therefore, we concluded that H2O catalyzes the isomeriza-
tion of enol ether 9 into cyclopentenone 10.
Table 2. Conversion of 9 into 10.
Entry
Spiroacetal
enol ether
Products
(% yield)
1
2
3
4
5
6
7
8
9
9b
9c
9d
9e
9f
9g
9h
9i
10b (83)
10c (86)
10d (89)
10e (80)
10f (87)
10g (77)
10h (74)
10i (77)
10j (72)
10k (87)
Scheme 4. Conversions of 11 and 14 into cyclopentenones. Reac-
tion conditions: (a) 2% HCl, THF, r.t.; (b) 5% NaOH in THF, r.t.
9j
9k
10
To obtain further insight into the mechanism of the
isomerization of spiroacetal enol ether 9 into cyclopen-
tenone 10, two other spiroacetal enol ether derivatives 11
and 14 were prepared according to known methods.[6h,9,10]
Similarly, treatment of 11 and 14 with aqueous HCl at room
temperature followed by base-catalyzed intramolecular al-
dol reaction afforded cyclopentenone 13 and 10b in 79 and
85% yield, respectively. As shown by TLC, the more polar
spots were very likely to be diketones 12 and 15, respec-
tively (Scheme 4). Enlightened by these results, we propose
a possible mechanism for the conversion of furandiol 8 and
spiroacetal enol ether 9 into cyclopentenone 10, and this
mechanism involves an intramolecular aldol reaction as the
key step (Scheme 5). Initially, in the presence of acid, a
water molecule attacks the 5-position of the furan ring of
furandiol 8 to form intermediate 17. Meanwhile, 8 can also
be partially transformed into enol ether 9 after loss of one
molecule of H2O, indicating that 8 can also be converted
Scheme 5. Mechanism for both substrates.
Conclusions
In summary, we have reported the novel conversion of
into 10 under anhydrous conditions. Under the same reac- special 2-furylcarbinols 8, bearing a hydroalkyl side chain
tion conditions, ring opening of 9 leads to carbocation 16, at the 5-position of the furan ring, into corresponding oxa-
which is then converted into the same intermediate 17 as bicyclic cyclopentenones 10 in good to excellent yields. In
that of 8. After prototropic shift and intramolecular aldol contrast, under the same reaction conditions spiroacetal
reaction steps, 17 is transformed into 20 and then into more enol ether 9, the dehydrate product of 8, can be isomerized
stable cyclopentenone 10. During the conversion of 8k into into 10 in comparable yields. To investigate the mechanism
10k, intermediate 9k was isolated as a mixture of cis and of the two conversions, the fact that H2O catalyzes the con-
trans isomers (2.8:1), indicating that enol ether 17 is proba- version of 9 into 10 is presented and intermediates 9k and
bly not always a pure isomer, as reported in the literature, 20i have been structurally verified. In addition, two other
and the configuration of its exo double bond depends on related conversions of spiroacetal enol ethers 11 and 14 de-
the nature of the unsaturated group. This results could be rived from 8 into cyclopentenones are also presented, for
helpful to explain the stereochemical outcome of the isom- which an intramolecular aldol reaction is the key step. On
erization of 2-furylcarbinols. It is worth noting that, fortu- the basis of these results, we proposed that these conver-
nately, intermediate 20i, which is two more polar spots than sions occur through an aldol condensation step instead of
8i on TLC, was isolated successfully as a mixture of E/Z electrocyclization of the 4π-electron system, which was pre-
isomers in a ratio of 1.5:1.[11] Its successful isolation may viously reported. This work might be helpful to disclose the
be possibly due to the more difficult formation of the seven- presently unclear mechanism of the acid-catalyzed isomer-
membered derivative than that of the six-membered deriva- ization reaction of 2-furylcarbinols into cyclopentenones.
tive.
Further study on the asymmetric rearrangement of 2-furyl-
Eur. J. Org. Chem. 2009, 2695–2699
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B.-L. Yin, Y.-L. Wu, J.-Q. Lai
FULL PAPER
1702, 1639, 1515, 1326, 1087, 1047, 809 cm–1. C15H16O3 (244.11):
calcd. C 73.75, H 6.60; found C 73.56, H 6.68.
carbinols into chiral cyclopentenones catalyzed by a chiral
aldol reaction catalyst is underway in our group, and the
results will be disclosed in due course.
5-(4-Nitrophenyl)-3,4,7,7a-tetrahydrocyclopenta[b]pyran-6(2H)-one
(10e): Yield: 388.6 mg (75%), yellow solid; m.p. 156–157 °C. 1H
NMR (300 MHz, CDCl3): δ = 8.28 (d, J = 9.3 Hz, 2 H), 7.51 (d,
J = 9.3 Hz, 2 H), 4.54 (dd, J = 6.3, 2.2 Hz, 1 H), 4.09 (br. d, J =
12.2 Hz, 1 H), 3.81 (m, 1 H), 3.05 (br. d, J = 11.8 Hz, 1 H), 2.92
(d, J = 18.3, 6.3 Hz, 1 H), 2.66 (dt, J = 14.8, 10.2 Hz, 1 H), 2.54
(dd, J = 18.6, 2.4 Hz, 1 H), 1.93 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 201.8, 171.3, 147.6, 137.2, 136.6, 130.2,
123.7, 75.8, 67.5, 42.2, 27.0, 26.9 ppm. MS: m/z (%) = 259 (74)
[M]+, 214 (100), 259 (74), 231 (66), 200 (40), 185 (60), 184 (66), 129
Experimental Section
General Remarks: IR spectra were recorded with Perkin–Elmer 983
or Shimadzu IR-440 spectrometers. 1H and 13C NMR spectra were
recorded with an AMX-300, DPX-300, Gemini-2000, or INOVA-
600 spectrometer with TMS as the internal standard. Mass spectra
were recorded with a Mariner (PE, for ESI), HP5973N or
HP5989A instrument. HRMS (EI or ESI) spectra were obtained
with a Kratos CONCEPT 1H or Bruker APEXIII 7.0 TESLA
mass spectrometer. Optical rotations were measured with a Perkin–
Elmer 241 MC polarimeter. Elemental analyses were carried out
at the Microanalytic Laboratory of Shanghai Institute of Organic
Chemistry. Flash column chromatography was performed on silica
gel H (10–40 m) with a petroleum ether/ethyl acetate or ethyl ace-
tate/ethanol system as eluent. Compounds 8,[6b] 9,[6g] 11,[6h] 13,[9]
and 14[10] were prepared according to literature procedures.
(50), 115 (79). IR (film): ν = 1714, 1641, 1596, 1510, 1344, 1137,
˜
1089, 852 cm–1. C14H13NO4 (259.08): calcd. C 64.86, H 5.05, N
5.41; found C 64.92, H 5.27, N 5.44.
5-(Thien-2-yl)-3,4,7,7a-tetrahydrocyclopenta[b]pyran-6(2H)-one
(10f): Yield: 365.3 mg (83%), yellow solid; m.p. 70–71 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.50 (d, J = 3.0 Hz, 1 H), 7.40 (d, J =
5.0 Hz, 1 H), 7.12 (dd, J = 5.0, 3.0 Hz, 1 H), 4.51 (br. d, J = 6.0 Hz,
1 H), 4.11 (br. d, J = 11.0 Hz, 1 H), 3.79 (m, 1 H), 3.46 (br. d, J =
15.0 Hz, 1 H), 2.87 (dd, J = 18.6, 6.0 Hz, 1 H), 2.61 (dt, J = 15.0,
10.0 Hz, 1 H), 2.48 (dd, J = 18.6, 2.7 Hz, 1 H), 1.90 (m, 2 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 201.3, 166.4, 131.1, 130.9, 127.7,
126.8, 126.4, 75.3, 69.1, 41.6, 26.6, 26.0 ppm. MS: m/z (%) = 220
(77) [M]+, 192 (100), 191 (64), 178 (32), 150 (36), 135 (36). IR
Typical Procedure for the Conversion of Furandiol 8 into Cyclopen-
tenone 10: A mixture of furandiol 8 (20 mmol), ZnCl2 (30 mg), and
water (20 mL) was heated under reflux until the starting material
was fully consumed (monitored by TLC). The reaction mixture was
then extracted with diethyl ether. The combined organic layer was
washed with brine and dried with Na2SO4. Removal of the solvent
yielded a crude product, which was purified by flash chromatog-
raphy to afford cyclopentenone 10.
(KBr): ν = 1710, 1630, 1429 cm–1. C H O S (220.06): calcd. C
˜
12 12
2
65.43, H 5.49; found C 65.31, H 5.22.
6-Phenyl-2,3,4,5,8,8a-hexahydro-7H-cyclopenta[b]oxepin-7-one
(10g): Yield: 355.9 mg (78%), syrup. 1H NMR (300 MHz, CDCl3):
δ = 7.42 (m, 5 H), 4.77 (m, 1 H), 3.90 (m, 1 H), 3.66 (m, 1 H), 2.94
(dd, J = 18.3, 6.7 Hz, 1 H), 2.77 (m, 1 H), 2.50 (dd, J = 18.3,
3.1 Hz, 1 H), 1.93–1.75 (m, 5 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 202.1, 167.5, 137.9, 130.4, 129.3, 128.6, 128.2, 75.5,
67.5, 42.4, 27.1, 26.8, 26.5 ppm. MS: m/z (%) = 228 (100) [M]+,
200 (36), 172 (38), 144 (49), 141 (33), 128 (35), 116 (48), 115 (48).
5-Phenyl-3,4,7,7a-Tetrahydrocyclopenta[b]pyran-6(2H)-one (10b):
Yield: 346.8 mg (81%), syrup. 1H NMR (300 MHz, CDCl3): δ =
7.34 (m, 5 H), 4.51 (dd, J = 6.6, 2.6 Hz, 1 H), 4.07 (ddd, J = 11.9,
5.0, 3.0 Hz, 1 H), 3.75 (m, 1 H), 3.04 (ddd, J = 14.6, 4.4, 3.3 Hz,
1 H), 2.85 (dd, J = 18.3, 6.5 Hz, 1 H), 2.52 (dt, J = 14.4, 9.5 Hz, 1
H), 2.47 (dd, J = 18.3, 2.4 Hz, 1 H), 1.83 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 202.7, 168.8, 138.2, 130.3, 129.1, 128.4,
128.1, 77.4, 67.4, 42.1, 26.9, 26.5 ppm. MS: m/z (%) = 214 (15)
[M]+, 186 (100), 185 (75), 116 (51), 115 (54), 144 (49), 129 (32), 128
IR (film): ν = 1689, 1112, 978, 700 cm–1. C H O (228.12): calcd.
˜
15 16
2
C 78.92, H 7.06; found C 79.03, H 7.35.
6-Phenyl-2,3,8,8a-tetrahydrocyclopenta[e][1,4]dioxepin-7(5H)-one
(10h): Yield: 345.1 mg (75%), syrup. 1H NMR (300 MHz, CDCl3):
δ = 7.44–7.27 (m, 5 H), 5.04–4.95 (m, 2 H), 4.65 (d, J = 18.7 Hz,
1 H), 4.14 (d, J = 13.0 Hz, 1 H), 3.98 (d, J = 13.0 Hz, 1 H), 3.84
(td, J = 10.7, 2.0 Hz, 1 H), 3.64 (td, J = 10.7, 2.0 Hz, 1 H), 2.99
(dd, J = 16.4, 6.6 Hz, 1 H), 2.54 (dd, J = 18.4, 2.2 Hz, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 202.6, 167.7, 138.1, 130.5, 129.2,
128.6, 128.2, 78.9, 75.8, 72.6, 71.4, 42.8 ppm. MS: m/z (%) = 230
(32) [M]+, 115 (90), 172 b (38), 142 (33), 141 (100), 116 (62), 128
(42), 102 (25). IR (film): ν = 1716, 1630, 1496, 1326, 1090,
˜
699 cm–1. C14H14O2 (214.10): calcd. C 78.48, H 6.59; found C
78.32, H 6.40.
5-(4-Methylphenyl)-3,4,7,7a-tetrahydrocyclopenta[b]pyran-6(2H)-
one (10c): Yield: 387.9 mg (85 %), syrup. 1H NMR (300 MHz,
CDCl3): δ = 7.21 (m, 4 H), 4.49 (d, J = 6.3 Hz, 1 H), 4.05 (dd, J
= 10.3, 2.2 Hz, 1 H), 3.74 (m, 1 H), 3.06 (br. d, J = 14.8 Hz, 1 H),
2.82 (dd, J = 18.2, 6.4 Hz, 1 H), 2.50 (dd, J = 15.0, 9.8 Hz, 1 H),
2.46 (dd, J = 18.2, 2.4 Hz, 1 H), 2.36 (s, 3 H), 1.82 (m, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 202.8, 169.2, 150.4, 137.4, 130.6,
120.7, 116.7, 75.6, 67.5, 42.1, 26.8, 26.6, 24.4 ppm. MS: m/z (%) =
228 (22) [M]+, 200 (28), 185 (100), 171 (49), 141 (23), 128 (30), 129
(36), 102 (35). IR (film): ν = 1703, 1442, 1284, 1141, 1005, 780, 767,
˜
702, 556 cm–1. C14H14O3 (230.09): calcd. C 73.03, H 6.13; found C
72.80, H 6.23.
6-(4-Methoxyphenyl)-2,3,8,8a-tetrahydrocyclopenta[e][1,4]dioxepin-
7(5H)-one (10i): Yield: 447.4 mg (86 %), syrup. 1H NMR
(300 MHz, CDCl3): δ = 7.26 (dd, J = 6.4, 2.4 Hz, 2 H), 6.94 (dd,
J = 6.4, 2.4 Hz, 2 H), 5.02 (d, J = 18.4 Hz, 1 H), 4.93 (d, J =
6.4 Hz, 1 H), 4.65 (d, J = 18.4 Hz, 1 H), 4.13 (d, J = 13.6 Hz, 1
H), 3.97 (d, J = 13.4 Hz, 1 H), 3.87–3.80 (m, 4 H), 3.66 (t, J =
8.4 Hz, 1 H), 2.95 (dd, J = 18.4, 6.8 Hz, 1 H), 2.52 (dd, J = 18.4,
2.4 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 202.8, 170.7,
(29), 115 (40). IR (film): ν = 1711, 1636, 1514, 1327, 1090 cm–1.
˜
C15H16O2 (228.12): calcd. C 78.92, H 7.06; found C 78.78, H 7.34.
5-(4-Methoxyphenyl)-3,4,7,7a-tetrahydrocyclopenta[b]pyran-6(2H)-
one (10d): Yield: 439.4 mg (90%), white solid; m.p. 108–109 °C. 1H
NMR (300 MHz, CDCl3): δ = 7.26 (d, J = 9.9 Hz, 2 H), 6.96 (d,
J = 9.8 Hz, 2 H), 4.49 (dd, J = 6.6, 1.8 Hz, 1 H), 4.09 (br. d, J =
12.0 Hz, 1 H), 3.82 (s, 3 H), 3.77 (m, 1 H), 3.09 (br. d, J = 12.2 Hz,
1 H), 2.86 (dd, J = 18.0, 3.0 Hz, 1 H), 2.55 (dt, J = 12.2, 2.4 Hz, 1 159.6, 137.8, 129.9, 122.5, 113.9, 78.5, 75.8, 72.4, 71.2, 55.2,
H), 2.47 (dd, J = 18.3, 3.0 Hz, 1 H), 1.81 (m, 2 H) ppm. 13C NMR 42.6 ppm. MS: m/z (%) = 274 (100) [M]+, 273 (96), 216 (68), 186
(100 MHz, CDCl3): δ = 203.1, 167.7, 159.5, 137.7, 130.6, 122.5, (46), 128 (47). IR (film): ν = 1700, 1501, 1436, 1354, 1241, 1138,
˜
114.2, 75.6, 67.4, 55.3, 42.1, 26.7, 26.5 ppm. MS: m/z (%) = 244
1044 cm–1. C15H16O4 (260.10): calcd. C 69.22, H 6.20; found C
(100) [M]+, 215 (31), 201 (18), 185 (51), 174 (32). IR (film): ν = 69.34, H 6.07.
˜
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Conversions of Furandiols and Spiroacetal Enol Ethers into Cyclopentenones
6-(4-Nitrophenyl)-2,3,8,8a-tetrahydrocyclopenta[e][1,4]dioxepin-
7(5H)-one (10j): Yield: 385.1 mg (70 %), syrup. 1H NMR 10b (182 mg, 85%).
(300 MHz, CDCl3): δ = 8.26 (d, J = 9.0 Hz, 2 H), 7.47 (d, J =
9.0 Hz, 2 H), 4.99 (m, 2 H), 4.64 (d, J = 18.8 Hz, 1 H), 4.16 (br.
crude product, which was purified by chromatography to afford
[1] G. Piancatelli, A. Scettri, S. Barbadoro, Tetrahedron Lett. 1976,
d, J = 13.2 Hz, 1 H), 4.01 (m, 1 H), 3.86 (m, 1 H), 3.66 (m, 1 H),
3.01 (m, 1 H), 2.56 (dd, J = 18.6, 2.7 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 202.9, 170.9, 147.8, 137.3, 136.8, 130.3,
123.9, 78.6, 75.9, 72.8, 71.7, 42.7 ppm. MS: m/z (%) = 275 (32)
[M]+, 202 (100), 58 (99), 115 (94), 141 (72), 140 (59), 139 (54), 170
17, 3555–3558.
[2] a) J. H. Dygos, K. A. Babiak, J. R. Behling, J. R. Medich, J. S.
Ng, J. J. Wieczorek, J. Org. Chem. 1991, 56, 2549–2552; b) G.
Piancatelli, M. D’Auria, F. D’Onofrio, Synthesis 1994, 867–
889; c) A. Rodriguez, M. Nomen, B. W. Spur, J. Godfroid, Eur.
J. Org. Chem. 1999, 2655–2662.
[3] a) G. Piancatelli, A. Scettri, G. David, M. D’Auria, Tetrahedron
1978, 34, 2775–2778; b) G. Piancatelli, A. Scettri, Tetrahedron
Lett. 1977, 18, 1131–1134; c) G. Piancatelli, A. Scettri, Synth.
Commun. 1977, 7, 116–117. For a review summarizing the
transformations of furans and their derivatives, see: d) G. Pian-
catelli, M. D’Auria, F. D’Onofrio, Synthesis 1994, 867–889.
[4] F. O. Nieto, C. Lopez, R. Alvarez, A. R. Lera, Chem. Eur. J.
2004, 10, 4324–4333.
[5] M. D’Auria, Heterocycles 2000, 52, 185–194.
[6] a) Y. Gao, W.-L. Wu, B. Ye, R. Zhou, Y.-L. Wu, Tetrahedron
Lett. 1996, 37, 893–896; b) Y. Gao, W.-L. Wu, Y.-L. Wu, B. Ye,
R. Zhou, Tetrahedron 1998, 54, 12523–12538; c) B.-L. Yin, Z.-
M. Yang, T.-S. Hu, Y.-L. Wu, Synthesis 2003, 1995–2000; d)
B.-L. Yin, T.-S. Hu, H.-J. Yue, Y. Gao, W.-M. Wu, Y.-L. Wu,
Synlett 2004, 306–310; e) L. Chen, H.-H. Xu, B.-L. Yin, C.
Xiao, T.-S. Hu, Y.-L. Wu, J. Agric. Food Chem. 2004, 52, 6719–
6723; f) B.-L. Yin, W.-M. Wu, T.-S. Hu, Y.-L. Wu, Eur. J. Org.
Chem. 2003, 4016–4022; g) J.-F. Fan, B.-L. Yin, Y.-F. Zhang,
Y.-L. Wu, Y.-K. Wu, Huaxue Xuebao 2001, 59, 1756–1762; h)
B.-L. Yin, L. Chen, H.-H. Xu, T.-S. Hu, Y.-L. Wu, Chin. J.
Chem. 2006, 24, 240–246.
(48), 171 (45). IR (film): ν = 1716, 1516, 1352, 1133, 852, 703,
˜
557 cm–1. C14H13NO5 (275.08): calcd. C 61.09, H 4.76, N 5.09;
found C 60.96, H 4.88, N 5.18.
5-[(E)-2-phenylethenyl]-3,4,7,7a-tetrahydrocyclopenta[b]pyran-
6(2H)-one (10k): Yield: 403.4 mg (84 %), syrup. 1H NMR
(400 MHz, CDCl3): δ = 7.73 (d, J = 16.4 Hz, 1 H), 7.47 (d, J =
8.0 Hz, 2 H), 7.34–7.31 (m, 2 H), 7.26–7.23 (m, 1 H), 6.72 (d, J =
16.4 Hz, 1 H), 4.40 (d, J = 5.2 Hz, 1 H), 4.04 (dd, J = 9.6, 2.0 Hz,
1 H), 3.71 (t, J = 8.8 Hz, 1 H), 3.11 (br. d, J = 14.6 Hz, 1 H), 2.76
(dd, J = 18.4, 6.4 Hz, 1 H), 2.39 (dd, J = 18.4, 2.8 Hz, 1 H), 2.36–
2.42 (m, 1 H), 1.91–1.84 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 203.3, 168.2, 137.3, 134.5, 133.1, 128.6, 128.1, 126.6,
116.1, 75.3, 67.2, 42.3, 26.8, 25.9 ppm. MS: m/z (%) = 240 (54)
[M]+, 212 (100), 211 (84), 144 (57), 170 (44), 154 (32), 128 (25). IR
(film): ν = 1708, 1674, 1582, 1348, 1128, 856, 713, 560 cm–1
.
˜
C16H16O2 (240.12): calcd. C 79.97, H 6.71; found C 79.88, H 6.56.
Typical Procedure for the Conversion of Furandiol 9 into Cyclopen-
tenone 10: To a 100-mL round-bottomed flask was added spiroace-
tal enol ether 9 (20 mmol), ZnCl2 (30 mg), water (20 mL), and eth-
ylene glycol dimethyl ether (20 mL). The reaction mixture was
heated under reflux until the starting material was fully consumed
(monitored by TLC). The reaction mixture was then extracted with
diethyl ether. The combined organic layer was washed with brine
and dried with Na2SO4. Removal of the solvent yielded a crude
product, which was purified by flash chromatography to afford cy-
clopentenone 10.
[7] M. Tada, K. Chiba, Agric. Biol. Chem. 1984, 48, 1367–1369.
[8] B.-L. Yin, Y.-K. Wu, Y.-L. Wu, J. Chem. Soc. Perkin Trans. 1
2002, 1746–1747.
[9] B.-L. Yin, J.-F. Fan, Y. Gao, Y.-L. Wu, Synlett 2003, 3, 309–
401.
[10] B.-L. Yin, T.-S. Hu, Y.-L. Wu, Tetrahedron Lett. 2004, 45,
2017–2021.
[11] Spectroscopic data for compound 20i: IR (KBr): ν = 3415,
˜
2934, 1708, 1610, 1513, 1250, 1179, 1123, 1031, 815 cm–1. H
NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 5.6 Hz, 0.6 H), 7.56
(d, J = 6.0 Hz, 0.4 H), 7.00 (m, J = 8.8 Hz, 2 H), 6.80 (d, J =
8.8 Hz, 2 H), 6.33 (d, J = 5.6 Hz, 0.4 H), 6.25 (d, J = 6.0 Hz,
0.6 H), 4.54 (dd, J = 20.8, 8.8 Hz, 0.8 H), 3.78–3.56 (m, 10 H),
3.03 (dd, J = 20.8, 8.8 Hz, 1.2 H) ppm. MS (ESI): m/z = 277
[M – H]+.
Procedure for the Conversion of 14 into 10b: To a solution of 14
(301 mg, 1 mmol) in THF (5 mL) was added 2% HCl (3 mL). The
reaction mixture was stirred at room temperature for 30 min until
the starting material was fully consumed (monitored by TLC).
Then, 5% NaOH was added to the mixture until pH 13. The reac-
tion mixture was stirred at room temperature for 4 h and then ex-
tracted with diethyl ether. The combined organic layer was washed
with brine and dried with Na2SO4. Removal of solvents yielded a
Received: February 7, 2009
Published Online: April 16, 2009
Eur. J. Org. Chem. 2009, 2695–2699
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2699