Electrohydrocyclization of alkoxy tether substituted mixed enone/enoate and bisenone systems: retention versus elimination

Article abstract of DOI:10.1016/j.tet.2007.07.025

The electrohydrocyclization of tethered enone/enoate or bisenone systems which contain an alkoxyl substituent in the tether was studied. Rather surprisingly, the cyclization of these compounds afforded very different products depending upon the alkoxy sub

Full text of DOI:10.1016/j.tet.2007.07.025

Tetrahedron 63 (2007) 9691–9698
Electrohydrocyclization of alkoxy tether substituted
mixed enone/enoate and bisenone systems:
retention versus elimination
*
Renuka Manchanayakage, Duncan Omune, Christopher Hayes and Scott T. Handy
Department of Chemistry, Middle Tennessee State University, Murfreesboro, TN 37132, United States
Received 11 June 2007; revised 9 July 2007; accepted 10 July 2007
Available online 15 July 2007
Abstract—The electrohydrocyclization of tethered enone/enoate or bisenone systems which contain an alkoxyl substituent in the tether was
studied. Rather surprisingly, the cyclization of these compounds afforded very different products depending upon the alkoxy substituent. This
behavior and its potential applications will be discussed.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
electrohydrocyclization reactions. Ultimately, the electrohy-
drocyclization of these alkoxy tether substituted enone/
enoate systems could be a versatile route to the basic skele-
ton of a variety of biologically active sesquiterpene natural
products such as equisetin and polygodial.4
The hydrodimerization reaction remains an important trans-
formation in organic chemistry.1 Although the intermolecu-
lar reaction is well appreciated and finds a number of
different applications from the academic to the industrial
scale, the intramolecular version (henceforth called the elec-
trohydrocyclization) has received much less attention. At the
same time, it does have some particularly attractive features,
including the rapid increase in molecular complexity result-
ing from the formation of one new ring and up to four new
stereocenters.2 In an effort directed at harnessing the power
of the electrohydrocyclization, we have recently reported
our results of a more detailed study of the effect of ring
size, tether length, b-substitution, and reaction conditions
on the electrohydrocyclization of cyclic five- and six-mem-
bered ring enones.3
Me
N
HO
O
O
OH
H
H
O
O
R'
H
R
H
H
O
O
Equisetin
R
R'
OR
OR
O
H
O
O
1
O
2
H
H
Encouraged by these initial results, we were interested in ex-
ploring the electrohydrocyclization of tether substituted sys-
tems such as 1 (Scheme 1). This tether substituent can be of
value in several different ways. First, it provides a means of
differentiating between the two carbonyls, particularly in
cases where both are ketones or esters. Second, it provides
a convenient handle for functionalization of the newly
formed ring. Third, and perhaps most importantly, it pro-
vides a possible entry into the generation of optically pure
cyclization materials and thereby an entry into asymmetric
Polygodial
Scheme 1. Tether substituted cyclization system and potential applications.
2. Results and discussion
As an initial exploration of these tether substituted cycliza-
tion reactions, two simple systems were explored: bisenone
4 and enone/enoate 3. The most obvious route to such cycli-
zation substrates is via a Baylis–Hillman reaction. Beyond
the advantage of convergency, this approach also has poten-
tial for the preparation of asymmetric cyclization substrates
via the growing number of asymmetric catalysts for Baylis–
Hillman reactions that have been reported in recent years.5
Keywords: Hydrodimerization; Reduction; Electrochemistry; Cyclization;
Elimination.
* Corresponding author. Tel.: +1 615 904 8114; fax: +1 615 898 5182;
e-mail: shandy@mtsu.edu
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.07.025

9692
R. Manchanayakage et al. / Tetrahedron 63 (2007) 9691–9698
In keeping with this approach, the synthesis of enone/enoate
cyclization precursor 3 involved a Baylis–Hillman reaction
between known aldehyde 8 with methyl acrylate in the pres-
ence of DABCO at room temperature6 (Scheme 2). The sol-
vent used for this reaction proved to be an important variable,
since typical solvent systems such as water/dioxane, metha-
nol or acetonitrile did not afford good yields, even after pro-
longed reaction times.7 Neat reaction conditions, however,
afforded enone/enoate system 3 in 82% yield after 48 h.
results of previous cyclizations in this group and was sup-
ported by the absence of any NOE between the angular
methyl group and the bridgehead proton.3b Further evidence
for the stereochemical outcome of this reaction came from
the structural studies of the cyclization products of the
ether-substituted compounds 5 and 6 (vide infra).
O
O
cce
O
O
Sn/Pt
Et4NCl
CH3CN/H2O
3 h
O
OH
H
O
O
CO2Me
OR
9 69%
OMe
3
O
DABCO
O
O
O
O
RT, 48 h
82%
8
cce
3 R = H
O
O
Sn/Pt
MEMCl
TBSCl
Et4NCl
CH3CN/H2O
3 h
5 R = MEM, 89%
6 R = TBS, 72%
OR
OR
H
O
O
5 R = MEM
6 R = TBS
10 R = MEM, 47%
11 R = TBS, 49%
Scheme 2. Synthesis of enone/enoate cyclization precursor 3.
Scheme 4. Electrochemical cyclizations of enone/enoate systems.
In addition to the hydroxy-substituted compound, two ether-
substituted cyclization substrates (5 and 6) were prepared
simply by treating alcohol 3 with MEMCl and TBSCl, re-
spectively, under standard reaction conditions.
On the basis of that assumption, the electrohydrocycliza-
tions of the two ether-substituted substrates 5 and 6 were
expected to also afford the same elimination product 9.
Interestingly, they did not follow the same pattern. Instead,
both of these compounds afforded cyclization products
with retention of the alkoxy substituents (10 and 11). More-
over, a single isomer of the retention product was observed,
indicating that the pre-existing stereocenter in the tether
served to direct the facial selectivity of the cyclization. Pre-
sumably this occurs with the substituent assuming a pseudo-
equatorial position in a chair-like transition state 12 (Fig. 1).
In keeping with this proposed transition state and the results
of our previous electrohydrocyclizations, the relative stereo-
chemistry of the four stereocenters in product 11 was deter-
mined to be as shown.3b This stereochemistry was
determined by the use of a NOESY spectrum of 11, which
revealed key cross-peaks between the angular methyl group
and Hc and between Ha and Hb, but not between the angular
methyl group and Hb or Ha. Compound 10 is also formed as
a single isomer, presumably with the same stereochemical
result as compound 11.
For the preparation of bisenone system 4, another Baylis–
Hillman reaction was employed, this time between aldehyde
8 and 2-cyclohexenone (Scheme 3). Standard conditions (in-
cluding neat reaction conditions) completely failed to afford
any of the desired products. Indeed, extensive optimization
of the reaction conditions eventually determined that the
more reactive Lewis-acid catalyzed conditions reported by
Li were the only ones that afforded significant amounts of
the desired product.8 Fortunately, these conditions did
work quite well, affording 4 in 82% yield. Treatment of 4
with MEMCl under standard conditions then afforded the
MEM-protected compound 7 in 93% yield.
O
O
OR
O
TiCl4
CH2Cl2
2 h, 82%
O
O
8
4 R = H
The next stage was to determine if the bisenone systems
would behave similarly. Cyclization of systems 4 and 7
under the same electrochemical conditions proceeded as
expected with compound 4, containing an unprotected
alcohol in the tether, affording the elimination product 13
and compound 7, with a MEM ether in the tether, affording
retention product 14 (Scheme 5). In this latter case, the prod-
uct was once again obtained as a single isomer.
MEMCl
7 R = MEM, 93%
Scheme 3. Synthesis of bisenone cyclization precursor 4.
With the cyclization substrates in hand, electrohydrocycliza-
tion was first explored under electrochemical conditions.
Compound 3 was subjected to a constant current (cce) of
100 mA for 5 h using a tin anode and a platinum cathode
in an undivided cell under an inert atmosphere of argon
with 0.1 M tetraethylammonium chloride as the supporting
electrolyte in aqueous acetonitrile9 (Scheme 4). The reaction
afforded cyclization product 9 in 69% yield. Although we
were somewhat surprised to observe the elimination product,
it was initially suspected that the intermediate enolate
formed during the electrohydrocyclization underwent elim-
ination of hydroxide to yield the a,b-unsaturated cyclic ester
(vide infra). With respect to the product stereochemistry, the
trans ring fusion was initially proposed based upon the
nOe
MeO
O
Hc
O
O
e-
CO2Me
OR
OR
OR
Hb
Ha
O
O
O
12
5, 6
nOe
10, 11
Figure 1. Proposed conformation for cyclization.

R. Manchanayakage et al. / Tetrahedron 63 (2007) 9691–9698
9693
corresponding acetate 17 by treatment with acetic anhydride
in pyridine. Either compound 16 or 17 could be converted
into the furanone systems by oxidation to the sulfoxide
with m-CPBA followed by thermal elimination in toluene
at reflux. From alcohol 1, the corresponding TBS and
MEM ethers 19 and 20 were prepared as before.
cce
O
O
Sn/Pt
H
Et4NCl
CH3CN/H2O
3 h
OH
H
O
O
O
13 69%
4
H
H
With the desired cyclization precursors in hand, cyclization
of 1 afforded elimination product 21 as expected (Scheme
7). Not too surprisingly, acetate protected compound 18
also afforded the same elimination product in essentially
the same yield. The two ether substrates, 19 and 20, afforded
the retention products 22 and 23, respectively, as single iso-
mers. Assignment of the stereochemistry of these products
was more difficult than in previous cases, since no NOE
was observed between the angular methyl group and Ha,
Hb, Hc or Hd. This favors the stereochemistry as shown,
but is clearly not definitive. Further support for the depicted
stereochemistry comes from previous cyclizations in this
group, which have afforded trans ring fusions for [6.6] sys-
tems and cis ring fusions for [6.5] systems and have always
afforded the anti relationship between the two pre-existing
rings (in this case the angular methyl group and Ha).3
cce
O
O
Sn/Pt
Et4NCl
CH3CN/H2O
3 h
OMEM
OMEM
H
O
7
14 58%
Scheme 5. Electrochemical cyclizations of bisenone systems.
The stereochemistry of these cyclization products was de-
termined via extensive NMR studies. For compound 14, a
NOESY revealed key correlations between the angular
methyl group and Hb on one face of the newly formed ring
and Ha, Hc, and Hd on the other face, which is consistent
with the proposed stereochemistry (Fig. 2). This outcome
is also consistent with previous cyclizations by Mandell
and in this group of tethered biscyclohexenones, which
have cleanly afforded the trans/anti/trans isomer as the
sole reaction product.3b,10 From this assignment, the stereo-
chemistry of 13 is predicted to be the same at the remaining
three stereocenters.11
O
O
cce
O
O
Sn/Pt
H
Et4NCl
CH3CN/H2O
3 h
OR
H
O
O
Hb
1 R = H
59% from 1
21
18 R = Ac
59% from 18
O
OMEM
Ha
Hc
O
Hb
O
O
cce
Hd
O
O
Sn/Pt
Ha
Et4NCl
CH3CN/H2O
3 h
= nOe observed
OR
OR
Hd Hc
O
O
Figure 2. Stereochemistry of product 14.
19 R = MEM
20 R = TBS
23 R = MEM, 61%
22 R = TBS, 59%
Scheme 7. Electrochemical cyclizations of enone/enoate systems.
On the basis of these encouraging results, the preparation of
enone/enoate 1, which would be more directly applicable to
the synthesis of drimane-type natural products, was under-
taken (Scheme 6). Initial attempts using a Baylis–Hillman
reaction between 2(5H)-furanone and the aldehyde 8 were
not successful under a variety of conditions.12 As a result,
more traditional methods for the synthesis of these types of
compounds were employed, in particular the use of a-thio-
g-lactones.13 With that in mind, 3-phenylsulfanyl-dihydro-
furan-2-one 15 was synthesized in two steps starting from
g-butyrolactone in 78% yield overall.14 Formation of the
enolate of 15 and condensation with aldehyde 8 then af-
forded aldol product 16. This product was converted to the
In an effort to compare the electrochemical results with con-
ventional synthetic methods, the cyclizations of the four sub-
strates in Scheme 7 were investigated using samarium
diiodide as the reducing agent15 (Table 1). Treatment with
4 equiv of freshly prepared samarium diiodide at room tem-
perature in THF under argon afforded the anticipated elimi-
nation product 21 from substrates 1 and 18. Similarly,
substrates 19 and 20 afforded alkoxy-retention cyclization
products 22 and 23 in keeping with those observed under
electrochemical conditions. The yields in all cases are
slightly lower than those obtained under the electrochemical
O
O
O
O
1. mCPBA
CH2Cl2
PhS
O
RT, 2 h
O
SPh
15
OR
OR
O
2. Toluene
reflux, 1 h
LDA
O
O
O
THF, -78 °C
3 h, 76%
8
1 R = H, 60%
18 R = Ac, 52%
16 R = H
Ac2O
17 R = Ac, 95%
MEMCl
TBSCl
Pyr/DMAP
20 R = MEM, 89%
19 R = TBS, 77%
Scheme 6. Synthesis of 2(5H)-furanone-containing substrates.

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R. Manchanayakage et al. / Tetrahedron 63 (2007) 9691–9698
Table 1. Cyclizations under electrochemical and SmI2 conditions
4.1.1. 3-Hydroxy-2-methylene-4-(2-methyl-6-oxo-cyclo-
hex-1-enyl)-butyric acid methyl ester [3]. A mixture of al-
dehyde 8 (1.40 g, 9.20 mmol), methyl acrylate (2.48 mL,
27.6 mmol), and 1,4-diazabicyclo[2.2.2]octane (1.03 g,
9.20 mmol) was stirred at room temperature for 48 h. The
mixture was diluted with 30 mL of methylene chloride and
extracted with 10% aqueous HCl (2ꢀ20 mL). The organic
layer was dried with magnesium sulfate, filtered, and con-
centrated in vacuo. The product was purified by flash column
chromatography (30% ethyl acetate/hexanes as eluent) to
obtain 1.80 g (82%) of 3 as a clear oil.
Substrate
Product
Yield, electrochemical
conditions
Yield, SmI2
conditions
1
21
21
22
23
59
59
59
61
45
40
50
39
18
19
20
conditions, but are similar. Further, no change in product ste-
reochemistry was observed.
One clear question in all of these tether substituted cycliza-
tions is why some afford elimination products and some re-
tention products. One possible explanation is based on the
pKa (and thus leaving group ability) of the conjugate acid
of the potential leaving group as seen in Table 2. The two
cases that afford elimination (acetoxy and hydroxy groups)
have the two lowest pKa values, while the MEM alcohol
and silanol cases afford retention of the substituent and
have higher pKa values.16 Other issues, such as the ability
of the initial products to adopt a configuration suitable for
elimination, may also contribute to this difference in reac-
tion outcome.
1
IR (CDCl3) 3310, 2923, 2848, 1722, 1645, 1438; H NMR
(360 MHz, CDCl3) d 6.23 (s, 1H), 5.95 (s, 1H), 4.47–4.44
(m, 1H), 3.74 (s, 3H), 2.71–2.67 (m, 1H), 2.57–2.55 (m,
1H), 2.41–2.35 (m, 4H), 2.01–1.99 (m, 5H); 13C NMR
(90 MHz, CDCl3) d 202.3, 167.0, 160.1, 142.7, 132.4,
125.2, 77.1, 51.8, 37.7, 33.4, 33.2, 22.2, 21.7. HRMS (EI)
calcd for C13H18O4 238.1205, found 238.1203.
4.1.2. 3-(2-Methoxy-ethoxymethoxy)-2-methylene-4-
(2-methyl-6-oxo-cyclohex-1-enyl)-butyric acid methyl
ester [5]. A mixture of 3 (100 mg, 0.42 mmol), DMAP
(10 mg, 0.08 mmol), and diisopropylethyl amine (330 mL,
1.89 mmol) in methylene chloride (4 mL) was cooled to 0 ꢁC
and 2-methoxyethoxymethyl chloride (98 mL, 0.84 mmol)
was added. The reaction mixture was warmed to room
temperature and stirred overnight. The mixture was diluted
with 10 mL methylene chloride and washed successively
with water, 10% HCl, saturated aqueous sodium bicarbon-
ate, and brine. The organic layer was dried with magnesium
sulfate, filtered, and concentrated in vacuo. The crude prod-
uct was purified by flash column chromatography (30%
ethyl acetate/hexanes as eluent) to afford 122 mg (89%) of
5 as a light yellow oil.
Table 2. Reaction outcome versus substituent and substituent pKa
Substituent
pKa
Product type
Acetate
Hydroxyl
OMEM
OTBS
4.7
15
19
21.5
Elimination
Elimination
Retention
Retention
3. Conclusion
1
In conclusion, we have noted that alkoxy tether substituted
enone/enoate and dienone systems can successfully undergo
the electrohydrocyclization. Either the elimination or the re-
tention product can be formed, with the product type being
determined by whether the oxygen group on the tether is
a simple hydroxyl or an ether. Further studies of the mecha-
nism of this reaction and applications in synthesis are under-
way and will be reported in due course.
IR (CDCl3) 2935, 2887, 1720, 1664, 1627, 1436, 1379; H
NMR (360 MHz, CDCl3) d 6.24 (s, 1H), 5.82 (s, 1H), 4.81
(s, 2H), 4.61–4.52 (m, 1H), 3.74 (s, 3H), 3.72–3.68 (m,
2H), 3.54–3.49 (m, 2H), 3.36 (s, 3H), 2.8–2.61 (m, 2H),
2.35–2.29 (m, 3H), 2.15 (s, 3H), 2.02–1.86 (m, 3H); 13C
NMR (90 MHz, CDCl3) d 198.4, 166.7, 158.3, 141.4,
132.1, 126.1, 93.7, 74.5, 71.8, 67.1, 59.2, 51.9, 37.9, 33.3,
31.5, 22.3, 22.0. HRMS (EI) calcd for C17H26O6 326.1729,
found 326.1730.
4. Experimental
4.1. General
4.1.3. 3-(tert-Butyl-dimethyl-silanyloxy)-2-methylene-
4-(2-methyl-6-oxo-cyclohex-1-enyl)-butyric acid methyl
ester [6]. To a solution of 3 (200 mg, 0.839 mmol) in 0.8 mL
DMF was added imidazole (172 mg, 2.53 mmol) followed by
tert-butyldimethylsilyl chloride (380 mg, 2.53 mmol). The
reaction mixture was stirred overnight at room temperature
and then was diluted with 15 mL of methylene chloride and
washed with water. The aqueous layer was extracted with
15 mL of methylene chloride and the combined organic layers
were dried over magnesium sulfate, filtered, and concentrated
in vacuo. The resulting crude oil was purified by flash column
chromatography (30% ethyl acetate/hexanes as eluent) to
afford 210 mg (72%) of 6 as a light yellow oil.
Proton (1H) and carbon (13C) nuclear magnetic resonance
(NMR) spectra were recorded on a Bruker AM 360 MHz
spectrometer as a solution in deuterochloroform. NOESY
spectra were collected on a JEOL ECA-500 500 MHz spec-
trometer. Chemical shifts are reported in parts per million
relative to tetramethylsilane. Infrared (IR) spectra were re-
corded on a Perkin–Elmer Spectrum Bx spectrophotometer.
All solvents were of reagent grade unless stated otherwise.
Reactions were monitored by thin layer chromatography
(TLC) with precoated silica gel plates. Silica gel (100–200
mesh) was used for all chromatographic purifications. All re-
actions were performed under an argon atmosphere unless
noted otherwise.
1
IR (CDCl3) 2993, 2851, 1752, 1721, 1660, 1620, 1465; H
NMR (360 MHz, CDCl3) d 6.15 (s, 1H), 5.87 (s, 1H), 4.68 (t,
J¼6.6 Hz, 1H), 3.75 (s, 3H), 2.62–2.54 (m, 2H), 2.34–2.27

R. Manchanayakage et al. / Tetrahedron 63 (2007) 9691–9698
9695
(m, 4H), 1.98–1.85 (m, 5H), 0.85 (d, J¼21.6 Hz, 9H), 0.05
(s, 3H), ꢂ0.09 (s, 3H); 13C NMR (90 MHz, CDCl3) d 198.3,
166.7, 157.5, 144.8, 132.0, 124.3, 69.9, 51.6, 37.6, 34.3,
33.0, 25.7, 25.6, 22.0, 21.9, 17.9, 14.1, ꢂ3.7, ꢂ5.2. HRMS
(EI) calcd for C19H32O4Si 352.2070, found 352.2069.
the reaction stirred for another 3 h at ꢂ50 ꢁC. At this point,
the reaction was poured onto cold saturated aqueous ammo-
nium chloride (20 mL). The organic layer was separated and
the aqueous layer was extracted twice with ether
(2ꢀ10 mL). The combined organic layers were dried with
magnesium sulfate, filtered, and concentrated in vacuo.
The product was purified by flash column chromatography
(30% ethyl acetate/hexanes as eluent) to obtain 251 mg
(76%) of 16 as a light yellow oil.
4.1.4. 2-[2-Hydroxy-2-(6-oxo-cyclohex-1-enyl)-ethyl]-3-
methyl-cyclohex-2-enone [4]. In a dry vial, aldehyde 8
(150 mg, 1 mmol), freshly distilled methylene chloride
(1.5 mL), and cyclohexenone (195 mL, 2 mmol) were cooled
to 0 ꢁC and titanium tetrachloride (165 mL, 1.5 mmol) was
added dropwise. The reaction mixture was warmed to
room temperature and stirred for 2 h, then diluted with meth-
ylene chloride, and extracted with saturated aqueous sodium
bicarbonate. The organic layer was separated and dried over
magnesium sulfate, filtered, and concentrated in vacuo. The
crude mixture was purified by flash column chromatography
(20% ethyl acetate/hexanes as eluent) to afford 200 mg
(82%) of 4 as a clear oil.
IR (CDCl3) 3426, 3058, 2924, 1776, 1651, 1573, 1472,
1139; H NMR (360 MHz, CDCl3) d 7.64–7.56 (m, 2H),
1
7.37–7.29 (m, 3H), 4.24–4.17 (m, 1H), 3.99–3.90 (m, 1H),
3.80–3.77 (m, 1H), 3.63 (br s, 1H, OH), 3.12–2.82 (m,
1H), 2.73–2.49 (m, 1H), 2.40–2.33 (m, 6H), 2.12 (d,
J¼6.0 Hz, 2H), 1.95–1.85 (m, 3H); 13C NMR (90 MHz,
CDCl3) d 201.6, 175.1, 159.7, 137.2, 136.7 (2C), 132.2, 130.0,
129.2 (2C), 72.1, 65.2, 59.1, 37.4, 33.0, 29.1, 27.9, 22.8, 21.5.
HRMS (EI) calcd for C19H22OS 347.1239, found 347.1236.
1
IR (CDCl3) 3473, 2857, 1779, 1716, 1698, 1471; H NMR
4.1.7. Acetic acid 2-(2-methyl-6-oxo-cyclohex-1-enyl)-1-
(2-oxo-3-phenylsulfanyl-tetrahydro-furan-3-yl)-ethyl es-
ter [17]. To a mixture of 16 (100 mg, 0.28 mmol) in pyridine
(0.56 mL) was added acetic anhydride (43 mL, 0.42 mmol)
followed by DMAP (17 mg, 0.14 mmol). The reaction was
stirred overnight at room temperature and then was diluted
with methylene chloride (20 mL) and extracted with 1 N
HCl (10 mL). The organic layer was dried over magnesium
sulfate, filtered, and concentrated in vacuo. The product was
purified by flash column chromatography (20% ethyl ace-
tate/hexanes as eluent) to afford 105 mg (95%) of 17 as
a light yellow oil.
(360 MHz, CDCl3) d 7.01 (t, J¼4.7 Hz, 1H), 4.42–4.36
(m, 1H), 3.98 (br, J¼5.4 Hz, 1H, OH), 2.66 (dd, J¼14.3,
4.0 Hz, 1H), 2.48–2.34 (m, 10H), 2.03 (s, 3H), 1.98–1.89
(m, 3H); 13C NMR (90 MHz, CDCl3) d 202.1, 200.1,
160.0, 145.5, 141.4, 132.9, 70.4, 38.8, 37.8, 33.7, 33.2,
25.8, 22.9, 22.3, 21.8. HRMS (EI) calcd for C15H20O3
248.1412, found 248.1414.
4.1.5. 2-[2-(2-Methoxy-ethoxymethoxy)-2-(6-oxo-cyclo-
hex-1-enyl)-ethyl]-3-methyl-cyclohex-2-enone [7]. A mix-
ture of 4 (100 mg, 0.40 mmol), DMAP (10 mg, 0.08 mmol),
and diisopropylethyl amine (316 mL, 1.80 mmol) in methyl-
ene chloride (4 mL) was cooled to 0 ꢁC and 2-methoxy-
ethoxymethyl chloride (92 mL, 0.80 mmol) was added. The
reaction mixture was warmed to room temperature and
stirred overnight at room temperature. The mixture was di-
luted with 10 mL methylene chloride and washed succes-
sively with H2O, 10% HCl, saturated aqueous sodium
bicarbonate, and brine. Organic layer was dried over magne-
sium sulfate, filtered, and concentrated in vacuo. The crude
product was purified by flash column chromatography (25%
ethyl acetate/hexanes as eluent) to afford 125 mg (93%) of 7
as a light yellow oil.
IR (CDCl3) 3067, 2937, 2870, 1780, 1663, 1629, 1583,
1
1227; H NMR (360 MHz, CDCl3) d 7.61 (d, J¼7.3 Hz,
2H), 7.42–7.32 (m, 3H), 5.34 (dd, J¼11.0, 3.7 Hz, 1H),
4.27 (dd, J¼8.4, 3.7 Hz, 2H), 3.05–2.98 (m, 1H), 2.83–
2.66 (m, 2H), 2.53 (s, 1H), 2.35–2.26 (m, 4H), 2.20–2.13
(m, 1H), 1.95–1.87 (m, 4H); 13C NMR (90 MHz, CDCl3)
d 198.3, 173.0, 170.0, 159.1, 137.3 (2C), 137.0, 130.1,
129.1, 128.9 (2C), 73.2, 71.6, 65.1, 37.4, 32.9, 30.5, 25.8,
21.9, 21.5, 20.6. HRMS (EI) calcd for C21H24O5S
389.1345, found 389.1348.
4.1.8. 3-[1-Hydroxy-2-(2-methyl-6-oxo-cyclohex-1-enyl)-
ethyl]-5H-furan-2-one [1]. To a solution of 16 (600 mg,
1.6 mmol) in methylene chloride (16 mL), was added
m-chloroperbenzoic acid (578 mg, 3.3 mmol). The reaction
was stirred for 2 h at room temperature and then was diluted
with 15 mL methylene chloride and washed with 20 mL of
saturated aqueous sodium bicarbonate. The aqueous layer
was extracted with 10 mL of methylene chloride. The com-
bined organic layers were washed with brine, dried over
magnesium sulfate, filtered, and concentrated in vacuo.
The crude product was dissolved in 5 mL of toluene and re-
fluxed 1 h. The solvent was then evaporated and the crude
mixture was purified by flash column chromatography
(50% ethyl acetate/hexanes as eluent) to afford 250 mg
(60%) of 1 as a light yellow oil.
1
IR (CDCl3) 2934, 1773, 1663, 1627, 1109, 1038; H NMR
(360 MHz, CDCl3) d 6.96 (t, J¼4.4 Hz, 1H), 4.63–4.52
(m, 3H), 4.67–4.62 (m, 1H), 3.55–3.46 (m, 3H), 3.35 (s,
3H), 2.81–2.75 (m, 1H), 2.59–2.53 (m, 1H), 2.41–2.28 (m,
10H), 2.02 (s, 3H), 1.95–1.85 (m, 2H); 13C NMR
(90 MHz, CDCl3) d 199.1, 199.0, 158.2, 146.8, 140.2,
132.7, 94.3, 73.2, 72.4, 67.6, 59.7, 39.3, 38.5, 33.8, 31.6,
26.5, 23.4, 22.9, 22.6. HRMS (EI) calcd for C19H28O5
336.1937, found 336.1936.
4.1.6. 3-[1-Hydroxy-2-(2-methyl-6-oxo-cyclohex-1-enyl)-
ethyl]-3-phenylsulfanyl-dihydro-furan-2-one [16]. Diiso-
propylamine (130 mL, 0.93 mmol) in THF (0.56 mL) was
cooled to ꢂ78 ꢁC and n-BuLi (372 mL, 0.93 mmol) was
added. Then the 3-phenylsulfanyl-dihydro-furan-2-one 15
(193 mg, 0.93 mmol) in THF (1.0 mL) was added and the re-
action warmed to ꢂ50 ꢁC and stirred for 1 h. Then aldehyde
1
IR (CDCl3) 3390, 2926, 2870, 1732, 1660, 1509, 1446; H
NMR (360 MHz, CDCl3) d 7.38 (t, J¼1.8 Hz, 1H), 4.76 (t,
7
17 (170 mg, 1.11 mmol) in THF (0.67 mL) was added and
J¼2.2 Hz, 2H), 4.41–4.38 (m, 1H), 4.33 (br s, 1H, OH),

9696
R. Manchanayakage et al. / Tetrahedron 63 (2007) 9691–9698
2.82 (d, J¼14.6 Hz, 1H), 2.52 (dd, J¼15.0, 9.8 Hz, 1H),
2.41–2.33 (m, 4H), 2.00 (9s, 3H), 1.95–1.85 (m, 2H); 13C
NMR (90 MHz, CDCl3) d 202.4, 172.9, 160.9, 145.3,
137.0, 131.8, 70.5, 67.9, 37.4, 33.0, 32.2, 21.9, 21.5.
HRMS (EI) calcd for C13H16O4 236.1049, found 236.1048.
bicarbonate, and brine. The organic layer was dried over
magnesium sulfate, filtered, and concentrated in vacuo.
The crude product was purified by flash column chromato-
graphy (30% ethyl acetate/hexanes as eluent) to afford
305 mg (89%) of 20 as a light yellow oil.
1
4.1.9. Acetic acid 2-(2-methyl-6-oxo-cyclohex-1-enyl)-1-
(2-oxo-2,5-dihydro-furan-3-yl)-ethyl ester [18]. To a solu-
tion of 17 (240 mg, 0.6 mmol) in methylene chloride (6 mL),
was added m-chloroperbenzoic acid (207 mg, 1.2 mmol).
The reaction was stirred for 2 h at room temperature and
then was diluted with 15 mL methylene chloride and washed
with 20 mL of saturated aqueous sodium bicarbonate. The
aqueous layer was extracted with 10 mL of methylene chlo-
ride. The combined organic layers were washed with brine,
dried over magnesium sulfate, filtered, and concentrated in
vacuo. The crude product was dissolved in 5 mL of toluene
and refluxed 1 h. The solvent was then evaporated and the re-
sulting mixture purified by flash column chromatography
(50% ethyl acetate/hexanes as eluent) to afford 91 mg
(54%) of 18 as a light yellow oil.
IR (CDCl3) 2930, 1718, 1673, 1629, 1440, 1367, 1248; H
NMR (360 MHz, CDCl3) d 7.33 (s, 1H), 4.73 (s, 2H),
4.62–4.57 (m, 2H), 4.51 (t, J¼6.6 Hz, 1H), 3.63–3.44 (m,
4H), 3.29 (s, 3H), 2.85–2.68 (m, 2H), 2.31–2.27 (m, 4H),
1.96 (s, 3H), 1.88–1.82 (m, 2H); 13C NMR (90 MHz,
CDCl3) d 198.4, 172.4, 158.8, 146.8, 134.6, 130.7, 93.9,
71.5, 70.6, 70.1, 67.0, 58.9, 37.5, 32.9, 30.0, 21.9, 21.7.
HRMS (EI) calcd for C17H24O6 324.1573, found 324.1573.
4.2. General procedure for preparative electrolysis
A solution of enone/enoate or bisenone compound (50 mg,
1 equiv) and tetraethylammonium chloride (0.1 N, 1.31 g,
36 equiv) in 70 mL of acetonitrile and 9 mL of water was de-
gassed by bubbling argon through it for 1 h. A constant cur-
rent of 100 mA was applied by using tin foil (2 cm2) as the
sacrificial anode and platinum (2 cm2) as the cathode. The
reaction progress was monitored by thin layer chromato-
graphy. Then the reaction mixture was poured into a separa-
tory funnel along with 20 mL of ether and extracted with
20 mL of 5% aqueous sodium chloride. The organic layer
was dried over magnesium sulfate, filtered, and concentrated
in vacuo. The crude product was purified by flash column
chromatography (20% ethyl acetate/hexanes as eluent) to
afford the cyclization products as light yellow oils.
1
IR (CDCl3) 2937, 2869, 1760, 1661, 1629, 1227, 1031; H
NMR (360 MHz, CDCl3) d 7.36 (s, 1H), 5.63–5.59 (m,
1H), 4.76–4.75 (m, 2H), 2.87–2.85 (m, 2H), 2.36–2.29 (m,
3H), 2.04–1.86 (m, 7H), 1.29–1.19 (m, 2H); 13C NMR
(90 MHz, CDCl3) d 198.2, 172.0, 170.3, 159.4, 147.0,
133.0, 129.3, 70.1, 67.7, 37.4, 33.0, 28.7, 21.9, 21.6, 20.8.
HRMS (EI) calcd for C15H18O5 278.1154, found 278.1155.
4.1.10. 3-[1-(tert-Butyl-dimethyl-silanyloxy)-2-(2-methyl-
6-oxo-cyclohex-1-enyl)-ethyl]-5H-furan-2-one [19]. To
a solution of 1 (30 mg, 0.12 mmol) in 0.5 mL DMF was
added imidazole (25 mg, 0.36 mmol) followed by tert-
butyldimethylsilyl chloride (55 mg, 0.36 mmol). The reac-
tion mixture was stirred overnight at room temperature.
The mixture was then diluted with 15 mL of methylene chlo-
ride and washed with water. The aqueous layer was extracted
with 15 mL of methylene chloride and the combined organic
layers were dried over magnesium sulfate, filtered, and
concentrated in vacuo. The crude oil was purified by flash
column chromatography (30% ethyl acetate/hexanes as
eluent) to afford 34 mg (77%) of 19 as a light yellow oil.
4.2.1. 8a-Methyl-5-oxo-1,4,4a,5,6,7,8,8a-octahydro-
naphthalene-2-carboxylic acid methyl ester [9]. The cy-
clization product 9 was obtained as a yellow oil (32 mg,
69%). IR (CDCl3) 2922, 1705, 1652, 1271, 1253; 1H NMR
(360 MHz, CDCl3) d 7.00–6.97 (m, 1H), 3.73 (s, 3H),
2.37–2.12 (m, 14H) 1.96–1.75 (m, 1H), 1.55 (s, 1H), 1.29–
1.24 (m, 5H), 0.94–0.85 (m, 4H); 13C NMR (90 MHz,
CDCl3) d 211.4, 167.9, 138.0, 136.9, 52.1, 51.8, 41.8,
40.2, 39.9, 37.6, 31.2, 28.1, 22.8. HRMS (EI) calcd for
C13H18O3 222.1256, found 222.1255.
4.2.2. 3-(2-Methoxy-ethoxymethoxy)-8a-methyl-5-oxo-
decahydro-naphthalene-2-carboxylic acid methyl ester
[10]. The cyclization product 10 was obtained as a light yel-
low oil (23.5 mg, 47%). IR (CDCl3) 2929, 2888, 1715, 1663,
1
IR (CDCl3) 2939, 2847, 1755, 1663, 1464, 1379, 1248; H
NMR (360 MHz, CDCl3) d 7.31 (t, J¼1.5 Hz, 1H), 4.73–
4.71 (m, 2H), 4.59 (t, J¼5.9 Hz, 1H), 2.68–2.65 (9m, 2H),
2.34–2.26 (m, 4H), 1.92 (s, 3H), 1.90–1.85 (m, 2H); 13C
NMR (90 MHz, CDCl3) d 198.3, 172.2, 157.7, 145.4,
138.3, 131.1, 70.1, 66.8, 37.5, 33.3, 32.9, 25.6 (3C), 21.9,
21.7, ꢂ5.1 (2C). HRMS (EI) calcd for C19H30O4Si
350.1936, found 350.1936.
1
1456, 1150; H NMR (360 MHz, CDCl3) d 4.79–4.75 (m,
2H), 4.47–4.41 (m, 1H), 3.78–3.66 (m, 4H), 3.58–3.53 (m,
3H), 3.39 (s, 3H), 2.78–2.67 (m, 1H), 2.56–2.36 (m, 2H),
2.22–2.09 (m, 1H), 2.05–1.90 (m, 4H), 1.56 (s, 3H), 1.34–
1.22 (m, 4H); 13C NMR (90 MHz, CDCl3) d 215.8, 164.0,
95.3, 81.2, 73.3, 71.8, 71.6, 67.0, 58.9, 51.6, 48.7, 43.3,
39.0, 29.3, 27.8, 26.9, 18.8. HRMS (EI) calcd for
C17H28O6 326.1885, found 326.1888.
4.1.11. 3-[1-(2-Methoxy-ethoxymethoxy)-2-(2-methyl-6-
oxo-cyclohex-1-enyl)-ethyl]-5H-furan-2-one [20]. A mix-
ture of 1 (250 mg, 1.0 mmol), DMAP (22 mg, 0.2 mmol),
and diisopropylethyl amine (786 mL, 4.5 mmol) in methyl-
ene chloride (1 mL) was cooled to 0 ꢁC and 2-methoxy-
ethoxymethyl chloride (229 mL, 2.0 mmol) was added. The
reaction mixture was warmed to room temperature and
stirred overnight at room temperature. The mixture was di-
luted with 10 mL methylene chloride and washed succes-
sively with water, 10% HCl, saturated aqueous sodium
4.2.3. 3-(tert-Butyl-dimethyl-silanyloxy)-8a-methyl-5-
oxo-decahydro-naphthalene-2-carboxylic acid methyl
ester [11]. The cyclization product 11 was obtained as a light
yellow oil (24.5 mg, 49%). IR (CDCl3) 2927, 2855, 1741,
1
1725, 1443; H NMR (360 MHz, CDCl3) d 4.48–4.46 (m,
1H), 3.65 (s, 3H), 3.03–2.99 (d, J¼16.1 Hz, 1H), 2.64–2.60
(dd, J¼14.6, 3.0 Hz, 1H), 2.33–2.29 (d, J¼15.0 Hz, 1H),

R. Manchanayakage et al. / Tetrahedron 63 (2007) 9691–9698
9697
2.09–1.94 (m, 3H), 1.84–1.75 (m, 1H), 1.61–1.54 (m, 5H),
1.24 (s, 3H), 0.79 (s, 9H), 0.04 (s, 3H), ꢂ0.05 (s, 3H); 13C
NMR (90 MHz, CDCl3) d 207.7, 173.9, 71.2, 66.9, 51.4,
44.6, 39.9, 32.1, 30.8, 30.4, 27.8, 26.9, 25.5 (3C), 20.1,
17.8, ꢂ4.5, ꢂ5.3. HRMS (EI) calcd for C19H34O4Si
354.2226, found 354.2225.
1.59–1.39 (m, 1H), 1.26–1.08 (m, 3H), 0.79–0.76 (m, 1H);
13C NMR (90 MHz, CDCl3) d 212.6, 174.6, 81.5, 72.8,
68.8, 60.5, 57.0, 55.8, 52.7, 49.0, 42.0, 41.1, 37.5, 31.7,
27.0, 22.8, 14.2. HRMS (EI) calcd for C17H26O6 326.1729,
found 326.1732.
References and notes
4.2.4. 4b-Methyl-2,3,4,4a,4b,5,6,7,8a,9-decahydro-phen-
anthrene-1,8-dione [13]. The cyclization product 13 was
obtained as a yellow oil (28.5 mg, 61%). IR (CDCl3) 2929,
1. Lund, H.; Hammerich, O. Organic Electrochemistry, 4th ed.;
Marcel Dekker: New York, NY, 1991, Chapter 21; Fry, A. J.
Synthetic Organic Electrochemistry, 2nd ed.; John Wiley and
Sons: New York, NY, 1989; pp 208–232; Bastida, R. M.;
Brillas, E.; Costa, J. M. J. Electroanal. Chem. 1987, 227, 55–
66; Baizer, M. M.; Anderson, J. D. J. Electrochem. Soc.
1964, 111, 223–226.
1
1715, 1652, 1253; H NMR (360 MHz, CDCl3) d 6.17 (s,
1H), 2.44–2.21 (m, 4H), 1.98–1.83 (m, 1H), 1.58–1.47 (m,
9H), 1.33–1.25 (m, 3H), 0.92–0.84 (m, 2H); 13C NMR
(90 MHz, CDCl3) d 212.6, 191.5, 148.7, 133.2, 55.5, 50.0,
48.9, 48.2, 40.9, 40.1, 38.0, 37.2, 30.5, 22.1, 14.1. HRMS
(EI) calcd for C15H20O2 232.1463, found 232.1465.
2. Little, R. D.; Schwaebe, M. K. Top. Curr. Chem. 1997, 185,
2–48.
4.2.5. 9-(2-Methoxy-ethoxymethoxy)-4a-methyl-dodeca-
hydro-phenanthrene-1,8-dione [14]. The cyclization prod-
uct 14 was obtained as a yellow oil (29 mg, 58%). IR
3. (a) Handy, S. T.; Omune, D. Org. Lett. 2005, 7, 1553–1555; (b)
Handy, S. T.; Omune, D. Tetrahedron 2007, 63, 1366–1371.
4. Polygodial: (a) Urones, J. G.; Marcos, I. S.; Perez, B. G.;
Lithgow, A. M.; Diez, D.; Gomez, P. M.; Basabe, P.; Garrido,
N. M. Tetrahedron 1995, 51, 1845–1860; (b) Barrero, A. F.;
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Tetrahedron Lett. 1994, 35, 2945–2948; (c) Jansen, B. J. M.;
Kreuger, J. A.; DeGroot, A. Tetrahedron 1989, 45, 1447–
1452; (d) Razmilic, I.; Lopez, J.; Sierra, J.; Cortes, M. Synth.
Commun. 1987, 17, 95–103; (e) Mori, K.; Watanabe, H.
Tetrahedron 1986, 42, 273–281; (f) Guillerm, D.; Delarue,
M.; Jalalinaini, M.; Lemaitre, P.; Lallemand, J. Y.
Tetrahedron Lett. 1984, 25, 1043–1046; (g) Holliinshead,
D. M.; Howell, S. C.; Ley, S. V.; Mahon, M.; Ratcliffe,
N. M.; Worthington, P. A. J. Chem. Soc., Perkin Trans. 1
1983, 1579–1586; Equisetin: (h) Burke, L. T.; Dixon, D. J.;
Ley, S. V.; Rodriguez, F. Org. Biomol. Chem. 2005, 274–280;
(i) Yuki, K.; Shindo, M.; Shishido, K. Tetrahedron Lett. 2001,
42, 2517–2519; (j) Turos, E.; Audia, J. E.; Danishefsky, S. J.
J. Am. Chem. Soc. 1989, 111, 8231–8236.
5. For more recent examples, see: (a) Wei, S. W.; Yalalov, D. A.;
Tsogoeva, S. B.; Schmatz, S. Catal. Today 2007, 121, 151–157;
(b) Shi, M.; Liu, Y. H.; Chen, L. H. Chirality 2007, 19, 124–
128; (c) Xu, J. Y.; Guan, Y. Y.; Yang, S. H.; Ng, Y. R.; Peh,
G. R.; Tan, C. H. Chem. Asian J. 2006, 724–729; (d)
Vasbinder, M. M.; Imbriglio, J. E.; Miller, S. J. Tetrahedron
2006, 62, 11450–11459; (e) Berkessel, A.; Roland, K.;
Neudorfl, J. M. Org. Lett. 2006, 8, 4195–4198; (f) Wang, J.;
Li, H.; Yu, X. H.; Zu, L. S.; Wang, W. Org. Lett. 2005, 7,
4293–4296; (g) Matsui, K.; Takizawa, S.; Sasai, H.
Tetrahedron Lett. 2005, 46, 1943–1946; (h) Hayashi, Y.;
Tamura, T.; Shoji, M. Adv. Synth. Catal. 2004, 346, 1106–
1110; (i) McDougal, N. T.; Trevellini, W. L.; Rodgen, S. A.;
Kliman, L. T.; Schaus, S. E. Adv. Synth. Catal. 2004, 346,
1231–1240; (j) Sohtome, Y.; Tanatani, A.; Hashimoto, Y.;
Nagasawa, K. Tetrahedron Lett. 2004, 45, 5589–5592; (k)
Krishna, P. R.; Kannan, V.; Reddy, P. V. N. Adv. Synth. Catal.
2004, 346, 603–606; (l) Mocquet, C. M.; Warriner, S. L.
Synlett 2004, 356–358; (m) McDougal, N. T.; Schaus, S. E.
J. Am. Chem. Soc. 2003, 125, 12094–12095.
1
(CDCl3) 2925, 2880, 1718, 1658, 1437, 1260; H NMR
(360 MHz, CDCl3) d 4.78 (d, J¼22.3 Hz, 2H), 3.73–3.54
(m, 5H), 3.38 (s, 3H), 2.38–2.11 (m, 3H), 2.00–1.72 (m,
4H), 1.63–1.45 (m, 5H), 1.37–1.24 (m, 6H), 0.86 (t,
J¼6.2 Hz, 2H); 13C NMR (90 MHz, CDCl3) d 211.0,
200.7, 93.7, 76.8, 72.4, 67.5, 61.2, 59.6, 56.6, 50.4, 49.4,
40.5, 38.1, 36.0, 30.3, 27.1, 25.9, 23.0, 14.5. HRMS (EI)
calcd for C19H30O5 338.2093, found 338.2093.
4.2.6. 9a-Methyl-1,5,5a,7,8,9,9a,9b-octahydro-naph-
tho[1,2-c]furan-3,6-dione [21]. The cyclization product
21 was obtained as a light yellow oil (28 mg, 59%). IR
(CDCl3) 2929, 1701, 1648, 1253; 1H NMR (360 MHz,
CDCl3) d 6.87 (t, J¼3.6 Hz, 1H), 4.45 (t, J¼10.0 Hz, 1H),
3.96 (t, J¼8.1 Hz, 1H), 3.17–3.09 (m, 1H), 2.51–2.31 (m,
5H), 2.01–1.87 (m, 2H), 1.76–1.71 (m, 1H), 1.24–1.21 (m,
1H), 0.98 (t, J¼13.9 Hz, 1H), 0.69 (s, 2H); 13C NMR
(90 MHz, CDCl3) d 209.4, 169.8, 135.3, 134.4, 67.1, 53.3,
48.3, 41.5, 40.3, 37.9, 23.2, 22.7, 13.3. HRMS (EI) calcd
for C13H16O3 220.1100, found 220.1098.
4.2.7. 4-(tert-Butyl-dimethyl-silanyloxy)-9a-methyl-deca-
hydro-naphtho[1,2-c]furan-3,6-dione [22]. The cycliza-
tion product 22 was obtained as a yellow oil (29 mg,
59%). IR (CDCl3) 2930, 2830, 1740, 1715, 1450, 1420,
1
1220; H NMR (360 MHz, CDCl3) d 4.42 (dd, J¼19.4,
2.6 Hz, 1H), 4.27 (dd, J¼16.5, 8.4 Hz, 1H), 4.13 (dd,
J¼11.4, 8.2 Hz, 1H), 2.89 (t, J¼13.5 Hz, 1H), 2.78–2.66
(m, 1H), 2.18 (d, J¼19.1 Hz, 1H), 1.95–1.67 (m, 1H),
1.69–1.55 (m, 6H), 1.25 (t, J¼7.3 Hz, 1H), 1.13–1.06 (m,
1H), 0.94 (d, J¼7.4 Hz, 2H), 0.88–0.81 (m, 9H), 0.11–
0.06 (m, 6H); 13C NMR (90 MHz, CDCl3) d 211.1, 175.5,
66.9, 64.2, 51.4, 44.7, 44.3, 35.6, 35.5, 32.6, 29.9, 25.6
(3C), 21.2, 19.9, 17.9, ꢂ4.9, ꢂ5.1. HRMS (EI) calcd for
C19H32O4Si 352.2070, found 352.2069.
4.2.8. 4-(2-Methoxy-ethoxymethoxy)-9a-methyl-decahy-
dro-naphtho[1,2-c]furan-3,6-dione [23]. The cyclization
product 23 was obtained as a yellow oil (31 mg, 61%). IR
6. Yu, C.; Liu, B.; Hu, L. J. Org. Chem. 2001, 66, 5413–5418.
7. For example, the use of water/dioxane (1:1) afforded 8% yield
after two days, while methanol afforded 34% yield after two
days.
8. Li, G.; Wei, H. X.; Gao, J. J.; Caputo, T. D. Tetrahedron Lett.
2000, 41, 1–5.
1
(CDCl3) 2928, 2812, 1716, 1663, 1449, 1362; H NMR
(360 MHz, CDCl3) d 4.81–4.64 (m, 4H), 4.23–3.99 (m,
1H), 3.70–3.63 (m, 2H), 3.54–3.48 (m, 2H), 3.35 (s, 3H),
2.30–2.19 (m, 2H), 2.14–2.05 (m, 4H), 1.97–1.74 (m, 3H),

9698
R. Manchanayakage et al. / Tetrahedron 63 (2007) 9691–9698
9. Conditions were adapted from those reported by Kise and
co-workers and are not optimized. Kise, N.; Iitaka, S.;
Iwasaki, K.; Ueda, N. J. Org. Chem. 2002, 67, 8305–8315.
10. Mandell, L.; Daley, R. F.; Day, R. A. J. Org. Chem. 1976, 41,
4087–4089.
11. Indeed, subjection of MEM ether compound 12 to elimination
afforded compound 11, further supporting the stereochemical
assignment of compound 11.
12. Baylis–Hillman reactions of furanones most likely proceed via
aldolization mechanisms and thus afford mixtures of a and g
products, with the g product often being major. For an example,
see: Franck, X.; Figadere, B. Tetrahedron Lett. 2002, 43, 1449–
1451.
13. (a) Carter, N. B.; Nadany, A. E.; Sweeney, J. B. J. Chem. Soc.,
Perkin Trans. 1 2002, 2324–2342; (b) Evans, P.; Leffray, M.
Tetrahedron 2003, 59, 7973–7981.
14. Calderon, A.; March, P. D.; Arrad, M.; Font, J. Tetrahedron
1994, 50, 4201–4214.
15. (a) Cabrera, A.; Lagadec, R. L.; Sharma, P.; Arias, J. L.;
Toscano, R. A.; Velasco, L.; Gavino, R.; Alvarez, C.;
Salmon, M. J. Chem. Soc., Perkin Trans. 1 1998, 3609–
3617; (b) Wu, H.; Ding, J. J. Chem. Res. 2002, 461–462;
(c) Banik, B. M.; Venkatraman, M. S.; Bnik, I.; Basu,
M. K. Tetrahedron Lett. 2004, 45, 4737–4739; (d) Zhou,
L.; Zhang, Y. Synth. Commun. 2000, 30, 597–607; (e)
Cabrera, A.; Rosas, N.; Sharma, P.; Le Lagadec, R.;
Velasco, L.; Salmon, M. Synth. Commun. 1998, 28, 1103–
1108.
16. Zhang, S.; Zhang, X.; Bordwell, F. G. J. Am. Chem. Soc. 1995,
117, 602–606.
17. Ho, P.-T.; Lee, S. F.; Chang, D.; Wiesner, K. Experientia 1971,
27, 1377–1379.