Synthesis of the tricyclic core of solanoeclepin A through intramolecular [2+2] photocycloaddition of an allene butenolide

Article abstract of DOI:10.1002/ejoc.200500609

Studies are reported towards the synthesis of solanoeclepin A (1), the hatching agent of potato cyst nematodes. Two approaches are investigated to access the tricyclic core including the intricate bicyclo[2.1.1]hexanone moiety. The first approach is based on the intramolecular [2+2] photocycloaddition of dioxenone butenolide 10 and is shown to be less practical due to the limited synthetic utility of the photoproduct 11. The second approach uses as the key step the intramolecular [2+2] photocycloaddition reaction of allene butenolide 39. This latter photosubstrate is prepared through silver-mediated coupling of silyloxyfuran 9 and allenic bromide 34. A five-step sequence starting with the Baylis-Hillman reaction between benzyl butadienolate and paraformaldehyde leads to bromide 34. The crucial photocycloaddition of 39 proceeds with excellent regioselectivity and produces the adduct 40 in good yield. This methylenecyclobutane-containing product 40 is deemed to contain the appropriate functionalities for future studies towards the natural product as is indicated through a model study leading to cyclobutanone 25. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200500609

FULL PAPER
DOI: 10.1002/ejoc.200500609
Synthesis of the Tricyclic Core of Solanoeclepin A through Intramolecular
[2+2] Photocycloaddition of an Allene Butenolide
B. T. Buu Hue,[a] Jan Dijkink,[a] Sanne Kuiper,[a] Sjoerd van Schaik,[a]
Jan H. van Maarseveen,[a] and Henk Hiemstra*[a]
Keywords: Allenes / Baylis–Hillman reaction / [2+2] Cycloaddition / Natural products / Photochemistry / Terpenoids
Studies are reported towards the synthesis of solanoeclepin
A (1), the hatching agent of potato cyst nematodes. Two ap-
proaches are investigated to access the tricyclic core includ-
ing the intricate bicyclo[2.1.1]hexanone moiety. The first ap-
proach is based on the intramolecular [2+2] photocycload-
dition of dioxenone butenolide 10 and is shown to be less
practical due to the limited synthetic utility of the photoprod-
uct 11. The second approach uses as the key step the intra-
molecular [2+2] photocycloaddition reaction of allene buten-
olide 39. This latter photosubstrate is prepared through sil-
ver-mediated coupling of silyloxyfuran 9 and allenic bromide
34. A five-step sequence starting with the Baylis–Hillman re-
action between benzyl butadienolate and paraformaldehyde
leads to bromide 34. The crucial photocycloaddition of 39
proceeds with excellent regioselectivity and produces the ad-
duct 40 in good yield. This methylenecyclobutane-containing
product 40 is deemed to contain the appropriate functionali-
ties for future studies towards the natural product as is indi-
cated through a model study leading to cyclobutanone 25.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
cyst nematode. The total synthesis[3–5] and some studies on
the structure-activity relationship of glycinoeclepin A have
been published.[6,7]
Introduction
Solanoeclepin A (1, Figure 1) is the most active natural
hatching agent of potato cyst nematodes (PCN) showing
activity at nanomolar concentration.[1] Its structure was fi-
nally elucidated in 1992 by X-ray analysis after a long
period of intensive studies through the joint efforts of a
number of Dutch research organizations.[2] The similarities
between solanoeclepin A and glycinoeclepin A (2), the
hatching agent of soybean cyst nematodes, are quite inter-
esting although the latter shows no stimulus for the potato
The great interest in the structure of the PCN hatching
agent results from the need to develop an environmentally
benign way to combat the nematodes, which cause serious
losses in potato production. The unavailability of the natu-
ral product in useful quantities from natural sources and
the unique structure render solanoeclepin A a challenging
synthetic target. Moreover, the synthetic work will provide
information on structure-activity relationships, which could
lead to simpler analogs of solanoeclepin A possessing suf-
ficient hatching activity for PCN.[8]
Our synthetic approach to solanoeclepin A is based on
the eventual chromium-mediated[9] coupling of aldehyde 3
with enol triflate 4 and subsequent closure of the seven-
membered ring (Scheme 1). We recently published[10] the
synthesis of aldehyde 3 in enantiopure form and the proof
of principle for the formation of the seven-membered ring
so that the next goal was the preparation of the tetracyclic
substructure 4. For the construction of this cyclobutane-
containing tricyclic core of solanoeclepin A, we planned to
make use of an intramolecular [2+2] photocycloadditon.[11]
This full paper presents our recent progress with regard to
the synthesis of 4, which has resulted in an expedient route
to 5, containing the intricate bicyclo[2.1.1]cyclohexane moi-
ety. The key step is an intramolecular [2+2] photocycload-
dition of a butenolide with either a dioxenone as in 6 or an
allene as in 7.
Figure 1. Natural hatching agents of cyst nematodes.
[a] Van ’t Hoff Institute for Molecular Sciences, University of Am-
sterdam,
Nieuwe Achtergracht 129, 1018 WS, Amsterdam, The Nether-
lands
Fax: +31-20-5255670
E-mail: hiemstra@science.uva.nl
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H. Hiemstra et al.
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Scheme 2. Reaction conditions: (a) hν, 300 nm, MeCN/acetone
(9:1, v/v); (b) LiAlH4 (5 equiv.), room temp., 52% (2 steps); (c)
TBSOTf, 2,6-lutidine, 83%; (d) KHMDS, –78 oC, 1 h; then CS2,
–10 °C, 2 h; then MeI, room temp., 1 h, 60%; (e) xylene, reflux,
1 h, 60%.
Scheme 1. Retrosynthesis of solanoeclepin A (arbitrary protective
groups indicated as R).
of the synthesis should be possible via ozonolysis[15] or an
alternative oxidative cleavage procedure. In other words, the
double bond could then function as an appropriate protec-
tive group for the four-membered ring ketone moiety.
Alcohol 13 was thus treated with potassium hexamethyl-
Results and Discussion
First Approach: [2+2] Photocycloaddition of a Dioxenone
The dioxenone structure has proved to be a versatile and
efficient building block in synthetic photochemistry al- disilazide (KHMDS) at –78 °C for 1 h followed by the suc-
lowing elegant cyclobutane ring formation via [2+2]cyclo- cessive addition of carbon disulfide and methyl iodide. In
addition.[12] In previous studies in our laboratory[13] it has this way, the desired xanthate 14 was successfully isolated
been discovered that acetone sensitized irradiation of diox- in 60% yield. Xanthate 14 turned out to be reasonably
enone 10 produced the bicyclo[2.1.1]cyclohexane skeleton stable and could be purified by column chromatography de-
11 in a very high yield (Scheme 2). In this process the lac- spite the fact that tertiary xanthates have been rarely char-
tone connection appeared essential to obtain the desired acterized due to their usual instability towards elimination
crossed regioselectivity.[13] While the convenient access to to give olefins or rearrangement to give S-alkyl dithiocar-
11 was encouraging, the well-known sensitivity of this bonates.[16] The stability of 14 is obviously associated with
structure to cyclobutane fragmentation limited its synthetic its cyclobutane nature preventing formation of a tertiary
possibilities. The most obvious way to remove the danger carbocation. Interestingly, elimination can only occur in an
of De Mayo fragmentation[12b] was exhaustive reduction. exocyclic fashion as the two adjacent cyclobutane carbons
Thus, LiAlH4 reduction of the cycloadduct 11 gave the tet- are quaternary. Indeed, upon heating at reflux in xylene for
rahydroxytricyclic system 12 in moderate overall yield 1 h, pyrolysis of 14 smoothly took place furnishing alkene
(52%) from 10.[13ab]
15 in 60% yield. The formation of the exocyclic methylene
Several studies were then directed at distinguishing the moiety of 15 is clearly apparent by the presence of two sing-
1
different hydroxy groups by subsequent chemoselective pro- lets at δ = 4.72 and 4.34 ppm in its H NMR spectrum.
tection, but this appeared difficult.[13a] The most selective Unfortunately, our attempts to transform the double bond
reaction found was the simultaneous silylation of the pri- of 15 into a cyclobutanone moiety via ozonolysis at this
mary and secondary hydroxyls which provided the tertiary stage were unsuccessful (vide infra).
alcohol 13 in good yield. An extensive investigation was
We then further investigated the feasibility of chemose-
also devoted to the utility of the dioxenone butenolide cor- lective reactions on the three protected hydroxy groups in
responding to 10 but lacking the C6 methyl group. In that order to deprotect the two rather similar primary alcohols
series of compounds the synthesis of the photochemistry of olefin 15. Treatment of 15 with 10 mol-% of CSA in a
precursor was much more difficult and selectivity in hy- mixture of CH2Cl2 and MeOH at 0 °C led to the formation
droxy group distinction was no better.[13d]
of diol 16 in a yield of 67% (Scheme 3).[17] Upon oxidation
We then decided to turn the presence of the methyl group of the two primary alcohols using the Dess–Martin
to our advantage and considered the elimination of the ter- periodinane reagent,[18] dialdehyde 17 was obtained and
tiary hydroxy group to the corresponding exocyclic alkene used for the next step without purification. Interestingly,
via pyrolysis of the derived xanthate.[14] The conversion of treatment of 17 with TBAF effected liberation of the sec-
this exocyclic methylene into the carbonyl in a later phase ondary hydroxy group which subsequently cyclized onto the
128
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Synthesis of the Tricyclic Core of Solanoeclepin A
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nearby aldehyde moiety to form lactol 18 in reasonable
yield as a single diastereomer. The relative stereochemistry
at the lactol stereocenter is unknown. Lactol 18 was then
treated with an excess (ca. 6 equiv.) of the potassium salt of
triethyl phosphonoacetate to give the desired unsaturated
ester 19a in 83% yield. Protection of the lactol led to cyclic
methyl acetal 19b as a 3:1 mixture of acetal stereoisomers.
At this point the earlier developed chemistry to introduce
the cyclopropane ring could be applied.[13c] In the mean-
time, however, we realized that the synthetic route was be-
coming lengthy and felt the urge to invent a more direct
approach.
Figure 2. Allene butenolide photocycloaddition precedent by
Coates (ref.[20]).
In order to examine the utility of allenes of type 7 having
a two-carbon linkage between allene and butenolide double
bonds, we synthesized allene 23 as a model system starting
from the commercially available cyclic anhydride 20
(Scheme 4).[21] The known butenolide 21[22] was readily con-
verted into silyl dienolate 22 and then treated with 1-
bromo-2,3-butadiene[23] in the presence of silver trifluo-
roacetate at low temperature to provide the desired photo-
substrate 23 in 64% from 21. We were very pleased with
this coupling result as the Jefford coupling procedure[19] was
not known for allyl bromides of the allenic type.
Scheme 3. Reaction conditions: (a) CSA (cat), CH2Cl2/MeOH, (9:1
v/v), 67%; (b) Dess–Martin periodinane, CH2Cl2, room temp.; (c)
TBAF, THF, 60% (2 steps); (d) triethyl phosphonoacetate,
KHMDS, THF, 0 °C, 83%; then CH(OMe)3, CH2Cl2, 87%.
Second Approach: [2+2] Photocycloaddition of Allene
Butenolides
Scheme 4. Reaction conditions: (a) NaBH4, THF, 60%; (b) TIP-
SOTf, iPr2NEt, CH2Cl2; (c) CH2=C=CHCH2Br, AgOCOCF3,
CH2Cl2, –78 °C, 64% (2 steps); (d) hν (300 nm), MeCN/acetone
(9:1 v/v), 5 h, 70%.
As shown in Scheme 1, compound 5 contains the tricy-
clic core of fragment 4 with the exocyclic methylene group
as a possible protective group for the ketone moiety. In the
above approach the double bond was introduced through a
four step sequence from dioxenone 6. We envisioned that
the structural motif of olefin 5 might be assembled in a
single step by using an intramolecular [2+2] photocycload-
dition of butenolide 7. This photochemistry precursor
would preserve the advantage of the lactone function, while
the allene moiety was anticipated to remedy the problems
associated with the dioxenone functionality. The substituted
allene butenolide 7 should be conveniently accessible based
on the coupling procedure developed by Jefford[19] between
the substituted allenic bromide 8 and silyloxyfuran 9.
Photocycloaddition of an Allene Butenolide Model Sys-
tem. When we began our study of allenes of type 7, there
was one literature example of an intramolecular [2+2] pho-
tocycloaddition of an α,β-unsaturated γ-lactone with an al-
lene at the γ-position. Coates et al. reported in 1982 the
photochemistry of the homologous system and observed
only rather low regioselectivity (Figure 2),[20] namely only
16% of the crossed adduct from reaction of the internal
double bond of the allene, while 40% of straight product
was obtained (33% reaction of the internal and 7% reaction
of the terminal allene double bond).
The key [2+2] photocycloaddition of allene 23 was car-
ried out in a 9:1 v/v acetonitrile acetone solution in a quartz
vessel (Rayonet RPR-3000 Å lamps) and was found to pro-
ceed remarkably well leading to the single product 24 as a
crystalline solid (m.p. 125–127 °C) in 70% yield. The struc-
ture of 24 was proven by X-ray analysis.[21] The exclusive
formation of 24 emphasizes the great preference for five-
membered ring formation in intramolecular [2+2]-photocy-
cloaddition (the so-called rule of five).[24] The selectivity dif-
ference with the allene studied by Coates (Figure 2)[20] may
be explained by the fact that five-membered ring formation
in the case of 23 leads to an allylic radical intermediate,
whereas five-membered ring formation from Coates’s sub-
strate gives a much less stable vinyl radical, so that other
cyclization modes can compete (see Figure 3).
Figure 3. Diradical intermediates in the intramolecular photocy-
cloaddition.
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H. Hiemstra et al.
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Further chemistry of 24 was then investigated in order to (Scheme 7).[31] The Baylis–Hillman reaction was initially
reach the model cyclobutanone 25. To that end, the lactone carried out by using an aqueous solution of formaldehyde,
function of 24 was reduced to diol 26 in good yield using generated in situ from paraformaldehyde and aqueous
LiAlH4 (Scheme 5). We planned to generate the angular phosphoric acid,[32] but this procedure was not successful.
methyl group by reductive removal of a sulfonate. Thus, a The use of an excess of dry paraformaldehyde and 20 mol-
protection–deprotection sequence then produced the pri- % of DABCO in THF turned out to be much better. The
mary alcohol 27 in good yield.[25] Tosylation of 27 followed temperature and the reaction time were found to seriously
by reduction with sodium triethylborohydride[26] gave 28 in influence the yield of the Baylis–Hillman reaction of allene
good yield. Cleavage of the alkene in 28 through ozonolysis 31. The reaction was best started at –10 °C and continued
appeared not possible. Osmium-mediated dihydroxylation at about 18 °C for 1.5 h. These optimized conditions re-
was only productive with stoichiometric amounts of os- sulted in a clean mixture of product 32 (60%) and the start-
mium tetroxide in a pyridine/water mixture at 65 °C.[27] In ing allene 31 (28%), which could easily be separated by col-
this way a single diol 29 was obtained. From 1H NMR umn chromatography.
NOE measurements it was clear that the dihydroxylation
The hydroxy group of allene 32 was then protected either
had taken place from the more open endo face of the alkene. as a triisopropylsilyl ether or as a benzyl ether.[33] Re-
Removal of the benzyl protective group by hydrogenolysis duction of the ester moiety using DIBAL-H[34] followed by
followed by oxidative cleavage of the diol with sodium peri- mesylation and substitution of the resulting alcohol gave
odate furnished the desired cyclobutanone 25 in acceptable the corresponding allenic bromide 34a,b in moderate yield
overall yield as a crystalline solid (m.p. 103–106 °C, IR ν = over three steps. The modest yield of this sequence is proba-
˜
1798 and 1766 cm–1). The structure was confirmed by X- bly due to the low efficiency of the reduction step which
ray analysis.[21] Interestingly, this rather strained β-hydroxy appeared to be greatly dependent upon the temperature, the
ketone appeared to be quite stable, although its stability in reaction time and the amount of DIBAL-H used
aqueous medium at different pH values was not studied.[28] (Scheme 6).
Scheme 6. Reaction conditions: (a) MeCOCl, Et3N, CH2Cl2, 82%;
(b) DABCO (cat), (CH2O)n, THF, 60% (28% of 31); (c) TIPSOTf,
Et3N, 79%; (d) PhCH2OC(NH)CCl3, TMSOTf (cat), 67%; (e)
DIBAL-H, CH2Cl2, –78 °C; (f) MsCl, Et3N; (g) LiBr, acetone.
Scheme 5. Reaction conditions: (a) LiAlH4, THF, 74%; (b) TBSCl,
imidazole, DMF; (c) BnBr, NaH, THF, Bu4NI (cat), 90% (2 steps)
(d) CSA (cat), MeOH/CH2Cl2 (9:1, v/v), 84%; (e) TsCl, pyridine;
(f) LiBHEt3, THF, 66% (two steps); (g) OsO4 (1.5 equiv.), pyridine
water, 65 °C, 60% (73% conv.); (h) H2 (1 atm), 10% Pd/C, ethanol,
65%; (i) NaIO4, acetone/water, 67%.
Preparation of Silyloxyfuran 9. With the required allenic
bromide 34 in our hands, we turned to the preparation of
its eventual coupling partner, silyloxyfuran 9. Starting from
the commercially available monoethylene acetal of 1,4-
Compound 25 contains the key structural features of the
core of solanoeclepin A. However, the ultimate natural
product requires one hydrogen atom of the cyclobutanone
ring in 25 to be replaced by a cyclopropanecarboxylic acid
function. In addition, the vinyl triflate moiety, the function-
ality for connecting fragments 3 and 4 of solanoeclepin A
(Scheme 1) needs to be installed on the six-membered ring.
The synthesis of the key intermediate 5 therefore requires
the preparation of the functionalized coupling components,
i.e. allenic bromide 8 and silyloxyfuran 9.
Allenic Bromide 8. The key step of the synthesis of this
allene is the well-known Baylis–Hillman reaction[29] of ethyl
butanedienoate (31), although formaldehyde had not yet
been reported as an electrophile in this type of DABCO-
catalyzed reaction.[30] Treatment of commercially available
triphenylphosphorane 30 with acetyl chloride in the pres-
Scheme 7. Reaction conditions: (a) (MeO)2CO, NaH, KH, 90%;
(b) iPr2NEt, Tf2O; (c) DIBAL, –78 °C to room temp.; (d) Pd-
(PPh3)4, CO, LiCl, Et3N, MeCN, reflux, 85% (3 steps); (e)
ence of Et3N furnished α-allenic ester 31 in good yield TIPSOTf, iPr2NEt, 0 °C to room temp., 20 h.
130 Eur. J. Org. Chem. 2006, 127–137
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Synthesis of the Tricyclic Core of Solanoeclepin A
FULL PAPER
cyclohexanedione (35), butenolide 38 was synthesized leading to three quaternary centres in a highly compact set-
through a four-step sequence as depicted in Scheme 7. ting is noteworthy.
Methoxycarbonylation of 35 was achieved in 90% yield
This account of our progress towards the synthesis of
with dimethyl carbonate by using sodium hydride in con- solanoeclepin A ends here. The photocycloadducts 40a and
junction with potassium hydride.[35] The enol 36 was sub- 40b are believed to contain appropriate functionalities for
sequently converted into its triflate upon treatment with further elaboration towards the right-hand substructure 4
Hünig’s base and triflic anhydride followed by reduction of of the natural product (Scheme 1). Application of the chem-
the ester moiety with DIBAL-H to give the allylic alcohol istry developed previously for the model 24 to the photocy-
37. Palladium-catalyzed carbonylation of the vinyl triflate cloadduct 40a or 40b should provide the angular methyl
furnished butenolide 38 in 85% overall yield as a crystalline and the cyclobutanone functions. The protected primary
solid (m.p. 100–104 °C). Exposure of 38 to TIPS-OTf and alcohol should serve as a handle for incorporating a cyclo-
Hünig’s base[36] in CH2Cl2 yielded the desired silyloxyfuran propanecarboxylic acid moiety at a later phase of the syn-
9 as an oil which was used for the next step without further thesis. The critical installation of the vinyl triflate from the
purification.
ketone could eventually accomplish the right hand sub-
Substituted Allene Butenolides and Photocyclization. The structure 4, a projected key intermediate in the eventual
coupling reaction between silyloxyfuran 9 and bromides synthesis of solanoeclepin A.
34a,b was then carried out. Treatment of a mixture of 34a
and 9 in CH2Cl2 at –78 °C with silver trifluoroacetate led
to the desired allene butenolide 39a in 22% yield Conclusions
(Scheme 8). This low yield is could be due to the instability
of the silyl ether group under the Lewis acidic conditions.
This explanation was confirmed when we found that a satis-
factory 60% yield of 39b was obtained from the coupling
The compact tricyclic core of solanoeclepin A (1), con-
taining the strained bicyclo[2.1.1]hexanone moiety, was pre-
pared by using as the key step an intramolecular [2+2] pho-
tocycloaddition reaction of an allene butenolide. This syn-
thetic strategy has efficiently produced the expedient inter-
mediate 40 in eight steps (longest linear sequence) from
ylide 30. Further studies are underway along the lines de-
scribed above and the results thereof will be reported in due
course.
reaction of 9 with benzyl-protected bromide 34b.
Experimental Section
General Information: All reactions involving oxygen or moisture
sensitive compounds were carried out under dry nitrogen. THF
and Et2O were distilled from sodium/benzophenone and CH2Cl2
was distilled from CaH2. DMF and toluene were distilled from
CaH2 and stored over 4 Å molecular sieves. Triethylamine was
stored over KOH pellets. DMSO was dried and stored over 4 Å
molecular sieves. Flash column chromatography was performed
using Acros silica gel (0.030–0.075 mm). Petroleum ether (PE, 60/
Scheme 8. Reaction conditions: (a) AgOCOCF3, CH2Cl2, –78 °C
to room temp.; (b) for 39a: MeCN/acetone (9:1 v/v); (c) for 39b:
benzene/acetone (9:1 v/v).
80) used for chromatography was distilled prior to use. TLC analy-
ses were performed on Merck F-254 silica gel plates. The Rf values
given pertain to the solvent system used for the chromatographic
purification. IR spectra were measured using a Bruker IFS 28 FT-
spectrophotometer and wavelengths (ν) are reported in cm–1. 1H
The key photocycloaddition of 39 was then investigated.
Acetone-sensitized irradiation of butenolide 39a at 300 nm
for 1 h in acetonitrile/acetone, 9:1, as the solvent resulted in
the desired crossed cycloadduct 40a in good yield. In con-
trast, irradiation of 39b under the same conditions led to
40b in only low yield along with extensive decomposition
of the starting material. Further investigation of the photo-
cycloaddition reaction of 39b revealed that it proceeded
best in a 9:1 mixture of benzene and acetone as the solvent.
Under such optimized conditions the photocycloadduct 40b
˜
NMR spectra were recorded on a Bruker AC 200 (200 MHz), a
Bruker ARX 400 (400 MHz) and Varian Inova (500 MHz). The
latter machines were also used for 13C NMR spectra (50, 100 and
125 MHz, respectively). Unless otherwise indicated, CDCl3 was
used as the solvent. Chemical shifts are given in ppm (δ) relative to
an internal standard of chloroform (δ =7.26 ppm for 1H NMR and
77.0 for 13C NMR). Mass spectra and accurate mass determi-
nations were performed on a JEOL JMS SX/SX102A, coupled to
a JEOL MS-MP7000 data system. Elemental analyses were per-
formed by Dornis u. Kolbe, Mikroanalytisches Laboratorium,
Mülheim an der Ruhr, Germany.
was isolated in 60% yield as a stable colourless oil (IR ν =
˜
1770 cm–1). The 1H NMR spectrum of the cycloadduct 40b
shows two singlets at δ = 4.78 and 4.76 ppm which clearly
corresponds to the exocyclic methylene moiety as observed
3-(tert-Butyldimethylsilanoxy)-1,7a-bis(tert-butyldimethylsilanoxy-
methyl)-8-methyloctahydro-1,3a-methanoinden-8-ol (13): To a solu-
tion of tetrahydroxy compound 12[13b] (40 mg, 0.17 mmol) in
previously with the model 24. The ease of the cycloaddition CH2Cl2 (1 mL) was added dropwise at 0 °C, TBDMSOTf (195 μL,
Eur. J. Org. Chem. 2006, 127–137
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131

H. Hiemstra et al.
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0.85 mmol) and 2,6-lutidine (200 μL, 1.7 mmol). The resulting mix-
ture was stirred at 0 °C for 1 h. The reaction was quenched by
addition of saturated aqueous NaHCO3 (1 mL). The combined or-
ganic layers were washed with brine, dried with MgSO4 and con-
centrated in vacuo. Purification by chromatography (EtOAc/PE =
1:40) afforded 13 (80 mg, 83%) as a colourless oil. Rf = 0.19. IR
aqueous phase was extracted with diethyl ether (3×10 mL). The
combined organic layers were washed with brine (40 mL), dried
with MgSO4 and concentrated in vacuo. Purification by
chromatography (PE/EtOAc = 2:1) afforded the diol 16 (67%) as
a colourless oil (R = 0.26). IR (CHCl ): ν = 3300, 2932, 1118,
˜
f
3
1042 cm–1. H NMR: δ = 4.39 (s, 1 H), 4.37 (d, J = 11 Hz, 1 H)
1
(CHCl ): ν = 2958, 2929, 2856, 1467, 1254, 1214, 1059 cm–1. 1H 4.36 (s, 1 H), 3.94 (dd, J = 2.5, J = 7 Hz, 1 H), 3.69 (d, J = 11 Hz,
˜
3
NMR: δ = 4.50 (dd, J = 10.6, 2.4 Hz, 1 H), 4.04 (d, J = 10.7 Hz,
1 H), 3.83 (dd, J = 7.5, 2.5 Hz, 1 H), 3.80 (d, J = 10.7 Hz, 1 H),
3.25 (d, J = 10.6 Hz, 1 H), 2.88 (s, 1 H), 2.86–2.77 (m, 1 H), 2.00
(dd, J = 12.3, 7.5 Hz, 1 H), 2.00–1.87 (m, 2 H), 1.64–1.59 (m, 2
H), 1.48–1.43 (m, 2 H), 1.48–1.43 (m, 2 H), 1.37–1.18 (m, 2 H),
1.13 (s, 3 H), 0.88 (s, 27 H), 0.04 (s, 3 H), 0.04 (s, 3 H), 0.03 (s, 3
H), 0.02 (s, 3 H), 0.00 (s, 3 H), –0.01 (s, 3 H). 13C NMR: δ = 85.0,
73.1, 63.6, 62.7, 57.7, 55.8, 50.6, 37.8, 27.3, 26.0, 25.9, 25.8, 22.0,
21.7, 21.1, 20.8, 18.24, 18.1, 18.0, –4.7, –5.1, –5.3, –5.5, –5.6, –
5.7. HRMS (FAB) calcd. for C31H65O4Si3 [MH+] 585.4191, found
585.4079.
1 H), 3.57 (d, J = 11 Hz, 1 H), 3.49 (d, J = 11 Hz, 1 H), 2.14 (d, J
= 11 Hz, 1 H), 2.12–1.94 (m, 2 H), 1.61–1.41 (m, 6 H), 1.25–1.20
(m, 1 H) 0.88 (s, 9 H), 0.04 (s, 3 H), 0.02 (s, 3 H). 13C NMR: δ =
155.7, 93.2, 72.9, 61.8, 60.8, 58.6, 58.2, 47.0, 39.2, 25.5, 24.8, 21.5,
21.1, 20.5, 17.8, –4.98, –5.27. HRMS (FAB) calcd. for C19H35O3Si
[MH+] 339.2355, found 339.2344.
Lactol 18: To a stirred solution of Dess–Martin periodinane (Ald-
rich) (0.4 g, 3 equiv.) in CH2Cl2 (2 mL) at room temp. was added
solution of diol 16 (100 mg, 0.295 mmol) in CH2Cl2 (2 mL). The
reaction mixture was stirred at room temp. for 1 h and diethyl ether
(5 mL) was added. The suspended mixture was poured into 1.3 m
aqueous NaOH (7 mL) and the aqueous layer was extracted with
diethyl ether (3 × 10 mL). The combined organic layers were
washed with brine (40 mL), dried with MgSO4 and concentrated
in vacuo to afford crude dialdehyde 17 that was used for the next
Xanthate 14: To a solution of alcohol 13 (900 mg, 1.54 mmol) in
freshly distilled THF (15 mL) at –78 °C was added dropwise
KHMDS in THF (0.5 m in toluene, 6 mL, 2 equiv.). The resulting
mixture was stirred at –78 °C for 1 h and then carbon disulfide was
added (0.5 mL, 5 equiv.). The reaction mixture was then warmed
up to –10 °C and stirred for an additional 2 h. Methyl iodide
(0.5 mL, 5 equiv.) was added and the reaction mixture was warmed
to room temp. and stirred for 1.5 h. The reaction was quenched by
saturated aqueous NH4Cl (15 mL). The layers were separated and
the aqueous phase was extracted with diethyl ether (3×15 mL).
The combined organic layers were washed with brine (50 mL),
dried with MgSO4 and concentrated in vacuo. Purification by
chromatography (3 % Et3N in PE) afforded the xanthate 14
1
step without purification. H NMR: 9.9 (s, 1 H), 9.8 (s, 1 H), 4.9
(s, 1 H), 4.6 (s, 1 H), 4 (d, J = 4 Hz, 1 H), 2.3–1.2 (m, 8 H), 0.9 (s,
9 H), 0.1 (s, 6 H).
To a solution of crude dialdehyde 17 in THF (3 mL) at 0 °C was
added TBAF (1 m in THF) (0.5 mL, 2 equiv.). The resulting mix-
ture was warmed to room temp. and stirred for 1 h. The reaction
was quenched by addition of saturated aqueous NaHCO3 (5 mL).
The layers were separated and the aqueous phase was extracted
with diethyl ether (3×5 mL). The combined organic layers were
washed with brine (20 mL), dried with MgSO4 and concentrated in
vacuo. Purification by chromatography (PE/EtOAc = 1:1) afforded
lactol 18 (38 mg, 60% over two steps) as a colourless oil and as a
(623 mg, 60%) as a colourless oil. R = 0.4. IR (CHCl ): ν = 2928,
˜
f
3
2855, 1471, 1234, 1064 cm–1. 1H NMR: δ = 4.48 (dd, J = 2, J =
11 Hz, 1 H), 3.95 (d, J = 11 Hz, 1 H), 3.89 (dd, J = 3, J = 7 Hz, 1
H), 3.82 (d, J = 11 Hz, 1 H), 3.28 (d, J = 11 Hz, 1 H), 2.54 (s, 3
H), 2.4 (dd, J = 7, J = 13 Hz, 1 H), 2.17–2.11 (m, 1 H), 1.97–1.75
(m, 1 H), 1.76–1.72 (m, 4 H), 1.69–1.20 (m, 6 H), 0.89–0.87 (m, 27
H), 0.18–0.00 (m, 18 H). 13C NMR: δ = 212.3, 99.1, 71.6, 62.4,
61.4, 59.5, 58.5, 50.2, 36.8, 25.73, 25.71, 25.5, 25.2, 21.57, 21.50,
20.2, 19.5, 17.98, 17.91, 17.8, 17.7, –4.9, –5.1, –5.3, –5.4, –5.6, –
5.7. HRMS (FAB) calcd. for C33H67O4S2Si3 [MH+] 675.3789,
found 675.3787.
single diastereoisomer (R = 0.3). IR (CHCl ): ν = 3401, 2931,
˜
f
3
2861, 1710, 800 cm–1. 1H NMR: δ = 9.85 (s, 1 H), 5.53 (d, J =
4 Hz, 1 H), 4.97 (s, 1 H), 4.64 (s, 1 H), 4.31 (d, J = 4 Hz, 1 H),
3.49 (d, J = 4 Hz, 1 H), 2.51 (d, J = 11 Hz, 1 H), 2.08 (dd, J = 4,
J = 11 Hz, 1 H), 2.06–1.05 (m, 8 H). 13C NMR: δ = 200.5, 149.8,
99.4, 96.5, 81.4, 65.3, 64.2, 60.1, 37.8, 21.1, 20.8, 20.6, 19.2.
Lactol Ester 19a: To a solution of triethyl phosphonoacetate
(43.4 μL, 1.2 equiv.) in THF (3 mL) was added KHMDS (0.5 m in
toluene) (1.3 mL, 1.2 equiv.) at 0 °C. The reaction mixture was
stirred at 0 °C for 1 h and the solution of lactol 18 (40 mg,
0.18 mmol) in THF (3 mL) was added dropwise. The resulting mix-
ture was stirred for 30 min and warmed to room temp. Saturated
aqueous NH4Cl (10 mL) was added and the mixture was stirred
for 15 min. The layers were separated and the aqueous phase was
extracted with diethyl ether (3×10 mL). The combined organic lay-
ers were washed with brine (30 mL), dried with MgSO4 and con-
centrated in vacuo. Purification by chromatography (PE/EtOAc =
Methylenecyclobutane 15: A solution of the xanthate 14 (224 mg,
0.33 mmol) in xylene (5 mL) was added dropwise to boiling xylene
(5 mL) and the resulting mixture was refluxed for 1.5 h and concen-
trated in vacuo. Purification by chromatography (5% Et3N in PE)
afforded alkene 15 (60%) as a colourless oil. Rf = 0.43. IR (CHCl3):
ν = 2930, 2857, 1471, 1255, 1066 cm–1. 1H NMR: δ = 4.72 (s, 1 H),
˜
4.35 (d, J = 12 Hz, 1 H), 4.34 (s, 1 H), 3.85 (dd, J = 2, J = 7 Hz,
1 H), 3.79–3.73 (m, 2 H), 3.38 (d, J = 11 Hz, 1 H), 2.28 (dd, J =
7, J = 11 Hz, 1 H), 1.93 (d, J = 13 Hz, 1 H), 1.63 (d, J = 2, J =
11 Hz, 1 H), 1.50–1.10 (m, 7 H), 0.89 (s, 9 H), 0.88 (s, 9 H), 0.87
(s, 9 H), 0.04 (s, 6 H), 0.01 (s, 6 H), 0.00 (s, 6 H). 13C NMR: δ =
157.4, 93.3, 73.2, 61.2, 61.0, 60.6, 59.5, 47.1, 38.4, 25.7, 25.6, 25.5,
25.3, 21.8, 21.2, 20.4, 18.0, 17.9, 17.7, –4.9, –5.2, –5.5, –5.7, –5.81,
–5.88. HRMS (FAB) calcd. for C31H63O3Si3 [MH+] 567.4085,
found 567.4097.
1.5:1) afforded ester 56 (43.3 mg, 83%) (R = 0.32). IR (CHCl ): ν
˜
f
3
1
= 3394, 2938, 1706, 1650 cm–1. H NMR: δ = 7.04 (d, J = 16 Hz,
1 H), 6.02 (d, J = 16 Hz, 1 H), 5.52 (s, 1 H), 4.68 (s, 1 H), 4.51 (s,
1 H), 4.27 (d, J = 4.5 Hz, 1 H), 4.18 (q, J = 7 Hz, 2 H), 3.50–3.30
(br., 1 H), 2.34 (d, J = 11 Hz, 1 H), 1.96 (dd, J = 5, J = 11 Hz, 1
H), 1.87–1.77 (m, 2 H), 1.62–1.25 (m, 5 H), 1.28 (t, J = 7 Hz, 3
H), 1.25–1.06 (m, 1 H). 13C NMR: δ = 166.4, 153.3, 143.0, 122.8,
100.0, 94.3, 81.9, 64.1, 60.1, 58.7, 58.5, 39.8, 20.8, 20.6, 20.5, 19.2,
14.0.
Diol 16: To a solution of olefin 15 (260 mg, 0.459 mmol) in CH2Cl2/
MeOH (8 mL, 9:1, v/v) at 0 °C was added CSA (13.5 mg,
0.11 equiv.). The reaction mixture was warmed to room temp. and
stirred for 4 h. The reaction was quenched by addition of saturated
aqueous NaHCO3 (10 mL). The layers were separated and the
Protected Lactol 19b: To a solution of the lactol 19a (175 mg,
0.6 mmol) in CH2Cl2 (10 mL) was added at room temp. trimethyl
132
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 127–137

Synthesis of the Tricyclic Core of Solanoeclepin A
FULL PAPER
orthoformate (0.8 mL, 12 equiv.) and PPTS (45 mg, 0.3 equiv.).
The reaction mixture was stirred at room temp. overnight. The re-
action was quenched by saturated aqueous NaHCO3 (10 mL). The
layers were separated and the aqueous phase was extracted with
diethyl ether (3 × 10 mL). The combined organic layers were
washed with brine (40 mL), dried with MgSO4 and concentrated
in vacuo. Purification by chromatography (PE/EtOAc = 4:1) af-
forded the product 62 (157 mg, 87 %, 3:1 mixture of two di-
kept under argon and irradiated for the time indicated. The reac-
tion was followed by monitoring the UV absorption of the starting
material on TLC. When complete conversion was observed, the
solvent was removed in vacuo.
Photocycloaddition Product 24: According to the general procedure
A, solution of allene 23 (85 mg, 0.45 mmol) in acetonitrile/acetone
(0.05 m, 9:1 v/v) was irradiated (300 nm) for 5 h to give 24 (60 mg,
0.32 mmol, 70%) as colourless crystals after column chromatog-
asteroisomers) as a colourless oil (R = 0.43). IR (CHCl ): ν = 2923,
˜
f
3
raphy (PE/EtOAc = 4:1), Rf = 0.40, m.p. 125–127 °C. IR (CHCl3):
1710, 1650 cm–1. H NMR (major): δ = 6.99 (d, J = 16 Hz, 1 H),
5.97 (d, J = 16 Hz, 1 H), 5.00 (s, 1 H), 4.68 (s, 1 H), 4.51 (s, 1 H),
4.25 (d, J = 4.6 Hz, 1 H), 4.19 (q, J = 7 Hz, 2 H), 3.41 (s, 3 H),
2.24 (d, J = 11 Hz, 1 H), 1.92–1.84 (m, 2 H), 1.75 (d, J = 11 Hz, 2
H), 1.61–1.32 (m, 4 H), 1.29 (t, J = 7 Hz, 3 H), 1.11–0.89 (m, 1
H).
1
1
ν = 2941, 1763, 1215 cm–1. H NMR: δ = 4.76 (s, 1 H), 4.61 (d, J
˜
= 3.9 Hz, 1 H), 4.56 (s, 1 H), 2.94 (s, 1 H), 2.17 (br. d, J = 13.8 Hz,
1 H), 2.10 (dd, J = 12.0, 4.1 Hz, 1 H), 1.87 (br. d, J = 15 Hz, 1 H),
1.73 (dd, J = 12.0, 2.3 Hz, 1 H), 1.62–1.45 (m, 4 H), 1.35 (m, 1 H),
0.96 (m, 1 H). 13C NMR: δ = 175.6, 150.8, 96.0, 79.6, 66.0, 53.9,
48.4, 36.6, 21.7, 21.1, 20.1, 19.3. Elemental analysis: calcd. for
C12H14O2, C 75.76, H 7.42; found C 75.65, H 7.40. The crystal
4,5,6,7-Tetrahydro-3H-isobenzofuran-1-one (21): To a stirred sus-
pension of NaBH4 (950 mg, 25.1 mmol) in THF (70 mL) at 0 °C structure of this compound was published elsewhere.[21]
was added dropwise over 2 h a solution of 3,4,5,6-tetra-
7a-Hydroxymethyl-8-methyleneoctahydro-1,3a-methanoinden-3-ol
hydrophthalic anhydride 20 (3.8 g, 25.0 mmol) in THF (100 mL).
(26): To a 1 m solution of LiAlH4 in THF (6.5 mL, 5 equiv.) at
The reaction mixture was stirred at 0 °C for 1 h and at room temp.
room temp. was added a solution of lactone 24 (250 mg,
for another 1 h. The reaction mixture was cooled to 0 °C and acidi-
1.315 mmol) in THF (5 mL). The resulting mixture was stirred at
fied with 2 m HCl (until pH 3). The layers were separated and the
room temp. for 30 min and carefully quenched with EtOAc. Satu-
aqueous phase was extracted with CH2Cl2 (2×100 mL). The com-
rated aqueous Na2SO4 (10 drops) was then added and the mixture
bined organic layers were washed with saturated aqueous NaHCO3
was stirred for 1 h. After addition of more solid Na2SO4 the mix-
(300 mL) and brine (300 mL), dried with MgSO4 and concentrated
ture was filtered through Celite® and concentrated in vacuo. Purifi-
in vacuo. Purification by chromatography (PE/EtOAc = 2:1) af-
cation by chromatography (EtOAc) afforded diol 26 as a colourless
forded 21 (2.13 g, 15.4 mmol, 60%) as a colourless solid, m.p. 56–
solid (189 mg, 74%). R = 0.30, m.p. 110–114 °C. IR (neat): ν =
˜
f
57 °C (ref.[22] m.p. 53–54 °C). IR (CHCl ): ν = 1735, 1678 cm–1. 1H
˜
3
3397, 2934, 1690 cm–1. 1H NMR (methanol): δ = 4.53 (s, 1 H), 4.35
(s, 1 H), 4.23 (dd, J = 11.9, 1.8 Hz, 1 H), 3.88 (dd, J = 7.6, 2.6 Hz,
1 H), 3.46 (d, J = 11.9 Hz, 1 H), 2.65 (s, 1 H), 2.10 (ddd, J = 11.8,
7.8, 1.7 Hz, 1 H), 2.03 (br. d, J = 13.4 Hz, 1 H), 1.89–1.85 (m, 1
H), 1.67–1.50 (m, 6 H), 1.30–1.26 (m, 1 H). 13C NMR (methanol):
δ = 158.0, 94.5, 73.3, 63.5, 60.3, 51.3, 47.1, 36.6, 28.8, 23.0, 22.8,
21.6.
NMR: δ = 4.67 (br. s, 2 H), 2.30 (m, 2 H), 2.22 (m, 2 H), 1.75 (m,
4 H). 13C NMR: δ = 174.1, 160.9, 126.0, 71.8, 23.3, 21.3, 21.2, 19.7.
Triisopropyl-(4,5,6,7-tetrahydroisobenzofuran-1-yloxy)silane (22):
To a stirred solution of lactone 21 (100 mg, 0.72 mmol) in CH2Cl2
(2 mL) at 0 °C was added dropwise triisopropylsilyl triflate (250 μL,
285 mg, 0.93 mmol) and diisopropylethylamine (251 μL, 186 mg,
1.44 mmol). The reaction mixture was warmed to room temp. and
stirred overnight. The reaction was quenched with ice-cold satu-
rated aqueous NH4Cl (2 mL). The layers were separated and the
aqueous phase was extracted with diethyl ether (3×10 mL). The
combined organic layers were washed with brine (30 mL), dried
with MgSO4, and concentrated in vacuo to afford 22 as a colour-
less oil, which was used for the next step without further purifica-
tion. 1H NMR: δ = 6.55 (s, 1 H), 2.46 (m, 2 H), 2.34 (m, 2 H),
1.63 (m, 4 H), 1.21 (m, 3 H), 1.07 (m, 18 H).
7a-(tert-Butyldimethylsilanyloxymethyl)-8-methyleneoctahydro-
1,3a-methanoinden-3-ol: To a stirred solution of diol 26 (158 mg,
0.81 mmol) in DMF (5 mL) at room temp. was added tert-butyldi-
methylsilyl chloride (182 mg, 1.5 equiv.) and imidazole (386 mg,
7 equiv.). The reaction mixture was stirred for 5 h and diluted with
EtOAc (10 mL). The organic phase was washed with 2% aqueous
solution of citric acid (10 mL), water (10 mL), and brine (10 mL),
dried with MgSO4 and concentrated in vacuo to provide 273 mg
(0.88 mmol) crude silyl-protected alcohol as a colourless oil. The
3-(Buta-2,3-dienyl)-4,5,6,7-tetrahydro-3H-isobenzofuran-1-one (23): crude silyl ether was used for the next step without further purifica-
1
To a solution of the crude silyloxyfuran 22 and 1-bromobuta-2,3-
diene[23] (144 mg, 1.08 mmol, 1.5 equiv.) in CH2Cl2 (25 mL) at
–78 °C was added silver trifluoroacetate (240 mg, 1.09 mmol). The
reaction mixture was stirred at –78 °C for 20 min and then at
–20 °C for 3 h and at room temp. overnight. The mixture was fil-
tered through Celite® and the filtrate was concentrated in vacuo.
Purification by chromatography (PE/EtOAc = 4:1) afforded 23
tion. IR (neat): ν = 3400, 2930, 1684 (w), 1254, 1080 cm–1. H
˜
NMR: δ = 4.51 (s, 1 H), 4.34 (s, 1 H), 3.94–3.80 (m, 2 H), 3.74 (d,
J = 10.9 Hz, 1 H), 3.12 (d, J = 6.8 Hz, 1 H), 2.61 (s, 1 H), 2.14
(ddd, J = 12.0, 7.6, 1.6 Hz, 1 H), 1.86–1.72 (m, 3 H), 1.67–1.48 (m,
5 H), 1.35–1.27 (m, 1 H), 0.90 (s, 9 H), 0.07 (s, 3 H), 0.06 (s, 3 H).
13C NMR: δ = 156.2, 93.7, 72.6, 63.8, 62.4, 50.4, 45.1, 36.5, 30.8,
25.7, 21.9, 21.5, 20.7, 18.0, –5.6, –5.8.
(85 mg, 0.45 mmol, 62% from 21) as a slightly yellow oil (Rf =
(3-Benzyloxy-8-methylenehexahydro1,3a-methanoinden-7a-ylmeth-
oxy)-tert-butyldimethylsilane: To a solution of the above crude
alcohol (273 mg, 0.88 mmol) in THF (5 mL) at room temp. was
added benzyl bromide (0.2 mL, 288 mg, 1.68 mmol), and sodium
hydride (60 wt.% dispersion in mineral oil, 80 mg, 2 equiv.). The
resulting mixture was stirred at room temp. for 30 min. Tetra-n-
butylammonium iodide (cat) was added and stirring was continued
overnight. The reaction was quenched with ice water. The layers
were separated and the aqueous phase extracted with diethyl ether
(3×10 mL). The combined organic layers were washed with brine
(30 mL), dried with MgSO4 and concentrated in vacuo to afford
1
0.17). IR (neat): ν = 2941, 2947, 1957, 1747, 1681 cm–1. H NMR:
˜
δ = 5.00 (m, 1 H), 4.88 (m, 1 H), 4.70 (m, 2 H), 2.58 (m, 1 H), 2.31
(m, 1 H), 2.22 (m, 4 H), 1.74 (m, 4 H). 13C NMR: δ = 209.3, 173.2,
162.7, 127.2, 83.2, 81.6, 75.2, 31.1, 23.1, 21.4 (2 C), 19.7. HRMS
(FAB) calcd. for C12H15O2 [MH+] 191.1072, found 191.1076.
General Procedure A for the Intramolecular [2+2] Photocycload-
ditions: The photoreaction was carried out in an air-cooled quartz
vessel in a Rayonet photoreactorvessel with Rayonet RPR 300 nm
lamps. A solution of the substrate in the indicated solvent was de-
gassed by bubbling argon through for 30 min. The solution was
Eur. J. Org. Chem. 2006, 127–137
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
133

H. Hiemstra et al.
FULL PAPER
the fully protected compound as a colourless oil after chromato-
1 H), 4.47 (d, J = 12.3 Hz, 1 H), 4.33 (s, 1 H), 3.69 (dd, J = 7.3,
2.8 Hz, 1 H), 2.51 (s, 1 H), 2.02 (ddd, J = 11.4, 7.3, 1.6 Hz, 1 H),
1.91–1.81 (m, 2 H), 1.66–1.42 (m, 6 H), 1.28–1.20 (m, 1 H), 1.16
(s, 3 H). 13C NMR: δ = 157.0, 139.1, 128.0 (2 C), 127.0, 126.9 (2
graphic purification (290 mg, 0.73 mmol, 90% from 26). IR (neat):
1
ν = 2929, 1684 cm–1 (w), 1077 cm–1. H NMR: δ = 7.35–7.24 (m,
˜
5 H), 4.56 (d, J = 12.2 Hz, 1 H), 4.52 (s, 1 H), 4.46 (d, J = 12.2 Hz,
1 H), 4.34 (s, 1 H), 4.23 (dd, J = 10.8, 1.7 Hz, 1 H), 3.69 (dd, J = C), 93.7, 79.8, 71.0, 61.0, 51.8, 41.2, 34.1, 33.8, 22.2, 21.8, 20.6,
7.3, 2.7 Hz, 1 H), 3.47 (d, J = 10.8 Hz, 1 H), 2.68 (s, 1 H), 2.09–
2.00 (m, 2 H), 1.87 (dd, J = 11.5, 1.9 Hz, 1 H), 1.64–1.46 (m, 6 H),
1.25–1.20 (m, 1 H), 0.88 (s, 9 H), 0.02 (s, 6 H). 13C NMR
(200 MHz): δ = 156.2, 139.0, 128.2 (2 C), 127.23, 127.18 (2 C),
94.0, 79.8, 72.1, 61.4, 59.7, 49.9, 46.2, 33.7, 26.9, 26.0, 21.9, 21.7,
21.1, 18.3, –5.31, –5.33.
16.4. HRMS (FAB) calcd. for C19H25O [MH+] 269.1905, found
269.1908.
3-Benzyloxy-8-hydroxymethyl-7a-methyloctahydro-1,3a-methanoin-
den-8-ol (29): To a stirred solution of 28 (113 mg, 0.42 mmol) in
pyridine/water (1:1, v/v, 5 mL) at room temp. was added OsO4
(161 mg, 0.63 mmol, 1.5 equiv.). The reaction mixture was heated
to 65 °C, stirred for 6 h at this temperature and then cooled to
room temp. Saturated aqueous NaHSO3 (10 mL) and solid Na2SO3
(50 mg) were added and the resulting mixture was stirred for
30 min. The layers were separated and the aqueous phase was ex-
tracted with EtOAc (3×10 mL). The combined organic layers were
washed with saturated aqueous NaHSO3 (30 mL), water (30 mL),
brine (30 mL), dried with MgSO4, and concentrated in vacuo to
afford the crude product. Chromatographic purification (hexanes/
EtOAc = 1:1) gave residual starting material (26.0 mg, 0.097 mmol)
and diol 29 (55.6 mg, 0.18 mmol, 60% yield, based on 73% conver-
(3-Benzyloxy-8-methylenehexahydro-1,3a-methanoinden-7a-yl)meth-
anol (27): To a stirred solution of the above silyl ether (312 mg,
0.78 mmol) in CH2Cl2/MeOH (9:1 v/v, 5 mL) at room temp. was
added camphorsulphonic acid (60 mg, 0.3 equiv.). The reaction
mixture was stirred at room temp. for 3 h and quenched with satu-
rated aqueous NaHCO3 (5 mL). The layers were separated and the
aqueous phase extracted with EtOAc (3×5 mL). The combined or-
ganic layers were washed with brine (20 mL), dried with MgSO4,
and concentrated in vacuo to give alcohol 27 as a slightly yellow oil
(185 mg, 0.65 mmol, 84%) after chromatography (hexane/EtOAc =
3:1). R = 0.26. IR (neat): ν = 3370, 2930, 1687, 1452 cm–1. 1H
f
sion) as a colourless oil. R = 0.37. IR (neat): ν = 3400, 2926, 1453,
˜
˜
f
1274, 1073 cm–1. 1H NMR: δ = 7.36–7.23 (m, 5 H), 4.62 (d, J =
12.3 Hz, 1 H), 4.50 (d, J = 12.3 Hz, 1 H), 4.38 (br. d, J = 11 Hz, 1
H), 4.25 (br. d, J = 11 Hz, 1 H), 4.15 (dd, J = 7.1, 2.2 Hz, 1 H),
3.15 (s, 1 H), 2.29 (s, 1 H), 2.24–2.11 (m, 1 H), 2.08–2.07 (m, 1 H),
1.92–1.91 (m, 2 H), 1.67–1.60 (m, 4 H), 1.46–1.32 (m, 3 H), 1.20
(s, 3 H). 13C NMR: δ = 139.3, 128.0 (2 C), 126.9 (3 C), 81.0, 80.8,
71.5, 67.8, 58.3, 48.3, 38.7, 33.0, 32.4, 22.0, 21.7, 21.2, 20.4.
NMR: δ = 7.34–7.26 (m, 5 H), 4.63 (d, J = 11.9 Hz, 1 H), 4.55 (s,
1 H), 4.48 (d, J = 11.9 Hz, 1 H), 4.37 (s, 1 H), 3.93 (d, J = 11.9 Hz,
1 H), 3.81–3.76 (m, 2 H), 2.66 (s, 1 H), 2.11 (br. s, 1 H), 2.05 (ddd,
J = 11.9, 7.1, 1.6 Hz, 1 H), 1.97 (br. d, J = 11 Hz, 1 H), 1.90–1.48
(m, 8 H). 13C NMR: δ = 155.3, 138.1, 128.2 (2 C), 127.4, 127.2 (2
C), 94.2, 79.5, 71.2, 63.7, 61.8, 49.8, 45.6, 33.6, 30.8, 21.8, 21.5,
21.2.
8-Hydroxymethyl-7a-methyloctahydro-1,3a-methanoindene-3,8-diol:
A mixture of benzyl ether 29 (48 mg, 0.159 mmol) and pre-equili-
brated 10% Pd/C (40 mg) in ethanol (2 mL) was treated with hy-
drogen at room temp. and atmospheric pressure for 30 min. The
mixture was filtered and the filtrate was evaporated to yield the
desired triol (22 mg, 0.104 mmol, 65%) as a colourless oil after
(3-Benzyloxy-8-methylenehexahydro-1,3a-methanoinden-7a-yl)-
methyl p-Toluenesulfonate: To a stirred solution of alcohol 27
(227 mg, 0.80 mmol) in pyridine (4 mL) at room temp. was added
p-toluenesulfonyl chloride (306 mg, 1.60 mmol). The reaction mix-
ture was stirred overnight and quenched with ice-cold 3% aqueous
citric acid (10 mL). The layers were separated and the aqueous
phase extracted with EtOAc (3×10 mL). The combined organic
layers were washed with water (30 mL), brine (30 mL), dried with
MgSO4, and concentrated in vacuo to afford the crude tosylate as
a colourless oil (341 mg, 0.78 mmol), that was used for the next
chromatographic purification (EtOAc). R = 0.30. IR (neat): ν =
˜
f
3400, 2932, 1058 cm–1. 1H NMR (CD3OD): δ = 4.36–4.32 (m, 1
H), 4.33 (d, J = 11.5 Hz, 1 H), 4.1 (d, J = 11.5 Hz, 1 H), 2.3–2.27
(m, 2 H), 2.24 (s, 1 H), 1.7 (dd, J = 1, J = 11 Hz, 1 H), 1.66–1.4
(m, 7 H), 1.16 (s, 3 H). 13C NMR: δ = 81.0, 73.9, 67.8, 58.0, 48.4,
38.6, 34.6, 33.2, 22.0, 21.35, 21.31, 19.9.
step without further purification. IR (CHCl ): ν = 2939, 1696,
˜
3
1598, 1452, 1356, 1175 cm–1. H NMR: δ = 7.73 (d, J = 8.3 Hz, 2
1
H), 7.37–7.21 (m, 7 H), 4.77 (dd, J = 10.5, 1.9 Hz, 1 H), 4.58 (s, 1
H), 4.42 (d, J = 12.0 Hz, 1 H), 4.38 (s, 1 H), 4.32 (d, J = 12.0 Hz,
1 H), 3.92 (d, J = 10.5 Hz, 1 H), 3.64 (dd, J = 7.3, 2.5 Hz, 1 H),
2.71 (s, 1 H), 2.41 (s, 3 H), 1.98–1.90 (m, 2 H), 1.67–1.41 (m, 7 H),
1.06–1.00 (m, 1 H). 13C NMR: δ = 154.4, 144.2, 138.3, 132.8, 129.5
(2 C), 128.1 (2 C), 127.8 (2 C), 127.2, 126.9 (2 C), 95.3, 78.8, 70.7,
68.7, 62.2, 49.7, 44.0, 33.0, 26.8, 21.4, 21.3, 21.0, 20.6. HRMS
(FAB) calcd. for C26H31O4S [MH+] 439.1943, found 439.1945.
3-Hydroxy-7a-methyloctahydro-1,3a-methanoinden-8-one (25): To a
stirred solution of the above triol (22 mg, 0.104 mmol) in acetone/
water (1:1, v/v, 2 mL) at 0 °C was added NaIO4 (45 mg, 2 equiv.).
The resulting mixture was warmed up to room temp. and stirred
for 30 min. Most of the acetone was evaporated in vacuo. The resi-
due was dissolved in EtOAc (5 mL) and the organic phase washed
with brine (5 mL) and concentrated in vacuo to provide cyclobut-
anone 25 as a colourless solid after chromatography purification
(hexanes/EtOAc = 4:1). Rf = 0.10. Recrystallization (diisopropyl
3-Benzyloxy-7a-methyl-8-methyleneoctahydro-1,3a-methanoindene
(28): Lithium triethyl borohydride (1 m in THF, 3 mL, 4 equiv.) was
added to a solution of the above tosylate in THF (10 mL) at 0 °C.
The reaction mixture was brought to reflux for 1 h and then cooled
to 0 °C. The reaction was quenched with ice/water and the layers
were separated. The aqueous layer was extracted with diethyl ether
(3×10 mL). The combined organic layers were washed with 3 n
aqueous NaOH (10 mL) and 30% aqueous H2O2 (10 mL), water
(30 mL), brine (30 mL), dried with MgSO4, and concentrated in
vacuo to provide 28 (142 mg, 0.53 mmol, 66% from 27) as a colour-
less oil after chromatography (hexane/EtOAc = 20:1). Rf = 0.50.
ether) gave colourless crystals (12 mg, 0.067 mmol, 64%), m.p. 103–
1
106 °C. IR (neat): ν = 3430, 2938, 1798, 1766 cm–1. H NMR: δ =
˜
4.08 (dd, J = 7.8, 2.8 Hz, 1 H), 2.63 (s, 1 H), 2.28 (ddd, J = 12.7,
7.8, 1.5 Hz, 1 H), 2.00 (ddd, J = 12.7, 3.0, 1.6 Hz, 1 H), 1.87 (br.
s, 1 H), 1.8–1.2 (m, 8 H), 1.31 (s, 3 H). 13C NMR: δ = 202.8,
70.0, 67.9, 61.0, 36.1, 35.3, 32.4, 22.2, 21.3, 18.8, 14.2. The crystal
structure of this compound was published elsewhere.[21]
Benzyl Buta-2,3-dienoate (31):[31] Benzyl (triphenylphosphoranyl-
idene)acetate (50.42 g, 123 mmol) was dissolved in CH2Cl2
(400 mL) in a three-necked, round-bottomed flask under nitrogen.
The solution was stirred at room temp. as solution of Et3N
IR (neat): ν = 2931, 2857, 2860, 1686, 1455, 1355, 867 cm–1. 1H
˜
NMR: δ = 7.36–7.24 (m, 5 H), 4.58 (d, J = 12.3 Hz, 1 H), 4.49 (s, (12.42 g, 1 equiv.) in CH2Cl2 (100 mL) was added dropwise
134
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Eur. J. Org. Chem. 2006, 127–137

Synthesis of the Tricyclic Core of Solanoeclepin A
FULL PAPER
(10 min). After 10 min, CH3COCl (9.66 g, 1 equiv.) in CH2Cl2
(100 mL) was added dropwise over a period of 20 min. Stirring was
continued for an additional 30 min, after which the clear, yellow
mixture was evaporated on a rotary evaporator at reduced pressure.
A portion of PE (800 mL) was added to the residue and the slurry
was allowed to stand for 2 h while it was shaken periodically to
facilitate solidification. The precipitate was removed by filtration
and the filter was washed with PE (2×50 mL). The filtrates were
combined and the solvent was evaporated. Purification by
chromatography (PE/EtOAc = 4:1) afforded the desired product
was added a solution of 2-[(triisopropylsilyloxy)methyl]buta-2,3-
dien-1-ol (3.345 g, 13.06 mmol) in CH2Cl2 (8 mL) followed by Et3N
(2.73 mL, 1.5 equiv.). The reaction mixture was warmed to room
temp. and stirred for 30 min. CH2Cl2 (10 mL) was added and the
organic phase was washed with water (30 mL), brine (30 mL), dried
with MgSO4 and concentrated in vacuo to afford the crude mesyl-
ate which was used for the next step without purification. 1H
NMR: δ = 4.95 (t, J = 2 Hz, 2 H), 4.83 (t, J = 1.8 Hz, 2 H), 4.33
(t, J = 2 Hz, 2 H), 3.02 (s, 3 H), 1.14–1.03 (m, 21 H).
To a stirred solution of LiBr (4.46 g, 4 equiv.) in acetone (20 mL)
at 0 °C was added a solution of the above crude mesylate in acetone
(20 mL). The reaction mixture was stirred at room temp. for 30 min
then water was added. The aqueous layer was extracted with
CH2Cl2 (3×20 mL) and the combined organic layers were washed
with brine (60 mL), dried with MgSO4 and concentrated in vacuo
to give allenyl methyl bromide 34a (2.91 g, 70% two steps) as a
(17.46 g, 82%) as a colourless oil. R = 0.43. IR (CHCl ): ν = 1969,
˜
f
3
1716, 1259, 1155, 855 cm–1. 1H NMR: δ = 7.37–7.31 (m, 5 H), 5.68
(t, J = 6.5 Hz, 1 H), 5.23 (d, J = 6.5 Hz, 2 H), 5.19 (s, 2 H). 13C
NMR: δ = 215.8, 165.2, 135.7, 128.3, 128.0, 127.9, 87.6, 79.2, 66.3.
Benzyl 2-(Hydroxymethyl)buta-2,3-dienoate (32): To a suspension
of paraformaldehyde (95%, 535 mg, 5 equiv.) (pre-dried under vac-
uum at 50 °C for 30 min) in THF (10 mL) at –10 °C was added
dropwise a solution of DABCO (pre-dried under vacuum for
30 min, 76 mg, 0.2 equiv.) in THF (5 mL) followed by a solution of
allenic ester 31 (590 mg, 3.39 mmol) in THF (5 mL). The reaction
mixture was warmed to 18 °C and stirred for 1.5 h. The reaction
was quenched by saturated aqueous NH4Cl (10 mL). The layers
were separated and the aqueous phase was extracted with ethyl
acetate (3×10 mL). The combined organic layers were washed with
brine (30 mL), dried with MgSO4 and concentrated in vacuo. Puri-
fication by chromatography (PE/EtOAc = 1.5:1) afforded the de-
sired product 32 (416 mg, 60%) as slightly brown oil along with
colourless oil after purification (PE/EtOAc = 2:1). Rf = 0.6. IR
1
(neat): ν = 2943, 2866, 1955 cm–1. H NMR (benzene): δ = 4.51–
˜
4.49 (m, 2 H), 4.35 (t, J = 2.4 Hz, 2 H), 3.97–3.96 (m, 2 H), 1.10–
1.01 (m, 21 H). 13C NMR (benzene): δ = 207.3, 102.8, 77.7, 62.6,
31.8, 18.8, 12.9.
Butenolide 38: To a stirred solution of β-keto ester 36[35] (8.56 g,
40 mmol) in CH2Cl2 (100 mL) at –78 °C was added dropwise DI-
PEA (35 mL, 5 equiv.) and triflic anhydride (8.1 mL, 1.2 equiv.).
The reaction mixture was warmed to room temp. for 4 h, and then
stirred for 18 h. The reaction mixture was washed with ice water
(100 mL), 10% aqueous solution of citric acid (2×100 mL), dried
with MgSO4 and concentrated in vacuo. The residue was dissolved
in EtOAc and filtered through silica and solvent was evaporated to
afford the crude vinyl triflate (14.45 g) as a yellow oil which was
used for the next step without purification. 1H NMR: δ = 4.05–
3.96 (m, 4 H), 3.80 (s, 3 H), 2.67–2.62 (m, 4 H), 1.90 (t, J = 6.4 Hz,
2 H).
the starting allene 31 (28%). R = 0.25. IR (CHCl ): ν = 3407,
˜
f
3
1966, 1708, 1262, 1027, 854 cm–1. 1H NMR: δ = 7.35–7.25 (m, 5
H), 5.26 (s, 2 H), 5.22 (s, 2 H), 4.34 (s, 2 H), 2.50 (s, br. s, 1 H).
13C NMR: δ = 213.0, 166.4, 135.5, 128.3, 128.0, 127.7, 99.5, 79.8,
66.5, 60.7.
Benzyl 2-(Triisopropylsilanyloxymethyl)buta-2,3-dienoate (33a): To
a solution of allenyl methyl alcohol 32 (350 mg, 1.71 mmol) in
CH2Cl2 (20 mL) at 0 °C was added TIPSOTf (0.7 mL, 1.5 equiv.)
followed by Et3N (260 mg, 1.5 equiv.). The reaction mixture was
stirred 0 °C for 1 h. The reaction was quenched by saturated aque-
ous NaHCO3 (20 mL). The layers were separated and the aqueous
phase was extracted with diethyl ether (3×20 mL). The combined
organic layers were washed with brine (60 mL), dried with MgSO4
and concentrated in vacuo. Purification by chromatography (PE/
EtOAc = 15:1) afforded the desired product (484 mg, 79%) as a
To a stirred solution of the crude triflate (3.46 g) in THF (75 mL)
at –78 °C was added DIBAL-H (1.5 m in toluene, 15.3 mL,
2.3 equiv.) over 40 min. The resulting mixture was stirred at –78 °C
for 2 h and warmed to room temp. Saturated aqueous Na2SO4 was
then added at 0 °C. After stirring for 1 h at room temp., solid
Na2SO4 was added. The mixture was stirred for 2 days at room
temp. and filtered through Celite® and concentrated in vacuo to
afford the crude alcohol 37 (3.06 g, 96%) which was used for the
next step without further purification. 1H NMR: δ = 4.19 (s, 2 H),
4.02–3.97 (m, 4 H), 2.60–2.50 (m, 4 H), 1.90 (t, J = 6.4 Hz, 2 H).
colourless oil (R = 0.3). IR (neat): ν = 2943, 2865, 1969, 1712,
˜
f
1258, 1064 cm–1. 1H NMR: δ = 7.35–7.29 (m, 5 H), 5.26 (t, J =
3 Hz, 2 H), 5.20 (s, 2 H), 4.47 (t, J = 3 Hz, 2 H), 1.25–1.01 (m, 21
H). 13C NMR: δ = 213.5, 165.6, 135.8, 128.2, 127.8, 127.6, 101.4,
80.6, 66.2, 59.7, 17.7, 11.7.
CO was bubbled through a solution of the crude 37 (3.06 g),
Pd(PPh3)4 (25.55 mg, 5 mol-%) and LiCl (20 mg, 5 mol-%) in
MeCN (30 mL) for 20 min. To this solution was added Et3N
(2.7 mL) and the resulting mixture was refluxed for 7 h under an
atmosphere of CO (1 bar, balloon). After cooling to room temp.,
the reaction mixture was filtered through Celite® and concentrated
in vacuo. The residue was purified by flash chromatography (PE/
EtOAc = 1:1) affording the desired butenolide 38 (1.59 g, 86%)
from 36 as white crystals (Rf = 0.17). M.p. 100–104 °C. IR (CHCl3):
2-[(Triisopropylsilyloxy)methyl]buta-2,3-dien-1-ol: To a stirred solu-
tion of allenic ester 33a (214 mg, 0.59 mmol) in dried toluene
(8 mL) at –78 °C was added DIBAL-H (1.5 m in toluene) (1.2 mL,
3 equiv.). The reaction mixture was stirred at –78 °C for 1 h and
carefully quenched with EtOAc at 0 °C. Saturated aqueous solution
of Na2SO4 (0.5 mL) was added and the resulting mixture was
stirred for 1 h. After adding solid Na2SO4, the mixture was filtered
through Celite® and the filtrate was concentrated in vacuo. Purifi-
cation by chromatography (PE/EtOAc = 5:1) afforded the title
compound (91.5 mg, 61 %) as a colourless oil (Rf = 0.26). IR
ν = 2935, 1755, 1682 cm–1. 1H NMR: δ = 4.67 (t, J = 2.6 Hz, 2 H),
˜
4.02 (s, 4 H), 2.56 (s, 2 H), 2.48–2.42 (m, 2 H), 1.87 (t, J = 6.4 Hz,
2 H). 13C NMR: δ = 173.0, 158.5, 126.0, 107.6 (2 C), 71.1, 64.7,
34.5, 30.7, 18.9. HRMS (EI) calcd. for C10H12O4 196.0736, found
196.0733.
(CHCl ): ν = 3396, 2943, 2866, 1961 cm–1. 1H NMR: δ = 4.86–4.84
˜
3
(m, 2 H), 4.40–4.39 (m, 2 H), 4.27–4.24 (m, 2 H), 2.32 (t, J = 6 Hz,
1 H), 1.31–1.01 (m, 21 H). 13C NMR (benzene): δ = 206.1, 104.53,
77.37, 64.2, 62.78, 18.0, 12.8.
Silyloxyfuran 9: To a stirred solution of lactone 38 (70 mg,
0.35 mmol) in CH2Cl2 (5 mL) at 0 °C was added dropwise triiso-
propylsilyl triflate (0.15 mL, 1.3 equiv.) and diisopropylethylamine
(0.1 mL, 2 equiv.). The reaction mixture was warmed to room
[2-(Bromomethyl)buta-2,3-dienyloxy]triisopropylsilane (34a): To a
solution of MsCl (1.54 mL, 1.5 equiv.) in CH2Cl2 (30 mL) at 0 °C temp. and stirred overnight. The reaction was quenched with ice-
Eur. J. Org. Chem. 2006, 127–137
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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135

H. Hiemstra et al.
FULL PAPER
cold saturated aqueous NH4Cl (5 mL). The layers were separated
and the aqueous phase was extracted with diethyl ether (3×10 mL).
The combined organic layers were washed with brine (30 mL),
dried with MgSO4, and concentrated in vacuo to afford 9 as a
colourless oil, which was used for the next step without further
purification. H NMR: δ = 6.58 (s, 1 H), 4.02–3.99 (m, 4 H), 2.69
(s, 2 H), 2.54 (t, J = 6.6 Hz, 2 H), 1.83 (t, J = 6.6 Hz, 2 H), 1.31–
1.17 (m, 3 H), 1.08 (s, 6 H), 1.06 (s, 6 H), 1.04 (s, 6 H).
step without further purification. IR (neat): ν = 3357, 1957, 1072,
˜
1
1018 cm–1. H NMR: δ = 7.50–7.25 (m, 5 H), 4.95–4.80 (m, 2 H),
4.54 (s, 2 H), 4.25 (br., 2 H), 4.20–4.10 (m, 2 H).
[2-(Bromomethyl)buta-2,3-dienyloxymethyl]benzene (34b): To a
solution of MsCl (0.5 mL, 1.5 equiv.) in CH2Cl2 (30 mL) at 0 °C
was added a solution of the above mixture of 2-(benzyloxymethyl)
buta-2,3-dien-1-ol and benzyl alcohol (803 mg) in CH2Cl2 (15 mL)
followed by Et3N (0.9 mL, 1.5 equiv.). The reaction mixture was
stirred at 0 °C for 30 min CH2Cl2 (10 mL) was added and the or-
ganic phase was washed with water, brine (30 mL), dried with
MgSO4 and concentrated in vacuo to afford the crude mesylate
(1.24 g) which was used for the next step without purification. To
a stirred solution of LiBr (432 mg, 4 equiv.) in acetone (10 mL) at
0 °C was added a solution of the crude mesylate (1.24 g) in acetone
(10 mL). The reaction mixture was stirred at room temp. for 30 min
then water was added. The aqueous layer was extracted with
CH2Cl2 and the combined organic layers were washed with brine
(20 mL), dried with MgSO4 and concentrated in vacuo to give al-
lenyl methyl bromide 34b (516 mg, 37% from 33b) as a colourless
oil after purification (PE and then PE/EtOAc = 7:1). Rf = 0.43. IR
1
General Procedure B for the Jefford Coupling Reaction: A mixture
of silver trifluoroacetate (1.2 equiv.), molecular sieves (4 Å) and the
allenic bromide 34 (1.2 equiv.) in CH2Cl2 (0.3 m) was stirred for
10 min at –78 °C before adding a solution of furanolate 9 (1 equiv.)
in CH2Cl2 (0.3 m). The resulting mixture was stirred at –78 °C for
20 min and at –20 °C for additional 2 h and then at room temp.
overnight. The reaction mixture was filtered through Celite® and
solvent evaporated in vacuo. The coupling product was purified by
column chromatography.
TIPS-Substituted Allenyl Butenolide 39a: According to procedure
B, allene bromide 34a (1.3 g, 1.5 equiv.) gave butenolide 39a
(260 mg, 22%). IR (neat): ν = 2944, 2867, 1960, 1758 cm–1. 1H
˜
(CHCl ): ν = 2857, 1951, 1207, 1071 cm–1. 1H NMR: δ = 7.35–7.27
˜
3
NMR: δ = 5.01–4.98 (m, 2 H), 4.83–4.75 (m, 2 H), 4.23 (qt, J =
12, J = 2.5 Hz, 2 H), 4.00 (br. s, 4 H), 2.60–2.34 (m, 6 H), 1.86–
1.77 (m, 2 H), 1.13–0.87 (m, 21 H). 13C NMR (in benzene): δ =
172.2, 160.9, 127.6, 108.7, 99.6, 80.8, 77.6 (not seen in CDCl3),
65.4, 65.19, 65.18, 53.9, 53.2, 32.4, 31.4, 20.0, 18.8, 12.9.
(m, 5 H), 4.90 (t, J = 2 Hz, 2 H), 4.53 (s, 2 H), 4.18 (t, J = 2 Hz,
2 H), 4.10 (t, J = 2 Hz, 2 H). 13C NMR: δ = 207.5, 137.6, 128.2,
127.6, 127.5, 98.6, 76.9, 72.0, 67.6, 31.3. HRMS (FAB) calcd. for
C12H14BrO [MH+] 253.0228, found 253.0228.
Benzyl-Substituted Allenyl Butenolide 39b: According to procedure
B, allenyl methyl bromide 34b gave the coupling product 39b after
Photocycloadduct 40a: According to procedure A, butenolide 39a
(260 mg, 0.599 mmol) in acetonitrile/acetone (9:1, v/v, 30 mL) was
irradiated for 15 min which gave 40a (155 mg, 60%) as a colourless
purification by chromatography (PE/EtOAc = 1:1) (Rf = 0.28). IR
1
(neat): ν = 2888, 1957, 1752, 1063 cm–1. H NMR: δ = 7.35–7.26
˜
oil after purification (PE/EtOAc = 4:1). R = 0.23. IR (CHCl ): ν
˜
f
3
(m, 5 H), 4.96 (br. s, 1 H), 4.86–4.80 (m, 2 H), 4.49 (s, 2 H), 4.08–
4.00 (m, 2 H), 3.99–3.95 (br. s, 4 H), 2.58–2.50 (m, 2 H), 2.46–2.36
(m, 3 H), 2.35–2.29 (m, 1 H), 1.84–1.78 (m, 2 H). 13C NMR: δ =
207.1, 172.0, 160.9, 137.7, 128.2, 127.6, 127.5, 126.2, 107.5, 95.2,
80.3, 70.2, 71.6, 70.9, 64.5, 34.2, 31.9, 30.4, 18.7. HRMS (FAB)
calcd. for C22H25O5 [MH+] 369.1702, found 396.1698.
= 2944, 2865, 1779, 1111 cm–1. H NMR: 4.77 (s, 2 H), 4.63 (d, J
= 4 Hz, 1 H), 3.96–3.85 (m, 6 H), 2.16–2.10 (m, 2 H), 2.03 (dd, J
= 14, J = 1.6 Hz, 1 H), 1.91–1.8 (m, 3 H), 1.65–1.61 (m, 1 H), 1.42
(td, J = 4, J = 14 Hz, 1 H), 1.10–0.99 (m, 21 H). 13C NMR: 174.5,
151.6, 108.4, 96.6, 79.8, 65.1, 64.4, 63.8, 59.1, 59.0, 54.5, 38.7, 30.8,
29.1, 17.7, 17.3, 11.6.
1
Photocycloaddition Product 40b: According to procedure A, solu-
tion of allene 39b in benzene/acetone (9:1, v/v) was irradiated
(300 nm) for 1 h to give 39b. Purification by chromatography (PE/
EtOAc = 2:1) afforded the cyclized adduct (Rf = 0.28). IR (CHCl3):
Benzyl 2-(Benzyloxymethyl)buta-2,3-dienoate (33b): To a solution
of allenyl methyl alcohol 32 (364 mg, 1.78 mmol) in CH2Cl2
(15 mL) at 0 °C was added benzyl trichloroacetimidate (0.34 mL,
1 equiv.) followed by TMSOTf (64 μL, 0.2 equiv.). The reaction
mixture was warmed to room temp. and stirred overnight. Solvent
was then evaporated under reduced pressure. PE/Et2O (6:1)
(20 mL) was added to the residue and the slurry was filtered
through a plug of silica gel to remove the formed trichloroacetam-
ide. The silica gel was washed with PE/Et2O (6:1) (3×10 mL). The
combined organic layers were washed with saturated aqueous
NaHCO3 (30 mL), brine (30 mL), dried with MgSO4 and concen-
trated in vacuo. Purification by chromatography (PE/EtOAc = 5:1)
ν = 2949, 2880, 1770, 1111 cm–1. 1H NMR: δ = 7.35–7.27 (m, 5
˜
H), 4.78 (s, 1 H), 4.76 (s, 1 H), 4.65 (d, J = 4 Hz, 1 H), 4.48 (s, 2
H), 3.96–3.83 (m, 4 H), 3.67 (d, J = 10.5 Hz, 1 H), 3.62 (d, J =
10.5 Hz, 1 H), 2.17–2.02 (m, 3 H), 1.91–1.80 (m, 3 H), 1.65–1.60
(m, 1 H), 1.4 (td, J = 4, J = 14 Hz, 1 H). 13C NMR: δ = 174.6,
151.3, 137.7, 128.2, 127.4, 127.2, 108.3, 96.8, 79.9, 73.0, 65.4, 65.2,
64.4, 63.8, 57.3, 54.9, 39.0, 30.8, 29.1, 17.4. HRMS (FAB) calcd.
for C22H25O5 [MH+] 369.1702, found 369.1703.
afforded the desired product 33b (312 mg, 60%) as a colourless oil
1
(R = 0.3). IR (neat): ν = 1965, 1708, 1260, 1070 cm–1. H NMR:
Acknowledgments
˜
f
δ = 7.39–7.27 (m, 10 H), 5.27 (t, J = 2 Hz, 2 H), 5.22 (s, 2 H), 4.57
(s, 2 H), 4.28 (t, J = 2 Hz, 2 H).
We thank the NUFFIC for financial support to B. T. Buu Hue
through a development cooperation project between the Universi-
ties of Amsterdam and Can Tho (Vietnam). We also acknowledge
Professors F.S. Guziec Jr. (Southwestern University, USA),
J. Lugtenburg (University of Leiden, The Netherlands) and P.
Wender (Stanford University, USA) for useful discussions.
2-(Benzyloxymethyl)buta-2,3-dien-1-ol: To a stirred solution of al-
lenyl ester 33b (1.6 g, 5.44 mmol) in dried CH2Cl2 (60 mL) at
–78 °C was added DIBAL-H (1.5 m in toluene) (11 mL, 3 equiv.).
The reaction mixture was stirred at –78 °C for 2 h and carefully
quenched with EtOAc at 0 °C. Saturated aqueous Na2SO4 (0.5 mL)
was added and the resulting mixture was stirred for 1 h. After add-
ing solid Na2SO4, the mixture was filtered through Celite® and the
filtrate was concentrated in vacuo. Purification by chromatography
(PE/EtOAc = 2:1) afforded a mixture of the desired 2-benzyloxy-
methyl-buta-2,3-dien-1-ol contaminated with benzyl alcohol
(803 mg) as a colourless oil (Rf = 0.23) which was used for the next
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Synthesis of the Tricyclic Core of Solanoeclepin A
FULL PAPER
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Received: August 10, 2005
Published Online: November 7, 2005
Eur. J. Org. Chem. 2006, 127–137
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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