Zeolite β-Induced Rearrangement of Alkoxybenzyl Allyl Ethers to Aldehydes and Ketones. 5.1 Variation of the Allylic Moiety

Article abstract of DOI:10.1021/jo972243o

Allylic PMB ethers rearranged in the presence of zeolite β to form 4-arylbutanals or 5-arylpentanones depending on the substituent pattern of the allylic moiety. Best results were obtained with substrates carrying simple substituents in the allylic 2-posi

Full text of DOI:10.1021/jo972243o

J . Org. Chem. 1998, 63, 3595-3598
3595
Zeolite â-In d u ced Rea r r a n gem en t of Alk oxyben zyl Allyl Eth er s to
Ald eh yd es a n d Keton es. 5.1 Va r ia tion of th e Allylic Moiety
J ohan Wennerberg, Charlotte Olofsson, and Torbjo¨rn Frejd*
Organic Chemistry 1, Department of Chemistry, Lund University, P.O. Box 124, S-221 00 Lund, Sweden
Received December 11, 1997
Allylic PMB ethers rearranged in the presence of zeolite â to form 4-arylbutanals or 5-arylpentanones
depending on the substituent pattern of the allylic moiety. Best results were obtained with
substrates carrying simple substituents in the allylic 2-position, but a couple of substrates lacking
a 2-substituent also rearranged. More functionalized substituents in this position were not tolerated.
A propargyl PMB ether and a homoallylic PMB ether rearranged as well, but the products were
mixtures of isomeric olefins. The 4-arylbutanals 2c and 2e and the 5-arylpentanone 2j were cyclized
in PPA to give naphthalene and dihydronaphthalene derivatives, respectively.
Sch em e 1. Su ggested Mech a n ism of th e Ben zAll
Rea r r a n gem en t
In tr od u ction
A new rearrangement to give 4-arylbutanals (2) was
recently uncovered when certain benzyl allyl ethers (1)
were treated with zeolite â or BF3‚OEt2. The mechanism
comprises a 1,4-rearrangement of the benzylic grouping
followed by, or concomitant with, a 1,2-hydride or 1,2-
alkyl shift (Scheme 1).1,2 For simplicity, we call the entire
sequence the BenzAll rearrangement (benzyl allyl ether
rearrangement). Among several catalysts tested, zeolite
â was found to give the best results even if a few other
catalysts also promoted the rearrangment.3 We here
report the results using a number of p-methoxybenzyl
(PMB) ethers carrying various substitued allylic moieties
as part of an investigation of the scope and limitations
of this rearrangement.
Resu lts a n d Discu ssion
allylic alcohol 2g. Indeed, a similar case was very
recently reported by Ley et al.6 However, since only 2b
was detected (52%), compound 2g may have been formed
in situ but in that case rearranged under the influence
of the zeolite. It is known that such acid-catalyzed allylic
alcohol to aldehyde rearrangements are particularly
facile for allylic alcohols branched at the 2-position.7
Alternatively, protiodesilylation to 1b could initially have
taken place followed by the BenzAll rearrangement to
give 2b. Further investigations are necessary to clearify
these details.
Despite the lack of a 2-substituent, the unsubstituted
1a and compound 1i rearranged efficiently. In the case
of 1i, a 2:1 mixture of ketone 2i and aldehyde 2b was
obtained as a result of competing 1,2-hydride and 1,2-
methyl shifts. This was noticed earlier for compound 1j
as well, which gave ketone 2j and aldehyde 2k also in a
2:1 ratio.2 A chloro substituent in the 2-position of the
allylic part should be able to delocalize the positive charge
in the intermediate, thus facilitating the BenzAll rear-
rangement. In line with this reasoning, the chloro
derivative 1h gave R-chloro aldehyde 2h , which, however,
was unstable toward chromatographic purification and
The reactions were performed on a 1 mmol scale by
treating the PMB ethers with 100 mg of zeolite â in
dichloromethane for 12 h at room temperature, unless
otherwise stated. Since a carbocation intermediate (B)
may be involved in the rearrangement, it was anticipated
that derivatives carrying cation-stabilizing substituents
in the 2-position would be ideal substrates. On the other
hand, for substrates carrying electron-withdrawing group
in this position, the rearrangement was expected to be
more difficult or even prevented. It should also be
mentioned that the migration of the benzyl unit is mostly
intramolecular, which we reported earlier by using
crossover experiments.2
As seen in Table 1, the 2-substituted PMB ethers
capable of forming a tertiary or secondary cation at the
2-position rearranged to give the corresponding aldehydes
2a -f in moderate to good yields. In particular, the allylic
silane 1g was expected to be a very good substrate due
to the â-silicon effect,4,5 and we expected to obtain the
(1) Wennerberg, J .; Eklund, L.; Polla, M.; Frejd, T. Chem. Commun.
1997, 445.
(2) Wennerberg, J .; Frejd, T. Acta Chem. Scand. 1998, 52, 95-99.
(3) Wennerberg, J .; Olofsson, C.; Frejd, T. Acta Chem. Scand. 1998,
52, 232-235.
(4) Kahn, S. D.; Keck, G. E.; Hehre, W. J . Tetrahedron Lett. 1987,
28, 279.
(6) Buffet, M. F.; Dixon, D. J .; Edwards, G. L.; Ley, S. V.; Tate, E.
Synlett 1997, 1055-1056.
(7) Yanovskaya, L. A.; Shakhidayatov, K. Russ. Chem. Rev. 1970,
39, 859-874.
(5) Keck, G. E.; Castellino, S. Tetrahedron Lett. 1987, 28, 281-284.
S0022-3263(97)02243-3 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/06/1998

3596 J . Org. Chem., Vol. 63, No. 11, 1998
Wennerberg et al.
Ta ble 1. Resu lts of th e Zeolite â-Ca ta lyzed
Rea r r a n gem en t of P MB Eth er s 1a -ja
F igu r e 1. Stereoview of a transition-state model of the
rearrangement of 1k .
Sch em e 3a
a
Reaction conditions: (a) PhSO2Na, DMF, rt, 24 h; (b) Cs2CO3,
PhSH, CH3CN, rt, 30 min; (c) NaH, dimethylmalonate, THF, rt,
30 min; (d) Et2NH, CH3CN, reflux 30 min.
a
b
Conditions: 1 mmol scale, 100 mg of zeolite â, 12 h, rt. PMP
) p-methoxyphenyl.
benzylic cation to the terminal olefinic carbon. Since the
nascent cation at position 2 would only be secondary, it
is possible that the steric repulsion between the aromatic
group and the methyl group is sufficient to hinder the
reaction. A more favorable tertiary cationic center as in
1f was, on the other hand, sufficient to allow the reaction
despite that there should be a steric hindrance similar
to that in 1k . In the absence of steric crowding as in 1a
and 1i, the rearrangement proceeded quite well even if
the intermediary cation would be secondary. The rapid
reaction of 1l and 1m may be explained by heterolysis of
the other ether bond due to the more favorable formation
of prenyl cation. Subsequent reactions of this electrophile
with p-methoxybenzyl alcohol would then give rise to
several products via electrophilic aromatic substitutions.
Sch em e 2
therefore had to be converted into a more stable com-
pound. As trapping agent, sodium benzenesulfinate
turned out to be convenient since it was easy to handle
and gave a smooth conversion of 2h into the stable phenyl
sulfone 3 at room temperature.
The results obtained in this work are partly in ac-
cordance with the characteristics of the acid-catalyzed
rearrangement of allylic alcohols to aldehydes or ketones.
In these reactions, protonation of the double bond leads
to a carbocation similar to A (Scheme 1), which then
undergoes a prototropic shift to generate the carbonyl
function. It was concluded that allylic systems having
the ability to form a tertiary cation reacted smoothly,
while those that could only form a secondary cation were
unreactive.7 Thus, this mechanism is closely related to
that suggested for the BenzAll rearrangement (Scheme
1),2 and most of the results presented in this report can
be rationalized accordingly. However, 1a and 1i did
rearrange, although only secondary carbocations may be
formed. In contrast, the allylic ethers 4-8 (Scheme 3)
were not useful in this rearrangement probably because
each contains an electronegative substituent on the
carbon attached to the carbon that will become positively
charged. Thus, the inductive electron-withdrawing effect
Despite their similar structures, PMB ethers 1k -n
behaved very differently (Scheme 2). While 1k and 1n
were essentially unaffected even after prolonged reaction
times and higher reaction temperatures, compounds 1l
and 1m rapidly gave a multitude of products already at
room temperature. The intramolecularity of the reaction
seems to account for the reluctance of 1n to rearrange.
Here, the terminal carbon of the double bond may not
come close enough to the benzyl carbon to make the 1,4-
migration possible. This is clearly seen by inspection of
molecular models. Also, the sluggish behavior of 1k is
possible to rationalize by the intramolecular migration
of the benzylic moiety presumably as a cation or cation-
like species. In this case, molecular models indicated
that the methyl group of the olefinic part and the
p-methoxyphenyl group could come in rather close con-
tact. In the model shown in Figure 1, the aromatic group
was oriented so as to mimic the approach of the assumed

Rearrangement of Alkoxybenzyl Allyl Ethers
J . Org. Chem., Vol. 63, No. 11, 1998 3597
Sch em e 4
Sch em e 5. Rin g Closu r e to Na p h th a len e
Der iva tives
will destabilize the nascent cationic center in particular
on Lewis acid coordination of the electronegative sub-
stituent.
Compound 4,8 available in two steps from 3-bromo-2-
(bromomethyl)propan-1-ol (DIBOL),9 was used as start-
ing material for the synthesis of the structurally diverse
allylic ethers 5-8 via substitution of bromine by different
C-, N-, and S-nucleophiles as indicated in Scheme 3.
Also, alkynes should be able to act as π-nucleophiles
toward cationic centers. Indeed, propargyl PMB ether 9
on treatment with zeolite â gave 10a and 10b (3:1) in
71% total yield (Scheme 4). Double-bond isomerization
obviously took place in the presence of the zeolite as
judged from GC analyses directly of the reaction mixture.
Rearrangement of the homoallylic compound 11 gave a
mixture of the three unsaturated alcohols 12a -c in a
total yield of 72% (Scheme 4). The carbocation interme-
diate generated in the first step apparently eliminates a
proton from either of three available positions.
converted to the phenyl sulfone 3. However, a number
of substrates carrying substituents containing heteroa-
toms in this position did not give satisfactory results. The
products formed in the rearrangement may be cyclized
to give dihydronaphthalene and/or naphthalene deriva-
tives. Thus, the entire reaction sequence may be devel-
oped into a versatile method for the synthesis of such
compounds, some of which are important natural prod-
ucts and drugs.12-19 These and other aspects of the
BenzAll rearrangement are being investigated in our
laboratory, and results concerning variation of the aro-
matic part will be reported in due course.
The rearrangement products, containing a benzene
ring and a four-carbon unit terminated with a carbonyl
functionality, are potential precursors for naphthalene
derivatives. As zeolites may act as both Bro¨nsted and
Lewis acids, we hoped that prolonged reaction times or
higher temperatures would result in ring closure in situ.
This did not occur with the examples tested here,
presumably because the methoxy group was located in
the meta position to the carbon that would undergo
attack of the electrophile. However, both aldehydes 2c
and 2e as well as ketone 2j gave good total yields of
naphthalene or hydronaphthalene derivatives on treat-
ment with PPA at 80 °C for 2 h (Scheme 5).10,11 Obvi-
ously, the ring closure was followed by water elimination
and oxidation. Since the oxidation occurred in the
reaction mixture as indicated by TLC analyses, it was
presumably caused by air dissolved in the PPA. In the
ring closure of 2e, a 1:1 mixture of the dihydronaphtha-
lenes 15a and 15b was formed, but no oxidation to
naphthalenes was noticed.
In conclusion, several allylic PMB ethers rearranged
in the presence of zeolite â to form 4-arylbutanals or
5-arylpentan-2-ones depending on the substituent pat-
tern of the allylic part. Best results were obtained with
substrates carrying simple substituents in the allylic
2-position. Rearrangement of the 2-chloro-substituted
ether 1h resulted in a moderate yield of the labile
R-chloro aldehyde derivative 2h , which was immediately
Exp er im en ta l Section
Gen er a l Meth od s. Gas chromatographic analyses were
performed on a DB vax (J &W Scientific) capillary column 30
m × 0.25 mm i.d., 0.25 µm stationary phase. NMR spectra
were recorded at 300 MHz using CDCl3 as internal standard.
Chromatographic separations were performed on Matrex
Amicon normal-phase silica gel 60 (0.035-0.070 mm). Thin-
layer chromatography was performed on Merck precoated TLC
plates with silica gel 60 F-254, 0.25 mm. After eluation, the
TLC plates were vizualized with UV light or sprayed with a
solution of p-methoxybenzaldehyde (26 mL), glacial acetic acid
(11 mL), concentrated sulfuric acid (35 mL), and 95% ethanol
(960 mL) followed by heating. Mass spectra were recorded in
the following modes: EI (70 eV) using both direct inlet and
inlet via a gas chromatograph equipped with a DB Wax column
as above, CI (CH4, 200 eV) and FAB. Chemicals were reagent
grade. Zeolite â was a gift from EKA Chemicals AB, Bohus,
Sweden, and was activated at 400 °C for 3 h before use. Zeolite
â is also commercially available.20 THF was distilled under
N2 from sodium benzophenone ketyl, and CH2Cl2 was distilled
from P2O5 prior to use. DMF and MeCN were stored over 4A
molecular sieves. Data for compounds 1b,c,g,j, 2b,c,j,k , and
4 can be found elsewhere.2,8
Typ ica l P r oced u r e for th e Syn th esis of Allyl 4-Meth -
oxyben zyl Eth er s. 3-[(4-Meth oxyben zyl)oxy]-2-p h en yl-
(12) J ardine, I. Podophyllotoxins in anticancer agents based on
natural product model; Academic Press: New York, 1980.
(13) Ward, R. S. Nat. Prod. Rep. 1993, 10, 1-28.
(14) Ward, R. S. Nat. Prod. Rep. 1995, 12, 183-205.
(15) Medarde, M.; Ramos, A. C.; Caballero, E.; Lopez, J . L.; de
Clairac, R. P.-L.; Feliciano, A. S. Tetrahedron Lett. 1996, 37, 2663.
(16) Perri, S. T.; Moore, H. W. Tetrahedron Lett. 1987, 28, 4507.
(17) Shibuya, M.; Toyooka, K.; Kubota, S. Tetrahedron Lett. 1984,
25, 1171.
(8) Wennerberg, J .; Frejd, T. Nat. Prod. Lett. 1997, 10, 1-6.
(9) Magnusson, G.; Ahlfors, S.; Dahmen, J .; J ansson, K.; Nilsson,
U.; Noori, G.; Stenvall, K.; Tjo¨rnebo, A. J . Org. Chem. 1990, 55, 3932-
3946.
(18) Buckley, T. F. J . Org. Chem. 1983, 48, 4222.
(19) Bremmer, M. L.; Khatri, N. A.; Weinreb, S. M. J . Org. Chem.
1983, 48, 3661.
(10) Chen, T. S.; Canonne, P.; Leitch, L. C. Synthesis 1973, 620-
621.
(11) Katritzky, A. R.; Zhang, G.; Xie, L. J . Org. Chem. 1997, 62,
721.
(20) PQ Corporation, Zeolites and Catalysts Division, P.O. Box 840,
Valley Forge, PA 19482.

3598 J . Org. Chem., Vol. 63, No. 11, 1998
Wennerberg et al.
p r op en e (1d ). A solution of 2-phenylpropenol (1.34 g, 10
mmol) in THF (5 mL) was slowly added to a suspension of
sodium hydride (440 mg,11.0 mmol, 60% in mineral oil) in
DMF at 0 °C under Ar followed by stirring for 30 min.
4-Methoxybenzyl chloride (1.61 g, 10.3 mmol) in THF (2 mL)
was then added, and the mixture was stirred for 2 h. The
mixture was thereafter distributed between ether and water,
and the organic phase was washed with water and brine
followed by drying (MgSO4). After removal of the solvent
under reduced pressure, the residue was purified by chroma-
tography (heptane-EtOAc 95:5), which gave 2.06 g (81%) of
1d : 1H NMR (CDCl3) δ 7.48 (m, 2 H), 7.30 (m, 5 H), 6.88 (d,
2 H), 5.56 (s, 1 H), 5.37 (s, 1 H), 4.51 (s, 2 H), 4.40 (s, 2 H),
3.81 (s, 3 H); 13C NMR (CDCl3) δ 159.2, 144.3, 138.8, 130.3,
129.5, 128.3, 127.8, 126.2, 114.5, 113.8, 71.7, 71.6, 55.3; HRMS
calcd for C17H18O2 254.1307, found 254.1313.
Typ ica l P r oced u r e for t h e R ea r r a n gem en t . 4-(4-
Meth oxyp h en yl)-2-p h en ylbu ta n a l (2d ). A solution of 1d
(1.0 mmol) in CH2Cl2 (2 mL) was added to activated zeolite â
(100 mg) under argon. The reaction mixture was stirred at
room temperature, and the progress of the reaction was
monitored with TLC. After completion of the reaction (ca. 12
h), the resulting colored mixture was filtered through Celite.
The Celite was washed with CH2Cl2, and the combined organic
extracts were concentrated at reduced pressure. Purification
by chromatography (heptane-EtOAc 10:1) gave 147 mg (54%)
of 2d : 1H NMR (CDCl3 δ 9.67 (d, J ) 1.8 Hz, 1 H), 7.36 (m, 3
H), 7.20 (m, 2 H), 7.06 (d, J ) 8.3 Hz, 2 H), 6.83 (d, J ) 8.7
Hz, 2 H), 3.79 (s, 3 H), 3.50 (m, 1 H), 2.55 (m, 2 H), 2.37 (m,
1 H), 2.03 (m, 1 H); 13C NMR (CDCl3) δ 200.7, 158.0, 136.1,
133.2, 129.4, 129.1, 129.0, 127.7, 113.9, 58.2, 55.3, 32.0, 31.3;
IR (film) 1730 cm-1; HRMS calcd for C17H18O2 254.1306, found
254.1306.
4-(4-Met h oxyp h en yl)-2-(p h en ylsu lfon yl)b u t a n a l (3).
Compound 1h was treated according to the typical procedure
for the rearrangement, but since the product, 2-chloro-4-(4-
methoxyphenyl)butanal (2h ), was unstable, characterization
was performed by conversion to the corresponding phenyl
sulfone 3. Thus, crude 2h was dissolved in DMF (7 mL)
followed by addition of the sodium salt of benzene sulfinic acid
(330 mg, 2.0 mmol), and the mixture was then stirred for 21
h. Water (10 mL) was added followed by extraction with ether.
The combined organic phases were washed with water, dried
(Na2SO4), and concentrated at reduced pressure. Chromatog-
raphy (heptane-EtOAc 2:1) gave 3 (168 mg, 53%): 1H NMR
(CDCl3) δ 9.72 (d, J ) 2.6 Hz, 1 H), 7.79-7.53 (m, 5 H), 7.01
(d, J ) 8.6 Hz, 2 H), 6.81 (d, J ) 8.7 Hz, 2 H), 3.85 (m, 1 H),
3.79 (s, 3 H), 2.71 (m, 1 H), 2.57 (m, 1 H), 2.26 (m, 2 H); 13C
NMR (CDCl3) δ 193.2, 158.4, 134.6, 131.1, 129.5, 129.4, 128.9,
128.7, 114.1, 73.7, 55.3, 31.4, 25.4; IR (film) 1730 cm-1; HRMS
calcd for C17H18O4S 318.0925, found 318.0931.
5) gave 6 (535 mg, 89%) as a colorless oil: 1H NMR (CDCl3) δ
7.27 (m, 7 H), 6.88 (d, J ) 8.7 Hz, 2 H), 5.11 (s, 1 H), 5.02 (s,
1 H), 4.42 (s, 2 H), 4.09 (s, 2 H), 3.79 (s, 3 H), 3.61 (s, 2 H); 13
C
NMR (CDCl3) δ 159.2, 141.5, 130.1, 129.0, 128.9, 128.8, 126.3,
125.9, 115.6, 113.8, 71.9, 71.2, 55.3, 37.4; HRMS calcd for
C
18H20O2S 300.1184, found 300.1183.
Dim eth yl [2-[[(4-m eth oxyben zyl)oxy]m eth yl]a llyl]m a -
lon a te (7). Dimethyl malonate (528 mg, 4.0 mmol) in THF
(20 mL) was added to a slurry of NaH (100 mg, 2.5 mmol, 60%
in mineral oil) in THF (5 mL). The mixture was stirred for
15 min, whereafter 48 (542 mg, 2.0 mmol) in THF (10 mL) was
added dropwise. Stirring was continued for 3 h, and then THF
was evaporated at reduced pressure. The residue was dis-
tributed between ether and water, the combined ether phases
were dried, and the solvent was removed under reduced
pressure. Chromatography of the residue (heptane-EtOAc
8:2) gave 8 (477 mg, 74%) as a colorless liquid: 1H NMR
(CDCl3) δ 7.28 (d, J ) 8.6 Hz, 2 H), 6.87 (d, J ) 8.7 Hz, 2 H),
5.11 (s, 1 H), 4.98 (s, 1 H), 4.41 (s, 2 H), 3.94 (s, 2 H), 3.80 (s,
3 H), 3.72 (s, 6 H), 3.68 (t, J ) 7.8 Hz, 1 H), 2.67 (d, J ) 7.8
Hz, 2 H); 13C NMR (CDCl3) δ 169.4, 159.2, 142.3, 130.9, 129.4,
114.3, 113.8, 72.5, 71.6. 55.3, 52.6, 50.3, 41.1; IR (film) 1730
cm-1; HRMS (FAB) calcd for C17H22O6Na 345.1314, found
345.1321.
3-[(4-Meth oxyben zyl)oxy]-2-[(d im eth yla m in o)m eth yl]-
p r op en e (8). A solution of diethylamine (293 mg, 4.0 mmmol)
in CH3CN (25 mL) was added to 48 (542 mg, 2.0 mmol). The
mixture was refluxed for 30 min, whereafter water (25 mL)
was added and the CH3CN was evaporated at reduced press-
sure. The aqueous phase was extracted with CH2Cl2, and the
combined organic phase was dried (Na2SO4) and concentrated
at reduced pressure. Chromatography of the residue (hep-
tane-EtOAc 8:2 + 1% triethylamine) gave 7 (352 mg, 67%)
as a yellow liquid: 1H NMR (CDCl3) δ 7.29 (d, J ) 8.7 Hz, 2
H), 6.88 (d, J ) 8.7 Hz, 2 H), 5.18 (s, 1H), 5.11 (s, 1 H), 4.43
(s, 2 H), 4.01 (s, 2 H), 3.80 (s, 3 H), 3.03 (s, 2 H), 2.47 (q, J )
7.1 Hz, 4 H), 1.01 (t, J ) 7.1 Hz, 6 H); 13C NMR (CDCl3) δ
159.1, 144.6, 142.7, 129.2, 113.7, 113.4, 71.9, 71.5, 56.6, 55.3,
46.7, 11.7; HRMS calcd for C16H26NO2 (M + H) 264.1964, found
264.1960.
Cycliza tion w ith P P A. Syn th esis of 2-Meth oxy-7-
(m eth yleth yl)n a p h th a len e (13). A mixture of aldehyde 2c
(220 mg, 1.0 mmol) and PPA (1 mL) was stirred at 80 °C for
2 h and then cooled to room temperature. Aqueous 10% NaOH
(10 mL) was then added followed by extraction with ether. The
combined organic phases were washed with water and satu-
rated aqueous NaHCO3 and then again with water. After
drying of the organic extract (MgSO4), the solvent was removed
under reduced pressure. Chromatography (heptane-EtOAc
8:2) of the residue gave 13 (151 mg, 75%): 1H NMR (CDCl3) δ
7.69 (m, 2 H), 7.57 (m, 1 H), 7.27 (m, 1 H), 7.08 (m, 2 H), 3.93
(s, 3 H), 3.04 (m, 1 H), 1.34 (d, J ) 6.9 Hz, 6 H); 13C NMR
(CDCl3) δ 157.0, 146.7, 142.7, 134.8, 129.0, 127.6, 123.5, 123.1,
117.8, 105.6, 55.3, 34.3, 24.0; HRMS calcd for C14H16O 200.1201,
found 200.1202.
2-[[(4-Meth oxyben zyl)oxy]m eth yl]-3-(p h en ylsu lfon yl)-
p r op en e (5). 2-(Bromomethyl)-3-[(4-methoxybenzyl)oxy]pro-
pene (4)8 (542 mg, 2.0 mmol) was dissolved in DMF (10 mL),
and sodium benzenesulfinate (657 mg, 4.0 mmol) was added.
The reaction mixture was stirred for 24 h and then poured
into water (10 mL). The aqueous phase was extracted with
ether, and the combined ether phases were dried (Na2SO4) and
concentrated at reduced pressure. Chromatography of the
residue (heptane-EtOAc 8:2) gave 5 (532 mg, 75%) as a
colorless oil, which crystallized upon standing: mp 51-53 °C;
1H NMR (CDCl3) δ 7.88 (d, J ) 7.1 Hz, 2H), 7.59 (m, 3 H),
7.24 (m, 2 H), 6.88 (d, J ) 8.7 Hz, 2 H), 5.37 (s, 1 H), 5.01 (s,
Ack n ow led gm en t. We thank the Swedish Natural
Research Council, The Knut and Alice Wallenberg
Foundation, and The Crafoord Foundation for economic
support.
1 H), 4.38 (s, 2 H), 3.98 (s, 2 H), 3.86 (s, 2 H), 3.81 (s, 3 H); 13
C
NMR (CDCl3) δ 159.3, 138.4, 134.2, 133.8, 129.9, 129.1, 129.0,
128.5, 121.8, 113.8, 72.1, 71.7, 59.5, 55.3; HRMS (FAB) calcd
for C18H20O4SNa 355.0980, found 355.0959.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra for
all compounds analyzed by HRMS. Data for compounds
1a ,e,f,h ,i,k -n , 2a ,e,f,i, 9, 10a ,b, 11, 12a -c, 14, and 15a ,b
(27 pages). This material is contained in libraries on micro-
fiche, immediately follows this article in the microfilm version
of the journal, and can be ordered from the ACS; see any
current masthead page for ordering information.
3-[(4-Meth oxyben zyl)oxy]-2-[(p h en ylth io)m eth yl]p r o-
p en e (6). Compound 48 (542 mg, 2.0 mmol) was dissolved in
CH3CN (20 mL), and thiophenol (300 µL, 2.9 mmol) and Cs2-
CO3 (771 mg, 2.37 mmol) were added. The mixture was stirred
for 30 min and was then poured into water (100 mL). The
water phase was extracted with ether, and the combined ether
phases were dried (Na2SO4) and concentrated at reduced
pressure. Chromatography of the residue (heptane-EtOAc 95:
J O972243O