An expedient route to p-tert-butylthiacalix[4]arene 1,3-diethers via Mitsunobu reactions

Article abstract of DOI:10.1016/S0040-4039(03)00285-5

Regioselective distal dialkylation of p-tert-butylthiacalix[4]arene with alcohols was performed under the Mitsunobu protocol using the DEAD/TPP system. The method provides a versatile tool for obtaining 1,3-diethers with different functional groups in the alkyl chains.

Full text of DOI:10.1016/S0040-4039(03)00285-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2261–2265
An expedient route to p-tert-butylthiacalix[4]arene 1,3-diethers
via Mitsunobu reactions
Istva´n Bitter* and Viktor Csokai
Department of Organic Chemical Technology, Budapest University of Technology and Economics, H-1521 Budapest, Hungary
Received 18 December 2002; revised 20 January 2003; accepted 31 January 2003
Abstract—Regioselective distal dialkylation of p-tert-butylthiacalix[4]arene with alcohols was performed under the Mitsunobu
protocol using the DEAD/TPP system. The method provides a versatile tool for obtaining 1,3-diethers with different functional
groups in the alkyl chains. © 2003 Elsevier Science Ltd. All rights reserved.
The large number of calixarene derivatives is partly
ascribed to the regio- and conformation selective reac-
tions developed during the last decades.1,2 Among
these, the partial O-alkylation and acylation, along
with aromatic nitration, halogenation, formylation, etc.
of calix[4]arenes provide important synthetic tools for
designing supramolecules of great variety. Similar
regioselective reactions, at least with the same
efficiency, have not been found in thiacalixarene chem-
istry. The lack of regio- and stereoselectivity in the
weak base (K2CO3, Et3N) mediated partial O-alkyla-
tion and acylation reactions of thiacalix[4]arenes can be
attributed to the substantially reduced differences
between the OH acidities3 and the 15% larger cavity as
compared with a calixarene counterpart. As a conse-
quence, tetraalkylation of thiacalix[4]arenes takes place
easily in the presence of different bases,4–7 but the
stereochemical outcome of the alkylation strongly
depends on the base used and the upper rim substitu-
tion (tert-butyl versus H).7 1,3-Diethers or diesters,
however, cannot be obtained simply by following the
1,3-dialkylation or diacylation procedure described for
calix[4]arenes. Actually, only a few 25,27-dialkoxythia-
calix[4]arenes (methoxy, propoxy and ethoxycarbonyl-
methoxy)8,9 and several partially acylated derivatives
have been prepared in moderate yields and
selectivities10–13 so far.
closure of thiacalixarenes with tetra- and pentaethylene
glycol derivatives in the presence of K2CO3. Therefore
the temporary protection of two distal OH groups was
required prior to cyclization. Due to the difficulties of
1,3-disubstitution in the thiacalixarene series mentioned
above, we failed to introduce regioselectively any pro-
tecting group either on alkylation or acylation. Thus,
we did not succeed in synthesizing diametrically bridged
thiacalix[4]monocrowns with unsubstituted 26,28-OH
groups.
To overcome the problems in base mediated alkyla-
tions, the Mitsunobu reaction14 appeared to be an
attractive alternative to O-alkylation. This reaction has
already been utilized in calixarene chemistry in particu-
lar cases to obtain glycosyl calixarenes15 and for the
alkylation of calix[4]arenes with benzylic and allylic
alcohols,16 but to our knowledge, it is unprecedented in
thiacalixarene chemistry. The alkylation of phenols
with alcohols effected by the triphenylphosphine/diethyl
azodicarboxylate (TPP/DEAD) system is well-docu-
mented in the literature.17 In recent papers the Mit-
sunobu reaction has been used to synthesize chiral
synthons for macrocyclic frameworks18 and for the
selective monoalkylations of 1,1%-bi-2-naphthol.19 The
success of the latter reaction prompted us to explore the
possibility of regioselective O-alkylations of thia-
calix[4]arenes under standard Mitsunobu conditions.
Recently studies conducted in our laboratory to synthe-
size thiacalix[4]monocrowns9 revealed, that unlike calix-
arenes, only biscrowns could be obtained by the ring
First, compound 1 was treated with a tenfold excess of
MeOH using 2.2 mol of TPP/DEAD in THF at ambi-
ent temperature. After 24 h a single product spot was
detected by TLC (hexane–EtOAc=9:1) besides unre-
acted starting 1 which was almost entirely consumed
after 72 h. By increasing the molar ratio of TPP/
Keywords: thiacalix[4]arenes; O-alkylation; Mitsunobu reaction.
* Corresponding author. Tel.: 36-1-463-1379; fax: 36-1-463-3648;
e-mail: ibitter@mail.bme.hu
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00285-5

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I. Bitter, V. Csokai / Tetrahedron Letters 44 (2003) 2261–2265
DEAD: 1 to three, the reaction took place in 24 h
affording 2a in 80% yield. The reaction was repeated
with a series of primary alcohols resulting in the forma-
tion of 1,3-dialkoxythiacalix[4]arenes 2b–h (Scheme
1).20 Under these conditions the reaction generally stops
at disubstitution and the tri- or tetraalkoxy products
could not be isolated. This protocol seems to be espe-
cially effective with long chain alcohols and glycol
monoethers, where the alkylating agents (halogenides
or tosylates) derived from them react sluggishly in
base-mediated reactions. It was disappointing that ben-
zyl and allyl alcohol did not give single products,
inseparable mixtures of compounds of different degrees
of alkylation were formed. By decreasing the molar
ratio of reagents to 2.2, the dibenzyl derivative 2l was
detected but we failed to isolate it in analytically pure
form even after chromatography. To achieve temporary
protection of the 25,27-OH groups in the thiacalixarene
skeleton, attempts were made to introduce the readily
removable bulky phthalimidomethyl group with N-
hydroxymethyl-phthalimide. Although this reaction was
successful and compound 2k was obtained in an excel-
lent yield in a relatively fast reaction using 2.2 equiv. of
reagents, it proved to be unstable during further, alkali
carbonate-mediated alkylation with BnBr. However,
the Mitsunobu benzylation of 2k helped to solve this
problem (see later).
a substantial quantity of the tetraalkylated product 4 at
ambient temperature when threefold excess of
a
reagents was used. Decreasing the molar ratio of TPP/
DEAD: 1 to 2.2, diether 2j could be isolated but only in
30% yield.20 On the contrary, 2-bromoethanol behaved
similarly to the other alcohols and resulted solely in
diether 2i. However, if the molar ratio of TPP/DEAD:
1 was increased to 6, tetraethers 3 and 4 were formed
exclusively in excellent yields. It is worth noting that
peralkylation of 1 by n-octanol affording 5 could also
be attained but only at elevated temperatures (110°C,
toluene). These examples represent an acceptable alter-
native for the tetraalkylation of thiacalixarenes.
The conformations of the compounds prepared were
proved by NMR measurements. The extremely simple
1H NMR spectra of diethers 2 showed the presence of
one conformer. Two pairs of singlets observed for the
aromatic and But protons appeared at 7.70–6.90 and
1.37–0.70 ppm, respectively, indicating a C2v symmetry
in the cone conformation, analogous to literature
results.8,9
Tetraethers 3, 4 and 5 were assigned the 1,3-alternate
conformer on the basis of chemical shifts and literature
analogy.21 The But and aromatic protons in the 1,3-alt
conformation are deshielded while those of the cone are
shielded by the attached phenyl rings. Consequently,
two singlets at lower field are expected for the 1,3-alt
conformation (7.2–7.4, 1.2–1.3 ppm), while these are at
higher field for the cone conformation (6.8–7.0, 0.75–
0.85 ppm). Furthermore, the OCH2 and CH2Br moi-
eties of 1,3-alt-3 are shielded by the adjacent phenyl
rings so that these protons should give resonances at
higher field (t, 4.11, t, 2.56) than those of cone-2i (t,
4.90, t, 3.98) (Fig. 1).
As was expected, secondary alcohols gave poor results
under mild reaction conditions but at elevated tempera-
tures (110°C, 24 h in toluene) (S)-ethyl lactate and
(R)-ethyl mandelate cleanly afforded the chiral diesters
2m,n in good yields with possible inversion of configu-
ration (the optical purities were not determined)
(Scheme 1). The sterically hindered (−)-menthol proved
to be unreactive even under vigorous conditions.
Unexpectedly, great differences in the reactivities and in
the outcome of the reaction were observed with halohy-
drins. 6-Bromohexanol and diethylene glycol
monochlorohydrin reacted sluggishly to afford diethers
2g and 2h with lower yields as compared to the other
long chain alcohols. 3-Chloropropanol, however, gave
The success of peralkylation involves the possibility of
preparing tetraethers with two different alkyl groups.
These after all, were utilized in the synthesis of dibenzyl
2l. The easily accessible 2k was cleanly dibenzylated by
BnOH (THF, rt, 48 h) affording compound 6 which,
unexpectedly, exists in the partial cone conformation
Scheme 1. Synthesis of thiacalix[4]arene 1,3-diethers via Mitsunobu reactions.

I. Bitter, V. Csokai / Tetrahedron Letters 44 (2003) 2261–2265
2263
cyclizations between the proximal OH groups took
place resulting in the formation of a molecular basket
doubly capped by ethylene bridges. We have attained
the same result when 2i was treated with K2CO3 in
boiling MeCN. Compounds 3 and 4 provide the possi-
bility of accessing koilands where the central 1,3-alt-thia-
calixarene core is fused with two (thia)calix units
through connecting chains.
Figure 1. Thiacalix[4]arene tetraethers.
In conclusion, we have demonstrated for the first time
the selective O-alkylation of p-tert-butylthia-
calix[4]arene with a series of alcohols under the Mit-
sunobu protocol, thus opening a simple access to
intermediates containing reactive functional groups
which are not available by other methods. Further-
more, a useful protecting group has also been intro-
duced into thiacalixarene chemistry.
exclusively in CDCl3. The 1H NMR spectrum of 6
reflects the lower symmetry when compared to the
1,3-alternate 3–5. The three singlets (1.57, 1.19 and 0.8
ppm in a 1:1:2 ratio) for the But groups, the two
singlets (4.99 and 4.97 ppm) for the OCH2Ph groups
and the splitting of the aromatic signals into two dou-
blets (7.65 and 7.25 ppm with meta coupling J=2.6 and
2.2 Hz, respectively) and two singlets (8.02 and 7.38
ppm) are all indicative of the paco structure 6, similar
to another literature example.7
Acknowledgements
After removing the phthalimidomethyl protecting
groups from 6 by simple base treatment (toluene/EtOH,
K2CO3, 1 h reflux), 2l was cleanly obtained in 60%
overall yield.20 This protection–deprotection route is
expected to work efficiently in the synthesis of diethers
not available by direct alkylation.
Financial supports by the Hungarian Scientific
Research Found (OTKA No. T 031864) are gratefully
acknowledged. Dr. Gy. Parlagh and Mr. J. Kovacs are
acknowledged for the mass spectra. One of the authors
(V.Cs.) thanks the Jo´zsef Varga Foundation for a
fellowship.
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Mitsunobu alkylation has not been utilized fully in
calixarene chemistry. To illustrate the advantages of
this method, we have prepared 25,27-bis(2-bro-
moethoxy)-26,28-dihydroxycalix[4]arene at ambient
temperature in a yield of 55% (not optimized) using
2-bromoethanol in THF under the Mitsunobu proto-
col.20 This compound has already been synthesized by
Zhang et al. in a 48 h reaction by the K2CO3 mediated
alkylation of calix[4]arene with an enormous excess of
1,2-dibromoethane (100 ml/12 mmol calixarene!) in
boiling MeCN, and a similar yield was reported.22
7. Lhotak, P.; Himl, M.; Stibor, I.; Petrickova´, H. Tetra-
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Intermediates 2g–j, 3 and 4, by replacement of the
terminal halogen atoms with nucleophiles, may have
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3 with the standard K2CO3-mediated alkylation of 1
with 1,2-dibromoethane.21 Instead, intramolecular

2264
I. Bitter, V. Csokai / Tetrahedron Letters 44 (2003) 2261–2265
14. Mitsunobu, O. Synthesis 1981, 1–28.
J=7.40 ArH), 7.28 (t, 2H, J=7.35 ArH), 7.12 (d, 2H,
ArH), 7.11 (s, 2H, ArH), 6.92 (s, 4H, ArH), 4.78 (t, 4H,
J=4.50, OCH2), 4.30 (t, 4H, J=4.50, OCH2), 4.13 (t, 4H,
J=4.50, OCH2), 4.05 (t, 4H, J=4.50, OCH2), 1.31 (s,
18H, But), 0.77 (s, 18H, But); 13C NMR: l 157.0, 156.1,
148.1, 142.7, 134.8, 134.7, 132.9, 129.4, 123.7, 122.3,
119.2, 107.1 (Ar), 73.8 (ArOCH2), 70.9, 70.0, 67.8
(OCH2), 34.4 (C(CH3)3), 34.2 (C(CH3)3), 31.7 (C(CH3)3),
30.9 (C(CH3)3), FAB-MS m/z: 1149 [M+H]+, 1171 [M+
Na]+, 1187 [M+K]+, 1234.8 [M+Rb]+, 1280.8 [M+Cs]+;
anal. calcd for C68H76O8S4 (1148.65): C, 71.05; H, 6.62,
found: C, 70.68; H, 6.55%.
Compound 2f. Mp 148–150°C (eluent: hexane–EtOAc=
8:2); 1H NMR: l 8.04 (s, 2H, OH), 7.68 (s, 4H, ArH),
6.95 (s, 4H, ArH), 4.76 (t, 4H, J=4.65, OCH2), 4.08 (t,
4H, J=4.68, CH2), 3.84 (m, 4H, J=4.68, CH2), 3.66 (t,
4H, J=4.65, OCH2), 3.40 (s, 6H, OCH3), 1.35 (s, 18H,
But), 0.80 (s, 18H, But); 13C NMR: l 156.13, 156.1, 148.0,
142.7, 134.8, 132.8, 129.3, 122.3 (Ar), 73.8 (ArOCH2),
72.2 (OCH3), 70.8, 70.7, 59.2 (CH2), 34.3 (C(CH3)3), 34.2
(C(CH3)3), 31.7 (C(CH3)3), 30.9 (C(CH3)3); FAB-MS
m/z: 946.3 [M+Na]+, 962.4 [M+K]+, 1008.1 [M+Rb]+,
1056 [M+Cs]+; anal. calcd for C50H68O8S4 (924.45): C,
64.91; H, 7.36, found: C, 64.63; H, 7.31%.
15. Dondoni, A.; Marra, A.; Scherrmann, M.-C.; Casnati,
A.; Sansone, F.; Ungaro, R. Chem. Eur. J. 1997, 3,
1774–1782.
16. Wang, J.; Gutsche, C. D. Struct. Chem. 2001, 12, 267–
274.
17. Hughes, D. L. Org. React. 1992, 42, 335–656.
18. Gryko, D. T.; Piatek, P.; Salanski, P.; Jurczak, J. Tetra-
hedron: Asymmetry 1998, 9, 1771–1778.
19. Takahashi, M.; Ogasawara, K. Tetrahedron: Asymmetry
1997, 8, 3125–3130.
20. NMR spectra were recorded at 298 K in CDCl3 at
500/125 MHz on a Bruker-Avance DRX-500 instrument.
General procedure for the synthesis of diethers 2. To the
stirred mixture of 1 (0.72 g, 1 mmol), TPP (0.8 g, 3
mmol), ROH (10 mmol) in 20 ml dry THF, a 40%
toluene solution of DEAD (1.3 ml, 3 mmol) was added
under ice-cooling and allowed to react at ambient tem-
perature for 24 h. The solvent was then removed under
reduced pressure and the residue was triturated with hot
MeOH (20 ml) and filtered to give white solids which
were recrystallized or purified by chromatography on
silica (eluent: hexane–EtOAc=9:1 unless otherwise
stated).
Compound 2a. Mp 246–248°C, (lit.9 mp 246–248°C); 1H
and 13C NMR data are identical with those of the sample
prepared by alkylation of 1 with MeI.9
Compound 2g. Mp 215–217°C (eluent: hexane–EtOAc=
1
95:5); H NMR: l 8.02 (s, 2H, OH), 7.66 (s, 4H, ArH),
6.93 (s, 4H, ArH), 4.73 (t, 4H, J=4.50, ArOCH2), 4.09
(t, 4H, J=4.63, ClCH2), 3.93 (t, 4H, J=5.95, OCH2),
3.74 (t, 4H, J=6.00, OCH2), 1.33 (s, 18H, But), 0.78 (s,
18H, But); 13C NMR: l 155.9, 155.8, 148.0, 142.7, 134.8,
132.8, 129.1, 122.1 (Ar), 73.6 (ArOCH2), 71.5, 70.6, 69.9
(CH2), 34.2 (C(CH3)3), 34.0 (C(CH3)3), 31.5 (C(CH3)3),
30.8 (C(CH3)3); FAB-MS m/z: 933.6 [M+H]+, 954.6 [M+
Na]+, 970.5 [M+K]+, 1016.6 [M+Rb]+, 1064.4 [M+Cs]+;
anal. calcd for C48H62O6S4Cl2 (932.19): C, 61.78; H, 6.65,
found: C, 61.43; H, 6.70%.
Compound 2b. Mp 222–224°C (EtOAc–MeOH); 1H
NMR: l 7.96 (s, 2H, OH), 7.67 (s, 4H, ArH), 6.96 (s, 4H,
ArH), 4.50 (t, 4H, J=6.58, OCH2), 2.00 (p, 4H, J=7.07,
CH2), 1.63 (m, 4H, CH2), 1.35 (s, 18H, But), 1.05 (t, 6H,
J=7.35, CH3), 0.80 (s, 18H, But); 13C NMR: l 156.6,
156.1, 147.9, 142.7, 134.5, 133.0, 129.1, 122.4 (Ar), 75.9,
(OCH2), 34.4 (C(CH3)3), 34.2 (C(CH3)3), 32.4 (CH2),
31.7 (C(CH3)3), 31.0 (C(CH3)3), 19.3 (CH2), 14.3 (CH3);
FAB-MS m/z: 831.6 [M+H]+, 870.6 [M+K]+, 1091.9 [M+
Cs]+; anal. calcd for C48H64O4S4 (832.15): C, 69.20; H,
7.69, found: C, 68.77; H, 7.71%.
1
Compound 2h. Mp 278–280°C; H NMR: l 7.92 (s, 2H,
OH), 7.69 (s, 4H, ArH), 6.97 (s, 4H, ArH), 4.50 (t, 4H,
J=6.50, OCH2), 3.47 (t, 4H, J=6.80, BrCH2), 2.04 (m,
4H, J=7.10, CH2), 4.05 (t, 4H, J=7.00 CH2), 1.61–1.65
(m, 8H, CH2), 1.36 (s, 18H, But), 0.82 (s, 18H, But); 13C
NMR: l 156.3, 155.8, 147.8, 142.6, 134.4, 132.8, 128.9,
122.2, (Ar), 75.8 (ArOCH2), 34.5 (C(CH3)3), 34.4
(C(CH3)3), 33.3 (CH2), 31.8 (C(CH3)3), 31.1 (C(CH3)3),
30.1, 28.4, 25.4 (CH2); FAB-MS m/z: 1047.9 [M+H]+,
1069.9 [M+Na]+; anal. calcd for C52H70O4S4Br2
(1047.13): C, 59.60; H, 6.69, found: C, 59.68; H, 6.64%.
Compound 2i. Mp 212–214°C; 1H NMR: l 7.76 (s, 2H,
OH), 7.70 (s, 4H, ArH), 6.98 (s, 4H, ArH), 4.90 (t, 4H,
J=6.18, OCH2), 3.98 (t, 4H, J=6.18 BrCH2), 1.37 (s,
18H, But), 0.82 (s, 18H, But); 13C NMR: l 155.8, 155.7,
148.6, 143.1, 134.6, 133, 129.1, 122.2 (Ar), 74.4, 67.3
(CH2), 34.4 (C(CH3)3), 34.3 (C(CH3)3), 31.7 (C(CH3)3),
30.9 (C(CH3)3); FAB-MS m/z: 934.1 [M+H]+; anal. calcd
for C44H54O4S4Br2 (932.51): C, 56.64; H, 5.79, found: C,
56.82; H, 5.74%.
1
Compound 2c. Mp 220–222°C; H NMR: l 7.94 (s, 2H,
OH), 7.67 (s, 4H, ArH), 6.96 (s, 4H, ArH), 4.49 (t, 4H,
J=6.73 OCH2), 2.03 (m, 4H, CH2), 1.58 (m, 4H, CH2),
1.42 (m, 4H, CH2), 1.35 (s, 18H, But), 1.31 (t, 6H, CH3),
1.26 (m, 4H, CH2), 0.89 (m, 8H, CH2), 0.81 (s, 18H, But);
13C NMR: l 156.8, 156.3, 148.1, 142.9, 134.7, 133.1,
129.3, 122.6 (Ar), 76.4, (OCH2), 34.6 (C(CH3)3), 34.4
(C(CH3)3), 32.3 (CH2), 31.9 (C(CH3)3), 31.2 (C(CH3)3),
32.3, 30.4, 29.9, 29.7, 26.2, 23.1 (CH2), 14.5 (CH3); anal.
calcd for C56H80O4S4 (944.79): C, 71.15; H, 8.47, found:
C, 70.79; H, 8.42%.
1
Compound 2d. Mp 208–209°C; H NMR: l 8.17 (s, 2H,
OH), 7.71 (s, 4H, ArH), 7.28 (t, 4H, ArH), 6.98 (s, 4H,
ArH), 6.96 (d, 4H, J=8.20, ArH), 6.92 (t, 2H, ArH),
4.87 (t, 4H, J=4.15, CH2), 4.20 (t, 4H, J=4.20, CH2),
1.37 (s, 18H, But), 0.82 (s, 18H, But); 13C NMR: l 158.9,
156.1, 156.0, 148.2, 142.8, 134.9, 132.9, 129.5, 129.4,
122.4, 121, 114.9 (Ar), 72.9, 67.3 (OCH2), 34.4
(C(CH3)3), 34.2 (C(CH3)3), 31.7 (C(CH3)3), 31.0
(C(CH3)3); FAB-MS m/z: 959.2 [M+H]+, 1044 [M+Rb]+,
1091.9 [M+Cs]+; anal. calcd for C56H64O6S4 (960.19): C,
69.98; H, 6.66, found: C, 69.59; H, 6.71%.
Compound 2j. (Molar ratio of TPP/DEAD:1=2.2). Mp
288–290°C; 1H NMR: l 7.75 (s, 2H, OH), 7.59 (s, 4H,
ArH), 6.93 (s, 4H, ArH), 4.53 (t, 4H, J=5.63, ArOCH2),
3.90 (t, 4H, J=6.45, ClCH2), 2.40 (t, 4H, J=6.16 (CH2),
1.23 (s, 18H, But), 0.75 (s, 18H, But); 13C NMR: l 156.2,
155.9, 148.4, 143.0, 134.6, 133.3, 128.9, 122.1 (Ar), 72.9
(ArOCH2), 42.1 (ClCH2), 34.4 (C(CH3)3), 34.2
Compound 2e. Mp 156–158°C (eluent: hexane–EtOAc=
1
8:2); H NMR: l 8.10 (s, 2H, OH), 7.68 (d, 2H, J=7.95
ArH), 7.63 (m, 4H, ArH), 7.61 (s, 4H, ArH), 7.37 (t, 2H,

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2265
(C(CH3)3), 33.5 (CH2), 31.7 (C(CH3)3), 30.9 (C(CH3)3);
FAB-MS m/z: 872.9 [M+H]+; anal. calcd for
C46H58O4S4Cl2 (872.09): C, 63.28; H, 6.65, found: C,
62.62; H, 6.59%.
[M+K]+, 1129.8 [M+Rb]+, 1177.7 [M+Cs]+; anal. calcd
for C60H68O8S4 (1043.58): C, 69.00; H, 6.52, found: C,
68.55; H, 6.44%.
Compound 3. (molar ratio of TPP/DEAD:1=6, 24 h).
1
Compound 2k. (Molar ratio of TPP/DEAD:1=2.2, 6 h).
Mp 320–322°C; 1H NMR: l 7.92 (m, 4H, phthalimide
ArH), 7.76 (m, 4H, phthalimide ArH), 7.52 (s, 4H, ArH),
7.29 (s, 2H, OH), 7.19 (s, 4H, ArH), 6.15 (s, 4H,
OCH2N), 1.25 (s, 18H, But), 0.96 (s, 18H, But); 13C
NMR: l 167.3 (CO), 155.7, 154.8, 148.3, 142.5, 134.4,
134.2, 133.5, 131.9, 129.1, 123.9, 121.4 (Ar), 77.2 69.7
(ArOCH2), 34.1 (C(CH3)3), 34.0 (C(CH3)3), 31.3
(C(CH3)3), 30.9 (C(CH3)3); FAB-MS m/z: 1038.9 [M+
H]+, 1061.8 [M+Na]+, 1077.8 [M+K]+, 1123.7 [M+Rb]+,
1171.6 [M+Cs]+; anal. calcd for C58H58O8N2S4 (1038.58):
C, 67.03; H, 5.59, found: C, 66.52; H, 5.50%.
Compound 2l. (Obtained quantitatively by treatment of 6
with K2CO3 in a 1:1 mixture of toluene/EtOH under 1 h
reflux). Mp 288–290°C; 1H NMR: l 7.98 (s, 2H, OH),
7.68 (s, 4H, ArH), 7.62 (d, 4H, J=7.3, BnH), 7.33–7.29
(m, 6H, BnH), 6.96 (s, 4H, ArH), 5.49 (s, 4H, ArOCH2),
1.34 (s, 18H, But), 0.79 (s, 18H, But); FAB-MS m/z:
899.5 [M+H]+; anal. calcd for C54H60O4S4 (900.34): C,
71.97; H, 6.66, found: C, 71.78; H, 6.63%.
Mp 326–328°C; H NMR: l 7.36 (s, 8H, ArH), 4.11 (t,
8H, J=8.03, OCH2), 2.56 (t, 8H, J=8.00, BrCH2), 1.31
(s, 36H, But); 13C NMR: l 153.4, 147.5, 128.1, 127.4 (Ar),
76.6, 67.3 (CH2), 34.7 (C(CH3)3), 31.6 (C(CH3)3); anal.
calcd for C48H60O4S4Br4 (1144.19): C, 48.25; H, 5.25,
found: C, 48.02; H, 5.19%.
Compound 4. (molar ratio of TPP/DEAD:1=6, 24 h).
Mp 354°C (hexane–EtOAc=95:5); 1H NMR: l 7.37 (s,
8H, ArH), 4.00 (t, 8H, J=6.78, ArOCH2), 3.20 (t, 8H,
J=6.65, ClCH2), 1.49 (m, 8H, CH2), 1.31 (s, 36H, But);
13C NMR: l 156.6, 146.6, 128.3, 127.6 (Ar), 66.2
(ArOCH2), 42.3, 34.6 (CH2), 32.4 (C(CH3)3), 31.5
(C(CH3)3); anal. calcd for C52H68O4S4Cl4 (1024.43): C,
60.92; H, 6.64, found: C, 60.47; H, 6.60%.
Compound 5. (Molar ratio of TPP/DEAD:1=6, toluene,
1
110°C, 24 h). Mp 220–222°C (hexane–EtOAc=95:5); H
NMR: l 7.27 (s, 8H, ArH), 3.78 (t, 8H, J=7.70,
ArOCH2), 1.24 (s, 36H, But), 1.23 (m, 8H, CH2), 1.19 (m,
16H, CH2), 1.13–1.05 (m, 16H, CH2), 0.98 (m, 8H,
J=6.50, CH2), 0.85 (t, 12H, J=6.75, CH3); 13C NMR: l
156.9, 145.1, 127.9, 127.4 (Ar), 68.7 (ArOCH2), 34.4
(C(CH3)3), 32.1 (CH2), 31.5 (C(CH3)3), 29.9, 29.8, 29.1,
26.1, 22.8, (CH2), 14.3 (CH3); anal. calcd for
C72H112O4S4 (1168.74): C, 73.93; H, 9.58, found: C,
73.46; H, 9.52%.
Compound 2m. (Molar ratio of TPP/DEAD:1=2.2, tolu-
ene, 110°C, 24 h). Mp 178–179°C; [h]D=−10 (c 1,
1
CHCl3); H NMR: l 7.68 (d, 4H, J=9.95 ArH), 7.56 (s,
2H, OH), 7.03 (s, 4H, ArH), 5.15 (q, 2H, J=6.68, OCH),
4.29 (q, 4H, J=6.85, OCH2), 1.89 (d, 6H, J=6.70, CH3),
1.35 (s, 18H, But), 1.32 (t, 6H, CH3), 0.85 (s, 18H, But);
13C NMR: l 171.6, 156.0, 155.7, 147.6, 142.4, 134.5,
132.9, 129.0, 122.3 (Ar), 74.8 (ArOCH), 61.4 (OCH2),
34.1 (C(CH3)3), 33.9 (C(CH3)3), 31.4 (C(CH3)3), 30.7
(C(CH3)3), 18.6, 14.1 (CH3); FAB-MS m/z: 920.7 [M+
H]+, 944 [M+Na]+, 959.9 [M+K]+, 1005.9 [M+Rb]+,
1053.9 [M+Cs]+; anal. calcd for C50H64O8S4 (920.42): C,
65.19; H, 6.95, found: C, 64.72; H, 6.88%.
Compound 2n. (Molar ratio of TPP/DEAD:1=2.2, tolu-
ene, 110°C, 24 h). Mp 201–203°C; [h]D=+76.8 (c 1,
CHCl3); 1H NMR: l 7.63 (m, 4H, ArH), 7.55 (d, 2H,
J=2.43, ArH), 7.48 (d, 2H, J=2.46, ArH), 7.42 (s, 2H,
OH), 7.32 (m, 6H, ArH), 6.90 (d, 2H, J=2.52, ArH),
6.85 (d, 2H, J=2.45, ArH), 6.00 (s, 2H, OCH), 4.22 (q,
4H, J=7.15, OCH2), 1.20 (s, 18H, But), 1.16 (t, 6H,
J=7.09, CH3), 0.72 (s, 18H, But); 13C NMR: l 170.1,
156.0, 155.5, 147.6, 142.3, 134.5, 132.9, 129.0, 122.1 (Ar),
85.4 (OCH2), 61.7 (ArOCH), 34.1 (C(CH3)3), 33.9
(C(CH3)3), 31.4 (C(CH3)3), 30.7 (C(CH3)3), 14.6 (CH3);
FAB-MS m/z: 1045.8 [M+H]+, 1067.9 [M+Na]+, 1083.9
Compound 6. (Molar ratio of TPP/DEAD:1=4, THF, rt,
1
24 h). Mp 234–236°C (hexane–EtOAc=95:5); H NMR:
l 8.02 (s, 2H, ArH), 7.90 (m, 4H, phthalimide ArH), 7.75
(m, 4H, phthalimide ArH), 7.65 (d, 2H, J=7.15, BnH),
7.38 (s, 2H, ArH), 7.35–7.29 (m, 6H, BnH), 7.25 (d, 2H,
J=2.6, ArH), 7.04 (d, 2H, J=7.25, BnH), 6.89 (d, 2H,
J=2.2, ArH), 5.71 (s, 4H, OCH2N), 4.99 (s, 2H, OCH2),
4.97 (s, 2H, OCH2), 1.57 (s, 9H, But), 1.19 (s, 9H, But),
0.80 (s, 18H, But); 13C NMR: l 167.1 (CO), 159.9, 156.8,
156.4, 146.6, 146.1, 144.9, 137.4, 137.1, 136.1, 134.2,
134.1, 133.7, 133.0, 132.0, 130.3, 130.2, 129.6, 128.5,
128.3, 128.1, 128.0, 127.8, 127.1, 123.6 (Ar), 76.0, 72.2,
69.6 (ArOCH2), 34.7, 34.3, 34.1 (C(CH3)3), 31.6, 31.5,
31.1 (C(CH3)3); FAB-MS m/z: 1219.7 [M+H]+; anal.
calcd for C72H70O8S4N2 (1218.40): C, 70.92; H, 5.75,
found: C, 70.78; H, 5.70%.
21. Akdas, H.; Bringel, L.; Bulach, V.; Graf, E.; Hosseini, M.
W.; De Cian, A. Tetrahedron Lett. 2002, 43, 8975–8979.
22. Zeng, X.; Chen, L.; Weng, L.; Ju, H.; He, X.; Zhang,
Z.-Z. J. Chem. Res. (S) 2000, 518–519.