Synthesis of Novel C-Pivot Lariat 18-Crown-6 Ethers and Their Efficient Purification

Article abstract of DOI:10.1055/s-0034-1378790

The syntheses of various lariat ethers including several not previously reported and their efficient purification are presented. The synthesis route brings together reactions from a variety of previous works leading to a robust and generalized approach to these C-pivot lariats. The main steps are condensation of functionalized diols with pentaethylene glycol ditosylate in the presence of potassium as a templating cation. Purification of the final products was achieved without chromatography by extracting from an aqueous potassium hydroxide solution.

Full text of DOI:10.1055/s-0034-1378790

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1977–1980
letter
1977
S. Jana et al.
Letter
Synlett
Synthesis of Novel C-Pivot Lariat 18-Crown-6 Ethers and Their
Efficient Purification
Susovan Jana
O
Vallabh Suresh
OH
R
X
O
O
O
O
Salvatore D. Lepore*
purify via extraction
with KOHaq
OP
R
X
OH
Department of Chemistry, Florida Atlantic University,
777 Glades Road, Boca Raton, FL 33431, USA
slepore@fau.edu
OH
O
Received: 20.04.2015
Accepted after revision: 12.06.2015
Published online: 29.07.2015
project, we required access to gram quantities of 18-crown-
6 (18-C-6) containing side arms possessing a hydroxyl
group including some derivatives not previously reported.
A careful review of the literature revealed a variety of lariat
ether synthesis strategies and purification methods. These
reports used either vacuum distillation or column chroma-
tography as the purification method.10,11 In this letter, we
report our development of an optimized route that takes
advantage of various elements of previous reports to effi-
ciently prepare a series of C-pivot 18-C-6 compounds.
We began with the synthesis of lariats 1d–3d (Scheme
1). Intermediate epoxides 1a–3a were synthesized from re-
action of the appropriate alcohol12 with epichlorohydrin in
aqueous sodium hydroxide in the presence of catalytic
TBAB.13 The resulting epoxides 1a–3a were converted14 into
functionalized diols 1b–3b that then reacted with penta-
ethylene glycol ditosylate and KOt-Bu in THF under reflux
conditions to afford benzyl-protected lariats 1c–3c. These
intermediates were debenzylated under hydrogenation
conditions2c (H2, Pd/C) to afford 18-C-6 lariat ethers 1d–3d
in 55–65% two-step yields after purification.
The overall yields for our lariat products were between
40% and 53%, a substantial improvement over previously re-
ported methods. For example, for compound 1d, synthe-
sized by a number of groups, our overall yield was 53% in
four steps. Fukunishi and coworkers reported overall yields
of 32% and 24%, respectively, for 1d using two different
pathways with product isolation accomplished by chroma-
tography on alumina.2c Others have reported overall yields
of 31% and 35% of 1d using a distillation technique to purify
the final compound.2d–f
DOI: 10.1055/s-0034-1378790; Art ID: st-2015-r0291-l
Abstract The syntheses of various lariat ethers including several not
previously reported and their efficient purification are presented. The
synthesis route brings together reactions from a variety of previous
works leading to a robust and generalized approach to these C-pivot
lariats. The main steps are condensation of functionalized diols with
pentaethylene glycol ditosylate in the presence of potassium as a tem-
plating cation. Purification of the final products was achieved without
chromatography by extracting from an aqueous potassium hydroxide
solution.
Key words 18-crown-6, C-pivot lariat ethers, crown compounds, po-
tassium hydroxide purification, macrocyles
Crown ethers have long been exploited as phase-trans-
fer agents in organic chemistry1 and thus their efficient
preparation has attracted the attention of numerous re-
searchers.2 An exciting variation of crown ethers involves
the inclusion of a side arm on the macrocyclic which often
contains metal-coordinating heteroatoms. These lariat
ethers, first studied by Gokel and co-workers,3 were found
to confer unique cation-binding properties.4 Carbon-pivot
lariat ethers are a subclass of these compounds in which the
side arm (podand) extend from a carbon atom in the mac-
rocycle. These compounds often exhibit increased guest
specificity.5,6
We have recently used lariat ethers as metal-chelating
leaving groups to expedite nucleophilic substitution reac-
tions7 with emphasis on the expedited radiofluorination of
small molecules.8 Following a similar strategy, we have ap-
pended chelating leaving groups to silicon for ultrafast sili-
con radiofluorination using K18F.9 In an attempt to further
improve the efficiency of silicon fluorination, we have be-
gun to use lariat ethers as nucleophilic catalysts. For this
The only synthesis of 5d, reported in the literature, uses
a radical process to functionalize the 18-C-6 with allyl alco-
hol in 8% yield.2h Colera and coworkers reported the synthe-
sis of 7d in an overall yield of 11% in six steps2l compared to
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1977–1980

1978
S. Jana et al.
Letter
Synlett
mixtures to the hydrogenolysis step. The resulting mixture
of debenzylated compounds was then separated on neutral
alumina using a gradient elution of 1–10% 2-propanol–di-
chloromethane or 1–10% MeOH–EtOAc eluent system.
However, this gradient method is a lengthy process requir-
ing copious amounts of solvent (> 3 L for 3 g of crude).
In an attempt to isolate the final lariat products more ef-
ficiently, we sought to take advantage of their metal-chelat-
ing properties to bring about a selective precipitation of the
desired compound from the product mixture. A few reports
demonstrate that complexation followed by precipitation
using KBF4 is a feasible approach.18 Along these lines, we
also found KNO3 to be effective in purifying lariat ether
products by precipitation. However, these methods were
problematic and unreliable on the multigram scale.
O
O
a
b
O
+
Cl
O
Ph
Ph
O
n
HO
n
1a (n = 0) 88%
2a (n = 1) 90%
3a (n = 2) 85%
n = 0, 1, 2
O
Ph
O
n
OH
O
c
O
OH
1c (n = 0)
2c (n = 1)
3c (n = 2)
Ph
O
O
O
n
1b (n = 0) 93%
2b (n = 1) 97%
3b (n = 2) 86%
O
O
O
As an alternative, we developed a simplified extraction
technique using aqueous potassium hydroxide. Thus crude
debenzylated reaction mixtures (ca. 5 g) were stirred with
50 mL of aq KOH (1 M) for 5 min. After this time, the impu-
rities were removed by extraction using ethyl acetate until
TLC showed the absence of any impurity (usually three ex-
tractions). The water layer was then extracted with di-
chloromethane (3 times, monitored by alumina TLC; 4% 2-
PrOH–CH2Cl2 eluent). The organic layer was collected, the
solvent was removed in vacuo, and the resulting material
was passed through a small plug of neutral alumina (10%
O
O
2-step yield
overall yield
O
O
O
O
1d (n = 0) 65%
2d (n = 1) 60%
3d (n = 2) 55%
53%
52%
40%
d
O
HO
n
Scheme 1 Synthesis of lariats 1d–3d. Reagents and conditions: (a) 40%
aq NaOH, TBAB, 0 °C for 1 h and then r.t. for 24 h; (b) 2% H2SO4, r.t., 5 h;
(c) KOt-Bu, pentaethyleneglycol ditosylate, THF, r.t. for 1 h and then re-
flux for 48 h; (d) Pd/C, H2, EtOH, r.t., 48 h.
the 41% overall yield in four steps in this work. In this letter,
we also report for the first time the synthesis of lariats 2d,
3d, 4d, and 6d.
a
b
R
O
n
Ph
R
OH
n
The above route to obtain functionalized diols worked
well for 1d–3d since the starting materials, benzyl alcohol
and its mono- and diethylene glycol derivatives, had rea-
sonable aqueous solubility. This was not the case for the
analogous reactions required to give lariats 4d–7d20 con-
taining alkanol side arms (Scheme 2). The analogous epi-
chlorohydrin addition reactions (not shown) led to low
yields (ca. 10%) even after significant attempts at optimiza-
tion. Therefore, an alternative approach was required. Our
synthesis began with a benzylation step using NaH and
BnBr to obtain alkene 4a–7a.15 Diols 4b–7b were then pre-
pared using OsO4/NMO following a literature procedure.16
Cyclization reactions between various diols and pentaeth-
yleneglycol ditosylate followed by debenzylation afforded
the desired crown ethers in reasonable overall yields (30–
40%).
4a (R = H, n = 2)
5a (R = H, n = 3)
6a (R = H, n = 4)
85%
81%
89%
R = H (n = 2)
R = H (n = 3)
R = H (n = 4)
7a (R = CH2OBn, n = 1) 87%
R = CH2OH (n = 1)
O
OH
O
O
R
O
O
c
R
O
Ph
n
O
n
Ph
OH
O
4b (R = H, n = 2)
5b (R = H, n = 3)
6b (R = H, n = 4)
85%
79%
81%
4c (R = H, n = 2)
5c (R = H, n = 3)
6c (R = H, n = 4)
7b (R = CH2OBn, n = 1) 85%
7c (R = CH2OBn, n = 1)
As mentioned, benzyl lariat ethers 1c–7c19 were formed
by condensation with pentaethylene glycol ditosylate in the
presence of potassium tert-butoxide using the well-known
template effect.17 These reactions usually required more
than 48 hours for all starting material to be consumed.
Upon completion, the reaction mixture contained byprod-
ucts that could not be conveniently separated using flash
chromatography. A variety of traditional eluent systems
and both silica gel and alumina stationary phases were
evaluated to no avail. We carried forward these product
2-step
yield
overall
yield
36%
31%
32%
41%
O
R
O
O
O
O
4d (R = H, n = 2)
5d (R = H, n = 3)
6d (R = H, n = 4)
50%
48%
45%
d
OH
n
7d (R = CH2OH, n = 1) 55%
O
Scheme 2 Synthesis of lariats 4d–7d. Reagents and conditions: (a) NaH,
BnBr, THF, 0 °C to r.t. over 6 h; (b) OsO4, NMO, acetone–H2O, r.t., 12 h;
(c) KOt-Bu, pentaethyleneglycol ditosylate, THF, r.t. for 1 h then reflux
for 48 h; (d) Pd/C, H2, EtOH, r.t., 48 h.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1977–1980

1979
S. Jana et al.
Letter
Synlett
MeOH–EtOAc as eluent) to furnish noncomplexed lariat
products. This process was significantly less tedious and of-
fered nearly identical isolated yields as those based on flash
chromatography.
(7) (a) Lepore, S. D.; Mondal, D. Tetrahedron 2007, 63, 5103.
(b) Lepore, S. D.; Bhunia, A. K.; Cohn, P. J. Org. Chem. 2005, 70,
8117.
(8) Lu, S.; Lepore, S. D.; Li, S. Y.; Mondal, D.; Cohn, P. C.; Bhunia, A.
K.; Pike, V. W. J. Org. Chem. 2009, 74, 5290.
In summary, bringing together reactions from a variety
of previous works, we have developed a robust approach to
a series C-pivot lariat ether compounds. This process in-
volves the condensation of functionalized diols with penta-
ethylene glycol ditosylate in the presence of templating cat-
ions. Purification of the final products was achieved by a
simple extraction method that obviated the need for te-
dious chromatography. We believe that this convenient
synthesis of lariat ethers will facilitate their use as novel bi-
functional catalysts.
(9) Al-huniti, M. H.; Lu, S.-Y.; Pike, V. W.; Lepore, S. D. J. Fluorine
Chem. 2014, 158, 48.
(10) Späth, A.; König, B. Beilstein J. Org. Chem. 2010, 6, 32.
(11) (a) Hu, H.; Bartsch, R. A. J. Heterocycl. Chem. 2004, 41, 557.
(b) Czech, B. P.; Desi, D. H.; Koszuk, J.; Czech, A.; Babb, D. A.;
Robison, T. W.; Bartsch, R. A. J. Heterocycl. Chem. 1992, 29, 867.
(c) Jungk, S. J.; Moore, J. A.; Gandour, R. D. J. Org. Chem. 1983, 48,
1116. (d) Fukunishi, K.; Czeck, B.; Regan, S. L. J. Org. Chem. 1981,
46, 1218. (e) Ikeda, I.; Yamamura, S.; Nakatsuji, Y.; Okahara, M. J.
Org. Chem. 1980, 45, 5355. (f) Czech, B. Tetrahedron Lett. 1980,
21, 4197.
(12) Xiao, Q.; Liu, Y.; Qiu, Y.; Zhou, G.; Mao, C.; Li, Z.; Yao, Z.-J.; Jiang,
S. J. Med. Chem. 2011, 54, 525.
Acknowledgment
(13) de Almeida, C. G.; Reis, S. G.; de Almeida, A. M.; Diniz, C. G.; da
Silva, V. L.; Hyaric, M. L. Chem. Biol. Drug Des. 2011, 78, 876.
(14) Tsujigami, T.; Sugai, T.; Ohta, H. Tetrahedron: Asymmetry 2001,
12, 2543.
We thank the National Institutes of Health (GM110651) for financial
support.
(15) (a) Ginotra, S. K.; Friest, J. A.; Berkowitz, D. B. Org. Lett. 2012, 14,
968. (b) Mantovani, S. M.; Angolini, C. F. F.; Marsaioli, A. J. Tetra-
hedron: Asymmetry 2009, 20, 2635.
Supporting Information
(16) (a) Borg, T.; Tuzina, P.; Somfai, P. J. Org. Chem. 2011, 76, 8070.
(b) Nishizono, N.; Akama, Y.; Agata, M.; Sugo, M.; Yamaguchi, Y.;
Oda, K. Tetrahedron 2011, 67, 358.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1378790.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
(17) Steed, J. W.; Atwood, J. L. Supramolecular Chemistry; John Wiley
and Sons: Chichester, 2009, 2nd ed. 745.
(18) Montanari, F.; Tundo, P. J. Org. Chem. 1982, 47, 1298.
(19) General Procedure for the Synthesis of Benzyl-Protected 18-
C-6 Lariat Ethers 1c–7c
References and Notes
(1) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 2495.
(2) (a) Montanari, F.; Tundo, P. Tetrahedron Lett. 1979, 5055.
(b) Czech, B. Tetrahedron Lett. 1980, 21, 4197. (c) Fukunishi, K.;
Czech, B.; Regen, S. L. J. Org. Chem. 1981, 46, 1218. (d) Jungk, S.
J.; Moore, J. A.; Gandour, R. D. J. Org. Chem. 1983, 48, 1116.
(e) Ikeda, I.; Emura, H.; Okahara, M. Synthesis 1984, 73.
(f) Bĕlohradský, M.; Stibor, I.; Holý, P.; Závada, J. Collect. Czech.
Chem. Commun. 1987, 52, 2500. (g) Zelechonok, J. B.; Orlovskii,
V. V.; Zlotskii, S. S.; Rakhmankulov, D. L. J. Prakt. Chem. 1990,
332, 719. (h) Hiraoka, M. Crown Ethers and Analogous Com-
pounds; Elsevier: Amsterdam, 1992. (i) Ghosh, A. K.; Bilcer, G.;
Schiltz, G. Synthesis 2001, 2203. (j) List, B.; Castello, C. Synlett
2001, 1687. (k) Hu, H.; Bartsch, R. A. J. Heterocycl. Chem. 2004,
41, 557. (l) Colera, M.; Costero, A. M.; Gavina, P.; Gil, S. Tetrahe-
dron: Asymmetry 2005, 16, 2673.
To a solution of benzylated diol 1b–7b (25 mmol) in THF (240
mL) was added KOt-Bu (100 mmol) at r.t. After the mixture was
allowed to react 1 h under a nitrogen atmosphere, a solution of
pentaethylene glycol ditosylate (27.5 mmol) in THF (48 mL) was
added over a period of 1 h with stirring. The mixture was
stirred for an additional 1 h at r.t., refluxed for 24 h, and cooled
to r.t. The volatile solvents were removed by distillation under
reduced pressure. The crude solids were dissolved in H2O, and
the resulting solution was extracted with CH2Cl2 (5 × 20 mL).
The combined organic layer was dried over anhydrous Na2SO4.
After filtration and evaporation, the crude product (approx. 3.5
g) was directly used for the debenzylation in the next step.
(20) General Procedure for the Synthesis of 18-C-6 Lariat Ethers
1d–7d
(3) Gokel, G. W. Crown Ethers and Cryptands; RSC: Oxford, UK,
1991.
To a dry round-bottom flask was added 10% (w/w) of 5% Pd/C
and anhydrous EtOH (200 mL) was added to the reaction flask.
The solution was degassed by bubbling the H2 gas through it
twice. Benzylated lariat ethers 1c–7c (approx. 3.5 g) dissolved in
anhydrous EtOH (20 mL) was added into the reaction flask. The
solution was degassed twice. The reaction mixture was stirred
for 48 h under 1.013 bar of hydrogen. TLC with alumina plates
using 4% 2-PrOH–CH2Cl2 as the eluent indicated the formation
of product (Rf = 0.15). The product mixture was filtered and
concentrated. The crude reaction mixture was then stirred into
KOH aq (1 M, 50 mL) for 5 min. After this time, the impurities
were removed by extraction using EtOAc until TLC showed the
absence of any impurity (usually three extractions). The H2O
layer was then extracted with CH2Cl2 (3 × 20 mL, monitored by
alumina TLC; 4% 2-PrOH–CH2Cl2 eluent). The organic layer was
collected, the solvent was removed in vacuo, and the resulting
(4) (a) Gokel, G. W.; Dishong, D. M.; Diamond, C. J. J. Chem. Soc.,
Chem. Commun. 1980, 1053. (b) Goli, D. M.; Dishong, D. M.;
Diamond, C. J.; Gokel, G. W. Tetrahedron Lett. 1982, 23, 5243.
(c) Gustowski, D. A.; Echegoyen, L.; Goli, D. M.; Kaifer, A.; Gokel,
G. W. J. Am. Chem. Soc. 1984, 106, 1633. (d) Echegoyen, L.;
Delgado, M.; Gatto, V. J.; Gokel, G. W. J. Am. Chem. Soc. 1986, 108,
6825.
(5) Rapi, Z.; Bakó, P.; Drahos, L.; Keglevich, G. Heteroat. Chem. 2014,
26, 63.
(6) (a) Gokel, G. W. Chem. Soc. Rev. 1992, 21, 39. (b) Gokel, G. W.;
Leevy, W. M.; Weber, M. E. Chem. Rev. 2004, 104, 2723.
(c) Gokel, G. W.; Schall, O. F. In Comprehensive Supramolecular
Chemistry; Pergamon Press: New York, 1996, 97.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1977–1980

1980
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Letter
Synlett
material was passed through a small plug of neutral alumina
(10% MeOH–EtOAc as eluent) to furnish noncomplexed lariat
products.
3.58–3.75 (m, 22 H, 11 × CH2), 3.75–3.90 (m, 3 H, 1 × CH2 and 1
× CH). 13C NMR (100 MHz, CDCl3): δ = 34.8 (CH2), 60.1 (CH2OH),
69.4 (CH2O), 70.6 (CH2O), 70.7 (CH2O), 70.77 (CH2O), 70.8
(CH2O), 70.86 (CH2O), 70.9 (CH2O), 71.0 (CH2O), 71.05 (CH2O),
71.7 (CH2O), 74.5 (CH2O), 77.7 (CH). ESI-HRMS: m/z [M + H]
calcd for C14H28O7: 309.1913; found: 309.1908.
2-Hydroxymethyl-18-C-6 (1d)2a–g
Obtained in 65% yield (1.74 g) as a colorless viscous oil. 1H NMR
(400 MHz, CDCl3): δ = 2.93 (s, 1 H, OH), 3.46–3.82 (m, 25 H, 12 ×
CH2 and 1 × CH). 13C NMR (100 MHz, CDCl3): δ = 63.0 (CH2OH),
69.6 (CH2O), 70.6 (CH2O), 70.7 (CH2O), 70.75 (2 × CH2O), 70.8
(CH2O), 70.83 (CH2O), 71.0 (CH2O), 71.03 (CH2O), 71.2 (CH2O),
71.8 (CH2O), 79.4 (CH). ESI-HRMS: m/z [M + H] calcd for
2-Hydroxypropyl-18-C-6 (5d)2h
Obtained in 48% yield (1.31 g) as a colorless viscous oil. 1H NMR
(400 MHz, CDCl3): δ = 1.51–1.68 (m, 4 H, 2 × CH2), 2.30 (s, 1 H,
OH), 3.50–3.76 (m, 24 H, 12 × CH2), 3.83–3.88 (m, 1 H, 1 × CH).
13C NMR (100 MHz, CDCl3): δ = 28.5 (CH2), 28.9 (CH2), 62.8
(CH2OH), 69.6 (CH2O), 70.6 (CH2O), 70.68 (CH2O), 70.7 (CH2O),
70.9 (2 x CH2O), 70.91 (CH2O), 70.92 (CH2O), 70.94 (CH2O), 71.0
(CH2O), 74.2 (CH2O), 79.0 (CH). ESI-HRMS: m/z [M + H] calcd for
C13H26O7: 295.1757; found: 295.1751.
2-[Hydroxy-(ethoxymethyl)]-18-C-6 (2d)
Obtained in 60% yield (1.66 g) as a colorless viscous oil. 1H NMR
(400 MHz, CDCl3): δ = 2.84 (s, 1 H, OH), 3.50–3.84 (m, 29 H, 14 ×
CH2 and 1 × CH). 13C NMR (100 MHz, CDCl3): δ = 61.8 (CH2OH),
69.8 (CH2O), 70.7 (CH2O), 70.73 (CH2O), 70.77 (CH2O), 70.8
(CH2O), 70.83 (CH2O), 70.9 (CH2O), 70.95 (CH2O), 71.0 (CH2O),
71.1 (CH2O), 71.13 (CH2O), 71.4 (CH2O), 72.7 (CH2O), 78.3 (CH).
ESI-HRMS: m/z [M + H] calcd for C15H30O8: 339.2019; found:
339.2017.
C
15H30O7: 323.2070; found: 323.2064.
2-Hydroxybutyl-18-C-6 (6d)
Obtained in 45% yield (1.24 g) as a colorless viscous oil. 1H NMR
(400 MHz, CDCl3): δ = 1.26–1.62 (m, 6 H, 3 × CH2), 2.48 (s, 1 H,
OH), 3.62–3.74 (m, 24 H, 12 × CH2), 3.80–3.85 (m, 1 H, 1 × CH).
13C NMR (100 MHz, CDCl3): δ = 21.9 (CH2), 31.5 (CH2), 32.9
(CH2), 62.7 (CH2OH), 69.5 (CH2O), 70.67 (4 × CH2O), 70.7 (CH2O),
70.8 (CH2O), 70.9 (CH2O), 71.0 (CH2O), 71.1 (CH2O), 74.3 (CH2O),
79.3 (CH). ESI-HRMS: m/z [M + H] calcd for C16H32O7: 337.2226;
found: 337.2221.
2-[Hydroxy-(ethoxy)-(ethoxymethyl)]-18-C-6 (3d)
Obtained in 55% yield (1.56 g) as a colorless viscous oil. 1H NMR
(400 MHz, CDCl3): δ = 2.76 (s, 1 H, OH), 3.47–3.81 (m, 33 H, 16 ×
CH2 and 1 × CH). 13C NMR (100 MHz, CDCl3): δ = 61.8 (CH2OH),
69.9 (CH2O), 70.4 (CH2O), 70.6 (CH2O), 70.7 (2 x CH2O), 70.73
(CH2O), 70.76 (CH2O), 70.8 (CH2O), 70.9 (2 × CH2O), 70.93
(CH2O), 71.0 (CH2O), 71.4 (CH2O), 71.5 (CH2O), 72.6 (CH2O), 78.3
(CH). ESI-HRMS: m/z [M + H] calcd for C17H34O9: 383.2281;
found: 383.2276.
1,2-Dihydroxymethyl-18-C-6 (7d)2l
Obtained in 55% yield (1.24 g) as a colorless viscous oil. 1H NMR
(400 MHz, CDCl3): δ = 2.60 (s, 1 H, OH), 3.44 (s, 1 H, OH), 3.59–
3.84 (m, 26 H, 12 × CH2 and 2 × CH). 13C NMR (100 MHz, CDCl3):
δ = 61.8 (2 × CH2OH), 70.2 (2 × CH2O), 70.3 (2 × CH2O), 70.5 (2 ×
CH2O), 70.9 (2 × CH2O), 70.91 (2 × CH2O), 80.7 (2 × CH). ESI-
HRMS: [M + H] calcd for C14H28O8: 325.1862; found: 325.1857.
2-Hydroxyethyl-18-C-6 (4d)
Obtained in 50% yield (1.35 g) as a colorless viscous oil. 1H NMR
(400 MHz, CDCl3): δ = 1.65–1.85 (m, 2 H, CH2), 3.01 (s, 1 H, OH),
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1977–1980