Modular chiral polyether podands and their lanthanide complexes

Article abstract of DOI:10.1016/j.tet.2003.06.008

A novel series of modular chiral polyether podands derived from enantiomerically pure hydrobenzoin and binaphthol has been prepared using a NaH/15-crown-5 mediated Williamson ether synthesis. These new homochiral ligands form catalytically active complexes with lanthanide triflates, two of which have been characterised by X-ray diffraction.

Full text of DOI:10.1016/j.tet.2003.06.008

Tetrahedron 59 (2003) 10453–10463
Modular chiral polyether podands and their lanthanide complexes
*
Helen C. Aspinall, Nicholas Greeves and Edward G. McIver
*
Department of Chemistry, University of Liverpool, Donnan and Robert Robinson Laboratories, Liverpool L69 7ZD, UK
Received 30 April 2003; accepted 4 June 2003
Abstract—A novel series of modular chiral polyether podands derived from enantiomerically pure hydrobenzoin and binaphthol has been
prepared using a NaH/15-crown-5 mediated Williamson ether synthesis. These new homochiral ligands form catalytically active complexes
with lanthanide triflates, two of which have been characterised by X-ray diffraction.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
Polyether ionophore antibiotics are a class of complex
naturally occurring chiral compounds containing several
oxygen atoms which act as ligands for the complexation of
inorganic cations.1,2 Coordination of the metal cations by
Having demonstrated the utility of the achiral ligands 1 and
2 in catalysis we then set out to prepare C2 symmetric tetra-
and penta- and hexadentate versions of these ligands and
the ionophores facilitates transport across membrane
barriers resulting in a range of important biological activity.
investigate their utility in catalysis. It was essential to
The similarity between alkali metal cations, which are the
prepare ligands with both ether and alcohol end groups so
that they would be compatible with both Diels–Alder and
carbonyl allylation reactions.
guests for ionophore antibiotics, and may be thought of as
featureless charged spheres and lanthanide 3þ cations,
which lack any directional preference for ligand binding, led
us to consider simpler chiral polyether podands as potential
ligands for lanthanide catalysis. They should have sufficient
flexibility3 to accept a range of lanthanide cations and yet be
conformationally biased by the chiral backbone.4
Functionalised oligoethylene glycols are also important
intermediates for the preparation of crown ethers and
cryptands5 and show enantiomeric recognition of secondary
amines.6,7
Earlier work from our laboratories has shown that the use of
polyether or polyethylene glycol ligands can enhance the
catalytic properties of lanthanide triflates by increasing their
solubility in organic solvents and by making them easier to
obtain in anhydrous form. Polyether ligands 1 worked well
for the Diels–Alder reaction, when activity was enhanced
The chiral units we chose for our ligands were hydrobenzoin
compared with that of uncomplexed Ln(OTf)3, whereas the
3 and binaphthol 4, both of which are readily available in
polyethylene glycol ligands 2 worked well for the carbonyl
enantiomerically pure form.9,10
allylation reaction.8
Keywords: polyether podand; lanthanide complex; Williamson ether
synthesis; c2-symmetric; chiral.
*
Corresponding authors. Fax: þ44-151-794-3588;
e-mail: hca@liverpool.ac.uk; ngreeves@liv.ac.uk
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.06.008

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H. C. Aspinall et al. / Tetrahedron 59 (2003) 10453–10463
2. Results and discussion
straightforwardly in high yield as shown in Scheme 1,
utilising our 15-crown-5 mediated etherification
procedure.11
2.1. Hydrobenzoin derived ligands
We prepared a series of tetra-, penta- and hexadentate
ligands 5–8 based on the hydrobenzoin chiral unit as shown
below. In this series of ligands we have a variety of end-
groups (ether or alcohol) and varying degrees of steric bulk
along the ligand backbone. Ligand 9 is a very bulky
1-naphthyl substituted analogue of 8.
The tetradentate diol ligand 6 was prepared according to
Scheme 2.
Our retrosynthetic strategy for the synthesis of the
pentadentate polyether ligand 7 is shown in Scheme 3.
This scheme required efficient routes to singly protected 1,2-
diols which can itselfbe problematic since many methods give
statistical mixtures of mono-, di- and unalkylated material.12
2.2. Alkyl ether strategy
This strategy required the selective monoalkylation of diol 3
followed by coupling to ditosylate 12. We aimed to
synthesise both Me and PMB ethers. In addition to being
a useful ligand in its own right, it was hoped that the PMB
ether could be converted into a chiral tetraethylene glycol
(R¼H), by selective removal of the PMB-groups. Mono-
alkylations of 3 were accomplished using a modified
procedure reported by Ohno et al. as shown in Scheme 4.13
Hydrobenzoin 3 was converted to tin acetal 14 by reaction
with1 equiv.ofdibutyltinoxideinrefluxingtoluene:thewater
was removed by azeotropic distillation into a Dean–Stark
head. Concentration under reduced pressure yielded acetal 14
which was used in the subsequent step without purification.
The tin acetal 14 was opened with CsF in DMF solvent, and
the resulting caesium alkoxide was trapped with either MeI,
or PMB chloride. As chloride is an inferior leaving group to
The tetradentate polyether ligand 5 was synthesised
Scheme 1.
Scheme 2.
Scheme 3.

H. C. Aspinall et al. / Tetrahedron 59 (2003) 10453–10463
10455
Scheme 4.
Scheme 5.
iodide, conversion to alcohol 13 had to be carried out in the
presence of KI catalyst: thus the PMB chloride probably
undergoes an in situ Finkelstein reaction, generating the
much more reactive alkyl iodide. The method of work-up
and purification turned out to be crucial. Quenching
with dilute HCl (aq.) resulted in product which was very
difficult to separate from the residual tin compounds. Non-
aqueous work-up on silica gel proved much more
satisfactory, giving high yields of tin-free material after
chromatography.
DMF and DMSO solvent in the presence of a KI catalyst
produced unacceptably low yields of polyether 7. However
use of our 15-crown-5 etherification procedure11 as shown
in Scheme 5 gave good results.
Our retrosynthetic analysis for the hexadentate hydrobenzoin
derived ligand 8 is shown in Scheme 6. We proposed that
ligands 8a and 8b could be prepared by treatment of ditosylate
15 with the appropriate alcohol 13a or 13b.
We prepared diol 16 in 60% yield by ozonolysis of diene 10
followed by NaBH4 work-up.14,15 This procedure had
previously not been applied to dienes. Ligands 8a and 8b
were prepared in modest yield using our NaH/15-crown-5
methodology.
Early attempts at the etherification were unsuccessful. When
alcohol 13 was deprotonated by sodium hydride followed by
treatment with ditosylate 12 in refluxing THF, only starting
materials could be isolated. Repetition of this reaction in
Scheme 6.
Scheme 7.

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H. C. Aspinall et al. / Tetrahedron 59 (2003) 10453–10463
Scheme 8.
Our strategy for the synthesis of the naphthyl substituted
hexadentate ligand 9 is outlined in Scheme 7.
enantioselective lanthanide catalysis and so we have
investigated its use as a chiral unit in polyether ligands.
The range of ligands we investigated are shown below:
Geometrically pure olefin 22 is not commercially available,
but several procedures involving a simple Wittig reaction
have been reported. However, the highest yield recorded for
the Wittig procedure was only 31%.16 Our revised route to
this olefin is shown in Scheme 8, with the key step being a
Wadsworth–Emmons reaction. Commercially available
1-naphthylene methanol was treated with PBr3, to give
bromide 28 in 91% yield. Subsequent Arbuzov reaction with
triethyl phosphite yielded the phosphonate ester 29.17
Conversion of phosphonate 29 to the alkene was achieved
by deprotonation with NaH, followed by reaction with
1-naphthaldehyde in the presence of a catalytic quantity of
15-crown-5.18 Work-up and purification of this reaction was
very simple, and yields of up to 95% of olefin 22 were
isolated, by simply washing the crude material with chilled
1
methanol. Comparison of the melting point and H NMR
spectrum with the literature16 indicated that the E-alkene
had been formed exclusively.
This procedure compares favourably with other routes to
this compound: it is high yielding, and the work-up and
purification is much easier than simple Wittig reactions, as
triphenylphosphine oxide can be difficult to remove.
Separation of water-soluble sodium diethyl phosphate
from this hydrophobic olefin occurs in the aqueous work-up.
Synthesis of the chiral diol 17 was achieved by the published
procedure using a ‘classical’ Sharpless AD reaction.16
2.3. Binaphthol derived ligands
Binaphthol has been the most successful ligand in
Scheme 9.

H. C. Aspinall et al. / Tetrahedron 59 (2003) 10453–10463
10457
Ligand 23 was prepared by the published method.11 Ligand
24 had been prepared by Cram19 as an intermediate to
chiral crown ethers, but had not been purified or
characterised. Ligand 25 was prepared according to
Scheme 9 by a similar method to that used for the
hydrobenzoin derived ligands 8.
2.4. Complexation
Preparation of complexes for in situ catalytic studies
was achieved by addition of a CH2Cl2 solution of an excess
of ligand to dried Ln(OTf)3. After brief sonication a
homogeneous solution was obtained and in all cases we
found the complexes prepared in this way to be extremely
soluble even in hydrocarbon solvents. Complexes of
ligands 6, 23 and 24 were of poor quality, but in two
cases (complexes 26 and 27 below) we were able to
isolate crystals of a sufficient quality for X-ray diffraction.
The structures of these complexes are shown in Figures 1
and 2.
Complex 26 is eight-coordinate, with one molecule of
coordinated H2O, and Yb and the four O atoms of the
polyether ligand are close to coplanar. The chelate rings
adopt ldl conformations dictated by the chiral substitution
pattern of the ligand. The only other published example of a
lanthanide complex with a triglyme ligand shows ddl
conformations.20 In other respects the coordination of the
polyether ligand in 26 is very similar to that of its achiral
analogue triglyme.
˚
Figure 1. (a) Structure of complex 26 (b) OTf omitted for clarity. Selected distances (A) and angles (8): Yb–O1, 2.325(7); Yb–O2, 2.440(5); Yb–O3,
2.375(9); Yb–O4, 2.353(6); Yb–O8, 2.306(7); O1–Yb–O2, 67.4(3); O2–Yb–O3, 66.2(3); O3–Yb–O4, 67.2(3).
˚
Figure 2. (a) Structure of complex 27 (b) OTf omitted for clarity. Selected distances (A) and angles (8): Eu–O1, 2.420(19); Eu–O2, 2.550(13); Eu–O3,
2.39(2); Eu–O4, 2.487(16); Eu–O5, 2.444(17); O1–Eu–O2, 63.2(8); O2–Eu–O3, 65.7(8); O3–Eu–O4, 64.0(6); O4–Eu–O5, 62.8(5).

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H. C. Aspinall et al. / Tetrahedron 59 (2003) 10453–10463
There are several examples of lanthanide complexes with
achiral tetraglyme ligands, but complex 27 is the first
published example of a chiral version of these complexes. In
achiral complexes the conformations of chelate rings are
essentially random; in complex 27 (as in complex 26) the
chiral substituents dictate that the hydrobenzoin derived
chelateringsadoptadconformation.TheEuatomandO1,O2,
O3, O4 are almost to coplanar; O5 is significantly displaced
from this plane and the Eu–O5 distance is somewhat longer
than the Eu–O1 distance. Similar distortions from planarity
have been observed in complexes of lanthanides with
tetraglyme, and probably arise in order to minimise steric
interactions between the terminal OMe groups of the
ligand.8,21–23 These steric interactions are expected to be
greater for the smaller, later lanthanides and indeed
measurement of stability constants for lanthanide tetra-
glyme complexes has shown a significant decrease in
stability from Tb–Lu.24
Sodium hydride (60% dispersion in mineral oil, 0.50 g,
12.61 mmol, 2.7 equiv.) was weighed into a 50 ml Schlenk
flask containing a magnetic stirrer bar, and washed
repeatedly with n-hexane. To a stirred suspension of the
base in anhydrous THF (15 ml) at 08C was slowly added
(via cannula) a solution of (S,S)-hydrobenzoin 3 (1.0 g,
4.67 mmol, 1 equiv.) in anhydrous THF (4 ml). After the
effervescence had subsided the flask was fitted with a reflux
condenser before adding 15-crown-5 (2.28 ml, 9.34 mmol,
2 equiv.) followed by 1-methoxy-2-(toluene-4-sulfonyl-
oxy)ethane30 (3.28 g, 14.24 mmol, 3 equiv.). The mixture
was allowed to warm to room temperature over 2 h, before
refluxing for a further 12 h. Most of the THF was removed
under reduced pressure, before cooling the flask in ice and
quenching the excess sodium hydride with brine (10 ml)
[CARE!]. The residue was extracted into Et2O (4£15 ml)
and the combined ethereal extracts were washed
(brine), dried (MgSO4), filtered and concentrated on
the rotary evaporator to give a yellow oil. Purification by
flash chromatography (eluent: petroleum ether–Et2O 4:1)
yielded a colourless oil (1.40 g, 91%); [a]1D7¼þ278 (c¼1.70,
CHCl3); C20H30O4N [MþNH4]þ requires 348.21748, found
3. Conclusions
We set out to prepare a series of modular chiral polyether
podands which would be capable of forming complexes with
lanthanide triflates of a range of sizes from La to Yb. The
ligand synthesis has been achieved and we have shown that
these ligands will indeed coordinate to a range of Ln(OTf)3.
Crystal structures have been determined for a Yb(OTf)3
complex with a tetradentate podand and a Eu(OTf)3 complex
with a pentadentate podand. We have found Ln(OTf)3
complexes with all of these ligands show Lewis acidity, but
enantioselectivitiesintheDiels–Alderandcarbonylallylation
reactions were very poor (generally ,5%). Although a degree
of preorganisation has been achieved in these ligands via the
chiral substituents, the flexibility required to allow coordi-
nation to the full range of Ln3þ ions means that chiral binding
sites are not sufficiently well-defined to achieve good
enantioselectivities in catalytic reactions. The necessary
degreeofstructuralrigiditycanbeachievedusingmacrocyclic
ligands,25 although such ligands may be applicable only to a
limited range of metal radii. Although our new chiral podands
have not been effective in enantioselective Lewis acid
catalysis it is worth noting that complexes of Sm(III) with
chiral diols related to 6, 7 and 23 have been used as chiral
proton sources resulting in ees of up to 93%.26–28 The very
properties that make lanthanides attractive for catalytic
applications (e.g. labile Ln–ligand bonds, flexible coordi-
nation geometry) make it extremely difficult to define an
effective chiral binding site for substrates in catalytic
reactions.29 The most effective and versatile ligands for
enantioselective lanthanide catalysis have so far been pybox
and binaphthol which are bothrathermorerigidthanour chiral
podands. The unique coordination chemistry of the lantha-
nides means that structural rigidity in ligands will generally be
required in order to define effective chiral binding sites.
348.21723; Rf (petroleum ether–EtOAc 4:6) 0.30; nmax
/
cm21 (neat) 3200–2900 (C–H); dH (CDCl3) 7.18–6.99
(10H, m, aromatic), 4.50 (2H, s, H-1), 3.58–3.47 (8H, m,
H-2 and 3), 3.33 (6H, s, CH3£2); dC (CDCl3) 138.46,
127.54, 127.32 and 127.06 (aromatic), 85.91 (C-1), 71.59
and 68.495 (C-2 and 3), 58.45 (CH3£2); m/z (CI) 348.2
(26%, [MþNH4]þ), 272.2 (30%, [M2CH2CH2OCH3þ
H]þ), 255.2 (100%, [M2OCH2CH2OCH3–H]þ).
4.1.2. (5S,6S)-5,6-Diphenyl-4-7-dioxa-1,9-decadiene 10.
Sodium hydride (60% dispersion in mineral oil, 2.80 g,
70.05 mmol, 3 equiv.) was placed in a 250 ml round
bottomed flask containing a magnetic stirrer, and repeatedly
washed with, and then suspended in anhydrous THF
(100 ml). The reaction vessel was cooled in an ice–water
bath whilst (S,S)-hydrobenzoin 3 (5.00 g, 23.35 mmol,
1 equiv.) in THF (50 ml) was carefully added. After the
initial effervescence had ceased, a reflux condenser was
fitted and allyl bromide (7.05 ml, 81.75 mmol, 3.5 equiv.)
was introduced. After refluxing for 2 h, the mixture was
cooled to room temperature, the solvent was removed under
reduced pressure and the residue was quenched with water
(50 ml) [CARE!]. The mixture was extracted with Et2O
(3£50 ml), and the combined ethereal extracts were washed
(brine), dried (MgSO4), filtered and concentrated on a rotary
evaporator to give a pale yellow oil. Purification by flash
chromatography (eluent petroleum ether–Et2O 9:1) gave a
colourless oil, (6.7 g, 98%). Data is consistent with
literature for racemate:31 [a]D21¼þ6.78 (c¼2.23, DCM); Rf
(petroleum ether–Et2O 9:1) 0.31; dH (CDCl3) 7.19–7.00
4. Experimental
4.1. General
4.1.1. (4S,5S)-4,5-Diphenyl-1,8-dimethoxy-3-5-dioxa-
octane 5.

H. C. Aspinall et al. / Tetrahedron 59 (2003) 10453–10463
10459
(10H, m, aromatic), 5.86 (2H, ddt, J¼17.6, 10.5, 5.5 Hz,
H-3), 5.22 (2H, ddt, J¼17.6, 1.7, 1.7 Hz, H-4trans), 5.11 (2H,
ddt, J¼10.5, 1.7, 1.7 Hz, H-4cis), 4.53 (2H, s, H-1), 4.06–
3.81 (4H, m, H-2); dC (CDCl3) 138.8, 135.1, 128.0 and
127.7 (aromatic), 127.5 (C-3), 116.4 (C-4), 85.0 (C-1), 70.2
(C-2); m/z (CI) 312 (1%, [MþNH4]þ), 237 (100%,
[M2OCH2CHvCH2]þ).
(50 ml). Upon dissolution of the gummy residues, the
aqueous layer was extracted into Et2O (4£30 ml), and the
combined organic extracts were washed (brine), dried
(MgSO4), filtered and concentrated under reduced pressure.
Purification of the thick yellow syrup by flash chromato-
graphy (eluent: petroleum ether–Et2O 4:1) followed by
recrystallisation from n-hexane–EtOAc yielded a white
crystalline solid, (0.91 g, 50%); mp 157–1598C;
[a]1D9¼227.58 (c¼1.85, DCM); (found: C, 83.18; H,
6.35%. C42H38O4 requires C, 83.14; H, 6.31%); Rf
(petroleum ether–EtOAc 1:4) 0.38; nmax/cm21 (nujol)
3550 (O–H), 3245–2825 (C–H); dH (CDCl3) 7.36–6.86
(30H, m, aromatic), 4.45 (2H, s, H-1), 4.06–3.58 (4H, AB-
system, J¼9.9 Hz, H-2) and 3.50 (2H, s, OH); dC (CDCl3)
144.6, 144.5, 128.1, 127.8, 127.1, 126.9 and 126.3
(aromatic), 87.4, 78.0 and 76.0; m/z (FAB) 629.1 (0.1%,
[MþNa]þ), 393.1 (2%, [M2OCH2C(OH)(Ph)2]þ), 197
(89%, [M2CH2C(OH)(Ph)2]þ).
4.1.3. (4S,5S)-4,5-Diphenyl-3-6-dioxaoctane-1,8-
dimethylester 11.
A 100 ml round bottomed flask charged with 2.5 M
methanolic NaOH solution (9.5 ml), DCM (38 ml) and
diene 10 (0.50 g, 1.70 mmol) was cooled to 2788C in an
acetone–dry ice bath. Ozone was passed through the
solution for 5 h until the bright yellow solution changed to
pale blue, then the excess ozone was displaced by bubbling
argon through the solution for 5 min. The mixture was
neutralised with dilute hydrochloric acid before partitioning
between water (50 ml) and DCM (50 ml). After extraction
of the aqueous phase with DCM (3£50 ml) the combined
organic extracts were washed (brine), dried (Na2SO4),
filtered and concentrated under reduced pressure. The
translucent white paste was purified by flash chromato-
graphy (gradient elution with petroleum ether–Et2O from
8:2 to 1:1) to yield a colourless oil, (0.33 g, 53%);
[a]1D9¼þ39.08 (c¼1.7, DCM); (found: C, 67.24; H, 6.25%.
C20H22O6 requires C, 67.03; H, 6.19%); Rf (petroleum
ether–Et2O 3:2) 0.22; nmax/cm21 (neat) 3064–2911 (C–H),
1757 (CvO); dH (CDCl3) 7.27–6.91 (10H, m, aromatic),
4.73 (2H, s, H-1), 4.19 and 4.08 (4H, AB system J¼16.5 Hz,
H-2), 3.70 (6H, s, OCH3); dC (CDCl3) 170.8 (CvO), 137.2
and 128.1–127.9 (m, aromatic), 86.2 (C-1), 66.9 (C-2), 51.7
(OCH3); m/z (CI) 376.2 (100%, [MþNH4]þ), 269 (45%,
[M2OCH2CO2CH3]þ).
4.2. General procedure for tin acetals 14
A 250 ml round bottomed flask charged with dibutyltin
oxide (26.46 mmol), the appropriate diol (26.46 mmol),
toluene (ca. 125 ml) and a magnetic stirrer bar was fitted
with a Dean–Stark head. The mixture was refluxed at ca.
1258C under argon until all of the water had been removed
azeotropically (typically 3 h). Solvent removal under
reduced pressure gave a solid, which was dried under
vacuum for 12 h at 858C. The tin acetals, obtained in
quantitative yield, were used in the subsequent step without
further purification.
4.3. General procedure for monoalkylation of aryl diols
4.1.4. (4S,5S)-1,1,4,5,8,8-Hexaphenyl-3,6-dioxa-1.8-octa-
nediol 6.
Tin acetal (11.22 mmol, 1 equiv.), caesium fluoride and
potassium iodide were weighed into a 100 ml Schlenk flask
containing a magnetic stirrer bar, and dried under vacuum
for 2 h at room temperature. Dry DMF (40 ml) followed the
alkyl halide were added and the mixture was stirred under
nitrogen at room temperature for a further 19 h. The
gelatinous suspension was concentrated under reduced
pressure to give a yellow solid, which was extracted into
hot EtOAc (50 ml), and filtered through a sintered glass
funnel, thoroughly washing the white residue with a further
50 ml of hot EtOAc. The filtrate was concentrated onto
silica gel and subjected to flash chromatography (eluent:
petroleum ether–EtOAc).
A 50 ml three-necked flask charged with magnesium
turnings (0.73 g, 29.9 mmol, 10 equiv.), anhydrous Et2O
(10 ml), a crystal of I2 and a magnetic stirrer bar was
equipped with a stopper, a rubber septa and a reflux
condenser. Bromobenzene (2.52 ml, 23.92 mmol, 8 equiv.)
in anhydrous ether (10 ml) was carefully added by syringe at
such a rate to maintain a gentle reflux. After addition was
complete the mixture was heated under reflux for a further
40 min. The reaction vessel was cooled in ice as diester 11
(1.07 g, 2.99 mmol, 1 equiv.) in Et2O (10 ml) was slowly
added by syringe. After heating under reflux for 17 h, the
flask was transferred to an ice bath and the excess Grignard
reagent was quenched with saturated ammonium chloride
solution (10 ml) [CARE!]. The mixture was partitioned
between Et2O (50 ml) and 2 M aqueous hydrochloric acid
Quantities and chromatography eluent for each alcohol are
shown below:
Alcohol CsF (equiv.) KI (equiv.) Alkyl halide (equiv.) Eluent ratio
13a
13b
21
1.26
1.19
1.19
None
1.33
1.33
MeI (4)
PMBCl (1.33)
PMBCl (1.33)
4:1
9:1
3:1

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H. C. Aspinall et al. / Tetrahedron 59 (2003) 10453–10463
by reaction of alcohol 13b (1.6 g, 4.8 mmol, 2.2 equiv.)
with diethyleneglycol ditosylate (0.9 g, 2.16 mmol,
1 equiv.) as outlined for polyether 7a. Reaction time: 6 h
at room temperature. Purification by flash chromatography
(eluent: petroleum ether–Et2O 3:1) yielded a colourless
syrup (1.07 g, 67%); [a]2D0¼þ32.78 (c¼1.27, DCM);
(found: C, 77.74; H, 6.86%. C43H50O7 requires C, 78.24;
4.3.1. (1S,2S)-1,2-Diphenyl-2-methoxyethanol 13a. White
solid (2.27 g, 89%). Data consistent with literature.32
4.3.2. (1S,2S)-1,2-Diphenyl-2-(4-methoxybenzyl)ethanol
13b. Cream solid (2.71 g, 72%); mp 85–878C; [a]2D0¼
þ18.78 (c¼1.24, DCM); (found: C, 78.83; H, 6.61%.
C22H22O3 requires C, 79.02; H, 6.63%); Rf (petroleum
ether–Et2O 3:2) 0.31; nmax/cm21 (nujol) 3524 (O–H),
3032–2925 (C–H); dH (CDCl3) 6.84–7.24 (14H, m,
aromatic), 4.69 (1H, dd, J¼8.24, 1.65 Hz, H-1), 4.46 and
4.25 (2H, AB system, J¼11.0 Hz, OCH2C6H4OMe), 4.32
(1H, d, J¼8.24 Hz, H-2), 3.80 (3H, s, CH3), 3.52 (1H, d,
J¼1.65 Hz, OH); dC (CDCl3) 159.5, 139.4, 137.8, 129.9,
129.7, 128.2, 128.1, 128.0, 127.9, 127.7, 127.4 and 114.0
(aromatic), 86.7 (C-2), 78.6 (C-1), 70.6 (OCH2C6H4OMe)
and 55.3 (OCH3); m/z (CI) 352.1 (3%, [MþNH4]þ), 214
(25%, [M2CH2(C6H4OMe)þH]þ).
H, 6.82%); Rf (petroleum ether–EtOAc 1:1) 0.70; nmax
/
cm21 (neat) 3105–2822 (C–H); dH (CDCl3) 7.18–6.76
(28H, m, aromatic), 4.49 (4H, s, H-1 and 2), 4.46 and 4.27
(4H, AB system, JAB¼12.1 Hz, CH2Ar£2), 3.77 (6H, s,
OCH3£2), 3.48 (8H, m, H-3 and 4); dC (CDCl3) 159.2,
139.0, 138.9, 130.8, 129.1, 128.1, 127.9, 127.75, 127.7,
127.5, 127.4 and 113.7 (aromatic), 86.3 and 84.7 (C-1 and
2), 70.6 and 69.2 (C-3, 4, and 55.3; m/z (FAB) 761.2 (0.5%,
[MþNa]þ), 739.3 (0.2%, [MþH]þ).
4.3.6. (4S,5S)-4,5-Diphenyl-3,6-dioxa-1,8-octanediol 16.
Diene 10 (5.89 g, 20.0 mmol) was placed in a 100 ml round
bottomed flask containing a magnetic stirrer bar and
dissolved in methanol (60 ml). After cooling to 2788C,
ozone was bubbled through the solution for 2.5 h, until a
permanent blue colour had developed. The excess ozone
was displaced by passing argon through the solution for
10 min, before warming to 08C. Sodium borohydride
(0.77 g, 20.0 mmol) was carefully added in portions and
the resulting mixture was stirred for 2 h. After quenching
with 2 M HCl (20 ml) and the solvents were removed under
reduced pressure to give a white residue which was
extracted with hot chloroform (3£50 ml). The organic
solution was dried (MgSO4), and concentrated under
reduced pressure gave a thick white paste. Purification by
flash chromatography (eluent: EtOAc), gave a colourless
oil, (3.64 g, 60%). Data are consistent with literature for
racemate:31 [a]D21¼þ288 (c¼0.5, CHCl3); (lit. for (4R,5R)-
16: [a]D¼2198 (c¼0.8, CHCl3)); C18H26O4N requires
320.18618, found 320.18662; Rf (Et2O) 0.21; nmax/cm21
(neat) 3410 (OH) and 3087–2871 (C–H); dH (CDCl3)
7.20–7.01 (10H, m, aromatic), 4.48 (2H, s, H-1), 3.78–3.41
(8H, m, H-2 and 3), 3.00 (2H, br s, OH£2); dC (CDCl3)
138.3, 128.1, 128.0 and 127.6 (aromatic), 86.9 (C-1), 71.1
(C-2), 61.8 (C-3); m/z (CI) 320.1 (100%, [MþNH4]þ),
258.1 (68%, [M2CH2CH2O]þ), 241.1 (58%, [M2OCH2-
CH2OH]þ).
4.3.3. (1R,2R)-1,2-(1-Naphthyl)-2-(4-methoxybenzyl)-
ethanol 21. Pale yellow oil, (3.70 g, 76%); [a]1D9¼þ118
(c¼1.91, DCM); C30H30NO3 [MþNH4]þ requires
452.22257, found 452.22289; Rf (petroleum ether–EtOAc
1:1) 0.69; n/cm21 (neat) 3549 (OH), 3052–2838 (CH),
1613, 1597, 1586, 1513; dH (CDCl3) 7.95–6.83 (18H, m,
aromatic), 5.74 (1H, dd, J¼8.3, 1.65 Hz, H-1), 5.33 (1H, d,
J¼8.3 Hz, H-2), 4.56–4.30 (2H, AB system J¼11 Hz,
–OCH2C6H4OCH3), 3.84 (3H, s, OCH3) and 3.81 (1H, d,
J¼1.65 Hz,OH); dC (CDCl3) 159.4, 135.9–123.4 (m) and
114.0 (aromatic), 83.8 (C-2), 75.2 (C-3), 70.8 (–OCH2C6-
H4OCH3), 55.4 (CH3); m/z (CI) 452.3 (4%, [MþNH4]þ),
434.3 (3%, Mþ), 314.2 (77%, [M2CH2C6H4OCH3þH]þ).
4.3.4. (1S,2S,10S,11S)-1,2,10,11-Tetraphenyl-1,11-
dimethoxy-3,5,9-trioxaundecane 7a. Sodium hydride
(60% dispersion in mineral oil, 0.36 g, 9.00 mmol,
3 equiv.) was weighed into a 25 ml Schlenk flask containing
a magnetic stirrer and repeatedly washed with hexane. To a
stirred suspension of the base in dry THF (2 ml) at 08C was
slowly added (via cannula) a solution of alcohol 13a (1.50 g,
6.58 mmol, 2.2 equiv.) in dry THF (1 ml). 15-Crown-5
(1.52 ml, 7.5 mmol, 2.5 equiv.) was slowly added, and after
the mild effervescence had subsided, diethyleneglycol dito-
sylate (1.26 g, 2.96 mmol, 1 equiv.) was added to the alkoxide
solution. The flask was fitted with a reflux condenser, and
reaction mixture was heated to 808C for 5 h. On allowing the
mixture to cool to room temperature the solvent was removed
under reduced pressure, before quenching with brine (10 ml)
[CARE!] and extracting into Et2O (3£15 ml). The combined
ethereal extracts were dried (MgSO4), filtered and concen-
trated under reduced pressure to give a yellow gel. Purification
by flash chromatography (eluent petroleum ether–Et2O 4:1)
yielded a colourless oil (1.26 g, 73%); [a]2D5¼þ348 (c¼1.44,
CHCl3); C34H42O5N [MþNH4]þ requires 544.30630, found
544.30707; Rf (petroleum ether–Et2O 1:1) 0.52; nmax/cm21
(neat) 2900–3200 (C–H); dH (CDCl3) 7.14–7.01 (20H, m,
aromatic), 4.48–4.30 (4H, AB system, J¼6.6 Hz, H-1 and 2),
3.51 (8H, m, H-3 and 4), 3.25 (6H, s, CH3£2); dC (CDCl3)
138.9, 138.6 and 127.9–127.4 (m, aromatic), 87.5 and 86.2
(C-1 and 2), 70.4 and 68.7 (C-3 and 4), 57.3 (CH3£2); m/z (CI)
544.4 (100%, [MþNH4]þ).
4.3.7. (4S,5S)-4,5-Diphenyl-1,8-bis(p-toluenesulfonyl-
oxy)-3,6-dioxaoctane 15. To a solution of diol 16 (0.80 g,
2.64 mmol, 1 equiv.) in DCM (25 ml) was added toluene-p-
sulfonyl chloride (2.5 equiv.), triethylamine (2.2 equiv.) and
DMAP (0.1 equiv.). The mixture was stirred at room
temperature for 48 h and was then quenched with saturated
aqueous NH4Cl (25 ml). After extraction of the aqueous
layer with DCM (3£25 ml), the combined organic extracts
were washed (brine), dried (MgSO4), filtered and concen-
trated under reduced pressure to give a brown oily solid.
Purification by flash chromatography (eluent EtOAc–
petroleum ether 1:4) yielded a colourless oil (1.48 g,
91%). Data are consistent with literature for racemate:31
[a]D21¼þ6.68 (c¼1.06, Me2CO), lit. [a]2D1 for (R,R)-61
24.68 (c¼0.5, Me2CO); (found: C, 62.95; H, 5.63%.
C32H34O8S2 requires C, 62.93; H, 5.61%); Rf (petroleum
ether–EtOAc 1:1) 0.73; dH (CDCl3) 7.75 and 7.31 (8H,
AA0BB0 system, J¼8.24, 2.2 Hz, (p-MeC6H4SO23 )£2),
4.3.5. (1S,2S,10S,11S)-1,2,10,11-Tetraphenyl-1,15-di(4-
methoxybenzyloxy)-3,5,7-trioxaundecane 7b. Prepared

H. C. Aspinall et al. / Tetrahedron 59 (2003) 10453–10463
10461
7.14–6.84 (10H, m, Ph£2), 4.35 (2H, s, H-1), 4.14–4.09
(4H, m, H-3), 3.59–3.55 (4H, m, H-2) and 2.45 (6H, s,
OCH£2); m/z (FAB) 632.9 (0.1%, [MþNa]þ), 394.9 (6%,
[M2OCH2CH2OTs]þ).
solid was repeatedly washed with chilled MeOH and dried
under vacuum to give a pale yellow UV-fluorescent solid,
(11.38 g, 95%). Data are consistent with literature:16 mp
158–1618C (found: C, 93.97; H, 5.75%. C22H16 requires C,
94.25; H, 5.75%); dH (CDCl3) 8.30–8.23 (2H, m), 7.93–
7.82 (8H, m) and 7.59–7.49 (6H, m); m/z (EI) 280 (100%,
Mþ).
4.3.8. (1S,2S,7S,8S,13S,14S)-1,2,7,8,13,14-Hexaphenyl-
1,14-dimethoxy-3,6,9,12-tetraoxatetradecane 8a. Di-
tosylate 15 (2.09 g, 3.27 mmol, 1 equiv.) was coupled to
alcohol 13a (1.71 g, 7.20 mmol, 2.2 equiv.) as outlined for
polyether 7a. Reaction time 18 h under reflux. Purification
by flash chromatography (eluent: petroleum ether–EtOAc
9:1) yielded a colourless oil, (1.26 g, 51%); [a]2D0¼þ32.48
(c¼0.56, CHCl3); (found: C, 79.34; H, 7.08%. C48H50O6
requires C, 79.75; H, 6.97%); Rf (petroleum ether–EtOAc
1:1) 0.69; nmax/cm21 (neat) 3089–2870 (C–H), 1493, 1453;
dH (400 MHz, CDCl3) 7.16–7.09 and 7.01–6.94 (30H, m,
aromatic), 4.49 (2H, s, H-1), 4.47 and 4.29 (4H, AB system
JAB¼6.59 Hz, H-4 and 5), 3.56–3.43 (8H, m, H-2 and 3),
3.27 (6H, s, CH3£2); dC (CDCl3) 138.8–138.6 (m) and
128.1–127.3 (m, aromatic), 87.6, 85.8 and 85.6 (C-1,4 and
5), 68.8 (C-2 and 3), 57.3 (OMe); m/z (FAB) 745.4 (1%,
[MþNa]þ).
4.3.11. (5R,6R)-5,6-Di(1-naphthyl)-4-oxa-6-(p-methoxy-
benzyloxy)hex-1-ene 20. Sodium hydride (60% dispersion
in mineral oil, 0.31 g, 7.02 mmol, 2 equiv.) was placed in a
100 ml round bottomed flask containing a magnetic stirrer
bar, and repeatedly washed with, and suspended in
anhydrous THF (10 ml). The reaction vessel was cooled in
an ice–water bath as alcohol 21 (1.7 g, 3.91 mmol, 1 equiv.)
in THF (20 ml) was carefully added. After the initial
effervescence had ceased, a reflux condenser was fitted and
allyl bromide (500 ml, 5.86 mmol, 1.5 equiv.) was added.
The mixture was heated under reflux for 2 h and then stirred
at room temperature overnight. After solvent removal under
reduced pressure the residue was quenched with water
(50 ml) [CARE!]. The mixture was extracted with Et2O
(3£50 ml), and the combined ethereal extracts washed
(brine), dried (MgSO4), filtered and concentrated on a rotary
evaporator to give a colourless oil which was found to be
analytically pure, (1.85 g, 100%); C33H34NO4 ([MþNH4]þ)
requires 492.25387, found 492.25385; Rf (petroleum ether–
Et2O 9:1) 0.20; nmax/cm21 (neat) 3051–2860 (C–H), 1644
(CvC) and 1513; dH (CDCl3) 8.25–8.05 (2H, m), 7.74–
7.57 (4H, m), 7.45–7.15 (8H, m), 7.04 (2H, m) and 6.74–
6.70 (2H, m, aromatic), 5.89–5.70 (1H, ddt, J¼17.0, 10.5,
5.5 Hz, H-3), 5.50 (2H, s, H-1 and 2), 5.13 (1H, ddt, J¼17.0,
1.7, 1.6 Hz, H-5trans), 5.04 (1H, ddt, J¼10.5, 1.7, 1.5 Hz,
H-5cis), 4.53–4.24 (2H, AB system, J¼11.55 Hz,
–OCH2Ar), 4.05–3.81 (2H, m, H-3), 3.76 (3H, s, OCH3);
dC (CDCl3) 159.0, and 135.1–124.0 (m, aromatic), 126.8
(C-4), 116.4(C-5),113.6(aromatic), 82.6and81.0(C-1and2),
70.8 and 70.5 (C-3 and –OCH2Ar) and 55.3 (OCH3); m/z (CI)
492.3 (2%, [MþNH4]þ), 434.4 (2%, [M2CH2vCHCH2þ
H]þ), 354.2 (4%, [M2CH2C6H4OCH3þH]þ).
4.3.9. (1S,2S,7S,8S,13S,14S)-1,2,7,8,13,14-Hexaphenyl-
1,14-di(4-methoxybenzyloxy)-3,6,9,12-tetraoxatetra-
decane 8b. Ditosylate 15 (1.29 g, 2.15 mmol, 1 equiv.) was
coupled to alcohol 13b (1.49 g, 4.65 mmol, 2.2 equiv.) as
outlined for polyether 7a. Reaction time 67 h under reflux.
Purification by flash chromatography (eluent: petroleum
ether–EtOAc 9:1) gave a colourless oil, (0.64 g, 33%);
[a]2D1¼þ20.78 (c¼1.3, DCM); (found: C, 79.24; H, 6.65%.
C62H62O8 requires C, 79.63; H, 6.68%); Rf (petroleum
ether–EtOAc 1:1) 0.69; n/cm21 (neat) 3080–2875 (C–H),
1483, 1456, 1114 (C–O); dH (400 MHz, CDCl3) 7.20–7.06
(26H, m), 6.99–6.94 (8H, m) and 6.81–6.78 (4H, m,
aromatic) 4.52 and 4.29 (4H, AB system, J¼11.6 Hz,
OCH2Ar£2), 4.46 (2H, s, H-1), 4.43 and 4.48 (4H, AB
system, H-4 and 5), 3.77 (6H, s, OCH3£2), 3.56–3.42 (8H,
m, H-2 and 3); dC (CDCl3) 159.1, 139.0, 138.8, 129.1,
128.2–127.2 (m) and 113.7 (aromatic), 85.9, 85.7 and 84.7
(C-1,4 and 5), 70.6 (OCH2C6H4OCH3), 69.0 (C-2 and 3)
and 55.3 (OCH3); m/z (FAB) 957.3 (0.1%, [MþNa]þ).
4.3.12. (4R,5R)-4,5-Di(1-naphthyl)-3-oxa-5-(p-methoxy-
benzyloxy)pentan-1-ol 19. Olefin 20 (1.3 g, 2.71 mmol,
1 equiv.) was dissolved in THF (130 ml) and water (30 ml)
in a 250 ml round bottomed flask. The mixture was stirred at
room temperature whilst OsO4 solution (2.5% in t-BuOH,
520 ml, 50.7 mmol) was added, and stirred for a further
30 min, during which time the solution turned dark brown.
NaIO4 (1.47 g, 6.87 mmol, 2.5 equiv.) was slowly added
over 20 min, and the mixture was stirred for a further 24 h at
room temperature. The flask was chilled to 08C prior to
addition of NaBH4 (0.62 g, 16.26 mmol, 6 equiv.) [CARE!].
After stirring at room temperature for a further 48 h, sodium
sulfite (0.34 g, 2.71 mmol, 1 equiv.) was added and the
solvent was removed under reduced pressure. The residue
was partitioned between 1 M HCl (30 ml) and DCM
(50 ml), and the aqueous phase was extracted with DCM
(4£50 ml).The combined organic extracts were washed with
water (2£100 ml), dried (MgSO4), filtered and concentrated
under reduced pressure to give a red–brown oil. Purification
by flash chromatography (eluent: petroleum ether–EtOAc
7:3) to give a colourless syrup, (0.91 g, 70%); [a]1D7¼28.98
(c¼0.73, CHCl3); C32H34NO4 [MþNH4]þ requires
4.3.10. (E)-1,2-Di(1-naphthyl)ethylene 22. Sodium
hydride (60% dispersion in mineral oil, 2.12 g,
53.06 mmol, 1.2 equiv.) was weighed into 250 ml round
bottomed flask and repeatedly washed with, and then
suspended in, anhydrous THF (50 ml) under argon. To a
stirred suspension of the base at 08C, a solution of
1-naphthylmethylphosphonic acid diethyl ester17 (12.31 g,
44.22 mmol, 1 equiv.) in THF (50 ml), followed by
1-naphthaldehyde (6.17 ml, 44.22 mmol, 1 equiv.) was
slowly added. 15-Crown-5 (2 ml, 0.01 mmol, 0.23 equiv.)
was introduced, which resulted in rapid evolution of H2 and
the formation of a gelatinous precipitate. The reaction was
allowed to warm to room temperature, and stirred for a
further 12 h. The solvent was removed on the rotary
evaporator before quenching the excess sodium hydride
with brine (20 ml) [CARE!]. After partitioning the mixture
between DCM (100 ml) and water (100 ml), the aqueous
layer was extracted with DCM (2£100 ml) and the
combined organic extracts were dried (MgSO4), filtered
and concentrated under reduced pressure. The resulting

10462
H. C. Aspinall et al. / Tetrahedron 59 (2003) 10453–10463
496.24878, found 496.24864; Rf (petroleum ether–EtOAc
7:3) 0.13; n/cm21 (neat) 3454 (O–H), 3052–2838 (C–H),
1613 and 1513; dH (CDCl3) 8.25–8.00 (2H, m), 7.76–7.59
(4H, m), 7.29–7.18 (8H, m), 7.05 (2H, m) and 6.75 (2H, m,
aromatic), 5.52–5.43 (2H, AB system J¼6.6 Hz, H-1 and
2), 4.52–4.21 (2H, AB system, J¼11.55 Hz, –OCH2Ar),
3.76 (3H, s, OCH3), 3.74–3.59 (3H, m, H-3£2 and H-4£1),
3.47–3.35 (1H, m, 1H-5) and 2.76 (1H, br s, OH); dC
(CDCl3) 159.3, 134.6–123.9 (m), and 113.8 (aromatic),
84.0 and 82.4 (C-1 and 2), 71.3 and 70.9 (C-3 and
–OCH2OC6H4OCH3), 61.9 (C-1) and 55.3 (OCH3); m/z
(CI) 496.2 (8%, [M2NH4]þ), 358.1 (15%, [M2CH2C6H4-
OCH3þH]þ), 341.1 (27%, [M2OCH2C6H42OCH3]þ),
314.1 (95%, [(Ar(CHOH))2]þ).
found 642.24121; Rf (petroleum ether–EtOAc 1:1) 0.53;
max/cm21 (nujol) 3510–3490 (OH), 2950–2850 (CH); dH
n
(CDCl3) 7.98–6.74 (24H, m, aromatic), 5.17 (2H, s, OH),
3.79 (4H, m, H-1), 3.11 (4H, m, H-2); dC (CDCl3) 155.3,
151.4, 134.1, 134.0, 130.8, 129.7, 129.6, 129.2, 128.2,
128.0, 127.2, 126.4, 125.2, 125.0, 124.3, 123.2, 117.9,
116.8, 115.7 and 115.6 (aromatic), 69.5 and 69.2 (C-1 and
2); m/z (FAB) 642.1 (24%, Mþ), 313.0 (21%), 286.0 (10%).
4.3.16. (SSS)-1,20-Dihydroxy-1,2:3,4:9,10:11,12:
17,18:19,20-hexa(1,2-naphthio)-5,8,13,16-tetraoxa-
1,3,9,11,17,19-icosahexaene 25b. A 50 ml round bottomed
flask was charged with potassium hydroxide pellets (85%,
0.91 g, 16.25 mmol), 0 THF (19.5 ml), water (0.5 ml),
(S)-2-benzhydryloxy-2 -hydroxyl-1,10-binaphthyl19 (3.40 g,
7.52 mmol, 2.2 equiv.) and (S)-1,10-di(p-toluenesulphonyl-
oxy)-4,5:6,7-di(1,2-naphtho)-3,8-dioxa-4,6-decadiene
(2.33 g, 3.42 mmol, 1 equiv.). After refluxing for 48 h, the
mixture was evaporated to dryness under reduced pressure
and the residue was partitioned between water (50 ml) and
DCM (50 ml). The aqueous phase was further extracted
with DCM (2£50 ml) and the combined organic extracts
were washed (brine), dried (MgSO4), filtered and concen-
trated to about 100 ml. Methanol (30 ml) followed by
concentrated HCl (5 ml) was added, and the solution was
refluxed for 48 h. After treatment with 10% aqueous NaOH
(50 ml), the aqueous layer was extracted with DCM
(2£100 ml), and the combined organic extracts were
dried, (MgSO4). Concentration under reduced pressure
produced a yellow solid which was purified by flash
chromatography (gradient elution with petroleum ether–
DCM from 9:1 to 1:1) to give a white foam, (3.11 g, 90%);
mp 119.28C; [a]1D8¼243.38 (c¼1.09, DCM); C64H46O6
requires 910.32944, found 910.32970; Rf (petroleum ether–
EtOAc 1:1) 0.61; nmax/cm21 (nujol) 3500 (OH), 2927–2856
(CH); dH (CDCl3) 7.83–6.71 (36H, m, aromatic), 5.03 (2H, s,
OH£2) and 3.82–3.62 (8H, m, OCH2CH2O£2); dC
(CDCl3) 155.5, 154.2, 151.4, 133.9–123.2 (m), 123.2,
120.5, 117.7, 116.6, 116.2 and 115.3 (aromatic), 69.2 and
68.8 (–OCH2CH2O); m/z (FAB) 910.2 (20%, Mþ), 313.0
(60%), 268.0 (75%). 239.0 (100%).
4.3.13. (4R,5R)-4,5-Di(1-naphthyl)-5-(p-methoxybenzyl-
oxy)-1-(p-toluenesulphonyloxy)-3-oxapentane 18. Alcohol
19 (0.88 g, 1.84 mmol) was tosylated according to the
procedure reported for 1-methoxy-2-(toluene-4-sulfonyl-
oxy)ethane.30 Reaction time: 38 h. Purification by flash
chromatography (eluent: petroleum ether–Et2O 1:1) gave a
white foam, (0.75 g, 64%); [a]2D0¼þ21.58 (c¼1.03, DCM);
(found: C, 73.66; H, 5.71%. C39H36O6S requires C, 74.03;
H, 5.73%); Rf (petroleum ether–EtO 1:1) 0.39; nmax/cm21
(nujol) 2926–2855 (C–H), 1377 and 1174 (SO); dH
(CDCl3) 8.15–7.88 (2H, m), 7.74–7.56 (6H, m), 7.40–
7.03 (12H, m), and 6.78–6.74 (2H, m, aromatic), 5.47–5.34
(2H, AB system, J¼6.1 Hz, H-3 and 4), 4.51–4.22 (2H, AB
system, J¼11.5 Hz, OCH2Ar), 4.19–4.07 (2H, m, H-1),
3.79 (3H, s, –OCH3), 3.59–3.52 (2H, m, H-2) and 2.38 (3H,
s, ArCH3); dC (CDCl3) 159.1, 144.5, 134.4, 134.0, 133.2–
123.9 (m) and 113.7 (aromatic), 84.3 and 82.0 (C-3 and 4),
70.9 (–OCH2Ar), 69.3 and 67.3 (C-1 and 2), 55.3 (OCH3)
and 21.6 (ArCH3); m/z (FAB) 655.2 (0.5%, [MþNa]þ),
633.2 (0.2%, [MþH]þ) and 495.1 (1.5%, [M2OCH2C6H4-
OCH3]þ).
4.3.14. (1R,2R,7R,8R,13R,14R)-1,2,7,8,13,14-Hexa(1-
naphthyl)-1,14-di(4-methoxy-benzyloxy)-3,6,9,12-tetra-
oxatetradecane 9. Tosylate 18 (0.60 g, 0.949 mmol,
2.1 equiv.) was coupled to diol 1716 (0.135 g, 0.431 mmol,
1 equiv.) as for polyether 5. The reaction was heated under
reflux for 44 h. Purification by flash chromatography gave a
white solid, (0.44 g, 83%); mp 91–968C; [a]2D1¼þ32.78
(c¼1.14, DCM); (found: C, 83.57; H, 6.22%. C86H24O8
requires C, 83.6; H, 6.04%); Rf (petroleum ether–EtOAc
4.4. General procedure for preparation of Ln(OTf)3
complexes
The appropriate rare earth triflate (0.098 mmol, 0.1 equiv.)
was dried in vacuo at 1408C for 4–16 h in a 25 ml Schlenk
flask. After cooling to room temperature the flask was filled
with nitrogen and a solution of ligand (0.147 mmol,
0.15 equiv.) in dry DCM (2 ml) was added by cannula.
The mixture was subjected to ultrasound for 2 min.
Complexes prepared in this way were used in situ for
catalytic studies.
1:1) 0.67;
n
max/cm21 (nujol) 2938–2855 (CH); dH
(400 MHz, CDCl3) 8.15–7.90 (4H, m), 7.68–7.51 (12H,
m), 7.32–6.93 (30H, m) and 6.67–6.61 (4H, m, aromatic),
5.41–5.29 (6H, m, H-1,4 and 5), 4.13–4.15 (4H, AB
system, J¼11.5 Hz, OCH2Ar£2), 3.71 (6H, s, OCH3£2),
3.52–3.35 (8H, m, H-2 and 3); dC (CDCl3) 158.92, 135.4–
124.1 (m) and 113.5 (aromatic), 83.8–82.6 (m, C-1,3 and
4), 70.8 and 69.4 (C-2,3 and –OCH2OC6H4OCH3), 55.2
(–OCH3); m/z (FAB) 1257.7 (0.8%, [MþNa]þ).
4.4.1. Europium(III) (1S,2S,10S,11S)-1,2,10,11-tetra-
phenyl-1,11-dimethoxy-3,5,9-trioxaundecane trifluoro-
methanesulphonate 27. A 50 ml Schlenk flask was
charged with europium(III) triflate nonahydrate (0.85 g,
1.1 mmol, 1 equiv.), ligand 7a (0.58 g, 1.1 mmol, 1 equiv.),
4.3.15. R,R-1,15-Dihydroxy-1,2:3,4:12,13:14,15-tetra-
(1,2-naphtho)-5,8,11-triaoxa-1,3,12,14-pentadeca-
tetraene 24. Ligand 24 was prepared according to the
published procedure.19 It was purified by flash chromato-
graphy (gradient elution with petroleum ether–DCM from
9:1 to 4:1) to give a pale pink foam (0.34 g, 66%);
[a]1D9¼225.08 (c¼1.205); C44H34O5 requires 642.24063,
˚
activated 4 A MS (ca. 1 g) and DCM (25 ml). The mixture
was stirred vigorously under nitrogen for 4 h, before
decanting the solution into another 50 ml Schlenk flask
via cannula. The solvent was removed under vacuum to give

H. C. Aspinall et al. / Tetrahedron 59 (2003) 10453–10463
10463
Dalley, N. K.; Izatt, R. M.; Lifson, S. J. Org. Chem. 1990, 55,
3129–3137.
a residue which was dried under vacuum at 808C for 4 h to
give a cream solid. This material was recrystallised by
dissolving this material in dry toluene (2 ml) in a Schlenk
tube under nitrogen. Dry petroleum ether (5 ml) was
carefully layered onto the toluene phase, and the mixture
was allowed to stand at room temperature. After about 5
weeks a cream crystalline solid had settled to the bottom of
the tube, (1.12 g, 90%); (found: C, 40.51; H, 3.57%.
C37H38O14F9S3Eu requires C, 39.47; H, 3.4%); dH (CDCl3)
14.78 (4H, br s), 8.34 (2H, br s), 7.51–6.85 (20H, br m,
aromatic), 5.94 (6H, br s, CH£2), 4.16 (4H, br s), 23.02
(2H, br s); m/z (FAB) 977.0 (100%, [M2OTf]þ), 828 (20%,
[M22OTf]þ).
7. Hirose, K.; Fujiwara, A.; Matsunaga, K.; Aoki, N.; Tobe, Y.
Tetrahedron: Asymmetry 2003, 14, 555–566.
8. Aspinall, H. C.; Dwyer, J. L. M.; Greeves, N.; McIver, E. G.;
Woolley, J. C. Organometallics 1998, 17, 1884–1888.
9. McKee, B. H.; Gilheany, D. G.; Sharpless, K. B. Org. Synth.
1992, 70, 47.
10. Cai, D. W.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J.
Tetrahedron Lett. 1995, 36, 7991–7994.
11. Aspinall, H. C.; Greeves, N.; Lee, W.-M.; McIver, E. G.;
Smith, P. M. Tetrahedron Lett. 1997, 38, 4679–4682.
12. Leznoff, C. C. Acc. Chem. Res. 1978, 11, 327–333.
13. Nagashima, N.; Ohno, M. Chem. Pharm. Bull. 1991, 39,
1972–1982.
4.5. X-ray crystallography
14. Marshall, J.; Garofalo, A. W.; Sedrani, R. C. Synlett 1992,
643–645.
Crystals were coated in nujol oil and frozen onto glass fibres
under a stream of N2 gas at 21208C. Data were collected on
a Rigaku AFC6S diffractometer using graphite-mono-
15. Marshall, J.; Garofalo, A. W. J. Org. Chem. 1993, 58,
3675–3680.
˚
chromated Mo Ka radiation l¼0.71073 A). Structures
16. Rosini, C.; Scamuzzi, S.; Uccello-Barretta, G.; Salvadori, P. J.
J. Org. Chem. 1994, 59, 7395–7400.
were solved using direct methods. CIF files have been
deposited with the Cambridge Crystallographic Data Base.
17. Jiwan, J. L. H.; Soumillion, J. P. J. Phys. Chem. 1995, 99,
14223–14230.
18. Baker, R.; Sims, R. J. Synthesis 1981, 117.
19. Kyba, E. P.; Gokel, G. W.; Jong, F.; Koga, K.; Sousa, L. R.;
Siegel, M. G.; Kaplan, L.; Sogah, G. D. Y.; Cram, D. J. J. Org.
Chem. 1977, 42, 4173–4184.
5. Supplementary data
Crystallographic data for complexes 26 and 27 have been
deposited with the Cambridge Crystallographic Data Centre
(Deposition numbers CCDC 209355 and 209356). Copies of
this data can be obtained free of charge on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(email: deposit@ccdc.cam).
20. Malandrino, G.; Benelli, C.; Castelli, F.; Fragala, I. L. Chem.
Mater. 1998, 10, 3434–3444.
21. Aspinall, H. C.; Williams, M. Inorg. Chem. 1996, 35,
255–257.
22. Moller, A.; Scott, N.; Meyer, G.; Deacon, G. B. Z. Anorg. Allg.
Chem. 1999, 625, 181–182.
23. Rogers, R. D.; Henry, R. F. J. Crystallogr. Spectrosc. Res.
1992, 22, 361–364.
Acknowledgements
24. Barthelemy, P. P.; Desreux, J. F.; Massaux, J. J. Chem. Soc.,
Dalton Trans. 1986, 2497–2499.
We are grateful to EPSRC for financial support (studentship
to E. G. M.) and to Mr J. V. Barkley and Dr A. Steiner for
assistance with crystal structure determination.
25. Hamada, T.; Manabe, K.; Ishikawa, S.; Nagayama, S.; Shiro,
M.; Kobayashi, S. J. Am. Chem. Soc. 2003, 125, 2989–2996.
26. Mikami, K.; Yamaoka, M.; Yoshida, A.; Nakamura, Y.;
Takeuchi, S.; Ohgo, Y. Synlett 1998, 607–608.
27. Nakamura, Y.; Takeuchi, S.; Ohira, A.; Ohgo, Y. Tetrahedron
Lett. 1996, 37, 2805–2808.
References
28. Takeuchi, S.; Nakamura, Y.; Ohgo, Y.; Curran, D. P.
Tetrahedron Lett. 1998, 39, 8691–8694.
1. Riddell, F. G. Chirality 2002, 14, 121–125.
2. Faul, M. M.; Huff, B. E. Chem. Rev. 2000, 100, 2407–2473.
3. Piguet, C.; Bunzli, J. C. G. Chem. Soc. Rev. 1999, 28,
347–358.
29. Aspinall, H. C. Chem. Rev. 2002, 102, 1807.
30. Terfort, A.; Brunner, H. J. Chem. Soc., Perkin Trans. 1 1996,
1467–1479.
4. Hoffmann, R. W. Angew. Chem. Int. Ed. 2000, 39,
2054–2070.
31. Crosby, J.; Stoddart, J. F.; Sun, X. Q.; Venner, M. R. W.
Synthesis 1993, 141–145.
5. Bartsch, R. A.; Cason, C. V.; Czech, B. P. J. Org. Chem. 1989,
54, 857–860.
6. Bradshaw, J. S.; Huszthy, P.; McDaniel, C. W.; Zhu, C. Y.;
32. Mizuno, M.; Kanai, M.; Iida, A.; Tomioka, K. Tetrahedron
1997, 53, 10699–10708.