Synthesis and conformational aspects of 20- and 40-membered macrocyclic mono and dinuclear uranyl complexes incorporating salen and (R)-BINOL units

Article abstract of DOI:10.1016/j.tet.2007.07.014

20- and 40-membered macrocyclic mono and dinuclear uranyl complexes 11-13 incorporating salen and (R)-BINOL units have been designed and synthesized starting from 4-tert-butylphenol in eight steps. NMR measurements (COSY, NOESY/EXSY) indicate that such co

Full text of DOI:10.1016/j.tet.2007.07.014

Tetrahedron 63 (2007) 9751–9757
Synthesis and conformational aspects of 20- and 40-membered
macrocyclic mono and dinuclear uranyl complexes
incorporating salen and (R)-BINOL units
Maria E. Amato, Francesco P. Ballistreri, Andrea Pappalardo, Domenico Sciotto,
*
Gaetano A. Tomaselli and Rosa Maria Toscano
Dipartimento Scienze Chimiche, University of Catania, Viale A. Doria 6, 95125 Catania, Italy
Received 12 April 2007; revised 19 June 2007; accepted 6 July 2007
Available online 13 July 2007
Abstract—20- and 40-membered macrocyclic mono and dinuclear uranyl complexes 11–13 incorporating salen and (R)-BINOL units have
been designed and synthesized starting from 4-tert-butylphenol in eight steps. NMR measurements (COSY, NOESY/EXSY) indicate that such
complexes in solution are involved in conformational equilibria, which for the 20-membered derivatives are observable already at room
temperature (k1¼300 sꢀ1 at 300 K) and which are probably related to a flipping motion of salicylaldehyde units. T-ROESY experiments
suggest that in solution, the dinuclear complexes do not assume structures wrapped around the metal ions.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
tert-butylphenol (2) (70%), which upon selective oxidation
(MnO2) was converted into 2-hydroxy-3-hydroxymethyl-5-
tert-butylbenzaldehyde (3) (62%). Allylation of 3 with allyl
bromide and K2CO3 in dry MeCN produced the 2-allyloxy
derivative 4 (88%), which underwent reaction with SOCl2
in CH2Cl2 to afford chloromethyl compound 5 (65%).
Subsequent alkylation of (R)-BINOL with 5 and K2CO3 in
refluxing MeCN to give bis-ether 6 (78%), followed by
Pd-catalyzed dealkylation, afforded the desired bis-salicyl-
aldehyde derivative 7 in 71% yield.
The design and synthesis of chiral macrocycles acting as
enantioselective receptors are of great interest in the field
of enzyme mimicking enantioselective catalysis1 as well as
in those of chiral resolution2 and chiral sensing.3 Recently
particular attention has been devoted to neutral ditopic
receptors able to simultaneously bind chiral ammonium cat-
ions and their counter anions.4–13 In this paper we describe
the synthesis of some chiral macrocyclic ligands incorporat-
ing both a salen unit containing a chiral diimine bridge and
the (R)-BINOL unit. The salen framework, due to the pres-
ence of two stereogenic carbon atoms in the diimine bridge,
generates a chiral pocket which can coordinate a metal cat-
ion, say the uranyl cation (via imine nitrogen and phenolic
oxygen atoms), which represents a Lewis acidic site able
to bind the counter anion of an ion pair as guest.14 On the
other hand, the (R)-BINOL unit can provide p electron
rich regions able to develop CH–p interactions thus facilitat-
ing the recognition of the pertinent counter cation.
Reaction of bis-aldehyde 7 with (1R,2R)-1,2-diphenylethyl-
enediamine (Scheme 2) in refluxing EtOH under high dilu-
tion conditions gave a mixture of 1:1 (20-membered) and
2:2 (40-membered) macrocycles 8 and 9, which were isolated
byflash chromatographyin13%and75%yields, respectively.
Likewise, reaction of bis-aldehyde 7 with (1R)-trans-1,
2-cyclohexanediamine in refluxing EtOH gave the 40-mem-
bered macrocycle 10 as the main product (96% isolated
yield) and hardly isolable quantities of the 20-membered
macrocycle.
2. Synthetic scheme
The synthesis of the key intermediate 7 from 4-tert-butyl-
phenol is illustrated in Scheme 1. Treatment of 1 with
CH2O and base gave the known 2,6-bis(hydroxymethyl)-4-
3. NMR spectra of macrocycles 8, 9 and 10
The 1H NMR spectra of compounds 8, 9 and 10 were
recorded both in CDCl3 and (CD3)2CO. In CDCl3 the spectra
consist of similar and relatively simple patterns of reso-
nances showing only one set of signals for each pair of
* Corresponding author. Tel.: +39 095338836; fax: +39 095580138; e-mail:
gtomaselli@unict.it
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.07.014

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M. E. Amato et al. / Tetrahedron 63 (2007) 9751–9757
b
d
a
c
OH
OH OH OH
OH
O
O
OH
OH
O
2 (70%)
3 (62%)
4 (88%)
1
OH
O
O
O
O
e
AllO
AllO
O
f
O
O
OH
Cl
O
O
O
5 (65%)
6 (78%)
7 (71%)
Scheme 1. Reagents and conditions: (a) NaOH, CH2O, 7 d, rt; (b) MnO2, CHCl3, 8 h, rt; (c) CH2]CHCH2Br, K2CO3, CH3CN, reflux 1.5 h; (d) SOCl2, CH2Cl2,
2 h; (e) (R)-2,20-dihydroxy-1,10-binaphthalene, K2CO3, CH3CN, reflux 15 h; (f) Pd(OAc)2, PPh3, Et3N, HCO2H, 80% EtOH, reflux 45 min.
N
N
N
N
OHHO
OHHO
N
N
O
O
O
O
O
O
O
O
OH O
OH O
a
O
O
b
OHHO
+
O
O
OHHO
OHHO
N
N
N
N
8 (13%)
7
10 (96%)
9 (75%)
c
c
c
N
N
N
O
N
M
O
O
M
O
N
O
N
O
O
O
M
O
O
O
O
O
O
O
O
O O
M
O
N
O
M
N
N
N
M=UO2
13
11
12
Scheme 2. Reagents and conditions: (a) (1R,2R)-1,2-diphenylethylenediamine, EtOH, reflux, 1 d; (b) (1R)-trans-1,2-cyclohexanediamine, EtOH, reflux, 1 d;
(c) UO2(AcO)2$2H2O, MeOH, 12 h, rt.
identical but not chemically equivalent groups. The presence
of the imine CH]N proton (at 8.38 ppm for 8, 8.32 ppm for
9 and 8.19 ppm for 10) and the contemporary disappearance
of the signal at 10.4 ppm of the aldehydic proton of 7 support
the imine formation. The low field singlets (d 12.83 ppm for
compound 8, 13.27 ppm for 9 and 13.30 ppm for 10)
indicate that the phenolic hydroxyls are strongly hydrogen
bonded to the imine nitrogens.15 Interestingly the two

M. E. Amato et al. / Tetrahedron 63 (2007) 9751–9757
9753
diimine bridge proton signals, which resonate at 3.23 ppm,
appear as an unresolved multiplet due to the scalar coupling
with the adjacent cyclohexyl ring methylene protons even
in (CD3)2CO.
4. Uranyl complexes 11, 12 and 13
Macrocycles 8, 9 and 10 were employed as ligands to bind
the uranyl cation to yield the corresponding mono and dinu-
clear complexes 11, 12 and 13 (Scheme 2). The structural
characterization of all new complexes was carried out by
1
FAB+ and by NMR spectroscopies (see Section 6). The H
NMR spectrum of 11 in CDCl3 solution when compared
with that of the corresponding free ligand 8 shows broaden-
ing of all the resonances, the absence of the phenolic OH sig-
nal and a significant downfield shift for several resonances in
agreement with the presence of a coordinated uranyl cation.
We have previously observed by X-ray measurements of
very strictly correlated complexes17 a pentagonal bipyrami-
dal coordination geometry for uranyl(VI) ion with two axial
oxo groups and with the fifth equatorial site occupied by an
adventitious water molecule. This site is also available
for complexation with anionic monodentate ligands Xꢀ
and its presence therefore makes the complex a potential
receptor for Q+Xꢀ onium salts (Q+¼quaternary ammonium
ion).
8.5
8.4
8.3
5.2
ppm
5.0
4.8
4.6
Figure 1. Selected 1H NMR spectral regions (500 MHz) of 9 in CDCl3 (top)
and in (CD3)2CO (bottom) displaying the splitting of imine, diimine bridge
and methylene proton signals in (CD3)2CO at 300 K.
diastereotopic methylene protons ArOCH2BINOL of mac-
rocycle 8 resonate as an AB system centred at d 4.67 ppm
(Dd 0.54 ppm, JAB¼12.0 Hz), while for 40-membered
macrocycles 9 and 10 the Dd difference is reduced to
ca. 0.09 ppm (JAB¼12.8 Hz) and to ca. 0.10 ppm
(JAB¼14.6 Hz), respectively, which might indicate that in
these compounds partial rotation about the ArO–CH2 bond
occurs and it is less hindered in 9 and 10 than in the smaller
and more strained macrocycle 8.
The aromatic region of the spectrum is fairly crowded
preventing detailed analysis. However, for conformational
analysis purposes the resonances arising from CH]N azo-
methine, diimine bridge and methylene protons are quite di-
agnostic. In fact the splitting of these signals, observed for
complex 11 and which was not present in the free ligand
8, supports the presence of a conformational equilibrium,
which at room temperature is already slow on the NMR
time-scale, in agreement with a larger degree of rigidity of
this complex. In order to get an insight into the conforma-
tional behaviour of compound 11, phase-sensitive NO-
ESY/EXSY spectra at 300 K of 11 have also been
acquired (Fig. 3).
By way of contrast, in (CD3)2CO for compound 9 splitting of
the signals of the imine as well as of the methyne protons of
diimine bridge is observed (Fig. 1). This observation might
be consistent with a dynamic interconversion process on
the NMR time-scale among different diastereomeric confor-
mations. Indeed, calculations performed by Macromodel
program16 pointed out the existence of a large number of
conformers having comparable energy indicative of a great
flexibility of macrocycle 9 (Fig. 2). For compound 10
The 2D map suggests that an exchange process is occurring
on the NMR time-scale involving the ArCH2OAr methylene
protons as well as the two imine and diimine bridge protons.
A rate constant, k, of ca. 300 sꢀ1 at 300 K can be estimated
assuming that the exchange process follows first order kinet-
ics.18 The process (Fig. 4) might envisage the flipping mo-
tion of the salicylaldehyde framework observed for uranyl
salophen complexes, which inverts the curvature of the sal-
ophen ligand.13–15,19
This observation seems to indicate that coordination of the
uranyl(VI) cation, owing to its large ionic radius, causes con-
formational stiffening, i.e., rigidity and then restricted rota-
tion, and therefore slows down the rate of the conformational
equilibrium with respect to that of the free ligand.
NMR spectra of dinuclear uranyl complexes 12 and 13 were
also obtained in (CD3)2CO. The methylene protons resonate
as an AB system at 5.56–5.79 ppm (JAB¼ca. 15.2 Hz) and at
5.45–5.57 ppm (JAB¼ca. 14.2 Hz) in 12 and 13, respec-
tively. The imine and the diimine proton signals which in
Figure 2. Computed optimized structure of macrocycle 9.

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M. E. Amato et al. / Tetrahedron 63 (2007) 9751–9757
4.6
5.0
5.4
5.8
4.6
5.0
5.4
5.8
6.2
6.2
ppm
ppm
6.
2
5.8
5.
ppm
4
5.0
4.6
6.2
5.8
5.
ppm
4
5.0
4.6
Figure 3. Selected spectral regions (500 MHz, CDCl3) of 2D-COSY (left) and EXSY (right) spectra of complex 11 at 300 K (mixing time¼50 ms).
(CD3)2CO appeared doubled in the spectrum of free ligand 9
are both narrow singlets now in the spectrum of correspond-
ing uranyl complex 12. The obvious interpretation of these at
first sight contrasting findings is the possibility that chemical
shift differences between doubled signals, already observed
in the corresponding free ligand 9 and which were assumed
to indicate the presence of a conformational equilibrium, in
the case of complex 12 are too small to be measured at room
temperature. In order to check such a hypothesis we ran the
1H NMR spectrum of 12 at variable temperatures in the
range 300–183 K (Fig. 5). As the temperature is gradually
lowered the proton NMR resonances of 12 showed a general
progressive small downfield shift, with the exception of the
tert-butyl group signal, which on the contrary was shifted
slightly upfield. The signals of methylene, imine and diimine
bridge protons start to collapse at 228 K and when the
temperature reaches 183 K at least two forms are present
in slow exchange. From the Eyring equation, a DGz¼
11.9 kcal molꢀ1 value at Tc¼228 K can be calculated for
the activation barrier of the interconversion equilibrium.
The aromatic portion and the tert-butyl group signals were
also significantly affected. Unfortunately, it was difficult to
determine the number of conformers in equilibrium and to
assign the resonances in order to establish their conforma-
tional structures because of the ambiguous line shape evolu-
tion and the extensive broadening.
Finally, the T-ROESY maps of 12 and 13, which show cross-
peaks corresponding to the almost unbroken pattern of
neighbouring protons already present in the spectra of free
ligands 9 and 10, indicate that no extra dipolar contacts
could be detected and suggest that these dinuclear
Figure 4. Computer calculated structures of conformers involved in the flipping motion of 11.

M. E. Amato et al. / Tetrahedron 63 (2007) 9751–9757
9755
carried out at 27 ꢁC on a Varian UNITY Inova 500 MHz
spectrometer (1H NMR at 499.88 MHz, 13C NMR at
125.7 MHz in CDCl3) equipped with pulse field gradient
module (Z axis) and a tunable 5 mm Varian inverse detection
probe (ID-PFG). The chemical shifts (ppm) were referenced
to TMS. IR spectra were obtained with a Perkin–Elmer 1340
spectrophotometer. ESI mass spectra were obtained by
employing an ES-MS Thermo-Finnigan LCQ-DECA spec-
trometer equipped with an ion trap analyzer. FAB(+) mass
spectra were obtained on an MS 50 spectrometer using
3-nitrobenzyl-alcohol as a matrix. All chemicals were of
reagent grade and were used without further purification.
T = 300K
T = 288K
T = 273K
6.1.1. 2,6-Bis-hydroxymethyl-4-tert-butylphenol (2). This
compound was prepared by a slight modification of a litera-
ture procedure.20 To a solution of NaOH (10.0 g, 0.25 mol)
in H2O (90 mL) was added 4-tert-butylphenol (1) (37.5 g,
0.25 mol), the suspension was slightly heated to give a clear
solution. The solution was cooled to 0 ꢁC and 37% formal-
dehyde (37.6 mL, 0.5 mol) was added dropwise under
mechanical stirring. The mixture was stirred at room temper-
ature for seven days. To complete the precipitation, NaCl
(42.5 g) was added and the precipitate was filtered off and
suspended in 500 mL of H2O. The suspension was cooled
and 5% aq HCl was added. The resulting white suspension
was extracted four times with CH2Cl2 and the combined
organic phases were dried (Na2SO4). The crude product
was column chromatographed [SiO2, eluent AcOEt/
petroleum ether 40–60 ꢁC (gradient 3:1 to 5:1)] to afford 2
(36.5 g, 70%) as a white solid. Mp 74–75 ꢁC.20 1H NMR
(500 MHz, CDCl3): d 1.29 (s, 9H), 4.82 (s, 4H), 7.10
(s, 2H).
T = 243K
T = 228K
T = 213K
T = 193K
10.0 9.5
9.0
8.5
8.0
7.5
ppm
7.0
6.5
6.0
5.5
5.0
Figure 5. Variable temperature 1H NMR spectrum of dinuclear complex 12
(500 MHz, (CD3)2CO) at relevant temperatures.
complexes do not, in solution, assume structures wrapped
around the metal ions.
6.1.2. 2-Hydroxy-3-hydroxymethyl-5-tert-butylbenzalde-
hyde (3). By adopting a literature procedure for similar com-
pounds,21 a mixture of 2 (10.5 g, 50 mmol) and MnO2
(43.5 g, 500 mmol) in CHCl3 (ca. 30 mL/g of phenol) was
stirred at room temperature for 6–8 h. After filtration, the
solid was subjected to Soxhlet extraction with CHCl3 over-
night. The removal of chloroform on a rotary evaporator
gave a residue, which was column chromatographed
(SiO2, eluent petroleum ether/AcOEt 20:1 to 10:1, v/v) to
give small amounts (5–6%) of 2,6-diformyl-4-tert-butylphe-
nol followed by the desired mono-aldehyde 3 (6.5 g, 62%);
yellow oil, which solidifies on standing. Mp 87–88 ꢁC (86–
87 ꢁC).22 1H NMR (500 MHz, CDCl3): d 1.34 (s, 9H), 4.78
(s, 2H), 7.49, 7.63 (d, J¼2.4 Hz, 1H each), 9.92 (s, 1H),
11.23 (s, 1H). ESI-MS: m/z 209 [MH]+. Anal. Calcd for
C12H16O3: C, 69.23; H, 7.69. Found: C, 69.58; H, 7.72.
5. Conclusions
We have synthesized new mono and dinuclear uranyl chiral
macrocyclic salen complexes and have determined their
structures in solution by NMR measurements. Our findings
point out that, as expected, the 20-membered mononuclear
complex displays a larger degree of rigidity than the
40-membered dinuclear complexes. However, all three
complexes are involved in conformational equilibria which
are observable already at room temperature for the 20-mem-
bered complex. Even if it is not possible to define the number
of conformers and their detailed structures involved in these
equilibria, it appears reasonable to assume that all con-
formers might be associated with the occurrence of a flipping
motion of the salicylaldehyde framework similar to that
already observed for uranyl salophen complexes. Therefore,
these complexes seem to have the requisites to work as
potential neutral ditopic enantioselective receptors.
6.1.3. 2-Allyloxy-3-hydroxymethyl-5-tert-butylbenzalde-
hyde (4). A stirred mixture of 3 (5.20 g, 25 mmol), allyl bro-
mide (6.05 g, 50 mmol) and anhydrous K2CO3 (3.45 g,
25 mmol) in dry MeCN (150 mL) was refluxed for 1.5 h. Af-
ter evaporation of the solvent, the residue was partitioned be-
tween 0.1 M HCl and CH2Cl2. The organic layer was washed
with water, dried over anhydrous Na2SO4 and concentrated.
The oily residue was purified by column chromatography
(SiO2, eluent petroleum ether/AcOEt 5:1, v/v) to give 4
6. Experimental
6.1. General
1
(5.45 g, 88%) as a pale yellow oil. H NMR (500 MHz,
CDCl3): d 1.34 (s, Bu, 9H), 2.13 (t, J¼5.9 Hz, CH2OH,
t
Melting points were determined on a Kofler hot stage appa-
ratus and are uncorrected. The NMR experiments were
1H), 4.53 (dt, J¼5.7, 1.3 Hz, OCH2CH]CH2, 2H), 4.78
(d, J¼5.9 Hz, CH2OH, 2H), 5.33 (ddd, J¼10.3, 2.6,

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M. E. Amato et al. / Tetrahedron 63 (2007) 9751–9757
1.5 Hz, OCH2CH]CHaHb, 1H), 5.44 (ddd, J¼17.1, 2.9,
1.5 Hz, OCH2CH]CHaHb, 1H), 6.11 (m, OCH2CH]CH2,
1H), 7.71, 7.82 (d, J¼2.6 Hz, ArH, 1H each), 10.34 (s, CHO,
1H). 13C NMR (125 MHz, CDCl3): d 31.2, 34.6, 60.7, 78.1,
118.9, 125.1, 128.7, 132.6, 132.8, 134.5, 147.8, 190.2. ESI-
MS: m/z 249 [MH]+. Anal. Calcd for C15H20O3: C, 72.59; H,
8.06. Found: C, 72.86; H, 8.01.
was dried (Na2SO4) and concentrated. The crude product
was purified by column chromatography (SiO2, eluent petro-
leum ether/AcOEt 7:1, v/v) to afford 7 (1.5 g, 71%). Mp
210–212 ꢁC (CH2Cl2/EtOH). 1H NMR (500 MHz, CDCl3):
d 0.94 (s, Bu, 18H), 5.11 and 5.14 (ABq, J¼13.0 Hz,
t
OCH2, 4H), 7.01 (d, J¼2.3 Hz, ArH, 2H), 7.20–7.25 (m,
6,60(7,70),8,80-binaphH and ArH, 6H), 7.32 (ddd, J¼8.1,
6.1, 1.8 Hz, 7,70(6,60)-binaphH, 2H), 7.58 (d, J¼9.0 Hz,
3,30-binaphH, 2H), 7.87 (d, J¼8.1 Hz, 5,50-binaphH, 2H),
7.99 (d, J¼9.0 Hz, 4,40-binaphH, 2H), 9.74 (s, CHO, 2H),
10.99 (s, OH, 2H). 13C NMR (125 MHz, CDCl3): d 30.9,
33.8, 64.8, 115.0, 119.1, 120.2, 123.7, 125.3, 125.5, 126.5,
128.0, 128.1, 129.5, 129.6, 132.6, 134.1, 142.5, 153.8,
156.0, 196.8. IR (KBr) nmax: 3037, 2954, 1651, 1260,
1210, 1050, 810 cmꢀ1. FAB(+) MS: m/z 667 [MH]+. Anal.
Calcd for C44H42O6: C, 79.28; H, 6.31. Found: C, 79.60;
H, 6.27.
6.1.4. 2-Allyloxy-3-chloromethyl-5-tert-butylbenzalde-
hyde (5). To a chilled solution of 4 (4.25 g, 17.1 mmol) in
CH2Cl2 (150 mL) was added dropwise under stirring a solu-
tion of SOCl2 (5.1 g, 43.2 mmol) in CH2Cl2 (50 mL). The
mixture was allowed to stir for 2 h. After removal of most
of the solvent, toluene (20 mL) was added and the mixture
was concentrated to dryness. The oily residue was parti-
tioned between brine and CH2Cl2 (3ꢂ15 mL), dried
(Na2SO4) and concentrated. The crude product was column
chromatographed (SiO2, eluent petroleum ether/AcOEt
10:1, v/v) to afford 5 (2.95 g, 65%) as a light yellow oil.
6.1.7. Macrocycles 8 and 9. Solutions of 7 (0.2 g, 0.3 mmol)
and (1R,2R)-1,2-diphenylethylendiamine (0.064 g, 0.3 mmol)
in abs EtOH (50 mL) were dropped separately but synchro-
nously from two dropping funnels into boiling abs EtOH
(50 mL) under rapid stirring. The reaction mixture was
refluxed for an additional 15 h, and cooled. After removal
of the solvent, the crude product was subjected to flash
chromatography (SiO2, eluent petroleum ether/AcOEt
20:1, v/v) to afford macrocycles 8 (Rf¼0.28, petroleum
ether/AcOEt 15:1; 32 mg, 13%) and 9 (Rf¼0.05, petroleum
ether/AcOEt 15:1; 190 mg, 75%).
t
1H NMR (500 MHz, CDCl3): d 1.34 (s, Bu, 9H), 4.59 (dt,
J¼5.9, 1.3 Hz, OCH2CH]CH2, 2H), 4.69 (s, CH2Cl, 2H),
5.35 (ddd, J¼10.4, 2.6, 1.3 Hz, OCH2CH]CHaHb, 1H),
5.47 (ddd, J¼17.1, 3.0, 1.5 Hz, OCH2CH]CHaHb, 1H),
6.13 (m, OCH2CH]CH2, 1H), 7.71, 7.86 (d, J¼2.6 Hz,
ArH, 1H each), 10.34 (s, CHO, 1H). 13C NMR (125 MHz,
CDCl3): d 31.1, 34.6, 40.4, 78.4, 118.9, 126.2, 129.1,
131.7, 132.5, 134.4, 148.1, 157.9, 189.8. ESI-MS: m/z 267
[MH]+. Anal. Calcd for C15H19ClO2: C, 67.67; H, 7.14.
Found: C, 67.97; H, 7.10.
1
6.1.5. (R)-2,20-Bis(2-allyloxy-3-formyl-5-tert-butyl-ben-
zyloxy)-1,10-binaphthalene (6). A stirred mixture of
(R)-2,20-dihydroxy-1,10-binaphthalene (1.17 g, 4.1 mmol), 5
(2.4 g, 9 mmol) and anhydrous K2CO3 (3.24 g, 23.5 mmol)
in dry MeCN (150 mL) was refluxed for 15 h under N2.
Usual workup followed by column chromatography (SiO2,
eluent petroleum ether/AcOEt 7:1, v/v) afforded bis-alde-
Compound 8: mp 186–188 ꢁC (CH2Cl2/EtOH). H NMR
(500 MHz, CDCl3): d 0.92 (s, Bu, 18H), 4.40 and 4.94
t
(AB, J¼12.0 Hz, O–CH2, 4H), 4.71 (s, CH–N, 2H), 6.77
and 7.06 (AB, J¼2.2 Hz, ArH, 4H), 7.12–7.14, (m, binaphH,
4H), 7.24–7.38 (m, ArH and binaphH, 14H), 7.88 (d,
J¼8.1 Hz, 5,50-binaphH, 2H), 7.90 (d, J¼9.0 Hz, 4,40-bi-
naphH, 2H), 8.38 (s, CH]N, 2H), 12.83 (s, OH, 2H). 13C
NMR (125 MHz, CDCl3): d 31.1, 33.7, 65.8, 81.1, 116.0,
117.3, 120.7, 123.5, 124.4, 125.6, 126.2, 126.7, 127.5,
127.6, 127.8, 127.9, 128.5, 129.5, 134.0, 140.4, 140.9,
155.10, 155.14, 165.5. FAB(+) MS: m/z 843 [MH]+. Anal.
Calcd for C58H54N2O4: C, 82.66; H, 6.41; N, 3.33. Found:
C, 82.93; H, 6.36; N, 3.34.
1
hyde 6 (2.4 g, 78%) as a thick colourless oil. H NMR
(500 MHz, CDCl3): d 1.02 (s, Bu, 18H), 4.13–4.22 (m,
t
OCH2CH]CH2, 4H), 5.09 and 5.14 (ABq, J¼12.2 Hz,
binaph–OCH2, 4H), 5.23 (dd, J¼10.4, 0.9 Hz, OCH2CH]
CHaHb, 2H), 5.29 (dd, J¼17.1, 1.2 Hz, OCH2CH]CHaHb,
2H), 5.89–5.97 (m, OCH2CH]CH2, 2H), 7.13 (d,
J¼2.4 Hz, ArH, 2H), 7.14 (d, J¼8.2 Hz, 8,80-binaphH,
2H), 7.19 (dt, J¼7.5, 1.1 Hz, 7,70(6,60)-binaphH, 2H), 7.33
(dt, J¼7.5, 1.1 Hz, 6,60(7,70)-binaphH, 2H), 7.54 (d,
J¼8.8 Hz, 3,30-binaphH, 2H), 7.66 (d, J¼2.4 Hz, ArH,
2H), 7.88 (d, J¼8.2 Hz, 5,50-binaphH, 2H), 8.00 (d,
J¼8.8 Hz, 4,40-binaphH, 2H), 10.22 (s, CHO, 2H). 13C
NMR (125 MHz, CDCl3): d 31.2, 34.6, 66.2, 77.9, 115.8,
118.7, 121.0, 124.2, 124.7, 125.3, 125.5, 126.8, 128.3,
128.6, 129.9, 131.4, 132.9, 134.3, 147.7, 153.9, 157.4,
190.3. FAB(+) MS: m/z 747 [MH]+, 770 [MNa]+. Anal.
Calcd for C50H50O6: C, 80.43; H, 6.70. Found: C, 80.32;
H, 6.75.
1
Compound 9: mp 272–274 ꢁC (CH2Cl2/EtOH). H NMR
(500 MHz, CDCl3): d 0.79 (s, Bu, 36H), 4.64 (s, CH–N,
t
4H), 5.06 and 5.15 (AB, J¼12.8 Hz, O–CH2, 8H), 6.66
and 6.87 (ABq, J¼2.4 Hz, ArH, 8H), 7.04–7.26, (m, ArH
and (6,60),(7,70),(8,80)-binaphH, 32H), 7.61 (d, J¼9.0 Hz,
3,30-binaphH, 4H), 7.83 (d, J¼8.1 Hz, 5,50-binaphH, 4H),
7.98 (d, J¼9.0 Hz, 4,40-binaphH, 4H), 8.32 (s, CH]N,
4H), 13.27 (s, OH, 4H). 13C NMR (125 MHz, CDCl3):
d 31.0, 33.6, 65.1, 80.2, 114.5, 116.8, 120.0, 123.4, 124.3,
125.3, 126.32, 126.35, 127.5, 127.7, 127.8, 127.9, 128.3,
1
129.3, 134.1, 139.7, 141.0, 153.9, 154.9, 166.7. H NMR
(500 MHz, CD3COCD3): d 0.83 (s, Bu, 36H), 4.97 (br s,
t
6.1.6. (R)-2,20-Bis(2-hydroxy-3-formyl-5-tert-butyl-ben-
zyloxy)-1,10-binaphthalene (7). A stirred mixture of 6
(2.35 g, 3.1 mmol), Pd(OAc)2 (47 mg, 0.2 mmol), PPh3
(255 mg, 1.1 mmol), Et3N (7.85 g, 77.5 mmol) and
HCO2H (3.58 g, 77.5 mmol) in 80% EtOH was refluxed
for 45 min. After removal of the solvent, the residue was par-
titioned between CH2Cl2 and 0.1 M HCl. The organic layer
CH–N, 4H), 5.06 and 5.21 (AB, J¼12.8 Hz, O–CH2, 8H),
6.77 and 7.02 (m, ArH, 8H), 7.01–7.32 (m, ArH and
(6,60),(7,70),(8,80)-binaphH, 32H), 7.71 (d, J¼9.3 Hz, 3,30-
binaphH, 4H), 7.94 (d, J¼8.1 Hz, 5,50-binaphH, 4H), 8.12
(d, J¼9.0 Hz, 4,40-binaphH, 4H), 8.53 (br s, CH]N, 4H),
13.29 (s, OH, 4H). IR (KBr) nmax: 3447, 2953, 1623, 1594,
1456, 1269, 1220, 885, 810 cmꢀ1. FAB(+) MS: m/z 1685

M. E. Amato et al. / Tetrahedron 63 (2007) 9751–9757
9757
[MH]+. Anal. Calcd for C116H108N4O8: C, 82.66; H, 6.41; N,
3.33. Found: C, 82.49; H, 6.46; N, 3.31.
Compound 13: (500 MHz, CD3COCD3): d 1.14 (s, tBu, 36H),
1.62–1.98 (m, CH2–CH2–CH–N, 8H), 2.11–2.59 (m, CH2–
CH2–CH–N, 8H), 4.11 (m, CH–N, 4H), 5.45 and 5.57
(AB, J¼14.2 Hz, O–CH2, 8H), 7.02–8.06 (m, ArH and
binaphH, 32H), 9.48 (s, CH]N, 4H). Anal. Calcd for
C100H100N4O12U2$2H2O: C, 58.25; H, 5.05; N, 2.72. Found:
C, 58.06; H, 5.08; N, 2.71.
6.1.8. Macrocycle 10. Solutions of 7 (0.2 g, 0.3 mmol) and
(1R)-trans-1,2-cyclohexanediamine (0.035 g, 0.3 mmol) in
abs EtOH (50 mL) were dropped separately but synchro-
nously from two dropping funnels into boiling abs EtOH
(50 mL) under rapid stirring. The reaction mixture was re-
fluxed for an additional 15 h, and cooled. After removal of
the solvent, the crude product was dissolved in CH2Cl2, fil-
tered on Celite and concentrated to afford after crystalliza-
tion macrocycle 10 (0.21 g, 96%). Mp 250–252 ꢁC
Acknowledgements
We thank MIUR and University of Catania for financial
support.
t
(hexane). 1H NMR (500 MHz, CDCl3): d 0.79 (s, Bu,
36H), 1.38–1.44 (m, CH2–CH2–CH–N, 8H), 1.76–1.82 (m,
CH2–CH2–CH–N, 8H), 3.20–3.26 (m, CH–N, 4H), 5.05
and 5.15 (AB, J¼14.6 Hz, O–CH2, 8H), 6.62 and 6.83
(ABq, J¼2.0 Hz, ArH, 8H), 7.13–7.26, ((6,60),(7,70),(8,80)-
binaphH, 12H), 7.61 (d, J¼8.5 Hz, 3,30-binaphH, 4H),
7.82 (d, J¼8.0 Hz, 5,50-binaphH, 4H), 7.97 (d, J¼9.0 Hz,
4,40-binaphH, 4H), 8.19 (s, CH]N, 4H), 13.30 (s, OH,
4H). 13C NMR (125 MHz, CDCl3): d 24.0, 31.0, 33.6,
34.0, 65.3, 73.0, 114.8, 117.0, 120.3, 123.4, 124.6, 125.4,
126.32, 126.36, 127.5, 127.9, 128.0, 128.1, 128.4, 129.5,
134.0, 139.5, 141.0, 154.0, 154.9, 165.8. 1H NMR
References and notes
1. Steed, J. W.; Atwood, J. L. Supramolecular Chemistry; John
Wiley & Sons: Chichester, UK, 2000.
2. Zheng, X.; Jones, C. W.; Weck, M. J. Am. Chem. Soc. 2007,
129, 1105–1112.
3. Shahgaldian, P.; Pieles, U. Sensors 2006, 6, 593–615.
4. Kubik, S. J. Am. Chem. Soc. 1999, 21, 5846–5855.
5. Kubik, S.; Goddard, R. Chem. Commun. 2000, 633–634.
6. Heinrichs, G.; Vial, L.; Lacour, J.; Kubik, S. Chem. Commun.
2003, 1252–1253.
7. Arduini, A.; Giorgi, G.; Pochini, A.; Secchi, A.; Ugozzoli, F.
J. Org. Chem. 2001, 66, 8302–8308.
8. Arduini, A.; Brindani, E.; Giorni, G.; Pochini, A.; Secchi, A.
J. Org. Chem. 2002, 67, 6188–6194.
9. Atwood, J. L.; Szumna, A. J. J. Am. Chem. Soc. 2002, 124,
10646–10647.
t
(500 MHz, CD3COCD3): d 0.79 (s, Bu, 36H), 1.46–1.54
(m, CH2–CH2–CH–N, 8H), 1.76–1.91 (m, CH2–CH2–CH–
N, 8H), 3.33–3.40 (m, CH–N, 4H), 4.98 and 5.17 (AB,
J¼12.8 Hz, O–CH2, 8H), 6.73–6.97 (m, ArH, 8H), 7.10–
7.33 (m, (6,60),(7,70),(8,80)-binaphH, 12H), 7.74 (d,
J¼8.5 Hz, 3,30-binaphH, 4H), 7.94 (d, J¼8.0 Hz, 5,50-bi-
naphH, 4H), 8.12 (d, J¼9.0 Hz, 4,40-binaphH, 4H), 8.35
(s, CH]N, 4H), 13.25 (s, OH, 4H). IR (KBr) nmax: 3446,
2963, 1679, 1634, 1549, 1429, 1360, 1269, 862 cmꢀ1
.
10. Mansikkamaki, H.; Nissinen, M.; Rissanen, K. Chem.
€
Commun. 2002, 1902–1903.
FAB(+) MS: m/z 1489 [MH]+. Anal. Calcd for
C100H104N4O8: C, 80.65; H, 6.99; N, 3.76. Found: C,
80.96; H, 7.03; N, 3.74.
€
11. Mansikkamaki, H.; Nissinen, M.; Schalley, C.; Rissanen, K.
New J. Chem. 2003, 26, 88–97.
12. Cametti, M.; Nissinen, M.; Dalla Cort, A.; Mandolini, L.;
Rissanen, K. Chem. Commun. 2003, 2420–2421.
13. Dalla Cort, A.; Mandolini, L.; Pasquini, C.; Schiaffino, L. Org.
Lett. 2004, 1697–1700.
14. Antonisse, M. M. G.; Reinhoudt, D. N. Chem. Commun. 1998,
443–448.
15. Dalla Cort, A.; Gasparrini, F.; Lunazzi, L.; Mandolini, L.;
Mozzanti, A.; Pasquini, C.; Pierini, M.; Rompietti, R.;
Schiaffino, L. J. Org. Chem. 2005, 70, 8877–8883.
16. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.;
Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still,
W. C. J. Comput. Chem. 1990, 11, 440–467.
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6.1.9. UO2 complexes 11–13. (AcO)2UO2$2H2O (5.94 mg,
0.014 mmol) was added as a solid to stirred solution of the
ligand 8, 9 or 10 (0.012 mmol) in MeOH (5 mL). The mix-
ture was allowed to stir overnight at room temperature and
was monitored by TLC (eluent: 5% EtOH in CH2Cl2). The
solvent was removed on a rotary evaporator under vacuum
and the residue was dissolved in CH2Cl2, filtered and con-
centrated to produce the pertinent uranyl complexes in
nearly quantitative yields.
Compound 11: 1H NMR (500 MHz, CDCl3): d 0.95 (s, tBu,
18H), 4.71 (d, J¼10.0 Hz, O–CH2, 2H), 5.01 (d, J¼10.0 Hz,
O–CH2, 2H), 5.61 (s, CH–N, 2H), 5.92 (s, CH–N, 2H), 6.02
(d, J¼10.0 Hz, O–CH2, 2H), 6.31 (d, J¼10.0 Hz, O–CH2,
2H), 6.89–8.25 (m, ArH and binaphH, 26H), 8.72 (s,
CH]N, 2H), 8.95 (s, CH]N, 2H). Anal. Calcd for
C58H52N2O6U$H2O: C, 61.70; H, 4.79; N, 2.48. Found: C,
61.48; H, 4.82; N, 2.46.
18. A flipping motion with k¼20 sꢀ1 at 298 K has been reported
for a uranyl salophen complex bearing a bulky substituent
such as a phenyl group on one imine carbon atom in order to
slow down the motion (see Ref. 13).
19. Dalla Cort, A.; Mandolini, L.; Calmieri, G.; Pasquini, C.;
Schiaffino, L. Chem. Commun. 2003, 2178–2179.
20. Glaser, T.; Lugger, T. Inorg. Chim. Acta 2002, 337, 103–112.
21. Hu, Y.; Hu, H. Synthesis 1991, 325–327.
22. Becker, H.-D.; Bremholt, T.; Alder, E. Tetrahedron Lett. 1972,
4205–4208.
Compound 12: 1H NMR (500 MHz, CD3COCD3): d 1.12 (s,
tBu, 36H), 5.56 and 5.79 (AB, J¼15.2 Hz, O–CH2, 8H), 6.24
(s, CH–N, 4H), 7.12–8.02 (m, ArH and binaphH, 52H), 9.38
(s, CH]N, 4H). Anal. Calcd for C116H104N4O12U2$2H2O:
C, 61.70; H, 4.79; N, 2.48. Found: C, 61.95; H, 4.81; N, 2.47.