A novel C3-symmetric triol as chiral receptor for ammonium ions

Article abstract of DOI:10.1002/ejoc.200600673

The enantiopure C₃-symmetric syn-benzotriborneol was efficiently obtained in an eight-step route. Of particular interest from a synthetic point of view are the potassium tert-butoxide promoted bromination of camphor hydrazone (4) and the observation that the protecting groups influence the syn/anti diasteroselectivity of the cyclotrimerization reaction of 12-14. Complexation studies in deuteriochloroform revealed the capability of the cyclotrimer syn-1 to act as host for ammonium ions, and in particular, the efficient chiral recognition of the two enantiomers of (1-phenylethyl)ammonium chloride. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200600673

FULL PAPER
DOI: 10.1002/ejoc.200600673
A Novel C3-Symmetric Triol as Chiral Receptor for Ammonium Ions
Fabrizio Fabris,*[a] Leonardo Pellizzaro,[a] Cristiano Zonta,*[a] and Ottorino De Lucchi[a]
Keywords: Chirality / Host-guest systems / Enantioselective recognition / Cyclotrimerization / Tripodal ligand
The enantiopure C3-symmetric syn-benzotriborneol was ef-
ficiently obtained in an eight-step route. Of particular inter-
est from a synthetic point of view are the potassium tert-bu-
toxide promoted bromination of camphor hydrazone (4) and
the observation that the protecting groups influence the
syn/anti diasteroselectivity of the cyclotrimerization reaction
vealed the capability of the cyclotrimer syn-1 to act as host
for ammonium ions, and in particular, the efficient chiral re-
cognition of the two enantiomers of (1-phenylethyl)ammo-
nium chloride.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
of 12–14. Complexation studies in deuteriochloroform re- Germany, 2007)
Introduction
The interest during the last two decades of various re-
search groups in the preparation of strained aromatic rings
led to the synthesis of a large number of compounds arising
from cyclotrimerization of three bicycloalkene units
(Scheme 1).[1–5] These compounds were used as precursors
of subunits of fullerene,[3j] as scaffolds for supramolecular
chemistry,[3e] as starting material for the synthesis of trind-
ane structures,[3m] and as basic structures for the study of
Scheme 1. Synthesis of benzocyclotrimers using the cyclotrimeri-
zation reaction leads to formation of the syn and anti isomers. The
most typical system involves the presence of a double bond with
Mills–Nixon effects or radical stabilization, which are fea-
tures intrinsic to these molecules.[4c] The use of different
reaction conditions and reagents largely improved the yields vicinal halogen and metal substituents.
of the cyclotrimers and the syn/anti diastereoselectivity, key
The rigid C3-symmetric structure of triol syn-1 (Fig-
points for the development of supramolecular hosts. In-
deed, syn cyclotrimers are valuable substrates because of
the presence of two rigid bowl-shaped pockets, which could
be properly functionalized in order to develop selective re-
ceptors. In particular, their deeper pocket conveys a pecu-
liar cavity displaying particular electronic features useful for
complexation.[3e]
ure 1), bearing three hydroxy groups on the concave side
of the molecule, prompted us to undertake a study of its
complexation properties. The importance of C3 symmetry
in chiral recognition has been pointed out.[6] The highly
chemo- and diastereoselective synthesis and the chiral re-
cognition properties of this molecule are herein reported.
Our contribution to this field was the development of an
original reaction involving trimerization of vicinal bromo-
trimethylstannyl olefins with a copper promoter.[2h] This
methodology led to the synthesis of a large variety of new
compounds and to a deeper knowledge of the mechanism
of cyclotrimerization reactions.
In a previous communication, the cyclotrimerization of
suitably hindered enantiopure bicyclic vicinal bromotri-
methylstannyl olefins bearing masked hydroxy groups was
reported to give good yields and high diastereoselectivities
in favor of the syn isomer.[2i]
Figure 1. syn-Benzotriborneol syn-1 presents three hydroxy groups
in a rigid conformation describing a hydrophilic cavity.
Results and Discussion
[a] Dipartimento di Chimica, Università Ca’ Foscari di Venezia,
Dorsoduro 2137, 30123 Venezia, Italy
Synthesis of Triols
Fax: +39-41-2348517
E-mail: fabrisfa@unive.it
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
The starting material for the preparation of the triol was
the readily available (–)-bornyl acetate that was oxidized to
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Scheme 2. Synthesis of the hydrazone precursor 4. Reagents and conditions: a) CrO3, AcOH, 140 °C (22%); b) KOH, EtOH, room
temperature (95%); c) H2NNH2·H2O, H2SO4 (cat.), nBuOH, 110 °C (98%).
5-oxobornyl acetate (2) with chromium(VI) oxide in acetic
acid with a constant 44% conversion and 50% yield based
on consumed starting material (Scheme 2).[7] Many
attempts were made in order to substitute chromium(VI)
with less noxious reagents: the use of oxygen in the presence
of hydroxyphthalimide with or without transition metals
[Co(acac)3] failed to produce a reasonable amount of the
desired product.[8] The use of tert-butyl hydroperoxide in
the presence of ruthenium(III) chloride afforded ketone 2
in reasonable amounts, but the purification was compli-
cated by the presence of large amounts of byproducts.[9]
The subsequent saponification was achieved with potas-
sium hydroxide in ethanol, affording 3 in nearly quantita-
Scheme 3. Synthesis of the bromobornenol 5. Reagents and condi-
tions: a) PyHBr3, Py, Et2O, room temperature, (2:1 ratio); b)
tive yield. The latter was converted into the hydrazone de-
rivative 4 (95% yield) by heating to reflux with hydrazine
hydrate in n-butanol using a Dean–Stark trap filled with
molecular sieves (4 Å) (Scheme 2).[10]
tBuOK, DMSO, 0 °C (58%); c) NBS, Py, 0 °C (62%); d) Br2,
tBuOK, Et2O, room temperature (74%).
The transformation of the hydrazone moiety into bromo
olefin 5 was attempted in a first run with the use of pyridi-
nium perbromate as the brominating reagent and pyridine
as a proton scavenger, producing a mixture of products,
1
identified by GC-MS and H NMR as the desired olefin 5
and dibromide 6, in a 2:1 ratio (Scheme 3).[2k] The mixture
treated with potassium tert-butoxide in DMSO afforded
Scheme 4. Protection of the bromobornenol 5. Reagents and condi-
tions: a) i) NaH, Et2O, 0 °C; ii) MeI or BnBr (80 or 74%); b)
MOMCl or MEMCl, iPr2NEt, CH2Cl2, room temperature (95 or
92%).
pure
5
in 58% yield after flash chromatography
(Scheme 3).[1b] In a second experiment, hydrazone 4 was
treated with N-bromosuccinimide in pyridine, producing in
a single step the olefin 5 free of dibromide 6 in 62% yield
(FC).[11] A further improvement was achieved performing
the reaction with bromine and potassium tert-butoxide in
diethyl ether under sonication. Under these conditions the
poor solubility of 4 and tert-butoxide in the solvent allowed
the maintenance of the low concentrations required by the
reaction. The use of potassium tert-butoxide as the base
permitted the complete suppression of intermediate 6 and
gave a clean reaction mixture that was conveniently purified
by sublimation at reduced pressure, obtaining 5 in 74%
yield (Scheme 3).
Scheme 5. Equilibrium between acetals 9 and 11. Reagents and
conditions: a) traces of silica gel, room temperature (variable
amounts).
The protection of the hydroxy group with ethers (methyl
or benzyl) and acetals [methoxymethyl (MOM) or 2-me-
thoxyethoxymethyl (MEM)] was achieved with standard propylamide (Scheme 6) to afford, in most cases, good
procedures, affording the expected products in good yields yields of stannyl derivatives [12 (83%), 13 (86%), 14 (93%)].
[80% (7), 74% (8), 95% (9), 92% (10)] (Scheme 4).[12–14]
On the contrary, benzyl ether 8 afforded quantitatively a
It was observed that samples of 9 slowly decomposed to compound without the trimethylstannyl moiety and with-
a compound less retained than 9 on silica gel. This side out the bromine atom. Complete characterisation, includ-
product was isolated and identified as the bis(acetal) 11, ing homo- and heteronuclear two-dimensional NMR spec-
which presumably arises from a transacetalization in the tra, and comparison with related structures[15] allowed the
presence of traces of silica gel in the samples (Scheme 5).
determination of the final structure as 15. This result was
The protected bromobornenols 7–10 were treated with rationalized by assuming that lithium diisopropylamide ab-
trimethyltin chloride in the presence of excess lithium diiso- stracts a benzylic hydrogen atom and the resulting carban-
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A Novel C3-Symmetric Triol as Chiral Receptor for Ammonium Ions
FULL PAPER
Scheme 6. Stannylation of protected bornenols 7, 9, 10. Reagents
and conditions: a) i) LDA, THF, room temperature; ii) Me3SnCl
(83, 86, 93%).
Scheme 8. Synthesis of cyclotrimers 16, 17, 18. Reagents and condi-
tions: a) CuTC, NMP, 0 °C to room temperature [syn-16 (78%),
syn-17 (72%), syn-18 (77%)].
ion intramolecularly attacks the olefin in the closer posi-
tion. The gem-bromo anion evolves to a carbene, which in-
serts at the methylene position (Scheme 7).[16] The high dia-
stereoselectivity observed at the benzylic position is proba-
bly determined by the equilibrium promoted by the excess
of lithium diisopropylamide.
purification and separation of the isomers of 17 and 18 by
flash chromatography was straightforward; syn- and anti-1
were obtained in nearly quantitative yields by the cleavage
of the acetals with hydrochloric acid in methanol at room
temperature[18] or with a sulfonated polystyrene (Bayer
K2613) in refluxing methanol. The latter methodology was
preferred because of the lower amount of water contained
1
in the resulting triols, as determined by H NMR analysis
(Scheme 9 and Table 1).
Scheme 7. Proposed mechanism of formation of 15.
Trimerizations were performed using the well-established
methodology based on the use of copper(I) 2-thiophenecar-
boxylate (CuTC).[2h–2k,3i–3l,5f] This reagent afforded good
yields of trimers [16 (82%), 17 (86%), 18 (93%)], with dif-
ferent syn/anti ratios, according to the protecting groups on
the alcoholic moieties (Scheme 8). The highest stereoselecti-
vity was obtained with methyl derivative 12, which gave es-
sentially pure syn-16, while MOM- and MEM-protected
bornenols 13 and 14 afforded 85:15 and 83:17 syn/anti mix-
tures, respectively.[2k]
The variable amounts of isomers can be explained by the
steric hindrance exerted by the protecting groups. Indeed,
in the anti structures, only two substituents are forced to
face each other, while in the syn isomers all the three ethers
are close together in the concave portions of the molecules,
and the energy gap increases with the bulkiness of the sub-
stituent. Nevertheless, a further interaction of ethers with
copper can be taken into consideration to justify such high
syn selectivity. In fact, the higher syn/anti ratios were ob-
tained only with substrates containing heteroatoms.[3k,3l]
Despite the higher diastereomeric ratio obtained in the
case of cyclotrimer 16, the high stability of the methyl ether,
Scheme 9. Deprotection of cyclotrimers 17 and 18. Reagents and
conditions: a) concd. HCl, MeOH, room temperature (quant.); b)
acid resin, MeOH, 70 °C (quant.).
Table 1. Yields and ratios obtained for the different protections of
hydroxy groups.
Protecting Protection Stannylation Cyclotrimerization syn/anti Deprotection
group
(%)
(%)
(%)
ratio
(%)
Me
80
95
92
83
86
93
82
86
93
99:1
85:15
83:17
–
MOM
MEM
98
95
Complexation Experiments
It has been shown that enantiopure C3-symmetric tripo-
which requires drastic cleavage conditions, makes this sub- dal ligands exhibit interesting enantiodiscrimination prop-
strate unappealing for the preparation of triol syn-1.[17] The erties toward chiral ammonium ions.[19] The complexation
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F. Fabris, L. Pellizzaro, C. Zonta, O. De Lucchi
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properties of triol syn-1 were studied by means of NMR (Figure 2) and 1H NMR titrations to determine the associa-
complexation experiments. In order to test the complex- tion constants (Table 2, Figure 3) and complexation-in-
ation capabilities and the chiral recognition properties of duced changes in chemical shifts. The Job plots showed the
syn-1, the chiral cation (1-phenylethyl)ammonium chloride clear formation of a 1:2 complex between the triol and the
(19) was chosen. Preliminary experiments showed that the ammonium salt. This phenomenon had already been ob-
addition of 1 equiv. of rac-(1-phenylethyl)ammonium chlo- served for systems possessing multiple binding sites.[20] In
ride to a solution of the triol syn-1 in deuteriochloroform the case of multivalency of the system, the binding of the
leads to a splitting of the proton and carbon resonances of ammonium ion and its counterion is followed by the bind-
the ammonium ion due to formation of diasteromeric cou- ing of a second ion pair. Ion pairs in fact tend to form
ples, and to a significant change in the chemical shifts of aggregates or dimers in solution, especially when the cation
the proton resonances of syn-1 caused by complexation.
has a small counteranion.[21]
In order to assess the chiral recognition capabilities of
The NMR titration experiments clearly showed that two
the triol, we started a deeper analysis of the system compar- different processes take place. The process that takes place
ing the complexation capabilities of the triol syn-1 with (1- at low concentrations is the complexation of the first ion
phenylethyl)ammonium chlorides (+)-19 and (–)-19. The pair, and the process at high concentrations is the binding
complexes were characterized in deuteriochloroform by me- of a second ion pair for the reformation of the dimer pres-
1
ans of H NMR Job plots to determine the stoichiometries ent in solution.[20] Binding association constants were deter-
1
Figure 2. H NMR Job plots for the binary mixtures syn-1 and (+)-19 and (–)-19.
1
Table 2. Association constants (K in –1) measured from H NMR titrations in deuteriochloroform at 295 K and limiting complexation-
1
induced changes in H NMR chemical shifts (∆δ in ppm).
K [–1][a]
a[b]
b
c
d
e
f
A
B
C
D
syn-1 + (–)-19 ⇔ syn-1·(–)-19
120Ϯ15
1220Ϯ210
230Ϯ18
0.0
0.0
–0.1
–0.3
–0.4
–0.8
0.0
0.0
0.0
0.0
–0.1
–0.1
0.0
0.0
0.0
0.0
–0.2
–0.1
–0.3
0.1
–0.2
0.0
–0.5
–0.2
0.0
0.0
0.0
0.0
syn-1·(–)-19 + (–)-19 ⇔ syn-1·[(–)-19]2
syn-1 + (+)-19 ⇔ syn-1·(+)-19
–0.4
–0.5
–0.8
–0.1
–0.1
–0.2
–0.1
–0.1
–0.2
–0.1
–0.2
–0.2
syn-1·(+)-19 + (+)-19 ⇔ syn-1·[(+)-19]2
2380Ϯ180
[a] Average values from at least two separate experiments. Titration data for 4 to 6 different signals were used to determine the association
constant in each case. Errors are quoted as twice the standard error from the weighted mean (weighting based on the observed change
in chemical shift). [b] See Figure 3 for the proton labelling.
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A Novel C3-Symmetric Triol as Chiral Receptor for Ammonium Ions
FULL PAPER
reagents were employed without further purification. Dry THF and
Et2O were distilled prior to use from sodium/benzophenone. Dry
diisopropylamine, DMSO and NMP were distilled prior to use
from calcium hydride. Copper(I) 2-thiophenecarboxylate (CuTC)
was obtained according to the procedure reported by Liebes-
kind.[23] The progress of the reactions was monitored by TLC, GC-
MS or 1H NMR spectroscopy. Gas-chromatographic analyses were
performed with a 30 m, 0.25 mm i.d., Rtx-5MS capillary column
(5:95 diphenyl/dimethylpolysiloxane). Flash-chromatographic puri-
fications were performed with 230–400 mesh silica gel Merk 60.
Melting points are uncorrected. Optical rotations were measured
in a 10 cm cell.
Figure 3. Proton labelling scheme for the titrations of Table 2.
mined using Hunter’s NMRTit HGG program, and com-
plexation was confirmed by NOESY experiments.[22] The
binding constants and the complexation-induced changes in
chemical shifts (CIS) are shown in Table 2. The titration
experiments for both the enantiomers indicate a small first
complexation constant followed by a larger second iso-
therm binding constant. CIS values are not easily interpret-
able due to the concurrent effects in the complexation com-
ing from the ring current and the positive charge of the
ammonium ion. The upfield chemical shifts for the proton
close to the alcoholic position (a,b,c) and the low variation
of the CIS for the methyl group at the top of the bridge
(d,e), indicate the formation of an inclusion complex involv-
ing the cavity formed by the triols. This is also confirmed
by the NOE observed between the methyne proton of the
triol and the o-aryl and benzylic protons of the ammonium
ion. The main difference between the two diastereoisomers
is represented by the CIS values in the first binding con-
stant. The largest upfield variation present for (+)-19 could
arise from a major level of interpenetration of the phenyl
ring in the cavity.
(1S,2R,4S)-2-Hydroxy-1,7,7-trimethylbicyclo[2.2.1]heptan-5-one
Hydrazone (4): A mixture of 3 (30 g, 178 mmol), hydrazine hydrate
(70 mL, 1.4 mol) and concd. H2SO4 (1.0 mL) in nBuOH (150 mL)
was refluxed in a Dean–Stark apparatus for 16 h, the trap being
filled with molecular sieves (4 Å) (100 mL). The resulting solution
was cooled, allowing the sulfate salts to settle on the bottom of the
flask, the supernatant was filtered by suction, and the salts were
washed with small amounts of Et2O (3ϫ10 mL). The filtrate was
concentrated in vacuo and the resulting solid was triturated with
n-hexane and filtered to afford a white powder (31.7 g, 98%). An
analytical sample of 4 was prepared by recrystallization from
CH2Cl2; m.p. 145–147 °C. [α]2D2 = +6.8 (c = 2.2, CHCl3). 1H NMR
(200 MHz, CDCl3): δ = 4.68 (br. s, 3 H), 4.15 (ddd, J = 9.8, 3.4,
1.6 Hz, 1 H), 2.52 (d, J = 17.0 Hz, 1 H), 2.46 (ddd, J = 13.6, 9.8,
4.6 Hz, 1 H), 2.26 (d, J = 4.6 Hz, 1 H), 1.84 (br. d, J = 17.0 Hz, 1
H), 1.25 (dd, J = 13.6, 3.4 Hz, 1 H), 0.99 (s, 3 H), 0.93 (s, 3 H),
0.84 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 162.4, 75.6,
53.5, 50.4, 48.3, 36.2, 29.8, 20.3, 17.8, 13.0 ppm. IR (KBr): ν =
˜
3323, 3152, 2950, 1679, 1628, 1449, 1386, 1339, 1106, 1047, 981,
894, 855, 654 cm–1. MS (EI, 70 eV): m/z (%) = 182 (17) [M+], 164
(10), 149 (14), 123 (40), 79 (43), 55 (48), 41 (100). C10H18N2O
(182.26): calcd. C 65.90, H 9.95; found C 65.88, H 9.94.
The analysis of the binding constants of the two enantio-
mers makes evident the enantiodiscrimination of the triol.
In each process, the affinity of the triol for (+)-19 is double
that of the other enantiomer, leading to the overall com-
plexation constant being four times larger.
(1S,4S,6R)-3-Bromo-6-hydroxy-1,7,7-trimethylbicyclo[2.2.1]hept-2-
ene (5). Method a: To a well-stirred slurry of pyridinium perbro-
mate (7.7 g, 24.0 mmol) and pyridine (3.8 mL, 38.0 mmol) in Et2O
(100 mL) was added dropwise a solution of 4 (2.2 g, 12.0 mmol) in
Et2O (150 mL). Evolution of gas (N2) was observed with a bubbler
during the addition. After the addition was complete, the mixture
was stirred for an additional 15 min, H2O (100 mL) was added,
and the layers were separated. The organic layer was washed with
2  hydrochloric acid (3ϫ50 mL), 3% NaHCO3 (2ϫ50 mL), and
brine (50 mL), and then dried with MgSO4. The resulting solution
was concentrated at reduced pressure to afford a crude product
containing a mixture of 5 and 6 in a 2:1 ratio. The mixture of 5
and 6 was diluted with dry DMSO (10 mL) and tBuOK (225 mg,
6.0 mmol) was added portionwise, at 0 °C under Ar. The resulting
dark solution was stirred an additional 45 min, diluted with water
(150 mL) and extracted with a 2:1 mixture of Et2O/pentane
(3 ϫ 40 mL). The combined organic extracts were washed with
water (3ϫ10 mL), brine (20 mL), dried with MgSO4 and concen-
trated. The residue was purified by flash chromatography (Et2O/
pentane, 3:7) to afford 6 (1.6 g, 58%) as a pale yellow solid. 1H
NMR (400 MHz, CDCl3): δ = 3.98 (br. d, J = 7.5 Hz, 1 H), 3.24
(d, J = 13.0 Hz, 1 H), 2.89 (d, J = 13.0 Hz, 1 H), 2.59 (d, J =
3.6 Hz, 1 H), 2.44 (m, 1 H), 2.21 (dd, J = 12.5, 2.5 Hz, 1 H), 1.33
(s, 3 H), 1.04 (s, 3 H), 0.88 (s, 3 H), (OH signal not observed) ppm.
MS (EI, 70 eV): m/z (%) = 232–230 (18) [M+ – HBr], 215–217 (17),
186–188 (16), 151 (67), 107 (100), 91 (91), 83 (91). Method b: To a
solution of NBS (3.0 g, 17.0 mmol) in dry pyridine (20 mL) main-
tained at 0 °C under Ar, was added a solution of 4 (1.5 g, 8.2 mmol)
in dry pyridine (10 mL). Evolution of gas (N2) was observed with
Conclusion
We described an effective procedure for the synthesis of
an enantiopure C3-symmetric functionalized cyclotrimer
bearing three hydroxy groups in the lower rim. The intro-
duction of functional groups in this rigid scaffold has been
the prerequisite for the development of structures suitable
for supramolecular chemistry investigations. In fact, the
preliminary analysis of the complexation capabilities of this
host revealed an interesting feature of the triol syn-1, that
displayed good complexation and enantiodiscrimination
capabilities with respect to the (1-phenylethyl)ammonium
ion. The unique features of the three hydroxy groups of the
triol and the possibility for further functionalization of the
system open new interesting frontiers for future applica-
tions, which are presently under investigation.
Experimental Section
General: Reactions were carried out using standard techniques in
flame-dried glassware cooled under argon. Commercial high purity
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F. Fabris, L. Pellizzaro, C. Zonta, O. De Lucchi
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a bubbler during the addition. After the addition was complete, the
mixture was stirred for an additional 45 min, H2O (300 mL) was
added and the mixture was extracted with a 2:1 mixture of Et2O/
pentane (3ϫ50 mL). The combined organic layers were washed
with 2  hydrochloric acid (3 ϫ50 mL) and brine (50 mL), and
were dried with MgSO4. The resulting solution was distilled to re-
move volatile materials and the residue was purified by flash
chromatography (eluent Et2O/pentane, 3:7) to afford 5 (1.2 g, 62%)
as a pale yellow solid. Method c: A flame-dried three-necked round-
bottomed flask, equipped with a mechanical stirrer, an argon inlet
with bubbler, and a dropping funnel, was placed in a sonication
bath. Bromine (9.8 mL, 82.8 mmol) was added to a slurry of 4
(6.10 g, 33.5 mmol) and tBuOK (15.0 g, 134 mmol) in dry Et2O
(350 mL) under sonication and vigorous stirring conditions over
1 h. During the addition evolution of gas (N2) was observed. Water
(100 mL) was added to the resulting mixture, the layers were sepa-
rated, and the lower layer was extracted with Et2O (3ϫ50 mL).
The combined organic extracts were dried with MgSO4, concen-
trated in vacuo, and the resulting red oil was purified by sublima-
tion (110 °C at 7.5ϫ10–2 Torr) to afford 5.7 g (74%) of 5 as color-
less crystals; m.p. 66–69 °C. [α]2D2 = +72 (c = 2.4, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 5.78 (br. s, 1 H), 4.15 (dd, J = 7.5, 2.6 Hz,
1 H), 2.47 (ddd, J = 13.1, 7.5, 3.8 Hz, 1 H), 2.40 (dd, J = 3.8,
1.0 Hz, 1 H), 1.12 (s, 3 H), 1.06 (dd, J = 13.1, 2.6 Hz, 1 H), 0.94
(s, 3 H), 0.80 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 133.8,
128.5, 78.5, 60.34, 60.29, 59.3, 37.8, 20.1, 18.8, 10.5 ppm. IR (KBr):
δ = 139.4, 136.1, 128.7, 127.8, 127.7, 125.8, 86.0, 71.8, 60.5, 60.1,
58.8, 34.4, 20.2, 19.5, 11.6 ppm. IR (film): ν = 2960, 2863, 1586,
˜
1455, 1096, 725, 683 cm–1. MS (EI, 70 eV): m/z (%) = 320 (1) [M+],
230 (65), 229 (59), 189 (40), 188 (56), 187 (46), 185 (72), 121 (72),
106 (100). C17H21BrO (321.25): calcd. C 63.56, H 6.59; found C
63.81, H 6.62.
General Procedure for the Protection of Bromobornenol with Ace-
tals: To a solution of 5 (2.3 g, 10.0 mmol) and iPr2NEt (3.5 mL,
30.0 mmol) in dry CH2Cl2 (15 mL), maintained at 0 °C under Ar,
was added MOMCl or MEMCl (15.0 mmol) through a syringe.
The mixture was allowed to warm to room temperature overnight.
Dry MeOH (0.2 mL) was added, and the solution was stirred for
an additional 30 min. Water (50 mL) was added, and the mixture
was extracted with Et2O (3ϫ50 mL). The combined ethereal ex-
tracts were washed with H2O (3ϫ20 mL), dried with MgSO4 and
concentrated in vacuo. The residue was purified by flash
chromatography.
(1S,4S,6R)-3-Bromo-6-(methoxymethoxy)-1,7,7-trimethylbicyclo-
[2.2.1]hept-2-ene (9): Eluent AcOEt/nhexane (0.5:9.5). Colorless oil
(95%). [α]2D2 = +33 (c = 2.2, CHCl3). 1H NMR (300 MHz, CDC13):
δ = 5.76 (br. s, 1 H), 4.63 (d, J = 6.9 Hz, 1 H), 4.59 (d, J = 6.9 Hz,
1 H), 4.14 (dd, J = 7.2, 2.8 Hz, 1 H), 3.34 (s, 3 H), 2.39 (br. s, 1
H), 1.23 (dd, J = 9.7, 2.8 Hz, 2 H), 1.13 (s, 3 H), 0.94 (s, 3 H), 0.81
(s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 135.7, 126.2, 96.2,
83.9, 60.5, 59.9, 58.8, 55.6, 35.1, 20.2, 19.4, 11.4 ppm. IR (film): ν
˜
ν = 3353, 2956, 2869, 1584, 1449, 1382, 1288, 1060, 1053 cm–1. MS
= 2957, 2887, 1755, 1586, 1452, 1390, 1365, 1277, 1225, 1151, 1102,
1047, 1000, 919, 831, 774, 732 cm–1. MS (EI, 70 eV): m/z (%) =
229–231 (5) [M+ – C2H6O], 186–188 (32), 119–121 (91), 105–107
(100), 91 (57). C12H19BrO2 (275.18): calcd. C 52.38, H 6.96; found
C 52.57, H 6.96. Samples of 9, upon standing at room temperature,
slowly decomposed to a colorless solid material that was collected
by suction filtration. Recrystallization from hot MeOH afforded
pure acetal 11, in variable amounts; m.p. 122–125 °C. [α]2D2 = +40
(c = 1.0, CHC13). 1H NMR (300 MHz, CDC13): δ = 5.76 (s, 2 H),
4.62 (s, 2 H), 4.24 (dd, J = 7.1, 2.6 Hz, 2 H), 2.40 (br. d, J = 3.5 Hz,
2 H), 2.32 (ddd, J = 12.6, 7.1, 3.5 Hz, 2 H), 1.21 (dd, J = 12.6,
2.6 Hz, 2 H), 1.13 (s, 6 H), 0.95 (s, 6 H), 0.83 (s, 6 H) ppm. 13C
NMR (50 MHz, CDCl3): δ = 135.2, 125.8, 92.5, 82.3, 60.0, 59.4,
˜
(EI, 70 eV): m/z (%) = 186–188 (24) [M+ – C2H3OH], 151 (10), 107
(99), 91 (100). C10H15BrO (231.13): calcd. C 51.97, H 6.54; found
C 51.79, H 6.51.
General Procedure for the Protection of Bromobornenol with Ethers:
A 60% dispersion of NaH in mineral oil (160 mg, 6.9 mmol) was
washed with pentane (3ϫ5 mL) under argon. The resulting powder
was suspended in dry Et2O (10 mL), cooled in a ice bath, and 5
(1.06 g, 4.6 mmol) was added in one portion. The mixture was
stirred for 15 min and BnBr or MeI (5.0 mmol) was added dropwise
through a syringe. The mixture was allowed to warm to room tem-
perature overnight, dry MeOH (0.2 mL) was added, and the mix-
ture was stirred for an additional 30 min. Water (50 mL) was
added, and the mixture was extracted with Et2O (3ϫ50 mL). The
combined ethereal extracts were washed with H2O (3ϫ20 mL),
dried with MgSO4 and concentrated in vacuo. The residue was
purified by flash chromatography (CH2Cl2/n-hexane, 1.5:8.5).
58.5, 34.4, 19.8, 19.0, 11.3 ppm. IR (KBr): ν = 2964, 2886, 1585,
˜
1390, 1168, 1097, 1044, 727 cm–1. MS (EI, 70 eV): m/z (%) = 243–
245 (3) [M+ – C10H13BrO], 229–231 (60), 187–189 (59), 171 (31),
163 (34), 149 (26), 121 (100). C21H30Br2O2 (474.27): calcd. C 53.18,
H 6.38; found C 53.40, H 6.39.
(1S,4S,6R)-3-Bromo-6-methoxy-1,7,7-trimethylbicyclo[2.2.1]hept-2-
ene (7): Colorless oil (80%); b.p. 96–98 °C at 7.5ϫ10–2 Torr. [α]2D2
= +54 (c = 1.4, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 5.75 (s,
1 H), 3.77 (dd, J = 7.0, 2.6 Hz, 1 H), 3.29 (s, 3 H), 2.41 (d, J =
4.0 Hz, 1 H), 2.26 (ddd, J = 12.5, 7.0, 4.0 Hz, 1 H), 1.20 (dd, J =
12.5, 2.6 Hz, 1 H), 1.13 (s, 3 H), 0.94 (s, 3 H), 0.82 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 135.12, 125.5, 88.0, 59.8, 59.4,
(1S,4S,6R)-3-Bromo-6-[(2-methoxyethoxy)methoxy)]-1,7,7-trimeth-
ylbicyclo[2.2.1]hept-2-ene (10): Eluent AcOEt/nhexane (1.5:8.5).
Colorless oil (92%). [α]2D2 = +41 (c = 0.9, CHC13). 1H NMR
(200 MHz, CDC13): δ = 5.75 (br. s, 1 H), 4.70 (br. s, 2 H), 4.20
(dd, J = 7.1, 2.6 Hz, 1 H), 3.80–3.50 (series of m, 4 H), 3.40 (s, 3
H), 2.39 (br. s, 1 H), 2.40–2.27 (m, 2 H), 1.22 (dd, J = 12.3, 2.6 Hz,
1 H), 1.11 (s, 3 H), 0.94 (s, 3 H), 0.82 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 135.2, 125.4, 94.8, 83.6, 71.7, 66.7, 60.0,
58.4, 57.5, 33.4, 19.7, 18.9, 11.1 ppm. IR (film): ν = 2959, 2873,
˜
2820, 1587, 1451, 1389, 1363, 1277, 1229, 1098, 997, 917, 830, 729,
544 cm–1. MS (EI, 70 eV): m/z (%) = 244–245 (2) [M+], 186–187
(55), 107 (100), 91 (48). C11H17BrO (245.16): calcd. C 53.89, H
6.99; found C 54.08, H 7.02.
59.4, 59.0, 58.4, 34.7, 19.8, 19.0, 11.0 ppm. IR (film): ν = 2956,
˜
2872, 1586, 1452, 1389, 1364, 1277, 1199, 1171, 1134, 1108, 1049,
1000, 982, 916, 852, 775 cm–1. MS (EI, 70 eV): m/z (%) = 243–245
(2) [M+ – C3H7O2], 239 (8), 229–231 (35), 221 (24), 186 (45), 163
(54), 121 (80), 107 (100), 89 (70). C14H23BrO3 (319.23): calcd. C
52.67, H 7.26; found C 52.59, H 7.26.
(1S,4S,6R)-3-Bromo-6-benzyloxy-1,7,7-trimethylbicyclo[2.2.1]hept-
2-ene (8): Colorless oil (74%). [α]2D2 = +36 (c = 5.0, CHCl3). 1H
NMR (300 MHz, CDCl3): δ = 7.40–7.25 (m, 5 H), 5.82 (br. s, 1
General Procedure for the Stannylation of Protected Bromo-
H), 4.57 (d, J = 12.4 Hz, 1 H), 4.41 (d, J = 12.4 Hz, 1 H), 3.97 (dd, bornenols: To a solution of dry diisopropylamine (3.3 mL,
J = 7.0, 2.6 Hz, 1 H), 2.42 (d, J = 3.7 Hz, 1 H), 2.24 (ddd, J = 25.0 mmol) in dry THF (25 mL), maintained at 0 °C under Ar, was
12.5, 7.0, 3.7 Hz, 1 H), 1.28 (dd, J = 12.5, 2.6 Hz, 1 H), 1.13 (s, 3 added dropwise nBuLi (10.0 mL, 2.5  solution in hexanes,
H), 0.94 (s, 3 H), 0.78 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): 25.0 mmol), and the mixture was maintained at 0 °C for 15 min.
288
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A Novel C3-Symmetric Triol as Chiral Receptor for Ammonium Ions
FULL PAPER
The protected bromobornenol (7–10) (10.0 mmol) was added
through a syringe, and the mixture was stirred for an additional
15 min. Trimethyltin chloride (2.0 g, 10.0 mmol) was added in one
portion, and the mixture was allowed to warm to room tempera-
ture overnight. The resulting solution was poured into water
(100 mL) and extracted with Et2O (3ϫ50 mL). The combined or-
ganic extracts were washed with H2O (50 mL), saturated aqueous
NaCl (50 mL), dried with MgSO4, and concentrated in vacuo to
afford an oil that was purified by flash chromatography.
General Procedure for the Cyclotrimerization of Protected Bromo-
(stannyl)bornenols: To a solution of the protected bromo(stannyl)-
bornenol (5.0 mmol) in dry NMP (15 mL), maintained at –20 °C
under Ar, CuTC (1.43 g, 7.5 mmol) was added portionwise. The
well-stirred mixture was allowed to warm to room temperature
overnight. The resulting slurry was diluted with 20% aqueous NH3
(50 mL) and extracted with AcOEt (3ϫ50 mL). The combined or-
ganic extracts were washed with H2O (50 mL) and saturated aque-
ous NaCl (50 mL), dried with MgSO4 and concentrated in vacuo
to afford an oil that was purified by flash chromatography.
(1S,4S,6R)-3-Bromo-6-methoxy-1,7,7-trimethyl-2-(trimethylstann-
yl)bicyclo[2.2.1]hept-2-ene (12): Eluent CH2Cl2/hexane (1:9). Color-
syn-(1R,2R,4S,5R,6R,8S,9R,10R,12S)-3,4,7,8,11,12-Hexahydro-
2,6,10-trimethoxy-1,5,9,13,13Ј,14,14Ј,15,15Ј-nonamethyl-
1
less oil (83%). [α]2D2 = +36 (c = 1.4, CHCl3). H NMR (200 MHz,
CDCl3): δ = 3.71 (dd, J = 7.0, 2.6 Hz, 1 H), 3.22 (s, 3 H), 2.40 (d, 1,4:5,8:9,12-trimethanotriphenylene (syn-16): Eluent Et2O/hexanes
J = 3.7 Hz, 1 H), 2.18 (ddd, J = 12.4, 7.0, 3.7 Hz, 1 H), 1.18 (dd,
J = 12.4, 2.6 Hz, 1 H), 1.15 (s, 3 H), 0.92 (s, 3 H), 0.80 (s, 3 H),
(1:9). Colorless crystals (78%) from hot MeOH; m.p. 139–140 °C.
[α]2D2 = +84 (c = 1.0, CHCl3). 1H NMR (200 MHz, CDCl3): δ =
0.22 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 148.6, 138.0, 3.82 (dd, J = 8.2, 3.0 Hz, 3 H), 3.08 (s, 9 H), 2.98 (d, J = 4.3 Hz,
88.0, 64.6, 62.1, 57.8, 57.2, 33.6, 20.0, 19.0, 13.2, –7.9 ppm. IR 3 H), 2.28 (ddd, J = 12.4, 8.2, 4.3 Hz, 3 H), 1.34 (s, 9 H), 1.25 (dd,
(film): ν = 2987, 2958, 2873, 2819, 1553, 1450, 1388, 1361, 1276,
J = 12.4, 3.0 Hz, 3 H), 0.94 (s, 9 H), 0.57 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 140.5, 134.0, 86.4, 57.1, 56.9, 56.4, 48.9,
˜
1183, 1113, 1095, 1051, 1013, 990, 773, 529, 513 cm–1. MS (EI,
70 eV): m/z (%) = 392 (36) [M+ – CH3], 334 (80), 255 (61), 228
(100). C14H25BrOSn (407.96): calcd C 41.22, H 6.18; found C
41.39, H 6.16.
33.3, 21.0, 19.3, 12.5 ppm. IR (KBr): ν = 3442, 2979, 2925, 2869,
˜
2819, 1445, 1386, 1363, 1231, 1190, 1109, 1039, 1001, 647 cm–1.
MS (EI, 70 eV): m/z (%) = 492 (6) [M+], 434 (39), 376 (54), 318
(100), 303 (31). C33H48O3 (492.73): calcd. C 80.44, H 9.82; found
C 80.62, H 9.83.
(1S,2S,3R,4S,6R,7R,9S)-9-Phenyl-5,5Ј,6-trimethyl-8-oxatetracyclo-
[4.3.0.02,4.03,7]nonane (15): Eluent CH2Cl2/hexanes (3:7). Colorless
l
crystals (97%); m.p. 71–73 °C. [α]2D2 = +28 (c = 0.5, CHCl3). H
anti-(1S,3R,4R,5R,6R,8S,9R,10R,12S)-1,2,7,8,11,12-Hexahydro-
3,6,10-tris(methoxymethoxy)-4,5,9,13,13Ј,14,14Ј,15,15Ј-nonameth-
yl-1,4:5,8:9,12-trimethanotriphenylene (anti-17): Eluent Et2O/hex-
NMR (300 MHz, CDCl3): δ = 7.40 (d, J = 7.1 Hz, 2 H), 7.33 (d,
J = 7.1 Hz, 2 H), 7.20 (d, J = 7.1 Hz, 1 H), 5.07 (s, 1 H), 4.17 (d,
J = 2.0 Hz, 1 H), 2.49 (d, J = 2.0 Hz, 1 H), 1.54–1.44 (m, 2 H), anes (2:8). Colorless crystals (13%) from hot MeOH; m.p. 105–
1.28 (t, J = 5.0 Hz, 1 H), 0.84 (s, 3 H), 0.85 (s, 3 H), 0.57 (s, 3 H) 107 °C. [α]2D2 = +62 (c = 0.8, CHCl3). 1H NMR (300 MHz, CDCl3):
ppm. 13C NMR (75 MHz, CDCl3): δ = 143.4, 127.9, 126.1, 125.0,
δ = 4.54–4.40 (series of m, 6 H), 4.17–4.09 (series of m, 6 H), 3.19
(s, 3 H), 3.18 (s, 3 H), 3.13 (s, 3 H), 2.98 (d, J = 4.1 Hz, 1 H), 2.72
(d, J = 4.0 Hz, 1 H), 2.67 (d, J = 4.0 Hz, 1 H), 2.51–2.29 (series of
m, 3 H), 1.46 (s, 3 H), 1.45 (s, 3 H), 1.37 (s, 3 H), 1.25 (dd, J =
12.5, 3.2 Hz, 1 H), 1.07 (dd, J = 10.6, 3.2 Hz, 1 H), 1.03 (dd, J =
10.0, 2.7 Hz, 1 H), 0.97 (s, 3 H), 0.93 (s, 6 H), 0.59 (s, 3 H), 0.54
(s, 3 H), 0.47 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 141.8,
139.08, 139.07, 137.8, 136.0, 132.7, 96.0, 95.9, 95.7, 83.0, 82.5, 82.3,
58.5, 58.1, 57.5, 57.3, 57.0, 56.9, 54.95, 54.94, 54.8, 49.4, 49.2, 48.4,
36.2, 35.9, 34.8, 20.8, 20.72, 20.68, 19.9, 19.8, 19.3, 14.1, 14.0,
87.3, 80.1, 52.5, 51.2, 45.4, 27.5, 22.2, 22.1, 19.4, 18.0, 8.4 ppm. IR
(KBr): ν = 3056, 2956, 2856, 1462, 1034, 991, 710 cm–1. MS (EI,
˜
70 eV): m/z (%) = 240.2 (11) [M+], 165 (7), 143 (75), 120 (29), 119
(100), 105 (29), 91 (65). C17H20O (240.44): calcd. C 84.96, H 8.39;
found C 84.66, H 8.42.
(1S,4S,6R)-3-Bromo-6-(methoxymethoxy)-1,7,7-trimethyl-2-(tri-
methylstannyl)bicyclo[2.2.1]hept-2-ene (13): Eluent CH2Cl2/n-hex-
ane (1:9). Colorless oil (86%). [α]2D2 = +38 (c = 1.0, CHCl3). 1H
NMR (300 MHz, CDC13): δ = 4.59 (d, J = 6.8 Hz, 1 H), 4.53 (d,
J = 6.8 Hz, 1 H), 4.10 (dd, J = 7.2, 2.7 Hz, 1 H), 3.34 (s, 3 H), 2.40
(d, J = 3.6 Hz, 1 H), 2.28 (ddd, J = 12.5, 7.2, 3.6 Hz, 1 H), 1.21
(dd, J = 12.5, 2.6 Hz, 1 H), 1.16 (s, 3 H), 0.93 (s, 3 H), 0.81 (s, 3
H), 0.23 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 147.0,
138.3, 95.6, 83.4, 64.4, 62.1, 57.7, 55.2, 34.8, 19.9, 19.0, 13.1,
12.5 ppm. IR (KBr): ν = 2931, 1152, 1048, 917 cm–1. C H O
˜
36 54
6
(582.81): calcd. C 74.19, H 9.34; found C 74.46, H 9.31.
syn-(1R,2R,4S,5R,6R,8S,9R,10R,12S)-3,4,7,8,11,12-Hexahydro-
2,6,10-tris(methoxymethoxy)-1,5,9,13,13Ј,14,14Ј,15,15Ј-nonameth-
yl-1,4:5,8:9,12-trimethanotriphenylene (syn-17): Eluent Et2O/hex-
anes (1:1). Colorless crystals (72%) from hot MeOH; m.p. 184–
186 °C. [α]2D2 = +111 (c = 0.8, CHCl3). 1H NMR (300 MHz,
–7.9 ppm. IR (film): ν = 2955, 2882, 1552, 1449, 1388, 1363, 1275,
˜
1186, 1151, 1102, 1046, 1013, 919, 773, 717, 529 cm–1. MS (EI,
70 eV): m/z (%) = 423–425 (29) [M+ – CH3], 335–337 (72), 229–231 CDCl3): δ = 4.46 (d, J = 6.6 Hz, 3 H), 4.39 (d, J = 6.6 Hz, 3 H),
(44), 165 (49), 41 (100). C15H27BrO2Sn (437.99): calcd. C 41.13, H
6.21; found C 41.19, H 6.20.
4.17 (dd, J = 8.0, 2.5 Hz, 3 H), 3.17 (s, 9 H), 3.00 (d, J = 3.9 Hz,
3 H), 2.38 (ddd, J = 12.4, 8.0, 3.9 Hz, 3 H), 1.35 (s, 9 H), 1.28 (dd,
J = 12.4, 2.5 Hz, 3 H), 0.97 (s, 9 H), 0.63 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 140.7, 134.0, 95.5, 82.7, 57.0, 56.7, 54.8,
(1S,4S,6R)-3-Bromo-6-[(2-methoxyethoxy)methoxy]-1,7,7-trimethyl-
2-(trimethylstannyl)bicyclo[2.2.1]hept-2-ene (14): Eluent AcOEt/n-
hexane (2:8). Colorless oil (93%). [α]2D2 = +37 (c = 1.2, CHCl3). 1H
NMR (200 MHz, CDCl3): δ = 4.69 (d, J = 7.0 Hz, 1 H), 4.64 (d,
J = 7.0 Hz, 1 H), 4.11 (dd, J = 7.2, 2.7 Hz, 1 H), 3.78–3.52 (series
49.0, 34.8, 20.9, 19.2, 12.3 ppm. IR (KBr): ν = 2929, 2871, 1447,
˜
1389, 1149, 1108, 1048, 922 cm–1. C36H54O6 (582.81): calcd. C
74.19, H 9.34; found C 73.99, H 9.33.
of m, 4 H), 3.41 (s, 3 H), 2.37 (d, J = 3.7 Hz, 1 H), 2.72 (ddd, J = syn-(1R,2R,4S,5R,6R,8S,9R,10R,12S)-3,4,7,8,11,12-Hexahydro-
12.3, 7.2, 3.7 Hz, 1 H), 1.18 (dd, J = 12.3, 2.7 Hz, 1 H), 1.16 (s, 3 2,6,10-tris[(2-methoxyethoxy)methoxy]-1,5,9,13,13Ј,14,14Ј,15,15Ј-
H), 0.89 (s, 3 H), 0.79 (s, 3 H), 0.20 (s, 9 H) ppm. 13C NMR nonamethyl-1,4:5,8:9,12-trimethanotriphenylene (syn-18): Eluent
(50 MHz, CDCl3): δ = 148.2, 138.4, 94.7, 83.6, 71.7, 66.7, 64.5,
Et2O/hexanes (7:3). Waxy solid (77%). [α]2D2 = +71 (c = 0.6,
CHCl3). H NMR (200 MHz): δ = 4.51 (d, J = 6.9 Hz, 3 H), 4.46
1
62.1, 59.0, 57.7, 34.8, 19.9, 19.0, 13.1, –7.9 ppm. IR (film): ν =
˜
2956, 2873, 1551, 1450, 1388, 1363, 1172, 1106, 1046, 1013, 773,
529, 512 cm–1. C17H31BrO3Sn (482.04): calcd. C 42.36, H 6.48;
found C 42.46, H 6.47.
(d, J = 6.9 Hz, 3 H), 4.19 (dd, J = 8.3, 2.8 Hz, 3 H), 3.59–3.37
(series of m, 12 H), 3.36 (s, 9 H), 2.96 (d, J = 4.1 Hz, 3 H), 2.37
(ddd, J = 12.5, 8.3, 4.1 Hz, 3 H), 1.31 (s, 9 H), 1.20 (dd, J = 12.5,
Eur. J. Org. Chem. 2007, 283–291
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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289

F. Fabris, L. Pellizzaro, C. Zonta, O. De Lucchi
FULL PAPER
2.8 Hz, 3 H), 0.93 (s, 9 H), 0.58 (s, 9 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 140.7, 133.8, 94.5, 82.4, 71.8, 66.3,65.9, 58.9, 57.0,
merization of the host and guest and yields the association constant
for formation of the 1:1 complex from the host and guest mono-
mers and the limiting chemical shifts of the fully bound complex.
56.9, 34.9, 20.8, 19.2, 12.3 ppm. IR (KBr): ν = 2977, 2873, 1716,
˜
1452, 1388, 1364, 1285, 1200, 1173, 1051, 932, 850 cm–1. C42H66O9
(714.97): calcd. C 70.56, H 9.30; found C 70.29, H 9.29.
Acknowledgments
syn-(1R,2R,4S,5R,6R,8S,9R,10R,12S)-3,4,7,8,11,12-Hexahydro-
2,6,10-trihydroxy-1,5,9,13,13Ј,14,14Ј,15,15Ј-nonamethyl-
1,4:5,8:9,12-trimethanotriphenylene (syn-1). Method a: A solution
of syn-17 (100 mg, 0.17 mmol) in MeOH (10 mL) containing
concd. HCl (3 drops) was stirred at room temperature for 24 h. The
resulting mixture was concentrated in vacuo and the solid residue
was washed with CH2Cl2 (3ϫ2 mL) to afford an off-white powder;
m.p. 250–252 °C. [α]2D2 = +105 (c = 0.8, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 4.11 (dd, J = 8.8, 2.7 Hz, 3 H), 3.00 (d, J
= 4.0 Hz, 3 H), 2.57 (dd, J = 13.2, 8.8, 4.0 Hz, 3 H), 2.49 (br. s, 3
H), 1.31 (s, 9 H), 0.98 (dd, J = 13.2, 2.7 Hz, 3 H), 0.92 (s, 9 H),
0.55 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 142.1, 133.8,
This work was co-funded by MIUR (Rome) within the PRIN
national framework.
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deman, J. K. Kochi, J. Am. Chem. Soc. 1997, 119, 9393–9404;
f) F. Fabris, A. De Martin, O. De Lucchi, Tetrahedron Lett.
1999, 40, 9121–9124; g) L. Zambrini, F. Fabris, O. De Lucchi,
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8719–8724; h) G. Borsato, O. De Lucchi, F. Fabris, L. Groppo,
V. Lucchini, A. Zambon, J. Org. Chem. 2002, 67, 7894–7897;
i) F. Fabris, L. Bellotto, O. De Lucchi, Tetrahedron Lett. 2003,
77.6, 58.2, 57.9, 48.6, 38.6, 21.2, 19.1, 12.0 ppm. IR (KBr): ν =
˜
3387, 2956, 1455, 1389, 1051 cm–1. Method b: A solution of syn-17
(1.41 g, 2.42 mmol) in MeOH (20 mL) containing acidic resin
K2613 from Bayer (1.5 g) was refluxed for 24 h. The resulting mix-
ture was filtered through a Celite pad, and the filter was washed
with MeOH (3ϫ10 mL). The filtrate was concentrated in vacuo
and the residue was recrystallized from hot hexanes to afford 1.68 g
(98%) of syn-1; m.p. 266–269 °C. [α]2D2 = +104 (c = 1.2, CHCl3).
1H NMR (300 MHz, CDCl3): δ = 4.11 (dd, J = 8.9, 2.6 Hz, 3 H),
2.99 (d, J = 4.0 Hz, 3 H), 2.64–2.52 (m, 3 H), 2.49 (br. s, 3 H), 1.31
(s, 9 H), 0.97 (dd, J = 13.3, 2.8 Hz, 3 H), 0.93 (s, 9 H), 0.55 (s, 9
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 142.1, 133.8, 77.6, 58.2,
44, 1211–1213; j) A. Dastan, E. Uzundumlu, M. Balci, F.
¸
Fabris, O. De Lucchi, Eur. J. Org. Chem. 2004, 183–192; k) F.
Fabris, L. Zambrini, E. Rosso, O. De Lucchi, Eur. J. Org.
Chem. 2004, 3313–3322.
57.9, 48.6, 38.6, 21.2, 19.1, 12.0 ppm. IR (KBr): ν = 3348, 2960,
˜
2367, 1663, 1571, 1459, 1058 cm–1. C30H42O3 (450.65): calcd. C
79.96, H 9.39; found C 80.17, H 9.38.
[3] Cyclotrimers of unsaturated bicyclo[2.2.1]heptenes: a) R. Durr,
O. De Lucchi, S. Cossu, V. Lucchini, Chem. Commun. 1996,
2447–2448; b) S. Cossu, O. De Lucchi, V. Lucchini, G. Valle,
anti-(1S,3R,4R,5R,6R,8S,9R,10R,12S)-1,2,7,8,11,12-Hexahydro-
3,6,10-trihydroxy-4,5,9,13,13Ј,14,14Ј,15,15Ј-nonamethyl-
1,4:5,8:9,12-trimethanotriphenylene (anti-1): Obtained by acid resin
cleavage of anti-17 in 96% yield; m.p. 132–135 °C. [α]2D2 = +64 (c =
M. Balci, A. Dastan, B. Demirci, Tetrahedron Lett. 1997, 38,
¸
5319–5322; c) R. Durr, S. Cossu, V. Lucchini, O. De Lucchi,
Angew. Chem. Int. Ed. Engl. 1997, 36, 2805–2807; d) C. Zonta,
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8185–8188; e) C. Zonta, S. Cossu, O. De Lucchi, Eur. J. Org.
Chem. 2000, 1965–1971; f) A. Paulon, S. Cossu, O. De Lucchi,
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De Lucchi, A. Paulon, C. Zonta, Tetrahedron Lett. 2001, 42,
3515–3518; h) S. Cossu, C. Cimenti, P. Peluso, A. Paulon, O.
De Lucchi, Angew. Chem. Int. Ed. 2001, 40, 4086–4089; i) G.
Borsato, O. De Lucchi, F. Fabris, V. Lucchini, M. Pasqualotti,
A. Zambon, Tetrahedron Lett. 2003, 44, 561–563; j) H. Sakurai,
T. Daiko, T. Hirao, Science 2003, 301, 1878; k) O. De Lucchi,
1
0.7, CHCl3). H NMR (300 MHz, CDCl3): δ = 4.22 (series of m,
3 H), 3.09 (d, J = 4.2 Hz, 1 H), 2.79 (d, J = 4.1 Hz, 1 H), 2.76 (d,
J = 4.0 Hz, 1 H), 2.71–2.58 (series of m, 3 H), 1.51 (s, 3 H), 1.50
(s, 3 H), 1.40 (s, 3 H), 1.20 (br. s, 3 H), 0.99 (s, 3 H), 0.97 (s, 6 H),
0.94–0.83 (series of m, 3 H), 0.58 (s, 3 H), 0.57 (s, 3 H), 0.53 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 145.1, 140.1, 139.5,
138.7, 138.4, 133.4, 76.9, 76.7, 76.6, 60.8, 60.0, 59.5, 58.01, 57.98,
57.97, 49.4, 49.1, 48.2, 39.8, 39.4, 39.3, 21.4, 21.32, 21.28, 19.41,
19.40, 19.0, 14.1, 14.0, 11.9 ppm. IR (KBr): ν = 3380, 2953, 1472,
˜
1400, 1051 cm–1. C30H42O3 (450.65): calcd. C 79.96, H 9.39; found
C 80.00, H 9.36.
A. Dastan, A. Altundas, F. Fabris, M. Balci, Helv. Chim. Acta
¸
¸
2004, 87, 2364–2367; l) C. Zonta, F. Fabris, O. De Lucchi, Org.
Lett. 2005, 7, 1003–1006; m) G. Borsato, M. Crisma, O.
De Lucchi, V. Lucchini, A. Zambon, Angew. Chem. Int. Ed.
2005, 44, 7435–7439.
1H NMR Titration Experiments: A 3.0 mL sample of host of
known concentration (of the order of 1–10 m) was prepared in
1
CDCl3. A portion (0.8 mL) of this solution was removed and a H
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NMR spectrum was recorded. An accurately weighted sample of
the guest was then dissolved in the remaining 2.2 mL of the host
solution. This solution was almost saturated with guest to allow
access to the top of the binding isotherm and contained host, so
that the concentration of the host remained constant during the
course of the titration. Aliquots of this solution were added suc-
cessively to an NMR tube containing 0.5 mL of CDCl3, the tube
1
was shaken to mix the two solutions, and the H NMR spectrum
was recorded after each addition. The changes in chemical shift for
each signal were recorded and analyzed with NMRTit HGG using
an Apple Macintosh microcomputer. This program uses a Simplex
procedure to fit the data to a binding isotherm that allows for di-
290
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Received: August 1, 2006
Published Online: November 9, 2006
Eur. J. Org. Chem. 2007, 283–291
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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