Cucurbit[8]uril recognition of rapidly interconverting diastereomers

Article abstract of DOI:10.1080/10610278.2014.934243

The diastereoselectivity of Cucurbit[8]uril (CB[8]) binding was probed towards a series of rapidly interconverting diastereomers containing a C_aryl-C_aryl chiral axis and at least one other stereocenter. Relative binding affinities of up to 4.9 were determined when CB[8] interacted with ortho, meta, ortho′-substituted biphenyls bearing a chiral dialkylsulfonium substituent at their meta-position. Diastereoselectivities of up to 2.4-fold were obtained for ortho′-substituted 2-phenylpyridinium derivatives that bear a chiral myrtenyl N-substituent prone to CB[8] binding.

Full text of DOI:10.1080/10610278.2014.934243

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Supramolecular Chemistry
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Cucurbit[8]uril recognition of rapidly interconverting
diastereomers
Roymon Josepha & Eric Massona
a Department of Chemistry and Biochemistry, Ohio University, Athens, OH, USA
Published online: 08 Aug 2014.
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Supramolecular Chemistry, 2014
http://dx.doi.org/10.1080/10610278.2014.934243
Cucurbit[8]uril recognition of rapidly interconverting diastereomers
Roymon Joseph and Eric Masson*
Department of Chemistry and Biochemistry, Ohio University, Athens, OH, USA
(Received 13 March 2014; accepted 14 May 2014)
The diastereoselectivity of Cucurbit[8]uril (CB[8]) binding was probed towards a series of rapidly interconverting
diastereomers containing a Caryl–Caryl chiral axis and at least one other stereocenter. Relative binding affinities of up to 4.9
were determined when CB[8] interacted with ortho, meta, ortho0-substituted biphenyls bearing a chiral dialkylsulfonium
substituent at their meta-position. Diastereoselectivities of up to 2.4-fold were obtained for ortho0-substituted
2-phenylpyridinium derivatives that bear a chiral myrtenyl N-substituent prone to CB[8] binding.
Keywords: Cucurbituril; diastereoselectivity; biaryl
Introduction
were obtained after Suzuki coupling with 2-methyl- and 2-
chlorophenylboronic acid, and guests 4a–4d were isolated
after subsequent methylation (see Scheme 1).
Diastereoselective recognition inside Cucurbit[n ]urils
(CB[n ]) (1–3) has been exploited a few years ago, in
particular by Sivaguru and Ramamurthy, towards the
stereoselective [2 þ 2] cycloadditions of olefin pairs
encapsulated into CB[8] (4–9). Kim and Inoue also
showed that CB[6] displays a 19-fold higher affinity
towards the (S)-2-methylbutylammonium cation when
flanked with two (R)-methylpiperazines at its portal than
when forming an exclusion complex with two (S)-
methylpiperazines (10). The same authors showed that
the affinity of dipeptide L-Phe-L-Leu-NHþ3 for CB[7] was
eight times higher than its diastereomer L-Phe-D-Leu-NH3þ
(10).
Although the diastereomers of guest 4a could not be
differentiated by 1H NMR spectroscopy, 13C NMR
experiments afforded two doublets for the methylsulfo-
nium unit in a 53:47 ratio that we attribute to two pairs of
enantiomers (the multiplicity originates from a coupling
with the neighbouring ortho-fluorine nucleus; coupling
constant 2.4 ppm). Upon addition of CB[8], all aromatic
hydrogens underwent an upfield shift, thereby indicating
that the biphenyl units are fully encapsulated inside the
cavity of the macrocycle, or that CB[8] oscillates rapidly
on the NMR time scale between both aromatic units (see
Figure 1). Upfield shifts are particularly significant in the
case of the 20-methyl substituent (0.76 ppm), because it is
located deep inside the CB[8] cavity (see Figure 1,
spectrum g, and Figure 2(i)). All signals of methyl and
ethyl sulfonium groups split into two sets of singlets
(methyl group), symmetrical multiplets (ethyl CH2 group)
and triplets (ethyl CH3), each characterising one pair of
enantiomers ((P, R) and (M, S) versus (P, S) and (M, R)),
with differences in chemical shifts as high as 0.41 ppm in
the case of the ethyl CH3 group (noted ‘9’ in Figure 1).
Aromatic hydrogens 4 and 60 also split into two sets of
symmetrical multiplets (see Figure 1). Unfortunately, we
did not manage to attribute absolute configurations to both
pairs of enantiomers, even after careful evaluation of two-
dimensional nuclear and rotating frame nuclear Over-
hauser effect spectroscopy (NOESY and ROESY)
experiments. A peculiar trend is observed with H(9)
hydrogens upon consecutive addition of CB[8]. While the
triplet pertaining to one pair of enantiomers undergoes a
monotonic upfield shift, the other triplet is first shifted
We have recently reported that biphenyl atropisomers,
which bear various ortho and ortho0-substituents as well as
a meta-dimethylsulfonium group, could be encapsulated
into CB[7] and CB[8] (11). Confinement of the guests into
1
the macrocycles triggered the H NMR signal splitting of
the two diastereotopic dimethylsulfonium groups, by
propagating efficiently the dissymmetry caused by the
substituents at the ortho0-positions. In this study, we
propose first to attach two different substituents to the
sulfur centre (thereby introducing a new stereocenter) and
to test the recognition of CB[8] towards these new rapidly
interconverting diastereomers.
Results and discussion
Biphenyls 4a–4d were obtained in four steps from 2,4-
difluorothiophenol. Alkylation with ethyl or isopropyl
bromide afforded intermediates 1a and 1b, and metalation
followed by electrophilic interception with iodine yielded
intermediates 2a and 2b. Four biphenyl derivatives 3a–3d
*Corresponding author. Email: masson@ohio.edu
q 2014 Taylor & Francis

2
R. Joseph and E. Masson
Scheme 1. Preparation of biphenyl guests 4a–4d.
upfield until 0.50 equiv. CB[8] is added, and later shifts
markedly downfield until saturation is reached (after the
addition of approximately 1.5 equiv. CB[8], see Figure 1).
This non-monotonic behavior likely indicates the con-
comitant formation of binary and ternary complexes
1a·CB[8] and 1a2·CB[8] in the presence of substoichio-
metric amounts of the macrocycle. Once fully encapsu-
lated into CB[8], guest 1a coexists as a 35:65 mixture of
diastereomers. This implies a 2.1-fold higher affinity of
CB[8] for one of the two pairs of enantiomers.
One may reasonably question whether the ratio of
diastereomers switches from 53:47 to 35:65 upon
Figure 1. 1H NMR spectra of biphenyl 4a (2.0 mM) in D2O (a) in the absence of CB[8], and (b)–(g) with increasing amounts of CB[8]
(0.5, 1.0, 1.5, 2.0, 3.0 and 4.0 mM).

Supramolecular Chemistry
3
Figure 2. (Colour online) 1H NMR spectra of (a) biphenyl 4a and (b) its inclusion complex with CB[8]; (c) biphenyl 4b, (d) assembly
4b·CB[8], (e) biphenyl 4c, (f) assembly 4c·CB[8], (g) biphenyl 4d and (h) assembly 4d·CB[8] (see Scheme 1 for numbering). (i) TPSS-D3
(BJ)-optimised structure of complex 4d·CB[8].
1
interaction with CB[8], or from 47:53 to 35:65. The H
NMR spectrum recorded in the presence of 0.25 equiv. CB
[8] (Figure 1, spectrum b) shows a weaker upfield H
(9) triplet at 1.33 ppm, while the weakest H(9)
signal appears downfield at 1.57 ppm in the presence of
4.0 equiv. CB[8] (see spectrum g), thereby suggesting a
reversal of diastereoselectivity upon encapsulation.
However, we note that the concomitant formation of
ternary complexes 1a2·CB[8] in the presence of 0.25 equiv.
CB[8], with their own diastereomeric ratios, may bias our
reasoning.
appear as a pair of doublets in the absence of CB[8] and
split into two pairs upon encapsulation (see Figure 2,
spectra e–h). Replacing the S-ethyl substituent with a
larger isopropyl group improves the diastereoseletive
recognition of CB[8], with ratios in the absence of the
macrocycles of 52:48 and 57:43 (in the case of guests 4c
and 4d, respectively) to 18:82 and 25:75 when
encapsulated by CB[8]. These ratios afford relative CB
[8] binding affinities between diastereomers of 4.9 and 4.0
for biphenyls 4c and 4d, compared with 2.1 and 1.9 in the
case of biphenyls 4a and 4b (see Table 1). CB[8] thus
efficiently relays the steric pressure of the S-substituent on
the remote ortho0-substituent (see Figure 2(i) for the
optimised structure of complex 4d·CB[8]; optimisation
carried out with the dispersion-corrected TPSS-D3(BJ)
1
Similar H NMR patterns are observed upon addition
of CB[8] to biphenyls 4b–4d (see Figure 2). In the case of
biphenyls 4c and 4d, the two methyl groups of the
isopropyl substituents are themselves diastereotopic,

4
R. Joseph and E. Masson
Table 1. Diastereomeric ratios of guests 4a–4d in the absence
and presence of CB[8].
Table 2. Diastereomeric ratios of guests 7a–7d in the absence
and presence of CB[8].
Diastereomeric ratioa
Diastereomeric ratio
Free guestsb
CB[8]-bound guestsc
Krel
Free guests
CB[8]-bound guests
Krel
4a
4b
4c
4d
53:47
54:46
52:48
57:43
35:65
38:62
18:82
25:75
2.1 (^0.2)
1.9 (^0.2)
4.9 (^0.6)
4.0 (^0.4)
7aa
7ba
7ca
7db
50:50
50:50
43:57
43:57
35:65
30:70
24:76
35:65
1.9 (^0.1)
2.3 (^0.2)
2.4 (^0.2)
1.4 (^0.1)
Note: Relative binding affinity of CB[8] towards the diastereomers
(standard deviation between parentheses).
Note: Relative binding affinity of CB[8] towards the diastereomers
(standard deviation between parentheses).
a The 95% confidence interval of each term of the ratios (as obtained after
repetitive integration of the relevant 1H or 13C NMR signals) is ^3 and
^6, respectively; signal integration is the main source of error (compared
with the error calculated from a set of different experiments).
b Ratios obtained from relevant signals in 13C NMR spectra.
c Ratios obtained from relevant signals in 1H NMR spectra.
a The 95% confidence interval of each term of the ratios (as obtained after
repetitive integration of the relevant 1H NMR signals) is ^3.
b Ratios obtained by fitting myrtenyl H(16) NMR signals with a sum of
two Gaussian functions; standard deviation ^1.
The ratios of dynamic diastereomers in the absence of
CB[8] (see Table 2) could be readily determined by
integrating the 1H NMR signals of their 6-methyl
hydrogens (appearing as two pairs of singlets at 1.18 and
0.61 ppm, see H(15) and H(16) in Figure 3, spectra a, c, e
and g). Upon addition of CB[8], all myrtenyl signals as
well as the hydrogen at position 6 of the pyridinium unit
underwent upfield shifts (up to 0.73 ppm), thereby
confirming encapsulation of the myrtenyl substituent.
All other hydrogens underwent slight downfield shifts as
anticipated when hydrogen nuclei are located close to the
carbonyl portal of the macrocycle. Myrtenyl 6-methyl
hydrogens were used again to determine diastereomeric
ratios in the case of CB[8]-bound guests 7a and 7b.
Relative CB[8] binding affinities for both diastereomers
were 1.9 in the case of guest 7a (ratios shifting from
50:50 to 35:65, see Figure 3, spectra a and b) and 2.3 for
guest 7b (ratios shifting from 50:50 to 30:70, spectra c
and d). In the case of guest 7c, H(15) and H(17) signals
were used to determine the diastereomeric ratios (24:76,
functional (12,13) and def2-SVP basis sets, together with
the COSMO (14,15) solvation model).
We then tested whether CB[8] could influence
diastereomeric distributions when it encapsulates a chiral
substituent, and not the biaryl unit itself. We replaced the
biphenyl scaffold with a 2-phenylpyridium unit bearing
ortho0-substituents (methyl, ethyl, isopropyl or tert-butyl)
and a chiral N-substituent prone to CB[8] binding. The
(2)-myrtenyl substituent is ideal in that regard, because it
is rigid, fits very well into the cavity of CB[8] and can be
easily grafted to the 2-phenylpyridine scaffold. Biaryls
6a–6d were obtained after coupling ortho-substituted
phenylboronic acids to 2-bromopyridine (2-tert-butylphe-
nylboronic acid 5b was prepared from the corresponding
aniline via Gattermann reaction to afford bromobenzene
5a, followed by bromine/lithium permutation, reaction
with trimethyl borate and hydrolysis). N-allylation with
(2)-myrtenyl bromide (obtained by radical allylic
bromination of (2)-b-pinene) (16) afforded the desired
pyridinium guests 7a–7d (see Scheme 2).
Scheme 2. Preparation of CB[8] guests 7a–7d.

Supramolecular Chemistry
5
1
Figure 3. (Colour online) H NMR spectra of (a) pyridinium 7a and (b) its inclusion complex with CB[8]; (c) pyridinium 7b, (d)
assembly 7b·CB[8], (e) pyridinium 7c, (f) assembly 7c·CB[8], (g) pyridinium 7d, (h) assembly 7d·CB[8] and (i) assembly 7d·CB[8] after
heating to 958C for 10 days (see Scheme 1 for numbering). (j) TPSS-D3(BJ)-optimised structure of complex 7d·CB[8].
compared with 43:57 in the absence of the macrocycle,
see spectra e and f), leading to a 2.4-fold selectivity for
CB[8] towards one of the two diastereomers. We noticed
that upon addition of CB[8] to guest 7d, the ratio of
diastereomers remained steady at 43:57 (see spectra g
and h). This led us to suspect that the bulky tert-butyl
substituent may prevent rotation along the Caryl–Caryl
axis at 258C. Indeed, equilibrium could only be reached
upon heating the sample to 958C for 10 days; a 35:65
ratio was then determined using H(16) signals (see
Figure 3, spectrum i; due to the poor resolution of the
two singlets, the ratios were obtained by fitting the signal
with a sum of two Gaussian functions). We also
confirmed that 43:57 represented the ratio of diaster-
eomers at equilibrium in the absence of CB[8], and not
merely a kinetic distribution arising from a weakly
diastereoselective allylation of 2-phenylpyridine 6d with
(2)-myrtenyl bromide. The mixture of diastereomers
was heated to 958C for up to 2 weeks without observing a
variation in distribution. CB[8] thus displays a mere 1.4-
fold preference for one of the two diastereomers (see
Table 2).

6
R. Joseph and E. Masson
Conclusions
(2,4-Difluorophenyl)(isopropyl)sulfane (1b)
We showed that CB[8] binding can be moderately
diastereoselective, with relative binding affinities of up to
4.9. To the best of our knowledge, this study is the first
attempt at determining the binding affinities of any
macrocycle towards rapidly interconverting diastereomers.
Prepared similarly from 2,4-difluorothiophenol (3.0 g,
20 mmol) and 2-bromopropane (7.6 g, 62 mmol); colour-
1
less liquid (2.6 g, 67%). H NMR: d 7.55 (q, J ¼ 8.4 Hz,
ArZH), 7.02 (q, J ¼ 8.6 Hz, ArZH), 3.39 (o, J ¼ 6.7 Hz,
SCH), 1.25 (d, J ¼ 6.7 Hz, (CH(CH3)2) ppm. 13C NMR:
165.3 (t, J ¼ 11.8 Hz, ArCF), 162.1 (t, J ¼ 11.3 Hz,
ArC F), 137.8 (dd, J ¼ 6.9, 2.3 Hz, ArC), 118.6 (d,
J ¼ 3.8 Hz, ArC), 112.8 (dd, J ¼ 17.6, 3.8 Hz, ArC), 105.2
(t, J ¼ 26.1 Hz, ArC), 39.2 (SCH), 23.4 (C(C H3)2) ppm.
Experimental section
Generalities
Reagents were ordered from Sigma-Aldrich (St. Louis,
MO), Alfa Aesar (Ward Hill, MA) and AK scientific
(Union City, CA). CB[6], CB[7] and CB[8] were prepared
using known procedures, from glycoluril and excess
amounts of formaldehyde (17–20). (2)-Myrtenyl bro-
mide was prepared as described in literature from (2)-b-
(2,4-Difluoro-3-iodophenyl)(ethyl)sulfane (2a)
A solution of butyllithium (1.8 mL, 3.6 mmol) in hexane
was added to a solution of diisopropylamine (0.39 g,
3.9 mmol) in dry THF (30 mL) and the reaction mixture
was kept at 2758C for 20 min. A solution of sulfide 1a
(0.50 g, 2.9 mmol) in THF (5.0 mL) was added dropwise,
and the reaction mixture was kept at 2758C for 2 h before
adding iodine (0.87 g, 3.4 mmol). The resulting reaction
mixture was allowed to warm to 258C before adding an
aqueous solution of Na2S2O3 (23 mg, 0.14 mmol). The
solution was diluted with water (20 mL) and extracted with
diethyl ether (3 £ 25 mL). The combined organic layers
were washed with water (50 mL) and brine (40 mL), dried
with sodium sulfate and evaporated. The title compound
was isolated as a light yellow oil (0.74 g, 86%). 1H NMR: d
7.47 (q, J ¼ 8.5 Hz, ArZH, 1H), 7.02 (t, J ¼ 7.7 Hz,
ArZH, 1H), 2.94 (q, J ¼ 7.2 Hz, SCH2, 2H), 1.26 (t,
J ¼ 7.4 Hz, CH2CH3, 3H) ppm. 13C NMR: 162.5 (dd,
J ¼ 243.0, 5.3 Hz, ArC F), 161.6 (dd, J ¼ 240.8, 6.0 Hz,
ArC F), 134.1 (dd, J ¼ 8.6, 3.0 Hz, ArC), 120.4 (dd,
J ¼ 21.0, 3.8 Hz, ArCS), 112.6 (dd, J ¼ 24.8, 3.8 Hz,
ArC), 72.3 (t, J ¼ 30.8 Hz, ArCI), 28.4 (d, J ¼ 2.3 Hz,
SC H2), 14.7 (CH2C H3) ppm.
1
pinene (16). All H NMR experiments were performed
using a 300-MHz Bruker NMR instrument. 1H-decoupled
13C NMR spectra were obtained at 75.5 MHz using the
same Bruker 300 spectrometer. Unless specified otherwise,
NMR experiments were performed at 258C, the solvent
was CD3CN and the internal reference was tetramethylsi-
lane-d 12 (d ¼ 0.00 ppm). When D2O was the solvent,
chemical shifts d refer to the residual signal of HDO
(d ¼ 4.80 ppm). High-resolution mass spectra were
obtained at the COSMIC facility of the Old Dominion
University (Norfolk, VA) using a Bruker Daltonics 12
Tesla APEX-Qe FTICR mass spectrometer with an Apollo
II ion source. Density functional calculations were
performed at the Ohio Supercomputer Center (Columbus,
OH), using the TURBOMOLE suite of programs (version
6.3.1).1
(2,4-Difluorophenyl)(ethyl)sulfane (1a)
Potassium hydroxide (0.42 g, 7.5 mmol) was added to a
solution of 2,4-difluorothiophenol (1.0 g, 6.8 mmol) in
ethanol under inert atmosphere. After stirring for 30 min,
ethyl bromide (1.1 g, 10 mmol) was added and the reaction
mixture kept at 258C for 12 h. Aqueous sodium hydroxide
(2.0 M, 4.0 mL) was then added, and ethanol was removed
under vacuum. The reaction mixture was diluted with
water (40 mL), extracted with dichloromethane (3 £
30 mL), and the combined extracts were washed with
water (50 mL), brine (50 mL), dried with sodium sulfate
and evaporated. The product was purified by chromatog-
raphy (silica gel; eluent: hexane/chloroform, 9:1) to afford
(2,4-Difluoro-3-iodophenyl)(isopropyl)sulfane (2b)
Prepared similarly to sulfide 2a, with (2,4-difluorophenyl)
(isopropyl)sulfane 1b (2.2 g, 12 mmol) instead of (2,4-
difluorophenyl)(ethyl)sulfane 1a. The product was purified
by chromatography (silica gel; eluent: hexane/chloroform,
18:2) to afford a light yellow liquid (3.0 g, 83%). 1H NMR:
d 7.48 (q, J ¼ 8.4 Hz, ArZH, 1H), 6.96 (t, J ¼ 7.5 Hz,
ArZH, 1H), 3.37 (octet, J ¼ 6.9 Hz, CH(CH3)2, 1H), 1.21
(d, J ¼ 6.6 Hz, CH(CH3)2) ppm. 13C NMR: 163.3 (dd,
J ¼ 244, 5.4 Hz, ArC), 162.8 (dd, J ¼ 241, 6.2 Hz, ArC),
137.3 (dd, J ¼ 9.0, 2.3 Hz, ArC), 119.2 (dd, J ¼ 21.5,
3.9 Hz, ArC), 112.6 (dd, J ¼ 24.2, 4.0 Hz, ArC), 72.4 (t,
J ¼ 30.0 Hz, ArC), 39.2 (SCH), 23.3 (C(C H3)2) ppm.
1
a colourless liquid (0.80 g, 67%). H NMR: d 7.48 (q,
J ¼ 8.4 Hz, ArZH, 1H), 7.01 (m, ArZH, 2H), 2.93 (q,
J ¼ 7.4 Hz, SZCH2, 2H), 1.24 (t, J ¼ 7.3 Hz, CH2ZCH3)
ppm. 13C NMR: 161.7 (dd, J ¼ 245.3, 11.3 Hz, ArC F),
162.6 (dd, J ¼ 244.5, 12.0 Hz, ArC F), 134.7 (dd, J ¼ 9.8,
3.0 Hz, ArC), 119.7 (dd, J ¼ 18.0, 3.8 Hz, ArCS), 112.9
(dd, J ¼ 21.5, 3.8 Hz, ArC), 105.1 (t, J ¼ 26.9 Hz, ArC),
28.5 (d, J ¼ 2.3 Hz, ArSCH2), 14.8 (ArSCH2C H3) ppm.
(2,6-Difluoro-20-methylbiphenyl-3-yl)(ethyl)sulfane (3a)
A solution of potassium carbonate (0.37 g, 2.7 mmol) in
water (5.0 mL) was added to a solution of sulfide 2a

Supramolecular Chemistry
7
(0.40 g, 1.3 mmol), o-tolylboronic acid (0.27 g, 2.0 mmol)
and palladium(0)tetrakis(triphenylphosphine) (0.14 g,
0.13 mmol) in N,N-dimethylformamide (25 mL) under
inert atmosphere. The resulting mixture was heated at
1208C for 12 h. After cooling to 258C, the reaction mixture
was filtered through a pad of celite. The filtrate was then
poured into ice-cold water (40 mL), acidified with 1.0 M
HCl and extracted with dichloromethane (3 £ 30 mL).
The organic fractions were washed with water (60 mL) and
brine (60 mL), dried with sodium sulfate and concentrated
in vacuo. The product was purified by column
chromatography (silica gel; eluent: hexane/ethyl acetate,
98:2) to afford a colourless oil (0.26 g, 74%). 1H NMR: d
7.53 (q, J ¼ 8.5 Hz, ArZH, 1H), 7.4–7.3 (m, ArZH, 3H),
7.27 (t, J ¼ 7.5 Hz, ArZH, 1H), 7.11 (t, J ¼ 8.8 Hz,
ArZH, 1H), 2.98 (q, J ¼ 7.4 Hz, SZCH2, 2H), 2.16 (s,
(ArC), 119.2 (t, J ¼ 21.8 Hz, ArC), 118.7 (dd, J ¼ 20.3,
3.8 Hz, ArC), 112.7 (dd, J ¼ 23.3, 4.5 Hz, ArC), 39.1
(SC H), 23.5 (C(C H3)2), 19.9 (ArC H3) ppm.
(20-Chloro-2,6-difluorobiphenyl-3-yl)(isopropyl)sulfane
(3d)
Prepared similarly to biphenyl 3b, with isopropyl sulfide
2b (0.90 g, 2.9 mmol) instead of ethyl sulfide 2a. The
product was purified by chromatography (silica gel;
eluent: hexane/chloroform, 99:1) to afford a colourless oil
1
(0.30 g, 35%). H NMR: d 7.60 (q, J ¼ 6.0 Hz, ArZH,
2H), 7.52–7.41 (m, ArZH, 3H), 7.11 (t, J ¼ 8.7 Hz,
ArZH, 1H), 3.43 (o, J ¼ 6.7Hz, SZCH, 1H), 1.27 (d,
J ¼ 6.7 Hz, CH(CH3)2, 6H) ppm. 13C NMR: 160.7 (dd,
J ¼ 246.8, 6.8 Hz, ArCF), 160.5 (dd, J ¼ 243.8, 7.5 Hz,
ArCF), 136.5 (dd, J ¼ 9.8, 2.3 Hz, ArC), 134.8, 133.2,
131.7, 130.6, 129.4, 128.2 (ArC), 119.0 (dd, J ¼ 19.5,
3.8 Hz, ArC), 117.3 (t, J ¼ 21.8Hz, ArC), 112.8 (dd,
J ¼ 22.5, 3.8 Hz, ArC), 39.2 (SCH), 23.4 (CH(CH3)2) ppm.
ArZCH3, 3H), 1.29 (t, J ¼ 7.4 Hz, CH2CH3, 3H) ppm. 13
C
NMR: 160.1 (dd, J ¼ 243.0, 6.8 Hz, ArCF), 159.4 (dd,
J ¼ 242.3, 7.5 Hz, ArCF), 138.3 (CCH3), 133.0 (dd,
J ¼ 9.8, 3.0 Hz, ArC), 131.5, 131.2, 130.2, 129.9, 126.8
(ArC), 120.0 (dd, J ¼ 19.5, 3.8Hz, ArCS), 119.2 (t,
J ¼ 22.5Hz, ArC), 112.8 (dd, J ¼ 23.3, 3.8 Hz, ArC), 28.4
(d, J ¼ 2.3 Hz, SCH3), 19.9(CCH3), 144.9 (CH2CH3) ppm.
(2,6-Fluoro-20-methylbiphenyl-3-yl)(ethyl)(methyl)
sulfonium tetrafluoroborate (4a)
Trimethyloxonium tetrafluoroborate (70 mg, 0.45 mmol)
was added to a solution of biphenyl 3a (0.10 g, 0.38 mmol)
in nitromethane (4.0 mL) under a nitrogen atmosphere.
The reaction mixture was heated to 608C for 12 h. After
cooling to 258C, methanol (10 mL) was added, and the
solvent was evaporated under vacuum. Addition of diethyl
ether resulted in the formation of the title compound as a
light yellow solid (0.12 g, 87%); mp 130–1318C. 1H
NMR: d 8.0 (q, J ¼ 8.7 Hz, ArZH, 1H), 7.52–7.30 (m,
ArZH, 5H), 3.70 (m, SZCH2, 2H), 3.28 (S, SZCH3, 3H),
2.20 (s, ArZCH3, 3H), 1.40 (t, J ¼ 7.3 Hz, CH2ZCH3,
3H) ppm. 13C NMR: 165.4 (dd, J ¼ 255.0, 8.3 Hz, ArC F),
161.1 (dd, J ¼ 252.0, 8.3 Hz, ArCF), 138.5 (ArCCH3),
133.6 (dd, J ¼ 13.5, 6.0 Hz, ArC), 131.6, 131.5, 130.9
(ArC), 127.5 (d, J ¼ 2.3 Hz, ArC), 127.2 (d, J ¼ 1.5 Hz,
ArC), 121.5 (t, J ¼ 23.2 Hz, ArC), 115.8 (dt, J ¼ 24.8,
3.0 Hz, ArC), 107.5 (dt, J ¼ 16.0, 3.0 Hz, ArCS), 47.6 (d,
J ¼ 3.0 Hz, SC H2), 26.03 (d, J ¼ 3.0 Hz, SC H3), 25.8 (d,
J ¼ 1.5 Hz, SCH3), 19.8 (ArC H3), 9.8 (d, J ¼ 6.8 Hz,
CH2C H3) ppm. HRMS (ESI) m/z calcd for C16H17F2S
([M]þ) 279.101354, found 279.100712.
(20-Chloro-2,6-difluorobiphenyl-3-yl)(ethyl)sulfane (3b)
Prepared similarly to biphenyl 3a, with 2-chlorophenyl-
boronic acid (0.91 g, 5.80 mmol) instead of o-tolylboronic
acid. The product was purified by chromatography (silica
gel; eluent: hexane/ethyl acetate, 99:1) to afford a
1
colourless oil (0.30 g, 27%). H NMR: d 7.61–7.43 (m,
ArZH, 5H), 7.11 (t, J ¼ 9.0 Hz, ArZH, 1H), 2.95 (q,
J ¼ 7.3 Hz, SZCH2, 2H), 1.27 (t, J ¼ 7.4 Hz, CH2ZCH3,
3H) ppm. 13C NMR: 160.0 (dd, J ¼ 245.2, 6.8 Hz, ArC F),
159.3 (dd, J ¼ 243.8, 7.5 Hz, ArC F), 134.8 (ArC), 133.8
(dd, J ¼ 9.8, 3.0 Hz, ArC), 133.24 (ArC), 131.7 (ArC),
130.6 (ArC), 129.4 (ArC), 128.2 (ArC), 120.1 (dd,
J ¼ 19.5, 4.5 Hz, ArC), 117.3 (t, J ¼ 21.8 Hz, ArC), 112.8
(dd, J ¼ 22.5, 3.8 Hz, ArC), 28.4 (d, J ¼ 2.3 Hz, SC H2),
14.8 (CH2C H3) ppm.
(2,6-Difluoro-20-methylbiphenyl-3-yl)(isopropyl)sulfane
(3c)
Prepared similarly to biphenyl 3a, with isopropyl sulfide
2b (0.70 g, 2.2 mmol) instead of ethyl sulfide 2a. The
product was purified by chromatography (silica gel;
eluent: hexane/chloroform, 49:1) to afford a colourless oil
(20-Chloro-2,6-difluorobiphenyl-3-yl)(ethyl)(methyl)
sulfonium tetrafluoroborate (4b)
1
(0.44 g, 71%). H NMR: d 7.59–7.40 (m, ArZH, 1H),
7.35–7.25 (m, ArZH, 4H), 7.11 (t, J ¼ 8.9 Hz, ArZH,
1H), 3.44 (o, J ¼ 6.7 Hz, SCH, 1H), 2.16 (s, ArZCH3,
3H), 1.28 (d, J ¼ 6.7 Hz, CH–(CH3)2, 6H) ppm. 13C
NMR: 160.7 (dd, J ¼ 244.5, 6.8 Hz, ArC F), C161.0 (dd,
J ¼ 243.0, 8.3 Hz, ArC F), 138.22 (ArC), 136.1 (dd,
J ¼ 9.8, 3.0 Hz, ArC), 131.4, 131.2, 129.9, 129.8, 126.8
Obtained similarly to sulfonium 4a, using biphenyl 3b
(0.10 g, 0.35 mmol) instead of biphenyl 3a. White solid
(0.70 g, 54%); mp 139–1408C. 1H NMR: d 8.06 (q,
J ¼ 7.7 Hz, ArZH, 1H), 7.68–7.52 (m, ArZH, 5H), 3.68
(m, SZCH2, 2H), 3.28 (s, S(CH3), 3H), 1.39 (t, J ¼ 7.2 Hz,
CH2ZCH3, 3H) ppm. 13C NMR: 165.3 (ddd, J ¼ 256.5,

8
R. Joseph and E. Masson
6.8, 3.8 Hz, ArC F), 161.1 (ddd, J ¼ 254.3, 6.0, 2.3 Hz,
ArC F), 134.7 (ArC), 134.5 (t, J ¼ 11.3 Hz, ArC), 133.2 (d,
J ¼ 3.0 Hz, ArC), 132.8 (ArC), 130.9 (ArC), 128.7 (ArC),
127.1 (d, J ¼ 2.3 Hz, ArC), 119.4 (t, J ¼ 21.8 Hz, ArC),
115.7 (ddd, J ¼ 24.8, 8.3, 3.8 Hz, ArC), 107.6 (t,
J ¼ 15.8 Hz, ArC), 41.6 (d, J ¼ 6.0 Hz, SCH3), 25.9 &
25.7 (d, J ¼ 2.3 Hz, SC H2), 9.8 (d, J ¼ 7.5 Hz, CH2C H3)
ppm. HRMS (ESI) m/z calcd for C15H14ClF2S ([M]þ)
299.046732, found 299.046874.
sodium nitrite (7.6 g, 0.11 mol) in water (10 mL). The
solution was kept at 08C for 2 h until the addition of 0.20 g
of copper powder. The resulting solution was stirred at 08C
until bubbling stopped, and finally heated to 508C for
30 min. The reaction mixture was diluted with water
(40 mL), extracted with diethyl ether (3 £ 50 mL) and
combined organic layers were washed with an aqueous
solution of potassium hydroxide (10%). The product was
purified by chromatography (silica gel; eluent:hexane) to
1
afford a light brown liquid (3.1 g, 30%). H NMR: d 7.65
(d, J ¼ 7.8 Hz, ArZH, 1H), 7.54 (d, J ¼ 8.0 Hz, ArZH,
1H), 7.34 (t, J ¼ 7.1 Hz, ArZH, 1H), 7.11 (t, J ¼ 8.7 Hz,
ArZH, 1H), 1.53 (s, (CH3)2, 9H) ppm.
(2,6-Difluoro-20-methylbiphenyl-3-yl)(isopropyl)(methyl)
sulfonium tetrafluoroborate (4c)
Obtained similarly to sulfonium 4a, using biphenyl 3c
(0.10 g, 0.36 mmol) instead of biphenyl 3a. White solid
1
(0.11 g, 81%); m.p. 128–1298C. H NMR: d 7.94 (m,
2-tert-Butylphenylboronic acid (5b) (21)
ArZH, 1H), 7.53–7.43 (m, ArZH, 3H), 7.40–7.28 (m,
ArZH, 2H), 4.06 (m, SZCH, 1H), 3.26 (s, S-(CH3), 3H),
2.19 (s, ArZCH3, 3H), 1.56 & 1.39 (d, J ¼ 6.7 Hz, CH-
(CH3)2, 6H) ppm. 13C NMR: 165.4 (dd, J ¼ 255.0, 7.5 Hz,
ArC F), 161.1 (dd, J ¼ 251.9, 7.5 Hz, ArCF), 138.5 (ArC),
133.7 (dd, J ¼ 11.3, 6.0 Hz, ArC), 131.6 (d, J ¼ 3.8 Hz,
ArC), 131.4 (d, J ¼ 2.3 Hz, ArC), 130.9 (d, J ¼ 2.3 Hz,
ArC), 127.5 (d, J ¼ 3.8 Hz, ArC), 127.2 (d, J ¼ 2.3 Hz,
ArC), 121.5 (t, J ¼ 22.2 Hz, ArC), 115.8 (ddd, J ¼ 28.5,
3.8 Hz, ArC), 106.7 (dt, J ¼ 15.8, 3.8 Hz, ArC), 53.4 (d,
J ¼ 4.5 Hz, SC H), 23.3 & 23.2 (d, J ¼ 2.3 Hz, S(C H3)),
19.8 (ArC H3), 18.5 (d, J ¼ 3.8 Hz, CH(C H3)), 18.2 (d,
J ¼ 5.3 Hz, CH(C H3)) ppm. HRMS (ESI) m/z calcd for
C19H19F2S ([M]þ) 293.117004, found 293.117180.
A solution of butyllithium (2.5 M) in hexane (1.0 g,
16 mmol) was added to a solution of 1-bromo-2-tert-
butylbenzene (3.0 g, 14 mmol) in dry THF (0.10 L), and
the solution was kept at 2758C for 2 h. The reaction
mixture was then added to a solution of trimethyl borate
(4.4 mL, 42 mmol) in THF (25 mL) and the solution kept at
2758C for 1 h followed by 2 h at 258C. The reaction
mixture was acidified with dilute HCl, diluted with water
(0.10 L) and extracted with diethyl ether (3 £ 50 mL). The
title compound crystallised as white needles in hexane
(1.8 g, 71 %); m.p. 128–1298C. 1H NMR: d 7.75 (d,
J ¼ 7.9 Hz, ArZH, 1H), 7.30–7.26 (m, ArZH, 2H), 7.15
(t, J ¼ 7.2 Hz, ArZH, 1H), 5.99 (s, B(OH)2, 2H), 1.40 (s,
C(CH3)2, 9H) ppm.
(20-Chloro-2,6-difluorobiphenyl-3-yl)(isopropyl)(methyl)
sulfonium tetrafluoroborate (4d)
2-o-Tolylpyridine (6a)
Prepared similarly to biphenyl 3a, with 2-bromopyridine
(0.50 g, 3.2 mmol) and tolylboronic acid (0.64 g, 4.7 mmol).
The product was purified by chromatography (silica gel;
hexane/dichloromethane, 7:3) to afford a light brown oil
(0.52 g, 96%). 1H NMR: d 8.68 (d, J ¼ 4.7 Hz, ArZH, 1H),
7.82 (t, J ¼ 7.7 Hz, ArZH, 1H), 7.47–7.40 (m, ArZH, 2H),
Obtained similarly to sulfonium 4a, using biphenyl 3d (60
mg, 0.20 mmol) instead of biphenyl 3a. White solid (45
mg, 56%); m.p. 127–1288C. 1H NMR (CD3CN): d 8.03–
7.96 (m, ArZH, 1H), 7.67 (d, J ¼ 8.1 Hz, ArZH, 1H),
7.61–7.48 (m, ArZH, 4H), 4.12–4.00 (m, CH(CH3)2,
1H), 3.27 (s, S(CH3), 3H), 1.56 (d, J ¼ 6.6 Hz, CH(CH3)2,
3H), 1.38 (d, J ¼ 6.6 Hz, CH(CH3)2, 3H) ppm. 13C NMR:
165.3 (dt, J ¼ 256.8, 7.3 Hz, ArC), 161.0 (dd, J ¼ 245.3,
3.8 Hz, ArC), 134.9–134.4 (m, ArC £ 2), 133.1 (d,
J ¼ 7.1 Hz, ArC), 132.7 (d, J ¼ 1.8 Hz, ArC), 130.9 (ArC),
128.6 (d, J ¼ 3.1 Hz, ArC), 127.1 (d, J ¼ 3.6 Hz, ArC),
119.8–119.1 (m, ArC), 115.8 (dd, J ¼ 24.2, 3.6 Hz, ArC),
106.8 (t, J ¼ 11.8Hz, ArC), 53.5 (d, J ¼ 18.8Hz, SCH3),
23.2(t, J ¼ 2.25Hz, SCH), 18.5(d, J ¼ 5.0 Hz, CH(CH3)2),
18.2 (CH(C H3)2) ppm. HRMS (ESI) m/z calcd for
C16H16ClF2S ([M]þ) 313.062382, found 313.062629.
7.33–7.30 (m, ArZH, 4H), 2.37 (s, ArZCH3, 3H) ppm. 13
C
NMR: 160.8, 150.1, 141.7, 137.3, 136.9, 131.7, 130.6, 129.2,
126.9, 125.0, 122.9 (ArC), 20.7 (ArCH3) ppm.
2-(2-Ethylphenyl)pyridine (6b)
Prepared similarly to tolylpyridine 6a, with 2-ethylbenze-
neboronic acid (0.71 g, 4.7 mmol) instead of tolylboronic
acid. The product was purified by chromatography (silica
gel; eluent: hexane–ethyl acetate, 8:2) to afford a
colourless oil (0.46 g, 79%). 1H NMR: d 8.67 (d,
J ¼ 5.6 Hz, ArZH, 1H), 7.81 (t, J ¼ 7.7 Hz, ArZH, 1H),
7.45–7.29 (m, ArZH, 6H), 2.74 (q, J ¼ 7.5 Hz, ArZCH2,
2H), 1.09 (t, J ¼ 7.5 Hz, CH3, 3H) ppm. 13C NMR: 161.1,
150.0, 143.2, 141.4, 137.4, 130.8, 130.2, 129.4, 126.8,
125.0, 122.9 (ArC), 26.9 (ArC H2), 16.2 (C H3) ppm.
1-Bromo-2-tert-butylbenzene (5a) (21)
To a solution of 2-tert-butylphenylamine (7.5 g, 50 mmol)
in 48% HBr (13 mL) at 08C was added a solution of

Supramolecular Chemistry
N-Myrtenyl-[2-(2-ethylphenyl)]pyridinium bromide (7b)
9
2-(2-Isopropylphenyl)pyridine (6c)
Prepared similarly to tolylpyridine 6a, with 2-isopropyl-
phenylboronic acid (0.58 g, 3.5 mmol) instead of tolyl-
boronic acid. The product was purified by chromatography
(silica gel; eluent: hexane–ethyl acetate, 9:1) to afford
light brown oil (0.39 g, 78%). 1H NMR: d 8.68 (d,
J ¼ 4.8 Hz, ArZH, 1H), 7.82 (t, J ¼ 7.7 Hz, ArZH, 1H),
7.51–7.34 (m, ArZH, 3H), 7.33–7.28 (m, ArZH, 3H)
ppm. 13C NMR: 161.3, 150.0, 147.6, 141.2, 137.3, 130.7,
129.6, 126.7, 126.5, 125.3, 122.9 (ArC), 30.1 (ArC H),
24.4 (CH3) ppm.
Obtained similarly to pyridinium 7a, using phenylpyridine
6b (0.10 g, 0.55 mmol) instead of phenylpyridine 6a.
1
White solid (89 mg, 41%); m.p. 141–1428C. H NMR
(D2O): d 8.92 (d, J ¼ 6.0 Hz, ArZH, 1H), 8.61 (t,
J ¼ 8.1 Hz, ArZH, 1H), 8.12 (d, J ¼ 6.9 Hz, ArZH, 1H),
8.07 (t, J ¼ 7.2 Hz, ArZH, 1H), 7.66 (t, J ¼ 7.2 Hz,
ArZH, 1H), 7.58 (d, J ¼ 7.0 Hz, ArZH, 1H), 7.49–7.39
(m, ArZH, 2H), 5.26 (d, J ¼ 17.7 Hz, C ¼ CH, 1H),
5.03–4.86 (m, N–CH2, 2H), 2.57–2.45 (m, CH, 1H),
2.40–2.31 (m, ArZCH2, 2H), 2.31–2.20 (m, CH, 2H),
2.08 (br, CH, 1H), 1.89 (q, J ¼ 6.3 Hz, CH, 1H), 1.19 (d,
J ¼ 6.0 Hz, CH3, 3H), 1.15–0.98 (m, CH3,CH, 4H), 0.64
(d, J ¼ 13.8 Hz, CH3, 3H) ppm. 13C NMR (D2O): 155.3
(d, J ¼ 6.8 Hz, ArC), 146.0 (d, J ¼ 3.2 Hz, ArC), 145.6 (d,
J ¼ 3.2 Hz, ArC), 142.3 (d, J ¼ 19.5 Hz, ArC), 140.9 (d,
J ¼ 3.8 Hz, ArC), 131.7 (ArC), 130.9 (d, J ¼ 6.0 Hz,
ArC), 130.3 (ArC), 129.4 (m, ArC), 129.1, 127.3 (ArC),
126.5 (d, J ¼ 8.6 Hz, ArC), 124.3 (d, J ¼ 4.5 Hz, ArC),
61.9 (d, J ¼ 3.4 Hz, NCH2), 43.5 (d, J ¼ 9.8 Hz, myrtenyl-
C), 40.0 (myrtenyl-C), 37.7 (d, J ¼ 7.5 Hz, myrtenyl-
C),31.0, 30.9 (myrtenyl-C), 25.8 (d, J ¼ 10.5 Hz, myrte-
nyl-C), 25.4 (d, J ¼ 2.3 Hz, myrtenyl-C), 20.4 (d,
J ¼ 17.3 Hz, myrtenyl-C), 14.4 (d, J ¼ 4.5 Hz, myrtenyl-
C) ppm. HRMS (ESI) m/z calcd for C23H28N ([M]þ)
318.221626, found 318.221780.
2-(2-tert-Butylphenyl)pyridine (6d)
Prepared similarly to tolylpyridine 6a, with 2-tert-
butylphenylboronic acid (5b; 0.70 g, 4.0 mmol) instead
of tolylboronic acid. The product was purified by
chromatography (silica gel; eluent: hexane–ethyl acetate,
1
17:3) to afford colourless oil (0.15 g, 22%). H NMR: d
8.59 (d, J ¼ 4.6 Hz, ArZH, 1H), 7.79 (t, J ¼ 7.8 Hz,
ArZH, 1H), 7.62 (d, J ¼ 8.0 Hz, ArZH, 1H), 7.42–7.32
(m, ArZH, 3H), 7.25 (t, J ¼ 7.4 Hz, ArZH, 1H), 7.06 (d,
J ¼ 7.5 Hz, ArZH, 1H), 1.19 (s, C(CH3)3, 9H) ppm. 13C
NMR: 164.5, 149.0, 148.8, 142.3, 136.9, 132.5, 128.9,
127.9, 126.2, 126.0, 122.9 (ArZC), 37.2 (C(CH3)2), 32.7
(C(C H3)2) ppm.
N-Myrtenyl-(2-o-tolyl)pyridinium bromide (7a)
N-Myrtenyl-[2-(2-isopropylphenyl)]pyridinium
bromide (7c)
A mixture of o-tolylpyridine (6a; 50 mg, 0.30 mmol) and
(2)-myrtenyl bromide (64 mg, 0.3 mmol) in acetone
(15 mL) was refluxed for 12 h. Addition of diethyl ether
(10 mL) resulted in the formation of the title compound as
A mixture of phenylpyridine 6c (0.10 g, 0.51 mmol) and
(2)-myrtenyl bromide (0.11 g, 0.51 mmol) in acetonitrile
was heated to 508C for 12 h. The product was crystallised
from acetonitrile/diethyl ether (2:1) to afford a white solid
that immediately turned to a thick oil when exposed to air
1
a white solid (31 mg, 27%); m.p. 167–1688C. H NMR
(D2O): d 8.93 (d, J ¼ 6.3 Hz, ArZH, 1H), 8.62 (t,
J ¼ 7.2 Hz, ArZH, 1H), 8.11 (t, J ¼ 6.3 Hz, ArZH, 1H),
8.03 (d, J ¼ 7.8 Hz, ArZH, 1H), 7.60 (t, J ¼ 6.3 Hz,
ArZH, 1H), 7.52–7.41 (m, ArZH, 3H), 5.23 (d,
J ¼ 14.7 Hz, C ¼ CH, 1H), 4.98 (m, N–CH2, 2H), 2.34
(m, CH2, 1H), 2.27 (br, CH2, 2H), 2.16 (s, ArZCH3, 3H),
2.08 (br, CH, 1H), 1.88 (m, CH2, 1H), 1.19 (d, J ¼ 4.8 Hz,
CH3, 3H), 1.01 (t, J ¼ 11.4 Hz, CH2, 1H), 0.62 (d,
J ¼ 7.5 Hz, CH3, 3H) ppm. 13C NMR (D2O): 156.2 (d,
J ¼ 6.0 Hz, ArC), 146.5 (d, J ¼ 4.5 Hz, ArC), 145.9 (s,
ArC), 141.6 (s, ArC), 137.0 (d, J ¼ 21 Hz, ArC), 132.0
(ArC), 131.5 (d, J ¼ 12.8 Hz, ArC), 131.4 (s, ArC), 131.3
(d, J ¼ 8.3 Hz, ArC), 129.9 (s, ArC), 129.5 (ArC), 127.6
(ArC), 126.5 (d, J ¼ 7.5 Hz, ArC), 124.8 (d, J ¼ 7.5 Hz,
ArC), 62.4 (d, J ¼ 3.2 Hz, NCH2), 44.0 (d, J ¼ 10.5 Hz,
myrtenyl-C), 40.5 (d, J ¼ 2.6 Hz, myrtenyl-C), 38.1 (d,
J ¼ 8.3 Hz, myrtenyl-C), 31.5 (myrtenyl-C), 31.3
(d, J ¼ 6.3 Hz, myrtenyl-C), 25.7 (myrtenyl-C), 20.6 (d,
J ¼ 19.5 Hz, myrtenyl-C), 19.3 (d, J ¼ 11.3 Hz, myrtenyl-
C) ppm. HRMS (ESI) m/z calcd for C22H26N ([M]þ)
304.205976, found 304.206121.
1
(50 mg, 24%). H NMR (D2O): d 8.87 (d, J ¼ 6.0 Hz,
ArZH, 1H), 8.56 (t, J ¼ 7.5 Hz, ArZH, 1H), 8.09–8.00
(m, ArZH, 2H), 7.68–7.64 (m, ArZH, 2H), 7.44–7.38
(m, ArZH, 2H), 7.34–7.32 (m, ArZH, 1H), 5.34 (d,
J ¼ 19.2 Hz, C ¼ CH, 1H), 4.98–4.71 (m, NCH2, 2H),
2.48–2.38 (m, ArZCH, 1H), 2.38–2.19 (m, CH2, CH,
3H), 2.06 (br, CH, 1H), 1.87 (t, J ¼ 5.4 Hz, CH, 1H), 1.23
(d, J ¼ 6.9 Hz, CH3, 3H), 1.17 (d, J ¼ 4.8 Hz, CH3, 3H),
1.08 (d, J ¼ 6.6 Hz, CH3, 3H), 0.97 (m, CH2, 1H), 0.65 (d,
J ¼ 22.8 Hz, CH3, 3H) ppm. 13C NMR (D2O): 156.2
(d, J ¼ 5.6 Hz, ArC), 147.8, 147.5 (ArC), 146.2 (d,
J ¼ 2.6 Hz, ArC), 145.6 (d, J ¼ 5.0 Hz, ArC), 141.4,
141.1, 132.5 (ArC), 131.4 (d, J ¼ 7.2 Hz, ArC), 130.11–
129.3 (ArC £ 2), 127.5–126.8 (ArC), 126.1–125.7 (m,
ArC), 62.8 (NC H2), 43.9, 40.8 (myrtenyl-C), 38.1 (d,
J ¼ 4.5 Hz, myrtenyl-C), 31.6–31.2 (myrtenyl-C £ 2),
25.6 (myrtenyl-C), 24.6 (d, J ¼ 7.2 Hz, myrtenyl-C),
23.7 (myrtenyl-C), 22.6 (d, J ¼ 8.9 Hz, myrtenyl-C), 20.7
(d, J ¼ 11.4 Hz, myrtenyl-C) ppm. HRMS (ESI) m/z calcd
for C24H30N ([M]þ) 332.237276, found 332.237442.

10
R. Joseph and E. Masson
N-Myrtenyl-[2-(2-tert-butylphenyl)]pyridinium
bromide (7d)
References
(1) Mock, W.L.; Shih, N.Y. J. Org. Chem. 1986, 51,
4440–4446.
(2) Lagona, J.; Mukhopadhyay, P.; Chakrabarti, S.; Isaacs, L.
Angew. Chem. Int. Ed. 2005, 44, 4844–4870.
(3) Masson, E.; Ling, X.; Joseph, R.; Kyeremeh-Mensah, L.;
Lu, X. RSC Adv. 2012, 2, 1213–1247.
Prepared similarly to pyridinium 7c with phenylpyridine
6d (0.10 g, 0.47 mmol). White solid (51 mg, 25%);
1
m.p. 58–598C. H NMR (D2O): d 8.86 (d, J ¼ 6.0 Hz,
ArZH, 1H), 8.57 (t, J ¼ 6.9 Hz, ArZH, 1H), 8.17–8.09
(m, ArZH, 2H), 7.85 (d, J ¼ 8.1 Hz, ArZH, 1H), 7.65 (t,
J ¼ 7.5 Hz, ArZH, 1H), 7.45–7.38 (m, ArZH, 1H), 7.22
(d, J ¼ 7.8 Hz, ArZH, 1H), 5.29 (s, C ¼ CH, 1H), 5.00–
4.67 (m, NCH2, 2H), 2.45–2.24 (m, CH2, CH, 3H), 2.10
(br, CH, 1H), 1.97–1.90 (m, CH, 1H), 1.24 & 1.19 (s, CH3,
3H), 1.16 (s, C(CH3)3, 9H), 1.06 (m, CH, 1H), 0.77 & 0.63
(s, CH3, 3H) ppm. 13C NMR (D2O): 158.6 (ArC), 148.8 (d,
J ¼ 21.8 Hz, ArC), 145.8 (d, J ¼ 4.8 Hz, ArC), 145.2 (d,
J ¼ 9.4 Hz, ArC), 141.3 (d, J ¼ 10.1 Hz, ArC), 141.4 (d,
J ¼ 10.1 Hz, ArC), 132.1–131.9 (m, ArC £ 2), 131.1 (d,
J ¼ 33 Hz, ArC), 129.6 (d, J ¼ 3.7 Hz, ArC), 129.1 (ArC),
127.7 (d, J ¼ 10.1 Hz, ArC), 126.7 (d, J ¼ 14.5 Hz, ArC),
125.2 (d, J ¼ 20.2, ArC), 62.8 (d, J ¼ 16.4 Hz, NC H2),
44.1, 40.5 (myrtenyl-C), 38.5 (d, J ¼ 17.0 Hz, myrtenyl-
C), 36.8, 32.3 (myrtenyl-C), 31.9 (d, J ¼ 4.4 Hz, myrtenyl-
C), 31.5 (d, J ¼ 8.3 Hz, myrtenyl-C), 25.8 (myrtenyl-C),
20.9 (d, J ¼ 32.0 Hz, myrtenyl-C) ppm. HRMS (ESI) m/z
calcd for C25H32N ([M]þ) 346.252926, found 346.253111.
(4) Maddipatla, M.V.S.N.; Pattabiraman, M.; Natarajan, A.;
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Acknowledgements
This work was supported by the American Chemical Society
Petroleum Research Fund (PRF No. 51053–ND4), the Depart-
ment of Chemistry and Biochemistry, the College of Arts and
Sciences and the Vice President for Research at Ohio University.
The authors thank the Ohio Supercomputer Center (OSC) in
Columbus for its generous allocation of computing time.
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Supramolecular Chemistry
11
Roymon Joseph and Eric Masson
Cucurbit[8]uril recognition of rapidly interconverting diastereomers
1–11