Expedient Synthesis of Heterobifunctional Triarylmethane Stoppers for Macromolecular Rotaxanes

Article abstract of DOI:10.1021/acs.joc.9b03063

Increasingly complex rotaxane-based molecular devices are interfaced with polymers and surfaces, but suitable bifunctional stoppering groups are lacking. Here, we report a two-step, high-yielding synthesis toward a new class of heterobifunctional triarylmethane stoppers. They possess hydroxyl and ester groups for further functionalization as well as halogen substituents conferring a diagnostic spectroscopic signature. Their utility was demonstrated with the synthesis of a chain-centered macromolecular rotaxane. This new stopper architecture should prove useful to connect rotaxanes with polymers and surfaces for applications in polymer mechanochemistry, single-molecule force spectroscopy, smart materials, and molecular machines.

Full text of DOI:10.1021/acs.joc.9b03063

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Note
Expedient Synthesis of Heterobifunctional Triarylmethane Stoppers
for Macromolecular Rotaxanes
Min Zhang, Olga Shvetsova, and Guillaume De Bo*
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ABSTRACT: Increasingly complex rotaxane-based molecular devices are
interfaced with polymers and surfaces, but suitable bifunctional stoppering
groups are lacking. Here, we report a two-step, high-yielding synthesis toward
a new class of heterobifunctional triarylmethane stoppers. They possess
hydroxyl and ester groups for further functionalization as well as halogen
substituents conferring a diagnostic spectroscopic signature. Their utility was
demonstrated with the synthesis of a chain-centered macromolecular rotaxane.
This new stopper architecture should prove useful to connect rotaxanes with
polymers and surfaces for applications in polymer mechanochemistry, single-
molecule force spectroscopy, smart materials, and molecular machines.
eterobifunctional stoppers are particularly useful to
interface rotaxane-based molecular machines and devices
Our recent investigation of the mechanochemistry of the
mechanical bond5a,b,7 lead us to assemble complex macro-
molecular [2]rotaxanes requiring a bulky heterobifunctional
stopper.5a Inspired by Gibson’s synthesis,4 which proceeds by
the acid-catalyzed addition of phenol on triarylmethanol
derivatives, we devised a strategy based on the addition of
phenol onto conjugated ester 2 (which is formed on gram-scale
from cheap commercially available diaryl ketones 1 and a
Wittig reagent, Figure 1). Our initial attempt, reproducing the
conditions used by Gibson, led entirely to the formation of
decarboxylated product 5a (entry 1, Table 1). Lowering the
temperature enables the formation of a small amount of the
desired product (3a) but at the expense of the total conversion
(entries 2 and 3). As chloride ions can assist decarboxylation
via a Krapcho mechanism,8 we hypothesized that acids with a
non-nucleophilic counterion could prevent the formation of
decarboxylated product 5a. Indeed, the use of HBF4 led to the
formation of 3a as the major product (entry 4). Hoping to
further diminish the decarboxylation, we performed the
reaction in the presence of molecular sieve that could arise
from the hydrolyzed ester, but this proved unsuccessful (entry
5). Using p-toluenesulfonic acid (TsOH) as a catalyst afforded
3a with moderate yield and selectivity after 16 h at 90 °C
(entry 6). A slightly improved conversion was obtained with
triflic acid (TfOH) under the same conditions (entry 7).
Reducing the reaction time to 1 h significantly improved the
formation of 3a (entry 8). Pleasingly, we found that 3a could
H
with polymers1a,e and surfaces.2a,g However, the most popular
are only suitable for relatively small macrocycles, and the
increasing complexity of rotaxane-based molecular devices is
often accompanied by the use of larger, tailored-made,
macrocycles.3a,h This need has been fulfilled with Gibson’s
very popular “bulky stopper”4 and, increasingly, with
commercially available alternatives such as 4 (Figure 1b),5a,f
Figure 1. (a) Synthetic strategy toward heterobifunctional stopper 3.
(b) Commercially available stopper 4.
which is slightly smaller but has the advantage of displaying an
enhanced solubility in organic solvent, and a diagnostic
fingerprint in NMR and MS spectra. Homobifunctional
counterparts of the “bulky stopper” are available,6 but no
easily accessible, heterobifunctional equivalent exists. Here, we
report the rapid synthesis of heterobifunctional triarylmethane
stoppers 3 derived from 4 with diagnostic spectroscopic
signatures and/or sites for further functionalization (Figure
1a). These stoppers should prove useful to connect rotaxanes
with polymers and surfaces, for applications in polymer
mechanochemistry, single-molecule force spectroscopy, mate-
rials chemistry, and molecular machines. This concept is
demonstrated with the synthesis of a chain-centered macro-
molecular [2]rotaxane.
Received: November 13, 2019
https://dx.doi.org/10.1021/acs.joc.9b03063
© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
A

The Journal of Organic Chemistry
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Note
a
Table 1. Screening the Reaction Conditions
c
d
entry
catalyst
T (°C)
time (h)
yield of 3a (%)
3a/5a
1
2
3
4
5
6
7
8
9
10
HCl
HCl
HCl
HBF4
HBF4
TsOH
TfOH
TfOH
TfOH
TfOH
170
90
65
90
90
90
90
90
90
45
16
16
16
16
16
16
16
1
1:100
1:6
1:3
1:0.7
1:1.2
1:1.9
1:2.2
1:0.2
7
7
54
17
26
31
83
99
99
b
0.25
0.75
>100:1
>100:1
a
Reaction conditions: 2a (0.2 mmol, 1.0 equiv), phenol (5.3 mmol,
26.5 equiv), catalyst (0.08 mmol, 0.4 equiv) under N2 atmosphere.
b
c
d
Molecular sieve (1.0 equiv) was added. Isolated yield. Determined
1
by H NMR.
be formed quantitively and with complete selectivity after 15
min at 90 °C (entry 9) or by maintaining the reaction mixture
just above the melting point of phenol (41 °C) for 45 min
(entry 10).
The scope of the reaction was explored by reacting phenol
with a range of 3,3-diarylacrylates under the optimized
conditions presented in entry 10 of Table 1. All halogen-
substituted substrates showed quantitative conversion (entries
1−3, Table 2), with no detectable amount of decarboxylated
a
Table 2. Scope of the Reaction
Figure 2. (a) Synthetic route toward chain-centered polymer 11. (i)
Propargyl bromide, K2CO3, MeCN, 70 °C, 12 h, 96%. (ii) LiOH,
H2O/THF, 1 M HCl, 12 h, rt, quantitative. (iii) (COCl)2, DCM, rt, 2
h, quantitative. (iv) DB24C8, diethanolamine 9, AgOTf, 2 h, rt, 42%.
(v) 12, Cu(MeCN)4PF6, DCM/MeCN, 12 h, rt, 74%. (vi) Methyl
acrylate, CuBr2/Me6TREN, copper wire, DMSO, rt, 40 min. (b) 19F
NMR comparison of 9·H+TfO− (top), rotaxane 11 (middle), and free
thread 10 (bottom). (c) 19F NMR comparison of rotaxane 11 (top)
and rotaxane 13 (bottom). (d) GPC trace of rotaxane centered
polymer 14. (e) Partial 1H NMR comparison of DB24C8 (top),
rotaxane 11 (middle) and free thread 10 (bottom).
b
entry
2
X
3
yield of 3 (%)
1
3
4
5
2a
2b
2c
2d
Cl
Br
3a
3b
3c
3d
99
96
99
0
F
OMe
a
Reaction conditions: 2 (0.2 mmol, 1.0 equiv), phenol (5.3 mmol,
26.5 equiv), TsOH (0.08 mmol, 0.4 equiv) under N2 atmosphere.
b
Isolated yield.
product. However, the presence of electron-donating groups
on the acceptor completely suppresses its reactivity (entry 4).
Advantageously, this reaction can be easily scaled up to gram
scale, as demonstrated by the production of 1.5 g of chloro
derivative 3a in 94% yield.
alkyne cycloaddition (CuAAC). Rotaxane 11 was obtained in
42% yield using Takata’s method9 by reacting activated stopper
8, diethanolamine 9, and dibenzo-24-crown-8 (DB24C8)
1
macrocycle in the presence of silver triflate. The H NMR
spectra (Figure 2e) of DB24C8 macrocycle, free-thread 10
(i.e., 11 without macrocycle), and rotaxane 11 confirm the
interlocked structure. The upfield shift of axle protons
Hm(ΔδHm = −0.43 ppm), ammonium protons Hq (ΔδHq =
−0.24 ppm), and macrocycle protons H6 (ΔδH6 = −0.16
ppm) and downfield shift of axle protons Hp(ΔδHp= 0.60
ppm) in the rotaxane compared to the free-thread/macrocycle
are indicative of the presence of the macrocycle around the
ammonium station. The 19F NMR spectra (Figure 2b) clearly
show the peaks associated with the triflate anion (−78.1 ppm)
To further demonstrate the utility of this new stopper, we
devised the synthesis of a chain-centered rotaxane starting
from ester 3c (Figure 2a). We anticipated that the p-fluoro
1
substituents would confer a distinctive pattern in the H and
19F NMR spectra of the various synthetic intermediates
(Figure 2b,c,e). Propargylation and subsequent hydrolysis of
3c afford acid 7, which adequately possesses an acid
functionality, to connect to the axle of the rotaxane, and an
alkyne, to append a polymer precursor by Cu-catalyzed azide−
B
https://dx.doi.org/10.1021/acs.joc.9b03063
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Note
3H); 13C{1H} NMR (126 MHz, CDCl3) δ = 166.1, 154.8, 139.4,
137.2, 131.9, 131.5, 131.0, 129.9, 124.4, 123.0, 117.7, 117.7, 51.6,
51.6; MS-ESI(+) m/z = 417.0(50, [M + Na]+), 419.0 (100, [M +
Na]+), 421.0 (30, [M + Na]+); HRMS (ESI-FTMS) m/z [M + H]+
calcd for C16H13O2Br2 394.9277, found 394.9281.
and the fluorophenyl groups (−116.3 ppm). Rotaxane 11 was
then appended with polymerization initiators (12) by CuAAC
to reach rotaxane 13. This reaction was catalyzed by
Cu(MeCN)4PF6, and 19F NMR analysis revealed the exchange
of TfO− counterion for PF6− in the process by the presence of
a doublet at −72.6 ppm (Figure 2c). Finally, chain-centered
macromolecular rotaxane 14 was obtained by single-electron-
transfer living radical polymerization (SET-LRP)10 of methyl
acrylate initiated from both ends of the axle. GPC (Mn = 45
Methyl 3,3-Bis(4-fluorophenyl)acrylate 2c. White solid, mp 46.1−
48.0 °C; yield 99% (543 mg); 1H NMR (500 MHz, CDCl3) δ = 7.16
(dd, J = 8.5, 9.0 Hz, 4H, Hb), 7.02 (d, J = 8.5 Hz, 2H), 6.95 (dd, J =
8.5, 9.0 Hz, 4H), 6.72 (d, J = 8.5 Hz, 2H), 4.92 (s, 1H), 3.63 (s, 2H),
3.42 (s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ = 171.5, 161.3 (d,
J = 246 Hz), 154.1, 142.5 (d, J = 3.3 Hz), 138.5, 130.7 (d, J = 7.8 Hz),
130.3, 114.9, 114.8 (d, J = 21.1 Hz), 54.3, 51.7 (d, J = 2.0 Hz), 46.6;
19F NMR (470 MHz, CDCl3) δ = −116.63; MS-ESI(−) m/z = 367.2
1
kDa, Đ = 1.16, Figure 2d) and H NMR (see the SI) indicate
the successful incorporation of the rotaxane in the polymer.
In conclusion, we have developed an expedient synthesis of a
new class of heterobifunctional stoppers. These stoppers can
be produced on a gram scale with high yields, and their
halogen substituents provide them with a diagnostic
spectroscopic signature and potential sites for further
functionalization. The utility of these building blocks was
demonstrated with the synthesis of a chain-centered macro-
molecular rotaxane. We anticipate that this new stopper
architecture should prove useful to connect rotaxanes with
polymers and surfaces, for applications in polymer mecha-
nochemistry, single-molecule force spectroscopy, materials
chemistry, and molecular machines.
(100, [M − H]−); HRMS (ESI-FTMS) m/z [M − H]− calcd for
C22H17O3F2 367.1151, found 367.1159.
Methyl 3,3-Bis(4-methoxyphenyl)acrylate 2d. White solid, mp
35.5−37.0 °C; yield 21% (125 mg); 1H NMR (500 MHz, CDCl3) δ =
7.24 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 8.6 Hz,
2H), 6.84 (d, J = 8.4 Hz, 2H), 6.23 (s, 1H), 3.85 (s, 3H), 3.82 (s,
3H), 3.62 (s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ = 166.9,
160.9, 159.8, 157.1, 134.0, 131.2, 131.0, 130.2, 114.4, 114.5, 113.8,
113.4, 55.5, 55.5, 55.4, 55.3, 51.3, 51.3; MS-ESI(+) m/z = 321.2 (30,
[M + Na]+); HRMS (ESI-FTMS) m/z [M + Na]+ calcd for
C18H18O4Na 321.1097, found 321.1086.
General Procedure for the Synthesis of Stopper 3. TfOH
(0.12 mmol, 40 mmol %) was added to a mixture of 2 (0.3 mmol, 1.0
equiv) and phenol (500 mg). The mixture was heated to 45 °C for 45
min in an oil bath. The crude product was washed with water and
purified by flash column chromatography (PE/EtOAc = 5:1) to yield
3 as a solid.
Methyl 3,3-Bis(4-chlorophenyl)-3-(4-hydroxyphenyl)propanoate
3a. White solid, mp 145.3−147.2 °C; yield 99% (119 mg); 1H NMR
(400 MHz, CDCl3) δ = 7.23 (d, J = 8.4 Hz, 4H), 7.13 (d, J = 8.8 Hz,
4H), 7.02 (d, J = 8.8 Hz, 2H), 6.73 (d, J = 8.8 Hz, 2H), 4.69 (b, 1H),
3.61 (s, 2H), 3.42 (s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ =
171.5, 154.4, 145.0, 137.7, 132.5, 130.5, 130.2, 128.2, 115.0, 54.5,
51.8, 46.2; MS-ESI(−) m/z = 399.1 (100, [M − H]−), 401.1 (80, [M
− H]−); HRMS (ESI-FTMS) m/z [M − H]− calcd for C22H17O3Cl2
399.0560, found 399.0566.
Methyl 3,3-Bis(4-bromophenyl)-3-(4-hydroxyphenyl)propanoate
3b. White solid, mp 162.9−164.7 °C; yield 96% (141 mg); 1H NMR
(500 MHz, CDCl3) δ = 7.38 (d, J = 8.5 Hz, 4H), 7.07 (d, J = 8.4 Hz,
4H), 7.01 (d, J = 9.0 Hz, 2H), 6.72 (d, J = 8.5 Hz, 2H), 4.83 (b, 1H),
3.61 (s, 2H), 3.42 (s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ =
171.2, 154.2, 145.4, 137.9, 131.2, 130.9, 130.3, 120.7, 115.0, 54.6,
51.7, 46.0; MS-ESI(−) m/z = 487.1 (50, [M − H]−); HRMS (ESI-
FTMS) m/z [M − H]− calcd for C22H17O3Br2486.9550, found
486.9545.
EXPERIMENTAL SECTION
■
Unless otherwise stated, all reagents and solvents were purchased
from commercial suppliers and used without further purification.
Cu(0) wire (diameter: 0.25 mm, purity 99.9%) was purchased from
Sigma-Aldrich. Me6TREN was purchased from Alfa Aesar. Com-
pounds 2a5a and 1211 were prepared according to literature
procedures. Gel permeation chromatography (GPC) analyses were
performed in THF solution (∼0.6 mg mL−1) at 35 °C using a
Malvern Viscotek GPCmax VE2001 solvent/sample module with 2 ×
PL gel 10 μm mixed-B and a PL gel 500 Å column and equipped with
a Viscotek VE3580 refractive index detector employing narrow
polydispersity polystyrene standards (Agilent Technologies) as a
calibration reference. Samples were filtered through a Whatman
Puradisc 4 mm syringe filter with a 0.45 μm PTFE membrane before
injection to equipment, and experiments were carried out with
injection volume of 200 μL, flow rate of 1 mL min−1. Results were
analyzed using n-dodecane as internal marker using Malvern
OmniSEC 5.10 software. Analytical TLC was performed on precoated
silica gel plates (0.25 mm thick, 60 F254, Merck, Germany) and
observed under UV light or stained with a phosphomolybdic acid
solution. Preparative TLC was performed on precoated silica gel
plates: 2 mm, UNIPLATE GF, Analtech Inc., DE. Flash column
chromatography was performed with silica gel 60 (230−400 mesh)
Methyl 3,3-Bis(4-fluorophenyl)-3-(4-hydroxyphenyl)propanoate
1
3c. White solid, mp 95.5−97.3 °C; yield 99% (109 mg); H NMR
1
from Sigma-Aldrich. H and 13C NMR spectra were obtained using
(500 MHz, CDCl3) δ = 7.16 (dd, J = 8.5, 9.0 Hz, 4H), 7.02 (d, J = 8.5
Hz, 2H), 6.95 (dd, J = 8.5, 9.0 Hz, 4H), 6.72 (d, J = 8.5 Hz, 2H), 4.92
(s, 1H), 3.63 (s, 2H), 3.42 (s, 3H); 13C{1H} NMR (126 MHz,
CDCl3) δ = 171.5, 161.3 (d, J = 246 Hz), 154.2, 142.5 (d, J = 3.3 Hz),
138.5, 130.7 (d, J = 7.8 Hz), 130.3, 114.9, 114.8 (d, J = 21.1 Hz),
54.3, 51.7 (d, J = 2.0 Hz), 46.6; 19F NMR (470 MHz, CDCl3) δ =
−116.63; MS-ESI(−) m/z = 367.2 (100, [M − H]−); HRMS (ESI-
FTMS) m/z [M − H]− calcd for C22H17O3F2 367.1151, found
367.1159.
either a Bruker Avance III 500 MHz Prodigy instrument or a Bruker
Avance III 400 MHz Prodigy instrument at the University of
Manchester. Chemical shifts are reported in parts per million (ppm)
from high to low frequency and referenced to the residual solvent
resonance. Coupling constants (J) are reported in hertz (Hz), and
splitting patterns are designated as follows: b = broad, s = singlet, d =
doublet, t = triplet, q = quartet, p = pentet, and m = multiplet. Mass
spectra were obtained through the mass spectrometry services in the
Department of Chemistry at the University of Manchester.
General Procedure for the Synthesis of 3,3-Diaryl Acrylates
2. A solution of 1 (2 mmol, 1.0 equiv) and methyl (triphenylphos-
phoranylidene) acetate (2.4 mmol, 1.2 equiv) in toluene (5 mL) was
heated to reflux for 36 h in an oil bath. The solvent was removed, and
the crude product was purified by flash column chromatography (PE/
EtOAc = 10:1) to give 2.
Synthesis of Rotaxane 13. Methyl 3,3-Bis(4-fluorophenyl)-3-(4-
(prop-2-yn-1-yloxy)phenyl)propanoate 6. To a solution of 3c (850
mg, 2.3 mmol, 1.0 equiv) and propargyl bromide (550 mg, 4.6 mmol,
2.0 equiv) in MeCN (5 mL) was added K2CO3 (476 mg, 3.45 mmol,
1.5 equiv). The mixture was heated to 70 °C in an oil bath overnight.
The crude was washed with NH4Cl (aq 5 mL) and extracted with
DCM (3 × 5 mL). The organic phase was combined and purified by
flash column chromatography (PE/EtOAC = 10:1) to yield 6 as a
Methyl 3,3-Bis(4-bromophenyl)acrylate 2b. White solid, mp
103.4−105.2 °C; yield 74% (586 mg); 1H NMR (500 MHz,
CDCl3) δ = 7.52 (d, J = 7.0 Hz, 2H), 7.46 (d, J = 7.0 Hz, 2H), 7.13
(d, J = 7.0 Hz, 2H), 7.06 (d, J = 7.0 Hz, 2H), 6.35 (s, 1H), 3.64 (s,
1
white solid (900 mg, 96% yield): mp 39.5−41.4 °C; H NMR (500
MHz, CDCl3) δ = 7.16 (dd, J = 8.5, 9.0 Hz, 4H), 7.09 (d, J = 8.5 Hz,
2H), 6.95 (dd, J = 8.5, 8.5 Hz, 4H), 6.83 (d, J = 8.5 Hz, 2H), 4.66 (d,
C
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Note
J = 2.0 Hz, 2H), 3.64 (s, 2H), 3.41 (s, 3H), 2.52 (t, J = 2.0 Hz, 1H);
13C{1H} NMR (126 MHz, CDCl3) δ = 171.3, 161.4 (d, J = 246 Hz),
Rotaxane 13. To a dry flask were added 11 (10 mg, 6.9 μmol, 1.0
equiv) and 12 (5.0 mg, 20.7 μmol, 3.0 equiv). DCM (0.8 mL) and
MeCN (0.2 mL) were added. The solution was degassed four times
by freeze−thaw cycles. The mixture was then cannulated to a
degassed vial containing Cu(MeCN)4PF6 (5.1 mg, 13.8 μmol, 2.0
equiv). The resulting solution was stirred at room temperature
overnight. The crude product was purified by flash column
chromatography (4% MeOH in DCM) yielding 13 as a white solid
(9.8 mg, 74% yield). 1H NMR (500 MHz, CDCl3) δ = 7.87 (bs, 2H),
6.98 (dd, J = 8.5, 8.5 Hz, 8H), 6.89−6.82 (m, 24H), 5.16 (s, 4H),
4.70 (t, J = 5.5 Hz, 4H), 4.57 (t, J = 5.5 Hz, 4H), 4.10 (t, J = 3.5 Hz,
8H), 3.93 (t, J = 4.5 Hz, 4H), 3.79 (t, J = 3.5 Hz, 8H), 3.64 (s, 8H),
3.50 (t, J = 4.0 Hz, 4H), 3.19 (s, 4H); 13C{1H} NMR (126 MHz,
CDCl3) δ = 171.2, 170.2, 161.3 (d, J = 246 Hz), 156.9, 147.6, 144.2,
142.0 (d, J = 3.4 Hz), 138.4, 130.6 (d, J = 7.8 Hz), 130.0, 124.3,
122.2, 114.8 (d, J = 21.0 Hz), 114.3, 113.0, 70.9, 70.5, 68.2, 64.0, 61.9,
59.8, 55.6, 54.1, 50.0, 47.5, 45.6, 30.7; 19F NMR (470 MHz, CDCl3) δ
= −72.63 (d, J = 712 Hz), −116.32; MS-ESI(+) 1774.5 (100, [M −
PF6]+); HRMS (ESI-FTMS) m/z [M − PF6]+ calcd for
C88H96N7O18Br2F41772.5109, found 1772.5047 (for isotopic distri-
bution, see the SI).
Synthesis of Rotaxane 14. Methyl acrylate was filtered through
basic alumina to remove the inhibitor prior to use. A stock solution of
Me6TREN (16 μL, 0.060 mmol) and CuBr2 (5.6 mg, 0.025 mmol) in
dry DMSO (1 mL) was prepared. To a 5 mL vial were added rotaxane
13 (10 mg, 5.2 μmol, 1.0 equiv), 42 μL of catalytic solution
(Me6TREN: 3.0 μmol, 0.48 equiv; CuBr2: 1.2 μmol, 0.2 equiv),
methyl acrylate (0.48 mL, 5.219 mmol, 1000.0 equiv), and dry DMSO
(0.4 mL). This solution was degassed by bubbling with N2 for 10 min.
A Cu(0) wire (∼2 cm, ∼20 mg, 0.315 mmol, ∼100.0 equiv, cleaned in
HClconc for 10 min) wrapped around a stirrer bar was added, and the
solution was degassed for a further 2 min before being allowed to stir
for 2 h. The solution was then precipitated out in stirring methanol,
recovered, and dried under a high vacuum for several days to yield a
white polymer (230 mg, Mn = 45 kDa, Đ = 1.16). Molecular weight
and polydispersity indices were recorded using an analytical GPC that
had been calibrated with polystyrene standards.
156.2, 142.4 (d, J = 3.4 Hz), 139.5, 130.8 (d, J = 7.9 Hz), 130.1, 114.8
(d, J = 21.1 Hz), 114.3, 78.7 (d, J = 2.1 Hz), 75.7 (d, J = 8.1 Hz),
55.9, 54.3, 51.7 (d, J = 2.1 Hz), 46.6; 19F NMR (470 MHz, CDCl3) δ
= −116.59; MS-ESI(+) m/z = 429.2 (100, [M + Na]+), 430.2 (20,
[M + Na]+); HRMS (ESI-FTMS) m/z [M + Na]+ calcd for
C25H20O3F2Na 429.1273, found 429.1262.
3,3-Bis(4-fluorophenyl)-3-(4-(prop-2-yn-1-yloxy)phenyl)-
propanoic Acid 7. To a solution of 6 (812 mg, 2.0 mmol, 1.0 equiv)
in MeOH (2 mL) was added a solution of LiOH (384 mg, 8.0 mmol,
4.0 equiv) in H2O (2 mL). The resulting solution was stirred at room
temperature overnight. The solvent was removed and acidified using 1
M HCl until pH = 2. The crude product was extracted by DCM (3 ×
5 mL) and concentrated. The crude product was used directly
without further purification: mp 95.2−97.0 °C; 1H NMR (500 MHz,
CDCl3) δ = 7.12 (dd, J = 8.5, 9.0 Hz, 4H), 7.07 (d, J = 8.5 Hz, 2H),
6.94 (dd, J = 8.5, 8.5 Hz, 4H), 6.87 (d, J = 9.0 Hz, 2H), 4.66 (d, J =
2.5 Hz, 2H), 3.63 (s, 2H), 2.52 (t, J = 2.5 Hz, 1H); 13C{1H} NMR
(126 MHz, CDCl3) δ = 176.0, 161.3 (d, J = 246 Hz), 156.2, 142.1 (d,
J = 3.4 Hz), 139.3, 130.7 (d, J = 7.8 Hz), 130.1, 114.9 (d, J = 21.2
Hz), 114.4, 78.6 (d, J = 2.0 Hz), 75.8 (d, J = 8.1 Hz), 55.9, 54.0, 46.4;
19F NMR (470 MHz, CDCl3) δ = −116.59.
3,3-Bis(4-fluorophenyl)-3-(4-(prop-2-yn-1-yloxy)phenyl)-
propanoyl Chloride 8. To a solution of 7 (588 mg, 1.5 mmol, 1.0
equiv) in DCM (3 mL) was added 2 drops of DMF. (COCl)2 (0.26
mL, 3 mmol, 2.0 equiv) was added dropwise. The resulting solution
was stirred at room temperature for 2 h. The solvent was removed and
dried under high vacuum. The crude product was used directly
without further purification
Free Thread 10. To a dry flask were added diethanolamine 9 (50
mg, 79 μmol, 1.0 equiv) and AgOTf (45 mg, 158 μmol, 2.2 equiv).
DCM (500 μL) was then added. The solution was cooled in an ice
bath before the addition of 8 (18 mg, 79 μmol, 1.2 equiv). The
resulting solution was stirred at room temperature overnight. The
crude product was purified by flash column chromatography (4%
MeOH in DCM) yielding 10 as a white solid (15 mg, 19% yield): 1H
NMR (500 MHz, CDCl3) δ = 7.76 (bs, 2H), 7.14 (dd, J = 8.5, 8.5 Hz,
8H), 7.07 (d, J = 9.0 Hz, 4H), 6.92 (dd, J = 8.5, 8.5 Hz, 8H), 6.84 (d,
J = 9.0 Hz, 4H), 4.63 (d, J = 2.0 Hz, 4H), 3.99 (t, J = 5.0 Hz, 4H),
3.70 (s, 4H), 2.92 (t, J = 5.5 Hz, 4H), 2.50 (t, J = 2.5 Hz, 2H);
13C{1H} NMR (126 MHz, CDCl3) δ = 171.1, 161.4 (d, J = 246 Hz),
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.9b03063.
■
sı
1H, 13C, 19F NMR spectra and rotaxanes isotopic
patterns (PDF)
156.2, 147.61, 141.1 (d, J = 3.3 Hz), 138.9, 130.7 (d, J = 7.6 Hz),
130.2, 114.9 (d, J = 21.3 Hz), 114.4, 78.6 (d, J = 2.1 Hz), 75.9 (d, J =
9.1 Hz), 59.0, 55.9, 54.3, 47.3, 46.1; 19F NMR (470 MHz, CDCl3) δ =
−78.28, −116.04; MS-ESI(+) 854.5 (100, [M − OTf]+), 855.5 (30,
[M − OTf]+); HRMS (ESI-FTMS) m/z [M − OTf]+ calcd for
C52H44NO6F4 854.3099, found 854.3086.
AUTHOR INFORMATION
Corresponding Author
■
Rotaxane 11. To a dry flask were added diethanolamine 9 (50 mg,
79 μmol, 1.0 equiv), dibenzo-24-crown-8(51 mg, 118 μmol, 2.0
equiv), and AgOTf (45 mg, 158 μmol, 2.2 equiv). DCM (100 μL)
was then added. The solution was stirred at room temperature for 2 h.
The solution was cooled in an ice bath before the addition of 8 (18
mg, 79 μmol, 1.2 equiv). The resulting solution was stirred at room
temperature overnight. The crude product was purified by flash
column chromatography (4% MeOH in DCM) yielding 11 as a white
solid (48 mg, 42% yield): 1H NMR (500 MHz, CDCl3) δ = 6.98 (dd,
J = 8.5, 9.0 Hz, 8H), 6.91 (d, J = 8.5 Hz, 4H), 6.89−6.84 (m, 16H),
6.81 (d, J = 9.0 Hz, 4H), 4.64 (d, J = 2.4 Hz, 4H), 4.11 (t, J = 3.5 Hz,
8H), 3.95 (t, J = 4.5 Hz, 4H), 3.81 (t, J = 3.5 Hz, 8H), 3.67 (s, 8H),
3.52 (t, J = 4.0 Hz, 4H), 3.22 (s, 4H), 2.54 (t, J = 2.5 Hz, 2H);
13C{1H} NMR (126 MHz, CDCl3) δ = 170.2, 161.3 (d, J = 246 Hz),
156.1, 147.6, 142.0 (d, J = 3.3 Hz), 139.0, 130.6 (d, J = 7.6 Hz),
130.0, 122.1, 114.8 (d, J = 21.0 Hz), 114.3, 113.0, 78.7 (d, J = 2.6
Hz), 75.9 (d, J = 10.3 Hz), 71.0, 70.5, 68.3, 59.8, 55.9, 54.0, 47.4,
45.5; 19F NMR (470 MHz, CDCl3) δ = −78.10, −116.32; MS-ESI(+)
1302.9 (100, [M − OTf]+), 1304.9 (20, [M − OTf]+); HRMS (ESI-
FTMS) m/z [M − OTf]+ calcd for C76H76NO14F41302.5196, found
1302.5155 (for isotopic distribution, see the SI).
Guillaume De Bo − Department of Chemistry, University of
Manchester, Manchester M13 9PL, United Kingdom;
orcid.org/0000-0003-2670-6370;
Email: guillaume.debo@manchester.ac.uk
Authors
Min Zhang − Department of Chemistry, University of
Manchester, Manchester M13 9PL, United Kingdom
Olga Shvetsova − Department of Chemistry, University of
Manchester, Manchester M13 9PL, United Kingdom
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.9b03063
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the Royal Society for a Newton International
Fellowship to M.Z., a summer studentship to O.S. (funded
■
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https://dx.doi.org/10.1021/acs.joc.9b03063
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
(5) (a) Zhang, M.; De Bo, G. Mechanical Susceptibility of a
Rotaxane. J. Am. Chem. Soc. 2019, 141, 15879−15883. (b) Zhang, M.;
De Bo, G. Impact of a Mechanical Bond on the Activation of a
Mechanophore. J. Am. Chem. Soc. 2018, 140, 12724−12727.
through a Research Grant), and a University Research
Fellowship to G.D.B.
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