Studies toward the synthesis of phenylacetylene macrocycle based rotaxane precursors as building blocks for organic nanotubes

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

FULL PAPER

DOI: 10.1002/ejoc.201200655

Studies Toward the Synthesis of Phenylacetylene Macrocycle Based Rotaxane

Precursors as Building Blocks for Organic Nanotubes

Katy Cantin,^[a]Antoine Lafleur-Lambert,^[a]Philippe Dufour,^[a]and Jean-François Morin*^[a]

Keywords: Macrocycles / Rotaxanes / Cross-coupling / Synthetic methods / Nanotubes

Synthetic efforts toward the preparation of rotaxane precur-

PAMs with different sizes and functions were prepared and

sors based on phenylacetylene macrocycles (PAM) are de- coupled to different blockers to assess whether or not the

scribed. The aim of this study was to determine the optimal

structural parameters to prepare high-molecular-weight rot-

axane precursors through a strategy involving two Sonoga-

shira couplings to attach bulky blockers on the PAM core.

resulting structure adopts a rotaxane-like conformation in

which the rigid rod forms after the Sonogashira coupling

threads through the PAM.

and versatile method to prepare stable organic nanotubes is

still lacking. Most of the methods reported so far to prepare

organic nanotubes rely on self-assembly, under very specific

conditions, of carefully designed building blocks. However,

because the interactions (H-bonding, van der Waals, hydro-

phobic and π–π interactions) that keep these building

blocks together are rather weak, many of the supramolec-

ular architectures reported to date are kinetically unstable.

The most well-known examples of supramolecular nano-

tubes are made from cyclic oligopeptides,^[8]cyclic oligosac-

charides,^[9]calixarene,^[10]phenylacetylene foldamers^[11]and

block copolymers.^[12]One way to increase the strength and

kinetic stability of supramolecular nanotubes is to cova-

lently link the building blocks to one another once the nano-

tube is formed by using specific reactions conducted under

self-assembly conditions. The reactions that have been used

for nanotube stabilization include photochemical and ther-

mal cross-linking,^[13]alkene metathesis,^[14]ring-opening me-

tathesis,^[14,15]atom transfer radical polymerization,^[16]nu-

cleophilic substitution reaction^[17]and metal–ligand coordi-

nation.^[18]

One of the major drawbacks of supramolecular chemis-

try to self-assemble the building blocks of nanotubes is that

specific functional groups have to be used to direct and

drive the self-assembly process, thus limiting the scope of

this strategy in terms of chemical diversity. Therefore, the

next logical step toward the preparation of monodisperse

and well-defined nanotubes is to develop a versatile strategy

that will not only allow control of the nanotubes’ shape but

also its function. The most obvious approach to obtain

such control is to grow nanotubes by using traditional cova-

lent chemistry from polymerizable building blocks. Re-

cently, Zimmerman et al. reported an elegant way to pre-

pare organic nanotubes from porphyrin-cored dendrimers

by using this strategy.^[14]Although their approach is syn-

thetically demanding and mostly leads to short nanotubes,

Introduction

The preparation of nanoarchitectures with finite size and

shape is a key aspect for the development of nanoscience.

Although the development of inorganic nanoarchitectures

has benefited from a great deal of attention from materials

scientists in the past two decades, lesser efforts have been

devoted to preparing their organic counterparts. Most of

the physical methods frequently used to prepare inorganic

nanoarchitectures, like nanoparticles, carbon nanotubes,

nanocrystals and so on, do not offer the same level of con-

trol and precision with regard to size and shape as organic

synthetic methods do at the molecular level. Moreover, the

versatility of organic synthesis allows the fine-tuning of

physical properties through precise chemical alterations of

the nanoarchitectures, opening the way to their use in vari-

ous applications ranging from electronics to biomedical

areas. Recent examples include the preparation of monodis-

perse organic nanocapsules from dendrimers,^[1]well-defined

graphene sheets and nanoribbons,^[2]ion channels^[3]and

semiconducting nanowires.^[4]

Among the organic nanoarchitectures reported so far,

the organic nanotube is undoubtedly the molecular archi-

tecture that attracted the most attention owing to its in-

ternal cavity that makes it a good candidate for host–guest

chemistry,^[5]scaffolding^[6]and site isolation.^[7]Although

interesting examples and proof-of-concept have been re-

ported for each of these applications, an efficient, reliable

[a] Département de Chimie and Centre de Recherche sur les

Matériaux Avancés (CERMA), Université Laval,

1045 Ave de la Médecine, G1V 0A6, Canada

Fax: +1-418-656-7916

E-mail: jean-francois.morin@chm.ulaval.ca

Homepage: http://ww w .chm.ulaval.ca/jfmorin/2009/Accueil.

html

Supporting information for this article is available on the

WWW under http://dx.doi.org/10.1002/ejoc.201200655.

Eur. J. Org. Chem. 0000, 0–0

1

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

K. Cantin, A. Lafleur-Lambert, P. Dufour, J.-F. Morin

FULL PAPER

we believe that the covalent approach ought to be further ture.^[19]However, the primary objective of their study was

explored to extend its scope and understand its limitations. the photophysical characterization of the polymer so no

Therefore, we decided to investigate a new strategy of cova- study of any relationship between structure and properties

lent growth of the nanotubes’ architecture involving a phen- was undertaken.

ylacetylene macrocycle (PAM) containing rotaxane precur-

sor as the building blocks. Our strategy (Figure 1) is similar

to the strategy developed by Zimmerman et al.; it consists

of preparing a polymerizable rotaxane precursor (I) in

which the macrocycle is a PAM and the rigid rod is an

oligophenyleneethynylene (OPE). The PAM structure has

been chosen for its shape-persistency, which is expected to

provide a rigid scaffold to the nanotubes that would help

preventing the nanotube from collapsing, as observed by

Zimmerman for a more flexible nanotube wall.^[14]This rot-

axane precursor will undergo a polymerization reaction

through its reactive end to give the rotaxane precursor poly-

Figure 2. Possible conformations for the rotaxane precursor ob-

tained after the coupling of PAM to the blockers.

mer (II) before cross-linkable units are attached to the outer

part of the macrocycles (III). Then, the macrocycles will

be covalently linked to each other, and the interior of the

Herein, we report synthetic efforts toward the prepara-

tion of PAM-containing [2]rotaxanes as building blocks for

rigid organic nanotubes. The synthesis of PAMs, blockers

macrocycle will be removed to leave a void inside the nano-

and rotaxane precursors with different sizes and functions

tube structure (IV). By using this strategy, the PAM will

is presented. The rotaxane architecture is not only interest-

ing as a potential building block for organic nanotubes, but

stay within the nanotube structure meaning that the dia-

meter of the nanotube could be tuned by changing the size

also as supramolecular scaffold for the development molec-

of the macrocycle used to template the assembly.

ular machines,^[20]photochemical devices^[22]and actua-

tors.^[21]All the structure-related optimizations reported here

were conducted with the sole goal of preparing rotaxane

building blocks for further nanotube synthesis.

Results and Discussion

The first step toward the preparation of a PAM-contain-

ing rotaxane precursor is the synthesis of a macrocycle con-

taining reactive functions at its core. We chose two aryl iod-

ides as a polymerizable unit, because they can react with

terminal alkynes in Sonogashira coupling reactions to a

give rigid phenyleneethynylene-based polymer backbone.

Figure 1. Strategy for the preparation of PAM-based nanotubes

The synthesis of the first PAM is depicted in Scheme 1. Be-

cause functional groups are needed inside the PAM to pre-

pare the rotaxane precursor, we used the template approach

inspired by Zimmerman et al.^[14]

However, before undertaking the preparation of such developed by Höger et al. to prepare our macrocycle.^[23]

nanotubes, many structural parameters of the rotaxane pre- This method allows the preparation of macrocycles in

cursor need to be optimized to ensure that the growth of the higher yields than through traditional ring-closing reactions

nanotube works efficiently. The most important question to under very dilute conditions. Our strategy was to prepare

answer is whether or not the rigid rod of the rotaxane pre- the half-PAM before connecting it to the template and clos-

cursor seen in structures I and II passes through the macro- ing the macrocycle by an Eglinton coupling. Protected

cycle, because steric congestion might arise from these amino groups were added on four out of six phenyl units

structures. Figure 2 shows two possible conformations for to allow the covalent attachment of cross-linkable units re-

the rotaxane precursor. Depending on the diameter of the quired for the preparation of the nanotubes’ wall (Figure 1,

nanotube and the steric congestion in the interior of the Steps IIǞIII). Compound 1^[24]was diiodinated in 62%

macrocycle, one of the two isomers could be formed prefer- yield (compound 2) by using a known method for phenols,

entially. Consequently, the first step toward the preparation followed by a methylation reaction to protect the phenol

of an organic nanotube through the rotaxane precursor group to give 3. Protection of the phenol group was neces-

strategy is to prepare [2]rotaxanes that are blocked at both sary, because attempts to acylate the benzylic amine group

ends with bulky moieties to assess whether or not the OPE selectively from the phenol were unsuccessful or poor-yield-

rigid rod can pass through the macrocycle. To the best of ing. Next, the di-tert-butyl dicarbonate (Boc) group was re-

our knowledge, only Höger et al. have reported the prepara- moved with trifluoroacetic acid (TFA) in dichloromethane,

tion of a PAM-based polymer with a rotaxane-like architec- and the resulting benzylic amine treated with lauroyl chlor-

2

www.eurjoc.org

Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

Phenylacetylene Macrocycle Based Rotaxane Precursors

ide and (dimethylamino)pyridine (DMAP) as the catalyst densation reactions. Acetylene groups were then installed

to give 4 in 91% yield. The phenol group was then depro- on 8 by using (triisopropylsilyl)acetylene (TIPSA) followed

tected in very high yield by using boron tribromide (com- by deprotection by using tetrabutylammonium fluoride

pound 5) and treated with chloroethanol in the presence of (TBAF) in THF. The alkynes were deprotected prior to the

sodium iodide to give 6. By using standard Sonogashira coupling of the half-macrocycle on the diiodo-containing

coupling reaction conditions two (trimethylsilyl)acetylene template molecule, because the ester groups were very sensi-

(TMSA) moieties were installed in excellent yield (com- tive in the presence of TBAF. Thus, deprotected analog 10

pound 7). The alkynes were then deprotected under alkaline of 9 was coupled to 11^[25]by using DMAP as the catalyst

conditions and immediately coupled to 3 by standard Sono- to provide the macrocycle precursor 12 in good yield. Fi-

gashira coupling to give half-macrocycle 8 in 31% yield. nally, the ring-closure reaction was performed under Eglin-

The free alkyne intermediate was not isolated owing to its ton conditions over 11 d to produce the final PAM 13. The

apparent instability under ambient conditions. The rela- yield of this reaction was very low relative to those usually

tively low yield obtained for the formation of 8 is attributed obtained for this kind of templated ring-closure reaction.

to the formation of a significant number of oligomers even Because the reactivity of the terminal alkyne is unlikely to

though a large excess (3 equiv.) of the diiodo derivative was be a limiting factor, we attributed this low yield to high

used to minimize the occurrence of AA/BB-type polycon- steric hindrance in the inner part of the macrocycle and to

the poor solubility of the resulting material. Because of the

very small quantity of macrocycle obtained, we did not at-

tempt to prepare the corresponding rotaxane precursor. In-

stead, we decided to prepare a very similar macrocycle with

a larger diameter. The synthetic pathway used to prepare a

larger macrocycle is presented in Scheme 2.

The strategy used to increase the macrocycle diameter

was to add a 1,4-dimethylphenyl unit on each side on the

half-macrocycle. To further increase the chance of success

for the ring-closure reaction, we removed the methoxy

group pointing inside the macrocycle cavity. Also, for the

larger macrocycle, a spacer that was a little longer (propyl

rather than ethyl) was used to link the half-macrocycle to

the templating unit. Starting from 5, a propanol chain was

attached by using the same conditions described for the

synthesis of 6 (Scheme 1) to give 14 in 77% yield. A Sono-

gashira coupling/alkyne deprotection sequence involving

TMSA, compound 16 (obtained from 1,4-diiodo-p-xyl-

ene^[26]), compound 19^[27]and TIPSA gave half-macrocycle

21 in 21% overall yield. The two alkynes were then depro-

tected with TBAF, and the resulting compound was treated

with 11 to give macrocycle precursor 22. Unexpectedly, 22

was very sparingly soluble in common organic solvents. An

attempt at a ring-closure reaction gave only insoluble mate-

rials, which likely contained small amounts of macrocycle

23. The poor solubility of 22 and 23 was likely owing to the

presence of six amide groups that can participate in inter-

molecular H-bonding interactions. Recently, we showed

that H-bonding could be used to direct the assembly of

PAM in different solvents.^[28]

Because the primary purpose of this study is to assess

whether or not a rotaxane can be formed by using a PAM

as macrocyclic unit and a rigid OPE as the rod, we replaced

the four amide groups on each corner of the PAM by

straight alkyl chains and the two other amide groups with

tert-butyl groups to improve the solubility of the final struc-

ture. As shown in Scheme 3, we started with the commer-

cially available 4-tert-butylphenol (24) that was iodinated by

using a known procedure.^[29]

After a propyl connector was installed on the phenol, suc-

cessive Sonogashira coupling/alkyne deprotection steps in-

Scheme 1. Synthesis of PAM 13.

Eur. J. Org. Chem. 0000, 0–0

volving TMSA, 16, 30^[24]and TIPSA gave half-macrocycle

www.eurjoc.org

3

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

K. Cantin, A. Lafleur-Lambert, P. Dufour, J.-F. Morin

FULL PAPER

Scheme 2. Synthesis of PAM 23.

32 in 16% overall yield. The compound was then coupled to

11 in excellent yield. Unlike 22, 33 is readily soluble in com-

mon organic solvents. Finally, an Eglinton ring closure reac-

tion was performed over 11 d to yield soluble PAM 34 in

very good yield (82%) after purification by flash chromatog-

raphy. This result supports our hypothesis regarding the ste-

ric hindrance and poor solubility issues for 13.

Scheme 3. Synthesis of PAM 34.

With PAM 34 in hand, we undertook the synthesis of a

blocker that is bulky enough to prevent the macrocycle meter of 34 at its narrowest point to be 20.9 Å. Therefore,

from threading off the rotaxane structure. By using mo- tris(biphenylyl)methane-based conical-shaped blocker

lecular modeling to aid design, we calculated the inner dia- with a larger diameter at its widest point should ensure the

a

4

www.eurjoc.org

Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

Phenylacetylene Macrocycle Based Rotaxane Precursors

macrocycle stays mechanically interlocked within the rotax-

On the basis of NMR analysis, it was impossible to de-

ane structure. The synthesis of target structure 40 is pre- termine whether or not 41 adopted a threaded structure in

sented in Scheme 4. Starting from commercially available which the OPE passes through the macrocycle. Thus, we

4Ј-bromo-1,1Ј-biphenyl-4-ol (35), the hydroxy group was moved on to the hydrolysis of the ester groups linking the

treated with iodooctane under standard nucleophilic substi- macrocycle and the OPE. If 41 is a threaded rotaxane pre-

tution conditions to give 36 in 90% yield. Next, 36 was cursor then the product of the hydrolysis reaction would be

treated with n-butyllithium at –78 °C followed by diethyl a [2]rotaxane. If not, the hydrolysis reaction would lead to

carbonate to provide tris(biphenylyl)methanol derivative 37 two distinct compounds – a macrocycle with two alcohol-

in 63% yield. Compound 37 was treated with acetyl chlor- terminating chains lying inside the cavity, and a free OPE

ide followed by ethynylmagnesium bromide to give 38 that with two carboxylic acid groups in its center. Unfortunately,

was further coupled to 39^[30]to give blocker 40 in 27% over- the hydrolysis reaction performed by using a mixture of so-

all yield. After deprotection of the alkyne, the blocker was dium hydroxide and lithium hydroxide in a mixture of

coupled to PAM 33 by Sonogashira coupling to give rotax- MeOH, H₂O and THF gave no trace of the desired rotax-

ane precursor 41 in 92% yield after purification by flash ane. Two explanations could account for this result. Com-

chromatography. Compound 41 is readily soluble in com- pound 41 might not present itself as a threaded compound

mon organic solvents including THF, chloroform, dichloro- but as a structure in which the OPE is parallel to the macro-

methane and toluene.

cycle (see Figure 2), or 41 is in fact a threaded rotaxane

precursor but the blockers were not bulky enough to pre-

vent the macrocycle unthreading (even though molecular

modeling suggests otherwise). Because the former hypothe-

sis is difficult to verify by using standard analytical tools,

we decided to test the latter by preparing a second rotaxane

precursor with the same macrocycle, but with larger block-

ers. According to molecular modeling, this new blocker has

a diameter of 33.9 Å at its largest point (Scheme 5) that is

expected to be large enough to avoid the macrocycle, which

has an internal cavity of 20.9 Å, to thread off the OPE rod.

The synthesis of the blockers is depicted in Scheme 5. Start-

ing from 3,5-diiodobromobenzene (42),^[24]a double chemo-

selective Sonogashira coupling was performed with TMSA

under standard Sonogashira coupling at room temperature

to provide 43 in 98% yield. Then, another Sonogashira cou-

pling reaction to install TIPSA was performed on the brom-

ine atom by using the more active Pd₂(dba)₃catalyst and

triphenylphosphane as the ligand at 60 °C to give 44. The

TMS-protected alkynes were deprotected selectively under

alkaline conditions (45) and then treated with an excess of

4,4Ј-diiodobiphenyl to give 46 in low yield (31%). Again,

the excess of 4,4Ј-diiodobiphenyl used for this reaction was

not enough to avoid the formation of polycondensation re-

actions leading to oligomeric materials. Compound 46 was

subsequently coupled to 47^[31]in 82% before the TIPS-pro-

tected alkyne was deprotected with TBAF and coupled to

39 by a Sonogashira coupling reaction to give TMS-pro-

tected blocker 49. Rotaxane precursor 50 was finally pre-

pared by deprotecting the alkyne by using TBAF and cou-

pling the resulting compound to PAM 34 in 52% overall

yield over two steps. The hydrolysis of the ester groups was

performed under the same conditions as previously de-

scribed. Unfortunately, PAM 51 was recovered in 90%

yield. The remaining 10% consisted of a mixture of

compounds that were inseparable by using standard

purification techniques. The presence of a very small

amount of the desired rotaxane cannot be completely ruled

out but the yield would be very low. This result suggests

that compound 50 was actually not threaded but that the

macrocycle attached to the OPE was lying parallel to it (see

Figure 2).

Scheme 4. Synthesis of 41.

Eur. J. Org. Chem. 0000, 0–0

www.eurjoc.org

5

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

K. Cantin, A. Lafleur-Lambert, P. Dufour, J.-F. Morin

FULL PAPER

ers that were prepared are large molecular architectures,

steric effects might play a very important role leading to the

kinetically most favorable products. In addition, the linker

used to attach both half-macrocycles might be too flexible

owing to the presence of sp³carbon atoms, allowing the

two iodo positions on the core to be on the same side of

the macrocycle. A more rigid linker with only sp²carbon

atoms might be better to ensure rotaxane precursor forma-

tion. However, our initial analysis suggests that the synthe-

sis of such a linker and its introduction to the half-macro-

cycles would be time-consuming without guarantee of suc-

cess. Finally, in order to ensure an efficient ring closure re-

action along with efficient rotaxane precursor formation,

relatively large PAMs have to be prepared, resulting in a

difficult and time-consuming synthetic process. Although

this strategy has never been tried before, we believe that

other more efficient and synthetically less demanding stra-

tegies need to be explored. As a plausible alternative, the

preparation of a rotaxane starting from a preformed rigid

rod and a non-covalently-bound macrocycle followed by the

capping of the rotaxane precursor could be envisioned (Fig-

ure 3).^[32]

Figure 3. Proposed strategy for the preparation of PAM-based

polyrotaxane.

Conclusions

Several attempts to obtain PAM-containing rotaxanes

through a rotaxane precursor strategy have been unsuccess-

ful, even though several structural parameters such as the

size of the macrocycles and blockers and the length of the

rigid rods were optimized. For the soluble structures tested,

the macrocycle prefers to stack parallel to the rigid rod

rather than encircle it. Nonetheless, the influence of the

structural parameters on the reactivity and solubility of the

molecular architectures reported in this study have been

highlighted and will guide us in developing a new strategy.

Experimental Section

Scheme 5. Synthesis of rotaxane precursor 50.

General Methods: Solvents used for organic synthesis (tetra-

hydrofuran, dichloromethane, dimethylformamide, toluene) were

dried and purified with a Solvent Purifier System (Vacuum Atmo-

sphere Co., Hawthorne, USA). Other solvents were used as re-

ceived. Tetrahydrofuran (THF), triethylamine (TEA) and diisopro-

pylethylamine (DIPEA) used for Sonogashira reactions were de-

gassed for 30 min prior to use. Pyridine used for Eglinton reactions

was degassed for 30 min prior to use. All anhydrous and air-sensi-

In light of these results, our strategy for the preparation

of PAM-based rotaxanes has some limitations. Our strategy

does not rely on supramolecular interactions to drive the

OPE rod to fit inside the PAM cavity as is the case, for

example, with ammonium crown ether rotaxanes under

thermodynamic control.^[20a]Because the PAMs and block- tive reactions were performed in oven-dried glassware under posi-

6

www.eurjoc.org

Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

Phenylacetylene Macrocycle Based Rotaxane Precursors

tive argon pressure. All silica used came from SiliCycle Inc. (Que-

bec, Canada): analytical thinlayer chromatography (TLC) was per-

formed with silica gel 60 F₂₅₄, 0.25 mm pre-coated TLC plates. Pre-

parative TLC was performed with 60 F₂₅₄, 2000 μm pre-coated

TLC plates. Compounds were visualized by using 254 nm and/or

365 nm UV wavelength and/or aqueous sulfuric acid solution of

ammonium heptamolybdate tetrahydrate (10 g in 100 mL of H₂SO₄

and 900 mL of H₂O). Flash column chromatography was per-

formed on 230–400 mesh silica gel R10030B. NMR spectroscopic

data were recorded at 400 MHz (¹H) and 100 MHz (¹³C). Signals

are reported as m (multiplet), s (singlet), d (doublet), dd (doublet

of doublet), t (triplet), q (quadruplet), br. m (broad multiplet) and

br. s (broad singlet). The chemical shifts are reported (δ) relative to

the residual solvent peak. HRMS data were recorded with an Ag-

ilent 6210 time-of-flight (TOF) LC-MS apparatus equipped with

an ESI or APPI ion source (Agilent Technologies, Toronto,

Canada). IR spectra were recorded by using a Nicolet Magna 850

Fourier transform infrared spectrometer (Thermo Scientific, Madi-

son, WI) with a liquid-nitrogen-cooled narrowband mercury cad-

mium telluride (MCT) detector and a Golden Gate ATR accessory

(Spacac Ltd., London, UK). Each spectrum was obtained from 64

scans (data resolution 4 cm^–1).

moved under reduced pressure. Then, CH₂Cl₂(70 mL) and 1,8-

diazabicyclo[5.4.0]undec-7-ene (3.7 mL, 24.6 mmol) were added to

the flask under argon. 4-(Dimethylamino)pyridine (0.501 g,

4.10 mmol), Et₃N (11.4 mL, 8.20 mmol) and dodecanoyl chloride

(5.1 mL, 21.5 mmol) were added, and the reaction mixture was

stirred at room temperature overnight before being neutralized with

H₂O. The aqueous layer was extracted three times with CH₂Cl₂.

The organic layers were combined, dried with MgSO₄, filtered, and

the solvent was removed under reduced pressure. The crude prod-

uct was purified by flash chromatography on silica gel (CH₂Cl₂) to

afford desired compound 4 (10.6 g, 91% yield) as a white solid. ¹H

NMR (CDCl₃, 400 MHz): δ = 7.65 (s, 2 H), 5.84 (m, 1 H), 4.32 (d,

J = 5.9 Hz, 2 H), 3.83 (s, 3 H), 2.23 (t, J = 7.6 Hz, 2 H), 1.66 (m,

2 H), 1.35–1.21 (br. m, 16 H), 0.88 (t, J = 6.7 Hz, 3 H) ppm. ¹³C

NMR (CDCl₃, 100 MHz): δ = 173.3, 157.9, 138.9, 138.5, 90.5, 60.7,

41.3, 36.7, 31.9, 29.6, 29.6, 29.6, 29.5, 29.4, 29.3, 25.7, 22.7,

14.1 ppm. HRMS (ESI-TOF): calcd. for C₂₀H₃₁I₂NO₂[M + H]⁺

572.0517; found 572.0524. FTIR (ATR): ν = 3276 (br. m), 2915

˜

(m), 1624 (s), 1547 (s), 1249 (m), 996 (s) cm^–1.

Compound 5: A 500 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound

4 (10.6 g,

18.6 mmol) and CH₂Cl₂(190 mL) under argon. Next, the mixture

was cooled to –78 °C. A solution of BBr₃in CH₂Cl₂(1.0 m, 74 mL,

74.4 mmol) was added dropwise to the reaction mixture. The reac-

Compound 2: A 3 L round-bottomed flask equipped with a mag-

netic stir bar was charged with MeOH (900 mL) and H₂O

(900 mL). Compound 1 (10.0 g, 44.8 mmol), NaClO₂(16.2 g, tion mixture was stirred at –78 °C to room temperature overnight,

179 mmol) and NaI (26.9 g, 179 mmol) were added. Next, concen- cooled to 0 °C, neutralized with MeOH and diluted with H₂O. The

trated HCl (20 mL) was added over 2 min. The reaction mixture

was stirred at room temperature for 10 min, neutralized with

NaHSO₃and diluted with ethyl acetate. The aqueous layer was

reaction mixture was warmed at room temperature and acidified

to pH = 5. The aqueous layer was extracted three times with

CH₂Cl₂. The organic layers were combined, dried with MgSO₄and

extracted four times with ethyl acetate. The organic layers were filtered. The solvent was removed under reduce pressure to afford

combined and washed with NaHSO₃. The organic layer was dried

with Na₂SO₄, the solvent was removed under reduced pressure and

the crude product was recrystallized first from EtOH/H₂O followed

by a second recrystallization from ethyl acetate/H₂O. The solid was

collected by filtration, washed with 2-propanol and dried under

vacuum to afford desired compound 2 (13.3 g, 62% yield) as a

desired compound 5 (10.4 g, quantitative yield) as a white solid. ¹H

NMR (CDCl₃, 400 MHz): δ = 7.59 (s, 2 H), 5.69 (br. s, 1 H), 4.30

(d, J = 5.9 Hz, 2 H), 2.21 (t, J = 7.6 Hz, 2 H), 1.65 (m, 2 H), 1.56

(br. s, 1 H), 1.35–1.21 (br. m, 16 H), 0.88 (t, J = 6.7 Hz, 3 H) ppm.

¹³C NMR (CDCl₃, 100 MHz): δ = 173.1, 153.0, 138.7, 134.7, 82.3,

41.4, 36.8, 32.0, 29.7, 29.6, 29.5, 29.4, 29.4, 29.3, 25.7, 22.7,

14.2 ppm. HRMS (ESI-TOF): calcd. for C₁₉H₂₉I₂NO₂[M⁺]

1

white solid. H NMR (CDCl₃, 400 MHz): δ = 7.59 (s, 2 H), 5.73

(br. s, 1 H), 4.82 (br. s, 1 H), 4.17 (d, J = 5.2 Hz, 2 H), 1.46 (s, 9

H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 155.9, 152.9, 138.4,

135.2, 82.4, 80.1, 42.7, 28.5 ppm. HRMS (ESI-TOF): calcd. for

557.0288; found 557.0287. FTIR (ATR): ν = 3447 (br. m), 3293

˜

(br. m), 2915 (s), 2849 (s), 1623 (s), 1546 (s), 1250 (m), 997 (s) cm^–1.

Compound 6: A 100 mL round-bottomed flask equipped with a

C₁₂H₁₅I₂NO₃[M⁺] 474.9141; found 474.9139. FTIR (ATR): ν =

˜

magnetic stir bar was charged with compound

5 (12.2 g,

3362 (w), 3053 (br. w), 1669 (s), 1534 (s), 1365 (m), 1156 (s) cm^–1.

21.9 mmol), acetone (30 mL), NaI (16.5 g, 110 mmol), 2-chloro-

ethanol (4.4 mL, 65.7 mmol) and K₂CO₃(9.08 g, 65.7 mmol). The

reaction mixture was stirred at reflux temperature overnight, cooled

to room temperature and then filtered. The solvent was removed

under reduced pressure, and the crude product was purified by

flash chromatography on silica gel (acetone/CH₂Cl₂, 1:49) to afford

Compound 3: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound

2 (2.00 g,

4.21 mmol), acetone (20 mL), iodomethane (0.52 mL, 8.42 mmol)

and K₂CO₃(1.74 g, 12.6 mmol). The reaction mixture was stirred

at reflux temperature overnight, cooled to room temperature, di-

luted with CH₂Cl₂and washed with H₂O. The aqueous layer was

extracted twice with CH₂Cl₂. The organic layers were combined,

dried with MgSO₄and filtered. The solvent was removed under

reduced pressure to afford desired compound 3 (2.04 g, quantitative

1

desired compound 6 (9.66 g, 73% yield) as a white solid. H NMR

(CDCl₃, 400 MHz): δ = 7.68 (s, 2 H), 5.80 (br. s, 1 H), 4.33 (d, J

= 5.5 Hz, 2 H), 4.14 (m, 2 H), 4.04 (m, 2 H), 2.32 (t, J = 5.9 Hz,

1 H), 2.31 (t, J = 7.2 Hz, 2 H), 1.66 (m, 2 H), 1.35–1.21 (br. m, 16

H), 0.88 (t, J = 5.8 Hz, 3 H) ppm. ¹³C NMR (CDCl₃, 100 MHz):

1

yield) as a white solid. H NMR (CDCl₃, 400 MHz): δ = 7.65 (s, 2

H), 5.08 (br. s, 1 H), 4.19 (d, J = 4.6 Hz, 2 H), 3.82 (s, 3 H), 1.46 δ = 173.2, 156.3, 139.1, 138.7, 90.9, 74.3, 65.2, 41.4, 36.7, 32.0,

(s, 9 H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 157.9, 155.8, 29.7, 29.6, 29.4, 29.4, 29.4, 25.7, 22.7, 14.2 ppm. FTIR (ATR): ν =

˜

138.9, 138.7, 90.6, 79.9, 60.7, 42.6, 28.4 ppm. FTIR (ATR): ν =

3287 (br. m), 2315 (s), 2849 (s), 1626 (s), 1535 (m), 1021 (w) cm^–1.

HRMS data for 6 could not be obtained in either ESI or APPI

mode.

˜

3309 (br. m), 1682 (s), 1530 (s), 1413 (m), 1290 (s), 1160 (s), 988

(s), 857 (m) cm^–1. HRMS data for 3 could not be obtained in either

ESI or APPI mode.

Compound 7: A 250 mL round-bottomed flask equipped with a

Compound 4: A 500 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 6 (9.60 g,

magnetic stir bar was charged with compound

20.5 mmol), CH₂Cl₂(200 mL) and trifluoroacetic acid (70 mL).

The reaction mixture was stirred for 2 h, and the solvent was re-

3

(10.0 g,

16.0 mmol), degassed THF (80 mL), degassed TEA (8.9 mL,

64.0 mmol), PdCl₂(PPh₃)₂(0.449 g, 0.640 mmol), CuI (0.244 g,

1.28 mmol) and (trimethylsilyl)acetylene (5.8 mL, 41.6 mmol) un-

Eur. J. Org. Chem. 0000, 0–0

www.eurjoc.org

7

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

K. Cantin, A. Lafleur-Lambert, P. Dufour, J.-F. Morin

FULL PAPER

der argon. The reaction mixture was stirred at room temperature

overnight, diluted with CH₂Cl₂, washed with NH₄Cl, and the aque-

ous layer was extracted twice with CH₂Cl₂. The organic layers were

combined, dried with MgSO₄and filtered. The solvent was re-

moved under reduced pressure, and the crude product was purified

by flash chromatography on silica gel (acetone/CH₂Cl₂, 1:99) to

2.26 (t, J = 7.6 Hz, 2 H), 1.67 (t, J = 6.8 Hz, 2 H), 1.47 (s, 18 H),

1.35–1.21 (br. m, 16 H), 1.14 (s, 42 H), 0.87 (t, J = 6.8 Hz, 3

H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 173.3, 161.2, 159.6,

156.0, 134.6, 134.3, 133.7, 133.1, 132.5, 117.6, 117.2, 102.1, 96.5,

90.3, 89.4, 79.7, 76.4, 61.8, 61.4, 43.5, 42.3, 36.7, 31.9, 29.6, 29.6,

29.5, 29.4, 29.3, 28.4, 25.7, 22.7, 18.7, 14.1, 11.3 ppm. HRMS (ESI-

TOF): calcd. for C₇₃H₁₀₉N₃O₉Si₂[M⁺] 1227.7702; found

1

afford desired compound 7 (10.6 g, 91% yield) as brown solid. H

NMR (CDCl₃, 400 MHz): δ = 7.29 (s, 2 H), 6.38 (t, J = 5.7 Hz, 1

1227.7693. FTIR (ATR): ν = 3333 (br. w), 2925 (m), 2864 (m),

˜

H), 4.35 (t, J = 4.2 Hz, 2 H), 4.28 (d, J = 5.8 Hz, 2 H), 3.80 (m, 2 1691 (m), 1465 (s), 1242 (s), 1164 (s), 881 (s) cm^–1.

H), 3.08 (t, J = 6.7 Hz, 1 H), 2.20 (t, J = 7.6 Hz, 2 H), 1.63 (m, 2

Compound 10: A 10 mL round-bottomed flask equipped with a

H), 1.35–1.21 (br. m, 16 H), 0.88 (t, J = 6.7 Hz, 3 H), 0.25 (s, 18

magnetic stir bar was charged with compound

9 (0.940 g,

H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 173.2, 160.3, 134.1,

133.2, 117.4, 100.4, 100.2, 75.8, 61.4, 42.1, 36.5, 31.8, 29.5, 29.5,

29.4, 29.3, 29.3, 29.2, 25.6, 22.6, 14.6, –0.3 ppm. HRMS (ESI-

TOF): calcd. for C₃₁H₅₁NO₃Si₂[M + H]⁺542.3480; found

0.765 mmol), THF (4 mL) and tetrabutylammonium fluoride

(1.0 m in THF, 1.9 mL, 1.91 mmol). The reaction mixture was

stirred at room temperature for 30 min, diluted with CH₂Cl₂,

washed with water, and the aqueous layer was extracted twice with

CH₂Cl₂. The organic layers were combined, dried with MgSO₄and

filtered. The solvent was removed under reduced pressure, and the

crude product was purified by flash chromatography on silica gel

(acetone/CH₂Cl₂, 1:19) to afford desired compound 10 (0.730 g,

quantitative yield) as a pale yellow oil. ¹H NMR (CDCl₃,

400 MHz): δ = 7.38 (s, 2 H), 7.35 (s, 4 H), 6.62 (br. s, 1 H), 5.41

(br. s, 2 H), 4.47 (t, J = 3.9 Hz, 2 H), 4.38 (d, J = 5.6 Hz, 2 H),

4.23 (d, J = 4.8 Hz, 4 H), 4.05 (s, 6 H), 3.90 (br. s, 2 H), 3.40 (br.

s, 1 H), 3.30 (s, 2 H), 2.27 (t, J = 7.6 Hz, 2 H), 1.67 (m, 2 H), 1.47

(s, 18 H), 1.35–1.21 (br. m, 16 H), 0.86 (t, J = 6.7 Hz, 3 H) ppm.

¹³C NMR (CDCl₃, 100 MHz): δ = 173.4, 161.3, 159.6, 156.0, 134.8,

134.4, 133.6, 133.2, 117.4, 117.1, 116.2, 102.1, 90.0, 89.6, 82.2, 79.7,

79.1, 76.3, 61.8, 61.6, 61.6, 43.4, 42.3, 36.7, 31.9, 29.6, 29.6, 29.5,

29.4, 29.3, 28.4, 25.7, 22.7, 14.1 ppm. HRMS (ESI-TOF): calcd.

542.3485. FTIR (ATR): ν = 3281 (br. m), 2922 (m), 2160 (m), 1651

˜

(m), 1247 (m), 837 (s) cm^–1.

Compound 8: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound

7 (4.50 g,

8.30 mmol), THF (20 mL), MeOH (20 mL) and KOH (2.5 m,

10 mL). The reaction mixture was stirred for 1 h, acidified to pH

= 7 and diluted with CH₂Cl₂. The aqueous layer was extracted

three times with CH₂Cl₂. The organic layers were combined, dried

with MgSO₄and filtered. The solvent was then removed under re-

duced pressure. A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with the crude product (3.38 g,

8.30 mmol), degassed THF (30 mL), degassed DIPEA (11.6 mL,

66.4 mmol), PdCl₂(PPh₃)₂(0.117 g, 0.166 mmol), CuI (0.126 g,

0.664 mmol) and compound 2 (12.2 g, 24.9 mmol) under argon.

The reaction mixture was stirred at room temperature overnight,

diluted with CH₂Cl₂, washed with NH₄Cl, and the aqueous layer

was extracted twice with CH₂Cl₂. The organic layers were com-

bined, dried with MgSO₄and filtered. The solvent was removed

under reduced pressure, and the crude product was purified by

flash chromatography on silica gel (CH₂Cl₂then acetone/CH₂Cl₂,

1:9) to afford desired compound 8 (2.87 g, 31% yield) as brown oil.

¹H NMR (CDCl₃, 400 MHz): δ = 7.66 (d, J = 1.4 Hz, 2 H), 7.36

(d, J = 8.3 Hz, 4 H), 6.91 (br. s, 1 H), 5.61 (br. s, 2 H), 4.43 (t, J

= 4.2 Hz, 2 H), 4.39 (d, J = 5.8 Hz, 2 H), 4.22 (d, J = 5.3 Hz, 4

H), 3.94 (s, 6 H), 3.90 (t, J = 4.1 Hz, 2 H), 2.29 (t, J = 7.6 Hz, 2

H), 1.68 (m, 2 H), 1.46 (s, 18 H), 1.35–1.21 (br. m, 17 H), 0.86 (t,

J = 6.8 Hz, 3 H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 173.5,

159.5, 159.2, 156.0, 138.8, 136.9, 134.6, 133.4, 133.0, 117.2, 117.0,

91.8, 90.0, 89.7, 79.8, 76.3, 61.7, 61.3, 43.0, 42.2, 36.6, 31.9, 29.6,

29.6, 29.5, 29.4, 29.3, 28.4, 25.7, 22.7, 19.0, 14.1 ppm. HRMS (ESI-

TOF): calcd. for C₅₁H₆₇I₂N₃O₉[M⁺]: 1119.2967; found 1119.2921.

for C H N O [M⁺] 915.5034; found 915.5029. FTIR (ATR): ν =

˜

55 69

3

9

3299 (br. m), 2925 (m), 1961 (s), 1523 (s), 1242 (s), 1164 (s), 876

(w) cm^–1.

Compound 12: A 10 mL round-bottomed flask equipped with a

magnetic stir bar was charged with the compound 11 (0.149 g,

0.327 mmol), CH₂Cl₂(2.5 mL), 4-(dimethylamino)pyridine

(0.008 g, 0.065 mmol), TEA (0.80 mL, 5.76 mmol) and compound

10 (0.660 g, 0.720 mmol) under argon. The reaction mixture was

stirred at room temperature overnight, diluted with CH₂Cl₂and

washed with water. The aqueous layer was extracted twice with

CH₂Cl₂. The organic layers were combined, dried with MgSO₄and

filtered. The solvent was removed under reduced pressure, and the

crude product was purified by flash chromatography on silica gel

(CH₂Cl₂, then acetone/CH₂Cl₂, 2:23). The crude product was then

passed through a preparative GPC in CHCl₃(column: Jordi gel

DVB 250ϫ22.0 mm, 2 μm, 500 Å with a guard column: Jordi gel

DVB, 50 ϫ22 mm, 5 μm at 5.0 mL/min) to afford desired com-

FTIR (ATR): ν = 3307 (br. w), 2925 (m), 1690 (s), 1645 (s), 1246

˜

1

(s), 1162 (s), 871 (m) cm^–1.

pound 12 (0.563 g, 78% yield) as a white solid. H NMR (CDCl₃,

400 MHz): δ = 8.02 (s, 2 H), 7.40 (s, 4 H), 7.34 (s, 4 H), 7.31 (s, 4

H), 6.15 (br. s, 2 H), 5.16 (br. s, 4 H), 4.77 (m, 4 H), 4.73 (m, 4 H),

4.38 (d, J = 5.7 Hz, 4 H), 4.20 (d, J = 5.0 Hz, 8 H), 4.04 (s, 12 H),

3.29 (s, 4 H), 2.24 (t, J = 7.6 Hz, 4 H), 1.65 (m, 4 H), 1.45 (s, 36

H), 1.35–1.21 (br. m, 32 H), 0.86 (t, J = 6.8 Hz, 6 H) ppm. ¹³C

NMR (CDCl₃, 100 MHz): δ = 173.3, 164.1, 161.5, 159.7, 155.9,

142.7, 137.4, 134.5, 134.3, 133.5, 133.1, 133.0, 117.5, 117.0, 116.3,

93.1, 90.2, 89.5, 82.2, 79.7, 79.2, 61.6, 61.5, 43.5, 42.3, 36.7, 31.9,

29.6, 29.6, 29.5, 29.4, 29.3, 28.4, 25.7, 22.7, 14.1 ppm. HRMS (ESI-

TOF): calcd. for C₁₁₈H₁₃₈I₂N₆O₂₀[M⁺] 2212.8055; found

Compound 9: A 25 mL round-bottomed flask equipped with a mag-

netic stir bar was charged with compound 8 (2.03 g, 1.81 mmol),

degassed THF (6 mL), degassed DIPEA (2.5 mL, 14.5 mmol),

PdCl₂(PPh₃)₂(0.025 g, 0.063 mmol), CuI (0.028 g, 0.15 mmol) and

(triisopropylsilyl)acetylene (2.0 mL, 9.05 mmol) under argon. The

reaction mixture was stirred at room temperature overnight, diluted

with CH₂Cl₂, washed with NH₄Cl, and the aqueous layer was ex-

tracted twice with CH₂Cl₂. The organic layers were combined,

dried with MgSO₄and filtered. The solvent was removed under

reduced pressure, and the crude product was purified by flash

chromatography on silica gel (acetone/CH₂Cl₂, 1:19) to afford de-

sired compound 9 (1.95 g, 88% yield) as a white solid. ¹H NMR

(CDCl₃, 400 MHz): δ = 7.35 (m, 6 H), 6.35 (br. s, 1 H), 5.24 (br. s,

2 H), 4.49 (t, J = 4.1 Hz, 2 H), 4.39 (d, J = 5.7 Hz, 2 H), 4.23 (d,

J = 4.8 Hz, 4 H), 4.05 (s, 6 H), 3.90 (br. s, 2 H), 3.36 (br. s, 1 H),

2212.8083. FTIR (ATR): ν = 3295 (br. w), 2925 (m), 1695 (s), 1391

˜

(m), 1238 (s), 1164 (s), 1042 (m), 876 (m) cm^–1.

Compound 13: A 250 mL round-bottomed flask equipped with a

magnetic stir bar was charged with CuCl (2.51 g, 25.4 mmol),

CuCl₂(0.569 g, 4.23 mmol) and degassed pyridine (85 mL). To this

8

www.eurjoc.org

Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

Phenylacetylene Macrocycle Based Rotaxane Precursors

suspension was added a solution of compound 12 (0.375 mg,

0.169 mmol) in degassed pyridine (25 mL) at room temperature un-

der argon over 96 h. After completion of the addition, the mixture

was stirred for an additional 7 d and then poured into a mixture

(10 mL). The reaction mixture was stirred for 1 h, acidified to pH

= 7 and diluted with CH₂Cl₂. The aqueous layer was extracted

three times with CH₂Cl₂. The organic layers were combined, dried

with MgSO₄and filtered. The solvent was then removed under re-

of CH₂Cl₂and water. The organic layer was extracted successively duced pressure. A 100 mL round-bottomed flask equipped with a

with water, NH₄OH (25%), water, acetic acid (10%), water, aque- magnetic stir bar was charged with the crude product (3.69 g,

ous sodium hydroxide (10%) and brine. The organic layers were

dried with MgSO₄, the solvent was removed under reduced pres-

sure, and the crude product was purified by flash chromatography

on silica gel (acetone/CH₂Cl₂, 1:9) to afford compound 13 (19 mg,

5% yield) as a beige solid. H NMR (CDCl₃, 400 MHz): δ = 8.63

(s, 2 H), 7.45–7.17 (br. m, 12 H), 5.61 (br. s, 2 H), 5.34 (br. s, 4 H),

8.96 mmol), degassed THF (40 mL), degassed DIPEA (10.8 mL,

61.8 mmol), PdCl₂(PPh₃)₂(0.217 g, 0.309 mmol), CuI (0.118 g,

0.618 mmol) and compound 16 (6.34 g, 19.3 mmol) under argon.

The reaction mixture was stirred at room temperature for 48 h,

diluted with CH₂Cl₂, washed with NH₄Cl, and the aqueous layer

was extracted twice with CH₂Cl₂. The organic layers were com-

1

4.59 (br. s, 4 H), 4.31 (br. s, 4 H), 4.16–3.90 (br. m, 24 H), 2.36 (m, bined, dried with MgSO₄and filtered. The solvent was removed

4 H), 1.75 (m, 4 H), 1.53 (s, 36 H), 1.42–1.14 (br. m, 32 H), 0.86

under reduced pressure, and the crude product was purified by

flash chromatography on silica gel (acetone/CH₂Cl₂, 1:49) to afford

desired compound 17 (5.00 g, 80% yield) as a brown solid. ¹H

NMR (CDCl₃, 400 MHz): δ = 7.30 (s, 2 H), 7.29 (s, 2 H), 7.27 (s,

2 H), 6.44 (t, J = 5.6 Hz, 1 H), 4.39 (t, J = 5.8 Hz, 2 H), 4.31 (d,

J = 5.6 Hz, 2 H), 3.89 (t, J = 5.4 Hz, 2 H), 2.52 (br. s, 1 H), 2.40

(s, 6 H), 2.37 (s, 6 H), 2.20 (t, J = 7.5 Hz, 2 H), 2.05 (m, 2 H), 1.63

(m, 2 H), 1.35–1.21 (br. m, 16 H), 0.87 (t, J = 6.9 Hz, 3 H), 0.27

(s, 18 H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 173.4, 159.0,

137.7, 137.0, 134.2, 132.9, 132.6, 132.4, 123.2, 122.6, 117.8, 103.7,

99.8, 92.9, 90.0, 72.6, 60.7, 42.2, 36.6, 32.8, 31.9, 29.6, 29.6, 29.5,

29.4, 29.3, 29.3, 25.8, 22.7, 20.0, 19.9, 14.1, 0.0 ppm. HRMS

(APPI-TOF): calcd. for C₅₂H₆₉NO₃Si₂[M + H]⁺812.4889; found

(t, J = 6.8 Hz, 6 H) ppm. FTIR (ATR): ν = 3328 (br. w), 2924 (m),

˜

1691 (m), 1520 (m), 1241 (s), 1164 (s), 1039 (m), 998 (w) cm^–1. ¹³C

NMR spectroscopic data for 13 could not be obtained owing to its

low solubility. HRMS data for 13 could not be obtained in either

ESI or APPI mode.

Compound 14: A 50 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound

5 (8.60 g,

15.4 mmol), acetone (20 mL), NaI (11.5 g, 77 mmol), 3-chloroprop-

anol (3.9 mL, 46.2 mmol) and K₂CO₃(6.38 g, 46.2 mmol). The

reaction mixture was stirred at reflux temperature overnight, cooled

to room temperature and then filtered. The solvent was removed

under reduced pressure, and the crude product was purified by

flash chromatography on silica gel (CH₂Cl₂) to afford desired com-

812.4887. FTIR (ATR): ν = 3289 (br. w), 2924 (m), 2148 (m), 1652

˜

(s), 1450 (s), 1248 (s), 840 (s), 760 (s) cm^–1.

1

pound 14 (7.31 g, 77% yield) as a white solid. H NMR (CDCl₃,

Compound 18: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 17 (4.89 g,

7.30 mmol), THF (40 mL) and tetrabutylammonium fluoride in

THF (1.0 m, 18.3 mL, 18.3 mmol). The reaction mixture was stirred

at room temperature for 30 min, diluted with CH₂Cl₂, washed with

water, and the aqueous layer was extracted twice with CH₂Cl₂. The

organic layers were combined, dried with MgSO₄and filtered. The

solvent was removed under reduced pressure, and the crude prod-

uct was purified by flash chromatography on silica gel (acetone/

CH₂Cl₂, 1:19) to afford desired compound 18 (3.64 g, 74%) as a

purplish solid. ¹H NMR (CDCl₃, 400 MHz): δ = 7.38 (s, 2 H), 7.37

(s, 2 H), 7.34 (s, 2 H), 5.86 (t, J = 5.0 Hz, 1 H), 4.44 (t, J = 5.7 Hz,

2 H), 4.39 (d, J = 5.7 Hz, 2 H), 3.93 (q, J = 5.5 Hz, 2 H), 3.35 (s,

2 H), 2.45 (s, 6 H), 2.41 (s, 6 H), 2.23 (t, J = 7.6 Hz, 2 H), 2.15 (t,

J = 5.6 Hz, 1 H), 2.08 (m, 2 H), 1.65 (m, 2 H), 1.35–1.21 (br. m,

16 H), 0.87 (t, J = 6.7 Hz, 3 H) ppm. ¹³C NMR (CDCl₃, 100 MHz):

δ = 173.2, 159.3, 138.0, 137.3, 134.3, 133.4, 133.0, 132.7, 123.0,

122.3, 118.1, 92.9, 90.0, 82.3, 72.8, 61.0, 42.4, 36.8, 32.8, 31.9, 29.7,

29.6, 29.5, 29.4, 29.3, 25.8, 22.7, 20.1, 20.0, 14.2 ppm. HRMS

(APPI-TOF): calcd. for C₄₆H₅₃NO₃[M + H]⁺667.4025; found

400 MHz): δ = 7.67 (s, 2 H), 5.76 (br. s, 1 H), 4.33 (d, J = 5.9 Hz,

2 H), 4.11 (t, J = 5.6 Hz, 2 H), 3.99 (q, J = 5.6 Hz, 2 H), 2.33 (t,

J = 7.5 Hz, 2 H), 2.14 (m, 2 H), 2.00 (t, J = 5.8 Hz, 1 H), 1.66 (m,

2 H), 1.35–1.21 (br. m, 16 H), 0.88 (t, J = 6.4 Hz, 3 H) ppm. ¹³C

NMR ([D₆]DMSO, 100 MHz): δ = 172.3, 156.3, 139.9, 138.3, 91.6,

70.8, 58.0, 35.3, 33.2, 31.3, 29.1, 29.0, 29.0, 28.8, 28.8, 28.8, 28.6,

25.3, 22.1, 14.0 ppm. FTIR (ATR): ν = 3287 (br. m), 2915 (s), 2849

˜

(s), 1645 (s), 1552 (s), 1042 (s), 924 (m) cm^–1. HRMS data for 14

could not be obtained in either ESI or APPI mode.

Compound 15: A 250 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 14 (7.20 g,

11.7 mmol), degassed THF (60 mL), degassed TEA (6.5 mL,

46.8 mmol), PdCl₂(PPh₃)₂(0.328 g, 0.468 mmol), CuI (0.178 g,

0.936 mmol) and (trimethylsilyl)acetylene (4.2 mL, 30.4 mmol) un-

der argon. The reaction mixture was stirred at room temperature

overnight, diluted with CH₂Cl₂, washed with NH₄Cl, and the aque-

ous layer was extracted twice with CH₂Cl₂. The organic layers were

combined, dried with MgSO₄and filtered. The solvent was re-

moved under reduced pressure, and the crude product was purified

by flash chromatography on silica gel (acetone/CH₂Cl₂, 1:99) to

afford desired compound 15 (6.51 g, quantitative yield) as a red oil.

¹H NMR (CDCl₃, 400 MHz): δ = 7.30 (s, 2 H), 5.82 (br. s, 1 H),

4.33 (m, 4 H), 3.96 (q, J = 5.7 Hz, 2 H), 2.35 (t, J = 5.5 Hz, 1 H),

2.21 (t, J = 7.6 Hz, 2 H), 2.03 (m, 2 H), 1.64 (m, 2 H), 1.35–1.21

(br. m, 16 H), 0.88 (t, J = 6.8 Hz, 3 H), 0.26 (s, 18 H) ppm. ¹³C

NMR (CDCl₃, 100 MHz): δ = 173.2, 160.7, 134.0, 133.6, 117.8,

100.3, 99.9, 72.4, 61.1, 42.5, 36.8, 32.7, 32.0, 29.7, 29.7, 29.6, 29.5,

29.5, 29.4, 25.8, 22.8, 14.2, –0.1 ppm. HRMS (APPI-TOF): calcd.

for C₃₂H₅₃NO₃Si₂[M + H]⁺556.3637; found 5556.3638. FTIR

667.4043. FTIR (ATR): ν = 3279 (br. m), 2919 (m), 1621 (s), 1532

˜

(s), 1441 (s), 1146 (m), 886 (s) cm^–1.

Compound 20: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 18 (3.64 g,

5.44 mmol), degassed THF (30 mL), degassed DIPEA (7.6 mL,

43.5 mmol), PdCl₂(PPh₃)₂(0.077 g, 0.11 mmol), CuI (0.083 g,

0.44 mmol) and compound 19 (7.25 g, 16.3 mmol) under argon.

The reaction mixture was stirred at room temperature overnight,

diluted with CH₂Cl₂, washed with NH₄Cl, and the aqueous layer

was extracted twice with CH₂Cl₂. The organic layers were com-

bined, dried with MgSO₄and filtered. The solvent was removed

under reduced pressure, and the crude product was purified by

flash chromatography on silica gel (acetone/CH₂Cl₂, 1:49) to afford

desired compound 20 (2.61 g, 37% yield) as a white solid. ¹H NMR

(ATR): ν = 3281 (br. w), 2923 (m), 2853 (m), 2158 (w), 1646 (m),

˜

1248 (s), 842 (s) cm^–1.

Compound 17: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 15 (4.98 g,

8.96 mmol), THF (20 mL), MeOH (20 mL) and KOH 2.5 m (CDCl₃, 400 MHz): δ = 7.79 (s, 2 H), 7.52 (s, 2 H), 7.47 (s, 2 H),

Eur. J. Org. Chem. 0000, 0–0

www.eurjoc.org

9

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

K. Cantin, A. Lafleur-Lambert, P. Dufour, J.-F. Morin

FULL PAPER

7.36 (s, 2 H), 7.36 (s, 2 H), 7.31 (s, 2 H), 6.70 (s, 2 H), 6.02 (t, J =

5.7 Hz, 1 H), 4.45 (t, J = 5.7 Hz, 2 H), 4.39 (d, J = 5.5 Hz, 2 H),

3.96 (m, 2 H), 2.46 (s, 6 H), 2.43 (s, 6 H), 2.33 (br. s, 1 H), 2.25 (t,

6 H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 173.3, 164.1, 159.4,

152.5, 142.7, 138.7, 138.0, 137.5, 137.2, 134.1, 132.8, 132.8, 132.6,

132.6, 129.6, 129.6, 124.3, 123.0, 122.9, 122.8, 121.5, 121.1, 118.1,

J = 7.5 Hz, 2 H), 2.10 (m, 2 H), 1.68 (m, 2 H), 1.52 (s, 18 H), 1.35– 93.6, 93.2, 92.8, 90.1, 88.9, 82.6, 81.1, 77.9, 70.8, 63.4, 42.5, 36.8,

1.21 (br. m, 16 H), 0.87 (t, J = 6.8 Hz, 3 H) ppm. ¹³C NMR 31.9, 29.7, 29.7, 29.6, 29.6, 29.4, 28.3, 25.8, 22.7, 20.2, 20.2,

(CDCl₃, 100 MHz): δ = 173.3, 159.2, 152.3, 139.5, 137.5, 137.3, 14.2 ppm. FTIR (ATR): ν = 3296 (br. w), 2923 (m), 1720 (m), 1597

˜

134.5, 134.2, 132.9, 132.8, 132.7, 127.0, 125.6, 122.9, 122.8, 120.3,

(m), 1432 (m), 1229 (s), 1155 (s), 867 (m) cm^–1. HRMS data for 22

118.0, 93.7, 93.1, 92.8, 90.2, 89.4, 81.2, 72.8, 61.0, 42.4, 36.8, 32.8, could not be obtained in either ESI or APPI mode.

31.9, 29.7, 29.6, 29.5, 29.4, 29.4, 29.4, 28.3, 25.8, 22.7, 20.1, 20.1,

Compound 25: A 1 L round-bottomed flask equipped with a mag-

14.2 ppm. HRMS (APPI-TOF): calcd. for C₆₈H₇₇I₂N₃O₇

netic stir bar was charged with MeOH (330 mL) and concentrated

[M + H]⁺1302.3924; found 1302.3926. FTIR (ATR): ν = 3280 (br.

˜

H₂SO₄(7.1 mL, 133 mmol). Then, 4-tert-butylphenol (10.0 g,

w), 2924 (m), 1702 (m), 1566 (s), 1259 (s), 1153 (s), 1033 (s), 851

66.6 mmol) and KI (22.1 g, 133 mmol) were added to the reaction

(m) cm^–1.

mixture. Finally, H₂O₂(30%, 27.2 mL, 266 mmol) was added. The

Compound 21: A 25 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 20 (0.500 g,

0.384 mmol), degassed THF (5 mL), degassed DIPEA (0.54 mL,

3.07 mmol), PdCl₂(PPh₃)₂(0.005 g, 0.0077 mmol), CuI (0.006 g,

0.031 mmol) and (triisopropylsilyl)acetylene (0.43 mL, 1.92 mmol)

under argon. The reaction mixture was stirred at room temperature

overnight, diluted with CH₂Cl₂, washed with NH₄Cl, and the aque-

ous layer was extracted twice with CH₂Cl₂. The organic layers were

combined, dried with MgSO₄and filtered. The solvent was re-

moved under reduced pressure, and the crude product was purified

by flash chromatography on silica gel (acetone/CH₂Cl₂, 1:19) to

afford desired compound 21 (0.519 g, 96% yield) as a brown solid.

¹H NMR (CDCl₃, 400 MHz): δ = 7.56 (s, 2 H), 7.46 (s, 2 H), 7.36

(s, 2 H), 7.35 (s, 2 H), 7.32 (s, 2 H), 7.30 (s, 2 H), 6.85 (s, 2 H),

6.19 (t, J = 5.5 Hz, 1 H), 4.44 (t, J = 5.5 Hz, 2 H), 4.39 (d, J =

5.2 Hz, 2 H), 3.96 (m, 2 H), 2.46 (s, 6 H), 2.44 (s, 6 H), 2.25 (t, J

= 7.5 Hz, 2 H), 2.10 (m, 2 H), 1.67 (m, 2 H), 1.52 (s, 18 H), 1.35–

1.21 (br. m, 17 H), 1.13 (s, 42 H), 0.87 (t, J = 6.8 Hz, 3 H) ppm.

¹³C NMR (CDCl₃, 100 MHz): δ = 173.4, 159.2, 152.6, 138.6, 137.4,

137.2, 134.2, 134.2, 132.8, 132.8, 132.6, 132.6, 129.6, 129.5, 124.4,

124.1, 123.0, 122.7, 121.5, 121.1, 118.0, 105.9, 93.8, 93.1, 91.4, 90.1,

89.6, 80.9, 72.7, 60.9, 42.4, 36.7, 32.8, 31.9, 29.6, 29.6, 29.5, 29.4,

29.3, 28.3, 28.3, 25.8, 22.7, 20.1, 20.1, 18.7, 14.1 ppm. HRMS

(APPI-TOF): calcd. for C₉₀H₁₁₉N₃O₇Si₂[M⁺] 1409.8587; found

reaction mixture was stirred at 40 °C for 2 h, cooled to room tem-

perature, diluted with CH₂Cl₂. The organic layer was washed with

NaHSO₃(0.1 m), washed with H₂O, dried with MgSO₄and filtered.

The solvent was removed under reduced pressure, and the crude

product was purified by flash chromatography on silica gel (EtOAc/

hexanes, 1:49) to afford desired compound 25 (18.6 g, 69% yield)

as a white solid. ¹H NMR (CDCl₃, 400 MHz): δ = 7.64 (s, 2 H),

5.58 (s, 1 H), 1.26 (s, 9 H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ

= 151.2, 147.5, 136.4, 82.2, 34.0, 31.3 ppm. HRMS (APPI-TOF):

calcd. for C₁₀H₁₂I₂O [M⁺] 401.8978; found 401.8984. FTIR (ATR):

ν = 3472 (br. m), 2962 (s), 1545 (w), 1460 (s), 1274 (m), 1154

˜

(m) cm^–1.

Compound 26: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 25 (9.00 g,

22.4 mmol), acetone (30 mL), NaI (13.4 g, 89.6 mmol), 3-chloro-

propanol (3.7 mL, 44.8 mmol) and K₂CO₃(9.29 g, 67.2 mmol).

The reaction mixture was stirred at reflux overnight, cooled to

room temperature and then filtered. The solvent was removed un-

der reduced pressure, and the crude product was purified by flash

chromatography on silica gel (EtOAc/hexanes, 1:9) to afford desired

compound 26 (7.01 g, 68% yield) as a white solid. ¹H NMR

(CDCl₃, 400 MHz): δ = 7.72 (s, 2 H), 4.09 (t, J = 5.8 Hz, 2 H),

3.98 (t, J = 6.0 Hz, 2 H), 2.88 (br. s, 1 H), 2.14 (m, 2 H), 1.26 (s,

9 H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 155.1, 151.4, 137.2,

90.7, 71.3, 60.7, 34.3, 32.6, 31.3 ppm. HRMS (APPI-TOF): calcd.

for C₁₃H₁₈I₂O₂[M + H]⁺460.9469; found 460.9466. FTIR (ATR):

1409.8566. FTIR (ATR): ν = 3296 (br. w), 2923 (m), 1420 (m),

˜

1264 (s), 1229 (s), 1155 (s), 867 (m) cm^–1.

Compound 22: A 10 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 21 (0.408 g,

0.289 mmol), THF (1.5 mL) and tetrabutylammonium fluoride in

THF (1.0 m, 0.72 mL, 0.723 mmol). The reaction mixture was

stirred at room temperature for 30 min, diluted with CH₂Cl₂,

washed with water, and the aqueous layer was extracted twice with

CH₂Cl₂. The organic layers were combined, dried with MgSO₄and

filtered. The solvent was removed under reduced pressure. A 10 mL

round-bottomed flask equipped with a magnetic stir bar was

charged with the crude product (0.317 g, 0.289 mmol), compound

11 (0.053 g, 0.12 mmol), CH₂Cl₂(0.4 mL), 4-(dimethylamino)pyr-

idine (0.003 g, 0.023 mmol), TEA (0.13 mL, 0.936 mmol) under ar-

gon. The reaction mixture was stirred at room temperature over-

night, diluted with CH₂Cl₂and washed with water. The aqueous

layer was extracted twice with CH₂Cl₂. The organic layers were

combined, dried with MgSO₄and filtered. The solvent was re-

moved under reduced pressure, and the crude product was purified

by flash chromatography on silica gel (EtOAc/toluene, 7:43) to af-

ford desired compound 22 (0.127 g, 42% yield) as a brown solid.

¹H NMR (CDCl₃, 400 MHz): δ = 8.09 (s, 2 H), 7.54 (s, 4 H), 7.46

(s, 4 H), 7.36 (s, 4 H), 7.30 (s, 4 H), 7.27 (s, 4 H), 7.18 (s, 4 H),

6.71 (s, 4 H), 6.01 (br. s, 2 H), 4.60 (m, 4 H), 4.45 (m, 4 H), 4.40

(m, 4 H), 3.05 (s, 4 H), 2.44 (s, 12 H), 2.39 (s, 12 H), 2.28 (m, 8

ν = 3344 (br. m), 2960 (s), 1531 (w), 1443 (s), 1265 (s), 1047

˜

(m) cm^–1.

Compound 27: A 250 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 26 (7.00 g,

15.2 mmol), degassed THF (75 mL), degassed TEA (8.5 mL,

60.8 mmol), PdCl₂(PPh₃)₂(0.427 g, 0.608 mmol), CuI (0.232 g,

1.22 mmol) and (trimethylsilyl)acetylene (5.5 mL, 39.5 mmol) un-

der argon. The reaction mixture was stirred at room temperature

overnight, diluted with CH₂Cl₂, washed with NH₄Cl, and the aque-

ous layer was extracted twice with CH₂Cl₂. The organic layers were

combined, dried with MgSO₄and filtered. The solvent was re-

moved under reduced pressure, and the crude product was purified

by flash chromatography on silica gel (EtOAc/hexanes, 1:9) to af-

ford desired compound 27 (5.49 g, 90% yield) as a brown solid. ¹H

NMR (CDCl₃, 400 MHz): δ = 7.40 (s, 2 H), 4.33 (t, J = 5.6 Hz, 2

H), 3.97 (q, J = 5.2 Hz, 2 H), 2.46 (t, J = 5.5 Hz, 1 H), 2.03 (m, 2

H), 1.28 (s, 9 H), 0.27 (s, 18 H) ppm. ¹³C NMR (CDCl₃, 100 MHz):

δ = 159.2, 146.4, 131.4, 116.7, 101.1, 98.6, 72.2, 61.1, 34.3, 32.6,

31.1, –0.1 ppm. FTIR (ATR): ν = 3464 (br. w), 2956 (m), 2152 (m),

˜

1246 (m), 1000 (m), 835 (s) cm^–1. HRMS data for 27 could not be

obtained in either ESI or APPI mode.

Compound 28: A 250 mL round-bottomed flask equipped with a

H), 1.68 (m, 4 H), 1.52 (s, 36 H), 1.35–1.21 (br. m, 32 H), 0.87 (m, magnetic stir bar was charged with compound 27 (5.40 g,

10

www.eurjoc.org

Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

Phenylacetylene Macrocycle Based Rotaxane Precursors

13.5 mmol), THF (35 mL), MeOH (35 mL) and KOH (2.5 m, 130.8, 125.0, 123.0, 122.8, 117.1, 93.8, 93.2, 92.2, 90.9, 89.1, 72.7,

14 mL). The reaction mixture was stirred for 1 h, acidified to pH

= 7 and diluted with CH₂Cl₂. The aqueous layer was extracted

twice with CH₂Cl₂. The organic layers were combined, dried with

MgSO₄and filtered. The solvent was then removed under reduced

pressure. A 100 mL round-bottomed flask equipped with a mag-

netic stir bar was charged with the crude product (3.46 g,

13.5 mmol), degassed THF (70 mL), degassed TEA (14.9 mL,

107 mmol), PdCl₂(PPh₃)₂(0.376 g, 0.536 mmol), CuI (0.204 g,

0.536 mmol) and compound 16 (10.4 g, 31.7 mmol) under argon.

The reaction mixture was stirred at room temperature for 48 h,

diluted with CH₂Cl₂, washed with NH₄Cl, and the aqueous layer

was extracted twice with CH₂Cl₂. The organic layers were com-

bined, dried with MgSO₄and filtered. The solvent was removed

under reduced pressure, and the crude product was purified by

flash chromatography on silica gel (CH₂Cl₂/hexanes, 1:3) to afford

desired compound 28 (5.93 g, 67% yield) as a white solid. ¹H NMR

(CDCl₃, 400 MHz): δ = 7.49 (s, 2 H), 7.39 (s, 2 H), 7.31 (s, 2 H),

4.44 (t, J = 5.7 Hz, 2 H), 3.91 (t, J = 5.7 Hz, 2 H), 2.47 (s, 6 H),

2.40 (s, 6 H), 2.25 (br. s, 1 H), 2.07 (m, 2 H), 1.33 (s, 9 H), 0.27 (s,

18 H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 157.8, 146.7, 137.8,

137.1, 132.9, 132.6, 130.9, 123.1, 122.9, 117.2, 103.8, 99.7, 92.2,

90.7, 72.7, 61.0, 34.3, 32.8, 31.2, 20.1, 20.0, 0.0 ppm. HRMS

(APPI-TOF): calcd. for C₄₃H₅₂O₂Si₂[M + H]⁺657.3579; found

61.1, 35.3, 34.3, 32.8, 31.9, 31.2, 31.1, 29.4, 29.2, 22.7, 20.1,

14.2 ppm. HRMS (APPI-TOF): calcd. for C₆₅H₇₄I₂O₂[M + H]⁺

1141.3851; found 1141.3842. FTIR (ATR): ν = 3408 (br. w), 2924

˜

(s), 2854 (m), 1553 (m), 1454 (m), 884 (m), 770 (s) cm^–1.

Compound 32: A 25 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 31 (1.54 g,

1.35 mmol), degassed THF (6 mL), degassed DIPEA (1.64 mL,

9.44 mmol), PdCl₂(PPh₃)₂(0.017 g, 0.024 mmol), CuI (0.018 g,

0.094 mmol) and (triisopropylsilyl)acetylene (1.08 mL, 5.90 mmol)

under argon. The reaction mixture was stirred at room temperature

overnight, diluted with CH₂Cl₂, washed with NH₄Cl, and the aque-

ous layer was extracted twice with CH₂Cl₂. The organic layers were

combined, dried with MgSO₄and filtered. The solvent was re-

moved under reduced pressure, and the crude product was purified

by flash chromatography on silica gel (CH₂Cl₂/hexanes, 1:3) to af-

1

ford desired compound 32 (1.40 g, 96% yield) as a yellow oil. H

NMR (CDCl₃, 400 MHz): δ = 7.50 (s, 2 H), 7.47 (s, 2 H), 7.43 (s,

2 H), 7.39 (s, 2 H), 7.30 (s, 2 H), 7.26 (s, 2 H), 4.46 (t, J = 5.6 Hz,

2 H), 3.96 (m, 2 H), 2.58 (t, J = 7.4 Hz, 4 H), 2.51 (s, 6 H), 2.49

(s, 6 H), 2.19 (br. s, 1 H), 2.10 (m, 2 H), 1.62 (m, 4 H), 1.35 (s, 9

H), 1.35–1.21 (br. m, 20 H), 1.14 (s, 42 H), 0.89 (t, J = 6.4 Hz, 6

H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 157.8, 146.8, 143.3,

137.5, 137.3, 132.8, 132.7, 132.4, 132.0, 131.5, 131.0, 123.7, 123.3,

123.1, 122.9, 117.2, 106.5, 94.2, 92.3, 90.8, 90.8, 88.4, 72.8, 61.2,

35.6, 34.4, 32.9, 31.9, 31.3, 31.3, 29.5, 29.3, 29.3, 22.7, 20.2, 18.7,

14.2, 11.3 ppm. HRMS (APPI-TOF): calcd. for C₈₇H₁₁₆O₂Si₂[M

657.3608. FTIR (ATR): ν = 3421 (br. w), 2956 (m), 2147 (m), 1452

˜

(m), 1247 (m), 837 (s), 758 (m) cm^–1.

Compound 29: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 28 (3.50 g,

5.33 mmol), THF (30 mL) and tetrabutylammonium fluoride in

THF (1.0 m, 13.3 mL, 13.3 mmol). The reaction mixture was stirred

at room temperature for 30 min, diluted with CH₂Cl₂and washed

with water. The aqueous layer was extracted twice with CH₂Cl₂.

The organic layers were combined, dried with MgSO₄and filtered.

The solvent was removed under reduced pressure, and the crude

product was purified by flash chromatography on silica gel

(CH₂Cl₂/hexanes, 3:7) to afford desired compound 29 (2.58 g, 94%)

+ H]⁺1249.8587; found 1249.8613. FTIR (ATR): ν = 2924 (s),

˜

2862 (s), 2154 (w), 1586 (m), 1462 (m), 1264 (w), 882 (m) cm^–1.

Compound 33: A 5 mL round-bottomed flask equipped with a mag-

netic stir bar was charged with compound 32 (0.250 g,

0.200 mmol), THF (1 mL) and tetrabutylammonium fluoride in

THF (1.0 m, 0.50 mL, 0.500 mmol). The reaction mixture was

stirred at room temperature for 30 min, diluted with CH₂Cl₂and

washed with water. The aqueous layer was extracted twice with

CH₂Cl₂. The organic layers were combined, dried with MgSO₄and

filtered. The solvent was removed under reduced pressure. A 5 mL

round-bottomed flask equipped with a magnetic stir bar was

charged with the crude product (0.187 g, 0.200 mmol), compound

11 (0.041 g, 0.091 mmol), CH₂Cl₂(1 mL), 4-(dimethylamino)pyr-

idine (0.002 g, 0.018 mmol) and TEA (0.22 mL, 1.60 mmol) under

argon. The reaction mixture was stirred at room temperature over-

night, diluted with CH₂Cl₂and washed with water. The aqueous

layer was extracted twice with CH₂Cl₂. The organic layers were

combined, dried with MgSO₄and filtered. The solvent was re-

moved under reduced pressure, and the crude product was purified

by flash chromatography on silica gel (CH₂Cl₂/hexanes, 1:1) to af-

1

as an orange oil. H NMR (CDCl₃, 400 MHz): δ = 7.49 (s, 2 H),

7.40 (s, 2 H), 7.35 (s, 2 H), 4.43 (t, J = 5.7 Hz, 2 H), 3.93 (q, J =

5.7 Hz, 2 H), 3.34 (s, 2 H), 2.48 (s, 6 H), 2.42 (s, 6 H), 2.13 (t, J =

5.7 Hz, 1 H), 2.08 (m, 2 H), 1.34 (s, 9 H) ppm. ¹³C NMR (CDCl₃,

100 MHz): δ = 157.9, 146.8, 138.0, 137.2, 133.4, 132.7, 131.1, 123.3,

122.1, 117.1, 92.0, 90.8, 82.4, 82.2, 72.8, 61.2, 34.4, 32.8, 31.3, 20.1,

20.0 ppm. HRMS (APPI-TOF): calcd. for C₃₇H₃₆O₂[M + H]⁺

513.2788; found 513.2790. FTIR (ATR): ν = 3455 (br. w), 3299

˜

(m), 2950 (m), 2101 (w), 1451 (m), 1222 (m), 1034 (s), 884 (s) cm^–1.

Compound 31: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 29 (2.58 g,

5.02 mmol), degassed THF (25 mL), degassed DIPEA (7.0 mL,

40.2 mmol), PdCl₂(PPh₃)₂(0.070 g, 0.10 mmol), CuI (0.077 g,

0.40 mmol) and compound 30 (6.68 g, 15.1 mmol) under argon.

The reaction mixture was stirred overnight at room temperature,

diluted with CH₂Cl₂, washed with NH₄Cl, and the aqueous layer

was extracted twice with CH₂Cl₂. The organic layers were com-

bined, dried with MgSO₄and filtered. The solvent was removed

under reduced pressure, and the crude product was purified by

flash chromatography on silica gel (CH₂Cl₂/hexanes, 3:7) to afford

1

ford desired compound 33 (0.179 g, 87% yield) as a yellow oil. H

NMR (CDCl₃, 400 MHz): δ = 8.11 (s, 2 H), 7.51 (s, 4 H), 7.48 (s,

4 H), 7.36 (s, 4 H), 7.32 (s, 8 H), 7.26 (s, 4 H), 4.60 (t, J = 6.0 Hz,

4 H), 4.46 (t, J = 5.5 Hz, 4 H), 3.05 (s, 4 H), 2.56 (t, J = 7.6 Hz, 8

H), 2.48 (s, 12 H), 2.43 (s, 12 H), 2.28 (m, 4 H), 1.59 (m, 8 H), 1.35

(s, 18 H), 1.35–1.21 (br. m, 40 H), 0.88 (t, J = 6.7 Hz, 12 H) ppm.

¹³C NMR (CDCl₃, 100 MHz): δ = 164.0, 157.9, 146.7, 143.4, 142.8,

137.8, 137.4, 137.2, 132.8, 132.7, 132.6, 132.4, 132.0, 131.9, 131.0,

123.5, 122.9, 122.3, 117.2, 93.9, 92.9, 92.3, 90.9, 88.6, 83.1, 77.4,

70.6, 63.5, 35.5, 34.4, 31.9, 31.2, 31.2, 29.4, 29.3, 29.2, 22.7, 20.2,

20.2, 14.2, 11.3 ppm. HRMS (APPI-TOF): calcd. for C₁₄₆H₁₅₂I₂O₆

1

desired compound 31 (1.54 g, 27% yield) as a dark oil. H NMR

(CDCl₃, 400 MHz): δ = 7.70 (s, 2 H), 7.50 (s, 4 H), 7.43 (s, 2 H),

7.36 (s, 2 H), 7.30 (s, 2 H), 4.45 (t, J = 5.6 Hz, 2 H), 3.95 (m, 2 H),

2.53 (t, J = 7.4 Hz, 4 H), 2.50 (s, 6 H), 2.47 (s, 6 H), 2.23 (br. s, 1

H), 2.10 (m, 2 H), 1.59 (m, 4 H), 1.35 (s, 9 H), 1.35–1.21 (br. m,

20 H), 0.89 (t, J = 6.4 Hz, 6 H) ppm. ¹³C NMR (CDCl₃, 100 MHz):

δ = 157.8, 146.7, 145.1, 137.4, 137.3, 137.2, 132.7, 132.7, 131.0,

[M⁺] 2254.9678; found 2254.9684. FTIR (ATR): ν = 3293 (br. m),

˜

2924 (s), 2854 (m), 1731 (m), 1586 (m), 1455 (m), 1233 (m), 1045

(m), 880 (m), 772 (s) cm^–1.

Compound 34: A 25 mL round-bottomed flask equipped with a

magnetic stir bar was charged with CuCl (0.387 g, 3.91 mmol),

Eur. J. Org. Chem. 0000, 0–0

www.eurjoc.org

11

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

K. Cantin, A. Lafleur-Lambert, P. Dufour, J.-F. Morin

CuCl₂(0.075 g, 0.56 mmol) and degassed pyridine (8 mL). To this 1.72 mmol) and acetyl chloride (20 mL) under argon. The reaction

FULL PAPER

suspension was added a solution of compound 33 (0.075 g,

0.56 mmol) in degassed pyridine (2 mL) at room temperature under

argon over 96 h. After completion of the addition, the mixture was

stirred for an additional 7 d and then poured into a mixture of

CH₂Cl₂/water. The organic layer was extracted successively with

water, NH₄OH (25%), water, acetic acid (10%), water, aqueous so-

dium hydroxide (10%) and brine. The organic layers were dried

with MgSO₄, the solvent was removed under reduced pressure, and

the crude product was purified by flash chromatography on silica

gel (CHCl₃). The crude product was suspended in hexanes and then

mixture was stirred overnight and, the solvent was removed under

reduced pressure. A 100 mL round-bottomed flask equipped with

a magnetic stir bar was charged with the crude product (1.53 g,

1.72 mmol), toluene (15 mL) and ethynylmagnesium bromide in

THF (0.5 m, 35 mL, 17.2 mmol) under argon. The reaction mixture

was stirred overnight, neutralized with water and extracted three

times with CH₂Cl₂. The organic layers were combined, dried with

MgSO₄and filtered. The solvent was removed under reduced pres-

sure, and the crude product was purified by flash chromatography

on silica gel (toluene/hexanes, 7:13) to afford desired compound 38

filtered to afford compound 34 (103 mg, 82% yield) as a white so- (0.536 g, 35% yield) as

a

yellow solid. ¹H NMR (CDCl₃,

lid. H NMR (CDCl₃, 400 MHz): δ = 8.39 (s, 2 H), 7.62 (s, 4 H), 400 MHz): δ = 7.48 (m, 12 H), 7.38 (d, J = 8.3 Hz, 6 H), 6.92 (d,

1

7.52 (s, 4 H), 7.51 (s, 4 H), 7.41 (s, 4 H), 7.34 (s, 4 H), 7.26 (s, 4

H), 4.81 (t, J = 8.2 Hz, 4 H), 4.41 (m, 4 H), 2.73 (t, J = 4.6 Hz, 4

H), 2.60 (t, J = 7.1 Hz, 8 H), 2.56 (s, 12 H), 2.54 (s, 12 H), 1.71–

1.49 (br. m, 8 H), 1.39–1.17 (br. m, 58 H), 0.89 (m, 12 H) ppm.

J = 8.7 Hz, 6 H), 3.93 (t, J = 6.5 Hz, 6 H), 2.70 (s, 1 H), 1.76 (m,

6 H), 1.44 (m, 6 H), 1.38–1.24 (br. s, 24 H), 0.88 (t, J = 6.4 Hz, 9

H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 158.8, 143.1, 139.4,

132.8, 129.8, 129.4, 128.0, 126.6, 126.3, 114.7, 89.7, 68.0, 31.9, 29.4,

FTIR (ATR): ν = 2920 (m), 1728 (m), 1583 (m), 1453 (m), 1275 29.3, 29.3, 26.1, 22.7, 14.2 ppm. HRMS (APPI-TOF): calcd. for

˜

(m), 1225 (s), 1045 (s), 874 (s) cm^–1. ¹³C NMR spectroscopic data

for 34 could not be obtained owing to its low solubility. HRMS

data for 34 could not be obtained in either ESI or APPI mode.

C₆₃H₇₆O₃[M + H]⁺881.5867; found 881.5873. FTIR (ATR): ν =

˜

2921 (m), 2853 (m), 1605 (m), 1493 (s), 1242 (s), 1175 (m), 806

(s) cm^–1.

Compound 40: A 10 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 38 (0.393 g,

0.446 mmol), degassed THF (2 mL), degassed TEA (0.25 mL,

1.78 mmol), PdCl₂(PPh₃)₂(0.006 g, 0.0089 mmol), CuI (0.003 g,

0.018 mmol) and compound 39 (0.268 g, 0.892 mmol) under argon.

The reaction mixture was stirred at room temperature overnight,

diluted with CH₂Cl₂, washed with NH₄Cl, and the aqueous layer

was extracted twice with CH₂Cl₂. The organic layers were com-

bined, dried with MgSO₄and filtered. The solvent was removed

under reduced pressure, and the crude product was purified by

flash chromatography on silica gel (toluene/hexanes, 1:3) to afford

desired compound 40 (0.362 g, 77% yield) as a white solid. ¹H

NMR (CDCl₃, 400 MHz): δ = 7.51 (d, J = 8.5 Hz, 12 H), 7.48–

7.39 (br. m, 10 H), 6.93 (d, J = 8.8 Hz, 6 H), 3.95 (t, J = 6.4 Hz, 6

H), 1.77 (m, 6 H), 1.45 (m, 6 H), 1.38–1.24 (br. s, 24 H), 0.88 (t, J

= 6.4 Hz, 9 H), 0.25 (s, 9 H) ppm. ¹³C NMR (CDCl₃, 100 MHz):

δ = 158.9, 143.6, 139.5, 132.9, 131.9, 131.6, 129.6, 128.1, 126.4,

123.8, 122.8, 114.9, 104.9, 97.7, 96.1, 85.1, 68.1, 55.2, 32.0, 29.5,

29.4, 29.4, 26.2, 22.8, 14.3, 0.1 ppm. HRMS (APPI-TOF): calcd.

for C₇₄H₈₈O₃Si [M + H]⁺1053.6575; found 1053.6575. FTIR

Compound 36: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with 4-bromo-4Ј-hydroxybiphenyl

(5.00 g, 20.1 mmol), acetone (25 mL), 1-iodooctane (10.9 mL,

60.3 mmol) and K₂CO₃(14.0 g, 101 mmol). The reaction mixture

was stirred at reflux overnight, cooled to room temperature and

then filtered. The solvent was removed under reduced pressure, and

the crude product was purified by flash chromatography on silica

gel (CH₂Cl₂/hexanes, 1:19) to afford desired compound 36 (6.53 g,

90% yield) as a white solid. ¹H NMR (CDCl₃, 400 MHz): δ = 7.52

(d, J = 8.4 Hz, 2 H), 7.45 (d, J = 8.6 Hz, 2 H), 7.39 (d, J = 8.4 Hz,

2 H), 6.94 (d, J = 8.6 Hz, 2 H), 3.97 (t, J = 6.5 Hz, 2 H), 1.79 (m,

2 H), 1.46 (m, 2 H), 1.38–1.24 (br. s, 8 H), 0.89 (t, J = 6.5 Hz, 3

H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 159.0, 139.8, 132.2,

131.8, 128.3, 127.9, 120.7, 114.9, 68.1, 31.9, 29.4, 29.3, 26.1, 22.7,

14.2 ppm. HRMS (APPI-TOF): calcd. for C₂₀H₂₅BrO [M + H]⁺

360.1162; found 360.1107. FTIR (ATR): ν = 2920 (m), 2853 (m),

˜

1604 (m), 1472 (m), 1287 (m), 1253 (m), 996 (m), 810 (s) cm^–1.

Compound 37: A 250 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 36 (6.47 g,

17.9 mmol) and THF (60 mL) under argon. The reaction mixture

was cooled to –78 °C. Then, n-butyllithium in hexanes (1.6 m,

12.2 mL, 18.2 mmol) was added dropwise. The reaction mixture

was stirred for 1 h, and diethyl carbonate (0.70 mL, 5.77 mmol)

was added dropwise. The reaction mixture was warmed to room

temperature and stirred overnight, neutralized with saturated

NaHCO₃and extracted three times with diethyl ether. The organic

layers were combined, dried with MgSO₄and filtered. The solvent

was removed under reduced pressure, and the crude product was

purified by flash chromatography on silica gel (EtOAc/hexanes,

1:19) to afford desired compound 37 (3.16 g, 63% yield) as a white

solid. ¹H NMR (CDCl₃, 400 MHz): δ = 7.49 (d, J = 8.5 Hz, 12 H),

7.36 (d, J = 8.3 Hz, 6 H), 6.93 (d, J = 8.7 Hz, 6 H), 3.97 (t, J =

6.5 Hz, 6 H), 2.99 (s, 1 H), 1.79 (m, 6 H), 1.46 (m, 6 H), 1.38–1.24

(br. s, 24 H), 0.89 (t, J = 6.6 Hz, 9 H) ppm. ¹³C NMR (CDCl₃,

100 MHz): δ = 158.8, 145.2, 139.7, 132.9, 128.4, 128.0, 126.2, 114.8,

81.7, 68.1, 31.9, 29.4, 29.3, 29.3, 26.1, 22.7, 14.2 ppm. HRMS

(APPI-TOF): calcd. for C₆₁H₇₆O₄[M + H]⁺873.5816; found

(ATR): ν = 2914 (m), 2854 (m), 2456 (w), 1607 (m), 1494 (s), 1244

˜

(s), 1172 (m), 840 (s), 817 (m) cm^–1.

Compound 41: A 5 mL round-bottomed flask equipped with a mag-

netic stir bar was charged with compound 40 (0.146 g,

0.139 mmol), THF (1 mL), MeOH (1 mL) and KOH 2.5 m

(0.14 mL). The reaction mixture was stirred for 1 h, acidified to pH

= 7 and diluted with CH₂Cl₂. The aqueous layer was extracted

three times with CH₂Cl₂. The organic layers were combined, dried

with MgSO₄and filtered. The solvent was then removed under re-

duced pressure. A 5 mL round-bottomed flask equipped with a

magnetic stir bar was charged with the crude product (0.137 g,

0.139 mmol), degassed THF (2 mL), degassed DIPEA (0.30 mL,

1.85 mmol), PdCl₂(PPh₃)₂(0.0003 g, 0.00046 mmol), CuI (0.0002 g,

0.00092 mmol) and compound 34 (0.052 g, 0.0236 mmol) under ar-

gon. The reaction mixture was stirred at room temperature for 48 h,

diluted with CH₂Cl₂, washed with NH₄Cl, and the aqueous layer

was extracted twice with CH₂Cl₂. The organic layers were com-

bined, dried with MgSO₄and filtered. The solvent was removed

under reduced pressure, and the crude product was purified by

flash chromatography on silica gel (CHCl₃/hexanes, 3:2) to afford

desired compound 41 (0.084 g, 92% yield) as a yellow solid. ¹H

NMR (CDCl₃, 400 MHz): δ = 8.32 (s, 2 H), 7.63–7.18 (br. m, 68

873.5807. FTIR (ATR): ν = 3454 (br. w), 2922 (m), 1607 (w), 1495

˜

(s), 1245 (s), 1176 (m), 817 (s) cm^–1.

Compound 38: A 50 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 37 (1.50 g,

12

www.eurjoc.org

Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

Phenylacetylene Macrocycle Based Rotaxane Precursors

H), 6.93 (d, J = 8.5 Hz, 12 H), 4.90 (t, J = 7.3 Hz, 4 H), 4.43 (br. 0.333 mmol), degassed THF (4 mL), degassed DIPEA (0.46 mL,

s, 4 H), 3.98 (t, J = 6.6 Hz, 12 H), 2.61 (br. s, 4 H), 2.58–2.41 (br. 2.66 mmol), PdCl₂(PPh₃)₂(0.005 g, 0.0067 mmol), CuI (0.005 g,

m, 32 H), 1.80 (m, 12 H), 1.58 (m, 8 H), 1.47 (m, 12 H), 1.41–1.18

0.0027 mmol) and 4,4Ј-diiodobiphenyl (0.406 g, 0.999 mmol) under

(br. m, 106 H), 0.89 (br. m, 30 H) ppm. ¹³C NMR (CDCl₃, argon. The reaction mixture was stirred at room temperature over-

100 MHz): δ = 165.2, 158.8, 157.3, 147.1, 143.7, 143.6, 139.4, 139.2,

137.8, 137.4, 134.7, 134.6, 133.0, 132.9, 132.7, 132.0, 131.8, 131.5,

131.2, 129.6, 128.1, 126.5, 126.4, 126.3, 124.4, 123.9, 123.1, 123.0,

122.4, 122.0, 117.8, 114.9, 114.9, 97.8, 96.8, 93.9, 92.4, 91.1, 89.3,

89.2, 85.1, 81.6, 74.4, 70.7, 68.2, 64.5, 55.4, 35.6, 34.5, 32.0, 32.0,

31.4, 31.2, 29.8, 29.6, 29.5, 29.4, 29.4, 29.4, 26.2, 26.2, 22.8, 20.3,

night, diluted with CH₂Cl₂, washed with NH₄Cl, and the aqueous

layer was extracted twice with CH₂Cl₂. The organic layers were

combined, dried with MgSO₄and filtered. The solvent was re-

moved under reduced pressure, and the crude product was purified

by flash chromatography on silica gel (CH₂Cl₂/hexanes, 1:9) to af-

ford desired compound 46 (0.089 g, 31% yield) as a white solid. ¹H

20.2, 14.3 ppm. FTIR (ATR): ν = 2923 (s), 2852 (s), 1494 (s), 1467 NMR (CDCl₃, 400 MHz): δ = 7.77 (d, J = 8.0 Hz, 4 H), 7.65 (s, 1

˜

(m), 1247 (s), 1042 (m), 819 (m) cm^–1. HRMS data for 41 could

not be obtained in either ESI or APPI mode.

H), 7.56 (br. m, 10 H), 7.33 (d, J = 8.0 Hz, 4 H), 1.15 (s, 21 H) ppm.

¹³C NMR (CDCl₃, 100 MHz): δ = 140.2, 139.9, 138.1, 134.7, 134.2,

132.4, 129.0, 127.0, 124.4, 124.0, 122.3, 105.3, 93.7, 92.5, 90.4, 88.9,

18.8, 11.4 ppm. HRMS (APPI-TOF): calcd. for C₄₅H₄₀I₂Si [M +

Compound 43: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 42 (4.00 g,

9.79 mmol), degassed THF (50 mL), degassed TEA (5.4 mL,

39.1 mmol), PdCl₂(PPh₃)₂(0.275 g, 0.390 mmol), CuI (0.750 g,

0.390 mmol) and (trimethylsilyl)acetylene (2.8 mL, 20.5 mmol) un-

der argon. The reaction mixture was stirred at room temperature

overnight, diluted with CH₂Cl₂, washed with NH₄Cl (3ϫ) and

dried with Na₂SO₄. The solvent was removed under reduced pres-

sure, and the crude product was purified by flash chromatography

on silica gel (hexanes) to afford compound 43 (3.41 g, 98% yield)

H]⁺863.1061; found 863.1042. FTIR (ATR): ν = 2937 (m), 2860

˜

(m), 1577 (m), 1478 (m), 1000 (m), 879 (m), 809 (s) cm^–1.

Compound 48: A 10 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 46 (0.309 g,

0.358 mmol), degassed THF (4 mL), degassed DIPEA (0.50 mL,

2.86 mmol), PdCl₂(PPh₃)₂(0.005 g, 0.0072 mmol), CuI (0.005 g,

0.0029 mmol) and compound 47 (0.458 g, 1.99 mmol) under argon.

The reaction mixture was stirred at room temperature overnight,

diluted with CH₂Cl₂, washed with NH₄Cl, and the aqueous layer

was extracted twice with CH₂Cl₂. The organic layers were com-

bined, dried with MgSO₄and filtered. The solvent was removed

under reduced pressure, and the crude product was purified by

flash chromatography on silica gel (CH₂Cl₂/hexanes, 1:9) to afford

desired compound 48 (0.314 g, 82% yield) as a white solid. ¹H

NMR (CDCl₃, 400 MHz): δ = 7.67 (s, 2 H), 7.65 (s, 1 H), 7.59 (d,

J = 7.8 Hz, 16 H), 7.47 (d, J = 8.7 Hz, 4 H), 6.87 (d, J = 8.7 Hz,

4 H), 3.97 (t, J = 6.5 Hz, 4 H), 1.79 (m, 4 H), 1.46 (m, 4 H), 1.38–

1.24 (br. m, 16 H), 1.15 (s, 21 H), 0.89 (t, J = 6.4 Hz, 6 H) ppm.

¹³C NMR (CDCl₃, 100 MHz): δ = 159.4, 140.6, 139.6, 134.7, 134.3,

133.2, 132.3, 132.1, 127.0, 127.0, 124.4, 124.0, 123.2, 122.1, 115.1,

114.7, 105.4, 92.4, 90.8, 90.5, 88.9, 88.0, 68.2, 32.0, 29.5, 29.4, 29.3,

1

as a colorless oil. H NMR (CDCl₃): δ = 7.53 (s, 2 H), 7.49 (s, 1

H), 0.23 (s, 18 H) ppm. ¹³C NMR (CDCl₃): δ = 134.7, 134.2, 125.3,

121.9, 102.6, 96.8, 0.01 ppm. HRMS (APPI-TOF): calcd. for

C₁₆H₂₁BrSi₂[M + H]⁺349.0438; found 349.0454. FTIR (ATR): ν

˜

= 2960 (m), 2160 (m), 1550 (m), 1249 (m), 842 (m) cm^–1.

Compound 44: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 43 (33.7 g,

9.64 mmol), degassed TEA (50 mL), Pd₂(dba)₃(0.353 g,

0.386 mmol), CuI (0.074 g, 0.39 mmol), PPh₃(0.506 g, 1.93 mmol)

and (triisopropylsilyl)acetylene (4.3 mL, 19.3 mmol) under argon.

The reaction mixture was stirred at 60 °C for 48 h, cooled to room

temperature, diluted with CH₂Cl₂, washed with NH₄Cl, and the

aqueous layer was extracted twice with CH₂Cl₂. The organic layers

were combined, dried with MgSO₄and filtered. The solvent was

removed under reduced pressure, and the crude product was puri-

fied by flash chromatography on silica gel (hexanes) to afford de-

sired compound 44 (4.02 g, 92% yield) as a colorless oil. ¹H NMR

(CDCl₃, 400 MHz): δ = 7.48 (br. m, 3 H), 1.11 (s, 21 H), 0.23 (s,

18 H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 135.1, 135.1, 124.1,

123.7, 105.3, 103.3, 95.7, 92.2, 18.8, 11.4, 0.0 ppm. FTIR (ATR):

26.2, 22.8, 18.8, 14.3, 11.4 ppm. FTIR (ATR): ν = 2919 (m), 2852

˜

(m), 2164 (w), 1598 (m), 1503 (s), 1247 (s), 1174 (s), 829 (s) cm^–1.

HRMS data for 48 could not be obtained in either ESI or APPI

mode.

Compound 49: A 10 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 48 (0.280 g,

0.262 mmol), THF (3 mL) and tetrabutylammonium fluoride in

THF (1.0 m, 0.34 mL, 0.341 mmol). The reaction mixture was

stirred at room temperature for 30 min, diluted with CH₂Cl₂,

washed with water. The aqueous layer was extracted twice with

CH₂Cl₂. The organic layers were combined, dried with MgSO₄and

filtered. The solvent was removed under reduced pressure. A 10 mL

round-bottomed flask equipped with a magnetic stir bar was

charged with the crude product (0.239 g, 0.262 mmol), degassed

THF (3 mL), degassed DIPEA (0.36 mL, 2.08 mmol), PdCl₂-

(PPh₃)₂(0.004 g, 0.0052 mmol), CuI (0.002 g, 0.010 mmol) and

compound 39 (0.312 g, 1.04 mmol) under argon. The reaction mix-

ture was stirred at room temperature overnight, diluted with

CH₂Cl₂, washed with NH₄Cl, and the aqueous layer was extracted

twice with CH₂Cl₂. The organic layers were combined, dried with

MgSO₄and filtered. The solvent was removed under reduced pres-

sure, and the crude product was purified by flash chromatography

on silica gel (CH₂Cl₂/hexane, 1:3) to afford desired compound 49

(0.204 g, 72% yield) as a pale yellow solid. ¹H NMR (CDCl₃,

400 MHz): δ = 7.67 (s, 1 H), 7.65 (s, 2 H), 7.58 (d, J = 9.0 Hz, 16

H), 7.46 (br. m, 8 H), 6.86 (d, J = 8.6 Hz, 4 H), 3.95 (t, J = 6.5 Hz,

4 H), 1.78 (m, 4 H), 1.45 (m, 4 H), 1.38–1.24 (br. m, 16 H), 0.89

ν = 2958 (s), 2865 (s), 2163 (m), 1250 (s), 843 (s) cm^–1. HRMS data

˜

for 44 could not be obtained in either ESI or APPI mode.

Compound 45: A 100 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 44 (4.02 g,

8.92 mmol), THF (20 mL), MeOH (20 mL) and KOH 2.5 m

(10 mL). The reaction mixture was stirred for 1 h, acidified to pH

= 7 and diluted with CH₂Cl₂. The aqueous layer was extracted

twice with CH₂Cl₂. The organic layers were combined, dried with

MgSO₄and filtered. The solvent was then removed under reduced

pressure, and the crude product was purified by flash chromatog-

raphy on silica gel (hexanes) to afford desired compound 45 (2.66 g,

1

97% yield) as a yellow oil. H NMR (CDCl₃, 400 MHz): δ = 7.55

(s, 2 H), 7.53 (s, 1 H), 3.09 (s, 2 H), 1.12 (s, 21 H) ppm. ¹³C NMR

(CDCl₃, 100 MHz): δ = 135.7, 135.2, 124.4, 122.9, 104.9, 92.8, 81.9,

78.6, 18.8, 11.4 ppm. HRMS (APPI-TOF): calcd. for C₂₁H₂₆Si [M

+ H]⁺307.1877; found 307.1879. FTIR (ATR): ν = 3301 (m), 2943

˜

(s), 2865 (s), 2160 (w), 1579 (m), 967 (m), 881 (s) cm^–1.

Compound 46: A 10 mL round-bottomed flask equipped with a

magnetic stir bar was charged with compound 45 (0.102 g,

Eur. J. Org. Chem. 0000, 0–0

www.eurjoc.org

13

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

K. Cantin, A. Lafleur-Lambert, P. Dufour, J.-F. Morin

(t, J = 6.4 Hz, 6 H), 0.26 (s, 9 H) ppm. ¹³C NMR (CDCl₃, (m), 1000 (s), 878 (s), 808 (s) cm^–1. HRMS data for 51 could not

FULL PAPER

100 MHz): δ = 159.4, 140.6, 139.6, 134.7, 134.3, 133.2, 132.3, 132.1,

131.6, 127.0, 127.0, 124.2, 124.0, 123.5, 123.2, 123.0, 122.0, 115.1,

114.7, 104.7, 96.7, 90.8, 90.7, 90.3, 89.9, 88.8, 88.0, 68.2, 32.0, 29.5,

29.4, 29.4, 26.2, 22.8, 18.8, 14.3, 0.1 ppm. HRMS (APPI-TOF):

calcd. for C₇₉H₇₄O₂Si [M + H]⁺1083.5531; found 1083.5534. FTIR

be obtained in either ESI or APPI mode.

Supporting Information (see footnote on the first page of this arti-

1

cle): H and ¹³C NMR spectra for new compounds.

(ATR): ν = 2921 (m), 2853 (m), 1508 (s), 1247 (s), 820 (s) cm^–1.

˜

Acknowledgments

Compound 50: A 5 mL round-bottomed flask equipped with a mag-

netic stir bar was charged with compound 49 (0.100 g,

0.0923 mmol), THF (2 mL) and tetrabutylammonium fluoride in

THF (1.0 m, 0.12 mL, 0.120 mmol). The reaction mixture was

stirred at room temperature for 30 min, diluted with CH₂Cl₂and

washed with water. The aqueous layer was extracted twice with

CH₂Cl₂. The organic layers were combined, dried with MgSO₄and

filtered. The solvent was removed under reduced pressure. A 10 mL

round-bottomed flask equipped with a magnetic stir bar was

charged with the crude product (0.094 g, 0.0923 mmol), degassed

THF (2 mL), degassed DIPEA (0.26 mL, 1.48 mmol), PdCl₂-

(PPh₃)₂(0.0003 g, 0.00037 mmol), CuI (0.0001 g, 0.00074 mmol)

and compound 34 (0.042 g, 0.0185 mmol) under argon. The reac-

tion mixture was stirred at room temperature for 48 h, diluted with

CH₂Cl₂, washed with NH₄Cl, and the aqueous layer was extracted

twice with CH₂Cl₂. The organic layers were combined, dried with

MgSO₄and filtered. The solvent was removed under reduced pres-

sure, and the crude product was purified by flash chromatography

on silica gel (CHCl₃/hexanes, 3:2) to afford desired compound 50

This work was supported by the National Science and Engineering

Council (NSERC) through a Discovery Grant. K. C. thanks the

Fonds de Recherche du Québec – Nature et Technologies for a PhD

scholarship. We are also grateful for professional support from the

Centre québécois sur les matériaux fonctionnels (CQMF) and the

Centre de recherche sur les matériaux avancés (CERMA).

[1] a) M. S. Wendland, S. C. Zimmerman, J. Am. Chem. Soc. 1999,

121, 1389–1390; b) L. G. Schultz, Y. Zhao, S. C. Zimmerman,

Angew. Chem. 2001, 113, 2016–2020; Angew. Chem. Int. Ed.

2001, 40, 1962–1966; c) S. C. Zimmerman, I. Zharov, M. S.

Wendland, N. A. Rakow, K. S. Suslick, J. Am. Chem. Soc.

2003, 125, 13504–13518; d) J. B. Beil, G. Lemcoff, S. C. Zim-

merman, J. Am. Chem. Soc. 2004, 126, 13576–13577; e) N. G.

Lemcoff, T. A. Spurlin, A. A. Gewirth, S. C. Zimmerman, J. B.

Beil, S. L. Elmer, H. G. Vandeveer, J. Am. Chem. Soc. 2004,

126, 11420–11421; f) S. L. Elmer, S. C. Zimmerman, J. Org.

Chem. 2004, 69, 7363–7366; g) J.-K. Lee, M. C. Kung, Y.-

W. H. H. Suh, H. H. Kung, Chem. Mater. 2008, 20, 373–375.

[2] a) J. Wu, L. Gherghel, M. D. Watson, J. Li, Z. Wang, C. D.

Simpson, U. Kolb, K. Müllen, Macromolecules 2003, 36, 7082–

7089; b) C. D. Simpson, G. Mattersteig, K. Martin, L.

Gherghel, R. E. Bauer, H. J. Räder, K. Müllen, J. Am. Chem.

Soc. 2004, 126, 3139–3147; c) J. Wu, W. Pisula, K. Müllen,

Chem. Rev. 2007, 107, 718–747; d) X. Y. Yang, X. Dou, A.

Rouhanipour, L. J. Zhi, H. J. Räder, K. Müllen, J. Am. Chem.

Soc. 2008, 130, 4216–4217; e) Y. Fogel, L. Zhi, A. Rouhanip-

our, D. Andrienko, H. J. Räder, K. Müllen, Macromolecules

2009, 42, 6878–6884; f) X. Yan, X. Cui, L.-s. Li, J. Am. Chem.

Soc. 2010, 132, 5944–5945; g) L. Dössel, L. Gherghel, X. Feng,

K. Müllen, Angew. Chem. 2011, 123, 2588–2591; Angew. Chem.

Int. Ed. 2011, 50, 2540–2543.

(0.039 g, 52% yield) as

a

yellow solid. ¹H NMR (CDCl₃,

400 MHz): δ = 8.34 (s, 2 H), 7.68–7-45 (br. m, 66 H), 7.40 (s, 4 H),

7.30 (s, 4 H), 7.21 (s, 4 H), 6.88 (d, J = 8.6 Hz, 8 H), 4.89 (t, J =

7.9 Hz, 4 H), 4.44 (br. s, 4 H), 3.97 (t, J = 6.4 Hz, 8 H), 2.67 (br.

s, 4 H), 2.57–2.47 (br. m, 32 H), 1.79 (m, 8 H), 1.56 (m, 8 H), 1.46

(m, 8 H), 1.41–1.17 (br. m, 90 H), 0.88 (br. m, 24 H) ppm. ¹³C

NMR (CDCl₃, 100 MHz): δ = 159.3, 157.1, 143.6, 140.4, 139.5,

137.7, 137.3, 134.4, 133.2, 133.1, 132.8, 132.7, 132.2, 132.2, 131.9,

131.9, 131.8, 131.7, 131.7, 131.4, 131.4, 131.1, 126.9, 126.9, 126.8,

123.8, 123.8, 123.7, 123.1, 123.0, 123.0, 122.9, 122.9, 122.0, 121.9,

117.6, 115.0, 114.5, 94.9, 92.3, 91.0, 90.6, 90.4, 89.0, 89.0, 88.8,

87.8, 81.5, 74.3, 68.1, 35.5, 35.5, 34.4, 31.9, 31.8, 31.2, 31.1, 31.1,

29.7, 29.6, 29.7, 29.5, 29.4, 29.4, 29.3, 29.2, 26.0, 22.7, 22.7, 20.6,

[3] F. Otis, C. Racine-Berthiaume, N. Voyer, J. Am. Chem. Soc.

2011, 133, 6481–6483.

20.1, 14.1 ppm. FTIR (ATR): ν = 2921 (s), 2852 (m), 1729 (w),

˜

[4] a) T. Yamaguchi, N. Ishii, K. Tashiro, T. Aida, J. Am. Chem.

Soc. 2003, 125, 13934–13935; b) T. Kiba, H. Suzuki, K. Hosok-

awa, H. Kobayashi, S. Baba, T. Kakuchi, S.-i. Sato, J. Phys.

Chem. B 2009, 113, 11560–11563; c) M. Fathalla, A. Neub-

erger, S.-C. Li, R. Schmehl, U. Diebold, J. Jayawickramarajah,

J. Am. Chem. Soc. 2010, 132, 9966–9967.

[5] a) R. B. Prince, T. Okada, J. S. Moore, Angew. Chem. 1999,

111, 245–249; Angew. Chem. Int. Ed. 1999, 38, 233–236; b)

R. B. Prince, S. A. Barnes, J. S. Moore, J. Am. Chem. Soc. 2000,

122, 2758–2762; c) A. Tanatani, M. J. Mio, J. S. Moore, J. Am.

Chem. Soc. 2001, 123, 1792–1793; d) C. Tan, M. R. Pinto,

M. E. Kose, I. Ghiviriga, K. S. Schanze, Adv. Mater. 2004, 16,

1208–1212; e) V. G. Organo, D. M. Rudkevich, Chem. Com-

mun. 2007, 3891–3899.

1581 (m), 1509 (s), 1247 (m), 821 (m) cm^–1. HRMS data for 50

could not be obtained in either ESI or APPI mode.

Compound 51: A 15 mL round heavy-wall pressure vessel equipped

with a magnetic stir bar was charged with compound 50 (0.030 g,

0.00746 mmol), THF (5 mL), LiOH 10% (0.02 mL), and NaOH

10% in MeOH (0.07 mL). The reaction mixture was stirred at

80 °C for 48 h, cooled to room temperature and acidified to pH =

6. The organic layer was washed with water. The aqueous layer was

extracted three times with CHCl₃. The organic layers were com-

bined, dried with MgSO₄and filtered. The solvent was removed

under reduced pressure, and the crude product was purified by

flash chromatography on silica gel (CHCl₃) to afford desired com-

[6] M. A. B. Block, C. Kaiser, A. Khan, S. Hecht, Top. Curr.

Chem. 2005, 245, 89–150.

1

pound 51 (0.014 g, 90%) as a pale yellow solid. H NMR (CDCl₃,

[7] S. Dawn, M. B. Dewal, D. Sobransingh, M. C. Paderes, A. C.

Wibowo, M. D. Smith, J. A. Krause, P. J. Pellechia, L. S. Shim-

izu, J. Am. Chem. Soc. 2011, 133, 7025–7032.

[8] a) M. R. Ghadiri, J. R. Granja, R. A. Milligan, D. E. McRee,

N. Khazanovich, Nature 1993, 366, 324–327; b) D. Seebach,

J. L. Matthews, A. Meden, T. Wessels, C. Baerlocher, L. B.

McCusker, Helv. Chim. Acta 1997, 80, 173–182; c) J. D. Hart-

gerink, T. D. Clark, M. R. Ghadiri, Chem. Eur. J. 1998, 4,

1367–1372; d) D. Ranganathan, M. P. Samant, I. L. Karle, J.

Am. Chem. Soc. 2001, 123, 5619–5624.

400 MHz): δ = 7.57 (s, 4 H), 7.49 (s, 4 H), 7.46 (s, 4 H), 7.39 (s, 4

H), 7.34 (s, 4 H), 7.30 (s, 4 H), 4.45 (t, J = 5.7 Hz, 4 H), 3.98 (m,

4 H), 2.60 (t, J = 7.5 Hz, 8 H), 2.53 (s, 12 H), 2.49 (s, 12 H), 2.13

(m, 4 H), 1.79 (m, 2 H), 1.63 (m, 8 H), 1.38–1.22 (br. m, 58 H),

0.89 (t, J = 6.3 Hz, 12 H) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ =

143.8, 137.7, 137.4, 132.9, 132.9, 123.9, 123.1, 123.0, 122.0, 117.4,

93.9, 92.4, 90.9, 89.0, 81.3, 74.2, 61.3, 35.7, 34.5, 33.0, 32.0, 32.0,

31.4, 31.3, 29.6, 29.4, 29.3, 26.2, 22.8, 20.3, 20.3, 14.3 ppm. FTIR

(ATR): ν = 2923 (s), 2854 (m), 1581 (m), 1494 (m), 1455 (m), 1380

˜

14

www.eurjoc.org

Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

Phenylacetylene Macrocycle Based Rotaxane Precursors

[9]

Soc. 2010, 132, 5334–5335; d) T.-J. Hsu, F. W. Fowler, J. W.

a) P. R. Ashton, C. L. Brown, S. Menzer, S. A. Nepogodiev,

J. F. Stoddart, D. J. Williams, Chem. Eur. J. 1996, 2, 580–591;

b) P. Ashton, S. J. Cantrill, G. Gattuso, S. Menzer, S. A. Nepog-

odiev, A. N. Shipway, J. F. Stoddart, D. J. Williams, Chem. Eur.

J. 1997, 3, 1299–1314; c) G. Giattuso, S. Menxer, S. A. Nepogo-

diev, J. F. Stoddart, D. J. Williams, Angew. Chem. 1997, 109,

1615–1617; Angew. Chem. Int. Ed. Engl. 1997, 36, 1451–1454;

d) Y. Liu, C.-C. You, H.-Y. Zhang, S.-Z. Kang, C.-F. Zhu, C.

Wang, Nano Lett. 2001, 1, 613–616.

a) V. Sidorov, F. W. Kotch, J. T. Davis, M. El-Kouedi, Chem.

Commun. 2000, 2369–2370; b) S. Kennedy, G. Karotsis, C. M.

Beavers, S. J. Teat, E. K. Brechin, S. J. Dalgarno, Angew. Chem.

2010, 122, 4301–4304; Angew. Chem. Int. Ed. 2010, 49, 4205–

4208.

Lauher, J. Am. Chem. Soc. 2012, 134, 142–145.

[14] Y. Kim, M. F. Mayer, S. C. Zimmerman, Angew. Chem. 2003,

115, 1153–1158; Angew. Chem. Int. Ed. 2003, 42, 1121–1126.

[15] T. Yamamoto, T. Fukushima, Y. Yamamoto, A. Kosaka, W.

Jin, N. Ishii, T. Aida, J. Am. Chem. Soc. 2006, 128, 14337–

14340.

[16] J. Couet, J. D. Jeyaprakash, S. Samuel, A. Kopyshev, S. Santer,

M. Biesalski, Angew. Chem. 2005, 117, 3361–3365; Angew.

Chem. Int. Ed. 2005, 44, 3297–3301.

[17] A. Harada, J. Li, M. Kamachi, Nature 1993, 364, 516–518.

[18] M. Schmittel, V. Kalsani, C. Michel, P. Mal, H. Ammon, F.

Jäckel, J. P. Rabe, Chem. Eur. J. 2007, 13, 6223–6237.

[19] K. Becker, P. G. Lagoudakis, G. Gaefke, S. Höger, J. M. Lup-

ton, Angew. Chem. 2007, 119, 3520–3525; Angew. Chem. Int.

Ed. 2007, 46, 3450–3455.

[20] For reviews, see: a) D. Thibeault, J.-F. Morin, Molecules 2010,

15, 3709–3730; b) V. Balzani, A. Credi, F. M. Raymo, J. F.

Stoddart, Angew. Chem. 2000, 112, 3484–3530; Angew. Chem.

Int. Ed. 2000, 39, 3348–3391; c) E. Coronado, P. Gavina, S.

Tatay, Chem. Soc. Rev. 2009, 38, 1674–1689.

[21] S. Saha, E. Johansson, A. H. Flood, H.-R. Tseng, J. I. Zink,

J. F. Stoddart, Chem. Eur. J. 2005, 11, 6846–6858.

[10]

[11] a) J. C. Nelson, J. G. Saven, J. S. Moore, P. G. Wolynes, Science

1997, 277, 1793–1796; b) R. B. Prince, J. G. Saven, P. G.

Wolynes, J. S. Moore, J. Am. Chem. Soc. 1999, 121, 3114–3121;

c) M. S. Gin, T. Yokozawa, R. B. Prince, J. S. Moore, J. Am.

Chem. Soc. 1999, 121, 2643–2644; d) R. B. Prince, L.

Brunsveld, E. W. Meijer, J. S. Moore, Angew. Chem. 2000, 112,

234–236; Angew. Chem. Int. Ed. 2000, 39, 228–230; e) S. Lahiri,

J. L. Thompson, J. S. Moore, J. Am. Chem. Soc. 2000, 122,

11315–11319; f) R. B. Prince, J. S. Moore, L. Brunsveld, E. W.

Meijer, Chem. Eur. J. 2001, 7, 4150–4154; g) L. Brunsveld,

E. W. Meijer, R. B. Prince, J. S. Moore, J. Am. Chem. Soc. 2001,

123, 7978–7984; h) K. Matsuda, M. T. Stone, J. S. Moore, J.

Am. Chem. Soc. 2002, 124, 11836–11837; i) J. M. Cary, J. S.

Moore, Org. Lett. 2002, 4, 4663–4666; j) T. V. Jones, R. A.

Blatchly, G. N. Tew, Org. Lett. 2003, 5, 3297–3299; k) M. T.

Stone, J. S. Moore, Org. Lett. 2004, 6, 469–472; l) J. M. Heem-

stra, J. S. Moore, J. Am. Chem. Soc. 2004, 126, 1648–1649; m)

T. V. Jones, M. M. Slutsky, R. Laos, T. F. A. de Greef, G. N.

Tew, J. Am. Chem. Soc. 2005, 127, 17235–17240; n) X. Zhao,

K. S. Schanze, Langmuir 2006, 22, 4856–4862; o) A. Khan, C.

Kaiser, S. Hecht, Angew. Chem. 2006, 118, 1912–1915; Angew.

Chem. Int. Ed. 2006, 45, 1878–1881; p) A. Khan, S. Hecht,

Chem. Eur. J. 2006, 12, 4764–4774; q) N. Zhu, W. Hu, S. Han,

Q. Wang, D. Zhao, Org. Lett. 2008, 10, 4283–4286; r) T. V.

Jones, M. M. Slutszky, G. N. Tew, New J. Chem. 2008, 32, 676–

679; s) B.-B. Ni, Q. Yan, Y. Ma, D. Zhao, Coord. Chem. Rev.

2010, 254, 954–971.

[12] a) K. Yu, A. Eisenberg, Macromolecules 1998, 31, 3509–3518;

b) B. M. Discher, Y.-Y. Won, D. S. Ege, J. C. M. Lee, F. S.

Bates, D. E. Discher, D. A. Hammer, Science 1999, 284, 1143–

1146; c) S. Stewart, G. Liu, Angew. Chem. 2000, 112, 348–352;

Angew. Chem. Int. Ed. 2000, 39, 340–344; d) S. Rosseli, A.-D.

Ramminger, T. Wagner, B. Silier, S. Wiegand, W. Haussler, G.

Lieser, V. Scheumann, S. Höger, Angew. Chem. 2001, 113,

3233–3237; Angew. Chem. Int. Ed. 2001, 40, 3137–3141.

[13] a) S. Hecht, A. Khan, Angew. Chem. 2003, 115, 6203–6206;

Angew. Chem. Int. Ed. 2003, 42, 6021–6024; b) J. Motoyanagi,

T. Fukushima, N. Ishii, T. Aida, J. Am. Chem. Soc. 2006, 128,

4220–4221; c) Y. W. Xu, M. D. Smith, M. F. Geer, P. J. Pelle-

chia, J. C. Brown, A. C. Wibowo, L. S. Shimizu, J. Am. Chem.

[22] Z. Xue, M. Mayer, J. Am. Chem. Soc. 2010, 132, 3274–3276.

[23] a) S. Höger, A.-D. Meckenstock, H. Pellen, J. Org. Chem. 1997,

62, 4556–4557; b) S. Höger, J. Polym. Sci., Part A 1999, 37,

2685–2698; c) S. Höger, A.-D. Meckenstock, Chem. Eur. J.

1999, 5, 1686–1691; d) M. Fischer, S. Höger, Eur. J. Org. Chem.

2003, 441–446; e) S. Höger, Chem. Eur. J. 2004, 10, 1320–1329;

f) A. Ziegler, W. Mamdouh, A. Ver Hayen, M. Surin, H. Uji-

I, M. M. S. Abdel-Mottaleb, F. C. De Schryver, S. De Feyter,

R. Lazzaroni, S. Höger, Chem. Mater. 2005, 17, 5670–5683.

[24] K. S. Chichak, A. J. Peters, S. J. Cantrill, J. F. Stoddart, J. Org.

Chem. 2005, 70, 7956–7962.

[25] Q. Zhou, T. M. Swager, J. Am. Chem. Soc. 1995, 117, 12593–

12602.

[26] S. Grunder, R. Huber, V. Horhoiu, M. T. Gonzalez, C.

Schönenberger, M. Calame, M. Mayor, J. Org. Chem. 2007, 72,

8337–8344.

[27] M. Bérubé, D. Poirier, Org. Lett. 2004, 6, 3127–3130.

[28] K. Cantin, S. Rondeau-Gagné, J. Néabo Roméo, M. Daigle, J.-

F. Morin, Org. Biomol. Chem. 2011, 9, 4440–4443.

[29] J. Iskra, S. Stavber, M. Zupan, Synthesis 2004, 11, 1869–1873.

[30] A. Lembo, P. Tagliatesta, D. M. Guldi, M. Wielopolski, M.

Nuccetelli, J. Phys. Chem. A 2009, 113, 1779–1793.

[31] S. Rondeau-Gagné, C. Curutchet, F. Grenier, G. D. Scholes, J.-

F. Morin, Tetrahedron 2010, 66, 4230–4242.

[32] For recent examples of the use of this strategy, see: a) T. J.

Kidd, T. J. A. Loontjens, D. A. Leigh, J. K. Y. Wong, Angew.

Chem. 2003, 115, 3501–3505; Angew. Chem. Int. Ed. 2003, 42,

3379–3383; b) F. Huang, H. W. Gibson, Prog. Polym. Sci. 2005,

30, 982–1018; c) T. Ikeda, M. Higuchi, D. G. Kurth, J. Am.

Chem. Soc. 2009, 131, 9158–9159.

Received: May 15, 2012

Published Online: ᭿

Eur. J. Org. Chem. 0000, 0–0

www.eurjoc.org

15

Job/Unit: O20655

/KAP1

Date: 31-07-12 16:28:11

Pages: 16

K. Cantin, A. Lafleur-Lambert, P. Dufour, J.-F. Morin

FULL PAPER

Phenylacetylene Macrocycles

Synthetic efforts towards phenylacetylene

macrocycle based rotaxane precursors are

presented. Macrocycles with different sizes

and functional groups have been prepared

and attached to bulky blockers through a

Sonogashira coupling reaction. Hydrolysis

of the ester groups that bind the macrocy-

cle to the rigid rod was undertaken to as-

sess whether or not the rotaxane precursor

conformation has been obtained.

K. Cantin, A. Lafleur-Lambert, P. Dufour,

J.-F. Morin* .................................... 1–16

Studies Toward the Synthesis of Phenyl-

acetylene Macrocycle Based Rotaxane Pre-

cursors as Building Blocks for Organic

Nanotubes

Keywords: Macrocycles

/

Rotaxanes

/

Cross-coupling

Nanotubes

/ Synthetic methods

16

www.eurjoc.org

Eur. J. Org. Chem. 0000, 0–0

Article Doi

Studies toward the synthesis of phenylacetylene macrocycle based rotaxane precursors as building blocks for organic nanotubes

DOI: 10.1002/ejoc.201200655

Source and publish data:

Authors:

Article abstract of DOI:10.1002/ejoc.201200655

Full text of DOI:10.1002/ejoc.201200655

Products guided by the article

R&D Labs maybe for 1404213-49-5

Relevant to this article

Hot Product