A modular "toolbox" approach to flexible branched multimacrocyclic hosts as precursors for multiply interlocked architectures

DOI: 10.1002/chem.200801289

A Modular “Toolbox” Approach to Flexible Branched Multimacrocyclic

Hosts as Precursors for Multiply ACTHREIUNG nterlocked Architectures

[c]

Bilge Baytekin,^[a]Sascha S. Zhu,^{[a, b]}Boris Brusilowskij,^[a]Jens Illigen,^[a]JenniRanta,

[c]

JuhaniHuuskonen, Luca Russo,^{[c, d]}KariRsisanen,

Lena Kaufmann,^[a]and

Christoph A. Schalley*^[a]

Abstract: Tetralactam macrocycles can

be functionalized by a variety of cross-

coupling reactions. A modular “tool-

box” strategy is presented that allows

1) several tetralactam macrocycles to

be covalently connected with each

other or with a central spacer, 2) the

macrocycles to be substituted with or

connected to different chromophores,

and 3) metal-coordination sites to be

attached to the macrocycles. With this

approach a series of different oligo-

macrocyclic hosts was obtained with

great structural diversity and enormous

potential for further functionalization.

Rotaxanes made on the basis of these

macrocycles have been synthesized to

demonstrate their utility in building

more complex supramolecular architec-

tures.

Keywords: coordinationcomplexes ·

cross-coupling

molecules

·

interlocked

supramolecular

·

chemistry · tetralactam macrocycles

Introduction

quired building blocks to a minimum, without restricting the

structural diversity of the end products. However, biopoly-

mers are not only diverse in structure, but also in function.

The implementation of functions such as catalysis, informa-

tion storage, or cell–cell communication has been realized in

living organisms. However, it requires more than just a mod-

ular approach to structurally diverse architectures. Natureꢀs

approach also makes structures programmable and optimiz-

able. The quite complex scaffolds of, for example, a large

protein allow evolution to optimize by adjusting the struc-

tures gradually in small steps. These great achievements

found in nature are a particularly stimulating source of in-

spiration to many chemists nowadays.

In nature, complex architectures are assembled using a lim-

ited set of well-selected modules, for example, twenty amino

acids, four nucleosides, and a series of monomeric carbohy-

drates, from which a sheer infinite variety of protein struc-

tures, nucleic acids, and linear or branched carbohydrate

oligo- and polymers can be generated. This modular strategy

is highly efficient in that it reduces the number of the re-

[a] B. Baytekin, Dipl.-Chem. S. S. Zhu, Dipl.-Chem. B. Brusilowskij,

Dr. J. Illigen, L. Kaufmann, Prof. Dr. C. A. Schalley

Institut für Chemie und Biochemie

A realization of a similar modular strategy for the genera-

tion of structurally diverse, more complex artificial architec-

tures is still a challenge. In the field of supramolecular

chemistry, the application of this approach requires the

design of modules that need to fulfill the following criteria:

1) The number of building blocks should be limited. 2) They

should be synthetically accessible through inexpensive syn-

theses that provide high yields of the desired building

blocks. 3) Chemistry needs to be identified or developed

with which these units can be easily and flexibly combined

into numerous supramolecular architectures with desired

structures and functions, either through covalent or nonco-

valent bonding. Self-assembly may well be helpful in reduc-

ing the synthetic efforts.^[1]Supramolecular chemists so far

have often followed the strategy to identify a goal, for ex-

Freie Universität Berlin

Takustraße 3, 14195 Berlin (Germany)

Fax : (+49)30-838-55817

E-mail: schalley@chemie.fu-berlin.de

[b] Dipl.-Chem. S. S. Zhu

Present address: KekulØ-Institut für Organische Chemie und Bio-

chemie

Universität Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn (Ger-

many)

[c] J. Ranta, Dr. J. Huuskonen, Dr. L. Russo, Prof. Dr. K. Rissanen

Nanoscience Center, Department of Chemistry

University of Jyväskylä

P. O. Box 35, 40014 Jyväskylä (Finland)

[d] Dr. L. Russo

Present address: School of Natural Sciences—Chemistry

Newcastle University, Newcastle upon Tyne

NE1 7RU (United Kingdom)

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ample, binding a guest molecule by a host through molecu-

lar recognition, followed by the design of a specific molecule

that might fulfill the task. This molecule has then been eval-

uated and has often been found to be less than perfectly

suited. A detailed analysis may then lead to a new design

concept, which requires the synthesis of a new host through,

by and large, a completely new synthetic route. This ap-

proach of finding one individual synthetic pathway for each

target molecule is reasonable and often preferred when the

number of targets is small. The modular route is a more pro-

cess-oriented way of chemical thinking and provides much

higher adaptability if a part of the specific target molecule

design needs to be modified at a later stage. The modular

approach has been explicitly described for various supra-

molecular assemblies, for example, receptors and capsules;^[2]

mechanically interlocked compounds,^[3]such as rotaxanes or

catenanes; metal–porphyrin complexes;^[4]and artificial

double helices.^[5]

As one of the fundamental scaffolds in supramolecular

chemistry, macrocyclic molecules have been widely used not

only for the binding of small guest molecules,^[6]but also for

the fabrication of mechanically interlocked architectures

such as rotaxanes or catenanes.^[7]In recent years, assemblies

consisting of several (at least two) host macrocycles linked

to a single core,^[8]which are shown in Figure 1a,b and which

we decide to simply call “branched multimacrocyclic hosts”,

have attracted increasing interest among supramolecular re-

searchers. The reason for this interest is the versatility of

these hosts which can either interact with mono-^[8a]or multi-

valent^[8e]guests without threading, or contain mono-^[8c–d]or

multivalent^[8b]guests threaded into them. In this contribu-

tion, we focus on hosts that open the gate to multiply me-

chanically interlocked architectures (MIAs). Among these

hosts, we further distinguish flexible branched multimacro-

cyclic hosts (FBMHs), in which each of the bonds between

macrocycle and core can rotate freely, from their rigid coun-

terparts (e.g., triptycene-^[8d]or triphenylene-based plat-

forms^[8b]), in which this rotation mode is disabled. Compared

with the inflexible hosts, FBMHs have the advantage that

1) they can better adapt to the structures of multivalent

guests, 2) they provide more possibilities for self-assembly,

and 3) one single FBMH can serve as precursor for quite

different MIAs (rotaxane-like as well as catenane-like

MIAs), inherently complying with the modular philosophy

of “few modules leading to many targets”.

FBMHs with this precursor function, which are rarely

known as such,^[8b]have not been obtained in great structural

diversity through a modular approach so far. Herein, we de-

scribe the synthesis and characterization of a family of

easily accessible, tetralactam-based FBMHs in which amide

coupling, cross-coupling reactions, and metal templates are

applied to combine the well-selected modules. We demon-

strate that a broad structural variety is accessible, which en-

compasses covalently linked FBMHs as well as some exam-

ples for noncovalently linked analogues that are complexed

to a metal core through rather weak coordinative bonds. On

the other hand, chromophore-centered FBMHs are present-

ed which relate to future functions through their photo-

chemical properties. From some of the macrocyclic precur-

sors, rotaxanes have been made either substituted with a

chromophore or with a metal-binding site. As a proof of

principle, the metal-coordination approach is applied to a

rotaxane.

Results and Discussion

Our FBMHs are based on the well-known Hunter–Vçgtle

tetralactam macrocycle, which was reported by Hunter^[9]

and Vçgtle et al.^[10]Since these macrocycles provide four

converging hydrogen bonds for interaction with guests,^[11]

they have been frequently applied in templated, high-yield

syntheses of mechanically interlocked molecules, such as

(pseudo-)rotaxanes and catenanes.^[12,13]Another advantage

is that tetralactam macrocycles provide high chemical stabil-

ity under many reaction conditions.

We aim to functionalize the macrocycles with a broad se-

lection of different groups. Two pathways can be imagined

(Figure 2): One possibility is to introduce the functional

Figure 1. Generic structures of branched multimacrocyclic hosts that

a) are connected to a common core through single bonds and can thus

freely rotate or b) are rigidified through multiple connection to the core.

c) to e) Examples for oligo-macrocycles that are not connected to a com-

Figure 2. The pre- versus post-macrocyclization pathway used to arrive at

macrocycles with specific ligand functions, for example, the pyridine

moiety (indicated by the dark gray arrow). Note that for the pre-macro-

cyclization pathway, the ligand function is incorporated into the macro-

A

ACHTREcUNG ycle.

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C. A. Schalley et al.

group, for example, the metal-coordinating site mentioned

in Figure 2, before macrocyclization. We call this route the

pre-macrocyclization pathway. In an earlier study,^[14]we re-

ported bisquinoline-bearing macrocycles, catenanes, and ro-

taxanes that were synthesized according to this route. The

alternative is to first perform the macrocyclization step fol-

lowed by attachment of the desired functional group. This

so-called post-macrocyclization pathway^[15]has the advant-

age that functionalization can start from a common macro-

cyclic intermediate. A variety of functional groups can thus

be introduced after the macrocyclization step—an approach

that saves a significant amount of synthetic effort.

On the post-macrocyclization route to our FBMHs, a cru-

cial key step is the connection of the macrocycles to a

common core. To limit the flexibility in these target mole-

cules to the rotation around the macrocycle core bond,

cross-coupling reactions were chosen to realize this key step.

may significantly alter the macrocyclization yields. This

makes the pre-macrocyclization pathway less flexible with

respect to a toolbox approach. Consequently, the pre-macro-

cyclization pathway is quite limited.

Crystal structure of macrocycle 3: X-ray quality crystals of 3

were grown after four weeks at the interface of a biphasic

system comprising a solution of 3 in dichloromethane and

an acidic (pH 4) aqueous solution of K₂PtCl₄. Conformation-

al isomorphism^[16]is observed in the crystal structure: The

unit cell contains one macrocycle in its “all-in” conforma-

tion (3A), in which all four amide protons converge into the

macrocyclic cavity, and two macrocycles as the “two-in-two-

out” conformer 3B, in which the amide protons pointing

into the macrocycle alternate with those pointing out of it

(see arrows in Figure 3a,b). The presence of two different

conformations of the macrocycle in the crystal indicates that

both conformations are energetically not too distant from

each other and can interconvert without being hampered by

a high barrier. This is in excellent agreement with a previous

theoretical study,^[11a]which predicted both features for simi-

lar macrocycles. The reason why both conformers appear in

the solid state presumably lies in crystal packing. In particu-

lar, intermolecular hydrogen bonds connect the macrocycles

and generate an infinite ribbon (Figure 3c,d). In this ribbon,

two macrocycles of 3B connect two molecules in conforma-

tion 3A. The latter macrocycle is disordered in the crystal

with respect to the positions of the pyridine and the tert-

butyl group. Either of the two possible orientations can

Synthesis of a tetralactam macrocycle through the pre-mac-

rocyclization pathway: As illustrated in Scheme 1, the pyri-

dine-containing tetralactam macrocycle 3 is accessible by

ꢀ

occur. The N O distances of the intermolecular N H···O=C

hydrogen bonds are 2.808 and 2.852 . In the crystal struc-

ture, the hydrogen-bonded assembly of one molecule of 3A

and two of 3B serves as a noncovalent “monomer unit” for

the twisted, ribbonlike, hydrogen-bonded polymer, in which

two parallel strands of 3B are interconnected by 3A

Scheme 1. Synthesis of tetralactam macrocycle 3: a) pyridine-3,5-dicar-

bonyl dichloride, NEt₃, CH₂Cl₂, RT, 2 d, 64%; b) 5-tert-butylisophthaloyl

dichloride, pyridine, NEt₃, CH₂Cl₂, high dilution, 408C, 2 d, 41%.

AHCTRE(UGN Figure 3d).

Synthesis of key intermediates and synthesis of macrocyclic

ligands using the post-macrocyclization pathway: To avoid

the above-mentioned potential weaknesses of the pre-mac-

rocyclization pathway, we explored the post-macrocycliza-

tion route to macrocyclic ligands. To be able to make use of

the large potential for cross-coupling reactions, a series of

key intermediates have been prepared that are already

equipped with the functional groups needed for cross-cou-

pling reactions (Scheme 2). From hydroxy-substituted mac-

rocycle 9, triflate 10 can be easily obtained with good yields.

Similarly, iodo- and bromo-substituted analogues 11 and 14

are obtained when extended diamine 6 or 7 is treated under

high-dilution conditions with the corresponding isophthaloyl

dichloride. Two more cross-coupling precursors are available

from the halogenated macrocycles: A Sonogashira cou-

pling^[17]followed by deprotection of the trimethylsilyl group

with potassium hydroxide provides acetylene-substituted 13,

which may serve as a precursor in a second Sonogashira

coupling. Besides this, it can also be employed in Glaser–

Hay coupling reactions^[18](see below) or potentially in Huis-

well-known literature procedures in two steps starting from

Hunterꢀs diamine 1.^[9]The pyridine nitrogen is in an exocy-

clic position and thus can be utilized for metal coordination,

through which several of these macrocycles can finally be

connected (see below). The pyridine is incorporated into the

corresponding building block before macrocyclization. The

advantage of this strategy is that the synthetic route is anal-

ogous to that of other well-known tetralactam macrocycles

and thus benefits from the experience that is available in

the chemical literature. However, the reaction conditions

still need to be significantly modified in the crucial and

yield-determining macrocyclization step due to solubility

problems with the intermediate extended diamine 2. This

optimization is quite time-consuming and such problems are

likely to be encountered when other functional groups are

attached to or incorporated into the building blocks. In our

experience, small structural changes in the building blocks

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Multimacrocyclic Hosts as Precursors for Multiply Interlocked Architectures

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characterized, in accordance

with the principles of modular

approach, by its easy accessibil-

ity, great flexibility, and high

adaptability.

A quick view at the cycliza-

tion yields again reveals them

to be dependent on the sub-

stituent: Whereas 3 and 8 are

obtained in similar yields of 41

and 43%, respectively, the

yields are significantly lower in

the case of halogenated ana-

logues 11 (15%) and 14 (20%).

The sometimes quite drastic ef-

fects might be rationalized not

only by invoking different dis-

tributions of macrocycle and

undesired oligomeric side prod-

ucts. Another major product

usually found in substantial

amounts is the corresponding

catenane. It consists of two

identical

macrocycles

that

become intertwined during the

macrocyclization by a hydro-

gen-bond-mediated

template

effect. This hydrogen-bonding

pattern is rather sensitive to

structural changes in the macro-

cycle structures.^[11]Some of the

catenanes have been isolated

and fully characterized in the

course of the present study.

However, we refrain from de-

scribing them in detail herein,

since unfortunately they turned

out to be rather unreactive in

cross-coupling reactions.

Figure 3. Crystal structure of 3: a) ORTEP plot of all-in conformer 3A (conformer 1). b) ORTEP plot of two-

in-two-out conformer 3B (conformer 2) (both conformers shown with 50% probability ellipsoids). c) Intermo-

lecular hydrogen bonds (dashed) between 3A (black) and 3B (dark gray, gray) (hydrogen atoms omitted for

clarity, except for the amide protons involved in hydrogen bonding). d) Visualization of the infinite molecular

“chain” in the form of a twisted, ribbonlike, hydrogen-bonded polymer (all hydrogen atoms omitted for

ACHTREUNGclarity).

The first Suzuki cross-cou-

pling reactions have been suc-

cessfully

performed

with

gen–Sharpless–Meldal click chemistry^[19](not described

herein). From 14, pinacolato boronate-substituted macrocy-

cle 15 is easily available through Miyaura borylation^[20]and

may, in addition to the two halogenated macrocycles 11 and

14, serve as another key intermediate for Suzuki cross-cou-

pling reactions.^[21]The scope of the cross-coupling reactions

mentioned herein can certainly be extended beyond the

scope of the present study. Just to mention one example,

which has not been explored in our study, boronates such as

15 may also be used in Chan–Lam^[22]couplings. Consequent-

ly, the set of key intermediates 10–15 represents a very ver-

satile and flexible, but at the same time compact, basis for

further functionalization of the tetralactam macrocycles.

This toolkit can be used for a broad spectrum of cross-cou-

pling reactions with a vast range of coupling agents and is

bromo-substituted 14 and the pinacolato boronates of

phenyl terpyridine, pyridine, and pyrimidine as shown in

Scheme 2. This approach turned out to be much more fruit-

ful compared with the second possible variant, that is,

Suzuki cross-coupling of 15 with the corresponding halogen-

ated heterocycles.^[23]The products of these coupling reac-

tions (16–18) all carry heterocycles that can coordinate to

transition-metal ions. This set of molecules can thus be con-

nected to each other through the use of metal ions with

their wide variety of coordination geometries.

Rotaxane synthesis: Scheme 3 shows attempts to synthesize

rotaxanes with ether axles from some of the macrocycles

following the anion-mediated template developed by Vçgtle

et al.^[24]Again, two different routes were explored. To shift

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Scheme 2. Synthesis of key intermediates and macrocyclic ligands: a) NEt₃, CH₂Cl₂, RT, 1 d, 64% (6) or 74% (7); b) 5-acetoxyisophthaloyl dichloride,

NEt₃, CH₂Cl₂, high dilution, RT, 1 d, 43%; c) KOH, dioxane, H₂O, reflux, 8 h, 95%; d) Tf₂O, pyridine, CH₂Cl₂, ꢀ258C, 2 h, 87%; e) 5-iodoisophthaloyl

dichloride, NEt₃, CH₂Cl₂, high dilution, RT, 1 d, 15%; f) trimethylsilyl acetylene, CuI, [PdCl₂ACHTRE(UGN PPh₃)₂], NEt₃, DMF, RT, 15 h, 41%; g) KOH, MeOH/

CH₂Cl₂, RT, 75%; h) 5-tert-butylisophthaloyl dichloride, NEt₃, CH₂Cl₂, high dilution, RT, 1 d, 20%; i) B₂pin₂, [PdCl

82%; j) 4-(2,2’;6’,2’’-terpyridine-4’-yl)phenyl-B(pin), [Pd(PPh₃)₄], Cs₂CO₃, toluene/DMF, 1208C, 2 d, 66%; k) (pyridine-4-yl)B

(pin), [Pd(PPh₃)₄], Cs₂CO₃, toluene/DMF, 1208C, 2 d, 83% (pin=pinacolato, dppf=1,1’-bis(diphe-

(dppf)], KOAc, DMSO, 808C, 6 h,

A

G

A

ACHTREUNG

toluene/DMF, 1208C, 2 d, 83%; l) (pyrimidine-5-yl)B

A

ACHTREUNG

nylphosphino)ferrocene).

the macrocycle functionalization step to as a late state of

the synthesis as possible, we first attempted to generate ro-

taxane 19 from bromo-substituted tetralactam macrocycle

14. Then, rotaxane 19 may serve as a precursor for the at-

tachment of a variety of different functional groups, such as

a pyridine moiety, finally yielding rotaxane 20. This ap-

proach would have another, practical advantage. Some of

the macrocycles cause solubility problems. As soon as the

axle is present, the resulting rotaxanes are usually soluble,

since the interactions of macrocycles with each other in the

crystal are disturbed by the stoppers protruding on both

sides. Consequently, rotaxane 19 would help to circumvent

solubility problems. From the Suzuki coupling of the pinaco-

lato boronate of pyridine with 19, only a disappointingly low

yield of around 6% of rotaxane 20 has been obtained. The

rotaxane can easily be identified by mass spectrometry^[25]as

tropy of the aromatic rings incorporated in the Hunter

diamines.

One of the major side products of this reaction is the free

AHCTREUNG

axle. This finding may help to identify the reason for the

low yield: Since the tritylphenol stoppers efficiently prevent

deslipping of the axle, even at elevated temperatures,^[27]

such a process is certainly not the reason for this finding.

Most likely, the cross-coupling catalyst activates the benzyl

ether bond and causes it to open and close reversibly. Once

it is cleaved, the mechanical bond is released and most of

the rotaxane is thus destroyed.

In the second approach, the order of the two steps is re-

versed. The pyridine is attached first to macrocycle 14 to

give 17 in an acceptable isolated yield of 83%. Rotaxane

synthesis with 17 then provided rotaxane 20 in 82% yield.

Thus, following this approach is by far superior compared

with the first strategy—at least when targeting rotaxanes

with ether axles. These experiments provide some insights

into some limitations that may occur. However, these limita-

1

well as by its H NMR spectrum. Axle protons that are lo-

cated inside the cavity of the macrocycle experience a signif-

icant upfield shift of up to Dd=1.8 ppm^[26]due to the aniso-

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Multimacrocyclic Hosts as Precursors for Multiply Interlocked Architectures

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Scheme 3. Synthesis of pyridyl rotaxane 20 using two different routes:

a) a,a’-dibromo-p-xylene, 4-tritylphenol, dibenzo[18]crown-6, K₂CO₃,

CH₂Cl₂, RT, 7 d, 38%; b) (pyridin-4-yl)B

A

ACHTREUNG

ene/DMF, 1208C, 2 d, 6%; c) (pyridin-4-yl)B

A

ACHTREUNG

toluene/DMF, 1208C, 2 d, 83 %; d) a,a’-dibromo-p-xylene, 4-tritylphenol,

dibenzo[18]crown-6, K₂CO₃, CH₂Cl₂, RT, 7 d, 82% (pin=pinacolato).

tions are not serious, if one considers that the tetralactam

macrocycles can also serve as wheels for rotaxanes with

more stable amide axles,^[13]which can certainly be expected

to survive the conditions of the cross-coupling reactions.

Synthesis of covalently linked, cross-coupled macrocycle

dimers and trimers: In principle, the key intermediates de-

scribed above can be converted into covalently linked

FBMHs in two ways: 1) by coupling two or more macrocy-

cles to a common core or 2) by homo- or heterocoupling of

two or more of the key intermediates directly to each other,

thus simultaneously building the joint core. According to

the first alternative, divalent benzene-centered FBMH 22

(Scheme 4) has been afforded through a standard Suzuki

coupling of bromo-substituted macrocycle 14 with diborylat-

ed benzene 21, a readily available core component. The use

of the brominated macrocycle requires elevated tempera-

tures (ca. 1208C), but the yield of 90% is quite high. In a

similar manner, trivalent benzene-centered FBMH 24 could

be synthesized in a Sonogashira reaction between readily

available triethynylbenzene 23 and iodomacrocycle 11. No

separate core component is required for the Glaser–Hay ho-

mocoupling of two acetylene-substituted macrocycles 13 to

butadiyne-spacered dimer 25. This reaction is an example

for the second pathway described above.

Scheme 4. Synthesis of FBMHs 22, 24, and 25: a) [Pd

ACHTRE(UNG PPh₃)₄], Cs₂CO₃,

toluene, DMF, 1208C, 1 d, 90%; b) CuI, PPh₃, [Pd(PPh₃)₂Cl₂], NEt₃,

AHCTREUNG

DMF, RT, 40 h, 40%; c) CuCl, O₂, DMF, RT, 12 h, 26%; d) Na₂S·

THF, 3 d, 608C (pin=pinacolato).

ACHTREUNG(H₂O)_x,

tant 25 were observed together with product 26 (Scheme 4),

which corresponds to the dominant signal. Such a transfor-

mation induces a change in the geometry of the tether con-

necting the two macrocycles.

These three examples of different coupling reactions, that

is, the Suzuki, the Sonogashira, and the Glaser–Hay reac-

tions, together with the possibility of postfunctionalization

of the butadiyne spacer may suffice to provide evidence for

the utility of our toolbox concept. In the following section,

we now apply the concept to chromophore-substituted mac-

rocycles and metal-coordination.

The butadiyne product itself represents a functional group

that permits further functionalization: In a preliminary ex-

periment, we treated a few mg of 25 with Na₂S^[28]and ana-

lyzed the raw product by mass spectrometry. In a fairly

clean ESI mass spectrum (Figure 4), minor amounts of reac-

Synthesis

of

chromophore-substituted

macrocycles:

Scheme 5 shows the syntheses of chromophore-substituted

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C. A. Schalley et al.

Figure 4. ESI-FTICR mass spectrum of the raw product obtained from

the reaction of 25 with Na₂S·(H₂O)_xyielding thiophene-centered 26.

AHCTREUNG

macrocycles starting with either bromo-substituted macrocy-

cle 14 or borylated analogue 15. All cross-coupling reactions

applied herein are Suzuki reactions. A naphthyl group is

easily coupled in good yields to one of the isophthalic acid

moieties of the macrocycle to provide easy access to 27.

Since pyrene boronic acid is commercially available, we ini-

tially attempted to use triflate-substituted macrocycle 10 to-

gether with pyrene boronic acid in an analogous Suzuki cou-

pling. Indeed, compound 28 could be isolated from that re-

action, but only with a disappointingly low yield of 19%.

Consequently, the procedure that had been successful for

naphthyl-attachment was applied and provided 28 in 87%

yield.

Boron dipyrromethene (BODIPY) dyes are interesting

chromophores because of their easy preparation, narrow ab-

sorption and emission bands, and high quantum yields,

which is of great importance for energy transfer and sensing

processes.^[29]Thus, it seemed attractive to add a BODIPY-

substituted macrocycle to the series of chromophore-substi-

tuted compounds presented herein. Again, a Suzuki cross-

coupling reaction can be used to synthesize aldehyde precur-

sor 30 from which target compound 31 is available in a

three-step one-pot reaction.^[30]The aldehyde is first convert-

ed into the corresponding dipyrromethane by an acid-cata-

lyzed reaction with 2,4-dimethyl pyrrole. The dipyrrome-

thane is oxidized to the dipyrromethene with p-chloranil

without workup of the intermediate. Finally, addition of

BF₃·Et₂O provides the desired product in 62% overall yield.

The last compound in the series of chromophore-substi-

tuted macrocycles (33) has a perylene as the core connecting

two macrocycles. It can be most easily prepared from bory-

lated macrocycle 15 and dibromo perylene 32. The yield of

45% is somewhat lower than that for the other Suzuki reac-

tions described so far and can be attributed to the rather

low solubility of the monosubstituted intermediate.

Scheme 5. Synthesis of chromophore-substituted macrocycles 27, 28, and

31 and FBMH 33. All coupling reactions are performed under standard

Suzuki conditions ([PdACHTER(UNG PPh₃)₄], Cs₂CO₃, toluene, DMF, 1208C, 1 d) and

proceeded in the following yields: a) 76, b) 87, c) 84, and e) 45%.

BODIPY-substituted macrocycle 31 was synthesized from 30 in a one-pot

reaction with d) i) 2,4-dimethyl pyrrole, trifluoro acetic acid (cat.), ii) p-

chloranil, iii) BF₃·Et₂O, 62%.

the visible range are 348 and 548 nm respectively. The

former maximum is not affected when the solvent was

changed from CH₂Cl₂to acetonitrile, whereas the latter

shifts by about 10 nm, which is again expected from the sol-

vatochromic behavior of 1,7-substituted perylene dyes.^[31]

The BODIPY macrocycle has the highest extinction coeffi-

cient (67200m^ꢀ1cm^ꢀ1at 498 nm) with the typical sharp peak

shape.

The UV/Vis spectra for compounds 28, 31, and 33 (shown

in Figure 5) display the typical absorbance patterns of the

photoactive groups in the host macrocycles. The absorbance

of the phenyl rings within the macrocycle body occurs up to

300 nm (the typical range is around 200 nm). In the case of

pyrene and perylene macrocycles, the absorbance maxima in

Self-assembly of macrocyclic ligands to metal-centered

FBMHs—pyridine coordination: Metal-directed self-assem-

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Multimacrocyclic Hosts as Precursors for Multiply Interlocked Architectures

FULL PAPER

Figure 5. UV/Vis spectra of a) pyrene macrocycle 28 (110^ꢀ6m; multi-

plied by 10), b) BODIPY macrocycle 31 (510^ꢀ6m), and c) FBMH 33

(1.610^ꢀ5m) in CH₂Cl₂.

bly is a powerful approach to complex supramolecular struc-

tures with controllable, predefined sizes and geometries.^[32]

It significantly reduces the synthetic effort that would be re-

quired for the generation of a similarly complex covalent

molecule. Other advantages of metal coordination com-

plexes are the variety of coordination geometries available,

the quite large range of accessible binding energies allowing

for weakly bound complexes that form reversible bonds as

well as for kinetically quite inert coordination.

Scheme 6. Self-assembly of 34 and 35²⁺

A

₂ACHTREUNG(PhCN)₂],

Macrocycles 3 and 16–18 have been equipped with differ-

ent metal coordination sites. Two of these ligands, 3 and 17,

carry monodentate pyridine moieties pointing away from

the cavities of the macrocycles. Depending on the choice of

the central metal complex, different number of macrocycles

can be combined in different orientations. In this study, we

have investigated the coordination to different d⁸-metal cen-

CH₂Cl₂, RT, 9 h, 49%; b) [Pd

then cooling, 3 d, 33%.

ACHRTUNEG(MeCN)₄]ACHTRENUG

ters: trans-[PdCl₂], [PdACHTERU(NG MeCN)₄]ACHETR(UNG BF₄)₂, and (dppp)PtAHCRTE(UNG OTf)₂.

These metal centers provide access to quite different com-

plex geometries.

When 3 was reacted with [PdCl₂CAHTRE(UNG PhCN)₂], which has two

trans-oriented coordination sites blocked with chloride, di-

valent Pd-centered FBMH 34 precipitated as a pale-yellow

solid (Scheme 6). Analogously, FBMH 36 (Scheme 7) was

obtained from macrocyclic ligand 17, which has a peripheral

pyridine attached to one of the isophthalic acid moieties.

Furthermore, tetravalent Pd-centered FBMH 35²⁺was af-

forded as the tetrafluoroborate salt upon addition of [Pd-

A

ACHTREUNG

of metallosupramolecular squares,^[33]we were able to obtain

divalent Pt-centered FBMH 37²⁺in which the macrocyclic

parts are almost perpendicular to each other. Since the pyri-

dine rings prefer to coordinate to the metal in an orientation

almost perpendicular to the plane defined by the four donor

atoms around the metal center, compounds 3 and 17 result

in different orientations of the macrocycles in the complex.

In 35²⁺, for example, the four macrocycles are likely to form

a propeller-shaped arrangement with the cavities opening

towards the neighbors. The analogous complex prepared

Scheme 7. Self-assembly of 36 and 37²⁺

CH₂Cl₂, RT, 16 h, then 408C, 1 h, 44%; b) (dppp)PtAHCTREUNG

quantitative (dppp=1,3-bis(diphenylphosphino)propane).

A

₂ACHTREUNG(PhCN)₂],

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10019

C. A. Schalley et al.

from 17 would result in an arrangement in which the pyri-

dines obtain their preferred perpendicular orientation,

whereas due to the aryl-aryl bond the macrocycles are in a

more or less flat arrangement with their cavities opening to

above and below the complex. Due to the larger macrocy-

cle–metal distance, the rings are likely to be able to rotate

without substantial rotation barriers caused by steric conges-

tion.

The formation of metal-centered FBMHs is confirmed by

ESIMS spectra and ¹H NMR spectra, in which the ortho-

pyridine protons show downfield shifts due to metal coordi-

nation. The (dppp)Pt^IIcorner in 37²⁺has the particular ad-

rocycles are arranged in the “all-in” conformation, which in-

dicates that 34 is a suitable host for the formation of multi-

ply interlocked architectures (MIAs). A highly interesting

feature of the crystal packing is the existence of infinite

channels passing through the macrocyclic cavities (Fig-

ure 6b). The channels, which are filled with quite disordered

solvent molecules in the crystal, might be an interesting

structural element for applications going beyond the use for

MIA formation.

Synthesis and molecular modeling of MIA 40: As a proof-

of-principle for the formation of multiply interlocked archi-

tectures through metal coordination, rotaxane 39 has been

synthesized and subsequently coordinated to a trans-[PdCl₂]

center (Scheme 8). The rotaxane can be easily made through

our previously published anion-template procedure.^[12c]Axle

centerpiece 38 is deprotonated at the phenolic hydroxy

group. The anion can—supported by one of the carbonyl

groups—then form rather strong hydrogen bonds with tetra-

lactam macrocycle 3. The axle centerpiece is fixed inside the

wheel in an orientation that ensures that triphenyl acetyl

stoppers are attached to the two amino groups from oppo-

site sides of the macrocycle. The axle is thus trapped in the

cavity; a rotaxane forms. The mechanically interlocked

structure of the rotaxane can be identified from strong up-

ꢀ

vantage that the Pt P coupling constants are very sensitive

to the coordination of the two pyridines. The coupling con-

1

stant in 37²⁺is J

A

ACHTRE(UNG Pt,P)=

AHCTREUNG

Crystal structure of metal-centered FBMH 34:^[34]When 34

was dissolved in approximately a 2:1:1 mixture of 1,4-diox-

ane, dichloromethane, and methanol and the solution was

left to stand in a parafilm-closed test-tube for two months,

pale-brown needlelike single-crystals of 34 were obtained.

According to X-ray crystal structure analysis, two molecules

of 3 are bound to the Pd center through their pyridine moi-

eties, forming the expected square-planar trans-Pd-complex

(Figure 6a). Since each corner of the unit cell, which is the

1

field shifts of the H NMR signals of those protons that are

located in the macrocycle cavity. For 39, the methylene

spacers between the stoppers and the central phenol are af-

¯

crystallographic inversion center in the P1 space group, is

occupied by a Pd atom, compound 34 is a perfectly centro-

symmetric molecule in the solid state. Compared with the

crystal structure of 3, the striking difference is that all mac-

Figure 6. Crystal structure of 34 (solvent molecules are omitted for clari-

ty): a) ORTEP plot (shown with 50% probability ellipsoids). b) Crystal

packing, space-filling view along the diagonal between the crystallograph-

ic a and c axes, showing the infinite channels.

Scheme 8. Synthesis of rotaxane 39 and assembly of MIA 40: a) tert-

butylACHTREUiNG mino-tris(dimethylamino)phosphorane (P₁base), NEt₃, triphenyl-

acetyl chloride, CH₂Cl₂, RT, 3 d, 14%; b) PdCl

then cooling, 7 d, 11%.

₂ACHTRE(UGN PhCN)₂, CH₂Cl₂, RT, 1 d,

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Multimacrocyclic Hosts as Precursors for Multiply Interlocked Architectures

FULL PAPER

fected most (Dd=0.9–1.0 ppm; see analytical data below).

The threaded topology can be also determined from tandem

MS experiments. In these experiments, fragmentations are

induced by collisions of the mass-selected rotaxane ions

with a collision gas (Ar) in an FTICR mass spectrometer.

Mass-selected 39 was thus subjected to this experiment. The

same experiment was then conducted under exactly the

same conditions with a 1:1 mixture of macrocycle 3 and the

free, stoppered axle. During ionization these two compo-

nents form a non-interlocked, hydrogen-bonded complex

with the same m/z value as 39. The two MS/MS spectra

differ much: The MS/MS spectrum of 39 still shows the ro-

taxane ion as the base peak, whereas the free axle appears

as a fragment with around 30% relative intensity accompa-

nied by axle fragments. In the same experiment conducted

with the hydrogen-bonded complex, all parent ions have dis-

sociated and the free axle is the only fragment visible. This

indicates that it is energetically much easier to dissociate the

hydrogen-bonded complex than to fragment the rotaxane, in

which a covalent bond needs to be broken to release the

mechanical bond. We have reported similar experiments on

an analogous rotaxane before with a similar outcome.^[12c,25]

Consequently, the rotaxane has unambiguously formed.

Subsequently, compound 39 was treated with [PdCl₂-

Figure 7. ESI-FTICR-MS spectrum of MIA 40.

ACHTREUNG(PhCN)₂] to give MIA 40 through metal-directed self-assem-

bly. In the ESI-FTICR mass spectrum of 40, the only intense

ion observed is the sodium adduct of 40, which shows the

fairly high stability of this rotaxane dimer (Figure 7). The

characteristic isotope pattern confirms the presence of the

PdCl₂unit. Compared to 39, a downfield shift of the ortho-

Figure 8. Space-filling representation of one example out of many possi-

ble low-energy conformations of MIA 40 calculated at the MM2 level

(dark gray: FBMH part of the MIA, black and light gray: axle compo-

nents).

1

pyridine protons was found in the H NMR spectrum of 40.

To obtain at least a rough idea of the structure of 40, molec-

ular modeling calculations were

performed with the augmented

MM2 force field implemented

in the CAChe 5.0 program.^[35]

Figure 8 shows one example out

of many possible low-energy

conformations of 40.

Self-assembly of macrocyclic li-

gands

to

metal-centered

FBMHs–terpyridine coordina-

tion: From terpyridine-substi-

tuted macrocycle 16, rotaxane

41 (Scheme 9) was synthesized

by the same procedure as that

used for 19. Again, rotaxane

synthesis was successful if car-

ried out after cross-coupling the

terpyridine moiety to bromo-

macrocycle 14. Figure 9 (top)

shows the aromatic region of

the ¹H NMR spectrum of 41.

The threaded topology of the

rotaxane can easily be deter-

mined from the unusual upfield Scheme 9. Synthesis of the dimeric Zn^II-complex 42²⁺of rotaxane 41. a) Zn

ACHTRE(UNG ClO₄)₂·6H₂O, CDCl₃, RT, quant.

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10021

C. A. Schalley et al.

macrocycle reacted in coupling reactions, however, with

unsatisfactory yields. This variety of different reactions

increases the range of accessible structures drastically.

3) Although only shown for one example, some of the

cross-coupling products can be converted into different

functional groups after the cross-coupling reaction, again

providing access to different geometries.

4) Rotaxanes can be made from almost all macrocycles re-

ported in this study—maybe with the exception of the

borylated macrocycle 15, which we did not test in the

threading reaction. As a proof of principle, we synthe-

sized two types of rotaxanes, one of which has benzyl

ether axles, the other one an amide axle. The benzyl

ethers do not survive a Suzuki coupling due to the Lewis

acidity of the catalyst. This finding points to a limitation

of our approach that, however, can be circumvented by

the use of other, more stable axles.

Figure 9. Top: Partial ¹H NMR spectrum of the rotaxane 41 synthesized

from terpyridine-substituted macrocycle 16. The unusual upfield shifts of

protons a, b, and c of the axle centerpiece indicate rotaxane formation.

Bottom: Partial ¹H NMR spectrum of dimeric Zn^II-complex 42²⁺of this

rotaxane. The appearance of one set of sharp signals at positions shifted

relative to those observed for the rotaxane indicates quantitative com-

plex formation.

5) The formation of metal complexes has been demonstrat-

ed up to a tetravalent complex of the pyridine macrocy-

cle. These studies also include metal-bridged rotaxane

dimers.

shifts of the protons located at the axle centerpiece (labeled

a, b, and c). They experience the anisotropy of the macrocy-

cleꢀs aromatic rings. In comparison to the signals of the free

axle, proton a shifts by around 1.7 ppm to higher field.

When half an equivalent of zinc perchlorate is added to

The present toolbox approach to macrocyclic and inter-

locked molecules is thus extremely versatile in several dif-

ferent aspects and opens a new playground for supramolec-

ular synthesis that can rely on a large set of different struc-

tures accessible from our five key intermediates. The syn-

thetic approach is a convergent one, since more complex

substituents that are to be coupled to the macrocycles can

be prepared independently from the macrocycle synthesis

and then coupled to it afterwards.

1

the solution of rotaxane 41, a H NMR spectrum is obtained

that contains only one set of well-resolved signals and thus

indicates that only one complex, that is, the Zn^II-bridged

dimer of the rotaxane, is almost quantitatively formed. Most

of the signals in the aromatic region are shifted to some

extent upon complexation of the rotaxane to the metal ion.

Conclusion

Experimental Section

In this study, we have developed a toolbox of building

blocks on the basis of tetralactam macrocycles for the supra-

molecular assembly of more complex, multiply interlocked

architectures. We can draw the following conclusions:

General methods: Reagents were purchased from Aldrich, ACROS, or

Fluka and used without further purification. Hunterꢀs diamine 1,^[9,12a]ex-

tended diamines 6 and 7,^[9,12a]4-(2,2’;6’,2’’-terpyridine-4’-yl)phenylboronic

acid pinacol ester,^[23]and perylene 32^[36]were synthesized according to lit-

erature procedures. All acid chlorides were obtained from the corre-

sponding isophthalic acids by reaction with SOCl₂.^[37]The only exception

was 5-iodoisophthaloyl dichloride, which was synthesized in two steps

from 5-aminoisophthalic acid. First, the amino group is converted into

the iodine substituent by a Schiemann reaction,^[38]then the 5-iodoisoph-

thalic acid is converted into the acid chloride with oxalyl chloride.^[39]

CH₂Cl₂, MeOH, EtOAc, and toluene were dried and distilled prior to use

by usual laboratory methods, whereas all other solvents were used from

commercial sources.

1) A quite limited set of five key intermediates, that is,

macrocycles with substituents suitable for cross-coupling

reactions, serves as the basis for quite different purposes.

Simple organic spacers can be used to connect several

macrocycles around a common core to provide access to

multivalent host molecules. Photoactive groups can be

attached and may have potential for future energy-trans-

fer studies. Metal-binding sites are easily coupled to the

macrocycles, which can then coordinate to a metal center

serving as a noncovalent core. Consequently, a large vari-

ety of different structures is now available based on the

small set of key intermediates.

2) Different key intermediates open the opportunity to use

almost any kind of cross-coupling reaction. Iodinated,

brominated, and borylated macrocycles have proven to

be excellent precursors for Suzuki cross-coupling reac-

tions. Iodinated and ethynyl derivatives can be utilized in

Glaser–Hay or Sonogashira reactions. Even the tosylated

Thin-layer chromatography (TLC) was performed on precoated silica gel

60/F₂₅₄plates (Merck KGaA). Silica gel (0.04–0.063, 0.63–0.100 mm;

Merck) and Al₂O₃(neutral; Riedel de Han) were used for column chro-

matography.

¹H, ¹³C, and ³¹P NMR spectra were recorded with Bruker ECX 400, DPX

400, DRX 500, or Jeol Eclipse 500 instruments. All chemical shifts are re-

ported in ppm with solvent signals taken as internal standards; coupling

constants are in Hertz. Mass spectra were recorded with a Varian/Ion-

Spec QFT-7 FTICR mass spectrometer equipped with a micromass Z-

spray ESI ion source, a Micromass Q-TOF2 mass spectrometer equipped

with a Z geometry nanospray ion source, or a Bruker APEX IV Fourier-

transform ion-cyclotron-resonance (FT-ICR) mass spectrometer with an

Apollo ESI ion source equipped with an off-axis 708 spray needle.

10022

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Multimacrocyclic Hosts as Precursors for Multiply Interlocked Architectures

FULL PAPER

Elemental analyses of the macrocyclic compounds reported herein

almost always fail due to solvent molecules that are encapsulated inside

the cavities of the macrocycles. These solvents cannot be removed by

high vacuum, not even when the substances are heated. They appear in

the NMR spectra and are also visible in the crystal structures with some

disorder. Therefore, elemental compositions were assessed by isotope

pattern analysis of the corresponding ions observed in the mass spectra

and/or by exact mass measurements.

26 mmol). The mixture was heated at reflux for 8 h. The solvents were re-

moved in vacuo and the remaining solid was suspended in water (2 mL).

The free acid was generated by dropwise addition of concd HCl. The

product was collected by filtration and washed several times with water

(1.04 g, 90%). ¹H NMR (300 MHz, CDCl₃): d=1.34 (s, 9H; C

ACHTREUNG(CH₃)₃),

1.46 (br, 4H; CH₂), 1.57 (br, 8H; CH₂), 2.09 (s, 12H; CH₃), 2.10 (s, 12H;

CH₃), 2.26 (br, 8H; CH₂), 6.92 (br, 8H; ArH), 7.44 (s, 2H; ArH), 7.50 (s,

1H; ArH), 7.73 (s, 1H; ArH), 8.11 ppm (s, 2H; ArH); ¹³C NMR

(75 MHz, CDCl₃): d=19.6, 24.3, 27.7, 32.2, 36.5, 36.8, 46.5, 119.1, 119.4,

125.4, 126.4, 127.7, 132.7, 132.8, 135.6, 136.42, 136.43, 137.3, 149.5, 149.6,

154.8, 160.0, 168.5, 168.7 ppm; ESIMS: m/z (%): 978 (6) [M+H]⁺, 1000

(100) [M+Na]⁺, 1016 (18) [M+K]⁺, 1977 (16) [M+Na⁺].

The following abbreviations are used: Ar=aryl, Cy=cyclohexyl, dppf=

1,1’-bis(diphenylphosphino)ferrocene, dppp=1,3-bis(diphenylphosphino)-

propane, isophth=isophthalamide moiety, naph=naphthyl, pin=pinaco-

lato, py=pyridyl, pyr=pyrimidyl, tpy=2,2’;6’2’’-terpyridyl.

Extended diamine 2: At room temperature, a solution of pyridine-3,5-di-

carbonyl dichloride (1.0 g, 5.0 mmol) in CH₂Cl₂(150 mL) was slowly

added over 5 h to a solution of 1 (10.2 g, 31.6 mmol) in CH₂Cl₂(50 mL)

and NEt₃(2 mL). The mixture was left stirring at room temperature for

48 h. The solvents were then evaporated and the product was isolated by

column chromatography (silica gel, elution with a (1:2) CH₂Cl₂/EtOAc

mixture) as a white solid (2.5 g, 64%). R_f=0.4; ¹H NMR (400 MHz,

CDCl₃): d=1.43–1.53 (m, 20H; CH₂), 2.13–2.16 (m, 24H; CH₃), 6.83 (s,

4H; ArH), 6.99 (s, 4H; ArH), 7.57 (s, 2H; NH), 8.70–8.71 (m, 1H;

ArH(py)), 9.17 ppm (d, J=2.0 Hz, 1H; ArH(py)); ¹³C NMR (100 MHz,

CDCl₃): d=18.2, 19.0, 23.2, 26.7, 37.4, 45.2, 121.7, 127.3, 127.4, 130.4,

130.6, 134.3, 134.8, 137.7, 140.4, 149.5, 150.9, 163.4 ppm; ESIMS: m/z

(%): 776 (100) [M+H]⁺, 798 (49) [M+Na]⁺; HRMS (ESI^ꢀ): m/z calcd

for C₅₁H₆₀N₅O₂^ꢀ: 774.4752 [MꢀH]^ꢀ; found: 774.4792.

Macrocycle 10: A solution of 9 (1,15 g; 1,18 mmol) in CH₂Cl₂(20 mL)

and pyridine (30 mL) was cooled to ꢀ308C. Trifluoromethanesulfonic

acid anhydride (0.78 mL) was added dropwise over 1 h taking care that

the temperature does not exceed ꢀ258C. After the mixture was then

stirred for 5 h at 08C, it was poured into ice (100 mL). The aqueous

phase was extracted two times with toluene and the combined organic

phases were washed with water, dried over MgSO₄, and evaporated in

vacuo. The solid was purified by column chromatography (silica gel, elu-

tion with a (8:1) CH₂Cl₂/EtOAc mixture) to give 10 as a beige solid

(275 mg, 21%). R_f=0.50; ¹H NMR (400 MHz, CDCl₃/CD₃OD): d=1.26

(s, 9H; CCATHER(UGN CH₃)₃), 1.36 (br, 4H; CH₂), 1.49 (br, 8H; CH₂), 2.01 (s, 24H;

CH₃), 2.17 (br, 8H; CH₂), 6.82 (s, 4H; ArH), 6.83 (s, 4H; ArH), 7.91 (s,

2H; 4,6-OTf-isophthH), 7.99 (s, 1H; 2-OTf-isophthH), 8.02 (s, 2H; 4,6-t-

Bu-isophthH), 8.30 ppm (s, 1H; 2-t-Bu-isophthH); ¹³C NMR (100 MHz,

CDCl₃/CD₃OD): d=18.11, 18.12, 22.6, 26.0, 30.7, 35.0, 44.9, 60.3, 116.8,

123.7, 123.8, 126.0, 126.3, 126.4, 128.1, 130.7, 131.1, 133.9, 134.72, 134.73,

136.8, 147.7, 148.0, 148.1, 149.9, 153.2, 164.1, 166.8 ppm; ESIMS: m/z

Macrocycle 3: A suspension that was obtained from adding 2 (2.44 g,

3.1 mmol) to a solvent mixture of CH₂Cl₂(500 mL), pyridine (10 mL),

and NEt₃(0.3 mL) was stirred in an ultrasonic bath for 1 h to afford a

clear, light green solution. This solution and a solution of 5-tert-butyl-

(%): 1110 (51) [M+H]⁺, 1131 (100) [M+Na]⁺, 1147 (5) [M+K]⁺; HRMS

+

(ESI^ꢀ): m/z calcd for C₆₅H₇₂F₃N₄O₇S₁

:

1109.507 [M+H]⁺; found:

ACHTREUNGisophthaloyl dichloride (0.77 g, 3.0 mmol) were simultaneously added

over 24 h to a flask containing CH₂Cl₂(2000 mL) heated at reflux by

using an automatic solvent pump. The reaction mixture was heated at

reflux for another 24 h. The solvents were then evaporated and the resi-

due was purified by column chromatography (silica gel, eluting with a

50:50:3 mixture of CH₂Cl₂/EtOAc/pyridine). The solid obtained from the

purification was redissolved in toluene and the solvent was evaporated;

this was done two more times. The product was again purified by column

chromatography (silica gel, elution with a (14:2:1) CH₂Cl₂/EtOAc/MeOH

mixture) to afford 3 as a white solid (0.93 g, 31%). R_f=0.54 (CH₂Cl₂/

EtOAc/MeOH 14:2:1); ¹H NMR (400 MHz, CDCl₃/CD₃OD (5:1)): d=

1109.503.

Macrocycle 11:

A solution of 5-iodoisophthaloyl dichloride (0.33 g,

1 mmol) in dry CH₂Cl₂(250 mL) and a mixture of 7 (0.83 g, 1 mmol) and

triethylamine (2 mL) in dry CH₂Cl₂(250 mL) were simultaneously added

dropwise to dry CH₂Cl₂(1200 mL) from separate dropping funnels, while

the system was kept under argon atmosphere. The addition was complet-

ed after 8 h and the solution was stirred at room temperature for another

72 h. The solvents were evaporated under reduced pressure. The residue

was purified by column chromatography (silica gel, eluting with a (6:1)

CH₂Cl₂/EtOAC mixture) to give 11 as a white solid (0.12 g, 11%).

1.24 (s, 9H; CACHTREUNG(CH₃)₃), 1.34–1.35 (br, 4H; CH₂), 1.47 (br, 8H; CH₂), 2.00

¹H NMR (500 MHz, CDCl₃): d=1.36 (s, 9H; C

ACHTRE(UNG CH₃)₃), 1.40–1.50 (br,

(s, 24H; ArCH₃), 2.16 (br, 8H; CH₂), 6.82 (s, 8H; ArH), 7.97 (br, 1H;

ArH), 8.01 (d, J=1.4 Hz, 2H; ArH), 8.74 (br, 1H; ArH(py)), 9.07 ppm

(d, J=1.9 Hz, 2H; ArH(py)); ¹³C NMR (100 MHz, CDCl₃/CD₃OD

(5:1)): d=18.3, 22.8, 26.2, 30.9, 35.0, 35.1, 45.0, 123.8, 126.1, 126.2, 128.3,

130.67, 130.73, 131.3, 134.0, 134.7, 134.9, 137.0, 147.8, 148.2, 149.5, 153.2,

163.6, 166.9 ppm; ESIMS: m/z (%): 960 (100) [MꢀH]^ꢀ; HRMS (ESI^ꢀ):

m/z calcd for C₆₃H₇₀N₅O₄^ꢀ: 960.5433 [MꢀH]^ꢀ; found: 960.5396.

4H; CH₂) 1.51–1.63 (br, 8H; CH₂), 2.08–2.11 (br, 24H; ArCH₃), 2.27 (br,

8H; CH₂), 6.92 (s, 8H; ArH), 8.03 (s, 1H; 2-t-Bu-isophthH), 8.12 (s, 2H;

4,6-I-isophthH), 8.20 (s, H; 2-I-isophthH), 8.41 ppm (s, 2H; 4,6-t-Bu

-isophthH); ¹³C NMR (125 MHz, CDCl₃): d=19.0, 23.0, 26.4, 31.3, 35.0,

45.2, 95.5, 122.9, 126.4, 128.5, 130.8, 131.1, 134.7, 135.4, 136.4, 139.9,

148.0, 148.3, 153.9, 163.9 ppm; ESIMS: m/z (%): 1087 (40) [M+H]⁺,

1109 (100) [M+Na]⁺; HRMS (ESI⁺): m/z calcd for C₆₄H₇₁IN₄O₄Na⁺:

1109.4412 [M+Na]⁺; found: 1109.4221.

Macrocycle 8:

A solution of 5-acetoxyisophthaloyl dichloride (0.8 g,

3.1 mmol) in dry CH₂Cl₂(250 mL) and a mixture of 6 (2.6 g, 3.1 mmol)

and triethylamine (1 mL) in dry CH₂Cl₂(250 mL) were simultaneously

added dropwise to dry CH₂Cl₂(1000 mL) from separate dropping fun-

nels, while the system was kept under argon atmosphere. The addition

was completed after 8 h, and the solution was stirred at room tempera-

ture for another 12 h. The solvents were evaporated under reduced pres-

sure. The residue was subjected to column chromatography (silica gel,

eluting with a (6:1) CH₂Cl₂/EtOAc mixture) to obtain 8 as a white prod-

uct (1.4 g, 43%). R_f=0.40; ¹H NMR (400 MHz, CDCl₃): d=1.40 (s, 9H;

Macrocycle 12: Macrocycle 11 (0.05 g, 0.046 mmol), [PdCl₂ACHTREUNG(PPh₃)₂]

(0.0064 g, 0.001 mmol) and CuI (0.0017 g, 0.001 mmol) were dissolved in

dry DMF (5 mL) under an argon atmosphere. After the addition of tri-

AHCTREeUNG thylamine (5 mL), trimethylsilyl acetylene (20 mL 0.14 mmol) was added

dropwise to the reaction mixture. After stirring for 15 h under an argon

atmosphere at room temperature the solvent was evaporated under re-

duced pressure. The residue was purified by column chromatography

(silica gel, eluting with a (15:1) CH₂Cl₂/EtOAc mixture) to give 12 as a

white solid (0.018 g, 41%). ¹H NMR (400 MHz, CDCl₃): d=0.26 (s, 9H;

CACHTREUNG(CH₃)₃), 1.52 (br, 4H; CH₂), 1.65 (br, 8H; CH₂), 2.05 (br, 3H; CH₃),

2.17 (br, 24H; CH₃), 2.33 (br, 8H; CH₂), 6.96 (br, 8H; ArH), 7.56 (br,

4H; NH), 7.87 (s, 2H; ArH), 8.04 (s, 1H; ArH), 8.12 (s, 1H; ArH),

8.19 ppm (s, 2H; ArH); ¹³C NMR (100 MHz, CDCl₃): d=18.91, 18.92,

20.9, 22.9, 26.3, 31.2, 35.3, 45.1, 59.3, 122.8, 122.9, 124.8, 126.4, 126.5,

128.6, 130.8, 131.1, 134.7, 134.7, 136.4, 147.4, 148.1, 148.1, 151.9, 153.9,

164.2, 165.7, 171.3 ppm; ESIMS: m/z: 1020 [M+H]⁺.

SiCACHTER(UNG CH₃)₃), 1.42 (s, 9H; CACHTRE(UGN CH₃)₃), 1.52–1.55 (br, 4H; CH₂), 1.62–1.65

(br, 8H; CH₂), 2.15–2.18 (br, 24H; ArCH₃), 2.30–2.32 (br, 8H; CH₂),

6.98 (br, 8H; ArH), 7.57 (br, 2H; 4,6-t-Bu-isophthH), 7.64 (br, 2H; 4,6-

acetylene-isophthH), 7.75 (s, H; 2-t-Bu-isophthH), 8.08 ppm (s, H; 2-acet-

ylene-isophthH); ¹³C NMR (125 MHz, CDCl₃): d=ꢀ0.1, 19.1, 23.0, 26.4,

31.3, 35.4, 45.2, 97.5, 103.0, 122.9, 126.4, 128.7, 131.1, 131.3, 134.2, 134.8,

135.1, 148.1, 148.2, 153.9, 165.9 ppm; ESIMS: m/z (%): 1057 (100)

[M+H]⁺, 1079 (90) [M+Na]⁺.

Macrocycle 9: Macrocycle 8 (1.20 g, 1.18 mmol) was dissolved in a diox-

ane (30 mL)/water (20 mL) mixture together with KOH (1.46 g,

Chem. Eur. J. 2008, 14, 10012 – 10028

ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

10023

C. A. Schalley et al.

Macrocycle 13: Macrocycle 12 (0.02 g, 0.019 mmol) was dissolved in a 1:1

mixture of CH₂Cl₂/CH₃OH. KOH (0.005 g, 0.095 mmol) was added and

the reaction mixture was stirred at room temperature for 12 h. Half of

the solvent was evaporated under reduced pressure and the remaining or-

ganic phase was washed three times with H₂O. The organic phases were

collected, dried over MgSO₄, and the solvent was evaporated under re-

duced pressure. Macrocycle 13 was obtained as a yellowish-white solid

7.24–7.28 (m, 2H; ArH(5,5’’-tpy)), 7.74 (d, J=8.3 Hz, 2H; ArH), 7.76–

7.81 (m, 2H; ArH(4,4’’-tpy)), 7.91 (d, J=8.3 Hz, 2H; ArH), 8.09 (s, 2H;

4,6-t-Bu isophthH), 8.13 (s, 1H; 2-t-Bu isophthH), 8.17 (s, 2H; 4,6-

isophthH), 8.37 (s, 1H; 2-isophthH), 8.43 (s, 4H; NH), 8.54 (d, J=8 Hz ,

2H; ArH(3,3’’-tpy)), 8.64 (d, J=4.6 Hz, 2H; ArH(6,6’’-tpy)), 8.71 ppm (s,

2H; ArH(3’,5’-tpy)); ¹³C NMR (100 MHz, CDCl₃/CD₃OD (4:1)): d=

18.6, 22.9, 26.3, 31.1, 35.2, 36.6, 45.2, 118.8, 121.9, 123.7, 124.2, 126.2,

127.7, 127.9, 128.5, 128.6, 128.7, 129.5, 130.9, 131.4, 131.5, 131.9, 132.0,

132.3, 134.2, 135.0, 135.2, 137.4, 138.0, 140.0, 142.1, 148.0, 148.1, 148.9,

149.7, 153.4, 155.9, 156.0, 163.1, 166.4, 166.8 ppm; ESIMS: m/z (%): 1268

(100) [M+H]⁺.

(0.014 g, 75%). ¹H NMR (400 MHz, CDCl₃): d=1.42 (s, 9H; C

ACHTRE(UNG CH₃)₃),

1.52–1.55 (br, 4H; CH₃), 1.62–1.66 (br, 8H; CH₂), 2.16–2.18 (br, 24H;

ArCH₃), 2.30–2.32 (br, 8H; CH₂), 6.97 (br, 8H; ArH), 7.34 (br, 2H; 4,6-

t-Bu-isophthH), 7.43 (br, 3H; 4,6-acetylene-isophthH, 2-t-Bu-isophthH),

7.99 ppm (s, H; 2-acetylene-isophthH); ¹³C NMR (125 MHz, CDCl₃): d=

19.0, 23.0, 26.5, 31.3, 35.4, 45.2, 79.9, 81.7, 122.9, 126.6, 128.6, 130.9, 131.1,

134.4, 134.7, 135.4, 148.1, 148.3, 154.0, 165.7 ppm; ESIMS: m/z (%): 985

(15) [M+H]⁺, 1007 (100) [M+Na]⁺; HRMS (ESI⁺): m/z calcd for

C₆₆H₇₂N₄NaO₄⁺: 1007.5446 [M+Na]⁺; found: 1007.5360.

Macrocycle 17: Pyridine-4-boronic acid pinacol ester (0.025 g,

0.120 mmol) was poured into a mixture of 14 (0.1 g, 0.096 mmol), [Pd-

AHCTRE(UGN PPh₃)₄] (0.0035 g, 0.003 mmol), and Cs₂CO₃(0.047 g, 0.144 mmol) in dry

toluene (10 mL) and dry DMF (10 mL). The temperature was raised to

1008C whilst argon was bubbled through the solution and then it was

heated at 120–1308C for 2 d under argon before the solvents were re-

moved at reduced pressure. The residue was purified by column chroma-

tography (silica gel, eluting with a 95:5 mixture of CH₂Cl₂/CH₃OH) to

give 10 as a white solid (82 mg, 83.4%). ¹H NMR (400 MHz, [D₇]DMF):

Macrocycle 14: A solution of 5-tert-butyl isophthaloyl dichloride (0.26 g,

1 mmol) in dry CH₂Cl₂(250 mL) and a mixture of 7 (0.85 g, 1 mmol) and

NEt₃(2 mL) were simultaneously added dropwise to dry CH₂Cl₂

(1200 mL) over 8 h by using an automatic solvent pump, while the

system was kept under an argon atmosphere. The cloudy solution was

stirred at room temperature overnight. The solvents were then evaporat-

ed and the product was isolated by column chromatography (silica gel,

eluting with a (15:1!6:1) CH₂Cl₂/EtOAc mixture) as a white solid

(0.21 g, 20%). ¹H NMR (500 MHz, CDCl₃/CD₃OD (5:1)): d=1.33 (s,

d=1.41 (s, 9H; CACHTRE(UGN CH₃)₃), 1.52–1.54 (br, 4H; CH₂), 1.62–1.64 (br, 8H;

CH₂), 2.18 (s, 12H; ArCH₃), 2.20 (s, 12H; ArCH₃), 2.47 (br, 8H; CH₂),

7.23 (s, 8H; ArH), 7.87 (d, J=6.1 Hz, 2H; ArH(py)), 8.21 (s, 2H; 4,6-t-

Bu-isophthH), 8.49 (s, 2H; 4,6-py isophthH), 8.77 (s, H; 2-t-Bu-

isophthH), 8.78 (d, J=6.1 Hz, 2H; ArH(py)), 8.92 (s, H; 2-py-isophthH),

9.30 (s, 2H; NH), 9.47 ppm (s, 2H; NH); ¹³C NMR (CDCl₃): d=18.9,

19.0, 22.9, 24.7, 26.4, 31.1, 31.3, 35.4, 36.5, 45.2, 121.7, 126.5, 128.5, 129.9,

131.2, 134.7, 134.9, 135.7, 150.3, 162.6, 164.7 ppm; ESIMS: m/z (%): 1038

(100) [M+H]⁺.

9H; CACHTREUNG(CH₃)₃), 1.43–1.44 (br, 4H; CH₂), 1.55–1.56 (br, 8H; CH₂), 2.08–

2.10 (br, 24H; ArCH₃), 2.24 (br, 8H; CH₂), 6.90 (s, 8H; ArH), 8.07 (s, H;

2-t-Bu-isophthH), 8.10 (s, 2H; 4,6-Br-isophthH), 8.19 (s, 2H; 4,6-t-Bu-

isophthH), 8.21 (s, H; 2-Br-isophthH), 8.65 (s, 2H; NH), 8.86 ppm (s, 2H;

NH); ¹³C NMR (125 MHz, CDCl₃/CD₃OD (5:1)): d=18.5, 31.1, 22.9,

26.4, 35.0, 45.1, 123.6, 126.0, 128.3, 131.2, 131.5, 133.9, 134.4, 135.3, 135.4,

136.1, 148.0, 148.2, 153.3, 164.9 ppm; ESIMS: m/z (%): 1041.5 (6)

Macrocycle 18: Pyrimidine-5-boronic acid pinacol ester (51.5 mg,

0.250 mmol) was added to a mixture of 14 (208 mg, 0.200 mmol), [Pd-

AHCTRE(UGN PPh₃)₄] (6.93 mg, 6.0 mmol), and Cs₂CO₃(97.8 g, 0.300 mmol) in dry tolu-

ene (10 mL) and dry DMF (10 mL) under argon. The reaction was

heated at 1208C for 2 d. All solvents were evaporated and the crude

product was purified by column chromatography (silica gel, eluting with

a (95:5) CH₂Cl₂/CH₃OH). The product, obtained as the second band

from the column, was dried at high vacuum (166 mg, 83%). ¹H NMR

[M+H]⁺, 1063.4 (52) [M+Na]⁺, 2081.9 (8)

[2M+Na⁺].

[2M+H⁺], 2102.9 (100)

ACHTREUNG

Macrocycle 15: Macrocycle 14 (360 mg, 0.345 mmol), bis(pinacolato)di-

boron (92.4 mg, 0.362 mmol), [PdCl₂A(dppf)] (14.1 mg, 0.0173 mmol), and

CTHREUNG

dried potassium acetate (101.7 mg, 1.035 mmol) were added to dried and

argon-bubbled DMSO (10 mL). The mixture was kept at 808C overnight

under an argon atmosphere. After cooling to room temperature, CH₂Cl₂

(20 mL) and water (20 mL) were added and the product was extracted

into the organic phase, which was washed three times with water

(20 mL). The combined organic phases were dried in vacuo and the resi-

due was examined by TLC. No bromo macrocycle starting material was

detected on the TLC plate, so the residue was applied to a 10 cm column

(silica gel, eluting with a (1:1) CH2L2/EtOAc mixture). The only band

was collected and dried to give 15 as a white solid (308 mg, 82%).

¹H NMR (250 MHz, CDCl₃): d=1.35 (s, 12H CH₃(pinacol)), 1.40 (s, 9H;

(250 MHz, CDCl₃): d=1.38 (s, 9H; CACHTRE(UNG CH₃)₃), 1.42–1.65 (b, 12H; CH₂),

2.14 (s, 24H; ArCH₃), 2.34 (b, 8H; CH₂), 6.97 (s, 8H; ArH), 7.96 (s, 2H;

NH), 8.15 (s, 1H; 2-isophthH), 8.19 (s, 2H; 4,6-isophthH); 8.40 (s, 2H;

4,6-isophthH), 8.56 (s, 2H; NH), 8.64 (s, 1H; 2-isophthH), 9.04 (s, 2H;

ArHACTHER(GNU pyr)), 9.16 ppm (s, 1H; ArHHCATRE(UGN pyr)) (the spectrum always showed

that there were two equivalents of DMF associated with the macrocycle

even after extensive drying); ¹³C NMR (62.5 MHz, CDCl₃): d=18.7, 18.8,

22.6, 26.1, 29.5, 30.6, 31.0, 35.1, 36.2, 44.8, 122.9, 125.9, 126.1, 128.2, 128.4,

128.5, 129.7, 131.1, 131.3, 131.4, 131.5, 131.9, 132.8, 134.2, 134.5, 134.7,

135.7, 147.7, 148.2, 153.6, 154.8, 157.5, 162.4, 164.3, 165.5 ppm; ESIMS:

+

m/z (%): 1039.6 [M+H]⁺; HRMS (ESI⁺): m/z calcd for C₆₈H₇₅N₆O₄

1039.5844 [M+H]⁺; found: 1039.579.

:

CACHTREUNG(CH₃)₃), 1.45–1.69 (b, 12H; CH₂), 2.14 (s, 12H; ArCH₃), 2.16 (s, 12H;

ArCH₃), 2.38 (b, 8H; CH₂), 6.94 (s, 8H; ArH), 7.94 (s, 1H; 2-isophthH),

8.19 (s, 2H; 4,6-isophthH), 8.31 (s, 1H; 2-isophthH), 8.51 ppm (s, 2H;

4,6-isophthH); ¹³C NMR (62.5 MHz, CDCl₃): d=18.7, 22.7, 24.7, 26.2,

29.5, 31.0, 35.2, 45.0, 121.9, 126.2, 128.4, 128.8, 130.8, 134.2, 134.5, 136.5,

147.8, 153.7, 165.3 ppm; ESIMS: m/z (%): 1087.56 (100) [M+H]⁺,

1109.54 (30) [M+Na]⁺, 1125.51 (46) [M+K]⁺.

Rotaxane 19: Dibenzo[18]crown-6 (13.0 mg, 0.036 mmol), 14 (150 mg,

0.144 mmol), potassium carbonate (198 mg, 1.44 mmol), a,a’-dibromo-p-

xylene (38.0 mg, 0.144 mmol), and tritylphenol (96.9 mg, 0.288 mmol)

were stirred in dry CH₂Cl₂(20 mL) for a week. The solvent was then

evaporated and the residue was eluted on a silica column with 2% meth-

anol in CH₂Cl₂. The second band was collected as the pure rotaxane

Macrocycle 16: 4-(2,2’;6’,2’’-Terpyridine-4’-yl)phenylboronic acid pinacol

ester (52.3 mg, 0.120 mmol) was poured into a mixture of 14 (100 mg,

0.096 mmol), [PdACHTREUNG(PPh₃)₄] (3.45 mg, 0.003 mmol), and Cs₂CO₃(46.9 mg,

1

(100 mg, 38%). R_f=0.5; H NMR (250 MHz, CDCl₃): d=1.27 (s, 9H; C-

AHCTRE(GNU CH₃)₃), 1.40–1.65 (br, 12H; CyCH₂), 1.81 (s, 12H; PhCH₃), 1.83 (s, 12H;

PhCH₃), 2.26 (br, 8H; CyCH₂), 4.22 (s, 4H; OCH₂), 5.98 (s, 4H; PhH_axle),

6.34 (d, J=4.5 Hz, 4H; PhH_stopper), 6.96 (s, 8H; PhH), 6.98 (d, J=4.5 Hz,

4H; PhH_stopper), 7.07–7.18 (m, 30H; PhH_stopper), 7.46 (s, 1H; 2-isophthH),

7.63 (s, 1H; 2-isophthH), 8.05 (s, 2H; 4,6-isophthH), 8.14 ppm (s, 2H;

4,6-isophthH); ¹³C NMR (62.5 MHz, CDCl₃+2 drops of CD₃OD): d=

18.3, 30.8, 35.0, 64.0, 110.5, 112.9, 113.1, 125.6, 125.8, 126.4, 126.5, 127.1,

0.144 mmol) in dry toluene (10 mL) and dry DMF (10 mL). The tempera-

ture was raised to 1008C whilst argon was bubbled through the solution

and then it was heated at 120–1308C for 2 d under argon before the sol-

vents were removed at reduced pressure. The remaining pale-pink solid

was first examined by TLC on silica gel with a 95:5 mixture of CH₂Cl₂/

CH₃OH to show that no appreciable amount of starting material re-

mained. The residue was purified by column chromatography (neutral

Al₂O₃, eluting with 1% CH₃OH in CH₂Cl₂) to give the product as a

white powder (80.2 mg, 66%). R_f=0.88; ¹H NMR (400 MHz, CDCl₃):

127.2, 127.3, 127.4, 130.5, 130.6, 130.7, 130.8, 132.3, 134.7, 134.8, 135.9,

+

140.8, 140.3, 161.6 ppm; HRMS (ESI⁺): m/z calcd for C₁₂₈H₁₃₃BrN₅O₆

1914.9434 [M+HNEt₃]⁺; found: 1914.9560.

:

d=1.35 (s, 9H; C

ArCH₃), 2.09 (s, 12H; ArCH₃), 2.26 (br, 8H; CH₂), 6.92 (s, 8H; ArH),

A

Rotaxane 20 (Synthesis starting from macrocycle 17): Dibenzo[18]crown-

6 (31.1 mg, 0.0863 mmol), 17 (367 mg, 0.345 mmol), potassium carbonate

10024

www.chemeurj.org

ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2008, 14, 10012 – 10028

Multimacrocyclic Hosts as Precursors for Multiply Interlocked Architectures

FULL PAPER

(476 mg, 3.45 mmol), a,a’-dibromo-p-xylene (91.0 mg, 0.345 mmol), and

tritylphenol (232 mg, 0.690 mmol) were stirred in dry CH₂Cl₂(20 mL) for

a week. The solvent was then evaporated and the residue was eluted on a

silica column with 2% methanol in CH₂Cl₂. The second band collected

was the pure rotaxane (512 mg, 82%). R_f=0.23; ¹H NMR (250 MHz,

(br, 3H; 4,6-t-Bu-isophthH, 2-t-Bu-isophthH), 8.17 (s, 4H; 4,6-acetylene-

isophthH), 8.30 ppm (s, 2H; 2-acetylene-isophthH); ¹³C NMR (125 MHz,

CDCl₃): d=18.6, 22.7, 26.6, 31.1, 35.2, 45.2, 71.2, 71.9, 126.3, 127.6, 131.2,

131.4, 134.2, 134.7, 135.1, 147.6, 148.1, 153.4, 165.4 ppm; ESIMS: m/z

(%): 1969 (10) [M+H]⁺, 1991 (100) [M+Na]⁺; HRMS (ESI⁺): m/z calcd

for C₁₃₂H₁₄₂N₈NaO₈⁺: 1991.0876 [M+Na]⁺; found: 1991.0860.

CDCl₃): d=1.40 (s, 9H; CACTHRE(UGN CH₃)₃), 1.49–1.72 (br, 12H; CyCH₂), 1.88 (s,

24H; PhCH₃), 2.32 (br, 8H; CyCH₂), 4.34 (s, 4H; OCH₂), 5.89 (s, 4H;

PhH_axle), 6.38 (d, J=9.1 Hz, 4H; PhH_stopper), 6.96 (d, J=9.1 Hz, 4H;

PhH_stopper), 7.00 (s, 8H; PhH), 7.01–7.22 (m, 30H; PhH_stopper), 7.36 (s, 2H;

4,6-isophH), 7.53 (d, J=6.4, 2H; H_py), 7.82 (s, 1H; 2-isophthH), 8.17 (s,

1H; 2-isophthH), 8.37 (s, 2H; 4,6-isophthH). 8.59 ppm (d, J=6.4 Hz, 2H;

H_py); ¹³C NMR (62.5 MHz, CDCl₃+2 drops of CD₃OD): d=18.4, 22.7,

29.4, 30.8, 35.3, 45.1, 64.0, 70.3, 113.1, 122.5, 125.9, 126.5, 127.3, 128.9,

130.7, 130.8, 131.9, 132.4, 132.6, 134.7, 134.8, 135.6, 140.9, 146.3, 148.5,

148.9, 153.4, 160.6, 165.9 ppm; ESIMS: m/z: 1813 [M+H]⁺.

Macrocycle 27: 2-Naphthyl boronic acid pinacol ester (0.120 mmol) was

poured into an argon-purged mixture of bromo macrocycle 14 (100 mg,

0.096 mmol), [PdACHTER(UNG PPh₃)₄] (3.45 mg, 0.003 mmol), Cs₂CO₃(46.9,

0.144 mmol) in dry toluene (10 mL) and dry DMF (10 mL) at 1008C.

Then it was kept at 120–1308C for 2 d under argon. The solvents were

evaporated at reduced pressure to dryness. After column chromatogra-

phy on silica eluting with CH₂Cl₂/ethyl acetate (6:1), macrocycle 27 was

obtained as the first band from the column dried at high vacuum

(80.0 mg, 76%). ¹H NMR (500 MHz, CDCl₃+2 drops CD₃OD): d=1.32

Rotaxane 20 (Synthesis starting from rotaxane 19): Pyridine boronic acid

(s, 9H; CAHCTER(GNU CH₃)₃), 1.40–1.62 (br, 12H; CH₂), 2.09 (s, 12H; PhCH₃), 2.11

pinacol ester (11.3 mg, 0.055 mmol) was added to a mixture of rotaxane

19 (80 mg, 0.044 mmol), [PdACTHRE(UGN PPh₃)₄] (1.53 mg, 1.32 mmol), and Cs₂CO₃

(s, 12H; PhCH₃), 2.27 (br, 8H; CH₂), 6.93 (s, 8H; PhH), 7.37–7.48 (m,

3H; ArH_naph), 7.71–7.79 (m, 4H; ArH_naph), 8.09 (s, 1H; 2-isophthH), 8.12

(s, 2H; 4,6-isophthH), 8.24 (s, 1H; 2-isophthH), 8.44 (s, 2H; 4,6-

isophthH), 8.62 (s, 2H; NH), 8.80 ppm (s, 2H; NH); ¹³C NMR

(62.5 MHz, CDCl₃+2 drops CD₃OD): d=18.4, 22.7, 26.1, 30.9, 34.9, 35.0,

44.9, 124.7, 125.9, 126.0, 126.3, 127.4, 128.1, 128.2, 128.5, 129.6, 131.1,

132.7, 133.3, 133.9, 134.9, 142.5, 147.7, 153.1, 166.4, 166.1 ppm; ESIMS:

m/z (%): 1088.61 (100) [M+H]⁺, 544.31 (52) [M+2H]²⁺; HRMS (ESI⁺):

m/z calcd for C₇₄H₈₀N₄O₄²⁺: 544.3084 [M+2H]²⁺; found: 544.3072.

(21.5 mg, 0.066 mmol) in dry toluene (5 mL) and dry DMF (5 mL) under

argon. The reaction was continued at 1208C for 2 d. All solvents were

evaporated and the crude product was purified by column chromatogra-

phy (silica, eluting with 2% methanol in CH₂Cl₂). The product was ob-

tained as the third band from the column and dried at high vacuum

(4.8 mg, 6%). For NMR and MS characterization see above.

FBMH 22: 1,4-Benzene diboronic acid pinacol ester (33.0 mg,

0.100 mmol) was added to a mixture of 14 (208 mg, 0.200 mmol), [Pd-

ACHTREUNG(PPh₃)₄] (7.0 mg, 6.0 mmol), and Cs₂CO₃(97.8, 0.300 mmol) in dry toluene

Macrocycle 28: 1-Pyrenyl boronic acid pinacol ester (0.120 mmol) was

poured into an argon-purged mixture of bromo macrocycle 14 (100 mg,

(10 mL) and dry DMF (10 mL) under argon. The reaction was continued

at 1208C for 1 d. All solvents were evaporated and the crude product

was purified by column chromatography (silica gel, eluting with a 10:1

mixture of CH₂Cl₂/CH₃OH). The product, obtained as the first band

from the column, was dried at high vacuum. ¹H NMR (500 MHz, CDCl₃/

0.096 mmol),

[Pd

A

0.003 mmol),

Cs₂CO₃

(46.9,

0.144 mmol) in dry toluene (10 mL) and dry DMF (10 mL) at 1008C.

Then it was kept at 120–1308C for 2 d under argon. The solvents were

evaporated at reduced pressure to dryness. After column chromatogra-

phy on silica eluting with CH₂Cl₂/ethyl acetate (8:1), macrocycle 28 was

obtained as the second band from the column and dried at high vacuum

CD₃OD (2:1)): d=1.39 (s, 18H; CACHTRE(UNG CH₃)₃), 1.45–1.65 (br, 24H; CH₂),

2.16 (s, 24H; ArCH₃), 2.18 (s, 24H; ArCH₃), 2.31 (br, 16H; CH₂), 6.98 (s,

16H; ArH), 7.86 (s, 2H; ArH), 8.16 (s, 4H; 4,6-t-Bu-isophthH), 8.17 (s,

2H; 2-isophthH), 8.37 (s, 2H; 4,6-t-Bu-isophthH), 8.43 ppm (s, 4H; 4,6-

isophthH); ¹³C NMR (62.5 MHz, CDCl₃/CD₃OD (2:1)): d=15.8, 17.9,

22.4, 25.9, 30.5, 34.7, 34.8, 44.7, 127.3, 128.1, 128.2, 128.4, 129.1, 131.0,

131.4, 131.5, 132.0, 133.7, 134.6, 141.6, 147.6, 147.7, 152.9, 160.7, 166.3,

166.7 ppm; ESIMS: m/z: 1997.151; HRMS (ESI⁺): m/z calcd for

(97.0 mg, 87%). ¹H NMR (500 MHz, CD₂Cl₂): d=1.44 (s, 9H; C

ACHTREUNG(CH₃)₃),

1.51–1.70 (br, 12H; CH₂), 2.20 (s, 12H; PhCH₃), 2.24 (s, 12H; PhCH₃),

2.40 (br, 8H; CH₂), 7.09 (s, 8H; PhH), 7.44 (s, 2H; 4,6-isophthH), 7.59 (s,

2H; 4,6-isophthH), 8.03–8.30 (m, ArH_pyrene), 8.37 ppm (s, 4H; NH);

¹³C NMR (62.5 MHz, CDCl₃): d=18.5, 19.1, 23.0, 26.4, 31.3, 35.5, 45.3,

58.5, 124.5, 124.8, 124.8, 125.0, 125.3, 125.6, 126.3, 126.6, 126.7, 127.4,

127.6, 128.0, 128.4, 128.5, 128.7, 130.9, 131.0, 131.3, 131.5, 133.1, 134.7,

134.8, 135.0, 135.3, 135.4, 143.8, 148.2, 154.1, 165.3, 165.7 ppm; ESIMS:

m/z (%): 1162 (100) [M+H]⁺.

C

₁₃₄H₁₄₇N₈O₈⁺: 1996.1336 [M+H]⁺; found: 1996.151.

FBMH 24: Macrocycle 11 (0.112 g 0.103 mmol) was placed under argon

atmosphere in a three-necked flask. Compound 23 (0.05 g, 0.033 mmol),

dry DMF (10 mL), and dry triethylamine (0.15 mL) were added. The sus-

pension was stirred until all of the starting material had dissolved, then

Macrocycle 30: 4-Formyl benzene boronic acid pinacol ester

(0.120 mmol) was poured into an argon-purged mixture of bromo macro-

cycle 14 (100 mg, 0.096 mmol), [PdACHTRE(UNG PPh₃)₄] (3.45 mg, 0.003 mmol),

PPh₃(0.003 g, 0.099 mmol), [Pd

A

Cs₂CO₃(46.9, 0.144 mmol) in dry toluene (10 ml) and dry DMF (10 mL)

at 1008C. Then it was kept at 120–1308C for 2 d under argon. The sol-

vents were evaporated at reduced pressure to dryness. After column

chromatography on silica eluting with CH₂Cl₂/CH₃OH (7:1), macrocycle

30 was obtained as a white powder (85.8 mg, 84%). ¹H NMR (400 MHz,

CuI (0.001 g, 0.005 mmol) were added. After stirring for 40 h at room

temperature, the solvent was evaporated under reduced pressure. The

residue was subjected to column chromatography (silica gel, eluting with

a 20:1 mixture of CH₂Cl₂/CH₃OH) to obtain 24 as a dark yellowish solid

(0.04 g, 40%). ¹H NMR (400 MHz, CD₂Cl₂/CD₃OD (10:1)): d=1.38 (s,

CDCl₃): d=1.37 (s, 9H; CCATHER(UNG CH₃)₃), 1.47–1.70 (br, 12H; CH₂), 2.12 (s,

27H; C

N

24H; PhCH₃), 2.31 (br, 8H; CH₂), 6.97 (s, 8H; PhH), 7.48 (br, 4H; NH),

7.68 (d, J=10.3 Hz, 2H; PhH), 7.75 (d, J=10.3 Hz, 2H; PhH), 7.99 (s,

1H; 2-isophthH), 8.14 (s, 2H; 4,6-isophthH), 8.25 (s, 1H; 2-isophthH),

8.37 (s, 2H; 4,6-isophthH), 9.93 ppm (s, 1H; CHO); ¹³C NMR (100 MHz,

CDCl₃): d=15.3, 19.1, 23.0, 26.4, 30.8, 31.3, 35.5, 45.3, 65.9, 122.7, 126.66,

126.74, 128.0, 128.6, 130.1, 130.4, 130.9, 131.1, 134.6, 134.8, 134.9, 135.1,

135.2, 135.3, 135.9, 141.9, 145.0, 148.1, 148.4, 154.1, 164.9, 165.8,

192.1 ppm; ESIMS: m/z (%): 1166.7 (100) [M+HNEt₃]⁺(ionization

turned out to be significantly easier, when 0.5% of NEt₃were added

which forms a complex with the macrocycle in high abundances).

2.14–2.16 (br, 72H; ArCH₃), 2.30–2.34 (br, 24H; CH₂), 6.97 (br, 24H;

ArH), 7.73 (s, 3H; ArH), 8.11 (br, 3H; 2-t-Bu-isophthH), 8.14 (br, 6H;

4,6-t-Bu-isophthH), 8.27 (br, 6H; 4,6-acetylene-isophthH), 8.30 ppm (s,

H; 2-acetylene-isophthH); ¹³C NMR (125 MHz, CD₂Cl₂/CD₃OD (10:1)):

d=15.8, 23.8, 27.1, 32.6, 42.7, 91.2, 123.7, 125.7, 128.9, 129.1, 131.8, 132.6,

132.7, 145.6, 152.4, 164.0 ppm; ESIMS: m/z (%): 1536 (50)

3027 (25) [M+H]⁺, 3050 (100) [M+Na]⁺; HRMS (ESI⁺): m/z calcd for

₂₀₄H₂₁₆N₁₂NaO₁₂⁺: 3050.6618 [M+Na]⁺; found: 3050.5579.

C

FBMH 25: Macrocycle 13 (0.014 g, 0.014 mmol) and CuCl (0.004 g,

0.0042 mmol) were dissolved in dry DMF (2 mL). After 12 h stirring at

room temperature the solvents were evaporated under reduced pressure.

The residue was purified by preparative TLC (silica gel, eluting with a

25:1 mixture of CH₂Cl₂/CH₃OH) to obtain 25 as a white solid (0.007 g,

26%). ¹H NMR (400 MHz, CDCl₃/CD₃OD (10:1)): d=1.31 (s, 18H; C-

Macrocycle 31: 2,4-Dimethyl pyrrole (19 mg, 0.2 mmol, 17mL) and alde-

hyde 30 (106.5 mg, 0.1 mmol) were dissolved in dry CH₂Cl₂(15 mL;

argon was bubbled for 10 min) under argon. One drop of trifluoroacetic

acid was added and the solution was stirred at room temperature for 4 h.

A solution of p-chloranil (24.5 mg, 0.1 mmol) in dry CH₂Cl₂(5 mL) was

added and stirring was continued for 30 min. Then, BF₃·Et₂O was added

and the reaction mixture was stirred for another 30 min. The reaction

ACHTREUNG

Chem. Eur. J. 2008, 14, 10012 – 10028

ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

10025

C. A. Schalley et al.

mixture was washed three times with water and dried over MgSO₄. The

solvent was evaporated and the residue was purified by silica gel column

chromatography eluting with CH₂Cl₂(79.4 mg, 62%). ¹H NMR

FBMH 36: Macrocycle 17 (0.021 g, 0.02 mmol) and bis(benzonitrile)pal-

ladiumdichloride (0.004 g, 0.01 mmol) were dissolved in CH₂Cl₂(20 mL)

under an argon atmosphere. After stirring for 16 h at room temperature,

the temperature was raised to 408C for 1 h. Two thirds of the solvent was

evaporated under reduced pressure and diethyl ether was slowly added.

The suspension was filtered and the crude product was recrystallized

from acetone/diethyl ether to give 36 as a brownish solid (0.010 g, 44%).

(250 MHz, CDCl₃): d=1.39 (s, 9H; CACHTRE(UNG CH₃)₃), 1.41 (s, 6H; CH₃of

BODIPY), 1.45–1.65 (br, 12H; CH₂), 2.30 (br, 8H; CH₂), 2.47 (s, 24H;

PhCH₃), 2.52 (s, 6H; CH₃of BODIPY), 5.97 (s, 2H; PyrroleH of

BODIPY), 6.97 (s, 8H; PhH), 7.38 (d, J=7.7 Hz, 2H; PhH), 7.38 (d, J=

7.7 Hz, 2H; PhH), 7.96 (s, 1H; 2-isophthH), 8.20 (s, 2H; 4,6-isophthH),

8.30 (s, 1H; 2-isophthH), 8.49 ppm (s, 2H 4,6-isophthH) (the spectrum

always shows three equivalents of DMF associated with the macrocycle

even after extensive drying); ¹³C NMR (62.5 MHz, CDCl₃): d=14.4, 18.8,

22.6, 30.8, 31.0, 35.1, 36.2, 44.8, 121.1, 126.1, 127.8, 128.5, 131.2, 131.3,

134.2, 134.47, 134.54, 134.7, 135.1, 162.4 ppm; ESIMS: m/z (%): 1306.7

(28) [M+Na]⁺, 1321.9 (100) [M+K]⁺, 1384.9 (18) [M+HNEt₃]⁺; HRMS

(ESI⁺): m/z calcd for C₈₉H₁₀₆BF₂N₇O₄: 1384.8404 [M+HNEt₃]⁺; found:

1384.854 (ionization turned out to be significantly easier when 0.5%

NEt₃was added to form a complex with the macrocycle in high abundan-

ces).

¹H NMR (500 MHz, [D₇]DMF): d=1.41 (s, 18H; C

ACHTRE(UNG CH₃)₃), 1.52–1.55 (br,

8H; CH₂), 1.62–1.67 (br, 16H; CH₂), 2.19 (s, 24H; ArCH₃), 2.21 (s, 24H;

ArCH₃), 2.48 (br, 14H; CH₂), 7.23 (s, 16H; ArH), 8.15 (d, J=6.1 Hz,

4H; ArH(py)), 8.20 (s, 4H; 4,6-t-Bu-isophthH), 8.57 (s, 4H; 4,6-py-

isophthH), 8.71 (s, 2H; 2-t-Bu-isophthH), 8.99 (s, H; 2-py-isophthH), 9.02

(d, J=6.1 Hz, 4H; ArH(py)), 9.35 (s, 4H; NH), 9.58 ppm (s, 4H; NH);

¹³C NMR (125 MHz, [D₇]DMF): d=19.1, 23.8, 27.1, 27.6, 31.6, 45.1,

124.0, 126.8, 128.7, 130.1, 133.7, 133.9, 135.8, 135.9, 137.3, 147.9, 148.1,

165.2, 166.0 ppm; ESIMS: m/z (%): 2216.04 (100) [MꢀCl]⁺, 2254.25 (50)

[MꢀH]⁺.

FBMH 37²⁺(OTf^ꢀ)₂: [Pt

ACHTREUNG ACHRET(GNU dppp)ACHRTEU(NG OTf)₂] (0.011 g, 0.012 mmol) and 10

(0.025 g, 0.024 mmol) were dissolved in DMF (0.5 mL) and stirred for

10 min at room temperature. The solvents were evaporated under re-

duced pressure to obtain the product as a green solid in quantitative

FBMH 33: 1,7-Dibromoperylene-3,4,9,10-tetracarbonic acid cyclohexyl-

A

ACHTREUNG

yield. ¹H NMR (500 MHz, [D₇]DMF): d=1.39 (s, 18H; C

ACHTRE(UNG CH₃)₃), 1.52–

in dry toluene (10 mL) and dry DMF (10 mL) under argon. The reaction

was continued at 1208C for 2 d. All solvents were evaporated and the

crude product was purified by column chromatography (silica gel, eluting

with a 5:95 mixture of CH₃OH/CH₂Cl₂). The product obtained was ana-

lyzed by ¹H NMR spectroscopy and ESIMS and was found to be conta-

minated with bismacrocycle. Thus, a second column was employed to

yield the product (112 mg, 45%; after second column). ¹H NMR

1.61 (br, 24H; CH₂), 2.15 (s, 48H; ArCH₃), 2.23 (br, 4H; P-CH₂), 2.45

(br, 16H; CH₂), 3.45 (br, 2H; P-CH₂), 7.20–7.22 (br, 16H; ArH), 7.47–

7.51 (br, 20H; PtArH), 7.85–7.88 (br, 4H; ArH(py)), 8.20 (br, 4H; 4,6-t-

Bu-isophthH), 8.30 (br, 4H; 4,6-t-Bu-isophthH), 8.66 (s, 2H; 2-t-Bu-

isophthH), 8.94 (s, 2H; 2-py-isophthH), 9.15–9.17 (br, 2H; ArH(py)),

9.25 (s, 4H; NH), 9.43 ppm (s, 4H; NH); ¹³C NMR (125 MHz,

[D₇]DMF): d=19.2, 31.8, 24.0, 25.6, 27.3, 45.9, 126.9, 127.0, 129.7, 130.5,

132.9, 133.1, 133.7, 134.0, 134.4, 135.9, 136.0, 137.3, 138.0, 148.2, 148.3,

151.1, 153.6, 165.1, 166.2 ppm; ³¹P NMR (200 MHz, [D₇]DMF): d=

(250 MHz, CDCl₃/CD₃OD (10:1)) d=1.32 (s, 18H; CACTHRE(UNG CH₃)₃), 1.40–155

(br, 48H; CH₂), 2.07 (s, 48H; ArCH₃), 2.23 (br, 16H; CH₂), 6.88 (s, 16H;

ArH), 8.02 (s, 2H; 2-isophthH), 8.05 (s, 4H; 4,6-isophthH), 8.10 (s, 4H;

4,6-isophthH), 8.23 (s, 2H; 2-isophthH), 8.40 (d, J=8.3 Hz, 2H;

ArH_perylene), 8.51 (s, 2H; ArH_perylene), 8.62 ppm (d, J=8.3 Hz, 2H;

ArH_perylene); due to the poor solubility of 33, no ¹³C NMR could be mea-

sured; ESIMS: m/z(%): 2574 (8) [ M+HNEt₃]⁺; HRMS (ESI⁺): m/z

calcd for C₁₇₀H₁₈₆N₁₁O₁₂⁺: 2573.428 [M+HNEt₃]⁺; found: 2573.440 (ioni-

zation turned out to be significantly easier when 0.5% NEt₃was added

to form a complex with the macrocycle in high abundances).

ꢀ16.52 ppm (¹J

ACHTRE(UNG Pt,P)=3023 Hz); ESIMS: m/z (%): 1794 (10)

[MꢀOTfꢀpy-macrocycle]⁺, 2833 (100) [MꢀOTf]⁺; HRMS (ESI⁺): m/z

calcd for C₁₆₆H₁₇₆F₃N₁₀O₁₁P₂PtS: 2833.2365 [MꢀOTf]⁺; found: 2833.2438.

Rotaxane 39: Under an argon atmosphere, P₁base (0.24 mL, 1.02 mmol)

was added to

a suspension of 38 (176 mg, 0.66 mmol) in CH₂Cl₂

(300 mL). After the reaction mixture was stirred for 1 h at room temper-

ature, macrocycle 3 (662 mg, 0.69 mmol) was added and stirring was con-

tinued for 15 min. Upon addition of triethylamine (0.18 mL), the reaction

mixture was cooled down to 0–58C, and a solution of triphenylacetyl

chloride (405 mg, 1.32 mmol) in CH₂Cl₂(10 mL) was added dropwise.

The reaction mixture was stirred for 3 d at room temperature, washed

twice with saturated aqueous ammonium chloride solution and twice

with deionized water. The organic layer was dried over magnesium sul-

fate, the solvents were then evaporated, and the residue was purified by

column chromatography (silica gel, EtOAc) and again by column chro-

matography (silica gel, CH₂Cl₂/EtOAc/MeOH 14:2:1). The product was

redissolved in diethyl ether, and after evaporation of solvents, rotaxane

39 was obtained as a white solid (165 mg, 0.09 mmol, 14%). R_f=0.41

FBMH 34: Under an argon atmosphere,

0.027 mmol) was slowly added to a solution of bis(benzonitrile)palladi-

um(II)chloride (4.8 mg, 0.013 mmol). After stirring for 9 h, pale-yellow

precipitate was filtered and dried (13.5 mg, 49%). ¹H NMR (400 MHz,

CDCl₃/CD₃OD (5:1)): d=1.31 (s, 18H; C(CH₃)₃), 1.43 (br, 8H; CH₂),

a solution of 3 (25.9 mg,

ACHTREUNG

AHCTREUNG

1.55 (br, 16H; CH₂), 2.06 (br, 48H; ArCH₃), 2.24 (br, 16H; CH₂), 6.88–

6.89 (m, 16H; ArH), 8.03 (br, 2H; ArH), 8.08 (br, 4H; ArH), 8.64 (br,

2H; ArH (py)), 9.38 ppm (br, 4H; ArH(py)); ¹³C NMR (125 MHz,

CDCl₃/CD₃OD (5:1)): d=18.4, 22.9, 26.3, 31.0, 35.0, 35.2, 45.1, 123.8,

126.1, 126.3, 128.3, 130.8, 131.3, 131.7, 134.0, 134.8, 135.0, 137.7, 147.9,

148.3, 153.3, 154.4, 162.1, 166.8 ppm; ESIMS: m/z (%): 2122 (100)

[M+Na]⁺, 2138 (60) [M+K]⁺; HRMS (ESI^ꢀ): m/z calcd for

1

(CH₂Cl₂/EtOAc/MeOH 14:2:1); H NMR (500 MHz, CD₂Cl₂): d=1.46 (s,

9H; CACHTREU(GN CH₃)₃), 1.59 (s, 4H; CyCH₂), 1.69 (br, 8H; CyCH₂), 1.92–1.94 (br,

C

₁₂₆H₁₄₁Cl₂N₁₀O₈Pd^ꢀ: 2099.9382 [MꢀH]⁺; found: 2099.9416.

24H; ArCH₃), 2.21–2.24 (br, 8H; CyCH₂), 2.43 (br, 4H; NCH₂, station

inside the wheel cavity), 3.52–3.63 (br, 4H; NCH₂, station outside the

wheel cavity), 6.64 (br, 4H; NH), 6.81 (t, J=8.0 Hz, 1H; ArH), 6.97–7.22

(br, 40H; ArH), 8.15 (br, 2H; NH), 8.19 (br, 2H; NH), 8.52 (br, 2H;

ArH), 8.62 (br, 1H; ArH), 9.08 (br, 1H; ArH (py)), 9.25 (d, J=1.0 Hz,

2H; ArH (py)), 15.54 ppm (s, 1H; OH); ¹³C NMR (125 MHz, CD₂Cl₂):

18.6, 23.5, 26.7, 31.5, 35.6, 36.1, 37.0, 45.6, 119.4, 124.1, 126.7, 126.9, 127.1,

127.8, 128.4, 128.5, 129.9, 130.5, 131.5, 132.1, 134.1, 135.0, 135.6, 135.8,

149.2, 149.3, 152.3, 153.9, 161.7, 164.4, 166.4, 177.5 ppm; FTICR-MS

(ESI^ꢀ, from MeOH): m/z (%): 1767 (100) [MꢀH]^ꢀ; HRMS (ESI^ꢀ): m/z

calcd for C₁₁₅H₁₁₆N₉O₉^ꢀ: 1766.8901 [MꢀH]^ꢀ; found: 1766.8863.

MIA 40: Under an argon atmosphere, a solution of rotaxane 39 (20.4 mg,

0.012 mmol) in CH₂Cl₂(2.5 mL) was slowly added to a solution of bis-

AHCTRE(UNG benzonitrile)palladium(II)dichloride (2.15 mg, 0.006 mmol) in CH₂Cl₂

(1.5 mL). The reaction mixture was stirred at room temperature for 1 d

and was then stored in the refrigerator. After a week, the pale precipitate

obtained was filtered to obtain the product (5 mg, 11%). ¹H NMR

ACHTREUNG

FBMH 35²⁺(BF₄^ꢀ)₂: A solution of 3 (27.3 mg, 0.028 mmol) was dissolved

in CDCl₃(500 mL) before a solution of tetra(acetonitrile)palladium(II)

tetrafluoroborate (2.6 mg, 0.006 mmol) in CD₃CN (60 mL) was slowly

added under an argon atmosphere. After CDCl₃(400 mL) was added to

the mixture, it was stirred for a day and then stored in the refrigerator.

After 3 d the white precipitate obtained was filtered to give the product

(9 mg, 33%). ¹H NMR (500 MHz, CDCl₃/CD₃OD (5:1)): d=1.31 (s,

36H; CACHTREUNG(CH₃)₃), 1.43 (br, 16H; CH₂), 1.55 (br, 32H; CH₂), 2.00–2.06 (br,

96H; ArCH₃), 2.22 (br, 32H; CH₂), 6.85–6.90 (m, 32H; ArH), 8.00 (br,

4H; ArH), 8.08 (d, J=1.6 Hz, 8H; ArH), 8.55 (br, 4H; ArH(py)),

9.71 ppm (d, J=1.7 Hz, 8H; ArH(py)); ¹³C NMR (125 MHz, CDCl₃/

CD₃OD (5:1)): d=18.4, 22.9, 26.3, 31.0, 35.1, 35.2, 45.1, 123.6, 126.2,

126.4, 128.3, 128.5, 130.4, 131.3, 134.1, 134.6, 134.8, 134.9, 147.9, 148.5,

152.2, 153.4, 162.1, 166.8 ppm; ESIMS: m/z (%): 3051 (100) [Mꢀmacro-

cycle+CH₃COO]⁺, 4014 (33) [M+CH₃COO]⁺; HRMS (ESI⁺): m/z calcd

for C₂₅₄H₂₈₇N₂₀O₁₈Pd⁺: 4010.1222 [M+CH₃COO]⁺; found: 4010.1530.

10026

www.chemeurj.org

ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2008, 14, 10012 – 10028

Multimacrocyclic Hosts as Precursors for Multiply Interlocked Architectures

FULL PAPER

(500 MHz, CDCl₃): d=1.43 (s, 9H;

C

(CH₃)₃), 1.57–1.62 (br, 12H;

1_calcd=1.036 gcm^ꢀ3m=1.800 mm^ꢀ1

, ; FACHTREU(NG 000)=1388.2; colorless; 0.10

CyCH₂), 1.88–1.95 (br, 24H; ArCH₃), 2.15–2.21 (br, 8H; CyCH₂), 2.34–

2.36 (br, 4H; NCH₂), 3.55–3.68 (br, 4H; NCH₂), 6.59 (br, 4H; NH), 6.85–

7.24 (br, 40H; ArH), 8.02 (br, 2H; NH), 8.17 (br, 2H; NH), 8.51–8.59

(br, 3H; ArH), 9.19 (br, 1H; ArH(py)), 9.53 ppm (br; 2H; ArH(py));

¹³C NMR (125 MHz, CDCl₃): d=18.5, 23.1, 26.4, 31.5, 35.6, 36.1, 36.9,

45.3, 51.1, 119.5, 123.8, 127.1, 127.6, 127.9, 128.1, 128.4, 128.7, 130.2,

130.4, 130.5, 131.5, 131.6, 134.6, 135.0, 135.4, 135.8, 141.7, 142.7, 153.7,

155.6, 161.3, 161.4, 166.4 ppm; ESIMS: m/z (%): 3738 (100) [M+Na]⁺;

HRMS (ESI⁺): m/z calcd for C₂₃₀H₂₃₄Cl₂N₁₈NaO₁₈Pd⁺: 3738.6328

[M+Na]⁺; found: 3738.6191.

0.150.20 mm³crystal; Bruker Nonius APEX II diffractometer; 9747 in-

dependent reflections; 5581 with I>2s; multiscan absorption correction;

min and max transmission: 0.7148 and 0.8405; 2121 restraints; 883 param-

eters; R1=0.1457; wR2=0.3410 [I>2s]; R1=0.2167, wR2=0.3825 (all

ꢀ3

data); GOF=1.067, largest diff. peak and hole: 1.078 and ꢀ0.66 e

.

CCDC-687761 and -687762 contain the supplementary crystallographic

data for this paper. These data can be obtained free of charge from The

Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_

request/cif.

Rotaxane 41: Dibenzo[18]crown-6 (13.0 mg, 0.036 mmol), 16 (150 mg,

0.144 mmol), potassium carbonate (198 mg, 1.44 mmol), a,a’-dibromo-

ACHTREUNGparaxylene (38.0 mg, 0.144 mmol), and tritylphenol (96.9 mg, 0.288 mmol)

were stirred in dry CH₂Cl₂(20 mL) for a week. The solvent was then

evaporated and the residue was eluted on an alumina column with 2%

methanol in CH₂Cl₂. The second band collected was the pure rotaxane

Acknowledgements

(100 mg, 38%). ¹H NMR (250 MHz, CDCl₃): d=1.31 (s, 9H; C

ACHTRE(UNG CH₃)₃),

We are grateful for funding from the Deutsche Forschungsgemeinschaft

(SFB 765 “Multivalency”), the Fonds der Chemischen Industrie (FCI)

and the Academy of Finland (K.R.: no. 122350 and 113437). C.A.S.

thanks the FCI for a Dozentenstipendium. S.S.Z. thanks the Studienstif-

tung des deutschen Volkes for a PhD scholarship.

1.50–1.70 (br, 12H; CyCH₂), 1.88 (s, 12H PhCH₃), 1.90 (s, 12H; PhCH₃),

2.33 (br, 8H; CyCH₂), 4.36 (s, 4H; OCH₂), 5.89 (s, 4H; PhH_axle), 6.40 (d,

J=4.5 Hz, 4H; PhH_stopper), 6.99 (d, J=4.5 Hz, 4H; PhH_stopper), 7.02 (s,

8H; PhH), 7.09–7.25 (m, 30H; PhH_stopper), 7.31 (d, J=7.7 Hz, 2H; 5,5’’-

tpyH), 7.54 (s, 1H; 2-isophthH), 7.75 (s, 1H; 2-isophthH), 7.76 (d, J=

8.3 Hz, 2H; PhH), 7.87 (t, J=7.7 Hz, 2H; 4,4’’-tpyH), 7.97 (d, J=8.3 Hz,

2H; PhH), 8.14 (s, 2H; 4,6-isophthH), 8.42 (s, 2H 4,6-isophthH), 8.86 (d,

J=7.7 Hz, 2H; 3,3’’-tpyH), 8.73 (d, J=7.7 Hz, 2H; 6,6’’-tpyH), 8.78 ppm

(s, 2H; 3,5’-tpyH); ¹³C NMR (62.5 MHz, CDCl₃): d=18.7, 23.1, 26.3,

31.2, 35.7, 45.4, 64.3, 70.9, 113.4, 118.8, 121.4, 121.7, 123.1, 123.8, 126.1,

126.9, 127.5, 127.8, 127.9, 129.2, 130.5, 130.9, 131.0, 131.2, 132.7, 134.6,

135.1, 135.4, 135.7, 136.9, 138.4, 139.5, 141.2, 142.9, 146.5, 149.1, 149.2,

149.2, 149.5, 154.2, 155.7, 156.1, 156.2, 165.2, 165.8 ppm; ESIMS: m/z

(%): 2043.0 (100) [M+H]⁺, 2144.1 (40) [M+HNEt₃]⁺; HRMS (ESI⁺): m/

z calcd for C₁₄₉H₁₄₇N₈O₆⁺: 2144.144 [M+HNEt₃]⁺; found: 2144.144.

[1] For reviews on self-assembly, see: a) D. Philp, J. F. Stoddart, Angew.

Chem. 1996 , 108 , 124 2 –1 286; Angew. Chem. Int. Ed. Engl. 1996 , 35 ,

115 4 –1 196; b) P. J. Stang, B. Olenyuk, Acc. Chem. Res. 1997 , 30 ,

50 2 –5 18; c) C. A. Schalley, A. Lützen, M. Albrecht, Chem. Eur. J.

2004 , 10 , 107 2 –1 080.

[2] For selected examples, see: a) I. Higler, H. Boerrigter, W. Verboom,

H. Kooijman, A. L. Spek, D. N. Reinhoudt, Eur. J. Org. Chem. 1998 ,

159 7 –1 607; b) E. S. Barrett, J. L. Irwin, P. Turner, M. S. Sherburn, J.

Org. Chem. 2001 , 66 , 822 7 –8 229; c) B. M. OꢀLeary, T. Szabo, N.

Svenstrup, C. A. Schalley, A. Lützen, M. Schäfer, J. Rebek, Jr. J.

Am. Chem. Soc. 2001, 123, 11519–11533; d) S. Y. Yu, H. Huang,

H. B. Liu, Z. N. Chen, R. B. Zhang, M. Fujita, Angew. Chem. 2003 ,

115 , 71 0 –7 14; Angew. Chem. Int. Ed. 2003 , 42 , 68 6 –6 90; e) J. W.

Steed, Chem. Commun. 2006 , 263 7 –2 649.

[3] For selected examples, see: a) T. Iijima, S. A. Vignon, H. R. Tseng,

T. Jarrosson, J. K. M. Sanders, F. Marchioni, M. Venturi, E. Apostoli,

V. Balzani, J. F. Stoddart, Chem. Eur. J. 2004 , 10 , 637 5 –6 392;

b) A. B. Braunschweig, W. R. Dichtel, O. S. Miljanic, M. A. Olson,

J. M. Spruell, S. I. Khan, J. R. Heath, J. F. Stoddart, Chem. Asian J.

2007 , 2 , 63 4 –6 47.

[4] For selected examples, see: a) D. M. Tiede, R. T. Zhang, L. X. Chen,

L. H. Yu, J. S. Lindsey, J. Am. Chem. Soc. 2004 , 126 , 1405 4 –1 4062;

b) J. Otsuki, T. Narita, K. Tsutsumida, M. Takatsuki, M. Kaneko, J.

Phys. Chem. A 2005 , 109 , 612 8 –6 134; c) E. Iengo, E. Zangrando, E.

Alessio, Acc. Chem. Res. 2006 , 39 , 84 1 –8 51.

[5] Y. Tanaka, H. Katagiri, Y. Furusho, E. Yashima, Angew. Chem.

2005 , 117 , 393 5 –3 938; Angew. Chem. Int. Ed. 2005 , 44 , 386 7 –3 870.

[6] For selected examples, see: a) C. J. Pedersen, J. Am. Chem. Soc.

1967 , 89 , 249 5 –2 496; b) R. M. Izatt, K. Pawlak, J. S. Bradshaw, R. L.

Bruening, Chem. Rev. 1995 , 95 , 252 9 –2 586.

[7] For selected examples, see: a) R. A. Bissell, E. Cordova, A. E.

Kaifer, J. F. Stoddart, Nature 1994 , 369 , 13 3 –1 37; b) J.-P. Sauvage,

Acc. Chem. Res. 1998 , 31 , 61 1 –6 19; c) C. A. Schalley, K. Beizai, F.

Vçgtle, Acc. Chem. Res. 2001 , 34 , 46 5 –4 76; d) A. M. Brouwer, C.

Frochot, F. G. Gatti, D. A. Leigh, L. Mottier, F. Paolucci, S. Roffia,

G. W. H. Wurpel, Science 2001 , 291 , 212 4 –2 128.

[8] For selected examples, see: a) M. Kocak, A. I. Okur, O. Bekaroglu,

J. Chem. Soc. Dalton Trans. 1994, 323–326; b) J. D. Badjic, V. Balza-

ni, A. Credi, S. Silvi, J. F. Stoddart, Science 2004 , 303 , 184 5 –1 849;

c) S. J. Loeb, D. A. Tramontozzi, Org. Biomol. Chem. 2005 , 3 , 139 3 –

1401; d) X. Z. Zhu, C. F. Chen, J. Am. Chem. Soc. 2005 , 127 , 1315 8 –

13159; e) O. Hayashida, M. Uchiyama, J. Org. Chem. 2007 , 72 , 61 0 –

616.

MIA 42²⁺

troduced into a metal solution containing half an equivalent of metal ion

from stock solution separately prepared from Zn(ClO₄)₂·6H₂O in

ACHTREUNG

(ClO₄^ꢀ)₂: Rotaxane 41 (12.0 mg, 5.87 mmol) in CDCl₃was in-

a

ACHTREUNG

CD₃CN. Two drops of CD₃OD (without which the NMR spectra seem to

be overwhelmingly broad in this case) was added to the mixture. The re-

1

sulting mixture was stirred for 1 d to yield the desired complex. H NMR

(500 MHz, CDCl₃+2 drops CD₃OD): d=1.27 (s, 18H; CCAHTRE(UNG CH₃)₃), 1.34–

1.65 (br, 24H; CyCH₂), 1.84 (s, 48H; ArCH₃), 2.57 (br, 16, CyCH₂), 4.35

(s, 8H; OCH₂), 6.18 (s, 8H; PhH_axle), 6.43 (d, J=8.65 Hz, 8H; PhH_stopper),

6.90 (d, J=8.65 Hz, 8H; PhH_stopper), 6.99 (s, 8H; PhH), 6.85–6.92 (m, 8H;

6,6’’; 3,3’’-tpyH) 7.02–7.11 (m, 60H; PhH_stopper), 7.30 (s, 2H; 2-isophthH),

7.41 (s, 4H; 4,6-isophthH), 7.60 (t, J=7.15 Hz, 4H; 5,5’’-tpyH), 7.70 (s,

2H; 2-isophthH), 7.83 (t, J=7.15 Hz, 4H; 4,4’’-tpyH), 7.97 (s, 4H; 4,6-

isophthH), 8.12 (d, J=7.05 Hz, 4H; PhH), 8.38 (s, 4H; 3’,5’-tpyH), 8.61

(d, J=7.05 Hz, 4H; Ph), 8.85 ppm (s, 4H; NH); ¹³C NMR (125 MHz,

CDCl₃+2 drops CD₃OD): d=18.1, 22.5, 25.8, 29.1, 30.5, 34.7, 35.0, 44.8,

63.8, 69.4, 112.9, 116.4, 120.0, 121.0, 122.6, 125.5, 126.1, 127.1, 127.3,

127.5, 127.8, 128.1, 128.3, 129.6, 130.4, 130.9, 131.9, 133.8, 134.7, 134.7,

134.9, 135.5, 139.8, 141.0, 141.1, 146.3, 147.2, 147.3, 147.8, 148.2, 149.3,

153.3, 155.6, 165.5, 165.9.

X-ray

crystallographic

data

for

3:

Chemical

formula:

C

_67.33H_82.33Cl_11.33N₅O₄, M_w=1427.48; T=173.0(1) K; Mo_Karadiation

¯

(0.71073 ); triclinic; P1; a=14.105(3), b=18.436(4), c=22.291(5) ;

a=70.38(3), b=88.36(3), g=89.41(3)8; V=5458(2) ³; Z=3; 1_calcd

1.303 gcm^ꢀ3m=0.480 mm^ꢀ1

=

,

;

FACHTRE(GNU 000)=2238; colorless; 0.400.12

0.06 mm³crystal; Bruker Nonius Kappa CCD diffractometer; 13974 In-

dependent reflections; 11756 with I>2s; Gaussian absorption correction;

min and max transmission: 0.8311 and 0.9718; 2121 restraints; 1220 pa-

rameters; R1=0.1609; wR2=0.4740 [I>2s]; R1=0.1757; wR2=0.4863

[all data]; GOF=2.296; extinction coefficient=0.038(6); largest diff.

ꢀ3

peak and hole: 2.57 and ꢀ1.04 e

X-ray crystallographic data

_144.40H_164.40Cl₃N₁₀O_23.80Pd; M_w=2633.63; T=173.0(1) K; Cu_Karadiation

.

for

34:

Chemical

formula:

C

¯

(1.54184 ); triclinic; P1; a=12.0618(8), b=16.091(2), c=24.424(2) ;

a=72.443(4), b=82.028(4), g=69.181(3)8; V=4221.8(6) ³; Z=1;

[9] a) C. A. Hunter, J. Chem. Soc. Chem. Commun. 1991 , 74 9 –7 51;

b) C. A. Hunter, J. Am. Chem. Soc. 1992 , 114 , 530 3 –5 311.

Chem. Eur. J. 2008, 14, 10012 – 10028

ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

10027

C. A. Schalley et al.

[10] a) F. Vçgtle, S. Meier, R. Hoss, Angew. Chem. 1992 , 104 , 162 8 –

1631; Angew. Chem. Int. Ed. Engl. 1992 , 31 , 161 9 –1 622; b) S.

Ottens-Hildebrandt, S. Meier, W. Schmidt, F. Vçgtle, Angew. Chem.

1994 , 106 , 181 8 –1 821; Angew. Chem. Int. Ed. Engl. 1994 , 33 , 176 7 –

1770.

[11] a) C. A. Schalley, W. Reckien, S. Peyerimhoff, B. Baytekin, F.

Vçgtle, Chem. Eur. J. 2004 , 10 , 477 7 –4 789; b) C. Spickermann, T.

Felder, C. A. Schalley, B. Kirchner, Chem. Eur. J. 2008 , 14 , 121 6 –

1227.

[12] For selected examples, see: a) F. Vçgtle, M. Händel, S. Meier, S.

Ottens-Hildebrandt, F. Ott, T. Schmidt, Liebigs Ann. 1995, 739–743;

b) B. A. Blight, K. A. Van Noortwyk, J. A. Wisner, M. C. Jennings,

Angew. Chem. 2005 , 117 , 152 3 –1 528; Angew. Chem. Int. Ed. 2005 ,

44 , 149 9 –1 504; c) P. Ghosh, G. Federwisch, M. Kogej, C. A. Schal-

ley, D. Haase, W. Saak, A. Lützen, R. M. Gschwind, Org. Biomol.

Chem. 2005 , 3 , 269 1 –2 700; d) B. A. Blight, X. Wei, J. A. Wisner,

M. C. Jennings, Inorg. Chem. 2007 , 46 , 844 5 –8 447.

[13] a) R. Jäger, F. Vçgtle, Angew. Chem. 1997 , 109 , 96 6 –9 80; Angew.

Chem. Int. Ed. Engl. 1997 , 36 , 93 0 –9 44; b) C. A. Schalley, T. Wei-

landt, J. Brüggemann, F. Vçgtle, Top. Curr. Chem. 2005, 248, 141–

200.

Schalley, G. Silva, C.-F. Nising, P. Linnartz, Helv. Chim. Acta 2002 ,

85 , 157 8 –1 596; also see: P. Ghosh, O. Mermagen, C. A. Schalley,

Chem. Commun. 2002 , 262 8 –2 629.

[25] C. A. Schalley, P. Ghosh, M. Engeser, Int. J. Mass Spectrom. 2004 ,

232–233 , 24 9 –2 58; also see: C. A. Schalley, J. Hoernschemeyer, X.-y.

Li, G. Silva, P. Weis, Int. J. Mass Spectrom. 2003 , 228 , 37 3 –3 88.

[26] T. Felder, C. A. Schalley, Angew. Chem. 2003 , 115 , 236 0 –2 363;

Angew. Chem. Int. Ed. 2003 , 42 , 225 8 –2 260.

[27] a) A. Affeld, G. M. Hübner, C. Seel, C. A. Schalley, Eur. J. Org.

Chem. 2001 , 287 7 –2 890; b) P. Linnartz, S. Bitter, C. A. Schalley,

Eur. J. Org. Chem. 2003 , 481 9 –4 829; c) P. Linnartz, C. A. Schalley,

Supramol. Chem. 2004 , 16 , 26 3 –2 67.

[28] J. Kagan, S. K. Arora, J. Org. Chem. 1983 , 48 , 431 7 –4 320.

[29] a) C. Goze, G. Ulrich, L. J. Mallon, B. D. Allen, A. Harriman, R.

Ziessel, J. Am. Chem. Soc. 2006 , 128 , 1023 1 –1 0239; b) Y.-H. Yu,

A. B. Descalzo, Z. Shen, H. Rçhr, Q. Liu, Y.-W. Wang, M. Spieles,

Y.-Z. Li, K. Rurack, X.-Z. You, Chem. Asian J. 2006 , 1 , 17 6 –1 87;

c) A. Harriman, L. J. Mallon, B. Stewart, G. Ulrich, R. Ziessel, Eur.

J. Org. Chem. 2007 , 319 1 –3 198; d) A. Loudet, K. Burgess, Chem.

Rev. 2007 , 107 , 489 1 –4 932.

[30] a) B. Turfan, E. U. Akkaya, Org. Lett. 2002 , 4 , 285 7 –2 859; b) A.

Coskun, B. T. Baytekin, E. U. Akkaya, Tetrahedron Lett. 2003 , 44 ,

564 9 –5 651.

[14] X. Y. Li, J. Illigen, M. Nieger, S. Michel, C. A. Schalley, Chem. Eur.

J. 2003 , 9 , 133 2 –1 347.

[15] The term “post-macrocyclization pathway” has previously been used

in: W. Van Rossom, W. Maes, L. Kishore, M. Ovaere, L. Van Meer-

velt, W. Dehaen, Org. Lett. 2008, 10, 585–588.

[16] C. Bilton, J. A. K. Howard, N. N. L. Madhavi, A. Nangia, G. R. De-

siraju, F. H. Allen, C. C. Wilson, Chem. Commun. 1999 , 167 5 –1 676.

[17] a) K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 1975 ,

16 , 446 7 –4 470; b) R. Chinchilla, C. Najera, Chem. Rev. 2007 , 107 ,

87 4 –9 22.

[31] a) Y. Li, H. Zheng, Y. Li, S. Wang, Z. Wu, P. Liu, Z. Gao, H. Liu, D.

Zhu, J. Org. Chem. 2007 , 72 , 287 8 –2 885; b) H. T. Baytekin, Fluores-

cent Sensing of Cations, Anions and Neutral Molecules Towards In-

formation Processing at Molecular Level, The Graduate School of

Natural and Applied Sciences of Middle East Technical University,

Ankara, 2002.

[32] B. J. Holliday, C. A. Mirkin, Angew. Chem. 2001 , 113 , 207 6 –2 097;

Angew. Chem. Int. Ed. 2001 , 40 , 202 2 –2 043.

[18] A. S. Hay, J. Org. Chem. 1962 , 27 , 332 0 –3 321.

[19] For a recent review, see: J. E. Moses, A. D. Moorhouse, Chem. Soc.

Rev. 2007 , 36 , 124 9 –1 262.

[20] T. Ishiyama, M. Murata, N. Miyaura, J. Org. Chem. 1995 , 60 , 750 8 –

7510.

[21] N. Miyaura, A. Suzuki, Chem. Rev. 1995 , 95 , 245 7 –2 483.

[22] a) D. M. T. Chan, K. L. Monaco, R. P. Wang, M. P. Winters, Tetrahe-

dron Lett. 1998 , 39 , 293 3 –2 936; b) P. Y. S. Lam, C. G. Clark, S. Sau-

bern, J. Adams, M. P. Winters, D. M. T. Chan, A. Combs, Tetrahe-

dron Lett. 1998 , 39 , 294 1 –2 944.

[33] P. J. Stang, D. H. Cao, J. Am. Chem. Soc. 1994 , 116 , 498 1 –4 982.

[34] For X-ray crystallographic data of 34, see the Experimental Section.

[35] CACHE 5.0 for Windows, Fujitsu, Krakow, (Poland), 2001.

[36] a) P. Rajasingh, R. Cohen, E. Shirman, L. J. W. Shimon, B. Rybtch-

inski, J. Org. Chem. 2007 , 72 , 597 3 –5 979; b) A. Bohm, H. Arms, G.

Henning, P. Blaschka, BASF, German Patent No. DE 19547209A1,

1997.

[37] a) H. Meyer, Monatsh. Chem. 1901, 22, 415; b) R. Jäger, T. Schmidt,

D. Karbach, F. Vçgtle, Synlett 1996 , 72 3 –7 25; c) R. Jäger, Disserta-

tion, Universität Bonn, Bonn (Germany), 1997.

[23] The bromo derivatives of pyridines, pyrimidines, and terpyridines

are relatively unreactive in Suzuki coupling reactions, therefore,

their boronates need to be used, see also: a) W. Goodall, K. Wild,

K. J. Arm, J. A. G. Williams, J. Chem. Soc. Perkin Trans. 1 2002,

1669–1681; b) C. J. Aspley, J. A. G. Williams, New J. Chem. 2001 , 25 ,

113 6 –1 147.

[38] J. S. Park, J. N. Wilson, K. I. Hardcastle, U. H. F. Bunz, M. Sriniva-

sarao, J. Am. Chem. Soc. 2006 , 128 , 771 4 –7 715.

[39] A. Kraft, Liebigs Ann./Recl. 1997, 1463–1471.

[24] a) G. M. Hübner, J. Gläser, C. Seel, F. Vçgtle, Angew. Chem. 1999 ,

111 , 39 5 –3 98; Angew. Chem. Int. Ed. 1999 , 38 , 38 3 –3 86; b) C. A.

Received: June 27, 2008

Published online: September 30, 2008

10028

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ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2008, 14, 10012 – 10028

Article Doi

A modular "toolbox" approach to flexible branched multimacrocyclic hosts as precursors for multiply interlocked architectures

DOI: 10.1002/chem.200801289

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Article abstract of DOI:10.1002/chem.200801289

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