Molecular gauge blocks for building on the nanoscale

DOI: 10.1002/chem.201201985

Molecular Gauge Blocks for Building on the Nanoscale

Sergio Grunder,^[a]Cory Valente,^[a]Adam C. Whalley,^[a]Srinivasan Sampath,^[a]

Jꢀrg Portmann,^[b]Youssry Y. Botros,^[c]and J. Fraser Stoddart*^{[a, d]}

Abstract: Molecular gauge blocks,

based on 1–7, 9–11 paraxylene rings,

have been synthesized as part of a ho-

mologous series of oligoparaxylenes

(OPXs) with a view to providing a mo-

lecular tool box for the construction of

nano architectures—such as spheres,

cages, capsules, metal–organic frame-

works (MOFs), metal–organic polyhe-

drons (MOPs) and covalent–organic

frameworks (COFs), to name but a

few—of well-defined sizes and shapes.

Twisting between the planes of contigu-

ous paraxylene rings is generated by

the steric hindrance associated with the

methyl groups and leads to the exis-

tence of soluble molecular gauge

blocks without the need, at least in the

case of the lower homologues, to intro-

duce long aliphatic side chains onto the

phenylene rings in the molecules. Al-

though soluble molecular gauge blocks

with up to seven consecutive benzenoid

rings have been prepared employing

repeating paraxylene units, in the case

of the higher homologues it becomes

necessary to introduce hexyl groups in-

stead of methyl groups onto selected

phenylene rings to maintain solubility.

A hexyl-doped compound with seven

substituted phenylene rings was found

to be an organogelator, exhibiting ther-

mally reversible gelation and a critical

gelation concentration of 10 mm in di-

methyl sulfoxide. Furthermore, control

over the morphology of a series of

hexyl-doped OPXs to give microfibers,

microaggregates, or nanofibers, was ob-

served as a function of their lengths ac-

cording to images obtained by scanning

electron microscopy. The modular syn-

theses of the paraphenylene derivatives

rely heavily on Suzuki–Miyaura cross-

coupling reactions. The lack of p–p

conjugation in these derivatives that is

responsible for their enhanced solubili-

ties was corroborated by UV/Vis and

fluorescent spectroscopy. In one partic-

ular series of model OPXs, dynamic

¹H NMR spectroscopy was used to

probe the stereochemical consequences

of having from one up to five axes of

chirality present in the same molecule.

The Losanitsch sequence for the com-

pounds with 1–3 chiral axes was estab-

lished, and a contemporary mathemati-

cal way was found to describe the se-

quence. The development of the ways

and means to make molecular gauge

building blocks will have positive re-

percussions on the control of nano-

structures in general. Their incorpora-

tion into extended structures with the

MOF-74 topology provides an excel-

lent demonstration of the potential

usefulness of these molecular gauge

blocks.

Keywords: atropisomers

coupling metal–organic frame-

works · oligoparaxylenes · oligo-

AHCTUNGTRENNGpUN henylenes

·

cross

·

[a] Dr. S. Grunder, Dr. C. Valente, Dr. A. C. Whalley, Dr. S. Sampath,

Prof. J. F. Stoddart

[d] Prof. J. F. Stoddart

NanoCentury KAIST Institute and

Department of Chemistry, Northwestern University

2145 Sheridan Road, Evanston, IL 60208-3113 (USA)

Fax : (+1)847-491-1009

Graduate School of EEWS (WCU)

Korea Advanced Institute of Science and Technology (KAIST)

373-1 Guseong Dong, Yuseong Gu

E-mail: stoddart@northwestern.edu

Daejon 305-701 (Republic of Korea)

[b] J. Portmann

Supporting information for this article is available on the WWW under

http://dx.doi.org/10.1002/chem.201201985.

Department of Mathematics, ETH Zꢀrich

Rꢁmistrasse 101, 8092 Zꢀrich (Switzerland)

[c] Dr. Y. Y. Botros

Department of Materials Science and Engineering

Northwestern University

2145 Sheridan Road, Evanston, IL 60208-3113 (USA)

and Intel Labs, Building RNB-6-61

2200 Mission College Blvd.,

Santa Clara, CA 95054-1549 (USA)

and National Center for Nano Technology Research

King Abdulaziz City for Science and Technology (KACST)

P.O. Box 6086, Riyadh, 11442 (Saudi Arabia)

15632

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2012, 18, 15632 – 15649

FULL PAPER

Introduction

Results and Discussion

The technical and financial limitations surrounding the fab-

rication of integrated systems by top-down approaches at

the lower end of the nanoscale regime are conspiring to-

gether to increase the importance of developing bottom-up

approaches to constructing either by strict self-assembly^[1]or

by template-directed synthesis^[2]—itself dependent on the

operation of both molecular recognition^[3]and self-assembly

processes^[4]—molecular building blocks at the higher end of

the ꢃngstrom scale.

For we as chemists to be able to control the size and

shape of nanoscale architectures built in three-dimensional

space—be they spheres,^[5]cages^[6]and capsules^[7]or metal–

organic frameworks (MOFs),^[8]metal–organic polyhedrons

(MOPs),^[9]covalent–organic frameworks (COFs),^[10]or other

artificial architectures^[4a,11]—it is crucial for us to evolve a

chemistry capable of providing modular building blocks for

construction^[12]on the nanoscale that are similar in concept

to the gauge blocks used by engineers working in the macro-

scopic world. In the interests of creating space inside cages

and capsules, and porosity within the extended structures of

MOFs and COFs, it is important to identify linkers which

are slender, rigid, and soluble, at least at the beginning of

the construction phase. It follows immediately that the reac-

tion toolbox available to the synthetic chemist can be ex-

ploited creatively for the synthesis of such molecules in an

efficient, convergent and streamlined fashion.

At the molecular level, obvious structural linkers are the

oligophenylenes^[13]except that, once they are longer than a

couple of phenylene units, the compounds are plagued by

low solubilities.^[14]We describe in this full paper, how, in

order to overcome the characteristic low solubilities of the

oligophenylenes, we have turned our attention to exploring

the chemistry of the related oligoparaxylenes (OPXs). It

transpires that, in the case of these OPXs, the steric hin-

drance experienced between the methyl groups located on

contiguous benzenoid rings induces a twist in the planes of

the paraxylene rings that results in the breaking of the p–p

conjugation,^[15]as well as the disruption of the intermolecu-

lar p···p stacking leading to a dramatic increase in their solu-

bilities in organic solvents. The OPXs have already been

recognized as rigid and non-conjugated gauges for charge

transfer investigations.^[14–16]

In this full paper, we report 1) design criteria and synthet-

ic strategies for building soluble, slender, and rigid organic

gauge blocks; 2) the detailed general synthesis of all the

OPX struts using an efficient, iterative, and convergent

cross-coupling approach; 3) the control over morphology as

a function of the length on the hexyl-doped OPX series; 4)

a complex stereochemical investigation of the atropisomers

with one up to as far as five axes of chirality and a mathe-

matical description of the Losanitsch sequence;^[17]and, as an

example of an application,^[18]5) we mention briefly our

work recently reported using those blocks for defining the

size of pore apertures in MOFs.

Synthesis: At the outset before tackling the syntheses of a

series of palindromic oligophenylenes we addressed the fol-

lowing issues and set ourselves certain goals accordingly.

1) Substituents and solubility: We decided to circumvent the

notoriously low solubilities of the parent oligophenylenes

by introducing pairs of methyl groups with para disposi-

tions onto all but the terminal phenylene rings in order

to impose torsional twists and hence nonplanarity be-

tween contiguous aromatic rings. This level of stereoelec-

tronic control reduces the p–p conjugation between the

rings and also impairs p···p stacking between the OPX

molecules, leading to the enhanced solubilities the OPXs

show with respect to their oligophenylene counterparts.

Ultimately, we discovered, however, that some of the

methyl groups had to be replaced on selected OPX rings

by hexyl substituents.

2) Functionality and additional substituents: We opted in

tackling the first homologous series of palindromic

OPXs to introduce a-hydroxycarboxylic acids (HCAs)

onto the terminal phenylene rings. The precursors to

these derivatives were benzyloxy methyl esters (BMEs).

Subsequently, we also synthesized a homologous series

of palindromic OPXs substituted on their terminal phen-

ACHUTNGERNyNUG lACHTGUNTRENNUeG ne rings with methyl esters (ME) and methyl groups

oriented meta to each other. This suite of OPXs was em-

ployed to probe the consequences of introducing pro-

gressively more and more axes of chirality into the

OPXs.

3) Quantities: We chose the methods of syntheses of the

OPXs such that we could access them in several gram

quantities with high purities. In order to accomplish this

goal, we synthesized the gauge block methyl 2-(ben

ACHTUNGTRENNUNGzyl-

AHCTUNGTREGoNNUN xy)-4-(pinacolboronic ester) benzoate (3) on a 100 g

scale, starting from the commercially available methyl 4-

iodosalicylate (1).

With many subsequent Suzuki–Miyaura cross-coupling re-

actions^[19]in mind, protection of the hydroxyl groups in the

HCAs had to be considered. The benzyl ether proved to be

suitable because of 1) its facile introduction and the ease of

isolation of the intermediates on a large scale, 2) its stability

towards the coupling conditions and 3) its straightforward

and efficient removal by hydrogenolysis.

Methyl 4-iodosalicylate (1) was reacted (Scheme 1) with

benzyl bromide in MeCN under reflux overnight and, after

removal of the insoluble salts by filtration, methyl 2-(ben

ACHTUNGTRENNUNGzyl-

AHCTUNGTREGoNNNU xy)-4-iodobenzoate (2) was obtained as a solid, which was

1

pure by H NMR spectroscopy. The boronic ester was then

introduced by using standard Pd-catalyzed chemistry to pro-

vide yellow needles of 3 in 78% yield after filtration of the

crude reaction mixture through Celite, concentration of the

filtrate and recrystallization of the residue.

Suzuki–Miyaura cross-coupling reactions^[19]were ideally

suited to the assembly of the OPX backbones. Conditions

Chem. Eur. J. 2012, 18, 15632 – 15649

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

15633

J. F. Stoddart et al.

Scheme 1. Preparation of 2-mer-HCA, 3-mer-HCA, and 4-mer-HCA.

involving [PdCl

(dppf)] (dppf=1,1’-bis(diphenylphosphino)-

96% yield. After hydrogenolysis and saponification, 3-mer-

HCA was obtained as a colorless solid in 87% yield over

the two reaction steps. In order to obtain 4-mer-HCA, 3 was

first of all reacted with 4,4’-diiodo-2,2’,5,5’-tetramethylbi-

phenyl (5)^[15a]yielding 4-mer-BME in 87% yield. Thereafter,

4-mer-BME was subjected to hydrogenolysis and saponifica-

tion in order to obtain the 4-mer-HCA as a colorless solid in

89% yield over the two reaction steps.

In order to synthesize the higher homologues of the

OPXs, a strategy was developed involving the extension of

the terminal boronic ester building blocks, bearing carboxyl

and hydroxyl groups, before coupling them to an appropri-

ate dihalide to constitute the midriffs of 6-mer-HCA and 7-

mer-HCA. The extension of the terminal building block was

achieved (Scheme 2) by reacting 3 with an excess of the ap-

propriate dihalide in order to statistically favor the mono-

coupled product. Thus, when 3 was reacted using the stand-

ard Suzuki–Miyaura conditions^[19]with 5.0 equivalents of

ferrocene) and CsF in a p-dioxane/H₂O (v/v 2:1) solvent

mixture were found to be high yielding, tolerant to the pro-

tecting groups, and generally applicable throughout the

entire series of the OPXs. Applying these conditions, hence-

forth referred to as the standard Suzuki–Miyaura cross-cou-

pling conditions,^[19]to the reaction of the key boronic ester

building block 3 with the iodide 2 led to the formation of

the 2-mer-BME, which precipitated out of the reaction mix-

ture and was isolated by filtration in 83% yield. In order to

remove the benzyl ether protecting groups, 2-mer-BME was

exposed to standard hydrogenolysis conditions of Pd/C in

THF under an atmosphere of H₂. Thereafter, the methyl

esters were saponified in a THF/0.5m aq NaOH (v/v 1:1)

mixture to yield 2-mer-HCA as a colorless solid after acidifi-

cation of the aqueous layer. Coupling 2.2 equivalents of the

key building block 3 with 1.0 equivalent of the commercially

available 2,5-dibromoparaxylene (4) afforded 3-mer-BME in

Scheme 2. Preparation of the boronic ester building blocks 7, 9, and 11.

15634

www.chemeurj.org

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2012, 18, 15632 – 15649

Molecular Gauge Blocks

FULL PAPER

2,5-dibromoparaxylene (4), the desired bromide 6 was iso-

lated by flash chromatography in 67% yield. Subsequently,

the bromide 6 was converted to the boronic acid pinacol

ester 7 in 94% isolated yield by employing a Pd-catalyzed

cross-coupling reaction. By applying a similar reaction pro-

cedure, but by using an excess of 4,4’-diiodo-2,2’,5,5’-tetra-

methylbiphenyl (5) as the dihalide, the terphenyl derivative

8 was obtained in 66% yield. In order to effect an increase

in the number of phenylene units, compound 7 was reacted

in another statistically driven Suzuki–Miyaura cross-cou-

pling reaction^[19]with an excess of the diiodide 5 to yield

(63%) compound 10, which was converted subsequently to

the boronic acid pinacol ester to provide building block 11

in 72% yield. With all the boronic ester building blocks in

hand, the assemblies of the longer OPX rods (Scheme 3)

were tackled.

analytical methods, because of their low solubilities in most

common solvents. In order to access even longer OPXs, we

had to find another way of increasing their solubilities.

Hence, we set out to prepare a series of hexyl-doped OPXs

in which a few selected methyl groups were replaced by

hexyl substituents.

A key building block for these hexyl-doped OPXs—

namely 1,4-dihexyl-2,5-diiodobenzene (12)—was prepared in

three steps, starting from 1,4-diiodobenzene following a re-

ported procedure.^[19]Coupling the boronic ester building

blocks 3, 7, 9, and 11 with 12 by using the standard Suzuki–

Miyaura coupling conditions led (Scheme 4) to the isolation

of hex-3-mer-BME, hex-5-mer-BME, hex-7-mer-BME, and

hex-9-mer-BME in 74–91% yields. Following hydrogenolysis

and subsequent saponification, hex-3-mer-HCA, hex-5-mer-

HCA, hex-7-mer-HCA, and hex-9-mer-HCA were isolated,

all as colorless solids, in quantitative yields.

Compound 7 was reacted with 2,5-dibromoparaxylene (4)

by using the standard Suzuki–Miyaura cross-coupling condi-

tions to yield 5-mer-BME in 77% yield. After hydrogenoly-

sis and saponification 5-mer-HCA was obtained as a color-

less solid. Coupling 7 with compound 5 led to the formation

of 6-mer-HCA after hydrogenolysis and saponification of 6-

mer-BME. With the objective of synthesizing 7-mer-HCA, 9

was coupled in a Suzuki–Miyaura reaction with 4 yielding

(85%) 7-mer-BME, which was still easily soluble in

common organic solvents. The solubility decreased dramati-

cally, however, after removal of these protecting groups:

more than 1000 scans were required to record an acceptable

¹H NMR spectrum on a saturated solution of 7-mer-HCA at

808C in CD₃SOCD₃. While it was possible to assemble the

backbones of the compounds having eight, nine, and ten

contiguous paraxylene units by coupling compounds 9 and

11 with 4 and 5, it was not possible to characterize the corre-

sponding n-mer-HCAs (n=8, 9, 10) employing the normal

The introduction of hexyl chains onto the central benze-

noid ring of the molecular struts not only led to increased

solubility, but it also gave rise to some self-assembly-based

phenomena. Experiments were conducted on hex-3-mer-

HCA, hex-5-mer-HCA, and hex-7-mer-HCA in Me₂SO.

Scanning electron microscopy (SEM) images of the dried

sample of hex-3-mer-HCA obtained by drop-casting a solu-

tion of the sample in Me₂SO revealed (Figure 1A) the pres-

ence of self-assembled tape-like morphologies. On the other

hand, self-assembly of hex-5-mer-HCA resulted (Figure 1B)

in the formation of microspheres. The SEM image of hex-7-

mer-HCA revealed (Figure 1C) the presence of intertwined

and extended fibrillar network morphologies. These SEM

images indicate the stronger self-assembling property of

hex-7-mer-HCA relative to that of hex-3-mer-HCA and hex-

5-mer-HCA. These superior self-assembling properties of

hex-7-mer-HCA were also observed in gelation experiments.

Scheme 3. Preparation of the OPXs 5-mer-HCA, 6-mer-HCA, and 7-mer-HCA.

Chem. Eur. J. 2012, 18, 15632 – 15649

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

15635

J. F. Stoddart et al.

Scheme 4. Preparation of the hexyl-doped OPXs hex-3-mer-HCA, hex-5-mer-HCA, hex-7-mer-HCA, and hex-9-mer-HCA.

While hex-3-mer-HCA and hex-5-mer-HCA do not form

gels, hex-7-mer-HCA produces an organogel in Me₂SO at

concentrations above 10 mm. Photographs of hex-7-mer-

HCA in the solution and gel state are displayed in Fig-

ure 1D. Upon heating the gel, the self-assembly breaks and

results in the formation of the solution state. Self-assembly

and gelation can be made to be reversible by cooling the

solution to room temperature, demonstrating its thermore-

versible characteristics.

Finally, we targeted the synthesis (Scheme 5) of hex-11-

mer-HCA with four hexyl substituents. The terphenylboron-

ic acid pinacol ester building block 9 was extended by reac-

tion with an excess of 12 under the standard Suzuki–

Miyaura coupling conditions^[19]to give the iodide 16 in 40%

yield as a colorless solid. In order for it to serve as the cen-

tral building block, the diboronic ester terphenyl derivative

15 was prepared, starting from 2,5-dibromo-paraxylene (4).

Both bromides in compound 4 were substituted with a bor-

onic ester to yield 13, which was subsequently treated with

an excess of 4 in a Suzuki–Miyaura reaction^[19]in order to

favor the statistical formation of the dibromo terphenyl de-

rivative 14. Once again, the bromides were substituted with

boronic esters, providing the diboronic ester building block

Figure 1. SEM images of A) hex-3-mer-HCA (scale bar 500 mm), B) hex-

5-mer-HCA (scale bar 20 mm), C) hex-7-mer-HCA (scale bar 10 mm). All

samples were dropcasted from Me₂SO onto a silicon wafer. D) Photo-

graphs of hex-7-mer-HCA in solution (left) and gel (right) state (10 mm

in Me₂SO).

15636

www.chemeurj.org

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2012, 18, 15632 – 15649

Molecular Gauge Blocks

FULL PAPER

Scheme 5. Preparation of the most extended OPX reported in this article hex-11-mer-HCA.

15 which (as 1.0 equiv) was reacted with 2.2 equivalents of

the iodide 16, applying the standard Suzuki–Miyaura cou-

pling conditions.^[19]The oligomer hex-11-mer-BME precipi-

tated out of the reaction mixture and was filtered off after

being cooled to room temperature, washed with H₂O and

MeOH, and finally purified by column chromatography.

After hydrogenolysis (H₂/Raney Ni in THF) and subsequent

saponification, hex-11-mer-HCA was isolated as a colorless

powder.

300 nm in the UV/Vis absorbance spectra of compounds 2-

mer-ME to 6-mer-ME do not change significantly on in-

creasing the number of phenylene units from 2–6. Since a

movement towards a lower energy of the absorption edge is

expected^[13e]on increasing the number of conjugated para-

phenylenes, we conclude that the paraxylene units are some-

what isolated electronically. The fluorescence spectra on the

other hand show a slight bathochromic shift as the oligomer

length is increased from 2–4 rings. The emission l_maxfor the

4, 5, and 6 ring oligomers (2-mer-ME to 6-mer-ME), howev-

er, is only shifted ever so slightly, leading to the conclusion

that the effective conjugation length in the excited state is

reached at four rings. These findings agree with previously

reported data.^[13c]

Since the steric hindrance between the ortho-methyl

groups on each biphenyl subunit renders the planar confor-

mation of the molecule an energy maximum and results in a

twist between the planes of adjacent phenylene units, non-

planar isomers are generated with chiral axes, the helical

sense of which is maintained as a result of hindered rotation

about the single bonds. The simplest example with only two

rotationally restricted phenylene units and one axis of chir-

ality results in two enantiomers. When the number of con-

tiguous rotationally restricted units is increased, however, a

more complex mixture of atropisomers is obtained. In order

to investigate and characterize these isomers, a series of

model compounds (2-mer-ME to 6-mer-Me) was prepared.

They lack the hydroxyl group on the terminal phenylene

rings, but have a methyl group in the meta position to the

carbonyl group instead so as to hinder all the phenylene

units rotationally. Since the rotational barrier is too low to

isolate individual conformational isomers, ¹H NMR spec-

Since the hindered rotation of the ortho-methyl-substitut-

ed oligophenylenes confers elements of axial chirality, it was

desirable that we investigate the resulting atropisomers. In

order to address this rich stereochemical feature,^[17]a series

of OPXs were synthesized in which the ortho-hydroxyl

groups were eradicated from both terminal phenylene units,

and methyl groups meta to the carboxyl groups were added

so as to restrict the relative torsional angles between every

single phenylene unit along the backbone of the OPXs.

Commercially available methyl-4-bromo-3-methylbenzoate

(17) was converted into its boronic ester 18, which was then

coupled—using the general Suzuki–Miyaura coupling condi-

tions^[19]—with 18, 4, and 5 to provide (Scheme 6) 2-mer-ME,

3-mer-ME, and 4-mer-ME, respectively. In order to obtain

higher homologues, 18 was extended by a further phenylene

unit by reacting it with an excess of dibromide 4 and subse-

quently substituting the bromide with a pinacol boronic

ester, leading to compound 20, which was coupled—using

the general Suzuki–Miyaura coupling conditions^[19]—with 4

and 5, providing 5-mer-ME and 6-mer-ME, respectively.

The reduced conjugation, induced by the twist between

the planes of the neighboring phenylene rings is evident

from spectrophotometric measurements (Figure S1 in the

Supporting Information). The absorption edge at around

ACHUTNGERNtNUG rosHCATUNGTRNEcNUGN opy was employed to gain a better understanding of

Chem. Eur. J. 2012, 18, 15632 – 15649

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

15637

J. F. Stoddart et al.

Scheme 6. Preparation of the sries of model compounds for the investigation of the atropisomers 2-mer-ME, 3-mer-ME, 4-mer-ME, 5-mer-ME, and 6-

mer-ME.

the different conformations present in solution. We have

two broad resonances for the constitutionally heterotopic

methyl group protons are observed at 352 K that both sub-

sequently separate out, giving a total of four equal intensity

anisochronous signals for the two homotopic pairs in the

enantiomers and the two enantiotopic pairs in the meso

isomer. A barrier to rotation of the paraxylene units linked

to each other of about 18 kcalmol^ꢀ1—consistent with previ-

ously reported values^[13e,15a]—was obtained using the Eyring

equation [Eq. (1)].^[21]

1

used the methyl groups in the OPXs as H NMR probes of

1

the stereochemistry. When H NMR spectroscopy was per-

formed on the OPX oligomers 2-mer-ME to 6-mer-ME in

order to characterize the isomers over a range of tempera-

tures from 360 down to 240 K, deuterated toluene (C₇D₈)

was found to lead to the best resolution between signals for

the probe methyl group protons in the different isomers

generated by multiple axes of chirality in the oligomers

1

from 3-mer-ME upwards. Thus, all H NMR spectra were re-

¼

ð1Þ

DG ¼ 0:0191 T_c½9:97 þ logðT_c=DvÞꢁ

corded at 10 K intervals in C₇D₈after the samples had been

left in the NMR probe to equilibrate at every temperature

for 15 min. In the case of 2-mer-ME consisting of two para-

xylene units and one chiral axis, two enantiomers are pres-

ent, namely (R)-2-mer-ME and (S)-2-mer-ME (Figure 2a).

As a consequence of the C₂symmetry present in both the R

and S isomers, both methyl groups are homotopic by inter-

nal comparison and equivalent by external comparison and

result in only one (isochronous) methyl resonance being ob-

Composed of four rotationally hindered paraxylene units,

4-mer-ME has three axes of chirality that lead to the exis-

tence (Table 1, Figure 2c) of six different isomers, namely,

three pairs of enantiomers, (RRR)-4-mer-ME/

ACHTUNGTREN(NUNG SSS)-4-mer-

ME, (RRS)-4-mer-ME/(SSR)-4-mer-ME, and (RSR)-4-mer-

AHCTUNGTRENNUNG

ME and (SRS)-4-mer-ME. The four conformational sym-

metrical (C₂) isomers namely, the RRR, SSS, RSR, and SRS

isomers all contain three enantiotopic pairs of constitution-

ally heterotopic methyl groups giving rise to three aniso-

1

served in the H NMR spectrum of the racemic modifica-

tion.

1

The oligomer 3-mer-ME with two axes of chirality can

exist (and does) as three isomers (Figure 2b), namely (RR)-,

(SS)- and (RS)-3-mer-ME in the ratio of 1:1:2. The two

enantiomers (RR)- and (SS)-3-mer-ME have C₂symmetry

and are, of course, chiral. The meso isomer, (RS)-3-mer-ME,

has reflection symmetry (C_i), which means it is achiral.

While the enantiomers behave as one compound in the

¹H NMR spectrum, they are diastereoisomeric with the

meso isomer. Thus, overall, in the case of the 3-mer-ME,

two compounds can be identified in a mixture (and equili-

chronous signals in the low-temperature H NMR spectrum

for each enantiomeric pair, that is, six resonances overall for

the RRR, SSS, RSR, and SRS isomers. In the case of the

conformationally unsymmetrical (C₁) enantiomers, (RRS)-4-

mer-ME/ACHTNUTRGNE(UNG SSR)-4-mer-ME, all six methyl groups are hetero-

topic when atropisomerism is slow on the ¹H NMR time-

scale and so give rise to six anisochronous resonances in

total in the low-temperature ¹H NMR spectrum. At high

temperatures, three broad resonances are observed in keep-

ing with the constitution of 4-mer-ME. On cooling down the

solution, these three resonances first of all separate into six

and then finally into 12 peaks (Figure 2e). These 12 peaks

constitute the sum of three peaks for the RRR and SSS

1

brating) in C₇D₈during variable-temperature H NMR spec-

troscopy (Figure 2d) at lower temperatures. Following some

coalescence behavior at higher (ca. 380 K) temperatures,

15638

www.chemeurj.org

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2012, 18, 15632 – 15649

Molecular Gauge Blocks

FULL PAPER

of chirality, and [ ] is the Gauss

bracket in which [(n+1)/2] is

the largest integer not greater

than (n+1)/2 (the real number

in the Gauss bracket is rounded

down).

½ðnþ1Þ=2ꢁꢀ1

A ¼ 2^nꢀ1þ 2

ð2Þ

In addition to our previously

reported work^[17]giving sub-

stance to the Losanitsch series,

we herein present a mathemati-

cal derivation of Equation (2).

While Losanitsch found the for-

mula for the Losanitsch se-

quence to be Equation (2)

based on fitting empirical data,

we have deduced what we be-

lieve to be an elegant way to

derive Equation (2) based on

contemporary

mathematical

methods. The chemical problem

of multiple isomers occurring as

mixtures and deducing the

number of isomers as a function

of the axes of chirality was ab-

stracted and reformulated into

a mathematical setting. In this

context, set theoretical and al-

gebraic methods were applied

to solve the problem mathemat-

ically. Involution and equiva-

lence classes were used as tech-

niques in the derivation. See

the Supporting Information for

more details.

Figure 2. a) (R)-2-mer-ME and its mirror image (S)-2-mer-ME. Both compounds have a C₂rotation axis of

symmetry which is perpendicular to the phenylene-connecting bond and an angle which is half the angle

formed by the two planes of the phenylenes. b) Three rotationally hindered phenylenes leads to three atrop-

Increasing the number of

chiral axes to n=4 and 5, the

number of isomers are A=10

and 20, respectively. For 5-mer-

ME (n=4), the 10 isomers lead

to 32 heterotopic methyl

groups, and for 6-mer-ME (n=

5), the 20 isomers lead to 80

heterotopic methyl groups. It

was not possible, however, to

resolve all these methyl peaks

ACHTUNGTRENNUNGisomers. Compounds (RR)-3-mer-ME and (SS)-3-mer-ME are chiral and have a C₂axis of rotation. (RS)-3-

mer-ME is achiral with a point of inversion as a symmetry element. c) The atropisomers with four hindered

phenylenes exist as three pairs of enantiomers, two of them (RRR/SSS & RSR/SRS) with a C₂axis of rotation,

one an asymmetric pair (RRS/SSR). Variable-temperature ¹H NMR experiments of d) compound 3-mer-ME

and e) 4-mer-ME in deuterated toluene (C₇D₈). The spectra were taken in 10 K increments and the system

was allowed to equilibrate at every temperature for 15 min. On the NMR timescale, all of the expected methyl

peaks are observed, resulting in a total number of four methyl peaks for compound 3-mer-ME and twelve for

compound 4-mer-ME.

enantiomers, three peaks for the RSR and SRS enantiomers

and six peaks for the RRS and SSR enantiomers.

in the variable-temperature NMR spectra (Figures S2 and

S3 in the Supporting Information).

The task of predicting the number of isomers (A) is not

trivial, since it depends on whether the number of chiral ele-

ments is odd or even. Losanitsch has already investigated

the isomers in paraffins and found the so-called Losanitsch

series (2, 3, 6, 10, 20, 36, 72, 136, 272…) which can be de-

Conclusion

We have developed a highly efficient strategy for the syn-

thesis of a series of oligoparaxylene rods terminated by car-

boxyl and hydroxyl groups and consisting of at least two and

ACHTUNGTRENNUNG

Chem. Eur. J. 2012, 18, 15632 – 15649

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

15639

J. F. Stoddart et al.

Table 1. Conformational analysis of the isomers.

tuted with two hexyl instead of methyl groups were soluble

up to the homologue containing nine benzenoid rings—

throughout the odd series of three, five, seven and nine

rings—all linked to each other in a head-to-tail manner. In

the series of oligoparaxylene ligands with two hexyl groups

on the central benzenoid ring, thermoreversible gelation

was observed in dimethyl sulfoxide for the member of the

series consisting of seven benzenoid rings. Finally, in order

to achieve the syntheses of soluble ligands consisting of

eleven benzenoid rings, two of the paraxylene rings—the

fourth and eighth ones situated along the linear display—

were substituted each with two hexyl instead of methyl

groups. These constitutional features and selected modifica-

tions provide a suite of stable and rigid rods, ranging from 5

all the way up to 50 ꢃ in increments of roughly 5 ꢃ.

Compound

Isomer

Symmetry

Heterotopic Me

individual^[a]

total^[b]

2-mer-ME

R/S

C₂

1

4

3-mer-ME

RR/SS

RS

C₂

C_i

2

4-mer-ME

RRR/SSS

RSR/SRS

RRS/SSR

C₂

C₁

3

6

12

32

5-mer-ME

RRRR/SSSS

RSSR/SRRS

RRRS/SSSR

RRSR/SSRS

RRSS

C₂

C₁

C_i

4

8

4

RSRS

C_i

One of the attractions of the oligoparaxylenes over the

oligoparaphenylenes is their greatly increased solubilities,

because of the destabilization of the linear conjugated p-

system framework in the former brought about by the

mutual steric hindrance between near-neighbor methyl

groups, which force contiguous benzenoid rings out of pla-

narity with each other. Another consequence of this twisting

of the planes of the paraxylene rings is the introduction of

axes of chirality between each of the benzenoid rings, lead-

ing to complex mixtures of atropisomers. A series of five

model compounds in which the hydroxyl groups are no

longer present on the terminal benzenoid rings, which in-

stead carry methyl groups meta to methoxycarbonyl groups,

were synthesized and investigated by dynamic ¹H NMR

spectroscopy. These model 2-, 3-, 4-, 5-, and 6-mers have, in

turn, 2, 3, 6, 10, and 20 isomers with the possibilities of ob-

serving, in turn, resonances for 1, 4, 12, 32, and 80 aniso-

chronous methyl groups. A partial unraveling of this com-

6-mer-ME

RRRRR/SSSSS

RRSRR/SSRSS

RSSSR/SRRRS

RSRSR/SRSRS

RRRRS/SSSSR

RRRSR/SSSRS

RRRSS/SSSRR

RRSSR/SSRRS

RRSRS/SSRSR

RSRRS/SRSSR

C₂

C₁

1

5

10

80

[a] Number of heterotopic Me groups in H NMR spectroscopy for every

individual isomer. [b] Number of total heterotopic Me groups in

¹H NMR spectroscopy for a mixture of all isomers of a certain length.

up to eleven paraxylene rings linked in head-to-tail fashion

to produce rigid, linear, partially conjugated ligands. The

synthetic protocols adopted have relied heavily upon modu-

lar Suzuki–Miyaura cross-coupling reactions.^[19]The conver-

gent approach that was employed for the preparation of

these struts reduces the number of synthetic steps signifi-

cantly as well as the manipulations that are required to

reach the final products, while maximizing their overall

yields. For example, the 7-mer-HCA and hex-7-mer-HCA

were each prepared in seven steps in 32 and 39% overall

yields (longest linear sequences), respectively, corresponding

in turn to 85 and 87% yields per step! The hex-9-mer-HCA

and hex-11-mer-HCA were prepared in a short nine and

eight synthetic steps, respectively, with overall yields of 19

and 14% (longest linear sequences). These percentages

equate with an average of 83 and 78% per step for the syn-

thesis of a 40 ꢃ (hex-9-mer-HCA) and 50 ꢃ (hex-11-mer-

HCA) long strut, respectively. Moreover, the design and

strategy that were implemented render these compounds

soluble in a variety of organic solvents, while the high yield-

ing and clean reactions facilitated the straightforward isola-

tion of these exotic compounds and intermediates by selec-

tive precipitation or flash chromatography.

1

plexity by low-temperature H NMR spectroscopy revealed

that the barriers to rotation between the benzenoid rings

are of the order of 18 kcalmol^ꢀ1, that is, not large enough to

give rise to isolable isomers at room temperature.

What about applications for these rigid, linear, partially

conjugated ligands? So far, the oligoparaxylene gauge

blocks have been introduced into isoreticular (IR)-MOF-74

extended structures. The six longest members of the series

of IR-MOF-74 structures have the largest pore apertures of

any metal–organic frameworks so far reported in the litera-

ture. It has been shown that large biomolecules such as vita-

min B₁₂, myoglobin, and green fluorescent protein are able

to pass through the pores of the larger IR-MOF-74 struc-

tures.

We have examined the limitations and scopes of preparing

a molecular toolbox consisting of a large variety of building

blocks, enabling the modular assembly of slender and robust

organic rods with distinct and precise lengths, ranging from

5–50 ꢃ (Figure 3). The combination of the availability of

several such building blocks and the possibility of assem-

bling them in a modular fashion provides a rich toolbox of

nanoscale gauge blocks. All of the reported gauge blocks

have already been incorporated into metal-organic frame-

works.^[18]This direct transmission of the shape onto the

Molecular gauge blocks based solely on paraxylene rings

were found to be soluble in polar organic solvents all the

way up to the homologue containing seven paraxylene rings.

Ligands in which the central paraxylene rings are disubsti-

15640

www.chemeurj.org

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2012, 18, 15632 – 15649

Molecular Gauge Blocks

FULL PAPER

then cooled to RT and the products were purified using techniques out-

lined with specific measures for the individual reactions discussed in the

section on synthetic procedures.

Hydrogenolysis: The starting material was dissolved in anhydrous THF.

The Pd/C catalyst was added (10 w%) under an atmosphere of N₂. The

reaction mixture was stirred overnight under an atmosphere of H₂, fil-

tered over a Celite plug, washed with solvent and concentrated to give

the crude product which was used directly in the next step.

Saponifications: The starting material was stirred in a THF/aq. 0.5m

NaOH (1:1 v/v) mixture at 508C overnight. The THF was then removed

in vacuo to provide typically an insoluble white solid in H₂O. While stir-

ring, the aqueous layer was acidified with concentrated HCl until a pH

<2 was attained and the resulting precipitate was collected by vacuum

filtration, washed with ample H₂O and air-dried for 24 h to provide the

target compound as a white powder.

Synthetic procedures

Synthesis of methyl 2-(benzyloxy)-4-iodobenzoate (2): Solid K₂CO₃

(76.1 g, 0.55 mol) was added to a solution of 1 (76.5 g, 0.28 mol) in

MeCN (550 mL) at RT. Benzyl bromide (32.7 mL, 0.28 mol) was added

by means of a syringe, and the resulting reaction mixture was warmed to

808C and stirred overnight. The reaction mixture was then cooled to RT

and filtered subsequently to remove insoluble salts, which were washed

further with EtOAc. The filtrate was concentrated in vacuo, before redis-

solving the residue in fresh EtOAc and filtering it a second time. The fil-

trate was concentrated in vacuo to provide an oil which solidified upon

standing to yield 2 (100.5 g, 99%) as a beige solid which required no fur-

ther purification. ¹H NMR (500 MHz, CDCl₃, 258C): d=7.54 (d, J=

8.0 Hz, 1H), 7.49 (d, J=7.5 Hz, 2H), 7.43–7.35 (m, 4H), 7.33 (t, J=

7.5 Hz, 1H), 5.15 (s, 2H), 3.89 ppm (s, 3H); ¹³C NMR (126 MHz, CDCl₃,

258C): d=166.3, 158.4, 136.2, 133.1, 130.1, 128.8, 128.1, 127.0, 123.3,

120.3, 100.0, 71.0, 52.3 ppm; HRMS (ESI): m/z calcd for C₁₅H₁₄IO₃:

367.9909 [M+H]⁺; found: 367.9893.

Figure 3. Modeled structures in a relative length scale of the compounds

consisting of one up to eleven phenylene rings. The hydrogen atoms and

hexyl groups are omitted for clarity.

nano architectures and the wide modularity demonstrates

that these molecular gauge blocks are very powerful tools

for building on the nanoscale.

Experimental Section

Synthesis of 3: Anhydrous p-dioxane (1.35 L) was added to a three-neck

round-bottomed flask equipped with a reflux condenser and charged

with methyl 2-(benzyloxy)-4-iodobenzoate (100.2 g, 0.27 mol), bis(pinaco-

lato)diboron (76.0 g, 0.30 mol), KOAc (80.1 g, 0.82 mol) and [PdCl₂-

Materials and methods: Anhydrous tetrahydrofuran (THF), dichloro-

ACHTUNGTRENNUNGmethACHTUNGTRENNUNGane (CH₂Cl₂) and acetonitrile (MeCN) were obtained from an

EMD Chemicals DrySolv^ꢄsystem. Anhydrous p-dioxane and Me₂SO

were purchased from Aldrich and stored under an atmosphere of argon.

CDCl₃, C₆D₆, CD₂Cl₂, [D₈]THF and (CD₃)₂CO were purchased from Al-

drich and used without further purification. All other reagents and sol-

vents were purchased from commercial sources and were used without

further purification, unless indicated otherwise. All reactions were car-

ried out under an atmosphere of N₂in flame-dried flasks using anhydrous

solvents, unless indicated otherwise. Thin-layer chromatography (TLC)

was carried out using glass or aluminum plates, precoated with silica-gel

60 containing fluorescent indicator (Whatman LK6F). The plates were

inspected by UV light (254 nm) and/or KMnO₄stain. Column chroma-

tography was carried out employing the flash technique using silica-gel

AHCTUNGTRENNG(NU Ph₃P)₂] (3.8 g, 5.4 mmol). The reaction mixture was purged at RT with

dry N₂(approx. 30 min) and the flask was transferred to an oil-bath pre-

warmed to 1308C. The reaction mixture was heated under reflux for 16 h,

before being cooled to RT and filtered to remove insoluble salts, which

were washed further with EtOAc (150 mL). The filtrate was concentrated

in vacuo and the residue was dissolved in EtOAc (900 mL). Ample acti-

vated carbon was added to the dark brown/black solution and the result-

ing solution was warmed to reflux for 15 min. The insoluble material was

removed by hot filtration through a pad of Celite to provide a yellow sol-

ution which was concentrated in vacuo to provide an oil. To facilitate sol-

idification, hexanes (200 mL) were added and the solution was concen-

trated in vacuo. To remove any residual p-dioxane and/or EtOAc, this

co-evaporation process with hexanes was repeated a further two times, to

yield a light brown solid which was insoluble in hexanes at RT. Hexanes

(500 mL) was added to the solid and warmed to reflux to provide a ho-

mogeneous solution that was removed from the heat source and left to

stand overnight to crystallize. Filtration provided 3 (78.1 g, 78%) as

yellow needles. ¹H NMR (500 MHz, CDCl₃, 258C): d=7.80 (d, J=

7.5 Hz, 1H), 7.53 (d, J=7.5 Hz, 2H), 7.48 (s, 1H), 7.44 (dd, J=7.5,

1.0 Hz, 1H), 7.40 (t, J=8.0 Hz, 2H), 7.31 (t, J=7.5 Hz, 1H), 5.22 (s, 2H),

3.90 (s, 3H), 1.36 ppm (s, 12H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=

166.9, 157.4, 136.9, 134.7 (br), 130.9, 128.5, 127.7, 127.0, 126.9, 123.1,

119.3, 84.3, 70.6, 52.1, 24.9 ppm; HRMS (ESI): m/z calcd for C₂₁H₂₅BO₅:

369.1873 [M+H]⁺, 391.1693 [M+Na]⁺; found: 369.1884, 369.1702.

60F (230–400 mesh). ¹H and ¹³C NMR spectra were recorded on

a

Bruker ARX500 (500 MHz) spectrometer. UV/Vis spectra were recorded

on a Shimadzu UV-3600 spectrophotometer. Fluorescence spectra were

recorded on a Shimadzu RF-5301PC spectrofluorometer. Variable-tem-

perature NMR spectra were recorder on a Bruker Avance 600 MHz

spectrometer, which was temperature-calibrated using neat ethylene

glycol or MeOH. The chemical shifts (d) for ¹H spectra, given in ppm,

are referenced to the residual proton signal of the deuterated solvent.

The chemical shifts (d) for ¹³C spectra are referenced relative to the

signal from the carbon of the deuterated solvent. SEM imaging was per-

formed on a FEI Quanta 600F sFEG ESEM scanning electron micro-

scope. High-resolution mass spectra were measured on a Finnigan LCQ

iontrap mass spectrometer (HR-ESI).

Synthesis of 2-mer-BME: By following the general coupling procedure

(based on 4.00 g of the aryl iodide), the desired product precipitated out

of solution. The aqueous (bottom) layer of the biphasic solution was re-

moved by syringe, and the product was collected by filtration of the re-

maining dark brown dioxane layer. The collected product was washed

with EtOAc (50 mL) and allowed to air-dry to provide 2-mer-BME

(4.35 g, 83%) as an off-white powder which required no further purifica-

General synthetic procedures

Suzuki–Miyaura cross-coupling reactions: A p-dioxane/H₂O mixture (2:1

v/v, 0.12m based on the aryl halide) was purged with N₂and transferred

subsequently through a cannula to a round-bottomed flask charged with

the aryl halide (1.00 equiv), the boronic acid pinacol ester (1.10 equiv per

halide), CsF (3.00 equiv per halide), and [PdCl

₂ACHTUNGTREN(NGNU dppf)] (5 mol% per

1

halide). The resulting mixture was heated under reflux overnight. It was

tion. H NMR (500 MHz, CDCl₃, 258C): d=7.91 (d, J=8.0 Hz, 2H), 7.52

Chem. Eur. J. 2012, 18, 15632 – 15649

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

15641

J. F. Stoddart et al.

(d, J=7.5 Hz, 4H), 7.42 (t, J=7.5 Hz, 4H), 7.34 (t, J=7.5 Hz, 2H), 7.16

(dd, J=8.0, 1.5 Hz, 2H), 7.08 (d, J=1.5 Hz, 2H), 5.23 (s, 4H), 3.93 ppm

(s, 6H); ¹³C NMR (125 MHz, CDCl₃, 258C): d=166.5, 158.6, 145.4, 136.7,

132.6, 128.8, 128.1, 127.0, 120.2, 119.6, 113.1, 70.9, 52.3 ppm; MS (ESI):

m/z calcd for C₃₀H₁₆O₆: 483.2 [M+H]⁺, 505.2 [M+Na]⁺, 987.3 [2M+Na]⁺;

found: 483.4, 505.4, 987.1.

Synthesis of 4-mer-HCA: Following the general hydrogenolysis proce-

dure, but using an EtOAc (10 mL)/EtOH (10 mL) mixture, Pd/C (0.15 g,

0.15 mmol) was added to

a flask charged with 4-mer-BME (1.00 g,

1.45 mmol). The filter cake was washed with THF (10 mL) and the com-

bined filtrate was concentrated in vacuo to provide the product that was

used directly in the next step. Following the general saponification proce-

dure, 4-mer-HCA (620 mg, 89% over hydrogenolysis and saponification)

was collected as a white solid. ¹H NMR (500 MHz, CD₃SOCD₃, 258C):

d=7.86–7.83 (m, 2H), 7.19 (s, 2H), 7.06 (s, 2H), 6.98–6.92 (m, 4H), 2.25

(s, 6H), 2.06 ppm (s, 6H); ¹³C NMR (126 MHz, CD₃SOCD₃): d=171.8,

160.9, 148.5, 140.3, 138.9, 132.8, 131.8, 131.3, 130.6, 130.1, 120.3, 117.3,

111.5, 19.6, 19.0 ppm; HRMS (ESI): m/z calcd for C₃₀H₂₆O₆: 481.1657

[MꢀH]^ꢀ; found: 481.1654.

Synthesis of 2-mer-HCA: EtOAc (50 mL) andTHF (50 mL) was used as

a solvent mixture. Pd/C (0.98 g, 0.90 mmol) was added to a flask charged

with 2-mer-BME (4.35 g, 9.0 mmol) and the general hydrogenolysis con-

ditions were followed. The filter cake was suspended in THF (30 mL)

and the suspension was warmed to reflux and hot-filtered subsequently.

This process was repeated five times in order to extract all the product

from the Pd/C. The combined organic layers were concentrated in vacuo

to provide the product which was used directly in the next step. Follow-

ing the general saponification procedure, 2-mer-HCA (2.0 g, 82% over

Synthesis of 6: Following the general coupling procedure, 3 (9.20 g,

25.0 mmol, 1.0 equiv) and 4 (35.9 g, 135.8 mmol, 5.4 equiv) were reacted

in a degassed 2:1 dioxane/H₂O mixture (300 mL) with CsF (11.4 g,

hydrogenolysis and saponification) was collected as

a white solid.

¹H NMR (500 MHz, CD₃SOCD₃, 258C): d=7.86 (d, J=9.0 Hz, 2H),

7.30–7.25 ppm (m, 4H); ¹³C NMR (126 MHz, CD₃SOCD₃, 258C): d=

171.7, 161.4, 145.5, 131.0, 117.9, 115.3, 113.0 ppm; HRMS (ESI): m/z

calcd for C₁₄H₁₀O₆: 273.0405 [MꢀH]^ꢀ; found: 273.0397.

75.0 mmol, 3.0 equiv) and [PdCl₂ACTHNUTRGNE(UNG dppf)] (1.11 g, 1.36 mmol, 5 mol%).

The reaction mixture was cooled to RT before being extracted with

CH₂Cl₂(300 mL) and H₂O (600 mL). The aqueous phase was washed

twice with CH₂Cl₂(400 mL). The combined organic phases were dried

(MgSO₄), filtered, and concentrated. The crude product was absorbed on

silica-gel and subjected to column chromatography (SiO₂, hexanes/

CH₂Cl₂=1:1!1:10) to give the compound 6 as a yellowish oil (7.75 g,

18.2 mmol, 67%). ¹H NMR (500 MHz, CDCl₃, 258C): d=7.87 (d, J=

7.9 Hz, 1H), 7.48 (m, 2H), 7.43 (s, 1H), 7.40 (m, 2H), 7.31 (m, 1H), 7.03

(s, 1H), 6.91 (dd, J=7.9, 1.5 Hz, 1H), 6.89 (d, J=1.3 Hz, 1H), 5.21 (s,

2H), 3.93 (s, 3H), 2.38 (s, 3H), 2.08 ppm (s, 3H); ¹³C NMR (126 MHz,

CDCl₃, 258C): d=166.7, 157.8, 146.4, 140.0, 136.6, 135.2, 134.5, 133.9,

131.8, 131.5, 128.6, 127.8, 126.8, 124.2, 121.3, 119.2, 114.9, 70.6, 52.1, 22.3,

19.5 ppm; HRMS (ESI): m/z calcd for C₂₃H₂₂BrO₃: 425.0747 [M+H]⁺;

found: 425.0755.

Synthesis of 3-mer-BME: Following the general coupling procedure

(based on 2.00 g of the aryl dibromide), the desired product precipitated

out of solution. The aqueous (bottom) layer of the biphasic solution was

removed by syringe, and the product was collected by filtration of the re-

maining dark brown dioxane layer. The collected product was washed

with EtOAc (30 mL) and left to dry in air to provide 3-mer-BME (4.29 g,

96%) as an off-white powder which required no further purification.

¹H NMR (500 MHz, [D₈]THF, 258C): d=7.96 (d, J=7.5 Hz, 2H), 7.66

(d, J=7.5 Hz, 4H), 7.48 (t, J=7.5 Hz, 4H), 7.39 (t, J=7.5 Hz, 2H), 7.24

(s, 2H), 7.22 (s, 2H), 7.10 (dd, J=8.0, 1.0 Hz, 2H), 5.36 (s, 4H), 3.98 (s,

6H), 2.30 ppm (s, 6H); ¹³C NMR (125 MHz, [D₈]THF, 258C): d=167.0,

159.3, 148.2, 141.8, 138.8, 133.7, 132.6, 132.6, 129.5, 128.6, 127.9, 122.2,

120.8, 116.1, 71.4, 52.2, 20.3 ppm; MS (ESI): m/z calcd for C₃₈H₃₄O₆:

587.2 [M+H]⁺, 609.2 [M+Na]⁺, 1195.5 [2M+Na]⁺; found: 587.4, 609.5,

1195.1. HRMS (ESI): m/z calcd for C₃₈H35O₆: 587.2514 [M+H]⁺; found:

587.2525.

Synthesis of 7: Compound 6 (7.75 g, 18.2 mmol, 1.0 equiv) was dissolved

in dry and degassed Me₂SO (80 mL). Bis(pinacolato)diboron (5.08 g,

20.0 mmol, 1.1 equiv), KOAc (5.36 g, 54.6 mmol, 3.0 equiv) and [PdCl₂-

AHCTUNGERTG(NNUN dppf)] (743 mg, 0.91 mmol, 5 mol%) were added and the reaction mix-

ture was heated to 808C for 14 h before being cooled to RT and extracted

with CH₂Cl₂(200 mL) and H₂O (400 mL). The aqueous phase was

washed twice with CH₂Cl₂(300 mL). The combined organic phases were

washed with H₂O, dried (MgSO₄), filtered, and concentrated. The crude

product was absorbed on silica-gel and subjected to column chromatogra-

phy (SiO₂, hexanes/EtOAc=5:1) to afford compound 7 as a colorless oil

Synthesis of 3-mer-HCA: Following the general hydrogenolysis condi-

tions but using a DMF (15 mL)/THF (60 mL) mixture, Pd/C (0.78 g,

0.73 mmol) was added to

a flask charged with 3-mer-BME (4.29 g,

7.32 mmol). The filter cake was washed with THF (10 mL) and the com-

bined filtrate was concentrated in vacuo to provide the product that was

used directly in the next step. Following the general saponification proce-

dure, 3-mer-HCA (2.4 g, 87% over hydrogenolysis and saponification)

was isolated as a white powder. ¹H NMR (500 MHz, CD₃SOCD₃, 258C):

d=14.0 (brs, 2H), 11.4 (brs, 2H), 7.85–7.82 (m, 2H), 7.18 (s, 2H), 6.98–

6.92 (m, 4H), 2.24 ppm (m, 6H); ¹³C NMR (126 MHz, CD₃SOCD₃,

258C): d=171.9, 160.9, 148.3, 139.7, 132.3, 131.3, 130.2, 120.3, 117.4,

111.7, 19.5 ppm; HRMS (ESI): m/z calcd for C₂₂H₁₇O₆: 377.1031

[MꢀH]^ꢀ; found: 377.1031.

1

(8.04 g, 17.0 mmol, 94%). H NMR (500 MHz, CDCl₃, 258C): d=7.91 (d,

J=7.8 Hz, 1H), 7.68 (s, 1H), 7.51 (m, 2H), 7.41 (m, 2H), 7.33 (m, 1H),

7.02 (s, 1H), 6.98–6.95 (m, 2H), 5.23 (s, 2H), 3.96 (s, 3H), 2.55 (s, 3H),

2.14 (s, 3H), 1.39 ppm (s, 12H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=

166.7, 157.8, 147.4, 143.1, 142.4, 138.1, 136.7, 131.7, 131.3, 130.8, 128.6,

127.8, 126.8, 121.3, 119.0, 114.9, 83.5, 70.6, 52.1, 25.1, 24.9, 21.7, 19.5 ppm;

HRMS (ESI): m/z calcd for C₂₉H₃₄BO₆: 472.2544 [M+H]⁺; found:

472.2530.

Synthesis of 8: Following the general coupling procedure, 3 (1.08 g,

2.92 mmol, 1.0 equiv) and 5 (5.40 g, 11.7 mmol, 4.0 equiv) were reacted in

degassed dioxane (150 mL) and H₂O (50 mL) with CsF (1.33 g,

Synthesis of 4-mer-BME: By following the general coupling procedure, 3

(4.78 g, 13.0 mmol, 3.0 equiv) and 5 (2.00 g, 4.33 mmol, 1.0 equiv) were

reacted in a degassed 2:1 dioxane/H₂O mixture (420 mL) with CsF

8.76 mmol, 3.0 equiv) and [PdCl₂ACTHNUTRGNE(UNG dppf)] (120 mg, 0.147 mmol, 5 mol%).

(3.95 g, 26.0 mmol, 6.0 equiv) and [PdCl₂ACTHNUTRGNEU(GN dppf)] (354 mg, 0.433 mmol,

The reaction mixture was cooled to RT before being extracted with

CH₂Cl₂(200 mL) and H₂O (300 mL). The aqueous phase was washed

twice with CH₂Cl₂(200 mL). The combined organic phases were dried

(MgSO₄), filtered, and concentrated. The crude product was absorbed on

silica-gel and subjected to column chromatography (SiO₂, hexanes/

10 mol%). The reaction mixture was cooled to RT, before being extract-

ed with CH₂Cl₂(300 mL) and H₂O (800 mL). The aqueous phase was

washed twice with CH₂Cl₂(300 mL). The combined organic phases were

dried (MgSO₄), filtered, and concentrated to afford the crude product

which was absorbed on silica-gel and subjected to column chromatogra-

phy (SiO₂, hexanes/EtOAc=5:1) to give 4-mer-BME as a colorless solid

(2.60 g, 3.82 mmol, 87%). ¹H NMR (500 MHz, CD₂Cl₂, 258C): d=7.86

(d, J=7.9 Hz, 2H), 7.51 (m, 4H), 7.40 (m, 4H), 7.33 (m, 2H), 7.13 (m,

2H), 7.06 (d, J=1.3 Hz, 2H), 7.03 (dd, J=7.9, 1.5 Hz, 2H), 7.01 (s, 2H),

5.29 (s, 4H), 3.89 (s, 6H), 2.20 (s, 6H), 2.09 ppm (s, 6H); ¹³C NMR

(126 MHz, CD₂Cl₂, 258C): d=166.8, 158.2, 147.7, 141.2, 140.0, 137.3,

133.7, 132.6, 131.9, 131.8, 131.2, 128.9, 128.2, 127.4, 121.9, 119.5, 115.4,

71.0, 52.3, 20.0, 19.5 ppm; HRMS (ESI): m/z calcd for C₄₆H₄₃O₆: 691.3051

[M+H]⁺; found: 691.3067.

EtOAc=5:1) to give the compound

8 as a colorless solid (1.11 g,

1.93 mmol, 66%). ¹H NMR (500 MHz, CDCl₃, 258C): d=7.90 (d, J=

8.2 Hz, 1H), 7.74 (s, 1H), 7.51 (d, J=8.5 Hz, 2H), 7.40 (t, J=7.6 Hz,

2H), 7.32 (t, J=7.3 Hz, 1H), 7.07 (s, 1H), 7.02–7.00 (m, 3H), 6.95 (s,

1H), 5.24 (s, 2H, CH₂), 3.94 (s, 3H, CH₃), 2.41 (s, 3H), 2.15 (s, 3H),

2.04 ppm (m, 6H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=166.8, 157.8,

147.3, 141.4, 140.2, 139.88, 139.81, 138.5, 136.8, 135.4, 133.2, 132.3, 131.7,

131.3, 130.9, 130.5, 128.6, 127.8, 126.8, 121.6, 118.9, 115.0, 99.6, 70.6, 52.1,

27.5, 19.8, 19.3, 19.0 ppm; HRMS (ESI): m/z calcd for C₃₁H₃₀IO₃:

577.1234 [M+H]⁺; found: 577.1229.

15642

www.chemeurj.org

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2012, 18, 15632 – 15649

Molecular Gauge Blocks

FULL PAPER

Synthesis of 9: Compound 8 (971 mg, 1.68 mmol, 1.0 equiv) was dissolved

in dry and degassed Me₂SO (7 mL). Bis(pinacolato)diboron (470 mg,

1.85 mmol, 1.1 equiv), KOAc (494 mg, 5.04 mmol, 3.0 equiv) and [PdCl₂-

pletion of the reaction, the reaction mixture was cooled to RT before

being extracted with CH₂Cl₂(150 mL) and H₂O (500 mL). The aqueous

phase was washed twice with CH₂Cl₂(200 mL). The combined organic

phases were dried (MgSO₄), filtered, and concentrated. The crude prod-

uct was absorbed on silica-gel and subjected to column chromatography

(SiO₂, hexanes/EtOAc=5:1) to give 5-mer-BME as a colorless solid

(765 mg, 0.962 mmol, 77%). ¹H NMR (500 MHz, CDCl₃, 258C): d=7.92

(d, J=8.2 Hz, 2H), 7.53 (m, 4H), 7.41 (m, 4H), 7.32 (m, 2H), 7.11 (s,

2H), 7.09 (m, 2H), 7.05–7.03 (m, 6H), 5.25 (s, 4H), 3.95 (s, 6H), 2.19 (s,

6H), 2.13 (s, 3H), 2.12 (s, 3H), 2.11 ppm (m, 6H); ¹³C NMR (126 MHz,

CDCl₃, 258C): d=166.8, 157.9, 147.6, 141.30, 141.23, 140.03, 139.98,

139.50, 139.47, 136.8, 133.50, 133.44, 132.84, 132.74, 132.10, 132.08, 131.67,

131.60, 130.79, 130.72, 130.70, 128.6, 127.8, 126.8, 121.7, 118.8, 115.11,

115.10, 70.6, 52.1, 19.84, 19.80, 19.51, 19.47, 19.34 ppm; HRMS (ESI): m/z

calcd for C₅₄H₅₁O₆: 795.3680 [M+H]⁺; found: 795.3659.

ACHTUNGTRENNUNG(PPh₃)₂] (69 mg, 0.084 mmol, 5 mol%) were added and the reaction mix-

ture was heated to 808C for 15 h. After cooling to RT, it was extracted

with H₂O (100 mL) and CH₂Cl₂(200 mL). The aqueous phase was

washed twice with CH₂Cl₂(200 mL). The combined organic phases were

washed with H₂O, dried (MgSO₄), evaporated, and subjected to column

chromatography (SiO₂, hexanes/EtOAc=9:1), to give compound 9 as a

colorless foam (810 mg, 1.41 mmol, 84%). ¹H NMR (500 MHz, CDCl₃,

258C): d=7.93 (d, J=8.2 Hz, 1H), 7.70 (s, 1H), 7.54 (d, J=8.0 Hz, 2H),

7.42 (t, J=7.5 Hz, 2H), 7.35 (t, J=7.3 Hz, 1H), 7.10 (s, 1H), 7.05 (m,

2H), 6.99 (s, 1H), 6.98 (s, 1H), 5.27 (s, 2H), 3.97 (s, 3H), 2.55 (s, 3H),

2.17 (s, 3H), 2.10 (s, 3H), 2.06 (s, 3H), 1.39 ppm (s, 12H); ¹³C NMR

(126 MHz, CDCl₃, 258C): d=166.8, 157.8, 147.5, 143.8, 142.0, 141.3,

139.5, 137.4, 136.8, 133.2, 132.1, 132.0, 131.7, 131.2, 130.9, 130.7, 128.6,

127.8, 126.8, 121.7, 118.8, 115.1, 83.5, 70.6, 52.1, 34.7, 31.6, 25.3, 24.98,

24.95, 22.7, 21.8, 20.8, 19.8, 19.3, 19.2, 14.3 ppm; HRMS (ESI): m/z calcd

for C₃₇H₄₁BO₅: 576.3156 [M+H]⁺; found: 576.3169.

Synthesis of 5-mer-HCA: Following the general hydrogenolysis proce-

dure with THF (20 mL), Pd/C (0.29 g, 0.27 mmol) and 5-mer-BME

(2.16 g, 2.72 mmol), the product was obtained as a colorless solid and

used directly in the next step. Following the general saponification proce-

dure, 5-mer-HCA (1.60 g, quantitative over hydrogenolysis and saponifi-

cation) was collected as an off-white solid. ¹H NMR (500 MHz,

[D₇]DMF, 258C): d=8.00 (d, J=8.0 Hz, 2H), 7.31 (s, 2H), 7.16–7.12 (m,

4H), 7.07 (dd, J=8.0, 1.5 Hz, 2H), 7.04–7.02 (m, 2H), 2.37 (s, 6H), 2.18–

2.16 (m, 6H), 2.15 ppm (s, 6H); ¹³C NMR (126 MHz, [D₇]DMF, 258C):

d=172.6, 149.2, 141.2, 140.20, 140.18, 139.5, 133.38, 133.35, 132.8, 132.2,

131.6, 130.90, 130.88, 130.78, 130.75, 130.3, 120.5, 117.6, 111.9, 19.38,

19.36, 18.82, 18.79, 18.7 ppm; ¹H NMR (600 MHz; CD₃SOCD₃, 1008C):

d=7.86 (d, J=8.6 Hz, 2H), 7.16 (s, 2H), 7.07 (s, 2H), 7.04 (s, 2H), 6.94–

6.93 (m, 4H), 2.26 (s, 6H), 2.08 (s, 6H), 2.07 ppm (s, 6H); ¹³C NMR

(151 MHz; CD₃SOCD₃, 1008C): d=171.8, 161.3, 149.2, 141.2, 140.2,

139.6, 133.3, 132.8, 132.1, 131.8, 130.98, 130.93, 130.6, 120.7, 117.9, 112.6,

19.8, 19.39, 19.27 ppm; HRMS (ESI): m/z calcd for C₃₈H₃₄O₆: 585.2283

[MꢀH]^ꢀ; found: 585.2299.

Synthesis of 10: Following the general coupling procedure, 7 (2.60 g,

5.50 mmol, 1.0 equiv) and 5 (10.2 g, 22.1 mmol, 4.0 equiv) were dissolved

in a degassed mixture of dioxane (500 mL) and H₂O (200 mL) at 808C

before CsF (2.50 g, 16.5 mmol, 3.0 equiv) and [PdCl₂ACHTNUTRGNEUNG(dppf)] (225 mg,

0.276 mmol, 5 mol%) were added. After the reaction was complete, the

mixture was cooled to RT before being extracted with CH₂Cl₂(400 mL)

and H₂O (1000 mL). The aqueous phase was washed twice with CH₂Cl₂

(2ꢅ200 mL). The combined organic phases were washed with brine,

dried (MgSO₄), and evaporated. The crude product was subjected to

column chromatography (SiO₂, hexanes/EtOAc=5:1) to give the product

as a colorless oil (2.34 g, 3.44 mmol, 63%). ¹H NMR (500 MHz, CDCl₃,

258C): d=7.94 (d, J=8.2 Hz, 1H), 7.77 (s, 1H), 7.55 (d, J=7.4 Hz, 2H),

7.43 (t, J=7.6 Hz, 2H), 7.35 (t, J=7.3 Hz, 1H), 7.13 (s, 1H), 7.09–7.03

(m, 5H), 6.99 (m, 1H), 5.27 (s, 2H), 3.97 (s, 3H), 2.45 (s, 3H), 2.20 (s,

3H), 2.14–2.06 ppm (m, 12H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=

166.8, 157.9, 147.5, 141.83, 141.77, 141.20, 141.14, 141.00, 140.1, 139.8,

139.53, 139.50, 139.41, 139.36, 138.39, 138.36, 136.8, 135.56, 135.49, 133.45,

133.39, 132.92, 132.83, 132.66, 132.56, 132.1, 131.66, 131.60, 131.54, 130.78,

130.73, 130.69, 130.62, 130.48, 130.45, 128.6, 127.8, 126.8, 121.7, 118.8,

115.1, 99.4, 70.6, 52.1, 34.70, 34.57, 27.4, 25.3, 20.7, 19.83, 19.79, 19.47,

19.44, 19.37, 19.31, 18.98, 18.85 ppm; HRMS (ESI): m/z calcd for

C₃₉H₃₈IO₃: 681.1860 [M+H]⁺; found: 681.1848.

Synthesis of 6-mer-BME: Following the general coupling procedure, 7

(600 mg, 1.27 mmol, 3.0 equiv) and 5 (196 mg, 0.423 mmol, 1.0 equiv)

were dissolved in a degassed 2:1 dioxane/H₂O mixture (45 mL) and re-

acted with CsF (386 mg, 2.54 mmol, 6.0 equiv) and [PdCl₂ACHTNUTRGNE(NUG dppf)] (35 mg,

0.043 mmol, 10 mol%). After completion of the reaction, the mixture

was cooled to RT before being extracted with CH₂Cl₂(600 mL) and H₂O

(400 mL). The aqueous phase was washed twice with CH₂Cl₂(100 mL).

The combined organic phases were dried (MgSO₄), filtered, and concen-

trated. The crude product was absorbed on silica-gel and subjected to

column chromatography (SiO₂, hexanes/EtOAc=5:1) to give 6-mer-

Synthesis of 11: Compound 10 (2.06 g, 3.02 mmol, 1.0 equiv) was dis-

solved in dry and degassed Me₂SO (20 mL). Bis(pinacolato)diboron

(843 mg, 3.32 mmol, 1.1 equiv), KOAc (888 mg, 9.06 mmol, 3.0 equiv)

BME as

(500 MHz, CDCl₃, 258C): d=7.93 (d, J=8.3 Hz, 2H), 7.53 (m, 4H), 7.40

(m, 4H), 7.33( m, 2H), 7.12–7.04 (m, 12H), 5.26 (s, 4H), 3.95 (s, 6H),

a

colorless solid (229 mg, 0.255 mmol, 60%). ¹H NMR

and [PdCl₂ACHTUNGTRENNUNG(dppf)] (123 mg, 0.151 mmol, 5 mol%) were added and the re-

action mixture was heated to 808C for 14 h before being cooled to RT

and extracted with CH₂Cl₂(100 mL) and H₂O (300 mL). The aqueous

phase was washed twice with CH₂Cl₂. The combined organic phases were

washed with H₂O (100 mL), dried (MgSO₄), filtered, and concentrated.

The crude product was absorbed on silica-gel and subjected to column

chromatography (SiO₂, hexanes/EtOAc=7:1) to give compound 11 as a

colorless solid (1.50 g, 2.2 mmol, 72%). ¹H NMR (500 MHz, CDCl₃,

258C): d=7.94 (d, J=8.3 Hz, 1H), 7.71 (s, 1H), 7.55 (d, J=7.7 Hz, 2H),

7.44–7.41 (m, 2H), 7.35 (m, 1H), 7.12 (s, 1H), 7.10–6.99 (m, 6H), 5.27 (s,

2H), 3.97 (s, 3H), 2.57 (s, 3H), 2.20 (s, 3H), 2.14–2.06 (m, 12H),

1.39 ppm (s, 12H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=166.8, 157.9,

147.6, 144.25, 144.19, 141.95, 141.93, 141.38, 141.31, 140.49, 140.44, 139.87,

139.82, 139.44, 139.41, 137.3, 136.8, 133.52, 133.46, 132.72, 132.65, 132.62,

132.55, 132.19, 132.14, 132.06, 132.04, 131.66, 131.60, 131.04, 130.96,

130.75, 130.61, 130.59, 130.40, 130.38, 128.6, 127.8, 126.8, 121.7, 118.8,

115.11, 115.10, 83.4, 77.1, 70.6, 52.1, 31.6, 25.06, 24.98, 24.96, 21.76, 21.73,

19.82, 19.78, 19.49, 19.45, 19.36, 19.31, 19.21, 19.08 ppm; HRMS (ESI):

m/z calcd for C₄₅H₅₀BO₅: 680.3782 [M+H]⁺; found: 680.3776.

ACHTUNGTRENNUNG

2.19 (s, 6H), 2.15–2.12 ppm (m, 18H); ¹³C NMR (126 MHz, CDCl₃,

258C): d=166.8, 157.9, 147.6, 141.4, 141.3, 140.8, 140.5, 140.44, 140.43,

140.38, 139.9, 139.83, 139.82, 139.78, 139.7, 139.5, 139.4, 136.81, 136.78,

133.54, 133.48, 133.9, 132.93, 132.88, 132.82, 132.75, 132.72, 132.65, 132.6,

132.08, 132.06, 131.71, 131.67, 131.5, 130.9, 130.83, 130.78, 130.7, 128.6,

127.8, 126.8, 121.7, 118.8, 115.1, 70.6, 52.1, 19.9, 19.8, 19.53, 1949, 19.47,

19.46, 19.38, 19.36 ppm. HRMS (ESI): m/z calcd for C₆₂H₅₉O₆: 899.4306

[M+H]⁺; found: 899.4330.

Synthesis of 6-mer-HCA: Following the general hydrogenolysis proce-

dure in THF (60 mL) with Raney Ni as catalyst (approx. 200 mg, com-

mercially purchased as a slurry in H₂O which was converted to a slurry in

THF by successive (5ꢅ20 mL) dilutions with THF, followed by removal

of the supernatant) and 6-mer-BME (2.0 g, 2.22 mmol). The reaction mix-

ture was stirred for 48 h before being cooled to RT and purged with a

stream of N₂. It was decanted into an Erlenmeyer flask (most of the Ni

remains bound to the magnetic stir bar) before being diluted with CHCl₃

(100 mL). The solution was then heated to reflux and hot-filtered

through a well-packed bed of Celite. The filter cake was rinsed further

with hot CHCl₃(100 mL). The filtrates were combined and concentrated

in vacuo to afford the product, which was used directly in the next step.

Following the general saponification procedure, 6-mer-HCA (1.35 g 90%

over hydrogenolysis and saponification) was collected as an off-white sol-

Synthesis of 5-mer-BME: Following the general coupling procedure, 7

(1.77 g, 3.75 mmol, 3.0 equiv) and 1,4-diiodo-2,5-dimethylbenzene^[22]

(447 mg, 1.25 mmol, 1.0 equiv) were dissolved in a degassed 2:1 dioxane/

H₂O mixture (150 mL) and reacted with CsF (1.14 g, 7.50 mmol,

6.0 equiv) and [PdCl₂ACHTUNGTRENNUNG(dppf)] (102 mg, 0.125 mmol, 10 mol%). After com-

Chem. Eur. J. 2012, 18, 15632 – 15649

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

15643

J. F. Stoddart et al.

id.¹H NMR (500 MHz, [D₈]THF, 258C): d=8.08 (d, J=8.0 Hz, 2H), 7.36

(s, 2H), 7.28–7.20 (m, 6H), 7.15 (s, 2H), 7.12–7.09 (m, 2H), 2.47 (s, 6H),

2.31 (s, 6H), 2.29 (s, 6H), 2.28 ppm (s, 6H); ¹³C NMR (126 MHz,

[D₈]THF, 258C): d=173.6, 163.7, 151.1, 142.8, 142.1, 141.7, 141.2, 134.6,

134.2, 134.1, 133.4, 133.0, 132.9, 132.2, 132.1, 132.0, 131.4, 121.5, 119.3,

112.5, 20.7, 20.6, 20.19, 20.18, 20.1, 20.0 ppm; ¹H NMR (600 MHz;

CD₃SOCD₃, 1008C): d=7.88 (d, J=7.8 Hz, 2H), 7.18 (s, 2H), 7.09 (s,

2H), 7.09 (s, 2H), 7.06 (s, 2H), 6.97–6.94 (m, 4H), 2.28 (s, 6H), 2.11 (s,

6H), 2.10 ppm (s, 12H); ¹³C NMR (151 MHz; CD₃SOCD₃, 1008C): d=

171.8, 161.3, 149.2, 141.3, 140.5, 140.1, 139.6, 133.4, 132.88, 132.77, 132.1,

131.8, 131.03, 130.95, 130.93, 130.6, 120.8, 117.9, 112.5, 19.8, 19.38, 19.32,

19.28 ppm; HRMS (ESI): m/z calcd for C₄₆H₄₂O₆: 689.2909 [MꢀH]^ꢀ;

found: 689.2912.

Synthesis of hex-3-mer-HCA: Following the general hydrogenolysis pro-

cedure, with the hex-3-mer-BME (2.20 g, 3.03 mmol, 1.0 equiv), THF

(50 mL), and Pd/C (10%, 321 mg), the product was obtained as a color-

less solid and used directly in the next step. Following the general saponi-

fication procedure, hex-3-mer-HCA was obtained as a colorless solid

(1.57 g, 3.03 mmol, quant). ¹H NMR (500 MHz, CD₃SOCD₃, 258C): d=

7.85 (d, J=8.4 Hz, 2H), 7.12 (s, 2H), 6.91 (m, 4H), 2.56 (m, 4H), 1.40

(m, 4H), 1.18–1.09 (m, 12H), 0.77 ppm (t, J=7.0 Hz, 6H); ¹³C NMR

(126 MHz; CD₃SOCD₃, 258C): d=171.8, 160.9, 148.5, 139.6, 136.9, 130.3,

130.1, 120.2, 117.3, 111.7, 31.7, 30.68, 30.55, 28.4, 21.8, 13.8 ppm; HRMS

(ESI): m/z calcd for C₃₂H₃₈O₆: 517.2596 [MꢀH]^ꢀ; found: 517.2593.

Synthesis of hex-5-mer-BME: Following the general coupling procedure,

7 (697 mg, 1.48 mmol, 2.2 equiv) 12 (334 mg, 0.670 mmol, 1.0 equiv) were

dissolved in a degassed mixture of dioxane (15 mL) and H₂O (7.5 mL)

Synthesis of 7-mer-BME: Following the general coupling procedure, 9

(100 mg, 0.174 mmol, 2.3 equiv) and 1,4-diiodo-2,5-dimethylbenzene^[22]

(27.0 mg, 0.0754 mmol, 1.0 equiv) were dissolved in a degassed mixture

of dioxane (3 mL) and H₂O (1.5 mL) and reacted with CsF (68.7 mg,

and reacted with CsF (610 mg, 4.02 mmol, 6.0 equiv) and [PdCl₂ACHTUNGTRENNUNG(dppf)]

(55 mg, 0.067 mmol, 10 mol%). After completion of the reaction, the

mixture was extracted with H₂O (400 mL) and CH₂Cl₂(100 mL). The

aqueous phase was washed twice with CH₂Cl₂(200 mL). The combined

organic phases were dried (MgSO₄) and concentrated. The crude product

was subjected to column chromatography (SiO₂, CH₂Cl₂/hexanes=1:1!

1:0) to give hex-5-mer-BME as a colorless solid (465 mg, 0.497 mmol,

74%). ¹H NMR (500 MHz, CDCl₃, 258C): d=7.95 (d, J=8.2 Hz, 2H),

7.56 (d, J=7.5 Hz, 4H), 7.44 (t, J=7.6 Hz, 4H), 7.35 (t, J=7.4 Hz, 2H),

7.14 (m, 4H), 7.09–7.06 (m, 6H), 5.28 (s, 4H), 3.98 (s, 6H), 2.49 (m, 2H),

2.40–2.35 (m, 2H), 2.22 (s, 6H), 2.15 (d, J=3H), 2.14 (s, 3H), 1.48 (m,

4H), 1.22 (m, 12H), 0.85 ppm (t, J=7.0 Hz, 6H); ¹³C NMR (126 MHz,

CDCl₃, 258C): d=166.8, 157.9, 147.6, 141.34, 141.25, 139.51, 139.49,

139.40, 139.37, 137.41, 137.36, 136.8, 133.64, 133.58, 132.00, 131.93, 131.82,

131.81, 131.66, 130.77, 130.74, 130.06, 130.00, 128.6, 127.8, 126.8, 121.7,

118.8, 115.1, 70.6, 52.1, 32.51, 32.46, 31.6, 30.75, 30.66, 29.00, 28.95, 22.5,

19.85, 19.81, 19.72, 19.58, 14.1 ppm; HRMS (ESI): m/z calcd for

C₆₄H₇₁O₆: 935.5245 [M+H]⁺; found: 935.5213.

0.452 mmol, 6.0 equiv) and [PdCl₂ACTHNUTRGNE(UNG dppf)] (6.2 mg, 10 mol%). After com-

pletion of the reaction, the mixture was cooled to RT and the precipitate

was filtrated off, washed with H₂O (100 mL) and MeOH (100 mL) and

dried under vacuum to give 7-mer-BME as a colorless solid (64 mg,

0.064 mmol, 84%). ¹H NMR (500 MHz, CDCl₃, 258C): d=7.95 (d, J=

8.0 Hz, 2H), 7.56 (m, 4H), 7.44 (m, 4H), 7.35 (m, 2H), 7.15–7.12 (m,

8H), 7.09–7.07 (m, 6H), 5.28 (s, 4H), 3.97 (s, 6H), 2.22 (s, 6H), 2.18–

2.15 ppm (m, 24H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=166.8, 157.9,

147.6, 141.43, 141.36, 140.58, 140.53, 140.47, 140.32, 140.27, 140.23, 140.21,

140.17, 139.82, 139.78, 139.77, 139.73, 139.45, 139.42, 136.8, 133.55, 133.49,

133.02, 132.96, 132.91, 132.89, 132.86, 132.83, 132.81, 132.78, 132.75,

132.72, 132.70, 132.62, 132.59, 132.08, 132.05, 131.72, 131.67, 130.90,

130.87, 130.78, 130.71, 130.64, 128.6, 127.8, 126.8, 121.7, 118.8, 115.1, 70.6,

52.1, 25.1, 19.84, 19.80, 19.54, 19.52, 19.49, 19.47, 19.38, 19.36 ppm;

HRMS (ESI): m/z calcd for C₇₀H₆₇O₆: 1003.4932 [M+H]⁺; found:

1003.4952.

Synthesis of hex-5-mer-HCA: Following the general hydrogenolysis pro-

cedure, with hex-5-mer-BME (455 mg, 0.467 mmol, 1.0 equiv), THF

(10 mL) and Pd/C (10%, 50 mg) the debenzylated compound was ob-

tained and used directly in the next step. Following the general saponifi-

Synthesis of 7-mer-HCA: The general hydrogenolysis procedure, with

THF (10 mL), benzene (10 mL), Pd/C (30.0 mg, 0.028 mmol), and the 7-

mer-BME (300 mg, 0.299 mmol) was followed. The reaction mixture was

stirred for 48 h at 120 psi of H₂at 608C. It was then cooled to RT, purged

with a stream of N₂and filtered. The filter cake was washed with hot

PhCl (50 mL) and the combined filtrate was concentrated in vacuo to

afford the product, which was used directly in the next step. Following

the general saponification procedure, 7-mer-HCA (237 mg) was collected

as an off-white very poorly soluble solid. Low solubility hindered full

cation procedure, hex-5-mer-HCA was obtained as

a colorless solid

(339 mg, 30.467 mmol, quant). ¹H NMR (600 MHz, CD₃SOCD₃, 1008C):

d=7.85 (d, J=8.4 Hz, 2H), 7.15 (s, 2H), 7.07 (s, 2H), 7.01 (s, 2H), 6.89

(m, 4H), 2.46 (m, 2H), 2.34 (m, 2H), 2.25 (s, 6H), 2.07 (s, 6H), 1.41 (m,

J=7.1 Hz, 4H), 1.15 (m, J=13.9, 7.1 Hz, 12H), 0.78 ppm (t, J=7.1 Hz,

6H); ¹³C NMR (126 MHz, CD₂Cl₂, 258C): d=171.8, 161.5, 148.9, 141.1,

139.79, 139.71, 137.5, 133.4, 132.1, 131.9, 130.9, 130.55, 130.44, 120.4,

117.8, 113.1, 32.5, 31.2, 30.4, 28.6, 22.1, 19.8, 19.4, 14.0 ppm; HRMS

(ESI): m/z calcd for C₄₈H₅₃O₆: 725.3848 [MꢀH]^ꢀ; found: 725.3834.

1

characterization. An H NMR spectrum in CD₃SOCD₃was only obtained

after a prolonged acquisition time and at elevated temperature. It did not

prove possible to record a ¹³C NMR spectrum. ¹H NMR (600 MHz;

CD₃SOCD₃, 808C): d=7.86 (d, J=7.9 Hz, 2H), 7.17 (s, 2H), 7.08 (m,

6H), 7.05 (s, 2H), 6.95–6.93 (m, 4H), 2.26 (s, 6H), 2.08 ppm (m, 24H);

HRMS (ESI): m/z calcd for C₅₄H₄₉O₆: 793.3535 [MꢀH]^ꢀ; found:

793.3525.

Synthesis of hex-7-mer-BME: Following the general coupling procedure,

9 (641 mg, 1.11 mmol, 2.2 equiv) and 12 (252 mg, 0.505 mmol, 1.0 equiv)

were dissolved in a degassed mixture of dioxane (11 mL) and H₂O

(5.5 mL) and reacted with CsF (460 mg, 43.03 mmol, 6.0 equiv) and

Synthesis of hex-3-mer-BME: Following the general coupling procedure,

3 (3.40 g, 9.23 mmol, 2.3 equiv) and 12 (2.00 g, 4.01 mmol, 1.0 equiv) were

dissolved in a degassed mixture of dioxane (80 mL) and H₂O (40 mL)

[PdCl₂ACTHNGUTERNNU(G dppf)] (41 mg, 0.050 mmol, 10 mol%). After completion of the re-

action, the mixture was cooled to RT and extracted with H₂O (300 mL)

and CH₂Cl₂(100 mL). The aqueous phase was washed twice with CH₂Cl₂

(100 mL). The combined organic phases were dried (MgSO₄) and concen-

trated. The crude product was subjected to column chromatography

(SiO₂, CH₂Cl₂) to give hex-7-mer-BME as a colorless solid (527 mg,

0.460 mmol, 91%). ¹H NMR (500 MHz, CDCl₃, 258C): d=7.95 (d, J=

8.2 Hz, 2H), 7.56 (d, J=7.6 Hz, 4H), 7.44 (t, J=7.6 Hz, 4H), 7.35 (t, J=

7.4 Hz, 2H), 7.17–7.06 (m, 15H), 5.28 (s, 4H), 3.98 (s, 6H), 2.51 (m, 2H),

2.39 (m, 2H), 2.22 (s, 6H), 2.18 (s, 3H), 2.15–2.12 (m, 15H), 1.50–1.45

(m, 4H), 1.28–1.17 (m, 12H), 0.85 ppm (m, 6H); ¹³C NMR (126 MHz,

CDCl₃, 258C): d=166.8, 157.9, 147.6, 141.50, 141.40, 140.5, 139.72,

139.64, 139.44, 139.40, 137.56, 137.51, 136.8, 133.55, 133.48, 133.25, 133.20,

133.14, 133.12, 133.02, 132.96, 132.95, 132.45, 132.43, 132.31, 132.09,

132.03, 131.76, 131.67, 131.58, 131.26, 131.21, 131.18, 131.12, 130.77,

130.58, 130.26, 130.17, 130.13, 128.6, 127.8, 126.8, 121.7, 118.8, 115.1, 70.6,

52.1, 32.8, 32.58, 32.53, 31.64, 31.59, 31.48, 31.08, 30.95, 30.85, 30.70,

29.15, 29.10, 29.07, 22.71, 22.58, 22.55, 19.86, 19.79, 19.62, 19.52, 19.49,

and reacted with CsF (3.65 g, 24.1 mmol, 6.0 equiv) and [PdCl₂ACTHNUTRGNEU(GN dppf)]

(328 mg, 10 mol%). After completion of the reaction, the mixture was

cooled to RT before being extracted with H₂O (600 mL) and CH₂Cl₂

(200 mL). The aqueous phase was washed twice with CH₂Cl₂(300 mL).

The combined organic phases were dried (MgSO₄) and concentrated.

The crude product was subjected to column chromatography (SiO₂, hex-

anes/EtOAc=5:1) to give hex-3-mer-BME as a colorless solid (2.60 g,

3.58 mmol, 89%). ¹H NMR (500 MHz, CD₂Cl₂, 258C): d=7.93 (d, J=

8.2 Hz, 2H), 7.53 (d, J=7.5 Hz, 4H), 7.42 (t, J=7.6 Hz, 4H), 7.34 (t, J=

7.3 Hz, 2H), 7.07 (s, 2H), 7.01 (m, 4H), 5.25 (s, 4H), 3.97 (s, 6H), 2.49 (t,

J=8.0 Hz, 4H), 1.42 (m, 4H), 1.25–1.15 (m, 12H), 0.85 ppm (t, J=

7.1 Hz, 6H); ¹³C NMR (126 MHz, CD₂Cl₂, 258C): d=166.7, 157.8, 147.3,

140.3, 137.5, 136.7, 131.7, 130.6, 128.6, 127.8, 126.8, 121.6, 119.0, 115.0,

70.6, 52.1, 32.6, 31.57, 31.47, 29.2, 22.6, 14.1 ppm; HRMS (ESI): m/z calcd

for C₄₈H₅₅O₆: 727.3993 [M+H]⁺; found: 727.3995.

15644

www.chemeurj.org

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2012, 18, 15632 – 15649

Molecular Gauge Blocks

FULL PAPER

19.44, 19.2, 14.16, 14.08 ppm; HRMS (ESI): m/z calcd for C₉₆H₁₀₃O₆:

1350.7676 [M+H]⁺; found: 1351.7733.

and the Celite was washed thoroughly with CH₂Cl₂. The CH₂Cl₂layer

was concentrated, causing compound 13 to precipitate from the EtOAc

as fine off-white needles, which were isolated by vacuum filtration

(14.6 g, 40.8 mmol, 43%). ¹H NMR (500 MHz, CDCl₃, 258C): d=7.53 (s,

2H), 2.48 (s, 6H), 1.34 ppm (s, 24H); ¹³C NMR (126 MHz, CDCl₃,

258C): d=140.7, 137.0, 83.5, 25.0, 21.6 ppm; HRMS (ESI): m/z calcd for

C₂₀H₃₃B₂O₄: 357.2632 [M+H]⁺; found: 357.2614.

Synthesis of hex-7-mer-HCA: Following the general hydrogenolysis pro-

cedure with hex-7-mer-BME (1.19 g, 1.04 mmol, 1.0 equiv), THF

(50 mL), and Pd/C (10%, 110 mg), the debenzylated compound was ob-

tained and used directly in the next step. Following the general saponifi-

cation procedure, in THF (130 mL) and 0.5m aq. NaOH (110 mL), hex-7-

mer-HCA was obtained as a colorless solid (973 mg, 1.04 mmol, quant).

¹H NMR (600 MHz, CD₃SOCD₃, 908C): d=7.86 (d, J=8.0 Hz, 2H), 7.17

(s, 2H), 7.09 (s, 2H), 7.07 (m, 6H), 6.96 (m, 4H), 2.26 (s, 6H), 2.08 (m,

18H), 1.42 (m, 4H), 1.20–1.12 (m, 16H), 0.80 ppm (t, J=6.6 Hz, 6H);

¹³C NMR (151 MHz, CD₃SOCD₃, 908C): d=171.9, 161.3, 149.2, 141.3,

140.5, 140.02, 139.96, 139.6, 137.7, 133.3, 133.0, 132.5, 132.1, 131.7, 131.4,

130.95, 130.88, 130.57, 130.51, 120.8, 117.9, 112.4, 32.6, 31.2, 30.9, 30.6,

29.8, 28.7, 22.2, 19.8, 19.4, 14.0 ppm; HRMS (ESI): m/z calcd for

C₆₄H₉₆O₆: 934.5172 [MꢀH]^ꢀ; found: 934.5162.

Synthesis of 14: Following the general coupling procedure, 13 (5.00 g,

13.9 mmol, 1.0 equiv) and 4 (18.4 g, 69.8 mmol, 5.0 equiv) were dissolved

in a degassed 2:1 dioxane/H₂O mixture (75 mL) and reacted with CsF

(12.7 g, 83.8 mmol, 6.0 equiv) and [PdCl₂ACTHNUTRGNEU(GN dppf)] (1.14 g, 1.40 mmol,

10 mol%). After completion of the reaction, the mixture was cooled to

RT, before being extracted with CH₂Cl₂(500 mL) and H₂O (500 mL).

The aqueous phase was washed twice with CH₂Cl₂(500 mL). The com-

bined organic phases were dried (MgSO₄), filtered, and concentrated.

The crude product was absorbed on silica-gel and subjected to column

chromatography (SiO₂, hexanes) to give compound 14 as a colorless solid

(2.18 g, 4.61 mmol, 33%). ¹H NMR (500 MHz, CD₂Cl₂, 258C): d=7.47

(s, 2H), 7.04 (m, 2H), 6.95 (s, 2H), 2.39 (s, 6H), 2.05 (m, 6H), 2.02 ppm

(s, 6H); ¹³C NMR (126 MHz, CD₂Cl₂, 258C): d=141.2, 139.91, 139.89,

135.9, 135.1, 133.5, 133.2, 133.1, 132.1, 132.0, 130.9, 123.4, 22.5, 22.4, 19.4,

19.3, 19.2 ppm.

Synthesis of hex-9-mer-BME: Following the general coupling procedure,

11 (916 mg, 1.35 mmol, 2.2 equiv) and 12 (305 mg, 0.612 mmol, 1.0 equiv)

were dissolved in a degassed mixture of dioxane (18 mL) and H₂O

(9 mL) and reacted with CsF (558 mg, 3.67 mmol, 6.0 equiv) and [PdCl₂-

ACHTUNGTRENNUNG(dppf)] (50.0 mg, 0.061 mmol, 10 mol%). After completion of the reac-

tion, the mixture was cooled to RT and the precipitate was filtered off,

washed with H₂O (200 mL) and MeOH (300 mL), dried under vacuum,

and subjected to column chromatography (SiO₂, CH₂Cl₂) to give hex-9-

mer-BME as a colorless solid (700 mg, 0.518 mmol, 85%). ¹H NMR

(500 MHz, CDCl₃, 258C): d=7.93 (d, J=8.3 Hz, 2H), 7.54 (d, J=7.2 Hz,

4H), 7.42 (t, J=7.6 Hz, 4H), 7.33 (t, J=7.4 Hz, 2H), 7.17–7.10 (m, 12H),

7.07–7.05 (m, 6H), 5.27 (s, 4H), 3.96 (s, 6H), 2.53–2.37 (m, 4H), 2.20 (s,

6H), 2.14 (m, 30H), 1.48 (m, 4H), 1.21 (m, J=6.7 Hz, 12H), 0.88–

0.81 ppm (m, 6H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=166.8, 157.9,

147.6, 141.45, 141.39, 140.71, 140.63, 140.56, 140.46, 140.37, 140.28, 140.18,

140.13, 140.09, 140.03, 139.93, 139.90, 139.81, 139.76, 139.70, 139.45,

139.43, 137.63, 137.60, 137.56, 137.54, 137.51, 136.8, 133.56, 133.51, 133.10,

133.05, 132.98, 132.94, 132.88, 132.73, 132.67, 132.64, 132.57, 132.53,

132.45, 132.39, 132.08, 132.06, 131.73, 131.68, 131.22, 131.13, 130.98,

130.95, 130.73, 130.65, 130.35, 130.30, 130.22, 130.17, 130.07, 130.03, 128.6,

127.8, 126.8, 121.7, 118.8, 115.1, 70.6, 52.1, 32.90, 32.85, 32.79, 32.67,

32.62, 32.57, 31.61, 31.49, 31.11, 31.02, 30.98, 30.88, 30.86, 30.72, 29.23,

29.18, 29.15, 29.12, 29.10, 29.05, 22.59, 22.57, 19.85, 19.81, 19.78, 19.76,

19.64, 19.60, 19.55, 19.50, 19.47, 19.40, 19.37, 19.33, 19.28, 14.17,

14.09 ppm; HRMS (ESI): m/z calcd for C₉₆H₁₀₃O₆: 1351.7749 [M+H]⁺;

found: 1351.7758.

Synthesis of 15: Compound 14 (1.00 g, 2.12 mmol, 1.0 equiv), bis(pinaco-

lato)diboron (1.13 g, 4.45 mmol, 2.1 equiv), [PdCl₂ACHTNUTRGNEUNG(dppf)] (173 mg,

0.212 mmol, 10 mol%), and KOAc (1.25 g, 12.7 mmol, 6.0 equiv) were

added to a flame-dried flask containing anhydrous Me₂SO (50 mL) and

the reaction mixture was heated under reflux for 16 h. It was cooled to

RT, added to H₂O (25 mL), and then extracted three times with CH₂Cl₂

(100 mL). The organic layer was then washed extensively with H₂O

(300 mL). The organic phase was dried (MgSO₄), filtered, and concen-

trated. The crude product was absorbed on silica-gel and subjected to

column chromatography (SiO₂, hexanes) to give compound 15 as a color-

less solid (371 mg, 0.655 mmol, 31%). ¹H NMR (500 MHz, CD₂Cl₂,

258C): d=7.66 (s, 2H), 6.99 (m, 4H), 2.54 (s, 6H), 2.10 (s, 6H), 2.04 (s,

6H), 1.39 ppm (s, 24H); ¹³C NMR (126 MHz, CD₂Cl₂, 258C): d=144.5,

142.2, 140.7, 137.7, 132.9, 132.8, 132.4, 131.3, 131.2, 130.7, 83.8, 25.1,

21.80, 21.78, 19.4, 19.3, 19.1 ppm; HRMS (ESI): m/z calcd for

C₃₆H₄₉B₂O₄: 565.3884 [M+H]⁺; found: 565.3864.

Synthesis of 16: Following the general coupling procedure, 9 (1.50 g,

2.61 mmol, 1.0 equiv) and 12 (5.20 g, 10.4 mmol, 4.0 equiv) were dissolved

in a degassed mixture of dioxane (100 mL) and H₂O (50 mL) at 808C

and reacted with CsF (1.19 g, 7.83 mmol, 3.0 equiv) and [PdCl₂ACHTUNGTRENNUNG(dppf)]

Synthesis of hex-9-mer-HCA: Following the general hydrogenolysis pro-

cedure with hex-9-mer-BME (827 mg, 0.612 mmol, 1.0 equiv), Raney Ni

(ca. 10mol%), and THF (50 mL), the debenzylated compound was ob-

tained and used directly in the next step. Following the general saponifi-

(106 mg, 0.131 mmol, 5 mol%). After completion of the reaction, the

mixture was cooled to RT and extracted with CH₂Cl₂(100 mL) and H₂O

(500 mL). The aqueous phase was washed twice with CH₂Cl₂(200 mL),

the combined organic phases were dried (MgSO₄), concentrated, absorb-

cation procedure, hex-9-mer-HCA was obtained as

a

colorless solid

ACHTUNGTRENeNNUG d on silica-gel, and subjected to column chromatography (SiO₂, hex-

(700 mg, 0.612 mmol, quant). ¹H NMR (600 MHz, CD₃SOCD₃, 1008C):

d=7.87 (d, J=8.1 Hz, 2H), 7.17 (s, 2H), 7.10 (s, 2H), 7.08 (m, 8H), 7.05

(s, 2H), 6.94 (m, 4H), 2.27 (s, 6H), 2.09 (m, 30H), 1.44 (m, 4H), 1.26 (m,

4H), 1.22–1.14 ppm (m, 12H), 0.81 (t, J=7.1 Hz, 6H); ¹³C NMR

(151 MHz, [D₈]THF, 558C): d=170.0, 160.4, 147.9, 139.5, 138.63, 138.55,

138.32, 138.23, 137.9, 131.2, 130.93, 130.86, 130.68, 130.49, 130.0, 129.57,

129.51, 129.2, 128.90, 128.73, 128.71, 128.67, 128.61, 128.0, 123.0, 118.1,

115.9, 109.2, 32.2, 29.62, 29.55, 28.0, 27.7, 27.02, 26.96, 20.5, 17.0, 16.73,

16.68, 16.59, 11.45, 11.38 ppm; HRMS (ESI): m/z calcd for C₈₀H₈₅O₆:

1141.6352 [MꢀH]^ꢀ; found: 1141.6295.

anes/EtOAc=5:1) to afford compound 16 as a colorless solid (856 mg,

1.04 mmol, 40%). ¹H NMR (500 MHz, CDCl₃, 258C): d=7.94 (d, J=

8.3 Hz, 1H), 7.76 (s, 1H), 7.55 (d, J=7.2 Hz, 2H), 7.43 (t, J=7.6 Hz,

2H), 7.35 (t, J=7.4 Hz, 1H), 7.13 (s, 1H), 7.10–7.00 (m, 6H), 5.28 (s,

2H), 3.98 (s, 3H), 2.72 (m, 2H), 2.42 (m, 1H), 2.31 (m, 1H), 2.21 (s, 3H),

2.15–2.11 (m, 6H), 2.06 (m, 3H), 1.46–1.14 (m, 16H), 0.93–0.83 ppm (m,

6H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=166.8, 157.9, 147.5, 142.3,

141.39, 141.26, 140.55, 140.52, 140.13, 140.08, 139.61, 139.53, 139.48,

139.36, 139.27, 136.8, 133.45, 133.37, 132.82, 132.67, 132.54, 132.13, 132.07,

131.67, 131.47, 130.90, 130.84, 130.78, 130.69, 130.50, 130.40, 128.6, 127.8,

126.8, 121.7, 118.8, 115.1, 99.2, 70.6, 52.1, 40.38, 40.34, 34.7, 32.4, 32.1,

31.7, 31.45, 31.36, 30.81, 30.66, 30.43, 30.30, 29.15, 29.08, 29.00, 25.3,

22.69, 22.50, 19.84, 19.77, 19.62, 19.47, 19.2, 14.15, 14.06 ppm; HRMS

(ESI): m/z calcd for C₄₉H₅₈IO₃: 821.3425 [M+H]⁺; found: 821.3424.

Synthesis of 13: 1,4-Dibromo-2,5-dimethylbenzene (25.0 g, 94.7 mmol,

1.0 equiv), bis(pinacolato)diboron (50.5 g, 199 mmol, 2.1 equiv), [PdCl₂-

ACHTUNGTRENNUNG

a

Me₂SO (300 mL). The reaction mixture was heated under reflux for 16 h.

It was then cooled to RT, added to H₂O (100 mL), before being extracted

three times with CH₂Cl₂(300 mL). The organic layer was then washed

extensively with H₂O (600 mL). The organic phase was dried (MgSO₄),

filtered, and concentrated. EtOAc (250 mL) was added to the crude mix-

ture, along with activated carbon (10 g) and the reaction mixture was

heated under reflux for 3 h. It was cooled to RT, filtered through Celite,

Synthesis of hex-11-mer-BME: Following the general coupling procedure,

15 (151 mg, 0.266 mmol, 1.0 equiv) and 16 (480 mg, 0.585 mmol,

2.2 equiv) were suspended in a degassed mixture of dioxane (12 mL) and

H₂O (6 mL) and reacted with CsF (242 mg, 1.60 mmol, 6.0 equiv) and

[PdCl₂ACTHUNRTGNEUNG(dppf)] (22 mg, 0.0269 mmol, 10 mol%). After completion of the

reaction, the mixture was cooled to RT and the precipitate was filtered

off, washed with H₂O (50 mL) and MeOH (50 mL) and dried at vacuum.

Chem. Eur. J. 2012, 18, 15632 – 15649

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

15645

J. F. Stoddart et al.

The beige crude product was subjected to column chromatography (SiO₂,

CH₂Cl₂) to yield hex-11-mer-BME as colorless solid (373 mg,

(dd, J=7.9, 1.3 Hz, 1H), 7.48 (s, 1H), 7.48 (s, 1H), 7.16 (d, J=7.9 Hz,

1H), 7.16 (d, J=7.9 Hz, 1H), 6.97 (s, 1H), 6.97 (s, 1H), 3.96 (s, 3H), 3.96

(s, 3H), 2.40 (s, 3H), 2.40 (s, 3H), 2.12 (s, 3H), 2.12 (s, 3H), 1.99 (s, 3H),

1.99 ppm (s, 3H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=167.2, 145.4,

139.8, 136.2, 135.05, 134.85, 133.5, 131.09, 130.98, 129.40, 129.23, 126.9,

123.8, 52.2, 22.4, 19.8, 19.0 ppm; HRMS (ESI): m/z calcd for C₁₇H₁₈Br₂:

333.0485 [M+H]⁺; found: 333.0479.

a

0.219 mmol, 82%). ¹H NMR (500 MHz, CDCl₃, 258C): d=7.96 (d, J=

8.2 Hz, 2H), 7.57 (d, J=7.6 Hz, 4H), 7.44 (t, J=7.6 Hz, 4H), 7.36 (t, J=

7.4 Hz, 2H), 7.19–7.07 (m, 22H), 5.29 (s, 4H), 3.99 (s, 6H), 2.54 (m, 4H),

2.41 (m, 4H), 2.23–2.14 (m, 46H), 1.54–1.46 (m, 8H), 1.28–1.17 (m,

24H), 0.87 ppm (m, 12H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=166.8,

157.9, 147.6, 141.53, 141.43, 140.68, 140.65, 140.57, 140.47, 140.33, 140.28,

140.21, 140.18, 140.02, 139.99, 139.90, 139.87, 139.78, 139.71, 139.68,

139.63, 139.60, 139.58, 139.45, 139.40, 137.67, 137.64, 137.61, 137.57,

137.54, 137.51, 137.49, 137.46, 137.44, 136.8, 133.57, 133.50, 133.21, 133.15,

133.05, 132.99, 132.87, 132.82, 132.76, 132.71, 132.66, 132.64, 132.60,

132.51, 132.50, 132.45, 132.42, 132.31, 132.09, 132.04, 131.78, 131.68,

131.60, 131.29, 131.24, 131.20, 131.16, 131.11, 130.90, 130.78, 130.71,

130.67, 130.59, 130.37, 130.32, 130.25, 130.19, 130.13, 130.10, 130.06,

130.04, 130.00, 128.6, 127.8, 121.7, 118.8, 115.1, 70.6, 52.1, 34.7, 32.8,

32.62, 32.61, 31.61, 31.50, 31.10, 31.01, 30.97, 30.87, 30.84, 30.72, 29.23,

29.18, 29.14, 29.10, 29.05, 22.60, 22.57, 20.8, 19.87, 19.80, 19.78, 19.64,

19.61, 19.53, 19.50, 19.48, 19.46, 19.37, 19.31, 19.25, 14.17, 14.09 ppm;

Synthesis of 20: Compound 19 (900 mg, 2.70 mmol, 1.0 equiv) and

bis(pin

anhydrous degassed Me₂SO (11 mL). KOAc (795 mg, 8.10 mmol,

3.0 equiv) and [PdCl₂A(dppf)] (110 mg, 0.135 mmol, 5 mol%) were added

ACHTUNGTRENaNUNG colato)diboron (754 mg, 2.97 mmol, 1.1 equiv) were dissolved in

CTHUNGTRENNUNG

and the reaction mixture was heated to 808C overnight, before being

cooled to RT and extracted with CH₂Cl₂(100 mL) and H₂O (500 mL).

The aqueous phase was washed twice with CH₂Cl₂(200 mL). The com-

bined organic phases were washed with H₂O, dried (MgSO₄), concentrat-

ed, and subjected to column chromatography (SiO₂, hexanes/EtOAc=

5:1) to give compound 20 as a colorless oil (880 mg, 2.38 mmol, 88%).

¹H NMR (500 MHz, CDCl₃, 258C): d=7.97 (s, 1H), 7.91 (dd, J=7.9,

1.4 Hz, 1H), 7.70 (s, 1H), 7.18 (d, J=7.9 Hz, 1H), 6.92 (s, 1H), 3.96 (s,

3H), 2.55 (s, 3H), 2.12 (s, 3H), 2.02 (s, 3H), 1.39 ppm (s, 12H); ¹³C NMR

(126 MHz, CDCl₃, 258C): d=167.3, 146.6, 143.2, 142.1, 137.4, 136.1,

131.6, 131.0, 130.2, 129.3, 128.9, 126.8, 83.5, 52.1, 34.7, 25.0, 21.7, 19.8,

19.0 ppm; HRMS (ESI): m/z calcd for C₂₃H₃₀BO₄: 380.2268 [M+H]⁺;

found: 380.2263.

HRMS (ESI): m/z calcd for

C

₁₂₂H₁₃₉O₆: 1700.0566 [M+H]⁺; found:

1700.0582.

Synthesis of hex-11-mer-HCA: Following the general hydrogenolysis pro-

cedure, hex-11-mer-BME (372 mg, 0.219 mmol, 1.0 equiv) and Raney Ni

(ca. 10 mol%) in THF (30 mL) provided the debenzylated compound

which was used directly in the next step. Following the general saponifi-

cation procedure provided the hex-11-mer-HCA as a colorless solid

(326 mg, 0.219 mmol, quant). ¹H NMR (600 MHz, CD₃SOCD₃, 1008C):

d=7.87 (d, J=7.8 Hz, 2H), 7.17 (s, 2H), 7.11–7.05 (m, 16H), 6.95 (m,

4H), 2.27 (s, 6H), 2.11–2.09 (m, 36H), 1.44 (m, 8H), 1.26–1.15 (m, 32H),

0.81 ppm (m, 12H); ¹H NMR (600 MHz, THF, 568C): d=7.92 (d, J=

8.0 Hz, 2H), 7.18 (s, 2H), 7.16 (s, 2H), 7.12 (t, J=9.7 Hz, 12H), 7.07 (s,

2H), 6.98 (s, 2H), 6.92 (d, J=7.8 Hz, 2H), 2.56 (m, 4H), 2.45 (m, 4H),

2.30 (s, 6H), 2.16 (s, 18H), 2.15 (s, 12H), 2.13 (s, 6H), 1.53 (m, 8H), 1.26

(s, 24H), 0.87 ppm (m, J=7.6 Hz, 12H); ¹³C NMR (151 MHz, [D₈]THF,

558C): d=171.9, 162.2, 149.7, 141.3, 140.61, 140.46, 140.1, 139.8, 137.6,

137.2, 133.12, 133.09, 132.85, 132.78, 132.65, 132.3, 131.9, 131.45, 131.29,

131.14, 131.09, 131.04, 130.74, 130.66, 130.56, 130.48, 130.31, 130.20,

130.06, 129.86, 124.9, 119.9, 117.8, 111.1, 32.8, 32.6, 31.48, 31.41, 30.90,

30.82, 30.68, 29.8, 29.6, 29.05, 28.95, 22.35, 22.33, 18.98, 18.89, 18.86,

18.76, 18.51, 18.47, 18.39, 13.32, 13.25 ppm; HRMS (ESI): m/z calcd for

Synthesis of 2-mer-ME: Following the general coupling procedure, 18

(830 mg, 3.01 mmol, 1.0 equiv) and 17 (690 mg, 3.01 mmol, 1.0 equiv)

were reacted in a degassed 2:1 dioxane/H₂O mixture (90 mL) with CsF

(1.37 g, 9.03 mmol, 3.0 equiv) and [PdCl₂ACTHNUTRGNEU(GN dppf)] (123 mg, 0.150 mmol,

5 mol%) for 15 h. The reaction mixture was cooled to RT before being

extracted with CH₂Cl₂and H₂O. The aqueous phase was washed twice

with CH₂Cl₂. The combined organic phases were dried (MgSO₄), filtered,

and concentrated. The crude product was absorbed on silica-gel and sub-

jected to column chromatography (SiO₂, hexanes/EtOAc=5:1) to give 2-

mer-ME as

a

colorless solid (502 mg, 1.68 mmol, 56%). ¹H NMR

(500 MHz, CDCl₃, 258C): d=7.99 (s, 2H), 7.93 (dd, J=7.9, 1.5 Hz, 2H),

7.18 (d, J=7.9 Hz, 2H), 3.97 (s, 6H), 2.10 ppm (s, 6H); ¹³C NMR

(126 MHz, CDCl₃, 258C): d=167.1, 145.5, 135.9, 131.2, 129.5, 129.0,

127.0, 52.2, 19.7 ppm; HRMS (ESI): m/z calcd for C₁₈H₁₉O₄: 299.1278

[M+H]⁺; found: 299.1288.

Synthesis of 3-mer-ME: Following the general coupling procedure, 18

(2.00 g, 7.24 mmol, 2.3 equiv) and 1,4-diiodo-2,5-dimethylbenzene^[21]

(1.13 g, 3.15 mmol, 1.0 equiv) were reacted in a degassed 2:1 dioxane/

H₂O mixture (150 mL) with CsF (2.87 g, 18.9 mmol, 3.0 equiv) and

C

₁₀₆H₁₂₃O₆: 1491.9314 [M+H]⁺; found: 1491.9260; HRMS (ESI): m/z

calcd for C₁₀₆H₁₂₁O₆:1489.9169 [MꢀH]^ꢀ; found: 1489.9145.

Synthesis of 18: Compound 17 (5.00 g, 21.8 mmol, 1.0 equiv) and bis(pin-

ACHTUNGTRENNUNG

[PdCl₂ACTHUNRTGNEUNG(dppf)] (260 mg, 0.315 mmol, 5 mol%) for 15 h. The reaction mix-

ture was cooled to RT before being extracted with CH₂Cl₂(100 mL) and

H₂O (300 mL). The aqueous phase was washed twice with CH₂Cl₂

(100 mL). The combined organic phases were dried (MgSO₄), filtered,

and concentrated. The crude product was absorbed on silica-gel and sub-

jected to column chromatography (SiO₂, hexanes/EtOAc=9:1) to give 3-

CHTUNGTRENNUNG

mixture was heated to 808C overnight, before being cooled to RT and ex-

tracted with CH₂Cl₂(100 mL) and H₂O (500 mL). The aqueous phase

was washed twice with CH₂Cl₂(200 mL). The combined organic phases

were washed with H₂O, dried (MgSO₄), concentrated, and subjected to

column chromatography (SiO₂, hexanes/EtOAc=5:1) to give compound

18 as a colorless oil (5.84 g, 21.2 mmol, 97%). ¹H NMR (500 MHz,

CDCl₃, 258C): d=7.81 (m, 3H), 3.91 (s, 3H), 2.57 (s, 3H), 1.35 ppm (s,

12H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=167.4, 144.9, 135.8, 131.8,

130.5, 125.6, 83.9, 52.1, 24.9, 22.1 ppm; HRMS (ESI): m/z calcd for

C₁₅H₂₂BO₄: 277.1608 [M+H]⁺; found: 277.1611.

mer-ME as

a

colorless solid (904 mg, 2.25 mmol, 71%). ¹H NMR

(500 MHz, CDCl₃, 258C): d=8.00 (s, 2H), 7.94 (d, J=7.9 Hz, 2H), 7.11

(m, 1H), 7.00 (d, J=6.9 Hz, 2H), 3.97 (s, 6H), 2.19 (m, J=5.9 Hz, 3H),

2.12 (m, J=6.8 Hz, 3H), 2.05–2.04 ppm (m, 6H); ¹³C NMR (126 MHz,

CDCl₃, 258C): d=167.31, 167.30, 146.44, 146.38, 145.5, 139.90, 139.86,

136.44, 136.35, 135.9, 132.62, 132.53, 131.19, 131.03, 130.3, 129.66, 129.57,

129.45, 129.02, 129.00, 128.96, 127.01, 126.89, 126.84, 52.2, 19.94, 19.80,

19.72, 19.2 ppm; HRMS (ESI): m/z calcd for C₂₆H₂₇O₄: 403.1904 [M+H]⁺

; found: 403.1903.

Synthesis of 19: Following the general coupling procedure, 18 (1.42 g,

5.14 mmol, 1.0 equiv) and 4 (6.79 g, 25.7 mmol, 5.0 equiv) were dissolved

in a degassed mixture of dioxane (500 mL) and H₂O (200 mL) at 808C

Synthesis of 4-mer-ME: Following the general coupling procedure, 18

(2.00 g, 7.24 mmol, 2.3 equiv) and 5 (1.46 g, 3.15 mmol, 1.0 equiv) were

reacted in a degassed 2:1 dioxane/H₂O mixture (150 mL) with CsF

before CsF (2.34 g, 15.4 mmol, 3.0 equiv) and [PdCl₂ACHTNUTRGNEUNG(dppf)] (210 mg,

0.260 mmol, 5 mol%) were added. After completion of the reaction, the

mixture was cooled to RT, before being extracted with CH₂Cl₂(300 mL)

and H₂O (700 mL). The aqueous phase was washed twice with CH₂Cl₂

(400 mL). The combined organic phases were washed with brine, dried

(MgSO₄), and concentrated. The crude product was subjected to column

chromatography (SiO₂, hexanes/EtOAc=10:1) to give the product as a

colorless oil (973 mg, 2.93 mmol, 57%). ¹H NMR (500 MHz, CDCl₃,

258C): d=7.97 (s, 1H), 7.97 (s, 1H), 7.91 (dd, J=7.9, 1.3 Hz, 1H), 7.91

(2.87 g, 18.9 mmol, 3.0 equiv) and [PdCl₂ACTHNUTRGNEU(GN dppf)] (260 mg, 0.315 mmol,

5 mol%) for 15 h. The reaction mixture was cooled to RT, before being

extracted with CH₂Cl₂(100 mL) and H₂O (400 mL). The aqueous phase

was washed twice with CH₂Cl₂(100 mL). The combined organic phases

were dried (MgSO₄), filtered, and concentrated. The crude product was

absorbed on silica-gel and subjected to column chromatography (SiO₂,

hexanes/EtOAc=9:1) to give 4-mer-ME as a colorless solid (940 mg,

15646

www.chemeurj.org

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2012, 18, 15632 – 15649

Molecular Gauge Blocks

FULL PAPER

1.86 mmol, 59%). ¹H NMR (500 MHz, CDCl₃, 258C): d=8.01 (s, 2H),

7.94 (d, J=7.9 Hz, 2H), 7.30 (m, 2H), 7.11–7.09 (m, 2H), 7.01 (d, J=

7.1 Hz, 2H), 3.98 (s, 6H), 2.21 (m, J=6.8 Hz, 6H), 2.12 (m, J=6.1 Hz,

6H), 2.05 ppm (m, 6H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=167.3,

146.71, 146.63, 140.71, 140.66, 140.61, 139.43, 139.40, 139.38, 139.34,

136.49, 136.44, 133.14, 133.04, 132.95, 132.39, 132.34, 132.29, 132.24,

131.19, 131.00, 130.91, 130.85, 130.1, 129.75, 129.65, 129.02, 128.91, 128.88,

126.86, 126.81, 52.1, 19.98, 19.84, 19.48, 19.47, 19.32, 19.28, 19.24 ppm;

HRMS (ESI): m/z calcd for C₃₄H₃₅O₄: 507.2530 [M+H]⁺; found:

507.2539.

[1] a) G. M. Whitesides, J. P. Mathias, C. T. Seto, Science 1991 , 254 ,

131 2 –1 319; b) G. M. Whitesides, B. Grzybowski, Science 2002 , 295 ,

241 8 –2 421; c) G. M. Whitesides, M. Boncheva, Proc. Natl. Acad.

Sci. USA 2002 , 99 , 476 9 –4 774; d) J.-M. Lehn, Science 2002 , 295 ,

240 0 –2 403; e) B. A. Grzybowski, C. E. Wilmer, J. Kim, K. P.

Browne, K. J. M. Bishop, Soft Matter 2009 , 5 , 111 0 –1 128.

[2] a) D. H. Busch, N. A. Stephenson, Coord. Chem. Rev. 1990, 100,

119–154; b) S. Anderson, H. L. Anderson, J. K. M. Sanders, Acc.

Chem. Res. 1993, 26, 469–475; c) R. Cacciapaglia, L. Madolini,

Chem. Soc. Rev. 1993, 22, 221–231; d) R. Hoss, F. Vçgtle, Angew.

Chem. 1994, 106, 389–398; Angew. Chem. Int. Ed. Engl. 1994, 33,

375–384; e) J. P. Schneider, J. W. Kelly, Chem. Rev. 1995, 95, 2169–

2187; f) T. J. Hubin, D. H. Busch, Coord. Chem. Rev. 2000, 200, 5–

52; g) J. F. Stoddart, H.-R. Tseng, Proc. Natl. Acad. Sci. USA 2002,

99, 4797–4800; h) M.-J. Blanco, J.-C. Chambron, M.-C. Jimenez, J.-

P. Sauvage, Top. Stereochem. 2002, 23, 125–173; i) C. A. Schalley, T.

Weilandt, J. Bruggemann, F. Vçgtle, Top. Curr. Chem. 2005, 248,

Synthesis of 5-mer-ME: Following the general coupling procedure, 20

(290 mg, 0.763 mmol, 2.2 equiv) and 1,4-diiodo-2,5-dimethylbenzene^[21]

(124 mg, 0.347 mmol, 1.0 equiv) were reacted in a degassed 2:1 dioxane/

H₂O mixture (24 mL) with CsF (316 mg, 2.08 mmol, 3.0 equiv) and

[PdCl₂ACHTUNGTRENNUNG(dppf)] (28.0 mg, 0.035 mmol, 5 mol%) for 15 h. The reaction mix-

ture was cooled to RT before being extracted with CH₂Cl₂(25 mL) and

H₂O (50 mL). The aqueous phase was washed twice with CH₂Cl₂

(30 mL). The combined organic phases were dried (MgSO₄), filtered, and

concentrated. The crude product was absorbed on silica-gel and subjected

to column chromatography (SiO₂, CH₂Cl₂/hexanes=1:1!1:0) to give 5-

´

141–200; j) F. Aricꢆ, J. D. Badjic, S. J. Cantrill, A. H. Flood, K. C.-F.

Leung, Y. Liu, J. F. Stoddart, Top. Curr. Chem. 2005, 249, 203–259;

k) C. D. Meyer, C. S. Joiner, J. F. Stoddart, Chem. Soc. Rev. 2007, 36,

1705–1723; l) M. S. Vickers, P. D. Beer, Chem. Soc. Rev. 2007, 36,

211–225; m) J. D. Crowley, S. M. Goldup, A.-L. Lee, D. A. Leigh,

R. T. McBurney, Chem. Soc. Rev. 2009, 38, 1530–1541; n) M. E. Be-

lowich, J. F. Stoddart, Chem. Soc. Rev. 2012, 41, 2003–2024.

mer-ME as

a

colorless solid (170 mg, 0.278 mmol, 80%). ¹H NMR

(500 MHz, [D₈]tol, 258C): d=8.16 (m, 2H), 8.08–8.04 (m, 2H), 7.16 (m,

4H), 7.11 (m, 2H), 6.98 (m, 2H), 3.63 (m, 6H), 2.19 (m, 6H), 2.15 (m,

6H), 2.08 (m, 6H), 2.02 ppm (m, 6H); ¹³C NMR (126 MHz, CDCl₃,

258C): d=167.4, 146.77, 146.70, 140.93, 140.88, 140.82, 140.17, 140.14,

139.29, 139.27, 136.52, 136.46, 133.20, 133.14, 133.09, 133.03, 132.90,

132.86, 132.81, 132.79, 132.77, 132.75, 132.71, 132.67, 132.32, 132.29,

132.21, 132.18, 131.00, 130.93, 130.74, 130.67, 130.1, 129.77, 129.67, 128.88,

128.85, 126.85, 126.80, 52.1, 19.98, 19.84, 19.50, 19.46, 19.35, 19.29,

19.24 ppm; HRMS (ESI): m/z calcd for C₄₂H₄₃O₄: 611.3156 [M+H]⁺;

found: 611.3160.

[3] a) M. C. T. Fyfe, J. F. Stoddart, Acc. Chem. Res. 1997 , 30 , 39 3 –4 01;

b) S. J. Cantrill, A. R. Pease, J. F. Stoddart, J. Chem. Soc. Dalton

Trans. 2000 , 371 5 –3 734; c) P. A. Gale, Acc. Chem. Res. 2006 , 39 ,

46 5 –4 75; d) J.-M. Lehn, Chem. Soc. Rev. 2007 , 36 , 15 1 –1 60; e) S. W.

Thomas III, G. D. Joly, T. M. Swager, Chem. Rev. 2007 , 107 , 133 9 –

1386; f) B. L. Schottel, H. T. Chifotides, K. F. Dunbar, Chem. Soc.

ˇ

´

Rev. 2008 , 37 , 6 8 –8 3; g) Q. Li, W. Zhang, O. S. Miljanic, C.-H. Sue,

Y.-L. Zhao, L. Liu, C. B. Knobler, J. F. Stoddart, O. M. Yaghi, Sci-

ence 2009 , 325 , 85 5 –8 59; h) B. Chen, S. Xiang, G. Qian, Acc. Chem.

Res. 2010 , 43 , 111 5 –1 124; i) L. M. Salonen, M. Ellermann, F. Dieder-

ich, Angew. Chem. 2011 , 123 , 490 8 –4 944; Angew. Chem. Int. Ed.

2011 , 50 , 480 8 –4 842; j) A. Harada, R. Kobayashi, Y. Takashima, A.

Hashidzume, H. Yamaguchi, Nat. Chem. 2011 , 3 , 3 4 –3 7.

Synthesis of 6-mer-ME: Following the general coupling procedure, 20

(290 mg, 0.763 mmol, 2.2 equiv) and 5 (160 mg, 0.347 mmol, 1.0 equiv)

were reacted in a degassed 2:1 dioxane/H₂O mixture (24 mL) with CsF

(316 mg, 2.08 mmol, 3.0 equiv) and [PdCl₂ACHTNUTGRNEUNG(dppf)] (28.0 mg, 0.035 mmol,

5 mol%) for 15 h. The reaction mixture was cooled to RT, before being

extracted with CH₂Cl₂(25 mL) and H₂O (50 mL). The aqueous phase

was washed twice with CH₂Cl₂(300 mL). The combined organic phases

were dried (MgSO₄), filtered, and concentrated. The crude product was

absorbed on silica-gel and subjected to column chromatography (SiO₂,

[4] 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. Jonkheijm,

P. van der Schoot, A. P. H. J. Schenning, E. W. Meijer, Science 2006 ,

313 , 8 0 –8 3; c) K. E. Griffiths, J. F. Stoddart, Pure Appl. Chem. 2008 ,

80 , 48 5 –5 06; d) J. F. Stoddart, H. M. Colquhoun, Tetrahedron 2008 ,

64 , 823 1 –8 263; e) Y. He, T. Ye, M. Su, C. Zhang, A. E. Ribbe, W.

Jiang, C. D. Mao, Nature 2008 , 452 , 19 8 –2 01; f) K. J. M. Bishop,

C. E. Wilmer, S. Soh, B. A. Grzybowski, Small 2009 , 5 , 160 0 –1 630;

g) B. H. Northrop, Y.-R. Zheng, K.-W. Chi, P. J. Stang, Acc. Chem.

Res. 2009 , 42 , 155 4 –1 563.

[5] a) A. Mꢀller, E. Krickemeyer, H. Bçgge, M. Schmidtmann, F.

Peters, Angew. Chem. 1998 , 110 , 356 7 –3 571; Angew. Chem. Int. Ed.

1998 , 37 , 335 9 –3 363; b) B. Olenyuk, M. D. Levin, J. A. Whiteford,

J. E. Shield, P. J. Stang, J. Am. Chem. Soc. 1999 , 121 , 1043 4 –1 0435;

c) M. D. Levin, P. J. Stang, J. Am. Chem. Soc. 2000 , 122 , 742 8 –7 429;

d) D. K. Chand, K. Biradha, M. Fujita, S. Sakamoto, K. Yamaguchi,

Chem. Commun. 2002 , 248 6 –2 487; e) M. Tominaga, K. Suzuki, M.

Kawano, T. Kusukawa, T. Ozeki, S. Sakamoto, K. Yamaguchi, M.

Fujita, Angew. Chem. 2004 , 116 , 573 9 –5 743; Angew. Chem. Int. Ed.

2004 , 43 , 562 1 –5 625; f) M. Fujita, M. Tominaga, A. Hori, B. Ther-

rien, Acc. Chem. Res. 2005 , 38 , 36 9 –3 78; g) K. Ghosh, J. Hu, H. S.

White, P. J. Stang, J. Am. Chem. Soc. 2009 , 131 , 669 5 –6 697; h) J.

Sun, R. Warmuth, Chem. Commun. 2011 , 47 , 935 1 –9 353; i) Y.-R.

Zheng, W.-J. Lan, M. Wang, T. R. Cook, P. J. Stang, J. Am. Chem.

Soc. 2011 , 133 , 1704 5 –1 7055.

CH₂Cl₂/hexanes=1:1!1:0) to give 6-mer-ME as

a colorless solid

(196 mg, 0.274 mmol, 79%). ¹H NMR (500 MHz, [D₈]tol, 258C): d=8.48

(m, 2H), 8.38 (m, 2H), 7.54–7.48 (m, 6H), 7.43 (m, 2H), 7.31 (m, 2H),

3.96 (m, 6H), 2.54–2.51 (m, 12H), 2.48–2.47 (m, 6H), 2.40 (m, 6H), 2.35–

2.33 ppm (m, 6H); ¹³C NMR (126 MHz, CDCl₃, 258C): d=167.4, 146.79,

146.71, 140.93, 140.88, 140.40, 140.35, 140.12, 140.07, 139.30, 139.27,

139.25, 136.52, 136.47, 133.2, 132.86, 132.80, 132.75, 132.72, 132.31, 132.29,

132.20, 132.17, 130.95, 130.93, 130.84, 130.74, 130.71, 130.63, 130.0, 129.77,

129.68, 128.88, 128.85, 126.85, 126.80, 52.1, 19.98, 19.84, 19.51, 19.50,

19.35, 19.29, 19.24 ppm; HRMS (ESI): m/z calcd for C₅₀H₅₁O₄: 715.3782

[M+H]⁺; found: 715.3791.

Acknowledgements

The research conducted at Northwestern University was supported in

part by the Non-equilibrium Energy Research Center which, is an

Energy Frontier Research Center funded by the US. Department of

Energy, Offices of Basic Energy Sciences under Award Number DE-

SC0000989. S.G. thanks the Swiss National Science Foundation for finan-

cial support. We are also thankful for the support of the National Center

for Nano Technology at KACST in Saudi Arabia—we thank Dr. Turki S.

Al-Saud, Dr. Soliman H. Alkhowaiter, and Dr. Mohamed B. Alfageeh

for their support of this research. J.F.S. was also supported by the WCU

Program (R31-2008-000-10055) at KAIST.

[6] a) S. Leininger, B. Olenyuk, P. J. Stang, Chem. Rev. 2000, 100, 853–

908; b) V. Balzani, M. Clemente-Leꢆn, A. Credi, J. N. Lowe, J. D.

´

Badjic, J. F. Stoddart, D. J. Williams, Chem. Eur. J. 2003, 9, 5348–

´

5360; c) J. D. Badjic, S. J. Cantrill, R. H. Grubbs, E. N. Guidry, R.

Orenes, J. F. Stoddart, Angew. Chem. 2004, 116, 3335–3340; Angew.

Chem. Int. Ed. 2004, 43, 3273–3278; d) H.-B. Yang, K. Ghosh, N.

Chem. Eur. J. 2012, 18, 15632 – 15649

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

15647

J. F. Stoddart et al.

Das, P. J. Stang, Org. Lett. 2006, 8, 3991–3994; e) B. H. Northrop, F.

Slabon-Turski, R. Scopelliti, A. H. Velders, K. Severin, J. Am.

Chem. Soc. 2010, 132, 14004–14005; h) J. R. Li, H. C. Zhou, Nat.

Chem. 2010, 2, 893–898.

´

Aricꢆ, N. Tangchiavang, J. D. Badjic, J. F. Stoddart, Org. Lett. 2006,

8, 3899–3902; f) Y. Inokuma, T. Arai, M. Fujita, Nat. Chem. 2010, 2,

780–783; g) A. Granzhan, T. Riis-Johannessen, R. Scopelliti, K. Se-

verin, Angew. Chem. 2010, 122, 5647–5650; Angew. Chem. Int. Ed.

2010, 49, 5515–5518; h) Y.-R. Zheng, Z. Zhao, M. Wang, K. Ghosh,

J. B. Pollock, T. R. Cook, P. J. Stang, J. Am. Chem. Soc. 2010, 132,

16873–16882; i) A. Granzhan, C. Schouwey, T. Riis-Johannessen, R.

Scopelliti, K. Severin, J. Am. Chem. Soc. 2011, 133, 7106–7115;

j) M. Wang, Y.-R. Zheng, T. R. Cook, P. J. Stang, Inorg. Chem. 2011,

50, 6107–6113.

[10] a) A. P. Cꢉtꢈ, A. I. Benin, N. W. Ockwig, M. OꢇKeeffe, A. J. Matzg-

er, O. M. Yaghi, Science 2005, 310, 1166–1170; b) R. W. Tilford,

W. R. Gemmill, H.-C. zur Loye, J. J. Lavigne, Chem. Mater. 2006 , 18 ,

529 6 –5 301; c) H. M. El-Kaderi, J. R. Hunt, J. L. Mendoza-Cortꢈs,

A. P. Cꢉtꢈ, R. E. Taylor, M. OꢇKeeffe, O. M. Yaghi, Science 2007 ,

316 , 26 8 –2 72; d) A. P. Cꢉtꢈ, H. M. El-Kaderi, H. Furukawa, J. R.

Hunt, O. M. Yaghi, J. Am. Chem. Soc. 2007, 129, 12914–12915; e) S.

Wan, J. Guo, J. Kim, H. Ihee, D. Jiang, Angew. Chem. 2008 , 120 ,

895 8 –8 962; Angew. Chem. Int. Ed. 2008 , 47 , 882 6 –8 830; f) R. W.

Tilford, S. J. Mugavero Iii, P. J. Pellechia, J. J. Lavigne, Adv. Mater.

2008 , 20 , 274 1 –2 746; g) S. Wan, J. Guo, J. Kim, H. Ihee, D. Jiang,

Angew. Chem. 2009 , 121 , 554 7 –5 550; Angew. Chem. Int. Ed. 2009 ,

48 , 543 9 –5 442; h) E. L. Spitler, W. R. Dichtel, Nat. Chem. 2010 , 2 ,

67 2 –6 77; i) M. Dogru, A. Sonnauer, A. Gavryushin, P. Knochel, T.

Bein, Chem. Commun. 2011 , 47 , 170 7 –1 709; j) S. Wan, F. Gꢊndara,

A. Asano, H. Furukawa, A. Saeki, S. K. Dey, L. Liao, M. W. Ambro-

gio, Y. Y. Botros, X. Duan, S. Seki, J. F. Stoddart, O. M. Yaghi,

Chem. Mater. 2011 , 23 , 409 4 –4 097; k) M. Dogru, A. Sonnauer, A.

Gavryushin, P. Knochel, T. Bien, Chem. Commun. 2011 , 47 , 170 7 –

1709; l) J. W. Colson, A. R. Woll, A. Mukherjee, M. P. Levendorf,

E. L. Spitler, V. B. Shields, M. G. Spencer, J. Park, W. R. Dichtel,

Science 2011 , 332 , 22 8 –2 31; m) D. N. Bunck, W. R. Dichtel, Angew.

Chem. 2012 , 124 , 192 1 –1 925; Angew. Chem. Int. Ed. 2012 , 51 , 188 5 –

1889; n) E. L. Spitler, J. W. Colson, F. J. Uribe-Romo, A. R. Woll,

M. R. Giovino, A. Saldivar, W. R. Dichtel, Angew. Chem. 2012 , 124 ,

267 7 –2 681; Angew. Chem. Int. Ed. 2012 , 51 , 262 3 –2 627.

[11] D. L. Caulder, K. N. Raymond, Acc. Chem. Res. 1999 , 32 , 97 5 –9 82.

[12] Besides controlling the size and shape of spheres, cages, capsules,

MOFs, COFs, MOPs, it is also desirable to identify building blocks

capable of directing the formation of these structures; to name a

few: a) block copolymers: F. S. Bates, G. H. Fredrickson, Annu. Rev.

Phys. Chem. 1990, 41, 525–557; b) dendrimers: S. M. Grayson,

J. M. J. Frꢈchet, Chem. Rev. 2001, 101, 3819–3867; c) membranes:

D. E. Discher, A. Eisenberger, Science 2002, 297, 967–973; d) lamel-

lar structures: M. Sofos, J. Goldberger, D. A. Stone, J. E. Allen, Q.

Ma, D. J. Herman, W.-W Tsai, L. J. Lauhon, S. I. A. Stupp, Nat.

Mater. 2009, 8, 68–75.

[13] a) V. H. O. Wirth, F. U. Herrmann, W. Kern, Makromol. Chem.

1964 , 80 , 12 0 –1 40; b) J. M. Tour, Adv. Mater. 1994 , 6 , 19 0 –1 98;

c) S. T. Pasco, G. L. Baker, Synth. Met. 1997 , 84 , 27 5 –2 76; d) A. J.

Berresheim, M. Mꢀller, K. Mꢀllen, Chem. Rev. 1999 , 99 , 174 7 –1 786;

e) N. I. Nijegorodov, W. S. Downey, M. B. Danailov, Spectrochim.

Acta Part A 2000, 56, 783–795; f) E. A. Weiss, M. J. Ahrens, L. E.

Sinks, A. V. Gusev, M. A. Ratner, M. R. Wasielewski, J. Am. Chem.

Soc. 2004 , 126 , 557 7 –5 584; g) E. A. Weiss, M. J. Tauber, R. F.

Kelley, M. J. Ahrens, M. A. Ratner, M. R. Wasielewski, J. Am.

Chem. Soc. 2005 , 127 , 1184 2 –1 1850; h) C. Li, M. Liu, N. G. Pschirer,

M. Baumgarten, K. Mꢀllen, Chem. Rev. 2010 , 110 , 681 7 –6 855.

[14] D. Hanss, O. S. Wenger, Eur. J. Inorg. Chem. 2009 , 377 8 –3 790.

[15] a) E. Lçrtscher, M. Elbing, M. Tschudy, C. v. Hꢁnisch, H. B. Weber,

M. Mayor, H. Riel, ChemPhysChem 2008 , 9 , 225 2 –2 258; b) D.

Hanss, O. S. Wenger, Inorg. Chem. 2008 , 47 , 908 1 –9 084.

[7] a) R. Wyler, J. de Mendoza, J. Rebek, Angew. Chem. 1993, 105,

1820–1821; Angew. Chem. Int. Ed. Engl. 1993, 32, 1699–1701;

b) M. M. Conn, J. Rebek, Chem. Rev. 1997, 97, 1647–1668; c) T.

Heinz, D. M. Rudkevich, J. Rebek, Nature 1998, 394, 764–766; d) B.

Olenyuk, J. A. Whiteford, A. Fechtenkotter, P. J. Stang, Nature 1999,

398, 796–799; e) N. Takeda, K. Umemoto, K. Yamaguchi, M. Fujita,

Nature 1999, 398, 794–796; f) B. Chatterjee, J. C. Noveron, M. J. E.

Resendiz, J. Liu, T. Yamamoto, D. Parker, M. Cinke, C. V. Nguyen,

A. M. Arif, P. J. Stang, J. Am. Chem. Soc. 2004, 126, 10645–10656;

g) X. Liu, Y. Liu, G. Li, R. Warmuth, Angew. Chem. 2006, 118, 915–

918; Angew. Chem. Int. Ed. 2006, 45, 901–904; h) Y. Liu, X. Liu, R.

Warmuth, Chem. Eur. J. 2007, 13, 8953–8959; i) A. C. McKinlay, B.

Xiao, D. S. Wragg, P. S. Wheatley, I. L. Megson, R. E. Morris, J. Am.

Chem. Soc. 2008, 130, 10440–10444; j) J. Rebek, Acc. Chem. Res.

2009, 42, 1660–1668; k) H. Dube, D. Ajami, J. Rebek, Angew.

Chem. 2010, 122, 3260–3263; Angew. Chem. Int. Ed. 2010, 49, 3192–

3195; l) C. Givelet, J. Sun, D. Xu, T. J. Emge, A. Dhokte, R. War-

muth, Chem. Commun. 2011, 47, 4511–4513; m) L. Avram, Y.

Cohen, J. Rebek, Chem. Commun. 2011, 47, 5368–5375; n) Z. Lin,

T. J. Emge, R. Warmuth, Chem. Eur. J. 2011, 17, 9395–9405.

[8] a) S. R. Batten, R. Robson, Angew. Chem. 1998, 110, 1558–1595;

Angew. Chem. Int. Ed. 1998, 37, 1460–1494; b) H. Li, M. Eddaoudi,

M. OꢇKeeffe, O. M. Yaghi, Nature 1999, 402, 276–279; c) M. Ed-

daoudi, D. B. Moler, H. Li, B. Chen, T. M. Reineke, M. OꢇKeeffe,

O. M. Yaghi, Acc. Chem. Res. 2001, 34, 319–330; d) S. Kitagawa, R.

Kitaura, S. Noro, Angew. Chem. 2004, 116, 2388–2430; Angew.

Chem. Int. Ed. 2004, 43, 2334–2375; e) G. Fꢈrey, C. Mellot-Draz-

nieks, C. Serre, F. Millange, J. Dutour, S. Surble, I. Margiolaki, Sci-

ence 2005, 309, 2040–2042; f) R. Matsuda, R. Kitaura, S. Kitagawa,

Y. Kubota, R. V. Belosludov, T. C. Kobayashi, H. Sakamoto, T.

Chiba, M. Takata, Y. Kawazoe, Y. Mita, Nature 2005, 436, 238–241;

g) A. G. Wong-Foy, O. Lebel, A. J. Matzger, J. Am. Chem. Soc. 2007,

129, 15740–15741; h) S. Ma, J. Eckert, P. M. Forster, J. W. Yoon,

Y. K. Hwang, J.-S. Chang, C. D. Collier, J. B. Parise, H.-C. Zhou, J.

Am. Chem. Soc. 2008, 130, 15896–15902; i) D. Britt, H. Furukawa,

B. Wang, T. G. Glover, O. M. Yaghi, Proc. Natl. Acad. Sci. USA

2009, 106, 20637–20640; j) H. Deng, C. J. Doonan, H. Furukawa,

R. B. Ferreira, J. Towne, C. B. Knobler, B. Wang, O. M. Yaghi, Sci-

ence 2010, 327, 846–850; k) R. A. Smaldone, R. S. Forgan, H. Furu-

kawa, J. J. Gassensmith, A. M. Z. Slawin, O. M. Yaghi, J. F. Stoddart,

Angew. Chem. 2010, 122, 8812–8816; Angew. Chem. Int. Ed. 2010,

49, 8630–8634; l) A. Corma, H. Garcia, F. X. L. Xamena, Chem.

Rev. 2010, 110, 4606–4655; m) H. Furukawa, N. Ko, Y. B. Go, N.

Aratani, S. B. Choi, E. Choi, A. O. Yazaydin, R. Q. Snurr, M.

OꢇKeeffe, J. Kim, O. M. Yaghi, Science 2010, 329, 424–428; n) D.

Zhao, D. J. Timmons, D. Q. Yuan, Acc. Chem. Res. 2011, 44, 123–

133; o) S. T. Meek, J. A. Greathouse, M. D. Allendorf, Adv. Mater.

2011, 23, 249–267.

[16] a) D. Hanss, O. S. Wenger, Inorg. Chem. 2009 , 48 , 67 1 –6 80; b) M. E.

Walther, O. S. Wenger, ChemPhysChem 2009 , 10 , 120 3 –1 206; c) D.

Hanss, M. E. Walther, O. S. Wenger, Chem. Commun. 2010 , 46 ,

703 4 –7 036; d) H. Zhao, J. Liao, J. Ning, Y. Xie, Y. Cao, L. Chen, D.

Yang, B. Wang, Adv. Synth. Catal. 2010 , 352 , 308 3 –3 088.

[9] a) M. Eddaoudi, J. Kim, J. B. Wachter, H. K. Chae, M. OꢇKeeffe,

O. M. Yaghi, J. Am. Chem. Soc. 2001, 123, 4368–4369; b) B. Moul-

ton, J. Lu, A. Mondal, M. J. Zaworotko, Chem. Commun. 2001,

[17] For a preliminary communication that gives substance to the Losan-

AHCTUNGTREGiNNUN tsch series see: S. Grunder, J. F. Stoddart, Chem. Commun. 2012,

ˇ

863–864; c) A. C. Sudik, A. R. Millward, N. W. Ockwig, A. P. Cotꢈ,

48, 3158–3160.

J. Kim, O. M. Yaghi, J. Am. Chem. Soc. 2005, 127, 7110–7118; d) H.

Furukawa, J. Kim, K. E. Plass, O. M. Yaghi, J. Am. Chem. Soc. 2006,

128, 8398–8399; e) D. J. L. Tranchemontagne, Z. Ni, M. OꢇKeeffe,

O. M. Yaghi, Angew. Chem. 2008, 120, 5214–5225; Angew. Chem.

Int. Ed. 2008, 47, 5136–5147; f) J. J. Perry IV, J. A. Perman, M. J. Za-

worotko, Chem. Soc. Rev. 2009, 38, 1400–1417; g) S. Mirtschin, A.

[18] For an example of where these slender and rigid organic gauge

blocks have been employed in reaction mixtures along with Mg-

AHCUTNERTGG(NNUN NO₃)₂·6H₂O in N,N-dimethylformamide, EtOH and H₂O at 1208C

for 24 h, to synthesize a series (IR-MOF-74) of metal–organic

frameworks see: H. Deng, S. Grunder, K. E. Cordova, C. Valente,

H. Furukawa, M. Hmadeh, F. Gꢊndara, A. C. Whalley, Z. Liu, S.

15648

www.chemeurj.org

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2012, 18, 15632 – 15649

Molecular Gauge Blocks

FULL PAPER

Asahina, H. Kazumori, M. OꢇKeefe, O. Terasaki, J. F. Stoddart,

O. M. Yaghi, Science 2012, 336, 1018–1023. The Supporting Infor-

mation accompanying this article provides the synthetic protocols

for the production of eight of these organic gauge blocks. In this full

paper, we present a discussion of the synthetic methodologies em-

ployed in their synthesis, as well as record the experimental proce-

dure at length.

h) E. A. B. Kantchev, C. J. OꢇBrien, M. G. Organ, Angew. Chem.

2007 , 119 , 282 4 –2 870; Angew. Chem. Int. Ed. 2007 , 46 , 276 8 –2 813;

i) G. P. McGlacken, L. M. Bateman, Chem. Soc. Rev. 2009 , 38 , 244 7 –

2464.

[20] A. I. Kovalev, K. Takeuchi, M. Asai, M. Ueda, A. L. Rusanov, Russ.

Chem. Bull. 2004 , 53 , 174 9 –1 754.

[21] J. Rotzler, H. Gsellinger, M. Neuburger, D. Vonlanthen, D. Hꢁus-

singer, M. Mayor, Org. Biomol. Chem. 2011 , 9 , 8 6 –9 1.

[22] a) S. M. Losanitsch, Ber. Dtsch. Chem. Ges. 1897 , 30 , 191 7 –1 926;

b) N. J. A. Sloane, Not. Am. Math. Soc. 2003, 50, 912–915.

[23] S. Grunder, R. Huber, V. Horhoiu, M. T. Gonzꢊlez, C. Schçnenberg-

er, M. Calame, M. Mayor, J. Org. Chem. 2007 , 72 , 833 7 –8 344.

[19] a) N. Miyaura, K. Yamada, A. Suzuki, Tetrahedron Lett. 1979 , 20 ,

343 7 –3 440; b) A. Suzuki, J. Organomet. Chem. 1999 , 576 , 14 7 –1 68;

c) S. R. Chemler, D. Trauner, S. J. Danishefsky, Angew. Chem. 2001 ,

113 , 467 6 –4 701; Angew. Chem. Int. Ed. 2001 , 40 , 454 4 –4 568; d) S.

Kotha, K. Lahiri, D. Kashinath, Tetrahedron 2002 , 58 , 963 3 –9 695;

e) E. Peris, R. H. Crabtree, Coord. Chem. Rev. 2004 , 248 , 223 9 –

2246; f) T. E. Barder, S. D. Walker, J. R. Martinelli, S. L. Buchwald,

J. Am. Chem. Soc. 2005 , 127 , 468 5 –4 696; g) N. T. S. Phan, M. Van

Der Sluys, C. W. Jones, Adv. Synth. Catal. 2006 , 348 , 60 9 –6 79;

Received: June 5, 2012

Published online: October 22, 2012

Chem. Eur. J. 2012, 18, 15632 – 15649

ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

15649

Article Doi

Molecular gauge blocks for building on the nanoscale

DOI: 10.1002/chem.201201985

Source and publish data:

Authors:

Article abstract of DOI:10.1002/chem.201201985

Full text of DOI:10.1002/chem.201201985

Products guided by the article

R&D Labs maybe for 1382734-98-6

Relevant to this article

Hot Product