Shape-persistent macrocycles with bipyridine units: Progress in accessibility and widening of applicability

FULL PAPER

Shape-Persistent Macrocycles with Bipyridine Units: Progress in Accessibility

and Widening of Applicability

Dorina M. Opris,^[a]Peter Franke,^[a]and A. Dieter Schlüter*^[a][‡]

Keywords: Cross-coupling / Macrocycles / Bipyridines / Aggregation / Polymerization

Several new symmetrical and nonsymmetrical bipyridine-

containing building blocks for shape-persistent macrocycles

were developed, whereby much emphasis was placed on es-

pecially efficient procedures. The building blocks were used

for the synthesis of several new cycles, the most important of

which carry only one selectively addressable hydroxymethyl

group at a corner. This group was converted into methacry-

late- and norbornene-type polymerizable units for free radi-

cal and ROMP polymerizations, respectively, rendering the

corresponding macrocycles the first macromonomers of this

kind. Initial polymerization studies are also reported.

Germany, 2005)

volved synthetic effort as judged by the number of steps

may be, by and large, higher. Several of their representatives

were synthesized on the 100-mg scale,^[6]some even on the

gram scale.^[7]Having made a couple of shape-persistent cy-

cles with bipyridine (bpy) and terpyridine units typically on

the 100-mg scale^[8]we are presently aiming significantly be-

yond the cycles themselves. We are exploring potential ap-

plications by investigating the cycles’ complexation behav-

ior^[9]and their polymerizability after conversion into

macromonomers as well as their potential as repeat units

for nanoconstructions including linear polymers in which

cycles are held together by transition metals. In light of such

goals, these cycles’ better availability was not quite the

golden opportunity it seemed anymore and improvements

were necessary. We therefore set out to straighten some of

the cycles’ syntheses and to also make representatives avail-

able which carry variable exocyclic functionality. There were

two options to improve the accessibility of bpy containing

cycles such as E (Scheme 1). One was to straighten the se-

quences leading to the precursors for cyclization and the

other was to improve the cyclization step itself. In the pres-

ent contribution we describe significantly facilitated syn-

thetic procedures to the main building blocks for cycle as-

sembly which led to cycle syntheses on the 1-gram scale.

Though the access to some of these cycles has been signifi-

cantly improved, the synthetic procedures suffer from the

fact that so far only symmetrical building blocks could be

used. This in the end means that the cycles have to be closed

from two precursors which by and large limit the yield of

the final cycle formation step to a value of approximately

20%. It also and perhaps even more importantly prevents

an nonsymmetrical decoration of the cycles which is of rele-

vance, for example, in regard to their use as switches.^[10]

Thus, this paper also reports on a nonsymmetrical building

block which, after some steps, would allow to close a cycle

Introduction

Recently much attention has been focused on the synthe-

sis of shape-persistent macrocycles.^[1]Their reduced confor-

mational mobility leads to an increased tendency to aggre-

gate and/or adsorb on surfaces compared to similarly sized

flexible cycles^[2]and establishes them as novel rigid scaf-

folds. Shape-persistent macrocycles may open up fascinat-

ing avenues into the generation of cylindrical nanopores^[3]

and regular surface patterns as well as endocyclic catalysis

or nanoconstructions. Most of these macrocycles known to-

day have hexagonal structures and their available interior

spans range from approximately one to several nanome-

ters.^[4]They can be divided into two subclasses: Ones whose

backbones do not contain transition metals as integral part

and ones that do. The latter are usually constructed from

linear, shape-persistent units which carry terminal anchor

groups for metal complexation and transition metal com-

plexes. The linear units end up as sides of the oligons and

the transition metals as corners. This approach produced a

bouquet of beautiful and useful structures.^[5]The price

which has to be paid for this, however, is the use of a con-

siderable amount of transition metal (e. g., Pt) which se-

verely limits the amount available and also has other disad-

vantages. Consequently many of the cycles were only pre-

pared on the milligram scale. This is where the subclass

without integral transition metals is at an advantage, na-

mely its generally better availability even though the in-

[a]

Institut für Chemie, Freie Universität Berlin,

Takustr. 3, 14195 Berlin, Germany.

[‡]

New address: Swiss Federal Institute of Technology, Depart-

ment of Materials, Institute of Polymers,

ETH Hönggerberg, HCI J 541, 8093 Zürich, Switzerland

Fax: +41-16331395.

Supporting information for this article is available on the

WWW under http://ww w .eurjoc.org or from the author.

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DOI: 10.1002/ejoc.200400744

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Shape-Persistent Macrocycles with Bipyridine Units

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Scheme 1. The synthetic strategy to bipyridine macrocycles of kind E

from one precursor. For such ring closures yields of 70% approximately 20%. The cyclizations themselves will not be

have been obtained.^[11]We finally report on the synthesis of treated here in any great detail anymore.

two macrocyclic macromonomers and initial results of their

Side A carries two bromo functions for further growth,

polymerization according to free radical and ring-opening side D two iodo ones. In contrast to the cyclization of C

metathesis mechanisms.

and D where the rate of the cross-coupling has impact on

the cyclization efficiency, the rate of assembly of C from A

and B does not matter. Oligomerization does not compete.

This is why side D and not side A is equipped with the more

highly reactive iodo groups. Attempts to cyclize C with A

gave practically zero cycle and only linear oligomer. Of

course, also side D instead of A can be used to enter the

sequence. Corner stones B carry acetylenes with selectively

deprotectable acetylenes [e. g. trimethylsilyl (TMS) and trii-

soproyplsilyl (TIPS)] in order to allow for its selective coup-

ling to C.

2. Results and Discussion

2a. General Remarks

The way by which the bpy-containing shape-persistent

cycles of kind E are normally prepared requires two side

stones A and D and a corner stone B (Scheme 1). Side A is

reacted with the acetylenic cornerstone B under Sonoga-

shira conditions to the cycle precursor C which, after silyl-

deprotection, is then reacted with side D again according

to a Sonogashira protocol and under pseudo high dilution

conditions to give a roughly 1:4 mixture of cycle E and

linear (zigzag) oligomers F. This mixture can additionally

contain a few higher cycles and possible catenanes. The

average yield based on numerous cyclization experiments is

Sides A and C can be either symmetrical (X¹= X²) or

nonsymmetrical (X¹϶ X²). Cycle E in Scheme 1 is shown

for a nonsymmetrical side A and a symmetrical side D. Of

the numerous possible combinations Scheme 2 shows com-

binations of peripheral substituent patterns which are con-

sidered especially interesting. E1 with its one tetrahydropy-

Scheme 2. Different macrocycles with different substitution pattern

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D. M. Opris, P. Franke, A. D. Schlüter

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ranyl (THP) protected alcohol group is attractive for its fur-

Improved Side Stone D: Side D was prepared using the

ther conversion into macromonomers in order to provide recently published facilitated synthesis of 5,5Ј-dibromo-

access to polymers with pendent macrocycles. E2^[12]with its 2,2Ј-bipyridine (9) and the silylated phenyl derivative 10 un-

two THP groups is attractive as source for unconventional der Suzuki cross coupling reaction conditions (Scheme 4).

diols for polyesters, polyamides and alike, and, finally, E4^[8b]According to Sauvage’s and Michl’s procedure,^[18]bpy 9 is

for its decoration with dendrons, self-recognizing and/or now available on the 10-g scale. Compound 10 was basically

.[19]

polymerizable groups, the latter of which would potentially prepared as described earlier

with one small but impor-

be useful for covalent stabilization of cylindrical cycle tant modification. The esterification (pinacolization) of the

stacks by solid-state polymerization similar to Rings- free boronic acid precursor of 10 (not shown) was now done

dorf’s^[13]and Gadhiri’s work.^[14]

in toluene with concomitant removal of water. This change

leads to an increase in yield for 10 from approximately 50%

to an average of 80% which allowed its preparation on the

30-g scale. Having these compounds available at such large

scale the obtainment of compound 11 on the 10-g scale was

no problem. Silyl groups on aromatics are known to be

place holders for various functional groups including iodo.

This also refers to some heteroaromatic examples.^[20]Com-

pound 11 could thus be quantitatively converted into side

12 on the 10-g scale by reacting it with iodochloride. An

alternative reaction pathway to compound 11 was also in-

vestigated (Scheme 4) though it is somewhat less attractive

since the moment that the above-mentioned improved ac-

cessibility of compound 9 has been published. Compounds

10 and 2 were coupled to 13 which was subsequently homo-

coupled in presence of Sn₂Bu₆and [Pd(PPh₃)₄].

Corner Stones B: Compounds B (Scheme 1) did not need

improvement. They are available on the 30-g scale.^[8a]

New Cycle Precursors of Kind C and Their Cyclization:

The new representatives of precursors C, 16 and 17, were

prepared according to known procedures (Scheme 5).^[8a,8b]

The ring closure was carried out under high dilution condi-

tions by means of a Sonogashira–Hagihara-type reaction

(Scheme 5). Cycles E1 and E4 were unambiguously charac-

terized by NMR spectroscopy and mass spectrometry.

Another New Cycle Precursor and Its Ring Closure: In the

2b. Improvements and New Building Blocks

The main objectives of the sequences’ overhaul was to

reduce the number of steps, increase their yields, replace

Stille cross-coupling wherever possible^[15]by the generally

more efficient Suzuki cross-coupling which, additionally,

does not involve potentially toxic stannyl compounds, and

improve work-up procedures.

Improved Side Stones A: Sides A can be obtained sym-

metrically and nonsymmetrically depending on whether the

X groups are like or unlike, respectively. Normally they are

prepared such that the bpy unit (and thus the completed

side) is generated in the last step by Stille cross-coupling

between compounds 4 and 5 (Scheme 3). The route starts

from 2,5-dibromopyridine (1) which was selectively con-

verted into the iododerivative 2 by Schlosser’s protocol.^[16]

Its iodo selective coupling with the phenylboronic acid ester

3 gave half sides 4a (X = Hex) and 4b (X = THP). Com-

pound 3 was prepared on the 10-g scale as described ear-

lier.^[17]Both pyridines 4a and 4b were stannylated to 5a and

5b, respectively, by a conventional procedure.^[15]The dif-

ferent combinations of these compounds gave the symmet-

rical sides 6 and 7 and the nonsymmetrical one 8.^[15]This

Stille reaction is the last of formerly three such cross-coup-

lings still remaining in the entire sequences to cycles E from case that only four substituents are needed or acceptable on

two “halves”. a cycle, a specifically easy route was devised which is based

Scheme 3. Synthesis of symmetrical (6, 7) and nonsymmetrical sides A (8); (a) n-butyllithium, 1.2-diiodoethane, diethyl ether, –78 °C,

75%; (b) [Pd(PPh₃)₄], 2 m Na₂CO₃/water, toluene, r. f., 3 d, 80–85%; (c) n-butyllithium, ClSnMe₃, toluene, –78 °C; (d) [Pd(PPh₃)₄], toluene,

r. f., 5 d, 30–35%

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Shape-Persistent Macrocycles with Bipyridine Units

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Scheme 4. Synthesis of side D; (a) [Pd(PPh₃)₄], toluene, 2 m Na₂CO₃, water, r. f., 3 d, 90%; (b) ICl, DCM, r. f., 2 d, 98%; (c) [Pd-

(PPh₃)₄], toluene, 2 m Na₂CO₃, water, r. f., 3 d, 90%; (d) Sn₂Bu₆, [Pd(PPh₃)₄], toluene, r. f., 5 d, 85%

Scheme 5. (a) (2-(3-Ethynyl-5-((hexyloxy)methyl)phenyl)ethynyl)triisopropylsilane (C), [Pd(PPh₃)₄], CuI, toluene, TEA, 80 °C, 2 d, 80–

85%; (b) Bu₄NF, THF, room temp., 1 d, 95%

on the commercial availability of (trimethylsilyl)acetylene Compound 18c was cyclized with its own precursor, 18b, to

(TMSA) and 1,3-diiodobenzene and has a further reduced give the known cycle E5 in a yield of 28% on the 540-mg

total number of steps from 17 to 13 (Scheme 6). It starts scale.

from 12 (side D) which is reacted with TMSA to give 18a

in an almost quantitative yield. After deprotection, 18b is

2c. A Nonsymmetrical Side

reacted with a large excess of 1,3-diiodobenzene to give the

In the quest for a nonsymmetrical building block with

new cycle precursor 18c in 60% yield and on the 2-g scale. two different, selectively addressable halogens which, after

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D. M. Opris, P. Franke, A. D. Schlüter

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Scheme 6. (a) [Pd(PPh₃)₄], CuI, TMSA, toluene, TEA, 60 °C, 1 d, 90%; (b) NaOH, THF, methanol, room temp., 1 d, 94%; (c) 1,3-

diiodobenzene, [Pd(PPh₃)₄], CuI, toluene, TEA, 60 °C, 3 d, 60%; (d) [Pd(PPh₃)₄], CuI, toluene, triethylamine, 60 °C, 5 d, 28%

some steps, would allow to close a cycle from one precursor, the bromide 13 to give 19a. As oftenly encountered in Stille

side 19b with one bromo and one iodo function was consid- coupling reactions not only the desired cross-coupling pro-

ered an ideal candidate (Scheme 7). Its synthesis was duct but also the two homocoupling products were formed

achieved by first coupling the stannyl compound 5a with (ratio 19a:11:6 = 4:1:1). Fortunately, the side products could

Scheme 7. (a) [Pd(PPh₃)₄], toluene, r. f., 5 d, 44%; (b) ICl, DCM, r. f., 2 d, 79%; (c) TMSA, [Pd(PPh₃)₄], CuI, toluene, TEA, 60 °C, 1 d,

88%; d)TIPSA, [Pd(PPh₃)₄], CuI, toluene, TEA, 80 °C, 1 d, 75%; (e) NaOH, THF, methanol, room temp., 1 d, 89%; (f) (2-{3-bromo-5-

[(tetrahydro-2H-pyran-2-yloxy)methyl]phenyl}ethynyl)trimethylsilane, [Pd(PPh₃)₄], CuI, toluene, TEA, 80 °C, 2 d, 71%; (g) NaOH, THF,

methanol, room temp., 1 d, 95%

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Shape-Persistent Macrocycles with Bipyridine Units

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Scheme 8. (a) HCl, DCM, MeOH, 1 d, 98%; (b) MAC, DCM, DMAP, TEA, 18 d, 0 °C (82%); (c) exo-5-norbornene-2-carboxylic acid,

DMAP, DCC, DCM, 0 °C, 18 h (96%)

be easily removed by column chromatography. Iododesilyl- cal side 8 (Scheme 9). This way the conditions for both the

ation of pure 19a afforded 19b on the 2-g scale as analyti- attachment of the polymerizable units and the polymeriza-

cally pure material. Some further steps towards a cycle were tion itself could be explored. The tetrahydropyranyl (THP)

also done. 19b was subjected to a series of Sonogashira-type protecting group on 8 was removed under acidic conditions

coupling reactions with various silyl-protected acetylenes to and the resulting alcohol 24 reacted with freshly distilled

give 19g. All these procedures went absolutely smoothly methacrylic acid chloride to give the FRP macromonomer

and were high-yielding so that 19g could be isolated on the 25. The norbornenic unit was introduced by active ester

not yet optimized 500-mg scale. We consider this a good chemistry using the commercially available exo/endo (2:8)

starting point for the missing steps to cycle as well as other mixture of norbornenic acid. For this test purpose the use

purposes.

of a mixture was considered acceptable. The bpy unit of

26 was blocked by converting it into the corresponding Ru

complex 27. Attempted ROMP of 26 with first generation

Grubbs catalyst^[22]gave basically unreacted material pre-

sumably because of a detrimental interference of its bpy

unit with the catalyst. FRP of 25 was done with AIBN in

toluene and actually gave polymer 28 (yield: 65%) with gel

permeation chromatography (GPC) molar masses versus

2d. Polymerization of Macrocycles with Pendant

Polymerizable Units

A motivation for research in the area of shape-persistent

macrocycles is to reach their self-assembly into columnar

stacks in which each pair of two consecutive cycles lies di-

rectly on top of each other. This way cylindrical confine-

ments with long pores would be generated which eventually

could lead to the generation of, for example, atomically thin

metal wires. In many of the single crystals obtained from

bpy and tpy containing macrocycles, the formation of cylin-

drical stacks, however, is avoided and more complex arran-

gements are preferred. One potential way to nevertheless

achieve a columnar packing^[3,21]is to attach them to a poly-

mer backbone. Spurred by this consideration the possibility

of polymerizing macrocycles with pendent polymerizable

units, like 22 and 23 was explored (Scheme 8). Such an en-

terprise would also be of interest to polymer synthesis be-

cause no such monomers have ever been subjected to poly-

polystyrene standard of M_p20,300 g/mol and M_w

=

27,600 g/mol (PDI = 1.56). The molar mass distribution

was monomodal. Also ROMP of 27 to furnish polymer 29

could be accomplished though the molar mass determi-

nation was not yet achieved. Polymer 29 carries two positive

charges per repeat unit and is thus a polyelectrolyte. An

accurate molar mass determination of polyelectrolytes is a

1

rather complex matter. The H NMR spectrum of polymer

29 shows the complete disappearence of olefinic signals en-

suring at least its oligomeric regime. 29 is soluble in chloro-

form, DMF, and NMP, but not in THF.

Next the macrocyclic macromonomers 22 and 30 were

merizations. Given their high molar mass as compared with prepared (Scheme 8, Scheme 10). Given the experience with

conventional monomers like methacrylate or norbornene, monomer 26, monomer 23 was not directly subjected to

22 and 23 are to be considered macromonomers. Polymer- ROMP conditions but rather first converted into its “pro-

izations of macromonomers tend to suffer from an en- tected” Ru complex 30 (Scheme 10). For the latter the exo

hanced chain transfer and the difficult to achieve extremely diastereomer of norbornenic acid was used.^[23]Both mono-

high monomer concentrations required in order to achieve mers were obtained on the 150–300-mg scale according to

decent molar masses. Free radical (FRP) and ring-opening routine procedures and obtained as fully characterized, an-

metathesis polymerizations (ROMP) are known to be rela- alytically pure substances. FRP of 22 was done like for

tively robust procedures and were therefore selected for model 25 at a monomer concentration of approximately

these initial studies.

0.11 m. In macromonomer polymerization the application

First model studies were done by using the noncyclic of an as high as possible concentration is essential. Other-

macromonomers 25 and 27 derived from the nonsymmetri- wise the concentration of the polymerizable units is so low

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D. M. Opris, P. Franke, A. D. Schlüter

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Scheme 9. (a) HCl, DCM, MeOH, 1 d, 93%; (b) MAC, DCM, DMAP, TEA, 18 d, 0 °C, 95%; (c) exo-endo-5-norbornene-2-carboxylic

acid, DMAP, DCC, DCM, 0 °C, 18 d, 70%; (d) [Ru(bpy)₂Cl₂], ethanol, water, r. f., 24 d, 66%; (e) toluene, AIBN, 80 °C, 1 d, 65%; (f)

(Cy₃P)₂Cl₂Ru=CHPh, DCM, room temp.

that the polymerization is slowed to the extent that side at δ = 4.9 and 5.3 ppm as is typical for norbornene ROMP

reactions can take over.^[24]A soluble product, to which polymers (see ESI).^[25]The polymerization was carried out

structure 31 is assigned, was obtained from precipitation in dichloromethane solution from which the polymer pre-

and had GPC molar masses of M_n= 10,500 g/mol and M_wcipitated. GPC measurements could not yet be performed

= 13,800 g/mol (PDI = 1.35). Figure 1 compares the ¹H because of 32’s polyelectrolyte character.

NMR spectrum of monomer 22 and polymer 31. As ex-

pected the olefinic signals of 22 are absent for 31 and all

signals are broadened. It is noteworthy that the signals as-

sociated with the cyclic substituent on 31’s backbone suffer

Experimental Section

General: All reactions involving air-sensitive compounds were car-

ried out under nitrogen using standard Schlenk techniques and dry,

oxygen-free solvents. Diethyl ether, toluene, THF, and triethyla-

mine were distilled under nitrogen from sodium/benzophenone and

dichloromethane was distilled from CaH₂. All reagents were pur-

chased from Aldrich or Acros and used without further purifica-

tion. BuLi was used as a 1.6 m solution in hexane. Compounds

B,^[8a]3a,^[17]6, 7, 2-(3,5-dibromobenzyloxy)tetrahydropyran^[15]9,^[18]

10,^[19]and 18a,b,^[8e]and exo-norbornenic acid ester^[26]were pre-

pared according to the literature procedures. Compounds

a considerable highfield shift of approximately 0.5 ppm.

This reflects the cycles’ close proximity and thus their mut-

ual influence. The bulk structure of polymer 31 is presently

under investigation.

The polymerization of 30 under the above ROMP condi-

1

tions gave polymer 32. Its H NMR spectrum shows the

ring-opened norbornene and gives no evidence for end

groups. Especially characteristic is the disappearance of the

norbornenic olefin signals at δ = 6.1 ppm with concom-

mitant appearance the olefinic signals of 32 which absorb 2,^[27]4a,b,^[15]and 12,^[8a]are known, but were prepared by different

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Shape-Persistent Macrocycles with Bipyridine Units

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Scheme 10. (a) [Ru(bpy)₂Cl₂], dioxane, propylene glycol, 24 h (54%); (b) benzene, AIBN, 80 °C, 5 d, 62%; (c) [(Cy₃P)₂Cl₂Ru=CHPh],

DCM, room temp.

1

Figure 1. H NMR spectra of 22 (CDCl₃, 20 °C, 270 MHz) and of corresponding polymer 31 (CD₂Cl₂, 20 °C, 270 MHz)

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D. M. Opris, P. Franke, A. D. Schlüter

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procedures. Therefore their analytical and spectroscopic data are

not given. All other compounds are new. All polymers were not

fully characterized by organic chemistry standards. Melting points:

Büchi SMP 510 (open capillaries, uncorrected values). NMR:

Bruker AC-250, AM-270, AMX-500 (¹H: CDCl₃at δ = 7.24 ppm,

¹³C: CDCl₃at δ = 77.00 ppm as internal standards, 20 °C). MS:

Perkin–Elmer Varian MAT-711, electron-impact (EI) mode. Ele-

mental analyses: Perkin–Elmer EA-240. Column chromatography:

Merck silica gel 60, 0.040–0.063 mm (230–400 mesh).

2-[3-Bromo-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl-

oxy]tetrahydropyran (3b): To a stirred solution of 2-(3,5-dibromobe-

nzyloxy)tetrahydropyran (20 g, 57.1 mmol) in dry diethyl ether

(200 mL) at –78 °C, a solution of 1.6 m BuLi in hexane (39.3 mL,

62.8 mmol) was added over a period of 15 min. After 3 d, triisopro-

pyl borate (13 g, 68.8 mmol) was added and the mixture warmed

to room temperature. The organic phase was washed with water

and the aqueous one extracted with diethyl ether. The combined

organic phases were dried with MgSO₄. The solvent was removed

and the resulting oil used for the esterification without further puri-

fication. The crude boronic acid and 2,3-dimethylbutane-2,3-diol

(5.91 g, 50.0 mmol) were dissolved in toluene (100 mL), and re-

fluxed for 2 d. The formed water was removed from the reaction

using a Dean–Stark trap. The solvent was removed and the oil was

purified by column chromatography through silica gel (hexane/

ethyl acetate, 20:1) to give 4.65 g of 3b (83%) as colorless oil. R_f

General Procedure for the Coupling of Terminal Acetylene with Aryl

Iodides or Aryl Bromides: A thick-walled flask was charged with

the terminal acetylene, aryl iodide or aryl bromides, [Pd(PPh₃)₄]

(0.02 equiv. per coupling), CuI (0.02 equiv. per coupling), dry tri-

ethylamine, and dry toluene. The reaction mixture was evacuated,

flushed with nitrogen, sealed with a Teflon screw cap, and stirred

at 60 °C for 24 h for iodo compounds and at 80 °C for bromo ones,

respectively. The reaction mixture was filtered and the solvent re-

moved. The compounds were purified by column chromatography

through silica gel.

1

(hexane/ethyl acetate, 20:1) = 0.12. H NMR (CDCl₃, 250 MHz):

δ = 1.31 (s, 12 H, CH₃), 1.46–1.91 (m, 6 H, THP), 3.53 (m, 1 H,

THP), 3.90 (m, 1 H, THP), 4.43 (d, 1 H, benzyl-H), 4.66 (s, 1 H,

THP), 4.72 (d, 1 H, benzyl-H), 7.60 (s, 1 H, phenyl-H), 7.66 (s, 1

H, phenyl-H), 7.84 (s, 1 H, phenyl-H) ppm. ¹³C NMR (CDCl₃,

63 MHz): δ = 19.28, 24.83, 25.42, 30.48, 62.08, 68.01, 84.15, 97.92,

122.51, 132.45, 133.46, 136.57, 140.04 ppm. MS (EI, 80 eV): m/z

(%) = 380.2 (1.20), 296.4 (60.67), 216.7 (21.90), 196.5 (14.75), 115.8

(12.68), 84.9 (100.00). C₁₈H₂₆BBrO₄(397.11): calcd. C 54.44, H

6.60; found C 54.41, H 6.35.

General Procedure for the Deprotection of Acetylenic Trimethylsilyl

Groups: A catalytic amount of 1 m NaOH solution was added to

the silyl compound in a mixture of THF/methanol (1:1) and stirred

at room temp. for 16 h. Then the reaction mixture was diluted with

diethyl ether and brine, and the phases were separated. The aque-

ous phase was extracted with diethyl ether and the combined or-

ganic phases were dried over MgSO₄, the solvent was removed, and

the compound purified by column chromatography through silica

gel.

General Procedure for the Synthesis of Pyridines 4a,b: To a degassed

mixture of the boronic ester 3 (11.10 g, 27.95 mmol), 2-bromo-5-

iodopyridine 2 (7.93 g, 27.95 mmol), Bu₄NBr (9.01 g, 27.95 mmol)

in toluene (160 mL) and aq. 2 m Na₂CO₃(80 mL), [Pd(PPh₃)₄]

(600 mg, 0.52 mmol) was added and the reaction degassed once

more. After the mixture was refluxed for 4 d the layers were sepa-

rated and the aqueous one extracted with toluene (2×50 mL). The

combined organic phases were dried (MgSO₄) and evaporated un-

der reduced pressure. The crude product was purified by column

chromatography through silica gel (hexane/ethyl acetate, 25:1) to

give 4 as a white solid (85–90%).

General Procedure for the Deprotection of Acetylenic Tri(isopropyl)

silyl Groups: To a stirred solution of the silyl compound in THF,

tetrabutylammonium fluoride trihydrate (1 equiv. per deprotection)

was added and the reaction stirred for 24 h at room temp. The

reaction mixture was diluted with diethyl ether and brine and the

phases were separated. The aqueous phase was extracted with di-

ethyl ether and the combined organic phases were dried over

MgSO₄. The solvent was removed and the compound purified by

column chromatography through silica gel.

General Procedure for the Synthesis of Symmetrical and Nonsym-

metrical Building Blocks A: To a stirred solution of 4 (10.9 mmol)

in dry toluene (120 mL) a 1.6 n solution of BuLi in hexane (7.2 mL,

11.5 mmol) was added drop wise at –78 °C. After 2 h, to the re-

sulting red solution Me₃SnCl (2.4 g, 12 mmol) was added in solid

form. The mixture was let to warm to room temp. and then com-

pound 4 (10.9 mmol) was added to the brownish solution of 5. The

mixture was degassed, [Pd(PPh₃)₄] (3 mol%) added, and the reac-

tion mixture degassed again. After refluxing for 5 d the mixture

was cooled to room temp. An aq. satd. KF solution (90 mL) was

added to the organic phase followed by an aq. 2 n Na₂CO₃solution

(150 mL). The phases were separated, the aqueous one was ex-

tracted with toluene (2×100 mL). The combined organic phases

were washed with water (100 mL) and dried (MgSO₄). The solvent

was removed to give a brown oil which was purified by column

chromatography trough silica gel.

General Procedure for Macrocycle Synthesis: A solution of C

(0.98 mmol) and D (0.98 mmol) in a mixture of dry triethylamine

(320 mL) and dry toluene (320 mL) was carefully degassed. After

the addition of [Pd(PPh₃)₄] (0.04 equiv.) and CuI (0.04 equiv.), the

mixture was stirred under nitrogen at 60 °C for 4 d and then at

95 °C for 24 h. The solvent was removed, the residue dissolved in

CH₂Cl₂(300 mL), and the resulting mixture treated with a solution

of KCN (265 mg) in water (200 mL). The phases were separated,

the aqueous one was extracted with CH₂Cl₂, and the combined

organic phases were washed with water. It was then dried with

MgSO₄and the solvent removed. The macrocycles were purified

by preparative GPC (Yields: 20–35%).

2-Bromo-5-iodopyridine (2): To a stirred suspension of 2,5-dibromo-

pyridine (1) (10 g, 42.2 mmol) in dry diethyl ether (280 mL) a solu-

tion of 1.6 m BuLi in hexane (28 mL, 44.8 mmol) was added drop

wise at –78 °C. After 3 h diiodoethane was added in solid form

(12.7 g, 45.1 mmol) to the resulting red suspension and the mixture

was warmed to room temp. Then water (100 mL) was added and

the phases were separated. The aqueous phase was extracted with

diethyl ether (2×100 mL) and the combined organic phases were

washed with water. The organic phase was dried (MgSO₄), the sol-

vent was removed, and the resulting solid was purified by column

chromatography over silica gel (hexane/ethyl acetate, 10:1) to give

9 g of 2 (75%) as a white solid.

5Ј-[3-Bromo-5-(hexyloxymethyl)phenyl]-5-[3-bromo-5-(tetrahydropy-

ran-2-yloxymethyl)phenyl]-2,2Ј-bipyridinyl

(8):

4a

(4.64 g,

10.86 mmol) and 4b (4.64 g, 10.86 mmol). The reaction mixture

was purified by column chromatography trough silica gel (hexane/

ethyl acetate, 4:1) to give 2.5 g (30–35%) of 8 as a white solid. R_f

1

(hexane/ethyl acetate, 4:1) = 0.38. H NMR (CDCl₃, 250 MHz): δ

= 0.42 (t, 3 H, CH₃), 1.24–1.45 (m, 6 H, γ-, δ-, ε-CH₂), 1.50–2.00

(m, 8 H, β-CH₂, THP), 3.47 (t, 2 H, α-CH₂), 3.60 (t, 1 H, THP),

3.91 (m, 1 H, THP), 4.56 (s, 2 H, benzyl-H), 4.56 (d, 1 H, benzyl-

830

www.eurjoc.org

Eur. J. Org. Chem. 2005, 822–837

Shape-Persistent Macrocycles with Bipyridine Units

FULL PAPER

H), 4.76 (t, 1 H, THP), 4.85 (d, 1 H, benzyl-CH₂), 7.53 (s, 2 H,

The solvent was removed under reduced pressure. The product was

phenyl-H), 7.59 (s, 2 H, phenyl-H), 7.71 (s, 2 H, phenyl-H), 8.00 purified by column chromatography through silica gel (hexane/

3

4

3

(dd, J = 8, J = 2 Hz, 2 H, pyridyl-H,), 8.53 (d, J = 8 Hz, 2 H,

pyridyl-H), 8.88 (s, 2 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃,

63 MHz): δ = 14.00, 19.29, 22.58, 25.38, 25.84, 29.66, 30.48, 31.64,

ethyl acetate, 9:1) to give 6.88 g of 13 (90%) as a white solid. R_f

(hexane/ethyl acetate, 6:1) = 0.74. H NMR (CDCl₃, 250 MHz): δ

= 0.31 (s, 9 H, Si(CH₃)₃), 0.88 (t, 3 H, CH₃), 1.30–1.41 (m, 6 H,

1

62.22, 67.87, 71.04, 71.85, 98.10, 121.12, 123.22, 124.60, 124.82, γ-, δ-, ε-CH₂), 1.63 (m, 2 H, β-CH₂), 3.52 (t, 2 H, α-CH₂), 4.57 (s,

129.03, 130.06, 130.23, 135.16, 135.33, 139.55, 141.58, 141.58,

142.00, 147.52, 153.18, 154.82 ppm. MS (EI, 80 eV): m/z (%) = 694

2 H, benzyl-H), 7.50–7.56 (m, 4 H, phenyl-H, pyridyl-H), 7.74 (dd,

³J = 8 Hz, 1 H, pyridyl-H), 8.58 (s, 1 H, pyridyl-H) ppm. ¹³C NMR

(8.67), 612 (17.07), 594 (100). C₃₅H₃₈Br₂N₂O₃(694.50): calcd. C (CDCl₃, 63 MHz): δ = –1.15, 14.01, 22.60, 25.91, 29.72, 31.67,

60.53, H 5.52, N 4.03; found 60.46, H 5.24, N 3.84.

33.10, 70.89, 72.69, 126.77, 127.91, 131.05, 132.59, 136.02, 136.35,

137.09, 139.01, 142.05, 148.61, 153.13 ppm. MS (EI, 80 eV): m/z

(%) = 421.0 (44.13), 418.9 (42.34), 406.0 (66.00), 404.0 (61.49), 321

(100.00), 318.9 (95.72). C₂₁H₃₀BrNOSi (420.46): calcd. C 59.99, H

7.19, N 3.33; found C 59.93, H 6.98, N 3.22.

5,5Ј-Bis[3-hexyloxymethyl-5-(trimethylsilanyl)phenyl]-2,2Ј-bipyridi-

nyl (11). First Route: To a degassed mixture of 10 (15.32 g,

39.2 mmol) and 5,5-dibromo-2,2Ј-bipyridine (9) (5.60 g,

17.8 mmol) in toluene/aq. 2 m Na₂CO₃2:1 (360 mL) [Pd(PPh₃)₄]

(1.20 g, 1.04 mmol) was added and the mixture degassed once

more. The reaction mixture was refluxed for 3 d and then the

phases were separated. The aqueous one was extracted with toluene

(2×100 mL) and the combined organic phases were dried with

MgSO₄. The solvent was removed and the resulting oil purified by

column chromatography through silica gel (hexane/ethyl acetate,

4:1) to give 11 g of 11 (90%) as a white solid. R_f(hexane/ethyl

acetate, 9:1) = 0.35.

5,5Ј-Bis(3-hexyloxymethyl-5-{3-hexyloxymethyl-5-[(triisopropylsil-

anyl)ethynyl]phenylethynyl}phenyl)-2,2Ј-bipyridinyl (14): B (X³

=

CH₂OHex) (3.41 g, 8.6 mmol), 6 (2.01 g, 2.90 mmol), triethylamine

(40 mL), toluene (20 mL). Column chromatography through silica

gel (hexane/ethyl acetate, 10:1) gave 3.07 g of 14 (80%) as a color-

less oil. R_f(hexane/ethyl acetate, 4:1) = 0.48. ¹H NMR (CDCl₃,

250 MHz): δ = 0.92 (t, 12 H, CH₃), 1.12 [s, 42 H, Si(C₃H₇)₃], 1.30–

1.48 (m_c, 24 H, γ-, δ-, ε-CH₂), 1.64 (m_c, 8 H, β-CH₂), 3.28 (m, 8

H, α-CH₂), 4.40 (s, 4 H, benzyl-H), 4.60 (s, 4 H, benzyl-H), 7.42

(s, 2 H, phenyl-H), 7.48 (s, 2 H, phenyl-H), 7.56 (s, 2 H, phenyl-H)

7.60 (s, 2 H, phenyl-H) 7.70 (s, 2 H, phenyl-H) 7.72 (s, 2 H, phenyl-

Second Route: To a degassed solution of 13 (4.64 g, 11.04 mmol) in

dry toluene (140 mL) 3 mL (50 mol%) of hexa-n-butyldistannane

and [Pd(PPh₃)₄] (290 mg, 0.25 mmol) were added and the reaction

mixture was degassed again. After refluxing for 5 d the mixture

was poured into aqueous EDTA (1 m, 40 mL). After stirring for

15 min the phases were separated. The aqueous one was extracted

with toluene and the combined organic phases were dried

(MgSO₄). After evaporation of the solvent, the raw product was

purified by column chromatography through silica gel (hexane/

ethyl acetate, 9:1) to give 3.23 g of 11 (85%) as a white solid. R_f

3

H), 8.04 (d, J = 8 Hz, 2 H, pyridyl-H), 8.52 (d, J = 8 Hz, 2 H,

pyridyl-H), 8.96 (s, 2 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃,

63 MHz): δ = 11.28, 14.03, 18.64, 22.61, 25.84, 29.67, 31.67, 70.81,

70.95, 71.92, 72.22, 89.17, 89.42, 91.41, 106.05, 121.03, 123.25,

123.98, 126.14, 129.25, 130.30, 130.43, 130.91, 134.15, 135.26,

135.63, 138.04, 139.37, 140.18, 147.67, 154.95 ppm. MS (EI,

80 eV): m/z (%)

=

1326 (10) [M⁺], 1282 (100). HRMS

(C₈₈H₁₂₀N₂O₄Si₂): calcd. 1280.81607; found 1280.81120.

1

(hexane/ethyl acetate, 9:1) = 0.35. H NMR (CDCl₃, 250 MHz): δ

= 0.35 [s, 18 H, Si(CH₃)₃], 0.93 (t, 6 H, CH₃), 1.24–1.45 (m, 12 H,

γ-, δ-, ε-CH₂), 1.68 (m, 4 H, β-CH₂), 3.58 (t, 4 H, α-CH₂), 4.64 (s,

4 H, benzyl-H), 7.54 (s, 2 H, phenyl-H), 7.63 (s, 2 H, phenyl-H),

5Ј-(3-Hexyloxymethyl-5-{3-hexyloxymethyl-5-[(triisopropylsilanyl)-

ethynyl]phenylethynyl}phenyl)-5-{3-[3-hexyloxymethyl-5-[(triiso-

propylsilanyl)ethynyl]phenylethynyl]-5-(tetrahydropyran-2-yloxy-

methyl)phenyl}-2,2Ј-bipyridinyl (15): 8 (1.78 g, 2.56 mmol), B (X³

= CH₂OHex) (3.01 g, 7.60 mmol), triethylamine (40 mL), toluene

(20 mL). Column chromatography through silica gel (hexane/ethyl

acetate, 6:1) gave 2.79 g of 15 (82%) as colorless oil. R_f(hexane/

ethyl acetate, 3:1) = 0.36. ¹H NMR (CDCl₃, 250 MHz): δ = 0.86

(t, 9 H, CH₃), 1.12 [s, 42 H, Si(C₃H₇)₃], 1.23–1.42 (m_c, 18 H, β-,

γ-, δ-CH₂), 1.50–1.90 (m_c, 12 H, β-CH₂, 6 H-THP), 3.45–3.6 (m, 7

H, α-CH₂, THP), 3.90 (m, 1 H, THP), 4.39 (s, 4 H, benzyl-H), 4.51

3

7.72 (s, 4 H, phenyl-H), 8.06 (d, J = 8 Hz, 2 H, pyridyl-H), 8.55

3

(d, J = 8 Hz, 2 H, pyridyl-H), 8.97 (s, 2 H, pyridyl-H) ppm. ¹³C

NMR (CDCl₃, 63 MHz): δ = –1.10, 14.02, 22.62, 25.94, 29.76,

31.70, 70.83, 72.85, 120.91, 126.92, 131.17, 132.35, 135.36, 136.80,

137.12, 138.88, 141.80, 147.80, 154.59 ppm. MS (EI): m/z (%) =

680 (100), 580 (22.26), 375 (13.14). HRMS (C₄₂H₆₀N₂O₂Si₂): calcd.

680.41931; found 680.41756.

5,5Ј-Bis(3-hexyloxymethyl-5-iodophenyl)-2,2Ј-bipyridinyl (12): Com-

pound 11 (7.58 g, 11.02 mmol) was placed into a flask, which was

evacuated and refilled with N₂. On the Schlenk line, dry CH₂Cl₂

(550 mL) and iodine monochloride (7.22 g, 44.47 mmol) were

added under nitrogen. The mixture was heated to 45 °C for 48 h.

Once it had cooled to room temperature, a solution of NaOH

(2.22 g, 55 mmol) and Na₂S₂O₃(6 g, 44.58 mmol) in water

(140 mL) was added and the mixture stirred for 12 h. The phases

were then separated, the aqueous one was extracted with CH₂Cl₂

(2×100 mL), and the combined organic phases were washed with

2 n NH₄OH (140 mL) and then dried with MgSO₄. Removal of

the solvent gave 8.00 g of 12 (98%) as a white solid.

2

(s, 2 H, benzyl-H), 4.56 (d, J = 12 Hz, 1 H, benzyl-H), 4.73 (t, 1

H, THP), 4.88 (d, ²J = 12 Hz, 1 H, benzyl-H), 7.41 (s, 2 H, phenyl-

H), 7.48 (s, 2 H, phenyl-H), 7.53 (s, 1 H, phenyl-H), 7.56 (s, 2 H,

phenyl-H), 7.61 (s, 3 H, phenyl-H), 7.71 (s, 2 H, phenyl-H), 7.53

(d, ³J = 8 Hz, 2 H, pyridyl-H), 8.00 (d, ³J = 8 Hz, 2 H, pyridyl-H),

8.91 (s, 2 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃, 126 MHz): δ =

11.17, 13.93, 18.19, 19.20, 22.51, 25.34, 25.74, 29.56, 30.41, 31.55,

61.98, 66.90, 68.03, 70.67, 70.81, 71.75, 72.04, 89.07, 89.37, 91.22,

97.86, 105.98, 120.89, 123.13, 123.83, 12589, 126.11, 129.03,

130.26, 130.71, 133.97, 135.02, 135.39, 137.79, 139.30, 139.68,

140.10, 147.42, 154.64 ppm. MS (FAB): m/z (%) = 1327 (7.20) [M

+ H]⁺, 496 (32.29). C₈₇H₁₁₆N₂O₅Si₂(1326.03): calcd. C 78.80, H

8.82, N 2.11; found C 78.42, H 8.83, N 1.94.

2-Bromo-5-[3-hexyloxymethyl-5-(trimethylsilanyl)phenyl]pyridine

(13): To a degassed mixture of 2-bromo-5-iodopyridine 2 (5.17 g,

18.2 mmol) and 10 (7.11 g, 18.2 mmol) in toluene (110 mL) and aq.

5,5Ј-Bis{3-[3-ethynyl-5-(hexyloxymethyl)phenylethynyl]-5-(hexyl-

2 m Na₂CO₃(55 mL) [Pd(PPh₃)₄] (410 mg, 0.35 mmol) was added. oxymethyl)phenyl}-2,2Ј-bipyridinyl (16): 14 (2.72 g, 2.05 mmol), am-

The mixture was degassed once more and refluxed for 3 d. Then the

phases were separated, the aqueous one was extracted with toluene

(2×100 mL) and the combined organic phases dried with MgSO₄.

monium fluoride trihydrate (1.36 g, 4.25 mmol). The compound

was purified by column chromatography through silica gel (ethyl

acetate/hexane, 1:6) to give 1.97 g of 16 (95%) as a white solid. R_f

Eur. J. Org. Chem. 2005, 822–837

www.eurjoc.org

831

D. M. Opris, P. Franke, A. D. Schlüter

FULL PAPER

= 0.07 (ethyl acetate/hexane, 1:3). H NMR (CDCl₃, 500 MHz): δ

8.00 (dd, ³J = 8 Hz, 4 H, pyridyl-H), 8.52 (d, 4 H, ³J = 8 Hz,

1

= 0.89 (t, 12 H, CH₃), 1.29 (m_c, 24 H, β-, γ-, δ-CH₂), 1.63 (m_c, 8 pyridyl-H), 8.88 (s, 4 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃,

H, β-CH₂), 3.1 (s, 2 H, acetylene-H), 3.50 (m, 8 H, α-CH₂), 4.46 126 MHz): δ = 14.05, 19.42, 22.65, 25.49, 25.92, 28.73, 30.61, 31.72,

(s, 4 H, benzyl-H), 4.59 (s, 4 H, benzyl-H), 7.42 (s, 2 H, phenyl-H),

62.29, 68.24, 70.93, 71.04, 71.99, 72.20, 89.35, 89.56, 98.15, 121.56,

7.52 (s, 2 H, phenyl-H), 7.57 (s, 2 H, phenyl-H) 7.59 (s, 2 H, phenyl- 123.45, 124.07, 125.51, 129.15, 130.14, 134.35, 135.32, 135.43,

3

H) 7.62 (s, 2 H, phenyl-H) 7.72 (s, 2 H, phenyl-H), 8.04 (d, J =

136.96, 139.51, 139.77, 140.18, 146.69, 153.36 ppm. MS (FAB):

m/z (%) = 1546 (19.72), 1462 (6.81). C₁₀₅H₁₁₆N₄O₇(1546.07): calcd.

C 81.57, H 7.56, N 3.62; found C 81.18, H 7.42, N 3.76.

3

9 Hz, 2 H, pyridyl-H), 8.55 (d, J = 9 Hz, 2 H, pyridyl-H), 8.95 (s,

2 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃, 126 MHz): δ = 14.04,

22.62, 25.85, 25.90, 29.69, 31.68, 70.89, 70.99, 71.85, 72.24, 88.97,

121.07, 122.59, 123.57, 123.95, 126.24, 129.28, 130.32, 130.92,

134.16, 135.29, 135.71, 138.1, 139.64, 140.25, 147.70, 153.57,

154.99 ppm. MS (FAB): m/z (%) = 1014 (100), 926 (57.53).

C₇₀H₈₀N₂O₄(1013.40): calcd. C 82.96, H 7.96, N 2.76 found C

81.21, H 7.59, N 2.53.

5,5Ј-Bis{3-hexyloxymethyl-5-[(3-iodophenyl)ethynyl]phenyl}-2,2Ј-

bipyridyl (18c): 18b (2.00 g, 3.42 mmol), 1,3-diiodobenzene (23 g,

70 mmol), toluene (230 mL), triethylamine (230 mL), [Pd(PPh₃)₄]

(0.04 equiv.) and CuI (0.04 equiv.), 3 d. The solvent was removed

and the crude product purified by column chromatography through

silica gel (hexane/ethyl acetate, 6:1) to give 2.00 g of 18c (60%) as

white solid. R_f(hexane/ethyl acetate, 6:1) = 0.17. ¹H NMR (CDCl₃,

250 MHz): δ = 0.91 (t, 6 H, CH₃), 1.23–1.42 (m, 12 H, γ-, δ-, ε-

CH₂), 1.65 (m, 4 H, β-CH₂), 3.53 (t, 4 H, α-CH₂), 4.56 (s, 4 H,

benzyl-H), 7.06 (t, 2 H, phenyl-H), 7.42 (d, 2 H, phenyl-H), 7.45

(s, 2 H, phenyl-H), 7.53 (s, 2 H, phenyl-H), 7.59 (d, 2 H, phenyl-

5Ј-{3-[3-Ethynyl-5-(hexyloxymethyl)phenylethynyl]-5-(hexyloxy-

methyl)phenyl}-5-{3-[3-ethynyl-5-(hexyloxymethyl)phenylethynyl]-5-

(tetrahydropyran-2-yloxymethyl)phenyl}-2,2Ј-bipyridinyl (17): 15

(2.90 g, 2.19 mmol), ammonium fluoride trihydrate (1.45 g,

4.52 mmol). The compound was purified by column chromatogra-

phy through silica gel (hexane/ethyl acetate, 1:3) to give 2.15 g 17

(97%) as a white solid. R_f(ethyl acetate/hexane, 1:3) = 0.36. ¹H

3

H), 7.64 (s, 2 H, phenyl-H), 7.83 (s, 2 H, phenyl-H), 7.96 (dd, J =

4

3

8, J = 2 Hz, 2 H, pyridyl-H), 8.54 (d, J = 8 Hz, 2 H, pyridyl-H),

NMR (CDCl₃, 500 MHz): δ = 0.86 (t, 9 H, CH₃), 1.18–1.38 (m_c, 8.94 (d, ⁴J = 2 Hz, 2 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃,

18 H, γ-, δ-, ε-CH₂), 1.50–2.00 (m_c, 12 H, β-CH₂, THP), 3.09 (s, 2 63 MHz): δ = 14.00, 22.58, 25.84, 29.68, 31.64, 70.95, 72.13, 88.18,

H, acetylene-H), 3.35–3.57 (m, 7 H, α-CH₂, THP), 3.91 (m, 1 H, 90.26, 93.67, 121.01, 123.70, 125.07, 126.22, 129.16, 129.81, 130.22,

THP), 4.39 (s, 4 H, benzyl-H), 4.47 (s, 2 H, benzyl-H), 4.51 (d, J

= 12 Hz, 1 H, benzyl-H), 4.71 (t, 1 H, THP), 4.82 (d, J = 12 Hz,

1 H, benzyl-H), 7.36 (s, 2 H, phenyl-H), 7.45 (s, 2 H, phenyl-H),

7.5 (s, 2 H, phenyl-H) 7.55 (s, 4 H, phenyl-H) 7.65 (s, 2 H, phenyl-

H) 7.94 (d, ³J = 8 Hz, 2 H, pyridyl-H), 8.48 (d, ³J = 8 Hz, 2 H,

pyridyl-H), 8.86 (s, 2 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃,

126 MHz): δ = 13.87, 19.17, 22.45, 25.29, 25.74, 29.51, 30.37, 31.49,

61.93, 67.98, 70.66, 71.56, 71.50, 77.81, 82.63, 88.86, 89.52, 97.85,

120.81, 122.42, 123.25, 123.70, 123.73, 125.82, 126.05, 128.93,

130.00, 130.18, 130.58, 130.68, 131.03, 133.89, 134.86, 135.21,

137.73, 139.47, 139.67, 140.07, 147.34, 154.63 ppm. MS (FAB):

m/z (%) = 1013 (12.30), 927 (6.35). C₆₉H₇₆N₂O₅(1013.35): calcd.

C 81.78, H 7.56, N 2.76; found C 81.22, H 7.34, N 2.38.

2

130.69, 135.16, 135.51, 137.38, 138.00, 140.17, 140.21, 147.59,

154.88 ppm. MS (EI, 80 eV): m/z (%) = 988.9 (57.17), 988.0 (96.83),

888.9 (43.63), 887.9 (100), 761.9 (26.69), 127.9 (45.09), 42.0 (49.08).

HRMS: (C₅₂H₅₀I₂N₂O₂): calcd. 988.19617; found 988.19436.

2

Macrocycle E5: 18c (1.9 g, 1.92 mmol), 18b (1.12 g, 1.92 mmol), tri-

ethylamine (600 mL), toluene (800 mL), [Pd(PPh₃)₄] (0.04 equiv.),

copper iodide (0.04 equiv.), gave 540 mg of cycle E5 (28%).

2-(5-{3-Bromo-5-[(hexyloxy)methyl]phenyl}pyridin-2-yl)-5-{3-[(hexyl-

oxy)methyl]-5-(trimethylsilyl)phenyl}pyridine (19a): To

a stirred

solution of 4a (3.03 g, 7.09 mmol) in dry toluene (50 mL) a 1.6 n

solution of BuLi in hexane (4.7 mL, 7.52 mmol) was added drop-

wise at –78 °C. To the resulting red solution Me₃SnCl (1.53 g,

7.68 mmol) was added in solid form after 2 h. The mixture was let

to warm to room temp. (overnight). Compound 13 (2.98 g,

7.09 mmol) was then added to the brownish solution of 5a. The

mixture was degassed and [Pd(PPh₃)₄] (3 mol%) added. The reac-

tion mixture was degassed once more and refluxed for 5 d. Then it

was cooled to room temp. and an aq. satd. KF solution (90 mL)

added followed by an aq. 2 n Na₂CO₃solution (150 mL). The

phases were separated, the aqueous one was extracted with toluene

(2×100 mL) and the combined organic phases washed with water

(100 mL) and dried (MgSO₄). The solvent was removed and the

crude brown oil purified by column chromatography through silica

gel (hexane/ethyl acetate, 9:1) to give 2.18 g of 19a (44%) as a white

solid, together with the homocoupling products 6 (0.64 g) and 11

Macrocycle E4: (X¹= X²= Hex, X³= CH₂OHex, Scheme 1). 16

(300 mg, 0.30 mmol), 12 (236 mg, 0.30 mmol), triethylamine

(100 mL), toluene (100 mL), [Pd(PPh₃)₄] (0.04 equiv.), and CuI

(0.04 equiv.), gave 83 mg of cycle E4 (19%). ¹H NMR (CDCl₃,

250 MHz): δ = 0.91 (t, 18 H, CH₃), 1.20–1.49 (m_c, 36 H, γ-, δ-, ε-

CH₂), 1.67 (m_c, 12 H, β-CH₂), 3.53 (m, 12 H, α-CH₂), 4.51 (s, 4

H, benzyl-H), 4.59 (s, 8 H, benzyl-H), 7.5 (s, 4 H, phenyl-H), 7.55

(s, 4 H, phenyl-H), 7.62 (s, 4 H, phenyl-H) 7.75 (s, 6 H, phenyl-H),

8.06 (dd, J = 8, J = 2 Hz, 4 H, pyridyl-H), 8.53 (d, J = 8 Hz, 4

H, pyridyl-H), 8.96 (s, 4 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃,

126 MHz): δ = 14.03, 22.63, 23.91, 25.89, 29.14, 29.74, 31.70, 70.90,

70.98, 71.99, 72.27, 89.23, 89.70, 121.11, 123.55, 124.04, 125.91,

129.55, 129.99, 130.16, 134.48, 135.12, 135.40, 137.92, 139.65,

140.25, 147.59, 154.96 ppm. MS (FAB): m/z (%) = 1546 (100), 1460

(57.85). C₁₀₆H₁₂₀N₄O₆(1546.11): calcd. C 82.34, H 7.82, N 3.62;

found C 81.27, H 7.54, N 3.50.

3

4

3

1

(0.43 g). H NMR (CDCl₃, 270 MHz): δ = 0.43 [s, 9 H, Si(CH₃)₃],

0.75–0.95 (m, 6 H, CH₃), 1.20–1.40 (m, 12 H, γ-, δ-, ε-CH₂), 1.60–

1.75 (m, 4 H, β-CH₂), 3.45–3.55 (m, 4 H, α-CH₂), 4.53 (s, 2 H,

benzyl-H), 4.59 (s, 2 H, benzyl-H), 7.53 (s, 3 H, phenyl-H), 7.61 (s,

Macrocycle E1 (20): (X¹= THP, X²= Hex, X³= CH₂OHex, 1 H, phenyl-H), 7.68 (s, 2 H, phenyl-H), 7.98 (dd, ³J = 8, ⁴J =

Scheme 1). 17 (1.84 g, 1.82 mmol), 12 (1.44 g, 1.82 mmol), triethyl-

amine (600 mL), toluene (600 mL), [Pd(PPh₃)₄] (80 mg, 0.04

equiv.), CuI (13 mg, 0.04 equiv.), gave 0.66 g of cycle 20 (23%). ¹H

2 Hz, 1 H, pyridyl-H), 8.03 (dd, ³J = 8, ⁴J = 2 Hz, 1 H, pyridyl-

H), 8.52 (d, ³J = 8 Hz, 2 H, pyridyl-H), 8.93 (s, 1 H, pyridyl-H),

8.93 (s, 1 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃, 63 MHz): δ =

NMR (CDCl₃, 250 MHz): δ= 0.88 (t, 15 H, CH₃), 1.20–1.44 (m_c, –1.24, 13.60, 13.88, 22.22, 22.45, 25.71, 25.78, 29.52, 29.60, 31.27,

30 H, γ-, δ-, ε-CH₂), 1.50–2.00 (m_c, 16 H, THP, β-CH₂), 3.40–3.64 31.52, 31.79, 33.65, 70.62, 70.80, 71.62, 72.62, 120.72, 120.81,

(m, 11 H, THP, α-CH₂), 3.92 (m, 1 H, THP), 4.46 (s, 4 H, benzyl-

123.04, 124.25, 126.65, 128.67, 129.69, 130.89, 132.15, 134.59,

H), 4.52 (s, 7 H, THP, benzyl-H), 4.76 (t, 1 H, THP), 5.84 (d, 1 H, 134.86, 135.00, 136.63, 136.81, 138.74, 139.43, 141.49, 141.82,

benzyl-H), 7.36–7.60 (m, 12 H, phenyl-H), 7.68 (s, 6 H, phenyl-H), 147.30, 147.58, 154.09, 155.00 ppm. MS (EI): m/z (%) = 688 (100),

832

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Eur. J. Org. Chem. 2005, 822–837

Shape-Persistent Macrocycles with Bipyridine Units

FULL PAPER

586 (35). HRMS (C₃₉H₅₁BrN₂O₂Si): calcd. 686.290319, found:

686.29333.

(EI): m/z (%) = 812.5 (5) [M]⁺, 769.4 (25), [M – C₃H₇]⁺. HRMS

(C₅₂H₇₂N₂O₂Si₂): calcd. 812.51324, found 812.51533.

2-(5-{3-Bromo-5-[(hexyloxy)methyl]phenyl}pyridin-2-yl)-5-{3-[(hexyl-

oxy)methyl]-5-iodophenyl}pyridine (19b): To a solution of 19a

(4.79 g, 6.96 mmol) in dry dichloromethane (350 mL), ICl (3.39 g,

20.8 mmol) was added under nitrogen. The reaction mixture was

refluxed for 2 d. After it was cooled to room temp., a solution of

NaOH (1 g) and Na₂S₂O₃(2.8 g) in water (30 mL) was added and

stirring continued for 2 h. The organic phase was separated,

washed with 2 n NH₄OH (65 mL) and dried with MgSO₄. The

solvent was removed and the mixture purified by column chroma-

tography through silica gel (hexane/ethyl acetate, 9:1) to give 1.86 g

5-{3-Ethynyl-5-[(hexyloxy)methyl]phenyl}-2-(5-{3-[(hexyloxy)-

lxmethyl]-5-[2-(triisopropylsilyl)ethynyl]phenyl}pyridin-2-yl)pyridine

(19e): 19d (1.28 g, 1.57 mmol), THF (20 mL), methanol (10 mL),

catalytic amount of 1 m NaOH solution, 24 h. The compound was

purified by column chromatography through silica gel (hexane/

ethyl acetate, 4:1) to give 1.14 g of 19e (89%) as colorless oil. R_f

1

(hexane/ethyl acetate, 4:1) = 0.61. H NMR (270 MHz, CDCl₃): δ

= 0.86 (t, 6 H, CH₃), 1.13 (s, 21 H, Si(C₃H₇)₃), 1.20–1.40 (m, 12

H, γ-, δ-, ε-CH₂), 1.61 (quintet, 4 H, β-CH₂), 3.13 (s, 1 H, ethynyl-

H), 3.42–3.55 (m, 4 H, α-CH₂), 4.50 (s, 2 H, benzyl-H), 4.51 (s, 2

of 19b (79%) as a white solid. R_f(hexane/ethyl acetate, 4:1) = 0.59. H, benzyl-H), 7.47 (s, 2 H, phenyl-H), 7.54 (s, 1 H, phenyl-H), 7.57

1

M. p. 87 °C. H NMR (CDCl₃, 270 MHz): δ = 0.87 (t, 6 H, CH₃), (s, 1 H, phenyl-H), 7.65 (s, 2 H, phenyl-H), 7.90–8.05 (m, 2 H,

1.10–1.40 (m, 12 H, γ-, δ-, ε-CH₂), 1.75–1.60 (m, 4 H, β-CH₂), 3.50 pyridyl-H), 8.48 (d, ³J = 8 Hz, 2 H, pyridyl-H) 8.87 (s, 1 H, pyridyl-

(t, 4 H, α-CH₂), 4.50 (s, 2 H, benzyl-H), 4.53 (s, 2 H, benzyl-H),

H), 8.89 (s, 1 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃, 68 MHz): δ

7.52 (s, 2 H, phenyl-H), 7.55 (s, 1 H, phenyl-H), 7.67 (s, 1 H, phe- = 11.12, 13.85, 18.49, 22.42, 25.69, 29.50, 31.48, 70.64, 71.79, 71.90,

nyl-H), 7.72 (s, 1 H, phenyl-H), 7.87 (s, 1 H, phenyl-H), 7.97 (m, 77.75, 83.07, 90.98, 106.47, 120.63, 122.84, 124.21, 125.68, 125.99,

³J = 8 Hz, 2 H, pyridyl-H), 8.48 (d, ³J = 8 Hz, 2 H, pyridyl-H)

129.31, 130.34, 134.71, 134.74, 134.99, 135.21, 137.57, 137.62,

8.86 (s, 2 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃, 68 MHz): δ = 139.77, 139.92, 147.25, 154.49, 154.58 ppm. MS (EI): m/z (%) =

14.03, 22.60, 25.85, 29.66, 31.64, 71.02, 71.72, 71.84, 95.01, 121.03,

123.20, 124.61, 125.34, 128.99, 130.03, 134.94, 134.98, 135.23,

136.00, 139.61, 139.68, 141.89, 141.95, 147.57, 154.98 ppm. MS

(FAB): m/z (%) = 741 (9.78) [M]⁺. C₃₆H₄₂BrIN₂O₂(741.54): calcd.

C 58.31, H 5.71, N 3.78; found 58.22, H 5.52, N 3.56.

740.4 (14) [M]⁺, 697.6 (100) [M – C₃H₇]⁺, 655.6 (23), [M – Hex].

HRMS (C₄₉H₆₄O₂N₂Si): calcd. 740.47369; found 740.47522.

5-{3-[(Hexyloxy)methyl]-5-(2-{3-[2-(trimethylsilyl)ethynyl]-5-[(tetra-

hydro-2H-pyran-2-yloxy)methyl]phenyl}ethynyl)phenyl}-2-(5-{3-

[(hexyloxy)methyl]-5-[2-(triisopropylsilyl)ethynyl]phenyl}pyridin-2-

yl)pyridine (19f): 15e (1.14 g, 1.54 mmol), (2-{3-bromo-5-[(tetra-

2-(5-{3-Bromo-5-[(hexyloxy)methyl]phenyl}pyridin-2-yl)-5-{3-[(hexyl-

oxy)methyl]-5-[2-(trimethylsilyl)ethynyl]phenyl}pyridine (19c): 19b hydro-2H-pyran-2-yloxy)methyl]phenyl}ethynyl)trimethylsilane

(3.83 g, 5.14 mmol), trimethylsilylethyne (0.53 g, 5.32 mmol), trie-

tylamine (70 mL), toluene (40 mL), reaction time: 24 h at 60 °C.

The crude product was purified by column chromatography

(0.68 g, 1.85 mmol), triethylamine (30 mL), toluene (40 mL), at

80 °C for 24 h. The compound was purified by column chromatog-

raphy through silica gel (hexane/ethylacetate, 6:1) to give 1.12 g of

15f (71%) as colorless oil. R_f(hexane/ethyl acetate, 4:1) = 0.48. ¹H

through silica gel (hexane/ethyl acetate, 10:1) to give 3.21 g of 19c

1

(88%) as colorless oil. H NMR (CDCl₃, 270 MHz): δ = 0.25 [s, 9 NMR (270 MHz, CDCl₃): δ = 0.24 [s, 9 H, Si(CH₃)₃], 0.75–0.95

H, Si(CH₃)₃], 0.75–0.98 (t, 6 H, CH₃), 1.20–1.45 (m, 12 H, γ-, δ-,

ε-CH₂), 1.55–1.75 (m, 4 H, β-CH₂), 3.42 (t, 4 H, α-CH₂), 4.41 (s,

2 H, benzyl-H), 4.44 (s, 2 H, benzyl-H), 7.42 (s, 3 H, phenyl-H),

(m, 6 H, CH₃), 1.12 [s, 21 H, Si(C₃H₇)₃], 1.20–1.90 (m, 22 H, β-,

γ-, δ-, ε-CH₂, THP-H), 3.40–3.58 (m, 5 H, α-CH₂, THP), 3.80–

3.89 (m, 1 H, THP), 4.43 (d, J = 12 Hz, 1 H, benzyl-H), 4.52 (s,

2

7.47 (s, 1 d, phenyl-H), 7.56 (s, 1 H, phenyl-H), 7.59 (s, 1 H, phenyl- 2 H, benzyl-H), 4.53 (s, 2 H, benzyl-H), 4.68 (s, 1 H, THP), 4.71

2

H), 7.81–7.89 (m, 2 H, pyridyl-H), 8.39 (d, ³J = 8 Hz, 2 H, pyridyl-

H), 8.75 (s, 1 H, pyridyl-H), 8.80 (s, 1 H, pyridyl-H) ppm. ¹³C

NMR (CDCl₃, 68 MHz): δ = 0.24, 13.87, 22.40, 25.66, 29.47, 31.44,

(d, J = 12 Hz, 1 H, benzyl-H), 7.41 (s, 1 H, phenyl-H), 7.47–7.57

(m, 6 H, phenyl-H), 7.64 (s, 1 H, phenyl-H), 7.69 (s, 1 H, phenyl-

3

H), 7.99 (d, J = 8 Hz, 2 H, pyridyl-H), 8.50 (d, J = 8 Hz, 2 H,

70.60, 70.71, 71.52, 71.86, 94.65, 104.44, 120.63, 122.93, 123.80, pyridyl-H) 8.90 (s, 2 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃,

124.12, 125.76, 128.54, 129.15, 129.60, 130.29, 134.47, 134.72,

135.14, 137.42, 139.25, 139.76, 141.68, 147.20, 147.25, 154.35,

154.71 ppm. MS (EI, 80 EV): m/z (%) = 712.2 (21) [M]⁺, 611.9

(100), [M – OHex]⁺. HRMS (C₄₁H₅₁O₂N₂Si⁷⁹Br): calcd. 710.29034;

found 710.29211.

68 MHz): δ = –0.20, 11.22, 13.96, 18.56, 19.13, 22.55, 25.33, 25.82,

29.61, 29.65, 30.36, 31.60, 61.89, 67.67, 70.78, 70.34, 72.08, 89.02,

89.42, 91.20, 94.88, 97.67, 103.99, 106.49, 120.85, 123.20, 123.49,

123.87, 124.37, 125.92, 129.06, 129.51, 130.11, 130.57, 130.82,

134.02, 135.05, 135.42, 135.53, 137.76, 137.89, 138.91, 139.90,

140.10, 147.52, 154.73, 154.80 ppm. MS (EI): m/z (%) = 1014.8

(10.82), 983.5 (27.09), 870.3 (8.88). HRMS (C₆₃H₇₉N₂O₄Si₂) [M-

C₃H₇]⁺: calcd. 983.55784; found 983.55705.

2-(5-{3-[(Hexyloxy)methyl]-5-[2-(triisopropylsilyl)ethynyl]phenyl}-

pyridin-2-yl)-5-{3-[(hexyloxy)methyl]-5-[2-(trimetylsilyl)ethynyl]-

phenyl}pyridine (19d): 19c (1.68 g, 2.36 mmol), triisopropylsilyle-

thyne (0.54 g, 3.07 mmol), triethylamine (50 mL), toluene (35 mL),

24 d, at 80 °C. The compound was purified by column chromatog-

raphy through silica gel (hexane/ethyl acetate, 4:1) to give 1.44 g of

19d (75%) as colorless oil. R_f(hexane/ethyl acetate, 4:1) = 0.53. ¹H

NMR (CDCl₃, 270 MHz): δ = 0.23 [s, 9 H, Si(CH₃)₃], 0.83 (t, 6 H,

5-{3-(2-{3-Ethynyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-

phenyl}ethynyl)-5-[(hexyloxy)methyl]phenyl}2-(5-{3-[(hexyl-

oxy)methyl]-5-[2-(triisopropylsilyl)ethynyl]phenyl}pyridin-2-yl)-

pyridine (19g): 19f (1 g, 0.97 mmol), THF (20 mL), methanol

(15 mL). Purification by column chromatography through silica gel

CH₃), 1.10 [s, 21 H, Si(C₃H₇)₃], 1.20–1.40 (m, 12 H, γ-, δ-, ε-CH₂), (hexane/ethyl acetate, 6:1) gave 0.88 g of 19g (95%) as colorless oil.

1.50–1.60 (m, 4 H, β-CH₂), 3.40 (t, 4 H, α-CH₂), 4.41 (s, 2 H, R_f(hexane/ethyl acetate, 6:1) = 0.38. ¹H NMR (CDCl₃, 270 MHz):

benzyl-H), 4.43 (s, 2 H, benzyl-H), 7.30–7.45 (m, 4 H, phenyl-H), δ = 0.84 (t, 6 H, CH₃), 1.11 (s, 21 H, Si(C₃H₇)₃), 1.20–1.50 (m, 12

7.58 (s, 2 H, phenyl-H), 7.87 (m, 2 H, pyridyl-H), 8.44 (d, ³J =

H, γ-, δ-, ε-CH₂), 1.50–1.95 (m, 10 H, THP, β-CH₂), 3.09 (s, 1 H,

acetylene-H), 3.40–3.52 (m, 5 H, α-CH₂, THP), 3.78–3.89 (m, 1 H,

8 Hz, 2 H, pyridyl-H) 8.81 (s, 2 H, pyridyl-H) ppm. ¹³C NMR

(CDCl₃, 68 MHz): δ = –0.31, 11.06, 13.81, 18.43, 22.39, 25.66, THP), 4.45 (d, ²J = 12 Hz, 1 H, benzyl-H), 4.48 (s, 2 H, benzyl-

29.45, 31.42, 70.53, 71.79, 90.84, 94.45, 104.46, 106.44, 120.54,

123.78, 124.14, 125.63, 129.08, 129.19, 130.16, 130.23, 134.63,

135.01, 135.10, 137.46, 137.51, 139.74, 147.21, 154.47 ppm. MS

H), 4.49 (s, 2 H, benzyl-H), 4.66 (t, 1 H, THP), 4.69 (d, ²J = 12 Hz,

1 H, benzyl-H), 7.40 (s, 1 H, phenyl-H), 7.45 (s, 1 H, phenyl-H),

7.51 (s, 2 H, phenyl-H), 7.52 (s, 1 H, phenyl-H), 7.55 (s, 1 H, phe-

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833

D. M. Opris, P. Franke, A. D. Schlüter

FULL PAPER

nyl-H), 7.62 (s, 1 H, phenyl-H), 7.66 (s, 1 H, phenyl-H), 7.96 (d, ³J

= 8 Hz, 2 H, pyridyl-H), 8.48 (d, J = 8 Hz, 2 H, pyridyl-H) 8.87

was stirred for 20 d, during which time the reaction warmed to

room temp. The solvent was removed, the solid dissolved in the

minimum amount of tetrahydrofurane, and the compound precipi-

tated by addition of methanol. The suspension was centrifugated

and the precipitate filtered and dried in vacuo to give 0.23 g of 23

(96%) as a white solid. ¹H NMR (CDCl₃, 270 MHz): δ = 0.80–

0.95 (m, 15 H, CH₃), 1.25–1.50 (m, 32 H, γ-, δ-, ε-CH₂, norbor-

nene), 1.58 (d, 1 H, norbornene), 1.60–1.72 (m, 10 H, β-CH₂),

3

(s, 2 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃, 68 MHz): δ = 11.10,

13.87, 18.49, 19.01, 22.44, 25.21, 25.71, 29.50, 30.20, 31.48, 61.74,

67.48, 70.67, 71.91, 77.83, 82.54, 88.75, 89.45, 91.05, 97.63, 106.30,

120.76, 122.40, 123.17, 123.62, 124.23, 125.79, 128.92, 129.35,

129.98, 130.45, 130.75, 133.90, 134.90, 135.28, 137.64, 138.98,

139.76, 139.97, 147.36, 154.55 ppm. MS (FAB+): m/z (%) = 955.4

(5.24), 884.9 (2.10). HRMS (C₆₀H₇₃N₂O₄Si): calcd. 913.53396; 1.95–2.05 (m, 1 H, norbornene), 2.30–2.40 (m, 1 H, norbornene),

found 913.53219.

2.95 (s, 1 H, norbornene), 3.12 (s, 1 H, norbornene), 3.50–3.65 (m,

10 H, α-CH₂), 4.50 (s, 4 H, benzyl-H), 4.55 (s, 6 H, benzyl-H), 5.17

(s, 2 H, benzyl-H), 6.14 (s, 2 H, norbornene), 7.46 (s, 5 H, phenyl-

H), 7.48 (s, 4 H, phenyl-H), 7.54 (s, 4 H, phenyl-H), 7.67 (s, 4 H,

phenyl-H), 7.71 (s, 1 H, phenyl-H), 7.99 (d, ³J = 8 Hz, 4 H, pyridyl-

H), 8.48 (d, ³J = 8 Hz, 4 H, pyridyl-H), 8.90 (s, 4 H, pyridyl-H)

ppm. ¹³C NMR (CDCl₃, 500 MHz): δ = 13.99, 22.56, 25.88, 29.68,

30.45, 31.66, 41.62, 43.05, 46.35, 46.60, 70.82, 70.87, 71.90, 72.10,

88.91, 89.13, 89.31, 89.52, 120.50, 123.13, 123.53, 123.88, 124.90,

125.35, 128.56, 129.11, 129.46, 129.85, 129.95, 133.73, 133.90,

134.04, 134.13, 135.63, 136.87, 137.18, 138.05, 139.06, 139.10,

139.45, 146.80, 154.24, 154.33, 154.54, 175.73. MS (FAB): m/z (%)

= 1582.8 (1.5), 448 (2.7), 391.6 (100) ppm. MS(MALDI-TOF,

dithranol): 1581.83 [M]⁺; monoisotopic mass calcd. for

C₁₀₈H₁₁₆N₄O₇1581.89, found 1581.83. C₁₀₈H₁₁₆N₄O₇(1582.10):

calcd. C 81.99, H 7.39, N 3.54; found C 80.63, H 7.16, N 3.30.

Macrocycle 21: A solution of 20 (E1) (0.47 g, 0.30 mmol) in DCM

(150 mL) and methanol (50 mL) was treated with a solution of hy-

drochloric acid (25%, 1.5 mL). The mixture was stirred at ambient

temperature for 24 h and then treated with a solution of NaHCO₃

(pH = 7). The phases were separated and the organic one was

washed with brine and dried with MgSO₄to give 0.43 g of 21 (98%)

as a white solid. ¹H NMR (CDCl₃, 270 MHz): to prevent aggrega-

tion some triethylammonium hydrochloride salt (TEA·HCl) was

added into the NMR tube: δ = 0.80–0.95 (m, 15 H, CH₃), 1.25–

1.50 (m, 30 H, γ-, δ-, ε-CH₂), 1.60–1.70 (m, 10 H, β-CH₂), 3.43–

3.52 (m, 10 H, α-CH₂), 4.44 (s, 4 H, benzyl-H), 4.50 (s, 6 H, benzyl-

H), 4.72 (s, 2 H, benzyl-H), 7.41 (s, 4 H, phenyl-H), 7.44 (s, 3 H,

phenyl-H), 7.49 (s, 1 H, phenyl-H), 7.51 (s, 3 H, phenyl-H), 7.59 (s,

3

1 H, phenyl-H), 7.64 (s, 6 H, phenyl-H), 7.96 (d, J = 8 Hz, 4 H,

pyridyl-H), 8.43 (d, J = 8 Hz, 4 H, pyridyl-H), 8.86 (s, 4 H, pyri-

3

dyl-H) ppm. ¹³C NMR (CDCl₃, 63 MHz): δ = 14.04, 22.63, 25.90,

29.69, 31.72, 70.90, 71.12, 71.99, 72.23, 88.95, 89.48, 120.46,

123.21, 123.33, 123.43, 124.71, 128.49, 129.30, 129.83, 133.80,

134.07, 136.52, 136.69, 138.89, 139.02, 141.96, 146.69, 154.18 ppm.

MS (FAB): m/z (%) = 1462.8 (100) [M + H]⁺; monoisotopic mass

calcd. for C₁₀₀H₁₀₉N₄O₆⁺: 1462.83; found: 1462.80.

{3-Bromo-5-[6-(5-{3-bromo-5-[(hexyloxy)methyl]phenyl}pyridin-2-

yl)pyridin-3-yl]phenyl}methanol (24): To a stirred solution of 8

(1.5 g, 2.16 mmol) in THF/methanol, 1:1 (60 mL), hydrochloric

acid (35%, 1 mL) was added. The reaction mixture was stirred at

room temp. for 24 h. Then DCM (100 mL) and a saturated aque-

ous solution of NaHCO₃(20 mL) were added and the phases sepa-

rated. The aqueous one was extracted with dichloromethane

(50 mL) and the combined organic phases were dried with MgSO₄.

The solvent was removed to give 1.23 g of 24 (93%) as a white

Macromonomer 22: To a mixture of alcohol 21 (0.2 g, 0.14 mmol),

triethylamine (70 µL), and catalytic amounts of 4-(dimethylamino)

pyridine (2.6 mg) in dry dichloromethane (60 mL) freshly distilled

methacryloyl chloride (60 µL) was added at 0 °C and the resulting

mixture stirred for 20 h. After letting it warm to room temp. a

saturated solution of NaHCO₃was added and the phases were sep-

arated. The organic phase was washed with brine and dried with

MgSO₄. The solvent was removed at room temp. The white solid

was dissolved in the minimum amount of tetrahydrofurane and pre-

cipitated with methanol. The suspension was centrifugated, the

white solid collected, and then dried at high vacuum to give 0.17 g

of 22 (82%) as a white solid. ¹H NMR (CDCl₃, 270 MHz): δ =

0.80–1.02 (m, 15 H, CH₃), 1.30–1.50 (m, 30 H, γ-, δ-, ε-CH₂), 1.60–

1.75 (m, 10 H, β-CH₂), 2.02 (s, 3 H, CH₃), 3.45–3.60 (m, 10 H, α-

CH₂), 4.48 (s, 4 H, benzyl-H), 4.50 (s, 6 H, benzyl-H), 5.19 (s, 2 H,

benzyl-H), 5.66 (s, 1 H, C=CH₂), 6.24 (s, 1 H, C=CH₂), 7.49 (s, 4

H, phenyl-H), 7.52 (s, 3 H, phenyl-H), 7.55 (s, 1 H, phenyl-H), 7.59

(s, 4 H, phenyl-H), 7.73 (s, 5 H, phenyl-H), 7.77 (s, 1 H, phenyl-

1

solid. H NMR (CDCl₃, 250 MHz): δ = 0.84 (t, 3 H, CH₃), 1.20–

1.40 (m, 6 H, γ-, δ-, ε-CH₂), 1.62 (m, 2 H, β-CH₂), 3.34 (s, 1 H,

OH), 3.50 (t, 2 H, α-CH₂), 4.52 (s, 2 H, benzyl-H), 4.72 (s, 2 H,

benzyl-H), 7.46 (s, 4 H, phenyl-H), 7.56 (s, 1 H, phenyl-H), 7.64 (s,

1 H, phenyl-H), 7.82 (d, 1 H, pyridyl-H), 7.92 (d, 1 H, pyridyl-H),

8.40 (2d overlapped in t, 2 H, pyridyl-H), 8.72 (s, 1 H, pyridyl-H),

9.89 (s, 1 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃, 63 MHz): δ =

13.98, 22.56, 25.82, 29.63, 31.62, 64.05, 71.05, 71.82, 121.11,

123.21, 123.26, 123.83, 124.53, 128.80, 128.92, 129.40, 130.04,

134.88, 135.08, 135.13, 135.22, 139.44, 141.94, 144.21, 147.40,

147.48, 154.77 ppm. MS (EI): m/z (%) = 610 (40.30), 509.8 (99.11),

430.7 (100). C₃₀H₃₀Br₂N₂O₂(610.38): calcd. C 59.03, H 4.95, N

4.59; found C 59.01, H 4.66, N 4.46.

3-Bromo-5-[6-(5-{3-bromo-5-[(hexyloxy)methyl]phenyl}-

pyridin-2-yl)pyridin-3-yl]benzyl Methacrylate (25): To a mixture of

alcohol 24 (50 mg, 0.08 mmol), triethylamine (30 µL), and catalytic

amounts of 4-(dimethylamino)pyridine (1.3 mg) in dry dichloro-

methane (2 mL) freshly distilled methacryloyl chloride (15 µL) was

added at 0 °C and the resulting mixture stirred for 20 h before it

was let to warm to room temp. Then a saturated solution of

NaHCO₃was added and the phases were separated. The organic

one was washed with brine and dry over MgSO₄. The solvent was

removed at room temp. and the compound dried to give 51 mg of

3

H), 8.04 (d, J = 8 Hz, 4 H, pyridyl-H), 8.52 (d, J = 8 Hz, 4 H,

pyridyl-H), 8.94 (s, 4 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃,

68 MHz): δ = 14.04, 18.40, 22.62, 25.62, 29.74, 31.69, 65.66, 70.93,

71.93, 72.20, 89.09, 89.63, 120.85, 123.46, 123.83, 124.21, 125.49,

125.86, 126.17, 129.12, 129.78, 130.11, 134.22, 134.72, 136.02,

137.44, 137.74, 139.41, 139.92, 147.27, 154.65, 160.74 ppm. MS

(MALDI-TOF) 1529.87. MS (FAB): m/z (%) = 1255.1 (100) [M +

Na]⁺. C₁₀₄H₁₁₂N₄O₇(1530.02): calcd. C 81.64, H 7.38, N 3.66;

found: C 81.48, H 6.94, N 3.29.

1

25 (95%) as a white solid. H NMR (CDCl₃, 250 MHz): δ = 0.88

(t, 3 H, CH₃), 1.3–1.45 (m, 6 H, γ-, δ-, ε-CH₂), 1.65 (m, 2 H, β-

CH₂), 1.99 (s, 3 H, CH₃), 3.52 (t, 2 H, α-CH₂), 4.54 (s, 2 H, benzyl-

H), 5.24 (s, 2 H, benzyl-H), 5.63 (s, 1 H, C=CH₂), 6.20 (s, 1 H,

C=CH₂) 7.54 (s, 2 H, phenyl-H), 7.56 (s, 2 H, phenyl-H), 7.68 (s,

Macrocycle 23: exo-5-Norbornene-2-carboxylic acid (50 mg,

0.36 mmol), 21 (0.22 g, 0.15 mmol), DMAP (44 mg, 0.36 mmol),

and dry dichloromethane (50 mL) were placed in a flask. DCC

(74 mg, 0.36 mmol) was added to the solution at 0 °C. The solution

3

1 H, phenyl-H), 7.73 (s, 1 H, phenyl-H), 7.99 (d, J = 8 Hz, 2 H,

834

www.eurjoc.org

Eur. J. Org. Chem. 2005, 822–837

Shape-Persistent Macrocycles with Bipyridine Units

FULL PAPER

3

pyridyl-H), 8.51 (d, 2 H, J = 8 Hz, pyridyl-H), 8.88 (s, 2 H, pyri- (m, norbornene-H), 3.21 (s, norbornene-H), 3.49 (t, α-CH₂), 4.46

dyl-H) ppm. ¹³C NMR (CDCl₃, 63 MHz): δ = 13.99, 18.31, 22.56, (s, benzyl-H), 5.03 (s, norbornene-H), 5.08 (s, norbornene-H), 6.15–

25.82, 29.63, 31.60, 65.19, 71.00, 71.81, 121.10, 123.20, 124.59, 6.18 (m, norbornene-H), 7.33 (s, phenyl-H), 7.50–7.60 (m, pyridyl-

125.13, 126.31, 128.96, 129.69, 130.07, 130.41, 135.30, 141.93,

147.47, 155.01, 176.87 ppm. MS (EI): m/z (%) = 678 (71.9) [M⁺],

578 (100), 497 (61.5). HRMS (C₃₄H₃₄Br₂N₂O₃): calcd. 678.09155;

found: 678.09355.

H, phenyl-H), 7.65–7.70 (m, pyridyl-H), 7.79 (d, ³J = 6 Hz, pyridyl-

3

H), 7.82–7.88 (m, pyridyl-H), 8.05–8.15 (m, pyridyl-H), 8.25 (d, J

= 8 Hz, pyridyl-H), 8.51 (d, ³J = 8 Hz, pyridyl-H), 8.61 (dd, ³J = 8,

⁴J = 3 Hz, pyridyl-H) ppm. ¹³C NMR ([D]acetonitrile, 126 MHz): δ

= 14.10, 22.73, 25.94, 29.33, 29.77, 31.77, 42.72, 43.37, 45.99, 49.81,

64.60, 71.19, 71.46, 123.40, 124.51, 124.75, 124.95, 125.67, 128.14,

128.44, 129.02, 129.67, 131.57, 131.88, 132.35, 136.45, 136.55,

136.71, 136.96, 138.18, 138.38, 138.52, 138.91, 139.21, 140.46,

143.03, 144.06, 148.81, 151.96, 155.75, 156.73, 157.13, 175.83 ppm.

MS (FAB) m/z (%) C₅₈H₅₄N₆O₃Br₂RuCl₂: 1178.7 (18), 1158.1 (25),

1143.1 (88) ppm. C₅₈H₅₄Br₂F₁₂N₆O₃P₂Ru (1433.83): calcd. C

48.59, H 3.79, N 5.86; found C 48.54, H 3.56, N 5.68.

26: exo,endo-5-Norbornene-2-carboxylic acid (115 µL, 0.5 mmol),

24 (0.3 g, 0.5 mmol), DMAP (0.12 g, 1 mmol), and dry dichloro-

methane (4 mL) were placed in a flask. DCC (0.2 g, 1 mmol) was

added to the solution at 0 °C. The solvent was stirred under nitro-

gen at room temp. for 18 h. After removal of the solvent, the pro-

duct was dissolved in acetone and a solution of 10% HCl was

added (pH = 7) followed by the addition of NH₄PF₆(0.8 g). The

resulting solid was collected and washed with water. The aqueous

phase was extracted with dichloromethane (2×100 mL). The sol-

vent was removed and the solid washed with diethyl ether. The

ether phase was treated with triethylamine and diluted with dichlo-

romethane and water. The organic phase was separated and dried

with MgSO₄to give 0.4 g of 26 (70%) as white solid. ¹H NMR

mixture of endo/exo 3:1 (from integration of the benzyl protons)

(CDCl₃, 270 MHz): exoδ = 0.75 (t, 3 H, CH₃), 1.10–1.55 (m, 10 H,

β-, γ-, δ-, ε-CH₂, nornornene-H), 1.58–1.68 (m, 2 H, norbornene-

H), 2.15–2.25 (s, 1 H, norbornene), 2.85–3.00 (m, 2 H, norbor-

nene), 3.36 (t, 2 H, α-CH₂), 4.36 (s, 2 H, benzyl-H), 5.01 (s, 2 H,

benzyl-H), 5.95–6.30 (m, 2 H, norbornene), 7.35 (s, 4 H, phenyl-

Polymerization of 25 (28): To a solution of 25 (63 mg, 0.1 mmol) in

freshly degassed toluene (50 µL) 100 µL (5 mol-%) of a 0.05 m

AIBN solution in toluene were added. The mixture was stirred in

a sealed tube at 80 °C for 24 h. The product was purified by prepar-

ative GPC to give 41 mg of 28 (65%). ¹H NMR (CDCl₃,

270 MHz): δ = 0.81 (br. s, 3 H, CH₃), 1.23 (br. s, 6 H, γ-, δ-, ε-

CH₂), 1.55 (br. s, 2 H, β-CH₂), 3.40 (s, 2 H, α-CH₂), 4.39 (s, 2 H,

benzyl-H), 4.91 (s, 2 H, benzyl-H), 7.46 (br. m, 6 H, phenyl-H),

7.69 (br. s, 2 H, pyridyl-H), 8.18 (br. s, 2 H, pyridyl-H), 8.62 (br. s,

2 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃, 68 MHz): δ = 14.06,

22.55, 25.80, 29.65, 31.62, 71.00, 71.77, 120.87, 123.20, 124.34,

125.15, 129.37, 130.05, 130.90, 132.53, 133.86, 134.80, 139.49,

147.27, 154.53, 171.98 ppm.

3

H), 7.49 (s, 1 H, phenyl-H), 7.53 (s, 1 H, phenyl-H), 7.75 (d, J =

3

8 Hz, 2 H, pyridyl-H), 8.29 (d, J = 8 Hz, 2 H, pyridyl-H), 8.67 (s,

2 H, pyridyl-H); endo: δ = 0.75 (t, 3 H, CH₃), 1.10–1.55 (m, 11 H,

β-, γ-, δ-, ε-CH₂, nornornene), 1.72–1.90 (m, 2 H, norbornene),

2.78 (s, 1 H, norbornene), 3.12 (s, 1 H, norbornene), 3.36 (t, 2 H,

α-CH₂), 4.36 (s, 2 H, benzyl-H), 4.96 (s, 2 H, benzyl-H), 5.75–5.80

(m, 1 H, norbornene), 6.03–6.10 (m, 1 H, norbornene), 7.35 (s, 4

H, phenyl-H), 7.49 (s, 1 H, phenyl-H), 7.53 (s, 1 H, phenyl-H), 7.75

(d, ³J = 8 Hz, 2 H, pyridyl-H), 8.29 (d, ³J = 8 Hz, 2 H, pyridyl-H),

8.67 (s, 2 H, pyridyl-H) ppm. ¹³C NMR (CDCl₃, 63 MHz) for the

exo-endo mixture: δ = 13.71, 22.27, 25.53, 28.96, 29.33, 30.13,

31.31, 41.33, 42.24, 42.71, 42.96, 45.48, 46.02, 46.30, 49.30, 64.37,

64.64, 66.64, 70.61, 71.37, 120.53, 122.80, 122.88, 122.92, 123.99,

124.45, 124.59, 126.45, 128.39, 128.98, 129.07, 129.50, 129.81,

129.93, 131.89, 132.18, 134.06, 134.43, 134.55, 135.28, 136.33,

137.53, 137.75, 139.03, 139.09, 139.15, 139.26, 139.32, 139.38,

141.67, 147.04, 147.08, 154.36, 154.63, 173.69, 175.23. MS (EI,

80 eV) m/z (%): 730.2 (100), 665.4 (17), 344.6 (57) ppm. HRMS

(C₃₈H₃₈⁷⁹Br₂N₂O₃): calcd. 728.12673; found 728.12494.

Polymerization of 27 (29): Monomer 27 (360 mg, 0.3 mmol) was

dissolved in CH₂Cl₂(0.5 mL) and stirred under nitrogen. The cata-

lyst ([M]/[C] 20:1) was placed in a second flask containing dried

and degassed CH₂Cl₂(0.2 mL) and was added dropwise to the mo-

nomer solution which was then stirred for 2 h at room temp. fol-

lowed by another 16 h at 40 °C. Nitromethane (1 mL) and ethyl

vinyl ether were then added to the reaction mixture. The solvent

was removed and the compound was dried at high vacuum pump.

¹H NMR (CD₃NO₂, 250 MHz): δ = 0.80 (br., 3 H, CH₃), 1.24 (br.,

7 H, γ-,δ-, ε-CH₂, CH), 1.50–1.80 (br., 4 H, β-CH₂, CH₂), 2.30–

3.00 (br., 4 H), 3.43 (br., 2 H, α-CH₂), 4.41 (s, 2 H, benzyl-H), 4.97

(br., 2 H, benzyl-H), 5.20–5.50 (br., 2 H, CH =), 7.30–7.60 (br., 10

H, phenyl-H, pyridyl-H), 7.90–8.15 (br., 10 H, pyridyl-H), 8.31 (br.,

2 H, pyridyl-H), 8.53 (br., 4 H, pyridyl-H), 8.64 (br.,2 H, pyridyl-

H) ppm. The polymer was not sufficiently soluble to record a¹³C

NMR spectrum.

[26·Ru(bpy)₂(PF₆)₂] (27):

A

stirred solution of 26 (0.33 g,

Macromonomer [(bpy)₂Ru·(23)·Ru(bpy)₂](Cl)₄(30): A stirred sus-

pension of 23 (0.23 mg, 0.14 mmol) and [Ru(bpy)₂Cl₂]×2H₂O

(155 mg, 0.30 mmol) in a mixture of dioxane (70 mL) and ethylene

glycol (23 mL) was refluxed for 24 h. The solvent was removed and

the residual orange material purified by column chromatography

through silica gel (methanol/2 m NH₄Cl/nitromethane, 7:2:1). The

combined orange fractions were diluted with DCM, the organic

phase was separated, and the solvent removed to give 0.2 g of 30

(54%) as an orange solid. A small amount of the complex was

precipitated by adding a solution of the complex in methanol to a

saturated solution of NH₄PF₆in H₂O (1 mL). The precipitated so-

lid was separated by filtration, washed with H₂O (4×2 mL), and

dried in vacuo (this complex was used for characterization). The

chloride complex was used for polymerization because of its higher

solubility in DCM. ¹H NMR (CDCl₃, CD₃NO₂, 270 MHz): δ =

0.45 mmol) and [Ru(bpy)₂Cl₂]×2H₂O (245 mg, 0.43 mmol) in a

mixture of ethanol (8 mL) and H₂O (3 mL) was refluxed for 24 h.

Then the solvent was removed and the residual orange material

purified by column chromatography through silica gel (methanol/2

m NH₄Cl/nitromethane, 7:2:1). The combined orange fractions

were diluted with CH₂Cl₂, the organic phase was separated, and

the solvent removed to give an orange solid 0.36 g of 27 (66%). A

small part of this solid was dissolved in methanol and added to a

concentrated solution of NH₄PF₆. The precipitated solid was sepa-

rated by filtration and washed with H₂O several times. The com-

pound was characterized as PF₆salt.

The product was obtained as a mixture of diastereoisomers with

an endo/exo ratio of 1:3. Its H NMR spectrum is therefore quite

complex and the number of atoms which cause the signals are not

1

given. ¹H NMR ([D]acetonitrile, 270 MHz): δ = 0.89 (t, CH₃), 0.83 (t, 15 H, CH₃), 1.25–1.48 (m, 32 H, γ-, δ-, ε-CH₂, 2 norbor-

1.25–1.45 (m, γ-, δ-, ε-CH₂, norbornene-H), 1.58–1.62 (m, β-CH₂), nene-H), 1.50–1.59 (m, 12 H, β-CH₂, 2 norbornene-H), 2.18–2.25

1.56–1.85 (m, norbornene-H), 2.93 (s, norbornene-H), 3.00–3.05

(m, 1 H, norbornene-H), 2.90 (s, 1 H, norbornene-H), 2.98 (s, 1 H,

Eur. J. Org. Chem. 2005, 822–837

www.eurjoc.org

835

D. M. Opris, P. Franke, A. D. Schlüter

FULL PAPER

2003, 9, 5430–5440; f) S. Höger, Chem. Eur. J. 2004, 10, 1320–

1329.

norbornene H), 3.40–3.50 (m, 10 H, α-CH₂), 4.38 (s, 6 H, benzyl-

H), 4.45 (s, 4 H, benzyl-H), 4.99 (s, 2 H, benzyl-H), 6.00–6.10 (m,

2 H, norbornene-H), 7.03 (s, 4 H, phenyl-H), 7.42–7.52 (m, 18 H,

8 pyridyl-H, 10 phehyl-H), 7.63 (s, 3 H, phenyl-H), 7.69 (s, 1 H,

phenyl-H), 7.75 (s, 4 H, phenyl-H), 7.81 (s, 8 H, pyridyl-H), 7.95 –

[2]

For a recently observed interesting packing behavior of some

flexible cycles, see: a) D. B. Werz, R. Gleiter, F. Rominger, J.

Am. Chem. Soc. 2002, 124, 10638–10639; b) R. Gleiter, D. B.

Werz, B. J. Rausch, Chem. Eur. J. 2003, 9, 2676–2683.

D. T. Borg, T. D. Clark, J. R. Granja, M. R. Ghadiri, Angew.

Chem. Int. Ed. 2001, 40, 988–1011.

For the presently largest cycle constructed from shape-persist-

ent elements, like phenylenes and acetylenes, see: M. Mayor, C.

Didschies, Angew. Chem. 2003, 115, 2384–2387; Angew. Chem.

Int. Ed. 2003, 42, 3176–3179. The cycle reported here, because

of its size and unfavorable bond angles in the planar conforma-

tion, will be significantly more flexible than most of cycles

which are usually referred to as shape-persistent.

For example, see: a) S. Leininger, B. Olenyuk, P. J. Stang,

Chem. Rev. 2000, 100, 853–908; b) G. R. Newkome, T. J. Cho,

C. N. Moorefield, R. Cush, P. S. Russo, L. A. Godinez, M. J.

Saunders, P. Mohapatra, Chem. Eur. J. 2002, 8, 2946–2954; c)

R. Takahashi, Y. Kobuke J. Am. Chem. Soc. 2003, 125, 2372–

2373; d) G. R. Newkome, T. J. Cho, C. N. Moorefield, P. P. Mo-

hapatra, L. A. Godinez, Chem. Eur. J. 2004, 10, 1493–1500; e)

P. S. Mukherjee, N. Das, Y. K. Kryschenko, A. M. Arif, P. J.

Stang, J. Am. Chem. Soc. 2004, 126, 2464–2473; f) G. Fuhr-

mann, T. Debaerdemaeker, P. Bäuerle, Chem. Commun. 2003,

948–949.

a) M. Fisher, S. Höger, Tetrahedron 2003, 59, 9441–9446; b) S.-

S. Sun, A. J. Lees, Organometallics 2001, 20, 2353–2358; c) C.

Grave, D. Lentz, A. Schäfer, P. Samori, J. P. Rabe, P. Franke,

A. D. Schlüter, J. Am. Chem. Soc. 2003, 125, 6907–6918; d)

Y. Tobe, N. Utsumi, A. Nagano, M. Sonoda, K. Naemura,

Tetrahedron 2001, 57, 8075–8083; e) K. Campbell, R. McDon-

ald, R. R. Tykwinski, J. Org. Chem. 2002, 67, 1133–1140; f)

P. N. W. Baxter, Chem. Eur. J. 2003, 9, 2531–2541.

a) J. R. Nitschke, T. D. Tilley, Angew. Chem. 2001, 113, 2200–

2203, Angew. Chem. Int. Ed. 2001, 40, 2142–2145; b) J.

R. Nitschke,T. D.Tilley, J. Am. Chem. Soc. 2001, 123, 10183–

10190; c) L. L. Schäfer, J. R. Nitschke, S. S. H. Mao, F.-Q. Liu,

G. Harder, M. Haufe, T. D. Tilley, Chem. Eur. J. 2002, 8, 74–83;

d) S. Höger, K. Bonrad, A. Mourran, U. Beginn, M. Möller, J.

Am. Chem. Soc. 2001, 123, 5651–5659.

3

8.07 (m, 8 H, pyridyl-H), 8.31 (d, J = 8 Hz, 4 H, pyridyl-H), 8.42

[3]

[4]

3

(d, J = 8 Hz, 8 H, pyridyl-H), 8.68 (d, J = 8 Hz, 4 H, pyridyl-H)

ppm. ¹³C NMR (CDCl₃, CD₃NO₂, 63 MHz): δ = 13.84, 22.47,

25.66, 29.53, 30.32, 31.52, 41.51, 42.93, 46.22, 46.44, 70.82, 70.93,

71.57, 71.67, 88.97, 89.74, 123.17, 123.95, 124.27, 124.41,124.77,

124.88, 125.00, 127.89, 128.27, 129.93, 130.98, 132.68, 133.62,

134.61, 134.97, 135.45, 136.30, 137.76, 138.09, 138.19, 139.29,

139.84, 140.83, 147.80, 151.41, 151.65, 155.50, 156.33, 156.87 ppm,

C=O missing. MS (MALDI-TOF, dithranol): m/z = 2843.75 [M –

PF₆]⁺, 2785.82 [M – PF₆– C₄H₉]⁺, 2698.82 [M – 2PF₆]⁺, 2553.86

[M – 3PF₆]⁺; monoisotopic mass calcd. for: C₁₄₈H₁₄₈F₁₈N₁₂O_7-

P₃Ru₂2843.86, found 2843.75. C₁₄₈H₁₄₈F₂₄N₁₂O₇P₄Ru₂(2988.83):

calcd. C 59.47, H 4.99, N 5.62; found C 58.82, H 4.96, N 5.31.

[5]

Polymerization of 22 (31): To a solution of monomer 22 (0.17 mg,

0.11 mmol) in degassed benzene (1 mL), a 0.05 m AIBN initiator

solution in benzene (112 µL, 5 mol-%) was added. The resulting

mixture was stirred in a sealed tube at 80 °C for 5 d. The purifica-

tion of the oligomer was done by GPC using THF as solvent to

1

give 108 mg of polymer 31 (62%). H NMR (270 MHz, CD₂Cl₂):

[6]

δ = 0.75–1.10 (br., 18 H, CH₃), 1.20–1.90 (br., 42 H, β-, γ-, δ-, ε-

CH₂, CH₂), 3.25–3.70 (br., 12 H, 10 α-CH₂, 2 benzyl-H), 4.00–4.55

(br., 10 H, benzyl-H), 6.50–8.80 (br., 30 H, phenyl-H, pyridyl-H)

ppm. ¹³C NMR (CD₂Cl₂, 63 MHz): δ = 14.36, 21.37, 23.19, 26.50,

29.25, 30.33, 32.32, 71.46, 72.56, 89.34, 89.90, 120.50, 123.79,

128.47, 130.02, 133.84, 136.62, 139.68, 146.78, 154.29, 156.84,

172.30 ppm.

[7]

[8]

Polymerization of 30 (32): Monomer 30 (100 mg, 0.04 mmol) was

dissolved in CH₂Cl₂(0.5 mL) and stirred under nitrogen. 130 µL

of a catalyst stock solution prepared from 12 mg of [(Cy₃P)

₂Cl₂Ru=CHPh] in 1 mL DCM, corresponding to monomer/cata-

lyst ratio of 20:1, was added dropwise to the monomer solution

which was then stirred for 24 h. The product was dried at high

vacuum. ¹H NMR (CDCl₃/CD₃NO₂): δ = 0.60–1.90 (br. 15 H,

CH₃), 1.10–1.45 (br. 34 H, γ-, δ-, ε-CH₂, CH₂), 1.45–1.60 (br., 11

H, β-CH₂, CH), 1.60–2.0 (br., 2 H, CH), 3.80–3.50 (br., 10 H, α-

CH₂), 4.3–4.48 (2 s, 10 H, benzyl-H), 4.60 (br., 2 H, benzyl-H),

4.85–5.10 (br., 1 H, = CH), 5.20–5.50 (br., 1 H, = CH), 7.0–7.23

(br., 4 H, Ph-H), 7.24–7.60, 7.60–7.90 (br., 34 H, pyridyl-H, Ph-

H), 7.90–8.15 (br., 8 H, pyridyl-H), 8.15–8.45 (br., 4 H, pyridyl-H),

8.70–9.10 (br., 8 H, pyridyl-H), 9.10–9.40 (br., 8 H, pyridyl-H)

ppm. ¹³C NMR (CDCl₃, CD₃NO₂): δ = 13.36, 22.05, 25.58, 25.72,

26.21, 26.40, 29.11, 31.10, 34.26, 45.44, 70.50, 71.21, 88.67, 89.29,

122.80, 123.93, 124.78, 125.89, 127.38, 127.77, 129.73, 130.59,

134.22, 134.67, 136.36, 137.69, 138.74, 139.66, 140.38, 147.43,

150.95, 155.45, 156.32, 156.83 ppm, C=O missing.

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Acknowledgments

Financial support by the Deutsche Forschungsgemeinschaft (Sfb,

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Received: October 18, 2004

Eur. J. Org. Chem. 2005, 822–837

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837

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Shape-persistent macrocycles with bipyridine units: Progress in accessibility and widening of applicability

DOI: 10.1002/ejoc.200400744

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