Novel Liquid Crystalline Compounds Containing Bicyclo[3.1.0]hexane Core Units

FULL PAPER

Novel Liquid Crystalline Compounds Containing Bicyclo[3.1.0]hexane

Core Units^[‡]

Sergei I. Kozhushkov,^[a]Rainer Langer,^[a]Dmitrii S. Yufit,^[b]Judith A. K. Howard,^[b]

Heiko Schill,^[a]Dietrich Demus,^[c]Kazutoshi Miyazawa,^[d]and Armin de Meijere*^[a]

Dedicated to Professor Reinhard W. Hoffmann on the occasion of his 70th birthday

Keywords: Cross-coupling / Cycloadditions / Liquid crystals / Small ring systems / Structure elucidation

Additions of ethyl or tert-butyl diazoacetates to 4-substituted

cyclopentenes 6 and 17 under dirhodium tetraacetate/tetra-

octanoate catalysis led to mixtures of tert-butyl endo,exo-

opting essentially the same synthetic strategy, but in an over-

all yield of only 8%, and 6-(4-cyanophenyl)-3-pentylbicyclo-

[3.1.0]hexane exo,exo-38b was obtained by Pd(OAc)₂cata-

and

exo,exo-3-carboxyl(aryl)bicyclo[3.1.0]hexane-6-carb- lyzed cyclopropanation of 4-pentylcyclopentene 34b with (4-

oxylates 7 and 18 in yields of 54−90% from which exo,exo-

cyanophenyl)diazomethane 36b in 29% yield. A comparison

diastereomers were isolated in yields of 39−63%. Diester of the liquid crystalline properties of these newly prepared

exo,exo-7 was saponified and converted into diaryl diesters

exo,exo-9a,b in overall yields of 42 and 46%, respectively.

The esters exo,exo-18 were reduced to the corresponding

hydroxymethyl derivatives, these were transformed to the

iodomethyl compounds which in turn were coupled with

compounds containing a bicyclo[3.1.0]hexane core with

those of the known analogous compounds with a cyclohex-

ane fragment shows that as a rule, a bicyclo[3.1.0]hexane

moiety decreases the transition temperature, while the di-

electric (∆ε) and optical (∆n) anisotropies are comparable.

various alkylmagnesium halides, via Li₂CuCl₄catalysis, to However, the bicyclo[3.1.0]hexane unit has a poorer meso-

give 3-aryl-6-alkylbicyclo[3.1.0]hexyl derivatives exo,exo-21

in overall yields of 72−83%. Fluorinated 3-(2-arylethyl)-6-

pentylbicyclo[3.1.0]hexane exo,exo-32 could be prepared in

five steps from 4-ethoxy-2,3-difluorobenzaldehyde 26a ad-

genic potential.

( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,

Germany, 2004)

Introduction

is difficult to name any another branch of synthetic organic

chemistry which continues to develop so impetuously.^[2]

Among the liquid crystalline compounds, cyclopropane de-

rivatives, especially 1,2-disubstituted cyclopropanes, provide

more rigid conformations than those with similar alkyl

groups that are widely used as fragments in liquid crystal-

line compounds. The first example of such a compound

with a cyclopropane ring appeared as early as 1971^[3]and,

according to the database LiqCryst4.4,^[4]more than 85,000

such compounds have been synthesized to date. However,

no liquid crystalline compound of type 1 with a 3,6-disub-

stituted bicyclo[3.1.0]hexane moiety is listed among them.

Starting from the first observations of the phenomenon

of liquid crystallinity by Reinitzer in 1888^[1a]and by

Lehmann in 1889,^[1b]the design and preparation of mol-

ecules possessing liquid crystalline properties has been of

interest to physical-organic chemists for a long time, and it

[‡]

Cyclopropyl Building Blocks in Organic Synthesis, 96. Part 95:

O. V. Larionov, S. I. Kozhushkov, A. de Meijere, Synthesis 2003,

1916Ϫ1919. Part 94: M. Gensini, A. de Meijere, Chem. Eur. J.,

in press.

[a]

Institut für Organische Chemie der Georg-August-Universität

Göttingen,

Tammannstrasse 2, 37077 Göttingen, Germany

Fax: (internat.) ϩ 49-551-399475

E-mail: Armin.deMeijere@chemie.uni-goettingen.de

[b]

Department of Chemistry, University of Durham,

Durham, South Rd., DH1 3LE, England

[c]

ISCO, International Scientific Consultant Office,

Veilchenweg 22, 06118 Halle, Germany

According to MOPAC/AM1 calculations, such com-

pounds have molecular shapes similar to analogues with a

1,4-disubstituted cyclohexane moiety and, because of the

[d]

Chisso Petrochemical Corporation, Specialty Chemicals

Research Center;

5-1 Goikaigan, Ichihara, Chiba 290-8551, Japan

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DOI: 10.1002/ejoc.200300448

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A. de Meijere et al.

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former being slimmer, they might have superior mesogenic as a key step. After chromatographic separation, the main

properties.^[5]These predictions prompted us to embark on diastereomer exo,exo-7, isolated in 64% yield, was sapon-

a program to prepare such compounds and test their ified and converted into diaryl diesters exo,exo-9a and

properties.

exo,exo-9b in yields of 42 and 46%, respectively, applying es-

tablished procedures (Scheme 1). An X-ray crystal structure

analysis of the diester 9a confirmed the exo,exo-orientation

of the substituents on the bicyclo[3.1.0]hexane skeleton

(Figure 1). Both diesters 9a and 9b exhibit liquid crystalline

properties (see below), yet they could not be considered for

practical applications due to the lack of chemical inertness

of the two ester groups.

Results and Discussion

Preparation

No general synthetic approach to 3,6-disubstituted bi-

cyclo[3.1.0]hexanes 1 has been reported, except for several

low-yielding non-selective reactions.^[6]The first liquid crys-

talline compound with such a skeleton was an aza analogue,

a Schiff’s base of 3-substituted (3-azabicyclo[3.1.0]hexyl)-

amine 5, which was prepared in 2000^[7]by applying the Kul-

inkovich-de Meijere^[8,9]reductive aminocyclopropanation

to N-arylpyrroline 4, which was obtained from (Z)-1,4-bis-

(methanesulfonyloxy)but-2-ene (2)^[10]and aniline, as a key

step (Scheme 1). Indeed, this compound did demonstrate

better liquid crystalline properties than its analogues with

a 1,4-disubstituted cyclohexane instead of the 3-azabicy-

clo[3.1.0]hexane moiety.^[7]However, due to the fact that

compounds of the type 5 are not chemically inert and are

poorly soluble in standard liquid crystalline base mixtures,

they cannot be practically applied. Therefore, synthetic ap-

Figure 1. Structure of bis(p-pentylphenyl) exo,exo-bicyclo[3.1.0]-

hexane-3,6-dicarboxylate (exo,exo-9a) in the crystal^[13]

However, the observed stereoselectivity of the rhodium

proaches to analogous compounds with an all-carbon catalyzed cyclopropanation of 4-substituted cyclopentenes

framework were developed. with an alkyl diazoacetate demonstrated that this reaction

The first model compound with a bicyclo[3.1.0]hexane could also be applied to the synthesis of more elaborate

skeleton was prepared by utilizing a dirhodium tetraacetate- exo,exo-3,6-disubstituted bicyclo[3.1.0]hexane derivatives of

catalyzed cyclopropanation^[11]with ethyl diazoacetate to types 10Ϫ12 containing typical moieties commonly applied

the known tert-butyl cyclopent-3-ene-1-carboxylate (6)^[12]for liquid crystalline compounds.^[14]

Scheme 1. Syntheses of 3-aryl-6-exo-(arylmethyleneamino)-3-azabicyclo[3.1.0]hexane 5 and diaryl bicyclo[3.1.0]hexane-3,6-dicarb-

oxylates 9a,b

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Novel Liquid Crystalline Compounds

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The first synthetic challenge en route to compounds

of type 10, i.e. the synthesis of appropriate 4-arylcyclo-

pentenes 17, was overcome by a palladium-catalyzed

[PdCl₂(dppf)]^[15]cross-coupling reaction^[16]of appropriately

substituted aryl halides 16 with the Grignard reagent pre-

pared from cyclopenten-4-yl bromide (14)^[17](Scheme 2).

The bromide 14 was prepared by conversion of cyclopent-

3-en-1-ol (13)^[18]with Ph₃P·Br₂in 90% yield.

an arylmagnesium bromide initially formed by a Grignard

exchange reaction.

Dirhodium tetraoctanoate catalyzed cyclopropanation of

these 4-arylcyclopentenes 17 with tert-butyl diazoacetate^[19]

led, in spite of the bulky substituent on the diazoacetate

and the bulky catalyst, only to a moderate excess of the

desired exo,exo-diastereomers exo,exo-18, which were iso-

lated in yields of 39Ϫ48% after crude chromatographic sep-

aration followed by recrystallization from methanol

(Scheme 2).

The configurational assignments rest on the ¹H NMR

spectra and on X-ray structural analyses of the esters endo,-

exo-18a and exo,exo-18b (Figure 2).

Figure 2. Structures of tert-butyl esters endo,exo-18a (A) and

exo,exo-18b (B) in the crystal^[13]

A comparison of these two structures reveals an interest-

ing feature in that the main difference between these two

molecules in the solid phase is the conformation of the five-

membered ring. Apparently, the bulky aryl substituents

strive for a quasi-equatorial position on the cyclopentane

ring in both the endo,exo-18a and the exo,exo-18b. As a

result, the bicyclo[3.1.0]hexane moiety in endo,exo-18a ad-

opts a chair-like conformation, while in exo,exo-18b it pre-

Scheme 2. Preparation of 4-arylcyclopentenes 17 and their di-

rhodium tetraoctanoate catalyzed cyclopropanation with tert-

butyl diazoacetate

Using such cross coupling, the 4-arylcyclopentenes fers the boat-like shape that prevails in unsubstituted bi-

17aϪe were obtained in yields of 75Ϫ98%, except for 17c cyclo[3.1.0]hexane according to both experimental^[20]and

because the treatment of 15 with the aryl bromide 16c gave computational results.^[21]Therefore, the configuration at

only the homocoupling product from 16c, presumably via carbon atom C3 may be of secondary importance for the

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achievement of a rod-like shape of the molecule in contrast

to the configuration at C6.

This synthetic protocol did not work quite as well for the

preparation of exo,exo-3-[2-(4-ethoxy-2,3-difluorophenyl)-

The transformation of the tert-butoxycarbonyl group in ethyl]-6-pentylbicyclo[3.1.0]hexane (exo,exo-32) because the

18 into an alkyl moiety was achieved in three steps by re- Li₂CuCl₄catalyzed cross coupling of 1-ethoxy-2,3-difluoro-

duction to the hydroxymethyl derivatives 19, their sub- 4-(iodomethyl)benzene (27) (prepared in two steps from the

sequent conversion into the iodomethyl derivatives 20 and corresponding aldehyde 26a in 95% overall yield) with

finally Li₂CuCl₄catalyzed cross-coupling with various cyclopent-4-ylmagnesium bromide (25) [prepared in three

alkylmagnesium bromides^[22a]according to the protocol of steps from the commercially available cyclopent-3-enecar-

Nicolaou et al.^[22b](Scheme 3). Thus, the 6-alkyl-3-arylbicy- boxylic acid (22) in 77% overall yield] furnished the target

clo[3.1.0]hexane derivatives 21a, 21b, 21d, and 21e were pre- product 29 in 25% yield only (Scheme 4) along with the

pared from the corresponding esters in overall yields of 75, homocoupling product 28 (51% yield). The former was con-

83, 72 and 76%, respectively.

verted into exo,exo-32 according to the synthetic sequence

described above i.e. dirhodium tetraoctanoate catalyzed

cyclopropanation with tert-butyl diazoacetate to give

exo,exo-30, its reduction to the hydroxymethyl compound,

conversion into the iodomethyl derivative exo,exo-31 and

eventually Li₂CuCl₄catalyzed cross coupling with n-butyl-

magnesium bromide with an overall yield of 35%

(Scheme 4).

The most convenient approach to 3-alkyl-6-arylbicy-

clo[3.1.0]hexanes of type 12 would be by direct cyclopro-

panation of appropriately 4-substituted cyclopentenes 34

with aryldiazomethanes 36. In spite of an inexhaustible

number of cyclopropanations with diazomethane itself, es-

pecially via Pd(OAc)₂catalysis,^[23]there are only 75 ex-

amples of corresponding cyclopropanations with aryldiazo-

methanes. Most of these reactions have been performed un-

der photolytic conditions^[24]or by catalysis with ZnX₂,^[25]

Scheme 3. Preparation of 6-alkyl-3-arylbicyclo[3.1.0]hexane deriva-

tives 21 as potentially liquid crystalline compounds of the type 10

Scheme 4. Preparation of the 3-(2-arylethyl)-6-pentylbicyclo[3.1.0]hexane derivative exo,exo-32 as a potentially liquid crystalline com-

pound of type 11

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Novel Liquid Crystalline Compounds

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CuBr^[26]or [Rh(OAc)₂]₂in pentamethylene sulfide^[27]fur-

nishing the corresponding aryl-substituted cyclopropanes in

moderate to good^[27]yields. In view of the intended ap-

proach to potentially liquid crystalline compounds of type

12, the corresponding 4-alkylcyclopentenes 34aϪc were

prepared by cross-coupling reactions of alkyl iodides with

cyclopentenylmagnesium bromide 15 or of 4-(iodomethyl)-

cyclopentene (33) with ethylmagnesium bromide (Scheme 5)

catalyzed by Li₂CuCl₄. The yields in both approaches were

only moderate (30Ϫ56%). The necessary aryldiazomethanes

36aϪc were obtained from the corresponding tosylhydra-

zones 35 using an established procedure.^[28]

Scheme 6. Preparation of exo,exo- and exo,endo-6-(4-cyanophenyl)-

3-pentyl-bicyclo[3.1.0]hexane (exo,exo-38b and exo,endo-38b) as

potentially liquid crystalline compounds of the type 12

Scheme 5. Synthesis of the main building blocks for the potentially

liquid crystalline compounds of type 12

Figure 3. Structure of compounds exo,exo-38b (A) and exo,endo-

38b (B) in the crystal.^[13]

Unfortunately, irradiation of aryldiazomethanes 36a,c in

As in the potentially liquid crystalline compounds endo,-

pentane solutions of the cyclopentenes 34a,b as well as slow exo-18a and exo,exo-18b (see Figure 2), the substituent on

additions of 36a,c to ethereal solutions of 34a,b in the pres- the cyclopentane ring (this time n-pentyl) adopts a quasi-

ence of palladium() acetate gave trans-stilbenes 37a,c as equatorial position in both exo,exo-38b and exo,endo-38b,

the sole products in almost quantitative yield (Scheme 6).

while the bicyclo[3.1.0]hexane unit adopts a boat-like con-

However, upon slow addition of aryldiazomethane 36b formation. However, the orientation of the p-cyanophenyl

to an ethereal solution of 4-pentylcyclopentene (34b) in the substituent on the three-membered ring determines the

presence of palladium() acetate (7 mol %) the target mol- overall shape of the molecule. Whereas exo,exo-38b is more

ecule 38b was obtained, albeit in 32% yield only, as a 9:1 rod-like, its diastereomer exo,endo-38b is more horseshoe-

mixture of exo,exo-38b and exo,endo-38b which was sepa- shaped. Surprisingly, a search for substituted bicyclo[3.1.0]-

rated by HPLC. Contrary to the cyclopropanation products hexanes in the Cambridge Crystallographic Database^[29]

obtained with tert-butyl diazoacetate (Scheme 2), these two displayed only 14 such molecules, and only one of them^[30]

diastereomers of 38b differ with respect to the orientation was a 3,6-disubstituted specimen. The analyses of the pre-

of the substituent on the three-membered ring, while the viously reported molecular structures as well as of the ones

n-pentyl group is exo on the five-membered ring in both described here reveal some interesting features. First of all,

molecules. The configurations at carbon atoms C3 and C6 the conformational flexibility of the bicyclo[3.1.0]hexane

in these compounds were established beyond all reasonable skeleton is noteworthy. Depending on the position and na-

doubt by X-ray crystal structure analyses (Figure 3).

ture of the substituents, the skeleton can adopt the whole

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range of conformations from ‘‘chair-like’’ as in endo,exo- a cyclopentane ring to adopt a quasi-equatorial orientation

18a to ‘‘boat-like’’ as in the unsubstituted bicyclo[3.1.0]hex- and the energetic advantage of a boat-like conformation in

anes^[20,21]and in the other derivatives reported here. The the bicyclo[3.1.0]hexane fragment (by ca. 3.1Ϫ3.3

dihedral angles between planes C1ϪC2ϪC4ϪC5 and kcal·mol^Ϫ1). As a result, bicyclo[3.1.0]hexanes 9a, exo,exo-

C2ϪC3ϪC4 vary from Ϫ35.0 to 39.9°, while that for the 18b, exo,endo-38b and exo,exo-38b adopt boat-like confor-

unsubstituted bicyclo[3.1.0]hexane was previously found to mations with quasi-equatorial orientations of the substitu-

be 25.2 Ϯ 2.8°.^[20b]Interestingly, in all the newly prepared ents at the 3-positions

substituted compounds, substituents on C3 occupy a quasi-

The packing of the studied molecules in the crystals dif-

equatorial position on the cyclopentane ring and the con- fers greatly from one to the other, but in all cases the most

figuration at C3 is therefore not crucial for the molecule to important short intermolecular interactions are of the type

achieve a rod-like shape (cf. endo,exo-18a and exo,exo-18b, CϪH···OϭC/NϵC, where the CH groups are either part of

Figure 2). However, the change of the substituent orien- an aromatic or a cyclopropyl ring. Interestingly, both types

tation on C6 from exo to endo as in exo,endo-38b is ac- of interaction exist simultaneously in all of the studied

companied by a change in the overall molecular shape from structures, which probably indicates similar strengths for

rod-like to horseshoe-like. The orientation of planar (aryl these attractive interactions.^[35]The molecules, linked by

or carboxyl) substituents on C6 is normal for alkyl- and these contacts, form herringbone-arranged ribbons in the

carboxyl-substituted cyclopropanes,^[31]and is either perpen- crystals of 9a, centrosymmetric dimers in 18a as well as in

dicular as in exo,endo-38b or bisected as in exo,exo-38b and 18b and layers in the crystals of both isomers of 38b.

carboxyl-substituted compounds.

In order to quantify the energetic effect of a 3-aryl sub-

stituent on the molecular shape in bicyclo[3.1.0]hexanes 9a,

endo,exo-18a, exo,exo-18b, exo,endo-38b, and exo,exo-38b,

the heats of formation of unsubstituted bicyclo[3.1.0]hex-

ane, endo-3-phenylbicyclo[3.1.0]hexane, and exo-3-phenyl-

bicyclo[3.1.0]hexane were calculated using the DFT method

(B3LYP)^[32]with the 6Ϫ31G** basis set. As found by vari-

ous computations before,^[21,33]bicyclo[3.1.0]hexane prefers

a boat-like over a chair-like conformation with ∆∆H ϭ

3.1Ϫ3.3 kcal·mol^Ϫ1, which is consistent with experimental

Liquid Crystalline Physical Properties of the New

Compounds

Phase transition temperatures, the dielectric anisotropies

(∆ε), birefringences (∆n), and bulk viscosities (η) of the

newly prepared bicyclo[3.1.0]hexanes exo,exo-9a, exo,exo-

21a,b,d,e, exo,exo-32, and exo,exo-38b (see Table 2) need to

be compared with data from the isomorphous liquid crys-

talline compounds 39Ϫ42 containing a 1,4-disubstituted

cyclohexane moiety.^[36,37]

results.^[20]For endo-3-phenylbicyclo[3.1.0]hexane (as

a

model for compound endo,exo-18a), the chair-like confor-

mation with a quasi-equatorial orientation of the phenyl

group was found to be lower in energy than the boat-like

conformation with a quasi-axial orientation of the phenyl

group but by ∆∆H ϭ 0.9 kcal·mol^Ϫ1only (Table 1). This

conformation was indeed observed for compound endo,exo-

18a in the crystal. Accordingly, the conformational energy

of a 3-phenyl substituent on bicyclo[3.1.0]hexane should be

at least 3.1 ϩ 0.9 ϭ 4.0 kcal·mol^Ϫ1: The eclipsing torsional

strain caused by the phenyl group in the boat conformation

overrides that in the chair conformation. Contrary to this,

in exo-3-phenylbicyclo[3.1.0]hexane (as a model for com-

pounds 9a, exo,exo-18b, exo,endo-38b and exo,exo-38b) the

molecule adopts a boat-like conformation with a quasi-

The comparison (Table 2) reveals that a bicyclo[3.1.0]hex-

equatorial orientation of the phenyl substituent and ∆∆H ϭ ane moiety, as a rule, decreases the clearing temperature

4.2 kcal·mol^Ϫ1. This must be attributable to the concerted (except for entry 7). The dielectric (∆ε) and optical (∆n)

action of two energetic factors namely the general prefer- anisotropies are comparable. However, the bicyclo[3.1.0]-

ence (by ca. 0.5Ϫ1.0 kcal·mol )

^{Ϫ1 [34]}of alkyl substituents on hexane moiety may induce a greater anisotropy of the pola-

Table 1. Total energies and heats of formation of bicyclo[3.1.0]hexane and its 3-phenyl derivatives calculated at the B3LYP/6Ϫ31G**

level of theory^[32]

Compound

Total Energy (Hartree)

chair

∆H_f° (kcal·mol^Ϫ1

)

boat

chair

Bicyclo[3.1.0]hexane

exo-3-Phenylbicyclo[3.1.0]hexane

endo-3-Phenylbicyclo[3.1.0]hexane

Ϫ234.498557

Ϫ465.474238

Ϫ465.468105

Ϫ234.493756

Ϫ465.467703

Ϫ465.469625

11.0

44.3

48.1

14.1

48.5

47.2

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Novel Liquid Crystalline Compounds

FULL PAPER

Table 2. Physical properties of the newly synthesized substances compared with those of the structurally analogous liquid crystalline

compounds 39Ϫ42

Entry

Compound

Phase-transition temperatures [°C]

∆ε

∆n

0.070^[a]

η [mPaS]

1

2

3

4

5

6

7

8

exo,exo-9a

39

exo,exo-21a

exo,exo-21b

exo,exo-21d

exo,exo-21e

40

exo,exo-32

41

exo,exo-38b

42

C 60.48 (N, 86.43) I

C 95.1 SA 131.1 (N, 155.3) I

C 18.5 SmB 107.9 I

C 12.8 I

0.5^[a]

Ϫ1.1^[a]

Ϫ

0.117^[a]

0.070^[b]

Ϫ0.090^[b]

0.090^[b]

0.117^[a]

0.124^[b]

0.020^[b]

0.074^[b]

0.124^[b]

0.118^[b]

[b]

0.3

1.4

23.3^[b]

16.5^[b]

52.0^[b]

61.3^[a]

44.3^[b]

Ϫ

[b]

[a]

[b]

C 30.1 I

10.1

Ϫ0.6

10.3

Ϫ3.46

Ϫ4.76

14.0

11.0

C 36.9 SmX 246.7 I

C 30.4 (N, 58.0) I

C Ͻ room temp. I

C 44.7 (N, 48.8) I

C 34.4 (N, 44.2) I

C 31 (N, 55) I

[b]

9

10

11

29.8^[b]

Ϫ

20.9^[b]

[b]

^[a]Extrapolated; 5% in the base nematic mixture Merck ZLI-1132. ^[b]Extrapolated; 15% in the base nematic mixture Merck ZLI-1132.

0.04 mmol, 0.25 mol %) in anhydrous dichloromethane (15 mL)

was added ethyl diazoacetate (1.79 g, 15.7 mmol) at ambient temp.

over a period of 12 h. The mixture was filtered through a pad of

alumina and concentrated under reduced pressure. The residue was

rizability, which tends to increase the ∆ε value according to

the equation of Maier and Meier^[38](entries 1,8,10). In

general, the bicyclo[3.1.0]hexane derivatives have a poorer

mesogenic potential than the isomorphous cyclohexane de-

rivatives.

1

essentially a 7:3 mixture of two diastereomers (according to its H

NMR spectrum). The main component was isolated by column

chromatography (170 g of silica gel, column 27 ϫ 4 cm, hexane/

Et₂O, 9:1) to give exo,exo-7 (2.52 g, 63%) as a colorless oil, R_fϭ

1

Experimental Section

0.30. H NMR: δ ϭ 1.20 (s, 9 H, 3 CH₃), 1.40 (t, J ϭ 7.0 Hz, 3 H,

CH₃), 1.45 (m, 1 H, CH), 1.80 (d, J ϭ 4.0 Hz, 2 H, 2 CH), 2.20 (d,

J ϭ 4.0 Hz, 4 H, 2 CH₂), 2.83 (quin, J ϭ 4.0 Hz, 1 H, CH), 4.15 (q,

J ϭ 7.0 Hz, 2 H, OCH₂) ppm. ¹³C NMR: δ ϭ 14.3 (CH₃) 23.6

(CH), 25.7 (3 CH₃), 27.0 (2 CH), 29.7 (2 CH₂), 44.1 (CH), 60.1

(CH₂), 79.9 (C), 171.7 (C), 175.3 (C) ppm. C₁₄H₂₂O₄(254.32):

calcd. C 66.11, H 8.72; found C 65.85, H 8.70.

General: NMR Spectra were recorded on a Bruker AM 250 instru-

ment (250 MHz for ¹H and 62.9 MHz for ¹³C NMR). Multiplicities

were determined by DEPT (Distortionless Enhancement by Polar-

ization Transfer) measurements. Chemical shifts refer to δ_TMS

ϭ

0.00 via the chemical shifts of residual CHCl₃signals. IR: Bruker

IFS 66 (FT-IR) spectrophotometer, measured as KBr pellets or oils

between KBr plates. MS (EI, 70 eV): Finnigan MAT 95 spec-

trometer. Melting points: Büchi 510 capillary melting point appa-

ratus, uncorrected values. TLC: MachereyϪNagel precoated sheets,

0.25 mm Sil G/UV₂₅₄. Column chromatography: Merck silica gel,

grade 60, 230Ϫ400 mesh. Transition temperatures: measured with

a polarizing microscope Nikon XTP-11 in conjunction with a

Mettler hot stage FP 82 and a control unit FP 80. The physical

properties of the synthesized liquid crystalline compounds were de-

termined using the following instruments and under the following

conditions: Dielectric anisotropies (∆ε) were measured at 25 °C

with a HewlettϪPackard 4284A LCR meter; birefringences (∆n)

exo,exo-Bicyclo[3.1.0]hexane-3,6-dicarboxylic Acid (exo,exo-8): To

a solution of diester exo,exo-7 (1.50 g, 5.90 mmol) in a 1:1 mixture

of MeOH and THF (25 mL) was added a solution of LiOH·H₂O

(1.47 g, 35 mmol) in H₂O (6 mL), and the resultant solution was

stirred at ambient temp. for 24 h. The reaction mixture was acidi-

fied to pH ഠ 3 with an aq. 1  solution of H₃PO₄and extracted

with Et₂O (4 ϫ 150 mL). The combined organic extracts were dried

and concentrated under reduced pressure to give crude exo,exo-8

(1.00 g, 100%) as a colorless solid which was used without purifi-

cation and characterization.

Bis(4-pentylphenyl) exo,exo-Bicyclo[3.1.0]hexane-3,6-dicarboxylate

(exo,exo-9a): To a stirred solution of diacid exo,exo-8 (368 mg,

2.16 mmol), 4-pentylphenol (710 mg, 4.33 mmol) and DMAP

(43 mg, 0.35 mmol, 8 mol %) in anhydrous DMF (2 mL) at 0 °C

was added DCC (1.037 g, 5.03 mmol), and the mixture was stirred

at ambient temp. for an additional 12 h. The mixture was taken up

in THF (50 mL), preadsorbed on silica gel (5 g) by evaporating of

all the volatiles, and purified by column chromatography (80 g of

silica gel, column 25 ϫ 3 cm, hexane/Et₂O, 3:1) to give exo,exo-9a

´

were measured at 25 °C with an Atago 4T & 2T Abbe refrac-

tometer; viscosities (µ) were determined at 20 °C with a Lauda

Viscoboy viscometer. Starting materials: tert-butyl cyclopent-3-ene-

1-carboxylate (6),^[12]PdCl₂(dppf),^[17]cyclopent-3-en-1-ol (13),^[18]

tert-butyl diazoacetate,^[19](cyclopenten-4-yl)methanol (23),^[39]and

(4-cyanophenyl)diazomethane (36b)^[28]were prepared according to

previously published procedures. All operations in anhydrous sol-

vents were performed under an argon atmosphere in flame-dried

glassware. Diethyl ether and THF were dried by distillation from

sodium benzophenone ketyl, pyridine and DMF from calcium hy-

dride, CH₂Cl₂and MeCN from P₂O₅. The appropriately substi-

tuted aryl halides, phenols and oligofluorinated compounds were

kindly supplied by the Chisso Petrochemical Corporation. All other

chemicals were used as commercially available. Organic extracts

were dried over MgSO₄.

1

(421 mg, 42%) as a colorless solid, m.p. 60Ϫ61 °C, R_fϭ 0.28. H

NMR: δ ϭ 0.90 (t, J ϭ 6.5 Hz, 6 H, 2 CH₃), 1.29Ϫ1.35 (m, 8 H, 4

CH₂), 1.45 (m, 1 H, CH), 1.55Ϫ1.67 (m, 4 H, 2 CH₂), 1.69Ϫ1.72

(m, 2 H, 2 CH), 2.25Ϫ2.45 (m, 4 H, 2 CH), 2.60 (t, J ϭ 8.0 Hz,

4 H, CH₂), 2.68Ϫ2.79 (m, 1 H, CH), 6.95Ϫ7.05 (m, 4 H, Ar-H),

7.14Ϫ7.23 (m, 4 H, Ar-H) ppm. ¹³C NMR: δ ϭ 14.0 (2 CH₃), 22.2

(CH), 22.5 (2 CH₂), 28.5 (2 CH), 31.1 (2 CH₂), 31.4 (2 CH₂), 31.5

(2 CH₂), 35.5 (2 CH₂), 39.5 (CH), 120.98 (2 CH), 121.15 (2 CH),

129.22 (2 CH), 129.27 (2 CH), 140.38 (C), 140.55 (C), 148.49 (C),

148.54 (C), 172.0 (C), 173.3 (C) ppm. MS (EI): m/z (%) ϭ 462 (22)

3-tert-Butyl

6-Ethyl

exo,exo-Bicyclo[3.1.0]hexane-3,6-dicar-

boxylate (exo,exo-7): To a stirred solution of tert-butyl cyclopent-3-

ene-1-carboxylate (6) (2.64 g, 15.7 mmol) and Rh₂(OAc)₄(0.0176 g,

Eur. J. Org. Chem. 2004, 289Ϫ303

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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

295

A. de Meijere et al.

[M^ϩ], 299 (100) [M^ϩϪ C₁₁H₁₅O], 164 (25), 107 (40). C₃₀H₃₈O₄light green or yellow, then to green or brown. The mixture was

FULL PAPER

(462.63): calcd. C 77.89, H 8.28; found C 78.15, H 7.92.

stirred for an additional 12 h at this temp., then poured into ice-

cold saturated aq. NH₄Cl solution (100 mL) and diluted with Et₂O

(100 mL). The organic phase was washed with 10% aq. NH₄Cl

solution, H₂O and brine (50 mL each), dried and concentrated un-

der reduced pressure. The residue was purified by column chroma-

tography.

Bis(4-propoxyphenyl)

exo,exo-Bicyclo[3.1.0]hexane-3,6-dicar-

boxylate (exo,exo-9b): Under the conditions of the previous experi-

ment, from diacid exo,exo-8 (300 mg, 1.76 mmol), 4-propoxy-

phenol (536 mg, 3.53 mmol), DCC (846 mg, 4.10 mmol), and

DMAP (43 mg, 0.35 mmol, 9.9 mol %) in anhydrous DMF (2 mL),

diester exo,exo-9b (356 mg, 46%) was obtained after column chro-

matography (80 g of silica gel, column 25 ϫ 3 cm, hexane/Et₂O,

3:1) as an oil, R_fϭ 0.25. IR (KBr): ν˜ ϭ 3110 cm^Ϫ1, 3067, 3046,

2968, 2940, 2880, 1743, 1592, 1505, 1310, 1243, 1192, 1144, 1016,

866, 770. ¹H NMR: δ ϭ 1.02 (t, J ϭ 7.5 Hz, 3 H, CH₃), 1.03 (t,

J ϭ 7.5 Hz, 3 H, CH₃), 1.69 (t, J ϭ 3.0 Hz, 1 H, CH), 1.72Ϫ1.86

(m, 6 H, 2 CH₂ϩ 2 CH), 2.16 (m, 2 H, CH₂), 2.22Ϫ2.49 (m, 2 H,

CH₂), 2.62Ϫ2.78 (quin, J ϭ 6.5 Hz, 1 H, CH), 3.82Ϫ3.93 (m, 4 H,

2 OCH₂), 6.68Ϫ7.05 (m, 8 H, Ar-H) ppm. ¹³C NMR: δ ϭ 10.4 (2

CH₃), 22.1 (CH), 22.5 (2 CH₂), 28.5 (2 C), 31.4 (2 CH₂), 39.4 (CH),

69.8 (CH₂), 70.2 (CH₂), 115.0 (2 CH), 115.5 (2 CH), 115.9 (2 CH),

122.0 (CH), 122.2 (CH), 143.8 (C), 143.9 (C), 153.2 (C), 156.8 (C),

172.3 (C), 173.6 (C) ppm. C₂₆H₃₀O₆(438.5): calcd. C 71.21, H 6.90;

found C 71.07, H 6.89.

1-(Cyclopenten-4-yl)-4-[(trans-4-pentyl)cyclohexyl]benzene

(17a):

From 4-[(trans-4-pentyl)cyclohexyl]phenyl bromide (16a) (5.73 g,

18.53 mmol), bromide 14 (6.81 g, 46.3 mmol), and PdCl₂(dppf)

(0.407 g, 0.56 mmol), compound 17a (4.10 g, 75%) was obtained

according to GP2 after column chromatography (300 g of silica gel,

column 40 ϫ 4.5 cm, hexane) as a colorless oil with m.p. ca. 10Ϫ12

1

°C, R_fϭ 0.53. H NMR: δ ϭ 0.98 (t, J ϭ 6.0 Hz, 3 H, CH₃), 1.14

(t, J ϭ 12.0 Hz, 2 H, CH₂cHex), 1.20Ϫ1.37 (m, 9 H), 1.54 (td,

J ϭ 2.8, 12.0, 2 H, CH₂cHex), 1.95 (m, 4 H, 2 CH₂cHex),

2.40Ϫ2.50 (m, 1 H, CH cHex), 2.51 (ddd, J ϭ 2.0, 8.8, 14.5 Hz, 2

H, CH₂cPent), 2.87 (dd, J ϭ 8.8, 14.5 Hz, 2 H, CH₂cPent), 3.51

(p, J ϭ 8.8 Hz, 1 H, CH cPent), 5.85 (br. s, 2 H, 2 ϭCH), 7.15 (d,

J ϭ 8.3 Hz, 2 H, Ar-H), 7.26 (d, J ϭ 8.3 Hz, 2 H, Ar-H) ppm. ¹³C

NMR: δ ϭ 14.1 (CH₃), 22.7 (CH₂), 26.7 (CH₂), 32.2 (CH₂), 33.6

(2 CH₂), 34.4 (2 CH₂), 37.3 (CH), 37.4, (CH₂), 42.9 (CH), 44.2

(CH), 44.3 (2 CH₂), 126.7 (2 CH), 126.8 (2 CH), 129.9 (2 CH),

144.6 (C), 145.3 (C) ppm. Bis(cyclopenten-4-yl) (0.683 g, R_fϭ 0.58,

oil) and 1,1Ј-bis{4-[(trans-4-pentyl)cyclohexyl]phenyl} (0.101 g,

R_fϭ 0.47, solid) were also isolated as by-products.

Preparation of Bromides 14 and 24, General Procedure 1 (GP1): To

a solution of triphenylphosphane (55.08 g, 210 mmol) in anhydrous

dichloromethane (250 mL) was added bromine (33.56 g, 10.82 mL,

210 mmol) at Ϫ30 to Ϫ15 °C over a period of 0.5 h under an argon

atmosphere. After an additional 15 min of stirring, a mixture of

the respective alcohol (200 mmol) and anhydrous pyridine

(200 mmol) was added dropwise at Ϫ15 °C over a period of 1 h,

and the mixture was stirred at 20 °C for an additional 12 h. After

this, volatile materials were ‘‘bulb-to-bulb’’ distilled, at first under

a water-aspirator vacuum and 30 °C oil bath temperature, and then

under further reduced pressure (0.1 Torr) with a 100 °C oil bath,

to a second flask which was cooled with acetone/dry ice. The distil-

lation was continued until the temperature in the first flask reached

80 °C. The receiver flask was allowed to warm to 20 °C, and the

solvent was removed by distillation at atmospheric pressure using

a 30 cm Vigreux column. The residue was distilled under reduced

pressure.

4-(3,4,5-Trifluorophenyl)cyclopentene (17b): From 1-bromo-3,4,5-

trifluorobenzene (16b) (4.22 g, 20 mmol), bromide 14 (7.35 g,

50 mmol), and PdCl₂(dppf) (0.439 g, 0.60 mmol), 17b (3.27 g, 82%)

was obtained according to GP2 after column chromatography

(300 g of silica gel, column 40 ϫ 4.5 cm, hexane) as a colorless oil,

1

R_fϭ 0.52. H NMR: δ ϭ 2.37 (ddd, J ϭ 2.0, 9.0, 14.5 Hz, 2 H,

CH₂), 2.82 (dd, J ϭ 6.7, 14.5 Hz, 2 H, CH₂), 3.39 (tt, J ϭ 6.7,

9.0 Hz, 1 H, CH), 5.76 (br. s, 2 H, 2 CH), 6.84 (ddd, J ϭ 4.5, 11.0,

13.5 Hz, 2 H, Ar-H) ppm. ¹³C NMR: δ ϭ 41.1 (2 CH₂), 43.1 (CH),

110.6 (ddd, J ϭ 6.4, 13.5, 20.3 Hz, 2 CH), 129.5 (2 CH), 151.0

(ddd, J ϭ 4.2, 9.9, 248.6 Hz, 2 C), 137.9 (dt, J ϭ 15.4, 247.8 Hz,

C), 143.9 (dt, J ϭ 4.5, 9.1 Hz, C) ppm. Bis(cyclopenten-4-yl)

(145 mg, R_f

ϭ 0.58, oil) and 1,1Ј-bis(3,4,5-trifluorophenyl)

4-Bromocyclopentene (14): From cyclopent-3-en-1-ol (13) (16.82 g,

200 mmol), triphenylphosphane (55.08 g, 210 mmol), bromine

(33.56 g, 10.82 mL, 210 mmol) and pyridine (15.82 g, 16.2 mL,

200 mmol), bromide 14 (26.44 g, 90%) was obtained according to

GP1 as a colorless liquid, b.p. 61 °C (92 mbar). The ¹H and ¹³C

NMR spectra of 14 were identical to those previously reported.^[40]

(202 mg, R_fϭ 0.35, solid) were also isolated as by-products.

4-[4-(3,4,5-Trifluorophenyl)phenyl]cyclopentene (17d): From 1-iodo-

4-(3,4,5-trifluorophenyl)benzene (16d) (5.74 g, 17.17 mmol), bro-

mide 14 (6.31 g, 42.9 mmol), and PdCl₂(dppf) (0.377 g, 0.52 mmol),

17d (4.17 g, 88%) was obtained according to GP2 after column

chromatography (250 g of silica gel, column 25 ϫ 6 cm, hexane) as

an oil with m.p. ca. 10 °C, R_fϭ 0.40. ¹H NMR: δ ϭ 2.50 (dd, J ϭ

7.0, 14.5 Hz, 2 H, CH₂), 2.90 (dd, J ϭ 9.0, 14.5 Hz, 2 H, CH₂),

3.54 (tt, J ϭ 7.0, 9.0 Hz, 1 H, CH), 5.84 (br. s, 2 H, 2 ϭCH), 7.19

(ddd, J ϭ 4.5, 6.5, 9.0 Hz, 2 H, Ar-H), 7.36 (d, J ϭ 8.3 Hz, 2 H,

Ar-H), 7.44 (d, J ϭ 8.3 Hz, 2 H, Ar-H) ppm. ¹³C NMR: δ ϭ 41.3

(2 CH₂), 42.7 (CH), 110.7 (ddd, J ϭ 7.1, 14.15, 21.2 Hz, 2 CH),

126.7 (2 CH), 126.8 (2 CH), 129.8 (2 CH), 135.7 (C), 137.1 (dt,

J ϭ 4.8, 7.9 Hz, C), 139.0 (dt, J ϭ 15.5, 251.2 Hz, C), 148.0 (C),

151.5 (ddd, J ϭ 4.3, 10.0, 249.1 Hz, 2 C) ppm.

4-(Bromomethyl)cyclopentene (24): From (cyclopenten-4-yl)me-

thanol (23) (41.61 g, 424 mmol), triphenylphosphane (116.77 g,

445 mmol), bromine (71.15 g, 22.9 mL, 445 mmol) and pyridine

(33.54 g, 34.3 mL, 424 mmol), bromide 24 (58.1 g, 85%) was ob-

tained according to GP1 as a colorless liquid, b.p. 83 °C (92 mbar).

The ¹H and ¹³C NMR spectra of 24 were identical to those pre-

viously reported.^[41]

General Procedure 2 (GP2) for the PdCl₂(dppf)-Catalyzed Cross

Coupling: A solution of (cyclopenten-4-yl)magnesium bromide (15)

freshly prepared from 4-bromocyclopentene (14) (45 mmol) and

magnesium (50 mmol) in anhydrous Et₂O (30 mL) was added via

a cannula in one portion to a mixture of the aryl halide 16

(18 mmol) and the catalyst (3 mol %) in anhydrous Et₂O (100 mL)

1-(Cyclopenten-4-yl)-4-{trans-4-[(trans-4-propyl)cyclohexyl]-

cyclohexyl}benzene (17e): From 4-[(trans-4-pentyl)cyclohexyl]-

phenyl iodide (16e) (5.50 g, 13.4 mmol), bromide 14 (4.40 g,

at ambient temp. Upon coupling of the aryl bromides, the initial 29.9 mmol), and PdCl₂(dppf) (0.263 g, 0.36 mmol), 17e (4.61 g,

orange color rapidly changed to yellow after 10 min of stirring,

then to green or brown. In the case of iodides, the reactions were

slightly exothermic, and the initial deep green color changed to

98%) was obtained according to GP2 after column chromatography

(250 g of silica gel, column 25 ϫ 6 cm, hexane) as a colorless solid,

m.p. 186Ϫ187 °C (MeOH), R_fϭ 0.46. IR (KBr): ν˜ ϭ 2957 cm^Ϫ1

,

296

 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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Eur. J. Org. Chem. 2004, 289Ϫ303

Novel Liquid Crystalline Compounds

FULL PAPER

2850, 1623, 1514, 1445, 1255, 1147, 978, 892, 820, 755, 697. ¹H

4.87 g (62%) of a non-separable mixture of two isomeric cycload-

NMR: δ ϭ 0.97 (t, J ϭ 7.0 Hz, 3 H, CH₃), 1.05Ϫ1.15 (m, 2 H, ducts exo,exo-18b and endo,exo-18b in a ratio of ca. 3:1 with R_fϭ

CH₂cHex), 1.20Ϫ1.30 (m, 6 H), 1.33Ϫ1.54 (m, 6 H), 1.85Ϫ2.03 0.31. The major component was formed in 47% yield as determined

(m, 9 H), 2.40Ϫ2.50 (m, 1 H, CH cHex), 2.53 (dd, J ϭ 7.9, 14.0 Hz, by ¹H NMR spectroscopy. After crystallization from methanol, ex-

2 H, CH₂cPent), 2.88 (dd, J ϭ 7.9, 14.0 Hz, 2 H, CH₂cPent), 3.52

o,exo-18b was obtained in pure form as colorless crystals (2.46 g,

(p, J ϭ 7.9 Hz, 1 H, CH cPent), 5.85 (br. s, 2 H, 2 ϭCH), 7.21 (d, 31%), m.p. 88 °C. After evaporation of the mother liquor, the re-

J ϭ 8.3 Hz, 2 H, Ar-H), 7.26 (d, J ϭ 8.3 Hz, 2 H, Ar-H) ppm. ¹³C maining oil (2.22 g) which consisted of these two diastereomers in

NMR: δ ϭ 14.5 (CH₃), 20.1 (CH₂), 30.1 (2 CH₂), 30.4 (2 CH₂),

a ratio of 1:2 was crystallized from MeOH again at Ϫ20 °C. This

33.6 (2 CH₂), 34.7 (2 CH₂), 37.6 (CH), 39.9 (CH₂), 41.3 (2 CH₂), procedure yielded an additional 0.610 g of exo,exo-18b; total yield

42.9 (CH), 43.0 (CH), 43.4 (CH), 44.2 (CH), 126.8 (2 CH), 126.9 39%. IR (KBr): ν˜ ϭ 3051 cm^Ϫ1, 2957, 2923, 2861, 1709, 1622, 1533,

(2 CH), 129.9 (2 CH), 144.7 (C), 145.4 (C) ppm. C₂₆H₃₈(350.56):

calcd. C 89.07, H 10.93; found C 89.02, H 10.80.

1404, 1368, 1321, 1151, 1036, 832, 692. ¹H NMR: δ ϭ 1.44 (s, 9

H, 3 CH₃), 1.54 (t, J ϭ 2.3 Hz, 1 H, CH cPr), 1.80 (dd, J ϭ 3.0,

12.3 Hz, 2 H, CH₂), 1.90 (m, 2 H, 2 CH cycloprop.), 2.23 (dd, J ϭ

7.3, 12.3 Hz, 2 H, CH₂), 2.63 (tt, J ϭ 7.3, 10.4 Hz, 1 H, CH), 6.76

(dd, J ϭ 6.5, 9.0 Hz, 2 H, Ar-H) ppm. ¹³C NMR: δ ϭ 23.0 (CH),

27.3 (2 CH), 28.1 (3 CH₃), 35.5 (2 CH₂), 39.5 (CH), 80.27 (C),

111.0 (ddd, J ϭ 6.8, 13.6, 20.4 Hz, 2 CH), 138.1 (dt, J ϭ 15.4,

264.2 Hz, C), 140.3 (dt, J ϭ 4.6, 6.7 Hz, C), 151.1 (ddd, J ϭ 4.5,

9.6, 250.0 Hz, 2 C), 172.7 (C) ppm. C₁₇H₁₉F₃O₂(312.32): calcd. C

65.37, H 6.13; found C 65.22, H 6.09. The configuration of this

compound has been determined by an X-ray crystal structure

analysis.

General Procedure 3 (GP3) for the [Rh(C₇H₁₅COO)₂]₂Catalyzed

Cyclopropanation of Cyclopentenes 17 with tert-Butyl Diazoacetate:

To a stirred solution of the respective cyclopentene 17 (25 mmol)

and dirhodium tetraoctanoate (0.5 mol %) in anhydrous dichloro-

methane (100 mL) was added tert-butyl diazoacetate (37.5 mmol)

at 0 to ϩ5 °C over a period of 12 h. After evaporation of the sol-

vent under reduced pressure, the residue was separated by column

chromatography. Since the compounds 18d,e are not soluble en-

ough in the eluting solvent mixture, they were pre-absorbed on sil-

ica gel (20 g) from dichloromethane before chromatography.

tert-Butyl exo,exo-3-[4-(3,4,5-Trifluorophenyl)phenyl]bicyclo[3.1.0]-

pentane-6-carboxylate (exo,exo-18d): Column chromatography

(450 g of silica gel, column 40 ϫ 5.6 cm, hexane/Et₂O, 10:1) of

the reaction mixture obtained from the cyclopentene 17d (4.07 g,

14.8 mmol), N₂CHCO₂tBu (3.51 g, 3.42 mL, 24.69 mmol) and

[Rh(C₇H₁₅COO)₂]₂(0.064 g, 0.082 mmol) according to GP3 gave a

non-separable mixture of the two isomers exo,exo-18d and endo,-

exo-18d with R_fϭ 0.30 which was recrystallized from MeOH/

CHCl₃(15:1) to give 2.07 g (36%) of exo,exo-18d as colorless crys-

tals, m.p. 150Ϫ151 °C. After evaporation of the mother liquor, the

residue was recrystallized again to give an additional 0.606 g of

tert-Butyl 3-{[4-(trans-4-pentyl)cyclohexyl]phenyl}bicyclo[3.1.0]-

hexane-6-carboxylates (exo,exo-18a and endo,exo-18a): Column

chromatography (350 g of silica gel, column 45 ϫ 4.5 cm, hexane/

Et₂O, 15:1) of the reaction mixture prepared from the cyclopentene

17a (4.10 g, 13.8 mmol), N₂CHCO₂tBu (2.95 g, 2.87 mL,

20.75 mmol) and [Rh(C₇H₁₅COO)₂]₂(0.054 g, 0.07 mmol) accord-

ing to GP3 yielded the two cycloadducts exo,exo-18a (2.73 g, 48%)

and endo,exo-18a (2.17 g, 38%) with R_fϭ 0.45 and 0.43, respec-

tively.

exo,exo-18a: Colorless crystals, m.p. 113Ϫ115 °C (MeOH). ¹H

NMR: δ ϭ 0.92 (t, J ϭ 6.8 Hz, 3 H, CH₃), 1.08 (t, J ϭ 12.0 Hz, 2

H, CH₂cHex), 1.10Ϫ1.31 (m, 10 H), 1.48 (s, 9 H, 3 CH₃), 1.62 (br.

s, 1 H, CH cPr), 1.95Ϫ2.05 (m, 9 H), 2.25 (dd, J ϭ 7.3, 12.5 Hz, 2

H, CH₂cPent), 2.45 (tt, J ϭ 2.6, 12.3 Hz, 1 H, CH₂cHex), 2.70

(tt, J ϭ 6.7, 8.9 Hz, 1 H, CH cPent), 7.13 (br. s, 4 H, Ar-H) ppm.

¹³C NMR: δ ϭ 14.1 (CH₃), 22.7 (CH₂), 23.0 (CH), 26.6 (CH₂),

27.8 (2 CH), 28.1 (3 CH₃), 32.2 (CH₂), 33.6 (2 CH₂), 34.3 (2 CH₂),

35.7 (2 CH₂), 37.2 (CH), 37.4 (CH₂), 39.6 (CH), 44.1 (CH), 79.9

(C), 126.7 (2 CH), 127.0 (2 CH), 141.1 (C), 145.7 (C), 173.1 (C)

ppm.

1

exo,exo-18d; total yield 46%. H NMR: δ ϭ 1.47 (s, 9 H, 3 CH₃),

1.62 (t, J ϭ 2.2 Hz, 1 H, CH cPr), 1.85Ϫ2.08 (m, 4 H, 2 CH cPr

ϩ CH₂), 2.28 (dd, J ϭ 7.3, 12.5 Hz, 2 H, CH₂), 2.75 (tt, J ϭ 7.3,

10.3 Hz, 1 H, CH), 7.17 (dd, J ϭ 6.5, 9.0 Hz, 2 H, Ar-H), 7.27 (d,

J ϭ 8.3 Hz, 2 H, Ar-H), 7.41 (d, J ϭ 8.3 Hz, 2 H, Ar-H) ppm. ¹³C

NMR: δ ϭ 23.1 (CH), 27.7 (2 CH), 28.2 (3 CH₃), 35.7 (2 CH₂),

39.7 (CH), 80.3 (C), 111.7 (ddd, J ϭ 7.1, 14.3, 21.3 Hz, 2 CH),

126.8 (2 CH), 127.9 (2 CH), 136.1 (C), 137.1 (dt, J ϭ 4.6, 6.7 Hz,

C), 139.1 (dt, J ϭ 23.8, 251.5 Hz, C), 144.3 (C), 151.3 (ddd, J ϭ 4.5,

10.3, 259.1 Hz, 2 C), 173.0 (C) ppm. C₂₃H₂₃F₃O₂(388.41): calcd. C

71.12, H 5.97; found C 70.88, H 6.03.

endo,exo-18a: Colorless crystals, m.p. 68Ϫ70 °C (MeOH). ¹H

NMR: δ ϭ 0.88 (t, J ϭ 6.8 Hz, 3 H, CH₃), 1.05 (t, J ϭ 12.0 Hz, 2

H, CH₂cHex), 1.10Ϫ1.31 (m, 9 H), 1.42 (t, J ϭ 6.5 Hz, 2 H), 1.49

(s, 9 H, 3 CH₃), 1.60 (br. s, 1 H, CH cPr), 1.75 (dd, J ϭ 2.0, 5.6 Hz,

2 H), 1.85 (dm, ϭ 9.5 Hz, 4 H), 1.95 (tt, J ϭ 2.4, 7.2 Hz, 2 H),

2.38 (dd, J ϭ 8.0, 13.2 Hz, 2 H, CH₂cPent), 2.40Ϫ2.55 (m, 1 H.),

2.89 (tt, J ϭ 6.5, 8.0 Hz, 1 H, CH cPent), 7.11 (br. s, 4 H, Ar-H)

ppm. ¹³C NMR: δ ϭ 14.1 (CH₃), 22.6 (CH₂), 23.5 (CH), 26.6

(CH₂), 27.9 (3 CH₃), 28.1 (2 CH), 32.1 (CH₂), 33.6 (2 CH₂), 34.3

(2 CH₂), 35.0 (2 CH₂), 37.3 (CH), 37.4 (CH₂), 41.8 (CH), 44.1

(CH), 80.2 (C), 126.7 (2 CH), 127.0 (2 CH), 143.0 (C), 145.4 (C),

170.7 (C). The structure of this compound was confirmed by a

single crystal X-ray diffraction study.

tert-Butyl exo,exo-3-{[trans-4-(trans-4-propylcyclohexyl)cyclohexyl]-

phenyl}bicyclo[3.1.0]hexane-6-carboxylate (exo,exo-18e): Column

chromatography (350 g of silica gel, column 45 ϫ 4.5 cm, hexane/

Et₂O, 15:1) of the reaction mixture obtained from the cyclopentene

17e (4.31 g, 12.3 mmol), N₂CHCO₂tBu (2.62 g, 2.55 mL,

18.44 mmol) and [Rh(C₇H₁₅COO)₂]₂(0.049 g, 0.06 mmol) accord-

ing to GP3 gave some recovered starting material 17e (0.889 g,

21%, R_fϭ 0.73) and the crudely separated cycloadducts endo,exo-

18e (1.52 g, 27%) and exo,exo-18e with R_fϭ 0.39 and 0.44, respec-

tively. After recrystallization from MeOH/CHCl₃(10:1), 2.68 g

(47%) of pure exo,exo-18e was obtained as colorless crystals, m.p.

281Ϫ283 °C (dec.). IR (KBr): ν˜ ϭ 3048 cm^Ϫ1, 3007, 2927, 2846,

1709, 1450, 1410, 1157, 1062, 840, 557. ¹H NMR: δ ϭ 0.88 (t, J ϭ

7.1 Hz, 3 H, CH₃), 0.97Ϫ1.18 (m, 8 H), 1.27Ϫ1.42 (m, 2 H), 1.45

(s, 9 H, 3 CH₃), 1.63 (br. s, 1 H, CH cPr), 1.73Ϫ1.97 (m, 16 H),

tert-Butyl exo,exo-3-(3,4,5-trifluorophenyl)bicyclo[3.1.0]hexane-6-

carboxylate (exo,exo-18b): Column chromatography (350 g of silica

gel, column 45 ϫ 4.5 cm, hexane/Et₂O, 20:1) of the reaction mix-

ture obtained from the cyclopentene 17b (4.99 g, 25.2 mmol), 2.23 (dd, J ϭ 7.0, 12.3 Hz, 2 H, CH₂cPent), 2.41 (tt, J ϭ 2.6,

N₂CHCO₂tBu (5.37 g, 5.24 mL, 37.8 mmol) and 12.0 Hz, 2 H, CH₂cHex), 2.67 (tt, J ϭ 7.0, 9.4 Hz, 1 H, CH cPent),

[Rh(C₇H₁₅COO)₂]₂(0.098 g, 0.13 mmol) according to GP3 gave

7.11 (br. s, 4 H, Ar-H) ppm. ¹³C NMR: δ ϭ 10.3 (2 CH₂), 14.4

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297

A. de Meijere et al.

FULL PAPER

(CH₃), 20.0 (CH₂), 23.0 (CH), 27.8 (2 CH), 28.2 (3 CH₃), 30.1 (2

exo,exo{3-[4-(3,4,5-Trifluorophenyl)phenyl]bicyclo[3.1.0]hex-6-

CH₂), 33.6 (2 CH₂), 34.6 (2 CH₂), 35.8 (2 CH₂), 37.6 (CH), 39.6 yl}methanol (exo,exo-19d): From the ester 18d (2.45 g, 6.31 mmol),

(CH), 39.8 (CH₂), 42.9 (CH), 43.4 (CH), 44.2 (CH), 80.0 (C), 126.7 the alcohol exo,exo-19d (2.00 g, 100%) was obtained according to

(2 CH), 127.1 (2 CH), 141.1 (C), 145.8 (C), 173.3 (C) ppm. GP4 as a colorless solid, m.p. 78Ϫ80 °C (hexane). IR (KBr): ν˜ ϭ

C₃₂H₄₈O₂(464.7): calcd. C 82.70, H 10.41; found C 82.53, H 10.19.

3300 cm^Ϫ1, 3087, 3025, 2995, 2945, 2930, 2859, 1615, 1539, 1510,

1443, 1403, 1363, 1250, 1120, 1048, 946, 866, 828, 767, 702, 539.

¹H NMR: δ ϭ 1.22 (tt, J ϭ 3.3, 7.0 Hz, 1 H, CH cPr), 1.35 (m, 2

H, 2 CH cPr), 1.89 (ddd, J ϭ 2.8, 11.0, 12.8 Hz, 2 H, CH₂), 2.06

(s, 1 H, OH), 2.22 (dd, J ϭ 7.5, 12.8 Hz, 2 H, CH₂), 2.79 (tt, J ϭ

7.5, 11.0 Hz, 1 H, CH), 3.48 (d, J ϭ 7.0 Hz, 2 H, CH₂O), 7.14 (dd,

J ϭ 6.5, 8.8 Hz, 2 H, Ar-H), 7.27 (d, J ϭ 8.3 Hz, 2 H, Ar-H), 7.40

(d, J ϭ 8.3 Hz, 2 H, Ar-H) ppm. ¹³C NMR: δ ϭ 22.2 (2 CH), 22.3

(CH), 35.7 (2 CH₂), 40.3 (CH), 65.7 (CH₂), 110.6 (ddd, J ϭ 7.1,

14.1, 21.3 Hz, 2 CH), 126.6 (2 CH), 127.9 (2 CH), 135.8 (C), 137.1

(dt, J ϭ 4.6, 7.8 Hz, C), 138.9 (dt, J ϭ 15.4, 251.4 Hz, C), 144.9

(C), 151.3 (ddd, J ϭ 4.4, 10.1, 249.2 Hz, 2 C) ppm. C₁₉H₁₇F₃O

(318.33): calcd. C 71.68, H 5.38; found C 71.51, H 5.11.

tert-Butyl exo,exo-3-[2-(4-Ethoxy-2,3-difluorophenyl)ethyl]bicyclo-

[3.1.0]hexane-6-carboxylate (exo,exo-30): Column chromatography

(100 g of silica gel, column 30 ϫ 3 cm, hexane/Et₂O, 10:1) of the

reaction mixture obtained from the cyclopentene 29 (0.692 g,

2.74 mmol), N₂CHCO₂tBu (0.974 g, 0.95 mL, 6.85 mmol) and

[Rh(C₇H₁₅COO)₂]₂(0.0107 g, 0.014 mmol) according to GP3 gave

1

exo,exo-30 (0.654 g, 65%) as a colorless oil, R_fϭ 0.23. H NMR:

δ ϭ 1.41 (t, J ϭ 7.0 Hz, 3 H, CH₃), 1.47 (s, 9 H, 3 CH₃), 1.50 (t,

J ϭ 2.5 Hz, 1 H, CH cPr), 1.55Ϫ1.70 (m, 2 H, CH₂), 1.85 (dd, J ϭ

2.5, 12.3 Hz, 2 H, CH₂), 1.90 (m, 2 H, 2 CH cPr), 2.23 (dd, J ϭ

7.3, 12.3 Hz, 2 H, CH₂), 2.42Ϫ2.51 (m, 3 H, CH₂, CH), 4.05 (q,

J ϭ 7.0 Hz, 2 H, OCH₂), 6.59 (dd, J ϭ 7.0, 7.6 Hz, 1 H, Ar-H),

6.72 (dd, J ϭ 7.6, 8.5 Hz, 1 H, Ar-H) ppm. ¹³C NMR: δ ϭ 14.7

(CH₃), 23.3 (CH), 27.6 (CH₂), 27.9 (2 CH), 28.0 (3 CH₃), 34.1 (2

CH₂), 35.0 (CH₂), 40.7 (CH), 65.3 (CH₂), 79.8 (C), 109.2 (CH),

123.0 (dd, J ϭ 4.5, 10.6 Hz, CH), 123.4 (d, J ϭ 5.1 Hz, C), 140.1

(dd, J ϭ 12.8, 251.0 Hz, C), 142.7 (dd, J ϭ 3.5, 9.2 Hz, C), 151.1

(dd, J ϭ 10.8, 250.0 Hz, C), 173.1 (C) ppm. C₂₁H₂₈F₂O₃(366.4):

calcd. C 68.82, H 7.70; found C 68.60, H 7.85.

exo,exo-(3-{[trans-4-(trans-4-Propylcyclohexyl)cyclohexyl]phenyl}-

bicyclo[3.1.0]hex-6-yl)methanol (exo,exo-19e): From the ester 18e

(2.68 g, 5.76 mmol), the alcohol exo,exo-19e (2.26 g, 100%) was ob-

tained according to GP4 as a colorless solid, m.p. 259Ϫ260 °C

(dec.) (hexane). IR (KBr): ν˜ ϭ 3325 cm^Ϫ1, 3018, 2958, 2847, 1515,

1445, 1119, 1062, 1020, 943, 895, 824, 559. ¹H NMR: δ ϭ 0.78 (m,

1 H, CH cPr), 0.89 (t, J ϭ 7.1 Hz, 3 H, CH₃), 1.03Ϫ1.61 (m, 8 H),

1.30Ϫ1.57 (m, 6 H), 1.73 (dd, J ϭ 7.8, 13.5 Hz, 1 H), 1.68 (s, 1 H,

OH), 1.73Ϫ1.95 (m, 11 H), 2.19 (dd, J ϭ 7.5, 12.5 Hz, 2 H, CH₂),

2.42 (tq, J ϭ 3.3, 11.9 Hz, 2 H), 2.72 (tt, J ϭ 7.5, 11.3 Hz, 1 H,

CH), 3.46 (d, J ϭ 7.3 Hz, 2 H, CH₂O), 7.13 (br. s, 4 H, Ar-H)

ppm. ¹³C NMR: δ ϭ 14.4 (CH₃), 20.0 (CH₂), 22.2 (2 CH), 22.3

(CH), 30.0 (2 CH₂), 30.3 (2 CH₂), 33.6 (2 CH₂), 34.6 (2 CH₂), 35.8

(2 CH₂), 37.6 (CH), 39.8 (CH₂), 40.3 (CH), 42.8 (CH), 43.4 (CH),

44.1 (CH), 66.0 (CH₂), 126.7 (2 CH), 127.1 (2 CH), 141.7 (C), 145.6

(C) ppm. C₂₈H₄₂O (394.62): calcd. C 85.22, H 10.73; found C

85.04, H 10.48.

General Procedure 4 (GP4) for the Reduction of tert-Butyl Esters

18: To a stirred solution of the respective tert-butyl ester 18

(10 mmol) in anhydrous diethyl ether (80 mL) was added LiAlH₄

(6.4 mL of a 1.17  solution in Et₂O, 7.5 mmol) at ambient tem-

perature over a period of 20 min. After this, the reaction mixture

was stirred at 34 °C for 1 h, cooled to 10 °C, quenched with a

saturated aq. solution of Na₂SO₄(1 mL), dried and concentrated

under reduced pressure. The resultant alcohols 19 were used with-

out further purification.

exo,exo{3-[4-(trans-4-Pentylcyclohexyl)phenyl]bicyclo[3.1.0]hex-6-

yl}methanol (exo,exo-19a): From the ester 18a (2.17 g, 5.29 mmol),

the alcohol exo,exo-19a (1.80 g, 100%) was obtained according to

GP4 as a colorless solid, m.p. 141 °C (hexane). IR (KBr): ν˜ ϭ 3325

cm^Ϫ1, 3017, 2957, 2931, 2851, 1514, 1465, 1443, 1415, 1368, 1289,

1264, 1237, 1208, 1117, 1062, 1022, 997, 943, 895, 827, 768, 725,

General Procedure 5 (GP5) for the Conversion of the Alcohols 19,

23 to Iodides 20, 33: To a stirred solution of the respective alcohol

19, 23 (4 mmol), imidazole (5.5 mmol), and Ph₃P (5.2 mmol) in a

mixture of anhydrous MeCN (30 mL) and anhydrous Et₂O (50 mL;

since the solubility of the alcohols 19a,e in this mixture was not

sufficient, anhydrous THF (20 mL) was also added in these two

cases) was added iodine (6.0 mmol) in one portion at Ϫ10 °C under

argon in the dark. After stirring at 0 °C for an additional 30 min,

the reaction mixture was diluted with Et₂O (100 mL) and washed

successively with saturated aq. Na₂S₂O₃solution (50 mL) and brine

(100 mL), then dried and concentrated under reduced pressure in

the dark. The residue was taken up with CH₂Cl₂(minimal quantity,

5Ϫ35 mL) and purified by column chromatography.

1

663, 556. H NMR: δ ϭ 0.91 (t, J ϭ 6.9 Hz, 3 H, CH₃), 1.04 (dq,

J ϭ 3.0, 12.3 Hz, 2 H), 1.17Ϫ1.34 (m, 8 H), 1.40 (pd, ϭ 3.0,

13.5 Hz, 4 H), 1.73 (dd, J ϭ 7.8, 13.5 Hz, 1 H), 1.83Ϫ1.91 (m, 7 H),

2.19 (dd, J ϭ 7.5, 12.5 Hz, 2 H, CH₂), 2.43 (tq, J ϭ 3.3, 12.5 Hz, 2

H), 2.72 (tt, J ϭ 7.4, 10.1 Hz, 1 H, CH), 3.46 (d, J ϭ 7.0 Hz, 2 H,

CH₂O), 7.13 (br. s, 4 H, Ar-H) ppm. ¹³C NMR: δ ϭ 14.1 (CH₃),

22.3 (2 CH), 22.4 (CH), 22.7 (CH₂), 26.7 (CH₂), 32.2 (CH₂), 33.6

(2 CH₂), 34.4 (2 CH₂), 35.8 (2 CH₂), 37.3 (CH), 37.4 (CH₂), 40.3

(CH), 44.1 (CH), 66.0 (CH₂), 126.7 (2 CH), 127.1 (2 CH), 141.7

(C), 145.6 (C) ppm. C₂₄H₃₆O (340.53): calcd. C 84.64, H 10.66;

found C 84.90, H 10.55.

exo,exo-6-Iodomethyl-3-[4-(trans-4-pentylcyclohexyl)phenyl]-

bicyclo[3.1.0]hexane (exo,exo-20a): Column chromatography (50 g

of silica gel, column 20 ϫ 3 cm, hexane/Et₂O, 5:1) of the reaction

mixture obtained from the alcohol exo,exo-19a (1.76 g, 5.17 mmol),

Im-H (482 mg, 7.08 mmol), Ph₃P (1.76 g, 6.71 mmol), and I₂

exo,exo{3-(3,4,5-Trifluorophenyl)bicyclo[3.1.0]hex-6-yl}methanol

(exo,exo-19b): From the ester 18b (2.42 g, 7.75 mmol), the alcohol

exo,exo-19b (1.87 g, 100%) was obtained according to GP4 as a (1.97 g, 7.75 mmol) according to GP5 gave the iodide exo,exo-20a

colorless solid, m.p. 40 °C. ¹H NMR: δ ϭ 1.09 (tt, J ϭ 3.3, 7.0 Hz, (2.28 g, 98%) as a colorless solid, m.p. 96Ϫ97 °C (hexane-MeOH),

1

1 H, CH cPr), 1.21Ϫ1.31 (m, 2 H, 2 CH cPr), 1.73 (ddd, J ϭ 3.8, R_fϭ 0.54. H NMR: δ ϭ 0.9 (t, J ϭ 6.6 Hz, 3 H, CH₃), 1.05 (t,

11.0, 12.5 Hz, 2 H, CH₂), 2.14 (dd, J ϭ 7.5, 12.5 Hz, 2 H, CH₂),

J ϭ 11.3 Hz, 2 H), 1.18Ϫ1.45 (m, 15 H), 1.71Ϫ1.81 (m, 1 H, CH),

2.44 (s, 1 H, OH), 2.63 (tt, J ϭ 7.5, 11.0 Hz, 1 H, CH), 3.40 (d, 1.85 (dd, J ϭ 8.0, 8.5 Hz, 4 H, 2 CH₂), 2.17 (dd, J ϭ 7.5, 12.5 Hz,

J ϭ 7.0 Hz, 2 H, CH₂O), 6.73 (dd, J ϭ 6.8, 9.0 Hz, 2 H, Ar-H)

2 H, CH₂), 2.42 (tt, J ϭ 3.1, 10.5 Hz, 1 H, CH), 2.70 (tt, J ϭ 7.5,

ppm. ¹³C NMR: δ ϭ 21.9 (2 CH), 22.1 (CH), 35.4 (2 CH₂), 40.0 11.2 Hz, 1 H, CH), 3.14 (d, J ϭ 7.5 Hz, 2 H, CH₂I), 7.09 (d, J ϭ

(CH), 65.3 (CH₂), 110.9 (ddd, J ϭ 6.7, 13.8, 20.4 Hz, 2 CH), 137.7 7.5 Hz, 2 H, Ar-H), 7.13 (d, J ϭ 7.5 Hz, 2 H, Ar-H) ppm. ¹³C

(dt, J ϭ 15.4, 250.0 Hz, C), 140.3 (dt, J ϭ 6.9, 11.3 Hz, C), 150.8

(ddd, J ϭ 4.1, 9.8, 248.7 Hz, 2 C) ppm.

NMR: δ ϭ 12.4 (CH₂), 14.1 (CH₃), 22.7 (CH₂), 24.5 (CH), 26.6

(CH₂), 30.6 (2 CH), 32.2 (CH₂), 33.6 (2 CH₂), 34.4 (2 CH₂), 36.2

298

 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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Novel Liquid Crystalline Compounds

FULL PAPER

(2 CH₂), 37.3 (CH), 37.4 (CH₂), 40.2 (CH), 44.1 (CH), 126.7 (2 LiAlH₄(4.60 mL of a 1.17  solution in Et₂O, 5.38 mmol) accord-

CH), 127.1 (2 CH), 141.4 (C), 145.7 (C) ppm. MS (EI): m/z (%) ϭ ing to GP4 to give 2.02 g (100%) of crude (4-ethoxy-2,3-difluoroph-

450 (8) [M^ϩ], 323 (100) [M^ϩϪ I]. HRMS (EI): calcd. for C₂₄H₃₅I

enyl)methanol. The latter was treated with Im-H (1.04 g,

15.27 mmol), Ph₃P (3.792 g, 14.46 mmol), and I₂(4.22 g,

16.7 mmol) according to GP5. The residue was vigorously stirred

with Et₂O (150 mL), filtered through a 3 cm pad of silica gel and

concentrated under reduced pressure to give the iodide 27 (3.04 g,

95%) as a colorless solid which contained some Ph₃PO impurity,

m.p. 89Ϫ92 °C, R_f(hexane/Et₂O, 10:1) ϭ 0.43. The iodide 27 was

used without further purification. ¹H NMR: δ ϭ 1.45 (t, J ϭ

7.0 Hz, 3 H, CH₃), 4.10 (q, J ϭ 7.0 Hz, 2 H, OCH₂), 4.41 (s, 2 H,

CH₂I), 6.65 (ddd, J ϭ 1.8, 7.3, 8.5 Hz, 1 H, Ar-H), 7.02 (ddd, J ϭ

2.2, 8.5, 9.0 Hz, 1 H, Ar-H) ppm. ¹³C NMR: δ ϭ 14.7 (CH₃), 65.2

(CH₂), 109.4 (CH), 123.4 (d, J ϭ 5.0 Hz, C), 124.0 (d, J ϭ 8.3 Hz,

CH), 140.8 (dd, J ϭ 14.1, 246.3 Hz, C), 146.8 (dd, J ϭ 3.0, 9.4 Hz,

C), 149.7 (dd, J ϭ 10.5, 247.1 Hz, C) ppm.

[M^ϩ] 450.1783, found 450.1783.

exo,exo-6-Iodomethyl-3-(3,4,5-trifluorophenyl)bicyclo[3.1.0]hexane

(exo,exo-20b): Column chromatography (80 g of silica gel, column

30 ϫ 3 cm, hexane/Et₂O, 5:1) of the reaction mixture obtained from

the alcohol exo,exo-19b (1.88 g, 7.76 mmol), Im-H (0.723 g,

10.62 mmol), Ph₃P (2.64 g, 10.08 mmol), and I₂(2.95 g,

11.61 mmol) according to GP5 gave the iodide exo,exo-20b (2.66 g,

98%) as a colorless oil, R_fϭ 0.60. ¹H NMR: δ ϭ 1.32 (tt, J ϭ 3.0,

7.5 Hz, 1 H, CH cPr), 1.33Ϫ1.36 (m, 2 H, 2 CH cPr), 1.72 (ddd,

J ϭ 3.0, 11.0, 12.8 Hz, 2 H, CH₂), 2.17 (dd, J ϭ 7.5, 12.8 Hz, 2 H,

CH₂), 2.65 (tt, J ϭ 7.5, 11.0 Hz, 1 H, CH), 3.11 (d, J ϭ 7.5 Hz, 2

H, CH₂I), 6.77 (ddd, J ϭ 3.2, 4.0, 8.8 Hz, 2 H, Ar-H) ppm. ¹³C

NMR: δ ϭ 11.5 (CH₂), 24.4 (CH), 30.1 (2 CH), 35.8 (2 CH₂), 39.9

(CH), 111.0 (ddd, J ϭ 6.6, 13.7, 20.4 Hz, 2 CH), 137.9 (dt, J ϭ

15.4, 249.1 Hz, C), 140.4 (dt, J ϭ 4.5, 11.3 Hz, C), 150.9 (ddd, J ϭ

4.3, 9.9, 249.0 Hz, 2 C) ppm. MS (EI): m/z (%) ϭ 352 (10) [M^ϩ],

225 (100) [M^ϩϪ I]. HRMS (EI): calcd. for C₁₃H₁₂F₃I [M^ϩ]

351.9936, found 351.9936. C₁₃H₁₂F₃I (352.13): calcd. C 44.34, H

3.44, I 36.04; found C 44.36, H 3.50, I 35.80.

exo,exo-6-Iodomethyl-3-[2-(4-ethoxy-2,3-difluorophenyl)ethyl]-

bicyclo[3.1.0]hexane (exo,exo-31): The ester exo,exo-30 (653 mg,

1.78 mmol) was treated with LiAlH₄(1.14 mL of a 1.17  solution

in Et₂O, 1.34 mmol) according to GP4 to give 527 mg (100%)

of crude exo,exo{3-[2-(4-ethoxy-2,3-difluorophenyl)ethyl]bicyclo-

[3.1.0]hex-6-yl}methanol as a colorless oil. ¹H NMR: δ ϭ 1.05Ϫ1.35

(m, 3 H, CH cPr), 1.39 (t, J ϭ 7.0 Hz, 3 H, CH₃), 1.55Ϫ1.70 (m,

4 H, 2 CH₂), 1.89 (dd, J ϭ 3.5, 12.0 Hz, 2 H, CH₂), 2.09Ϫ2.15 (m,

1 H, CH), 2.30 (s, 1 H, OH), 2.46 (dd, J ϭ 6.3, 14.0 Hz, 2 H, CH₂),

3.31 (d, J ϭ 7.5 Hz, 2 H, OCH₂), 4.02 (q, J ϭ 7.0 Hz, 2 H, OCH₂),

6.58 (dd, J ϭ 7.0, 8.6 Hz, 1 H, Ar-H), 6.72 (dd, J ϭ 8.6, 10.5 Hz,

1 H, Ar-H) ppm. ¹³C NMR: δ ϭ 14.6 (CH₃), 22.1 (2 CH), 24.9

(CH), 27.5 (CH₂), 34.1 (2 CH₂), 35.2 (CH₂), 43.1 (CH), 65.1 (CH₂),

65.3 (CH₂), 109.1 (d, J ϭ 3.2 Hz, CH), 123.0 (dd, J ϭ 5.3, 9.6 Hz,

CH), 123.5 (d, J ϭ 5.4 Hz, C), 141.3 (dd, J ϭ 14.8, 246.6 Hz, C),

146.1 (dd, J ϭ 2.8, 8.1 Hz, C), 149.5 (dd, J ϭ 10.4, 245.1 Hz, C)

ppm. This was treated with Im-H (166 mg, 2.44 mmol), Ph₃P

(607 mg g, 2.31 mmol), and I₂(680 mg, 2.68 mmol) according to

GP5 to give the iodide exo,exo-31 (687 mg, 95%) as a colorless oil

after column chromatography (70 g of silica gel, column 25 ϫ 3 cm,

exo,exo-6-Iodomethyl-3-[4-(3,4,5-trifluorophenyl)phenyl]bicyclo-

[3.1.0]hexane (exo,exo-20d): Column chromatography (100 g of sil-

ica gel, column 35 ϫ 3 cm, hexane/Et₂O, 10:1) of the reaction mix-

ture obtained from the alcohol exo,exo-19d (2.00 g, 6.29 mmol),

Im-H (0.508 g, 7.46 mmol), Ph₃P (1.86 g, 7.09 mmol), and I₂

(2.19 g, 8.62 mmol) according to GP5 gave the iodide exo,exo-20d

(2.44 g, 91%) as a colorless oil, R_fϭ 0.55, which solidified upon

standing at 0 °C overnight, m.p. 60Ϫ61 °C. ¹H NMR: δ ϭ 1.29 (tt,

J ϭ 3.0, 7.5 Hz, 1 H, CH cPr), 1.35Ϫ1.47 (m, 2 H, 2 CH cPr), 1.86

(ddd, J ϭ 3.0, 10.8, 12.8 Hz, 2 H, CH₂), 2.24 (dd, J ϭ 7.5, 12.8 Hz,

2 H, CH₂), 2.79 (tt, J ϭ 7.5, 10.8 Hz, 1 H, CH), 3.17 (d, J ϭ

7.5 Hz, 2 H, CH₂I), 7.17 (ddd, J ϭ 0.5, 7.2, 8.8 Hz, 2 H, Ar-H),

7.28 (d, J ϭ 8.3 Hz, 2 H, Ar-H), 7.37 (d, J ϭ 8.3 Hz, 2 H, Ar-H)

ppm. ¹³C NMR: δ ϭ 12.1 (CH₂), 24.4 (CH), 30.5 (2 CH), 36.1 (2

CH₂), 40.1 (CH), 111.7 (dd, J ϭ 18.3, 32.0 Hz, 2 CH), 126.6 (2

CH), 127.9 (2 CH), 135.9 (C), 136.9 (dt, J ϭ 4.5, 15.0 Hz, C), 139.0

(dt, J ϭ 15.4, 251.9 Hz, C), 144.6 (C), 151.2 (ddd, J ϭ 4.3, 10.1,

249.3 Hz, 2 C) ppm. C₁₉H₁₆F₃I (428.22): calcd. C 53.29, H 3.77, I

29.63; found C 52.69, H 3.80, I% 29.50.

1

hexane/Et₂O, 10:1), R_fϭ 0.40. H NMR: δ ϭ 1.10Ϫ1.35 (m, 3 H,

CH cPr), 1.40 (t, J ϭ 7.0 Hz, 3 H, CH₃), 1.57Ϫ1.78 (m, 4 H, 2

CH₂), 1.90 (dd, J ϭ 2.8, 12.5 Hz, 2 H, CH₂), 2.11Ϫ2.17 (m, 1 H,

CH), 2.41 (dd, J ϭ 5.8, 13.5 Hz, 2 H, CH₂), 3.15 (d, J ϭ 7.8 Hz,

2 H, CH₂I), 4.05 (q, J ϭ 7.0 Hz, 2 H, OCH₂), 6.60 (dd, J ϭ 7.0,

8.5 Hz, 1 H, Ar-H), 6.72 (dd, J ϭ 8.5, 9.4 Hz, 1 H, Ar-H) ppm.

¹³C NMR: δ ϭ 12.2 (CH₂), 14.3 (CH₃), 22.3 (2 CH), 24.7 (CH),

27.6 (CH₂), 34.3 (2 CH₂), 35.1 (CH₂), 43.3 (CH), 65.2 (CH₂), 109.5

(d, J ϭ 3.0 Hz, CH), 123.5 (dd, J ϭ 5.7, 10.1 Hz, CH), 123.8 (d,

J ϭ 5.3 Hz, C), 141.8 (dd, J ϭ 14.0, 245.4 Hz, C), 146.6 (dd, J ϭ

3.2, 9.2 Hz, C), 150.1 (dd, J ϭ 10.8, 246.3 Hz, C) ppm. C₁₇H₂₁IF₂O

(406.24): calcd. C 50.26, H 5.21; found C 49.95, H 5.15.

exo,exo-6-Iodomethyl-3-{[trans-4-(trans-4-propylcyclohexyl)cyclo-

hexyl]phenyl}-bicyclo[3.1.0]hexane (exo,exo-20e): Column chroma-

tography (100 g of silica gel, column 35 ϫ 3 cm, hexane/Et₂O, 10:1)

of the reaction mixture obtained from the alcohol exo,exo-19e

(1.87 g, 4.74 mmol), Im-H (0.442 g, 6.49 mmol), Ph₃P (1.61 g,

6.14 mmol), and I₂(1.80 g, 7.10 mmol) according to GP5 gave the

iodide exo,exo-20e (2.36 g, 99%) as a colorless solid, m.p. 197 °C

(dec.) (hexane), R_fϭ 0.64. IR (KBr): ν˜ ϭ 3020 cm^Ϫ1, 2925, 2846,

1512, 1446, 1223, 1167, 976, 842, 820, 560. ¹H NMR: δ ϭ 0.81 (m,

1 H, CH cPr), 0.85 (t, J ϭ 7.1 Hz, 3 H, CH₃), 1.05Ϫ1.80 (m, 2 H),

1.22Ϫ1.31 (m, 6 H), 1.34Ϫ1.46 (m, 6 H), 1.67Ϫ1.93 (m, 13 H),

2.18 (dd, J ϭ 7.4, 12.5 Hz, 2 H, CH₂), 2.42 (tt, J ϭ 3.0, 11.8 Hz,

1 H, CH), 2.70 (tt, J ϭ 7.4, 11.3 Hz, 1 H, CH), 3.15 (d, J ϭ 7.8 Hz,

2 H, CH₂I), 7.12 (s, 4 H, Ar-H) ppm. ¹³C NMR: δ ϭ 12.5 (CH₂),

14.4 (CH₃), 20.0 (CH₂), 24.4 (CH), 30.1 (2 CH₂), 30.3 (2 CH₂),

30.6 (2 CH), 33.6 (2 CH₂), 34.6 (2 CH₂), 36.2 (2 CH₂), 37.6 (CH),

39.8 (CH₂), 40.1 (CH), 42.9 (CH), 43.4 (CH), 44.1 (CH), 126.7 (2

CH), 127.1 (2 CH), 141.4 (C), 145.6 (C) ppm. C₂₈H₄₁I (504.51):

calcd. C 66.65, H 8.19, I 25.15; found C 66.39, H 8.08, I 25.05.

4-(Iodomethyl)cyclopentene (33): The alcohol 23 (15.05 g,

153.3 mmol) was treated with Im-H (14.30 g, 210 mmol), Ph₃P

(50.58 g, 192.8 mmol), and I₂(58.36 g, 230 mmol) according to

GP5, but the iodine was added in small portions at 0 °C over a

period of 1 h. ‘‘Bulb-to-bulb’’ distillation of the residue at 100 °C/

1

0.1 Torr gave the iodide 33 (26.8 g, 84%) as a colorless oil. The H

and ¹³C NMR spectra of 33 were identical to those reported pre-

viously.^[42]

General Procedure 6 (GP6) for the Li₂CuCl₄Catalyzed Cross Coup-

ling of the Iodides with Alkylmagnesium Bromides: A solution of

the respective alkylmagnesium bromide (1.5Ϫ2 equiv.) in Et₂O was

added in one portion to a solution of the respective iodide (5 mmol)

in anhydrous THF (50 mL) at Ϫ5 °C. The mixture was stirred for

5 min before a solution of Li₂CuCl₄(5Ϫ10 mol %), freshly pre-

1-Ethoxy-2,3-difluoro-4-(iodomethyl)benzene (27): 4-Ethoxy-2,3-di-

fluorobenzaldehyde (26a) (2.00 g, 10.74 mmol) was reduced with

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299

A. de Meijere et al.

FULL PAPER

pared from anhydrous LiCl (0.5Ϫ1.0 mmol) and anhydrous CuCl₂

8.3 Hz, 2 H, Ar-H), 7.41 (d, J ϭ 8.3 Hz, 2 H, Ar-H) ppm. ¹³C

(0.25Ϫ0.5 mmol) in THF (3 mL), was added in one portion. After NMR: δ ϭ 14.1 (CH₃), 20.0 (CH), 22.7 (CH₂), 24.2 (2 CH), 29.4

completion of the vigorous exothermic reaction, the mixture was

(CH₂), 29.5 (CH₂), 29.6 (CH₂), 31.9 (CH₂), 32.9 (CH₂), 36.3 (2

stirred for an additional 0.5 h at 0 °C and then poured into a mix-

CH₂), 40.7 (CH), 110.7 (ddd, J ϭ 7.0, 13.9, 21.2 Hz, 2 CH), 126.6

ture of ice-cold saturated aq. NH₄Cl solution (50 mL) and diethyl (2 CH), 128.0 (2 CH), 135.7 (C), 137.2 (dt, J ϭ 4.7, 12.5 Hz, C),

ether (100 mL). The organic phase was washed with saturated aq.

NH₄Cl solution and brine (50 mL each), dried and concentrated at

139.1 (dt, J ϭ 14.9, 241.5 Hz, C), 145.6 (C), 151.4 (ddd, J ϭ 4.4,

10.1, 249.3 Hz, 2 C) ppm. C₂₅H₂₉F₃(386.48): calcd. C 77.69, H

reduced or ambient pressure. The residue was purified by column 7.56; found C 77.37, H 7.60.

chromatography or distilled under ambient or reduced pressure.

exo,exo-6-Heptyl-3-{[trans-4-(trans-4-propylcyclohexyl)cyclohexyl]-

exo,exo-3-[4-(trans-4-pentylcyclohexyl)phenyl]-6-propylbicyclo-

[3.1.0]hexane (exo,exo-21a): Column chromatography (300 g of sil-

phenyl}bicyclo[3.1.0]hexane (exo,exo-21e): Column chromatography

(300 g of silica gel, column 50 ϫ 4.5 cm, hexane) of the reaction

ica gel, column 50 ϫ 4.5 cm, hexane) of the reaction mixture ob- mixture obtained from the iodide exo,exo-20e (2.31 g, 4.581 mmol),

tained from the iodide exo,exo-20a (2.28 g, 5.06 mmol), EtMgBr C₆H₁₃MgBr (9.16 mmol, 13.67 mL of a 0.67  solution), LiCl

(7.56 mmol, 2.32 mL of 3.26 solution), LiCl (0.021 g, (0.030 g) and CuCl₂(0.049 mg) according to GP6 gave the hydro-

0.5 mmol) and CuCl₂(0.034 g, 0.25 mmol) according to GP6 gave carbon exo,exo-21e (1.65 g, 78%) as a colorless solid, m.p. 237Ϫ239

the hydrocarbon exo,exo-21a (1.36 g, 77%) as a colorless solid, m.p.

°C (MeOH/CHCl₃, 10:1), R_fϭ 0.57. IR (KBr): ν˜ ϭ 3019 cm^Ϫ1

100Ϫ101 °C (MeOH), R_fϭ 0.55. IR (KBr): ν˜ ϭ 2957 cm^Ϫ1, 2850, 2957, 2850, 1513, 1466, 1441, 1050, 997, 892, 818, 722, 549. ¹H

1514, 1465, 1444, 1378, 1297, 1263, 1212, 1182, 1144, 1112, 1050, NMR: δ ϭ 0.71 (tt, J ϭ 2.9, 6.5 Hz, 1 H, CH cPr), 0.87 (t, J ϭ

1018, 973, 896, 825, 730, 585. ¹H NMR: δ ϭ 0.72 (tt, J ϭ 3.6, 7.3 Hz, 3 H, CH₃), 0.89 (t, J ϭ 6.7 Hz, 3 H, CH₃), 0.98Ϫ1.12 (m,

a



,

6.8 Hz, 1 H, CH cPr), 0.89 (t, J ϭ 7.0 Hz, 3 H, CH₃), 0.92 (t, J ϭ

7.5 Hz, 3 H, CH₃), 1.05Ϫ1.50 (m, 16 H), 1.71Ϫ1.81 (m, 1 H, CH),

12 H), 1.12Ϫ1.52 (m, 13 H), 1.61 (br. s, 2 H), 1.67Ϫ2.00 (m, 12

H), 2.11 (dd, J ϭ 7.3, 12.5 Hz, 2 H, CH₂), 2.40 (tt, J ϭ 3.3, 11.8 Hz,

1.84 (dd, J ϭ 8.0, 8.8 Hz, 8 H, 4 CH₂), 2.11 (dd, J ϭ 7.3, 12.3 Hz, 1 H, CH), 2.68 (tt, J ϭ 7.3, 11.0 Hz, 1 H, CH), 7.11 (br. s, 4 H,

2 H, CH₂), 2.42 (tt, J ϭ 3.1, 12.0 Hz, 1 H, CH), 2.67 (tt, J ϭ 7.5, Ar-H) ppm. ¹³C NMR: δ ϭ 14.1 (CH₃), 14.4 (CH₃), 19.9 (CH),

11.0 Hz, 1 H, CH), 7.09 (d, J ϭ 7.6 Hz, 2 H, Ar-H), 7.13 (d, J ϭ

7.6 Hz, 2 H, Ar-H) ppm. ¹³C NMR: δ ϭ 14.07 (CH₃), 14.12 (CH₃),

20.0 (CH₂), 22.7 (CH₂), 24.2 (2 CH), 29.4 (CH₂), 29.5 (CH₂), 29.6

(CH₂), 30.1 (2 CH₂), 30.4 (2 CH₂), 31.9 (CH₂), 32.9 (CH₂), 33.6 (2

19.7 (CH), 22.69 (CH₂), 22.71 (CH₂), 24.2 (2 CH), 26.6 (CH₂), 32.2 CH₂), 34.6 (2 CH₂), 36.4 (2 CH₂), 37.6 (CH), 39.8 (CH₂), 40.6

(CH₂), 33.6 (2 CH₂), 34.4 (2 CH₂), 35.1 (CH₂), 36.4 (2 CH₂), 37.3 (CH), 42.9 (CH), 43.4 (CH), 44.2 (CH), 126.6 (2 CH), 127.1 (2

(CH), 37.7 (CH₂), 40.6 (CH), 44.1 (CH), 126.6 (2 CH), 127.1 (2

CH), 142.4 (C), 145.4 (C) ppm. C₃₄H₅₄(462.77): calcd. C 88.24, H

CH), 142.4 (C), 145.4 (C) ppm. C₂₆H₄₀(352.58): calcd. C 88.56, H 11.76; found C 88.09, H 11.64.

11.44; found C 88.85, H 11.25.

1-[2-(Cyclopentene-4-yl)ethyl]-4-ethoxy-2,3-difluorobenzene

(29):

exo,exo-6-Heptyl-3-(3,4,5-trifluorophenyl)bicyclo[3.1.0]hexane

(exo,exo-21b): Column chromatography (100 g of silica gel, column

35 ϫ 3 cm, hexane) of the reaction mixture obtained from the iod-

ide exo,exo-20b (2.55 g, 7.24 mmol), C₆H₁₃MgBr (10.86 mmol,

The reaction mixture obtained from iodide 27 (3.58 g, 12.0 mmol),

(cyclopentene-4-yl)methylmagnesium bromide [freshly prepared

from 4-(bromomethyl)cyclopentene (24) (2.901 g, 18 mmol) and

Mg (0.433 g, 18 mmol)], LiCl (0.101 g) and CuCl₂(0.161 g) accord-

16.21 mL of a 0.67  solution), LiCl (0.030 g) and CuCl₂(0.049 g) ing to GP6 was concentrated under reduced pressure, and the resi-

according to GP6 gave the hydrocarbon exo,exo-21b (1.91 g, 85%)

due was recrystallized from hexane/benzene, 2:1 to give 1,2-bis(4-

as a colorless oil, m.p. ca. 10Ϫ12 °C, R_fϭ 0.60. ¹H NMR: δ ϭ

ethoxy-2,3-difluorophenyl)ethane (28) (1.05 g, 51%) as a colorless

1

0.67 (tt, J ϭ 3.3, 6.7 Hz, 1 H, CH cPr), 0.89 (t, J ϭ 6.5 Hz, 3 H, solid. H NMR: δ ϭ 1.43 (t, J ϭ 7.0 Hz, 6 H, 2 CH₃), 2.86 (s, 4

CH₃), 1.10 (t, J ϭ 6.3 Hz, 2 H), 1.17 (t, J ϭ 6.8 Hz, 2 H), 1.21Ϫ1.41 H, 2 CH₂), 4.08 (q, J ϭ 7.0 Hz, 4 H, 2 OCH₂), 6.63 (dt, J ϭ 1.5,

(m, 10 H), 1.73 (ddd, J ϭ 3.3, 11.0, 12.1 Hz, 2 H, CH₂), 2.13 (dd, 7.3 Hz, 1 H, Ar-H), 6.68 (dt, J ϭ 2.0, 8.0 Hz, 1 H, Ar-H), 7.46

J ϭ 7.5, 12.1 Hz, 2 H, CH₂), 2.64 (tt, J ϭ 7.5, 11.0 Hz, 1 H, CH),

(ddd, J ϭ 2.3, 7.3, 12.5 Hz, 1 H, Ar-H), 7.67 (ddd, J ϭ 1.5, 8.0,

6.80 (ddd, J ϭ 3.3, 7.3, 13.7 Hz, 2 H, Ar-H) ppm. ¹³C NMR: δ ϭ 12.0 Hz, 1 H, Ar-H) ppm. ¹³C NMR: δ ϭ 14.7 (2 CH₃), 29.2 (2

14.1 (CH₃), 20.0 (CH), 22.7 (CH₂), 29.4 (CH₂), 29.5 (CH₂), 29.6 CH₂), 65.3 (2 CH₂), 109.1 (2 CH), 121.6 (d, J ϭ 13.6 Hz, 2 C),

(CH₂), 31.9 (CH₂), 32.8 (CH₂), 32.9 (2 CH), 36.0 (2 CH₂), 40.5 123.5 (dd, J ϭ 5.7, 10.3 Hz, 2 CH), 141.5 (dd, J ϭ 15.3, 248.6 Hz,

(CH), 111.0 (ddd, J ϭ 6.3, 13.8, 20.2 Hz, 2 CH), 137.8 (dt, J ϭ 2 C), 146.8 (dd, J ϭ 3.5, 8.1 Hz, 2 C), 148.1 (dd, J ϭ 9.9, 243.8 Hz,

15.3, 248.7 Hz, C), 141.5 (dt, J ϭ 4.5, 11.1 Hz, C), 150.9 (ddd, J ϭ

2 C) ppm. The mother liquor was concentrated under reduced

4.3, 14.3, 252.9 Hz, 2 C) ppm. C₁₉H₂₅F₃(310.39): calcd. C 73.52, pressure and purified by column chromatography (100 g of silica

H 8.12; found C 73.25, H 8.08.

gel, column 30 ϫ 3 cm, hexane/benzene, 2:1) to give compound 29

(0.758 g, 25%) as a colorless oil, R_fϭ 0.50. H NMR: δ ϭ 1.44 (t,

1

exo,exo-6-Heptyl-3-[4-(3,4,5-trifluorophenyl)phenyl]bicyclo-

[3.1.0]hexane (exo,exo-21d): Column chromatography (120 g of sil-

ica gel, column 40 ϫ 3 cm, hexane) of the reaction mixture ob-

tained from the iodide exo,exo-20d (2.34 g, 5.47 mmol),

C₆H₁₃MgBr (10.94 mmol, 16.33 mL of a 0.67  solution), LiCl

(0.030 g) and CuCl₂(0.049 g) according to GP6 gave the hydro-

carbon exo,exo-21d (1.67 g, 79%) as a colorless oil which solidified

J ϭ 7.0 Hz, 3 H, CH₃), 1.68 (q, J ϭ 7.6 Hz, 2 H, CH₂), 2.02 (dd,

J ϭ 7.0, 14.0 Hz, 2 H, CH₂), 2.23 (sept, J ϭ 7.0 Hz, 1 H, CH),

2.51 (dd, J ϭ 9.0, 14.0 Hz, 2 H, CH₂), 2.61 (t, J ϭ 7.0 Hz, 2 H,

CH₂), 4.09 (q, J ϭ 7.0 Hz, 2 H, OCH₂), 5.67 (s, 2 H, 2 ϭCH), 6.64

(dt, J ϭ 2.0, 8.0 Hz, 1 H, Ar-H), 6.81 (dt, J ϭ 2.0, 8.0 Hz, 1 H,

Ar-H) ppm. ¹³C NMR: δ ϭ 14.8 (CH₃), 27.2 (CH₂), 37.0 (CH),

37.1 (CH₂), 38.8 (2 CH₂), 65.3 (CH₂), 109.3 (d, J ϭ 2.7 Hz, CH),

123.2 (dd, J ϭ 4.5, 10.4 Hz, CH), 123.4 (d, J ϭ 4.3 Hz, C), 129.8

(2 CH), 141.5 (dd, J ϭ 14.7, 246.5 Hz, C), 146.2 (dd, J ϭ 2.8,

11.1 Hz, C), 149.8 (dd, J ϭ 10.6, 245.1 Hz, C) ppm. C₁₅H₁₈F₂O

(252.3): calcd. C 71.40, H 7.19; found C 71.11, H 6.95.

at 0 °C, m.p. 34 °C (MeOH), R_fϭ 0.51. IR (KBr): ν˜ ϭ 2923 cm^Ϫ1

,

1613, 1536, 1509, 1364, 1250 (CF), 1029, 826, 764, 561, 534. ¹H

NMR: δ ϭ 0.77 (tt, J ϭ 3.5, 6.8 Hz, 1 H, CH cPr), 0.93 (t, J ϭ

6.8 Hz, 3 H, CH₃), 1.15 (m, 2 H), 1.22 (t, J ϭ 6.8 Hz, 2 H),

1.25Ϫ1.45 (m, 10 H), 1.87 (ddd, J ϭ 3.3, 11.0, 12.3 Hz, 2 H, CH₂),

2.20 (dd, J ϭ 7.5, 12.3 Hz, 2 H, CH₂), 2.78 (tt, J ϭ 7.5, 11.0 Hz, exo,exo-3-[2-(4-Ethoxy-2,3-difluoro-phenyl)ethyl]-6-pentylbicyclo-

1 H, CH), 7.17 (dd, J ϭ 6.5, 8.8 Hz, 2 H, Ar-H), 7.29 (d, J ϭ [3.1.0]hexane (exo,exo-32): Column chromatography (80 g of silica

300

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Novel Liquid Crystalline Compounds

FULL PAPER

gel, column 25 ϫ 3 cm, hexane) of the reaction mixture obtained

General Procedure 7 (GP7) for the Preparation of Tosylhydrazones

from the iodide exo,exo-31 (686 mg, 1.69 mmol), C₄H₉MgBr 35: To a solution of tosylhydrazine (5.05 mmol) in methanol

(3.39 mmol, 3.9 mL of a 0.87  solution), LiCl (14.3 mg) and

CuCl₂(22.7 mg) according to GP6 gave the product exo,exo-32

(325 mg, 57%) as a colorless oil, R_fϭ 0.25. ¹H NMR: δ ϭ 0.92 (t,

(10 mL) was added a solution of the respective arene carbaldehyde

(5 mmol) in MeOH (5 mL) in one portion at 65 °C. The reaction

mixture was stirred for an additional 30 min at this temp. and co-

J ϭ 6.8 Hz, 3 H, CH₃), 0.99Ϫ1.55 (m, 15 H), 1.44 (t, J ϭ 7.0 Hz, oled to 0 °C. The precipitate was filtered, washed with cold MeOH

3 H, CH₃), 1.91 (dd, J ϭ 5.8, 11.8 Hz, 2 H, CH₂), 2.15Ϫ2.21 (m,

(5 mL) and dried at ambient temp. under reduced pressure (10^Ϫ2

1 H, CH), 2.52 (dd, J ϭ 6.0, 14.0 Hz, 2 H, CH₂), 4.07 (q, J ϭ Torr) for 24 h.

7.0 Hz, 2 H, OCH₂), 6.63 (ddd, J ϭ 1.8, 7.25, 8.1 Hz, 1 H, Ar-H),

Tosylhydrazone of 4-Ethoxy-2,3-difluorobenzaldehyde (35a): From

6.78 (t, J ϭ 8.1 Hz, 1 H, Ar-H) ppm. ¹³C NMR: δ ϭ 14.1 (CH₃),

14.7 (CH₃), 20.4 (CH), 22.7 (CH₂), 24.2 (2 CH), 27.8 (CH₂), 29.3

(CH₂), 31.8 (CH₂), 32.9 (CH₂), 34.7 (2 CH₂), 36.4 (CH₂), 44.2

(CH), 65.3 (CH₂), 109.2 (d, J ϭ 3.0 Hz, CH), 123.1 (dd, J ϭ 5.8,

10.5 Hz, CH), 123.4 (d, J ϭ 5.1 Hz, C), 141.5 (dd, J ϭ 15.0,

246.8 Hz, C), 146.3 (dd, J ϭ 2.9, 8.2 Hz, C), 149.7 (dd, J ϭ 10.2,

244.9 Hz, C) ppm. C₂₁H₃₀F₂O (336.45): calcd. C 74.96, H 8.98;

found C 74.71, H 8.95.

4-ethoxy-2,3-difluorobenzaldehyde (26a) (1.00 g, 5.37 mmol) and

tosylhydrazine (1.05 g, 5.64 mmol), tosylhydrazone 35a (1.90 g,

98%) was obtained as a colorless powder according to GP7, m.p.

149Ϫ151 °C (decomp.). IR (KBr): ν˜ ϭ 3185 cm^Ϫ1, 2982, 2930,

1623, 1518, 1458, 1334, 1167, 1083. ¹H NMR ([D₆]DMSO): δ ϭ

1.33 (t, J ϭ 7.0 Hz, 3 H, CH₃), 2.35 (s, 3 H, CH₃), 4.14 (q, J ϭ

7.0 Hz, 2 H, OCH₂), 7.02 (t, J ϭ 8.2 Hz, 1 H, Ar-H), 7.38 (d, J ϭ

8.7 Hz, 2 H, Ar-H), 7.41 (t, J ϭ 8.2 Hz, 1 H, Ar-H), 7.74 (d, J ϭ

8.7 Hz, 2 H, Ar-H), 7.97 (s, 1 H, ϭCH), 11.89 (s, 1 H, NH) ppm.

¹³C NMR ([D₆]DMSO): δ ϭ 14.3 (CH₃), 20.9 (CH₃), 65.1 (CH₂),

110.3 (d, J ϭ 2.5 Hz, CH), 114.9 (d, J ϭ 8.1 Hz, C), 120.7 (t, J ϭ

4.1 Hz, CH), 127.0 (2 CH), 129.6 (2 CH), 136.0 (C), 139.1 (CH),

140.0 (dd, J ϭ 13.5, 244.9 Hz, C), 143.4 (C), 149.0 (dd, J ϭ 11.4,

251.2 Hz, C), 149.1 (dd, J ϭ 3.3, 7.7 Hz, C) ppm.

4-Propylcyclopentene (34a): A) The reaction mixture obtained from

iodide 33 (23.735 g, 114.1 mmol), ethylmagnesium bromide

(228 mmol, 65 mL of a 3.51  solution in Et₂O), LiCl (0.483 g) and

CuCl₂(0.766 g) according to GP6 was concentrated under ambient

pressure using a 30 cm rectification column, and the residue was

distilled under ambient pressure to give 34a (6.803 g, 54%) as a

colorless liquid, b.p. 119Ϫ122 °C (ref.^[43]115 °C). ¹H NMR: δ ϭ

0.83 (t, J ϭ 6.6 Hz, 3 H, CH₃), 1.15Ϫ1.43 (m, 4 H, 2 CH₂), 1.94

(dd, J ϭ 6.6, 13.9 Hz, 2 H, CH₂), 2.00Ϫ2.23 (m, 1 H, CH), 2.45

(dd, J ϭ 8.6, 13.9 Hz, 2 H, CH₂), 5.59 (br. s, 2 H, 2 ϭCH) ppm.

¹³C NMR: δ ϭ 14.3 (CH₃), 21.5 (CH₂), 37.4 (CH), 38.8 (CH₂),

38.9 (2 CH₂), 130.0 (2 CH) ppm.

Tosylhydrazone of 4-Cyanobenzaldehyde (35b): From 4-cyanoben-

zaldehyde (26a) (10.0 g, 76.3 mmol) and tosylhydrazine (12.3 g,

66.1 mmol), tosylhydrazone 35b (17.7 g, 89%) was obtained as a

colorless powder according to GP7, m.p. 154Ϫ156 °C (ref. 44,

1

155Ϫ156 °C). The H and ¹³C NMR spectra of 35b were identical

to those reported earlier.^[44]

B) Under the same conditions as above, the cyclopentene 34a

(2.0 g, 30%) was obtained from n-propyl iodide (10.2 g, 6.92 mL, (4-Ethoxy-2,3-difluorophenyl)diazomethane (36a): This compound

60 mmol), (cyclopentene-4-yl)magnesium bromide [freshly pre- was prepared as a yellow oil in 98% yield on a 5 mmol scale accord-

pared from 4-bromocyclopentene (14) (11.03 g, 75 mmol) and Mg

ing to the procedure of Creary.^[26]IR (film): ν

˜ ϭ 2988 cm^Ϫ1, 2066,

(1.80 g, 75 mmol)], LiCl (0.509 g) and CuCl₂(0.807 g).

1617, 1511, 1304, 1082. ¹H NMR: δ ϭ 1.40 (t, J ϭ 6.0 Hz, 3 H,

CH₃), 4.13 (q, J ϭ 6.0 Hz, 2 H, CH₂), 5.00 (s, 1 H, HCϭN), 6.55

(t, J ϭ 8.5 Hz, 1 H, Ar-H), 7.70 (t, J ϭ 8.5 Hz, 1 H, Ar-H) ppm.

¹³C NMR: δ ϭ 14.4 (CH₃), 63.3 (CH), 65.7 (CH₂), 110.8 (CH),

115.5 (CH), 121.6 (d, J ϭ 13.5 Hz, C), 142.4 (dd, J ϭ 21.0,

265.0 Hz, C), 145.6 (dd, J ϭ 22.0, 247.0 Hz, C), 146.8 (dd, J ϭ 3.2,

8.5 Hz, C) ppm.

4-Pentylcyclopentene (34b): Column chromatography (350 g of sil-

ica gel, column 50 ϫ 4.5 cm, hexane) of the reaction mixture ob-

tained from n-pentyl iodide (9.90 g, 6.53 mL, 50 mmol), (cyclopen-

tene-4-yl)magnesium bromide [freshly prepared from 4-bromo-

cyclopentene (14) (8.82 g, 60 mmol) and Mg (1.45 g, 60 mmol)],

LiCl (0.212 g) and CuCl₂(0.360 g) according to GP6 gave the

cyclopentene derivative 34b (3.667 g, 53%) as a colorless oil, R_fϭ

0.65. ¹H NMR: δ ϭ 0.86 (t, J ϭ 6.1 Hz, 3 H, CH₃), 1.18Ϫ1.53 (m,

8 H, 4 CH₂), 1.94 (dd, J ϭ 7.4, 14.1 Hz, 2 H, CH₂), 2.21 (sept, J ϭ

7.4 Hz, 1 H, CH), 2.45 (dd, J ϭ 8.0, 14.1 Hz, 2 H, CH₂), 5.66 (br.

s, 2 H, 2 ϭCH) ppm. ¹³C NMR: δ ϭ 14.1 (CH₃), 22.7 (CH₂), 28.1

(CH₂), 32.1 (CH₂), 36.5 (CH₂), 37.7 (CH), 39.0 (2 CH₂), 130.0 (2

CH) ppm. C₁₀H₁₈(138.24): calcd. C 86.88, H 13.12; found C 86.54,

H 13.11.

exo,exo-6-(4-Cyanophenyl)-3-pentylbicyclo[3.1.0]hexane (exo,exo-

38b): To a stirred solution of 34b (0.966 g, 6.99 mmol) and pal-

ladium acetate (0.110 g, 0.49 mmol, 7 mol %) in diethyl ether

(15 mL) was added dropwise a solution of 4-cyanophenyldiazome-

thane (36b)^[26](1.10 g, 7.68 mmol) in Et₂O over a period of 12 h at

ambient temp. The reaction mixture was filtered through a pad of

silica gel, concentrated under reduced pressure and separated by

HPLC (eluting with MeOH/H₂O 85:15) to give exo,exo-38b

(0.513 g, 29%) and exo,endo-38b (0.053 g, 3%) as colorless solids.

4-Heptylcyclopentene (34c): Column chromatography (350 g of sil-

ica gel, column 50 ϫ 4.5 cm, hexane) of the reaction mixture ob-

tained from n-heptyl iodide (11.31 g, 8.2 mL, 50 mmol), (cyclopen-

tene-4-yl)magnesium bromide [freshly prepared from 4-bromo-

cyclopentene (14) (8.82 g, 60 mmol) and Mg (1.45 g, 60 mmol)],

LiCl (0.212 g) and CuCl₂(0.360 g) according to GP6 gave the

cyclopentene derivative 34c (4.66 g, 56%) as a colorless oil, R_fϭ

0.62. ¹H NMR: δ ϭ 0.88 (t, J ϭ 6.6 Hz, 3 H, CH₃), 1.16Ϫ1.36 (m,

12 H, 6 CH₂), 1.90 (dd, J ϭ 7.4, 13.0 Hz, 2 H, CH₂), 2.20 (sept,

J ϭ 7.4 Hz, 1 H, CH), 2.45 (dd, J ϭ 7.4, 13.0 Hz, 2 H, CH₂), 5.66

exo,exo-38b: M.p. 34Ϫ35 °C. ¹H NMR (C₆D₆): δ ϭ 0.88 (t, J ϭ

6.5 Hz, 3 H, CH₃), 1.50 (m, 14 H), 2.08 (dd, J ϭ 12.0, 3.0 Hz, 2 H,

2 CH), 7.04 (d, J ϭ 8.5 Hz, 2 H, Ar-H), 7.48 (d, J ϭ 8.5 Hz, 2 H,

Ar-H) ppm. ¹³C NMR (C₆D₆): δ ϭ 14.0 (CH₃), 22.5 (2 CH), 22.6

(CH), 24.2 (CH₂), 28.2 (CH₂), 31.8 (CH₂), 32.8 (2 CH₂), 36.2 (CH),

36.5 (CH₂), 109.4 (C), 118.5 (C), 130.2 (2 CH), 132.0 (2 CH), 144.9

(C) ppm. MS (EI): m/z (%) ϭ 253 (100) [M^ϩ], 182 (95) [M^ϩ

Ϫ C₅H₁₁], 168 (16), 154 (40), 142 (65), 137 (35), 127 (15), 116 (50).

1

(br. s, 2 H, 2 ϭCH) ppm. ¹³C NMR: δ ϭ 14.1 (CH₃), 22.7 (CH₂), exo,endo-38b: M.p. 45Ϫ47 °C. H NMR (C₆D₆): δ ϭ 0.79 (t, J ϭ

28.4 (CH₂), 29.4 (CH₂), 29.8 (CH₂), 31.9 (CH₂), 36.6 (CH₂), 37.7

(CH), 39.0 (2 CH₂), 130.0 (2 CH) ppm. C₁₂H₂₂(166.3): calcd. C

86.66, H 13.34; found C 86.44, H 13.11.

7.5 Hz, 3 H, CH₃), 0.93Ϫ1.03 (m, 8 H), 1.08 (p, J ϭ 6.0 Hz, 1 H,

CH), 1.11Ϫ1.21 (m, 4 H, 2 CH₂), 1.59 (t, 1 H, CH), 1.65 (dd, J ϭ

6.0, 12.0 Hz, 2 H, 2 CH), 6.80 (d, J ϭ 8.5 Hz, 2 H, Ar-H), 7.01 (d,

Eur. J. Org. Chem. 2004, 289Ϫ303

www.eurjoc.org

 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

301

A. de Meijere et al.

FULL PAPER

Table 3. Crystallographic data and parameters for the refinements of compounds 9a, endo,exo-18a, exo,exo-18b, exo,exo-38b, and

exo,endo-38b.

Compound

exo,exo-9a

endo,exo-18a

exo,exo-18b

exo,exo-38b

exo,endo-38b

Empirical formula

Molecular mass

Temperature, K

Wavelength, A

Crystal system

Space group

C₃₀H₃₈O₄

462.63

133(2)

0.71073

monoclinic

C2/c

C₂₈H₄₂O₂

410.62

120(2)

C₁₇H₁₉F₃O₂

312.32

120.0(2)

C₁₈H₂₃N

253.37

120(2)

C₁₈H₂₃N

253.37

220.0(2)

˚

monoclinic

P2₁/c

triclinic

¯

P1

˚

Unit cell dimensions (A,°)

a

b

c

28.793(1)

5.9710(5)

32.423(3)

90

111.767(7)

90

5176.8(5)

8

1.269

20.075(1)

9.9072(6)

12.7752(7)

90

101.10(2)

90

2493.3(3)

4

1.094

5.7364(3)

11.0353(6)

12.8208(7)

76.584(2)

87.759(2)

87.674(2)

788.43(7)

2

9.7909(4)

11.8250(5)

14.2577(6)

104.734(1)

103.126(1)

97.423(1)

1523.8(1)

4

6.0817(5)

8.5321(7)

15.048(3)

81.97(3)

85.25(3)

87.91(3)

770.29(18)

2

α

β

γ

3

˚

Volume (A )

Z

Density (calculated, Mg.m^-3)

1.316

0.108

1.104

0.063

1.092

0.063

µ, mm^Ϫ1

0.087

0.066

F(000)

2128

Ϫ

24.06

904

328

552

276

Crystal size, mm³

θ_max(°) for data collection

Reflections collected

0.28 ϫ 0.20 ϫ 0.03 0.36 ϫ 0.21 ϫ 0.16 0.40 ϫ 0.24 ϫ 0.10 0.40 ϫ 0.25 ϫ 0.20

27.50

22856

4802 [0.1501]

30.17

8036

4178 [0.0295]

30.00

13531

8684 [0.0309]

30.55

6797

4553 [0.0303]

28013

4058 [0.0696]

Independent reflections [R_int

Refinement method

]

Full-matrix least-squares on F²

Data/restraints/parameters

4058/0/309

1.053

4802/0/419

0.894

4178/0/275

1.039

8684/0/527

0.935

4553/0/272

0.948

Goof on F²

R₁, wR₂indices [I Ͼ 2σ(I)]

R₁, wR₂indices (all data)

Largest diff. peak and hole, e·A

0.0506, 0.1342

0.0690, 0.1421

0.0796, 0.1829

0.1563, 0.2124

0.0434, 0.1096

0.0573, 0.1191

0.0489, 0.1171

0.0783, 0.1300

0.0487, 0.1249

0.0893, 0.1401

Ϫ3

˚

0.587 and Ϫ0.373 0.369 and Ϫ0.242 0.347 and Ϫ0.207 0.313 and Ϫ0.190 0.236 and Ϫ0.149

³J ϭ 8.5 Hz, 2 H, Ar-H) ppm. ¹³C NMR (C₆D₆): δ ϭ 14.2 (CH₃),

22.8 (2 CH), 24.3 (CH), 24.4 (CH₂), 28.6 (CH₂), 32.2 (CH₂), 32.9

(2 CH₂), 36.5 (CH), 36.9 (CH₂), 110.4 (C), 119.0 (C), 130.1 (2 CH),

132.1 (2 CH), 144.1 (C) ppm.

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Crystal Structure Determinations: Suitable crystals of the com-

pounds for X-ray crystal structure determinations were grown by

slow evaporation of an Et₂O/hexane solution (9a, exo,exo-38b and

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Acknowledgments

This work was supported by the Fonds der Chemischen Industrie

and the EPSRC (UK). The authors are grateful to BASF AG,

Bayer AG, Chemetall GmbH, and Degussa AG for generous gifts

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Novel Liquid Crystalline Compounds

FULL PAPER

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Article Doi

Novel Liquid Crystalline Compounds Containing Bicyclo[3.1.0]hexane Core Units

DOI: 10.1002/ejoc.200300448

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