Scholarly article on 1-(4'-ethylbiphenyl-4-yl)-3-[2-(tetrahydropyran-2-yloxy)ethyl]bicyclo[1.1.1]pentane 271768-12-8 from European Journal of Organic Chemistry p. 1137

FULL PAPER

Nickel- and Palladium-Catalyzed Cross-Coupling Reactions at the Bridgehead

of Bicyclo[1.1.1]pentane Derivatives – A Convenient Access to Liquid

Crystalline Compounds Containing Bicyclo[1.1.1]pentane Moieties

Matthias Messner,^[a]Sergei I. Kozhushkov,^[a]and Armin de Meijere*^[a]

Dedicated to Professor Günther Wulff on the occasion of his 65th birthday

Keywords: Bicyclo[1.1.1]pentane / Haloarenes, cross-coupling of / [1.1.1]Propellane / Palladium / Catalysis / Small-ring

systems

Radical addition reactions of organyl iodides 7a–s onto

[1.1.1]propellane (2) followed by halogen–lithium exchange

and transmetallation with zinc chloride, as well as additions

of Grignard reagents to 2, have furnished a variety of 3-sub-

disubstituted bicyclo[1.1.1]pentyl derivatives 17, 20, and 23,

several of which exhibit liquid crystalline properties, in mod-

erate to very good yields. The coupling products 20ca, 23ab,

23ae, 23ff, and 23fg have been further transformed to yield

stituted bicyclo[1.1.1]pentyl-1-magnesium (14) and -zinc (19) bicyclo[1.1.1]pentyl derivatives 32, 24ab, 24ae, 27ff, and

derivatives. The latter have been coupled with various alk-

enyl, aryl, and biaryl halides and triflates under NiCl₂dppe,

Pd(PPh₃)₄, or PdCl₂(dppf) catalysis to give a number of 1,3-

27fg, respectively, bearing alkynyl, cyano, and/or alkenyl

groups.

Introduction

The design and preparation of rigid rod-like molecules

has long been of interest to physical-organic chemists.^[1]

Among such structures, 1,3-disubstituted derivatives of bi-

cyclo[1.1.1]pentane (1) have, for several reasons, attracted

particular attention during the past decade. In spite of the

considerable strain energy of the bicyclo[1.1.1]pentane

unit,^[2,3]such derivatives are remarkably thermally stable,

persisting up to 300 °C, and are resistant to oxygen and

many mild reagents.^[4]They are also transparent to visible

and UV light and, being intrinsically linear, are capable of

stabilizing mesophases.^[4b]Since the preparation of the first

bicyclo[1.1.1]pentane derivatives in 1966,^[5]a wide range of

such systems has now become readily accessible, the key

development being the discovery of an efficient two-step

Results and Discussion

1. Preparation of Starting Materials

The key intermediates used in the cross-coupling reac-

preparation^[6]of the ideal precursor, [1.1.1]propellane (2),^[7]tions with haloarenes were 1-bicyclo[1.1.1]pentylzinc or

from commercially available starting materials (for recent -magnesium reagents of type 6. The simplest access to metal

improvements in the preparation of 2, see also ref.^[8]). The derivatives 6, in which R is an aryl, alkyl, or functionalized

chemistry of [1.1.1]propellanes and bicyclo[1.1.1]pentanes alkyl substituent, is offered by halogen–metal exchange re-

derived therefrom has been studied quite extensively since actions of the corresponding bridgehead iodinated bicyclo-

1989,^[9]and the results have been reviewed several [1.1.1]pentyl derivatives 8. The latter are easily accessible

times.^{[3,4a,8a,10–12]}However, to date most attention has been through the radical addition of alkyl iodides across the

paid to compounds containing two or more bicyclo[1.1.1]- central σ-bond in [1.1.1]propellane (2) under photochemical

pentane units (the so-called [n]staffanes, for a review see conditions^[4a,13](Scheme 1, conditions B) or under methylli-

ref.^[3]) and to functionalized derivatives of 1 and their chem- thium catalysis.^[12,14]It was found^[15]that by using a stoichi-

ical transformations.^[8a,9]In the present contribution, we de- ometric quantity of MeLi (Scheme 1, conditions A), better

scribe our results concerning the preparation of quasi-linear and more reproducible yields of compounds 8 (Table 1)

molecules of types 3–5 using a metal-catalyzed cross-coup- were obtained. For example, compounds 8a and 8c had pre-

ling reaction as a key synthetic step.

viously been prepared by photochemical means in 65%^[13b]

and 34% yield,^[4a]respectively, whereas under MeLi medi-

ation, the additions gave significantly higher yields (83%

and 97%). Nevertheless, in the cases of 8f and 8j, better

results were achieved under photochemical conditions be-

[a]

Institut für Organische Chemie der Georg-August-Universität

Göttingen,

Tammannstrasse 2, 37077 Göttingen, Germany

Eur. J. Org. Chem. 2000, 1137Ϫ1155

WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000

1434Ϫ193X/00/0407Ϫ1137 $ 17.50ϩ.50/0

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M. Messner, S. I. Kozhushkov, A. de Meijere

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cause of competing side reactions (β-elimination) in the Thus, the acids 10c–e,h,i,o were obtained in yields of 44–

presence of MeLi. Products 8k and 8l could not be obtained 60%, while 10b was produced almost quantitatively. Satis-

by additions of vinyl and allyl iodides; under the action of factory results were also achieved with most of the other

MeLi, only the methyl derivative was formed, which was electrophiles investigated (Table 2). As in the published pro-

isolated in yields of 55% and 60%, respectively. Under irra- cedure,^[9]the addition of lithium derivatives 9 to nitriles fur-

diation, the main components of the reaction mixtures were nished a good yield of ketone 12b only in the case of p-

oligobicyclo[1.1.1]pentyl diiodides (diiodostaffanes^[3]) and fluorobenzonitrile. Generally better results were achieved

rearranged products, although the photochemically induced using acid chlorides as electrophiles (Table 2). Chlorozinc

addition of allyl iodide to 2 has been reported.^[13]The vinyl reagents may be prepared almost quantitatively from 9 by

derivative 8k was indeed formed in ca. 20% yield (as estim- transmetallation with anhydrous ZnCl₂(see below).

ated by NMR), but could not be isolated from the complex

reaction mixture. With 4-substituted 1-iodocyclohexanes

7o–q, 2:1 mixtures of cis- and trans-1,4-disubstituted cyclo-

hexane derivatives 8o–q were obtained, irrespective of the

configuration of the starting iodide. Compounds 8 were

found to be rather unstable, both thermally and towards

silica gel, which prevented their further purification in most

cases. Nevertheless, the purity of the crude products, Ն 95% iodides 8 by lithiation/electrophilic substitution

under MeLi mediation, is normally adequate for any sub-

Scheme 2. For details see Table 2

Table 2. Functionalization of 3-substituted bicyclo[1.1.1]pent-1-yl

sequent transformations and, moreover, compounds 8 may

be stored at –78 °C for several months.

Scheme 1. For details see Table 1

Table 1. Addition of alkyl and aryl iodides 7 to [1.1.1]propellane (2)

Bicyclo[1.1.1]pentyl iodides 8, in which R is an aryl or

substituted aryl group, cannot be prepared as easily as iod-

ides 8a–j,m–q, because the addition of aryl iodides to the

central bond in 2 proceeds only under photochemical con-

ditions and gives the adducts in moderate yields only.^[4,8a]

In the majority of publications, 3-phenylbicyclo[1.1.1]pentyl

iodide (8r) has been used without purification,^[4a]which is

unacceptable for transition metal catalyzed coupling reac-

tions. The alternative route to 8r reported by Della et al.^[8a]

is a tedious six-step preparation starting from 2. Upon puri-

fication by chromatography on silica gel, the phenyl and p-

The corresponding lithium derivatives were obtained tolyl derivatives, 8r and 8s, respectively, could be isolated in

from the iodides 8 by treatment with either lithium 4,4Ј-di- pure form, albeit only in yields of 21% and 10% due to

tert-butylbiphenylide (LiDBB^[16a]) or tert-butyllithium at – significant decomposition. Moreover, the yield decreased

78 °C,^{[8a,9a,9d,16b,16c]}and trapped with a variety of elec- considerably upon increasing the scale of the preparation.

trophiles. Comparison of the two series of experiments As an alternative access to 3-aryl-substituted bridgehead

(Scheme 2, Table 2) showed that better yields were fre- metal derivatives of type 6, the known addition of Grignard

quently obtained following lithiation with tert-butyllithium. reagents to [1.1.1]propellanes^[12a,17]was examined, in spite

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Eur. J. Org. Chem. 2000, 1137Ϫ1155

Nickel- and Palladium-Catalyzed Cross-Coupling Reactions

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of the long reaction times and moderate yields reported for paration of 14a, as well as halogen–metal exchange prod-

this process. The bridgehead bicyclo[1.1.1]pentylmagnesium ucts. Compounds 8r, 15a, and 18a were identified by means

bromide derivatives thus formed were trapped with various of GC and NMR analyses of the reaction mixture. It is

electrophiles (Scheme 3 and Table 3).

noteworthy that the spectroscopic data of 3,3Ј-di-

phenyl[2]staffane (16a) isolated from this reaction mixture

were in complete agreement with those reported by Michl

et al.,^[4a,19]but not with those erroneously attributed to this

compound in an earlier study;^[20]it was later established

that the latter product was in fact 1-phenylbicyclo[1.1.1]-

pentane (15a).^[4a]Coupling of 14b with p-substituted bro-

mobenzenes under NiCl₂(PPh₃)₂catalysis provided the de-

sired products 17ba and 17bb in even lower yields

(Scheme 4).

Scheme 3. For details see Table 3

Table 3. Formation of 3-arylbicyclo[1.1.1]pent-1-ylmagnesium

bromides 14 and their reactions with electrophiles

The results of these test runs showed that this procedure

could only favorably be used for the addition of unsubsti-

tuted phenyl- and p-(n-propyl)phenylmagnesium bromide,

mainly because of difficulties encountered in purifying any

of the other final coupling products (see below). Com-

pounds 15ca and 15da were not isolated following these test

runs; the relative yields of the overall reactions (Grignard

additions and subsequent trapping) were determined by GC

and NMR analyses. Attempted additions of vinyl- and al-

lylmagnesium bromides to 2 were unsuccessful. This may

be attributed to the limited solubilities of the Normant re-

agent and 13e in diethyl ether (Table 3).

Scheme 4

Apparently, the rate of cross-coupling under these condi-

tions was prohibitively slow. Improvements could be

achieved by (i) employing an excess of the organometallic

intermediate 14, (ii) by a better choice of the metal in the

intermediate of type 6, and (iii) by a better choice of cata-

lyst. Utilization of four equivalents of 14a in the presence

of 10 mol-% of catalyst improved the yields of the cross-

coupling products to a certain extent (Table 4), but, taking

into consideration the difficulties associated with producing

2. Metal-Catalyzed Cross-Coupling of

Bicyclo[1.1.1]pentylmetal Derivatives 6 with Aryl Halides

The first catalysts to be tested in the cross-coupling of 14, the overall approach remained less than satisfactory.

bridgehead magnesium derivatives of type 14 were the pho- The best yield (41%) was obtained for the cross-coupling

sphanenickel(II) complexes reported by Kumada et al.^[18]product of 3-iodopyridine, 17ad. The coupling product of

However, neither with NiCl₂(PPh₃)₂nor NiCl₂dppe were 1-bromocyclooctene, 17af, could not be obtained in suffi-

good yields of the diarylbicyclo[1.1.1]pentanes 17 obtained ciently pure form under these experimental conditions.

in attempted cross-coupling reactions of 14 with aryl iod-

Attempted coupling of 14a with iodobenzene in the pres-

ides. Thus, coupling of the phenyl derivative 14a with ence of 5 mol-% Pd(PPh₃)₄led to essentially the same re-

phenyl iodide in the presence of 3 mol-% NiCl₂dppe led sults as those presented in Scheme 4; the yield of 17aa was

only to a complex mixture (Scheme 4), which apparently only 8%. No significant improvement was observed when

contained products derived from all conceivable cross-coup- 14a was coupled after transmetallation with ZnCl₂.^[21]

ling reactions of the starting materials, including reactions Chlorozinc derivatives of type 19 (Scheme 5), easily pre-

of some residual phenylmagnesium bromide used in the pre- pared from the corresponding bridgehead lithium derivat-

Eur. J. Org. Chem. 2000, 1137Ϫ1155

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M. Messner, S. I. Kozhushkov, A. de Meijere

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Table 4. NiCl₂dppe-catalyzed cross-coupling of aryl and alkenyl coupling reactions of bicyclo[1.1.1]pentylmagnesium and

halides with 4 equivalents of 3-phenylbicyclo[1.1.1]pent-1-ylmagne-

sium bromide 14a at 25 °C

-zinc halide derivatives, 14 and 19, respectively (Table 5).

Table 5. PdCl₂(dppf)-catalyzed cross-coupling of aryl and alkenyl

halides with 3-phenylbicyclo[1.1.1]pent-1-ylmagnesium bromide

14a at 25 °C

In the presence of 2 mol-% PdCl₂(dppf), couplings of 3-

phenylbicyclo[1.1.1]pent-1-ylmagnesium bromide (14a)

with essentially the same series of aryl and alkenyl halides

ives 9 by transmetallation with ZnCl₂THF^[21]in diethyl as used in the NiCl₂dppe-catalyzed reactions (Table 4) gave

ether/pentane mixtures, also gave discouraging results in compounds 17ae and 17af in much better yields. However,

their cross-coupling reactions with aryl iodides under the cross-coupling product of 3-iodopyridine (17ad), which

Pd(PPh₃)₄catalysis in that the rate of homocoupling still was obtained in the highest yield under NiCl₂dppe catalysis,

exceeded that of the cross-coupling reaction.

was not formed at all in this case. Instead, a trace of 1,3-

diphenylbicyclo[1.1.1]pentane (17aa) was detected, which

must have resulted from a coupling reaction with bromob-

enzene or phenylmagnesium bromide, probably still present

in the reaction mixture after the preparation of 14a. Thus,

for the coupling of heterocycles,^[24]NiCl₂dppe may

complement PdCl₂(dppf) as a catalyst (for methods of C–

C bond formation in different heterocycles through Ni- and

Pd-catalyzed cross-coupling, see ref.^[24]).

To test the viability of chlorozinc derivatives 19 in cross-

coupling reactions, one and two equivalents of 19b were

treated with one equivalent of 4-iodotoluene in the presence

of 5 mol-% PdCl₂(dppf). After 1 h at room temperature, the

coupling product 20bb had been formed in 82–86% yield

(GC) along with 9–13% of the homocoupling product 4,4Ј-

dimethylbiphenyl (18b). Neither longer reaction times, the

Scheme 5

Even using a two-fold excess of 9b, the three coupling use of an excess of the chlorozinc reagent, nor its por-

products 20bb, 16b, and 18b were obtained in yields of just tionwise addition, had any significant influence on the re-

33%, 12%, and 53%, respectively (Scheme 5).

sults (Scheme 6).

Since dichloro[1,1Ј-bis(diphenylphosphanyl)ferrocene]-

Under optimized conditions, various p-substituted bro-

palladium(II) [PdCl₂(dppf)] was found to be by far the most mobenzenes, as well as iodobenzene and 2-bromopyrimid-

active and selective catalyst for the coupling of n-, sec-, and ine, were coupled with various 3-substituted bicyclo[1.1.1]-

tert-alkylzinc and -magnesium halides with aromatic hal- pentylzinc chlorides 19. With the exception of the product

ides,^[22]and in view of the fact that this catalyst has also derived from p-dibromobenzene (20ca) the yields were reas-

been successfully employed in the preparation of various onably good throughout (Table 6). However, the p-bromo-

liquid crystalline materials,^[23]it was tested in the cross- phenyl derivative 20ca may easily be obtained in almost

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Nickel- and Palladium-Catalyzed Cross-Coupling Reactions

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ing aryl halide and the coupling product had identical R_f

values upon TLC analysis, which presented additional diffi-

culties in the purification of the final products. This was

not too serious for small scale preparations (1 mmol), but

on a 15–20-mmol scale the product had to be distilled or

recrystallized following column chromatography (see Ex-

perimental Section). The fact that the p-cyanophenyl deriv-

ative 20ec was isolated in 75% yield demonstrates the toler-

ance of chlorozinc reagents towards a cyano group under

the coupling conditions. The addition product of 19e, i.e.

the ketone 21, was isolated in just 2.5% yield.

Scheme 6

As in the attempted coupling of the bridgehead Grignard

reagent 14a, treatment of 3-phenylbicyclo[1.1.1]pent-1-yl-

zinc chloride (19r) with 2- or 5-iodopyrimidine led exclus-

ively to the metal–halogen-exchanged product 3-phenyl-1-

iodobicyclopentane (8r).

Table 6. PdCl₂(dppf)-catalyzed cross-coupling of various aryl hal-

ides with 3-substituted bicyclo[1.1.1]pent-1-ylzinc chlorides 19 in

THF at 25 °C

PdCl₂(dppf)-catalyzed coupling of 3-substituted bicyclo-

[1.1.1]pentylzinc chlorides 19 was also tested in the prepara-

tion of biaryl derivatives such as phenylpyrimidines and bi-

phenyls containing bicyclo[1.1.1]pentyl moieties. Besides bi-

aryl bromides, triflates of hydroxybiaryls^[26]can also be em-

ployed in such reactions (Table 7).^[27]With appropriate vari-

ation of the solvent and proportions of reagents,

diarylbicyclo[1.1.1]pentyl derivatives containing one or two

bicyclo[1.1.1]pentane units were obtained in moderate to

good yields (examples 23ac,be,de,ee). Actually, the crude

yields were even better, as losses were incurred during work-

up. For unknown reasons, the (tetrahydropyranyloxyethyl)-

substituted bicyclo[1.1.1]pentylzinc chloride 19f gave the

correspondingly substituted (p-ethylbiphenyl) derivative

23ff in particularly low yield (10%). As in the case of the

monoaryl derivatives, the starting materials and coupling

products tended to be inseparable by column chromato-

graphy on silica gel, although the final products could be

purified by recrystallization from methanol, albeit with

slightly decreased yields. The mono- and bis-coupling prod-

ucts of 4,4Ј-dibromobiphenyl (22a), i.e. 23aja and 23ajb,

could be separated by column chromatography using ben-

zene as a co-eluent.

3. Chemical Transformations of the Coupling Products

In order to introduce certain functional groups, e.g. a cy-

ano group,^[28]with a view to improving particular liquid

crystalline features of the molecules, a series of subsequent

quantitative yield by bromination of the p-(trimethylsilyl)- manipulations had to be performed with the coupling prod-

phenyl derivative 20cb in methanol^[25](see Experimental ucts, as the correspondingly substituted products were not

Section). The trimethylsilyl derivative 20cb was obtained in directly accessible by such coupling reactions. Although it

good yield only when two equivalents of the chlorozinc re- should be possible to couple 4-bromo-4Ј-cyanobiphenyl

agent 19c were employed. All the products 20 were accom- (see, e.g., the successful coupling of p-bromobenzonitrile,

panied by the aryl halide homocoupling products, i.e. the Table 6), the desired p-cyanobiphenyl-substituted end prod-

correspondingly disubstituted biaryls, in yields of 10–13%.

ucts 24ab,ae can also readily be prepared from 23ab,ae, the

Only 20ca was formed alongside a 58% isolated yield of products of monocoupling of 4,4Ј-dibromobiphenyl

4,4Ј-dibromobiphenyl. Amazingly, in many cases the start- (Scheme 7).

Eur. J. Org. Chem. 2000, 1137Ϫ1155

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M. Messner, S. I. Kozhushkov, A. de Meijere

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Table 7. PdCl₂(dppf)-catalyzed cross-coupling of biaryl halides and triflates p-Ar–X (22) with 0.5–4 equiv. of 3-substituted bicyclo[1.1.1]-

pent-1-ylzinc chlorides 19 in Et₂O or THF at 25 °C

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Nickel- and Palladium-Catalyzed Cross-Coupling Reactions

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addition of 1,1,1-trichloroethane to propellane 2^[29]and

subsequent twofold dehydrochlorination. Attempts to per-

form a direct coupling of the bicyclo[1.1.1]pentylzinc chlor-

ide derivative 19c with 1-iodo-2-(trimethylsilyl)ethyne^[30]

under PdCl₂(dppf) catalysis failed completely: the metal–

halogen exchange product 8c was formed exclusively and

could be isolated in almost quantitative yield. Therefore, a

new approach based on the well-known rearrangement of

vinyl carbenoids (the so-called Fritsch–Buttenberg–Wichell

rearrangement^[31]) was elaborated. In view of the facile pre-

paration of bicyclo[1.1.1]pentyl ketones from bridgehead

bicyclo[1.1.1]pentyllithium derivatives and acid chlorides

(see Table 2), the n-propylbicyclo[1.1.1]pentylcarboxylic

acid 10b was converted into the acid chloride 29,^[8a]and

this in turn was reacted with the (p-lithiophenyl)bicyclo-

[1.1.1]pentyl derivative obtained from 20ca and tBuLi to

give the ketone 30 in 78% yield (Scheme 9).

Scheme 7

Since all attempts to prepare 3-vinyl- and 3-allylbicyclo-

[1.1.1]pentyl iodides 8k,l have hitherto proved unsuccessful

(Table 1), the preparation of compounds of type 23 con-

taining a double bond in the end group was attempted by

transformation of the tetrahydropyranyl-protected hydroxy-

alkyl derivatives 23ff,fg,gh. The latter can be smoothly de-

protected to give hydroxyalkyl derivatives such as 25, or

directly transformed by treatment with triphenylphosphane/

bromine to give bromides 26ff,fg. Dehydrobromination of

26ff with tBuOK/DMSO proceeded normally, although the

solubility of 26ff in DMSO was extremely low (Scheme 8).

In the case of 26fg, however, a mixture of the tert-butoxide

substitution product 28 and the allyl rearrangement prod-

uct 27fg was obtained (Scheme 8).

Scheme 9

Wittig olefination with chloromethylenetriphenylphos-

phorane, followed by treatment of the chloroalkene 31 with

BuLi, provided the desired internal acetylene 32 in 53%

yield, along with the 1,1-disubstituted ethylene 33 resulting

from metal–halogen exchange on 31 and subsequent hydro-

lysis.

To summarize the results presented herein, PdCl₂(dppf)-

catalyzed coupling of 3-substituted bridgehead bicyclo-

[1.1.1]pentylzinc chlorides constitutes the most powerful

tool for the construction of rod-like molecules containing

bicyclo[1.1.1]pentyl fragments. Several of these new bicyclo-

[1.1.1]pentyl derivatives do indeed exhibit quite interesting

liquid crystalline properties, which have been reported sep-

arately.^[32]

Scheme 8

Particular difficulties were encountered when attempts

were made to construct molecules with ethynyl groups dir-

ectly bound to bicyclo[1.1.1]pentyl moieties. A previously

Experimental Section

General: ¹H and ¹³C NMR: Spectra were recorded at 200 or

pursued strategy involved the low-yielding photochemical 250 MHz (¹H), and at 62.9 MHz [¹³C and additional DEPT (Dis-

Eur. J. Org. Chem. 2000, 1137Ϫ1155

1143

M. Messner, S. I. Kozhushkov, A. de Meijere

tortionless Enhancement by Polarization Transfer)] with Varian XL 1-Heptyl-3-iodobicyclo[1.1.1]pentane (8d): From 1-iodoheptane

FULL PAPER

200 and Bruker AM 250 instruments in CDCl₃solution; CHCl₃/

CDCl₃as internal reference; δ in ppm, J in Hz. – IR: Perkin–Elmer

298. – FT-IR: Bruker IFS 66; samples in KBr pellets or as films

between NaCl plates. – MS (EI): Finnigan MAT 95 spectrometer

(70 eV). – M.p.: Büchi 510 capillary melting point apparatus; un-

corrected values. – GC analyses: Siemens Sichromat 1–4, 25-m ca-

pillary column CP-SIL-5-CB. – GC separations: Intersmat 130 in-

strument, 20% SE-30 on Chromaton W-AW-DMCS, 1500 ϫ

(4.30 g, 3.12 mL, 19 mmol), compound 8d (4.48 g, 81%) was ob-

tained according to GP 1. – IR: ν˜ ϭ 2926 cm^–1, 1466, 1378, 1261,

1

1174, 1130, 1022, 984, 839, 722, 669. – H NMR: δ ϭ 0.88 (t, J ϭ

6.6 Hz, 3 H, CH₃), 1.23 (m, 10 H, 5 CH₂), 1.48 (t, J ϭ 6.4 Hz, 2

H, CH₂), 2.19 (s, 6 H, 3 CH₂). – ¹³C NMR: δ ϭ 14.1 (CH₃), 60.6

(3 CH₂), 22.6, 26.8, 29.2, 29.4, 31.8, 32.1 (CH₂), 8.2, 48.6 (C).

1-Iodo-3-octylbicyclo[1.1.1]pentane (8e): From 1-iodooctane (4.08 g,

3.07 mL, 17 mmol), compound 8e (5.10 g, 98%) was obtained ac-

cording to GP 1. – IR: ν˜ ϭ 2990 cm^–1, 2960, 2925, 2875, 2855,

8.2 mm column.

– TLC: Macherey–Nagel precoated sheets,

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

grade 60, 230–400 mesh. – Starting materials: Anhydrous diethyl

ether and THF were obtained by distillation from sodium benzo-

phenone ketyl, pyridine from CaH₂, and dichloromethane from

P₄O₁₀. Compounds 2,^[6,8a,10]7f,^[33]7g,^[34]7i,^[35]4-bromobutyl- and

propylbenzenes,^[36]4-bromo-4Ј-ethylbiphenyl (22f),^[37](4-bromo-

phenyl)trimethylsilane,^[38]22g,^[39]lithium 4,4Ј-di-tert-butylbi-

phenylide,^[16a]and PdCl₂(dppf)^[22]were prepared according to pub-

lished procedures. Vinyl iodide was obtained in 50% yield by treat-

ing vinylmagnesium bromide with I₂in THF solution. Iodides

7j,^[40]7h, and 7m^[41]were prepared from the corresponding alco-

hols^[42]in 88%, 80%, and 67% yield, respectively, using the I₂/Ph₃P/

ImH reagent;^[43]compounds 7o,p were obtained using the reagent

[(PhO)₃PMe]I.^[44]– 7j: ¹H NMR: δ ϭ 1.14 (t, J ϭ 7.5 Hz, 3 H,

CH₃), 2.18 (qt, J ϭ 7.5, 2.2 Hz, 2 H, CH₂), 2.76 (qt, J ϭ 7.1,

2.2 Hz, 2 H, CH₂), 3.24 (t, J ϭ 7.1 Hz, 2 H, CH₂I). – ¹³C NMR:

δ ϭ 14.0 (CH₃), 2.6, 12.4, 24.1 (CH₂), 78.1, 83.8 (C). – 22f: ¹H

NMR: δ ϭ 1.26 (t, J ϭ 7.5 Hz, 3 H, CH₃), 2.69 (q, J ϭ 7.5 Hz, 2

H, CH₂), 7.25 (d, J ϭ 8.6 Hz, 2 H, C₆H₄), 7.35–7.55 (m, 6 H,

C₆H₄). – ¹³C NMR: δ ϭ 15.6 (CH₃), 28.5 (CH₂), 126.8, 128.4,

128.5, 131.8 (2 CH), 121.2, 137.3, 140.0, 142.8 (C). All other chem-

icals were used as received from commercial suppliers (Merck,

Acros, BASF, Bayer, Hoechst, Degussa AG, or Hüls AG). All reac-

tions were performed under argon. Organic extracts were dried

with MgSO₄.

1

1450, 1175, 840. – H NMR: δ ϭ 0.89 (t, J ϭ 6.6 Hz, 3 H, CH₃),

1.27 (m, 12 H, 6 CH₂), 1.42–1.55 (m, 2 H, CH₂), 2.18 (s, 6 H, 3

CH₂). – ¹³C NMR: δ ϭ 14.1 (CH₃), 60.5 (3 CH₂), 22.6, 26.8, 29.4,

29.5, 29.6, 31.8, 32.1 (CH₂), 8.1, 48.5 (C).

1-Iodo-3-[3-(tetrahydropyran-2-yloxy)propyl]bicyclo[1.1.1]pentane

(8g): From 7g (20.0 g, 74 mmol), compound 8g (24.4 g, 98%) was

1

obtained according to GP 1. – H NMR: δ ϭ 1.45–1.90 (m, 10 H,

5 CH₂), 2.17 (s, 6 H, 3 CH₂), 3.25–3.35 (m, 1 H, OCH₂), 3.35–3.50

(m, 1 H, OCH₂), 3.60–3.70 (m, 1 H, OCH₂), 3.70–3.85 (m, 1 H,

OCH₂), 4.54 (t, J ϭ 3.2 Hz, 1 H, OCH). – ¹³C NMR: δ ϭ 60.3 (3

CH₂), 19.5, 25.3, 26.9, 28.7, 30.5, 62.2, 66.9 (CH₂), 98.6 (CH), 7.6,

48.1 (C).

1-Iodo-3-[4-(tetrahydropyran-2-yloxy)butyl]bicyclo[1.1.1]pentane

(8h): From 7h (5.1 g, 18 mmol), compound 8h (6.1 g, 96%) was ob-

tained according to GP 1. – IR: ν˜ ϭ 2938 cm^–1, 1453, 1353, 1329,

1261, 1200, 1175, 1128, 1078, 1035, 988, 906, 869, 837. – ¹H NMR:

δ ϭ 1.22–1.90 (m, 12 H, 6 CH₂), 2.18 (s, 6 H, 3 CH₂), 3.36 (dt,

J ϭ 9.5, 6.6 Hz, 1 H, OCH₂), 3.42–3.56 (m, 1 H, OCH₂), 3.71 (dt,

J ϭ 9.5, 6.9 Hz, 1 H, OCH₂), 3.85 (ddd, J ϭ 11.4, 7.5, 3.5 Hz, 1

H, OCH₂), 4.57 (t, J ϭ 3.2 Hz, 1 H, OCH). – ¹³C NMR: δ ϭ 60.4

(3 CH₂), 19.6, 23.5, 25.4, 29.5, 30.6, 31.8, 62.3, 67.2 (CH₂), 98.8

(CH), 7.8, 48.3 (C).

1-Iodo-3-[8-(tetrahydropyran-2-yloxy)octyl]bicyclo[1.1.1]pentane

General Procedure (GP 1) for the Preparation of 8a–e,g–i,m–q: To

(8i): From 7i (4.70 g, 13.8 mmol), compound 8i (5.44 g, 97%) was

a

solution of the appropriate iodoalkane

7

(28 mmol) and

1

obtained according to GP 1. – H NMR: δ ϭ 1.22–1.38 (m, 10 H,

[1.1.1]propellane (2) (30 mmol) in anhydrous Et₂O (100 mL), a 1.56

 solution of MeLi in Et₂O (18 mL, 28 mmol) was added dropwise

at –40 °C. The reaction mixture was allowed to warm to room

temp., stirred for 24 h, and then cooled to –40 °C once more,

whereupon MeOH (20 mL) was added. The resulting solution was

poured into an ice-cold mixture of H₂O (50 mL) and pentane

(50 mL). After separation of the layers, the organic phase was

washed with H₂O (2 ϫ 50 mL), dried, and concentrated under re-

duced pressure at 0 °C. The residue was used for the next step

without purification.

5 CH₂), 1.39–1.92 (m, 10 H, 5 CH₂), 2.18 (s, 6 H, 3 CH₂), 3.36 (dt,

J ϭ 9.5, 6.6 Hz, 1 H, OCH₂), 3.43–3.53 (m, 1 H, OCH₂), 3.71 (dt,

J ϭ 9.5, 6.9 Hz, 1 H, OCH₂), 3.85 (ddd, J ϭ 11.4, 7.5, 3.5 Hz, 1

H, OCH₂), 4.55 (t, J ϭ 3.2 Hz, 1 H, OCH). – ¹³C NMR: δ ϭ 60.5

(3 CH₂), 19.6, 25.4, 26.1, 27.0, 29.3, 29.4, 29.6, 30.7, 32.0, 62.3,

67.5 (CH₂), 98.7 (CH), 8.1, 48.5 (C).

1-Iodo-3-[(E)-pent-3-enyl]bicyclo[1.1.1]pentane (8m): From (E)-5-

iodopent-2-ene (9.729 g, 49.63 mmol), compound 8m (13.0 g,

1

100%) was obtained according to GP 1. – H NMR: δ ϭ 1.58 (t,

J ϭ 8.0 Hz, 2 H, CH₂), 1.61 (d, J ϭ 5.6 Hz, 3 H, CH₃), 1.85–2.05

(m, 2 H, CH₂), 2.20 (s, 6 H, 3 CH₂), 5.25–5.51 (m, 2 H, CHϭ

CH). – ¹³C NMR: δ ϭ 17.9 (CH₃), 60.5 (3 CH₂), 29.8, 31.8 (CH₂),

125.3, 130.4 (CH), 8.0, 48.3 (C).

1-Iodo-3-methylbicyclo[1.1.1]pentane (8a): From MeI (2.56 g,

1.12 mL, 18 mmol), compound 8a^[13b](3.11 g, 83%) was obtained

according to GP 1. – ¹H NMR: δ ϭ 1.22 (s, 3 H, CH₃), 2.21 (s,

6 H, 3 CH₂). – ¹³C NMR: δ ϭ 18.3 (CH₃), 62.1 (3 CH₂), 7.0,

44.6 (C).

1-Cyclohexyl-3-iodobicyclo[1.1.1]pentane (8n): From iodocyclohex-

ane (1.09 g, 0.67 mL, 5.2 mmol), compound 8n (1.21 g, 84%) was

1-Iodo-3-propylbicyclo[1.1.1]pentane (8b): From PrI (6.80 g,

3.92 mL, 40 mmol), compound 8b (8.88 g, 94%) was obtained ac-

cording to GP 1. – IR: ν˜ ϭ 2980 cm^–1, 2960, 2910, 2870, 1446,

1

obtained according to GP 1. – H NMR: δ ϭ 0.68–0.97 (m, 2 H,

CH₂), 1.00–1.82 (m, 9 H), 2.17 (s, 6 H, 3 CH₂). – ¹³C NMR: δ ϭ

58.6 (3 CH₂), 25.9, 29.6 (2 CH₂), 25.8 (CH₂), 39.3 (CH), 8.9, 52.4

(C).

1

1171, 985, 836. – H NMR: δ ϭ 0.88 (t, J ϭ 7.4 Hz, 3 H, CH₃),

1.18–1.34 (m, 2 H, CH₂), 1.48 (t, J ϭ 7.8 Hz, 2 H, CH₂), 2.19 (s,

6 H, 3 CH₂). – ¹³C NMR: δ ϭ 14.0 (CH₃), 60.7 (3 CH₂), 20.0, 34.2

(CH₂), 7.9, 48.5 (C).

1-Iodo-3-(4-phenylcyclohexyl)bicyclo[1.1.1]pentane (8o): From cis-4-

phenylcyclohexyl iodide 7o (4.49 g, 15.7 mmol), compound 8o

(5.26 g, 95%) was obtained according to GP 1 as a 2:1 mixture of

cis and trans isomers. An analytical sample of trans-8o was ob-

tained after repeated (4 times) recrystallization from pentane; m.p.

1-Butyl-3-iodobicyclo[1.1.1]pentane (8c): From BuI (14.72 g,

9.10 mL, 80 mmol), compound 8c^[4a](19.41 g, 97%) was obtained

according to GP 1.

1144

Eur. J. Org. Chem. 2000, 1137Ϫ1155

Nickel- and Palladium-Catalyzed Cross-Coupling Reactions

FULL PAPER

105 °C (dec.). – IR: ν˜ ϭ 3080 cm^–1, 3055, 3020, 2985, 2960, 2910,

2870, 2850, 1600, 1592, 1546, 1173, 968, 852, 835, 800, 756, 700. –

¹H NMR: δ ϭ 1.07 (dq, J ϭ 12.8, 3.2 Hz, 2 H, CH₂), 1.43 (dq,

J ϭ 12.8, 3.2 Hz, 2 H, CH₂), 1.52 (tt, J ϭ 12.4, 3.4 Hz, 1 H, CH),

1.75 (dm, J ϭ 13.2, Hz, 2 H, CH₂), 1.91 (dm, J ϭ 13.2 Hz, 2 H,

CH₂), 2.19 (s, 6 H, 3 CH₂), 2.41 (tt, J ϭ 12.2, 3.2 Hz, 1 H, CH),

7.12–7.33 (m, 5 H, Ph). – ¹³C NMR: δ ϭ 58.6 (3 CH₂), 29.8, 33.5

(2 CH₂), 125.9, 126.7 (2 CH), 38.8, 43.8, 128.3 (CH), 8.6, 52.1,

147.1 (C). – C₁₇H₂₁I (352.3): calcd. C 57.96, H 6.01, I 36.03; found

C 57.81, H 6.06, I 36.03. – After evaporation of the solvent from

the mother liquor, another recrystallization from pentane gave an

analytical sample of cis-8o; m.p. 49 °C (dec.). – IR: ν˜ ϭ 3075

cm^–1, 3060, 3020, 2985, 2960, 2870, 2845, 1595, 1490, 1442, 1358,

1-Iodo-3-phenylbicyclo[1.1.1]pentane (8r): From iodobenzene (7r)

(645 mg, 354 µL, 3.16 mmol), compound 8r^[4a](179 mg, 21%) was

obtained according to GP 2.

1-Iodo-3-(p-tolyl)bicyclo[1.1.1]pentane (8s): From 4-iodotoluene (7s)

(678 mg, 3.11 mmol), compound 8s^[45](89 mg, 10%) was obtained

according to GP 2.

General Procedure (GP 3) for the Lithiation of 3-Substituted 1-Iodo-

bicyclo[1.1.1]pentanes 8: To a 0.3  solution of LiDBB in THF

(50 mL, 15 mmol), a solution of 8 (6 mmol) in THF (10 mL) was

added dropwise at –78 °C. After stirring the deep-blue reaction

mixture for 1 h at this temp., a 10-fold excess of powdered dry ice

was added in a single portion. The mixture was allowed to warm

to room temp. and then extracted with 5% NaHCO₃solution (2 ϫ

50 mL). The combined aqueous phases were acidified to pH ϭ 2–

3 with conc. HCl at 0 °C, saturated with NaCl, and extracted with

Et₂O (4 ϫ 50 mL). The combined organic phases were dried and,

after evaporation of the solvent under reduced pressure, purified as

specified below.

1

1162, 858, 839, 825, 818, 746, 700. – H NMR: δ ϭ 1.07 (dq, J ϭ

12.8, 3.2 Hz, 2 H, CH₂), 1.43 (dq, J ϭ 12.8, 3.2 Hz, 2 H, CH₂),

1.52 (tt, J ϭ 12.4, 3.4 Hz, 1 H, CH), 1.75 (dm, J ϭ 13.2 Hz, 2 H,

CH₂), 1.91 (dm, J ϭ 13.2 Hz, 2 H, CH₂), 2.19 (s, 6 H, 3 CH₂), 2.41

(tt, J ϭ 12.2, 3.2 Hz, 1 H, CH), 7.12–7.33 (m, 5 H, Ph). – ¹³C

NMR: δ ϭ 58.6 (3 CH₂), 29.8, 33.5 (2 CH₂), 125.9, 126.7 (2 CH),

38.8, 43.8, 128.3 (CH), 8.6, 52.1, 147.1 (C).

General Procedure (GP 4) for the Lithiation of 3-Substituted 1-Iodo-

bicyclo[1.1.1]pentanes 8: To a solution of 8 (30 mmol) in Et₂O

(100 mL), a 1.5  solution of tBuLi in n-pentane (40 mL, 60 mmol)

was added over a period of 40 min at Ϫ78 °C. After stirring the

reaction mixture for 1 h at this temp., the appropriate electrophile

was added and the mixture was worked-up under the conditions

specified below.

1-[4-(4-Fluorophenyl)cyclohexyl]-3-iodobicyclo[1.1.1]pentane (8p):

From cis-7p (155 mg, 0.51 mmol), compound 8p (174 mg, 92%) was

obtained according to GP 1 as a 2:1 mixture of cis and trans iso-

mers. – ¹H NMR: δ ϭ 0.95–1.96 (m, 9 H), 2.18 (s, 6 H, 3 CH₂,

trans), 2.28 (s, 6 H, 3 CH₂, cis), 2.39 (m, 1 H, CH, trans), 2.60 (m,

1 H, CH, cis), 6.90–7.02 (m, 2 H, C₆H₄), 7.05–7.20 (m, 2 H, C₆H₄).

1-Iodo-3-[4-(4-propylphenyl)cyclohexyl]bicyclo[1.1.1]pentane (8q):

From trans-7q (17 mg, 0.05 mmol), compound 8q (18 mg, 88%) was

obtained according to GP 1 as a 2:1 mixture of cis and trans iso-

3-Propylbicyclo[1.1.1]pentane-1-carboxylic Acid (10b): From 8b

(17.71 g, 75 mmol), compound 10b (11.22 g, 97%) was obtained ac-

cording to GP 4, in almost pure form following work-up as in GP

3. An analytical sample was recrystallized from hexane; m.p. 71–

1

mers. – H NMR: δ ϭ 0.92 (t, J ϭ 7.2 Hz, 3 H, CH₃), 1.01–2.00

(m, 11 H), 2.20 (s, 6 H, 3 CH₂, trans), 2.31 (s, 6 H, 3 CH₂, cis),

2.35–2.50 (m, 1 H, CH), 2.54 (t, J ϭ 7.0 Hz, 2 H, CH₂), 7.05–7.12

(m, 4 H, C₆H₄).

1

72 °C. – H NMR: δ ϭ 0.89 (t, J ϭ 6.7 Hz, 3 H, CH₃), 1.15–1.35

(m, 2 H, CH₂), 1.40 (t, J ϭ 7.0 Hz, 2 H, CH₂), 1.90 (s, 6 H, 3 CH₂),

9.65 (s, 1 H, OH). – ¹³C NMR: δ ϭ 14.2 (CH₃), 51.5 (3 CH₂), 19.5,

33.4 (CH₂), 37.5, 40.2, 176.5 (C). – C₉H₁₄O₂(154.2): calcd. C 70.10,

H 9.15; found C 70.04, H 9.07

General Procedure (GP 2) for the Preparation of 8f,j,r,s: A solution

of the appropriate iodoalkane 7f,j,r,s (29 mmol) and [1.1.1]pro-

pellane (2) (30 mmol) in anhydrous Et₂O (100 mL) was irradiated

in a Pyrex vessel at 0 °C for 1 h (7f,j) or 4 h (7r,s) with light from

a 500-W medium-pressure Hanovia mercury lamp. The volatiles

were then evaporated, and the residue was either used without fur-

ther purification (8f), recrystallized from pentane at –30 °C (8j), or

chromatographed (8r,s) (25 g of silica gel, column 16 ϫ 2 cm, pent-

ane).

3-Butylbicyclo[1.1.1]pentane-1-carboxylic Acid (10c): From 8c

(1.06 g, 4.24 mmol), compound 10c^[4a](430 mg, 60%) was obtained

according to GP 3 and subsequent column chromatography (5 g of

silica gel, column 12 ϫ 1 cm, hexane/Et₂O, 4:1).

3-Heptylbicyclo[1.1.1]pentane-1-carboxylic Acid (10d): From 8d

(4.27 g, 14.6 mmol), compound 10d (1.66 g, 54%) was obtained ac-

cording to GP 3 and subsequent column chromatography (100 g of

silica gel, column 20 ϫ 4 cm, hexane/Et₂O, 9:1, gradient Et₂O),

R_fϭ 0.60 (Et₂O); m.p. 42 °C. – IR: ν˜ ϭ 2957 cm^–1, 2913, 2853,

2589, 1704, 1517, 1469, 1425, 1339, 1317, 1287, 1214, 960, 751,

1-Iodo-3-[2-(tetrahydropyran-2-yloxy)ethyl]bicyclo[1.1.1]pentane

(8f): From 7f (25.61 g, 0.1 mol), compound 8f (29.67 g, 92%) was

1

obtained according to GP 2. – H NMR: δ ϭ 1.40–1.85 (m, 6 H,

3 CH₂), 1.75 (t, J ϭ 6.9 Hz, 2 H, CH₂), 2.22 (s, 6 H, 3 CH₂), 3.20–

3.40 (m, 1 H, OCH₂), 3.40–3.60 (m, 1 H, OCH₂), 3.60–3.70 (m, 1

H, OCH₂), 3.71–3.92 (m, 1 H, OCH₂), 4.49 (t, J ϭ 3.2 Hz, 1 H,

OCH). – ¹³C NMR: δ ϭ 60.8 (3 CH₂), 19.3, 25.3, 30.5, 31.7, 62.1,

65.0 (CH₂), 98.7 (CH), 7.4, 46.3 (C).

1

723. – H NMR: δ ϭ 0.89 (t, J ϭ 6.6 Hz, 3 H, CH₃), 1.22 (m, 10

H, 5 CH₂), 1.43 (t, J ϭ 6.4 Hz, 2 H, CH₂), 1.92 (s, 6 H, 3 CH₂),

10.50 (s, 1 H, OH). – ¹³C NMR: δ ϭ 14.1 (CH₃), 51.5 (3 CH₂),

22.7, 26.3, 29.6, 29.7, 31.2, 31.8 (CH₂), 37.6, 40.3, 176.7 (C). –

C₁₃H₂₂O₂(210.3): calcd. C 74.24, H 10.55; found C 74.16, H 10.70.

1-(Hex-3-ynyl)-3-iodobicyclo[1.1.1]pentane (8j): From 7j (17.7 g,

85 mmol), compound 8j was obtained according to GP 2 [crude:

3-Octylbicyclo[1.1.1]pentane-1-carboxylic Acid (10e): From 8e

15.6 g, 67%; pure 8j can be isolated, albeit in moderate yield, from (1.24 g, 4.05 mmol), compound 10e (410 mg, 45%) was obtained

the residual starting iodide (which is more active in a coupling reac-

according to GP 3 and subsequent column chromatography (5 g of

tion) by low-temperature recrystallization from pentane; recrystal-

silica gel, column 12 ϫ 1 cm, hexane/Et₂O, 4:1); m.p. 33–36 °C. –

lized pure material: 9.53 g, 41%]; m.p. 32–34 °C. – H NMR: δ ϭ ¹H NMR: δ ϭ 0.88 (t, J ϭ 6.6 Hz, 3 H, CH₃), 1.29 (m, 12 H, 6

1.08 (t, J ϭ 7.5 Hz, 3 H, CH₃), 1.67 (t, J ϭ 6.9 Hz, 2 H, CH₂), CH₂), 1.40–1.52 (m, 2 H, CH₂), 1.91 (s, 6 H, 3 CH₂), 10.20 (s, 1

2.05–2.18 (m, 4 H, 2 CH₂), 2.23 (s, 6 H, 3 CH₂). – ¹³C NMR: δ ϭ H, OH). – ¹³C NMR: δ ϭ 14.1 (CH₃), 51.6 (3 CH₂), 22.7, 26.3,

14.1 (CH₃), 60.5 (3 CH₂), 12.3, 16.3, 31.2 (CH₂), 7.4, 47.8, 78.4, 29.3, 29.6, 29.7, 31.2, 31.9 (CH₂), 37.6, 40.4, 176.6 (C). – C₁₄H₂₄O₂

1

82.2 (C).

(224.3): calcd. C 74.95, H 10.78; found C 74.64, H 10.81.

Eur. J. Org. Chem. 2000, 1137Ϫ1155

1145

M. Messner, S. I. Kozhushkov, A. de Meijere

FULL PAPER

3-[4-(Tetrahydropyran-2-yloxy)butyl]bicyclo[1.1.1]pentane-1-carb-

oxylic Acid (10h): From 8h (9.50 g, 27.1 mmol), compound 10h

(4.10 g, 56%) was obtained according to GP 3 in almost pure form

reaction mixture was worked-up as described above for 11b. After

evaporation of the solvent, the residue was purified by bulb-to-bulb

distillation under reduced pressure to give 11cd (153 mg, 78%). –

1

as an oil. – ¹H NMR: δ ϭ 0.95–1.80 (m, 12 H, 6 CH₂), 1.92 (s, 6 H, IR: ν˜ ϭ 2965 cm^–1, 2940, 2910, 2875, 1475, 1256, 910, 845. – H

3 CH₂), 3.40–4.35 (m, 4 H, OCH₂), 4.55 (t, J ϭ 3.2 Hz, 1 H, OCH).

NMR: δ ϭ 0.08 (s, 9 H, 3 CH₃), 0.87 (t, J ϭ 7.0 Hz, 3 H, CH₃),

1.10–1.36 (m, 6 H, 3 CH₂), 1.52 (s, 6 H, 3 CH₂). – ¹³C NMR: δ ϭ

–3.4 (3 CH₃), 14.1 (CH₃), 50.2 (3 CH₂), 22.9, 28.4, 33.6 (CH₂),

29.4, 46.3 (C).

3-[8-(Tetrahydropyran-2-yloxy)octyl]bicyclo[1.1.1]pentane-1-carb-

oxylic Acid (10i): From 8i (5.0 g, 12.3 mmol), compound 10i

(2.12 g, 53%) was obtained as an oil according to GP 3 and sub-

sequent filtration with Et₂O through a 1 cm pad of silica gel. – IR:

ν˜ ϭ 3100 cm^–1, 2980, 2930, 2890, 2860, 1719, 1220, 1208, 1192,

1140, 1125, 1040, 1027. – ¹H NMR: δ ϭ 1.10–1.32 (m, 10 H, 5

CH₂), 1.35–1.82 (m, 10 H, 5 CH₂), 1.84 (s, 6 H, 3 CH₂), 3.38 (dt,

J ϭ 9.5, 6.9 Hz, 1 H, OCH₂), 3.45–3.56 (m, 1 H, OCH₂), 3.73 (dt,

J ϭ 9.5, 6.9 Hz, 1 H, OCH₂), 3.87 (ddd, J ϭ 11.4, 7.5, 3.7 Hz, 1

H, OCH₂), 4.55 (t, J ϭ 3.2 Hz, 1 H, OCH), 10.68 (s, 1 H, OH). –

¹³C NMR: δ ϭ 51.4 (3 CH₂), 19.4, 25.4, 26.1, 26.2, 29.3, 29.4, 29.5,

29.6, 29.6, 31.1, 62.1, 67.6 (CH₂), 98.6 (CH), 37.5, 40.2, 175.8 (C). –

MS (EI): m/z (%) ϭ 324 (1) [M^ϩ], 323 (4) [M^ϩ– H], 85 (100). –

C₁₉H₃₂O₄(324.5): calcd. C 70.33, H 9.94; found C 70.45, H 9.83.

1-[8-(Tetrahydropyran-2-yloxy)octyl]bicyclo[1.1.1]pentane (11i): The

lithium derivative 9i, prepared from 8i (1.220 g, 3 mmol) according

to GP 4, was quenched with MeOH (2 mL). After work-up as de-

scribed above for 11b followed by column chromatography of the

residue (30 g of silica gel, column 15 ϫ 3 cm, hexane/Et₂O, 9:1),

1

11i (784 mg, 93%) was obtained as an oil, R_fϭ 0.25. – H NMR:

δ ϭ 1.10–1.39 (m, 10 H, 5 CH₂), 1.43–1.90 (m, 10 H, 5 CH₂), 1.58

(s, 6 H, 3 CH₂), 2.40 (s, 1 H, CH), 3.36 (dt, J ϭ 9.5, 6.6 Hz, 1 H,

OCH₂), 3.42–3.52 (m, 1 H, OCH₂), 3.70 (dt, J ϭ 9.5, 6.9 Hz, 1 H,

OCH₂), 3.84 (ddd, J ϭ 11.4, 7.5, 3.7 Hz, 1 H, OCH₂), 4.55 (t, J ϭ

3.2 Hz, 1 H, OCH). – ¹³C NMR: δ ϭ 50.3 (3 CH₂), 19.6, 25.5,

26.2, 26.5, 29.4, 29.5, 29.7, 30.7, 32.5, 52.3, 62.2, 67.6 (CH₂), 27.3,

98.7 (CH), 45.8 (C). – C₁₈H₃₂O₂(280.4): calcd. C 77.09, H 11.50;

found C 76.93, H 11.45.

3-(4-Phenylcyclohexyl)bicyclo[1.1.1]pentane-1-carboxylic

Acid

(10o): From 8o (5.20 g, 14.76 mmol, 2:1 mixture of cis and trans

isomers), compound 10o (1.77 g, 44%) was obtained according to

1

GP 3 as an oil. – H NMR: δ ϭ 0.80–1.95 (m, 9 H), 1.91 (s, 6 H,

1-(4-Fluorobenzoyl)-3-propylbicyclo[1.1.1]pentane (12b): To the li-

thium derivative 9b, prepared from 8b (427 mg, 1.8 mmol) accord-

ing to GP 4, a solution of 4-fluorobenzonitrile (247 mg, 2.0 mmol)

in anhydrous Et₂O (5 mL) was added dropwise at –78 °C. After

stirring the reaction mixture for 1 h at room temp., 5% aq. HCl

(2 mL) was added and stirring was continued for a further 1 h at

this temp. The organic phase was subsequently washed with 5%

NaHCO₃solution and brine (10 mL each), dried, and concen-

trated. Column chromatography of the residue (50 g of silica gel,

column 15 ϫ 3 cm, hexane/Et₂O, 9:1) furnished 12b (327 mg, 78%)

as an oil, R_fϭ 0.35. – IR: ν˜ ϭ 3075 cm^–1, 2970, 2920, 2880, 1669,

1602, 1508, 1359, 1241, 1230, 1207, 1158, 935, 855, 620. – ¹H

NMR: δ ϭ 0.91 (t, J ϭ 7.2 Hz, 3 H, CH₃), 1.21–1.40 (m, 2 H,

CH₂), 1.40–1.53 (m, 2 H, CH₂), 2.09 (s, 6 H, 3 CH₂), 7.06 (tt, J ϭ

8.6, 2.4 Hz, 2 H, C₆H₄), 8.03 (m, 2 H, C₆H₄). – ¹³C NMR: δ ϭ

14.2 (CH₃), 53.4 (3 CH₂), 19.5, 33.5 (CH₂), 115.4 (d, J ϭ 21.7 Hz),

131.5 (d, J ϭ 9.3 Hz) (2 CH), 40.8, 44.0, 133.0, 165.4 (d, J ϭ

254.3 Hz), 196.19 (C).

3 CH₂, trans), 2.03 (s, 6 H, 3 CH₂, cis), 2.44 (m, 1 H, CH, trans),

2.56–2.75 (m, 1 H, CH, cis), 7.15–7.35 (m, 5 H, Ph), 10.09 (s, 1

H, OH).

2-(3-Propylbicyclo[1.1.1]pent-1-yl)propan-2-ol (11b): To the lithium

derivative 9b, prepared from 8b (5.10 g, 21.6 mmol) according to

GP 4, anhydrous acetone (2.50 g, 3.20 mL, 43 mmol) in Et₂O

(10 mL) was added dropwise at –78 °C. The mixture was allowed

to warm to room temp. and then washed with brine (2 ϫ 30 mL).

The organic phase was dried, the solvent was evaporated, and the

residue was separated by preparative GC at 130 °C to give 11b

(1.91 g, 52%); m.p. 34 °C. – IR: ν˜ ϭ 3420 cm^–1, 2970, 2920, 2870,

1

1450, 1372, 1266, 1185, 951. – H NMR: δ ϭ 0.90 (t, J ϭ 7.2 Hz,

3 H, CH₃), 1.14 (s, 6 H, 2 CH₃), 1.23 (s, 1 H, OH), 1.19–1.41 (m,

4 H, 2 CH₂), 1.50 (s, 6 H, 3 CH₂). – ¹³C NMR: δ ϭ 25.7 (2 CH₃),

14.3 (CH₃), 47.1 (3 CH₂), 19.8, 34.1 (CH₂), 37.2, 46.4, 69.1 (C). –

MS (EI): m/z (%) ϭ 167 (0.1) [M^ϩ– H], 153 (6) [M^ϩ– CH₃], 150

(5) [M^ϩ– H₂O], 135 (51), 121 (100), 107 (70), 59 (84), 49 (99). –

C₁₁H₂₀O (168.27): calcd. C 78.51, H 11.98; found C 78.53, H 11.92.

1-(3-Octylbicyclo[1.1.1]pent-1-yl)propan-1-one (12e): To the lithium

derivative 9e, prepared from 8e (1.07 g, 3.49 mmol) according to

GP 4, a solution of propionyl chloride (1.02 g, 956 µL, 11 mmol)

in Et₂O (5 mL) was added dropwise at –78 °C. The mixture was

allowed to warm to room temp. and then the reaction was

quenched with MeOH (5 mL). The resulting mixture was washed

with 5% NaHCO₃solution and brine (15 mL each), dried, and con-

centrated. Column chromatography of the residue (40 g of silica

gel, column 15 ϫ 3 cm, hexane/Et₂O, 9:1) furnished 12e (620 mg,

trans-1-(3-Butylbicyclo[1.1.1]pent-1-yl)-4-phenylcyclohexanol (11ca):

To the lithium derivative 9c, prepared from 8c (2.50 g, 10 mmol)

according to GP 4, 4-phenylcyclohexanone (1.74 g, 10 mmol) in

Et₂O (20 mL) was added over a period of 15 min at –78 °C. After

work-up as described above for 11b, column chromatography of

the residue (150 g of silica gel, column 15 ϫ 5 cm, hexane/Et₂O,

1:1) furnished 11ca (2.10 g, 70%), R_fϭ 0.40; m.p. 95 °C (pent-

ane). – IR: ν˜ ϭ 3450 cm^–1, 3080, 3060, 3025, 2960, 2920, 2870,

1602, 1445, 1276, 1254, 1150, 1138, 988, 960, 760, 700. – ¹H NMR:

δ ϭ 0.89 (t, J ϭ 7.0 Hz, 3 H, CH₃), 0.99 (s, 1 H, OH), 1.16–1.38

(m, 4 H, 2 CH₂), 1.51 (s, 6 H, 3 CH₂), 1.40–1.94 (m, 10 H, 5 CH₂),

1

75%) as an oil, R_fϭ 0.38. – H NMR: δ ϭ 0.89 (t, J ϭ 6.8 Hz, 3

H, CH₃), 1.02 (t, J ϭ 7.7 Hz, 3 H, CH₃), 1.28 (m, 12 H, 6 CH₂),

1.44 (t, J ϭ 6.8 Hz, 2 H, CH₂), 1.85 (s, 6 H, 3 CH₂), 2.43 (q, J ϭ

7.7 Hz, 2 H, CH₂).

2.43 (tt, J ϭ 12.3, 3.6 Hz, 1 H, CH), 7.14–7.33 (m, 5 H, Ph). – ¹³

C

NMR: δ ϭ 14.1 (CH₃), 46.6 (3 CH₂), 31.6, 33.4 (2 CH₂), 22.9, 28.8,

1-{3-[4-(Tetrahydropyran-2-yloxy)butyl]bicyclo[1.1.1]pent-1-yl}

butan-1-one (12h): Compound 12h was prepared from 8h (350 mg,

1 mmol) and butyryl chloride (217 mg, 208 µL, 2 mmol) as de-

scribed in the preceding preparation. Column chromatography

(20 g of silica gel, column 15 ϫ 2 cm, hexane/Et₂O, 4:1) furnished

12h (233 mg, 79%) as an oil, R_fϭ 0.30. – H NMR: δ ϭ 0.90 (t,

J ϭ 7.2 Hz, 3 H, CH₃), 1.22–1.95 (m, 14 H, 7 CH₂), 1.85 (s, 6 H,

3 CH₂), 2.39 (t, J ϭ 7.1 Hz, 2 H, CH₂), 3.37 (dt, J ϭ 9.5, 6.9 Hz,

29.0 (CH₂), 125.9, 126.9 (2 CH), 44.0, 128.3 (CH), 37.4, 46.4, 68.4,

147.4 (C). – MS (EI): m/z (%): 298 (0.7) [M^ϩ], 280 (13) [M^ϩ

–

H₂O], 149 (59), 91 (100), 55 (51). – C₂₁H₃₀O (298.5): calcd. C 84.51,

H 10.13; found C 84.34, H 10.14.

1

1-Butyl-3-(trimethylsilyl)bicyclo[1.1.1]pentane (11cb): The lithium

derivative 9c, prepared from 8c (250 mg, 1 mmol) according to GP

4, was quenched with TMSCl (326 mg, 381 µL, 3 mmol) and the

1146

Eur. J. Org. Chem. 2000, 1137Ϫ1155

Nickel- and Palladium-Catalyzed Cross-Coupling Reactions

1 H, OCH₂), 3.44–3.55 (m, 1 H, OCH₂), 3.73 (dt, J ϭ 9.5, 6.9 Hz, 265 (24) [M^ϩ– C₃H₇], 185 (25), 143 (37), 123 (100), 95 (22). –

FULL PAPER

1 H, OCH₂), 3.87 (ddd, J ϭ 11.4, 7.5, 3.8 Hz, 1 H, OCH₂), 4.58

(t, J ϭ 3.2 Hz, 1 H, OCH).

C₂₁H₂₁FO (308.4): calcd. C 81.79, H 6.86; found C 81.69, H 6.73.

1-(4-Chlorobenzoyl)-3-(4-propylphenyl)bicyclo[1.1.1]pentane (15bc):

From 4-chlorobenzonitrile (550 mg, 4 mmol) and 14b [prepared

from the same quantities of its precursors as in the preceding pre-

paration], 15bc (602 mg, 49%) was obtained following the same

procedure as above, R_fϭ 0.38; m.p. 98 °C. – IR: ν˜ ϭ 3095 cm^–1,

3080, 3035, 2980, 2960, 2920, 2880, 1666, 1588, 1404, 1362, 1303,

1295, 1212, 1092, 880, 861, 791. – ¹H NMR: δ ϭ 0.93 (t, J ϭ

7.4 Hz, 3 H, CH₃), 1.63 (sext., J ϭ 7.4 Hz, 2 H, CH₂), 2.52 (s, 6

H, 3 CH₂), 2.56 (t, J ϭ 7.2 Hz, 2 H, CH₂), 7.13 (d, J ϭ 8.2 Hz, 2

H, C₆H₄), 7.17 (d, J ϭ 8.2 Hz, 2 H, C₆H₄), 7.39 (dd, J ϭ 8.6,

2.0 Hz, 2 H, C₆H₄), 7.97 (dd, J ϭ 8.6, 2.0 Hz, 2 H, C₆H₄). – ¹³C

NMR: δ ϭ 16.7 (CH₃), 55.0 (3 CH₂), 24.4, 37.6 (CH₂), 125.8,

128.3, 128.7, 130.2 (2 CH), 42.2, 43.0, 134.9, 136.8, 139.1, 141.3,

196.2 (C). – MS (EI): m/z (%) ϭ 326/324 (9:24) [M^ϩ], 295 (15), 281

(22), 185 (37), 113 (58), 109 (100). – C₂₁H₂₁ClO (324.8): calcd. C

77.64, H 6.52; found C 77.52, H 6.63.

1-[3-(4-Phenylcyclohex-1-yl)bicyclo[1.1.1]pent-1-yl]propan-1-one

(12o): Compound 12o was prepared from 8o (700 mg, 2 mmol, 2:1

mixture of cis and trans isomers) and propionyl chloride (370 mg,

348 µL, 4 mmol) as described for 12e. Column chromatography

(20 g of silica gel, column 15 ϫ 3 cm, hexane/Et₂O, 9:1) furnished

1

12o (416 mg, 74%) as an oil, R_fϭ 0.32. – H NMR: δ ϭ 0.91 (t,

J ϭ 7.4 Hz, 3 H, CH₃), 1.02–1.84 (m, 9 H), 1.85 (s, 6 H, 3 CH₂,

trans), 1.97 (s, 6 H, 3 CH₂, cis), 2.38–2.48 (m, 1 H, CH, trans), 2.44

(t, J ϭ 7.3 Hz, 2 H, CH₂), 2.53–2.72 (m, 1 H, CH, cis), 7.15–7.35

(m, 5 H, Ph).

General Procedure (GP 5) for the Preparation of 3-Arylbicy-

clo[1.1.1]pent-1-ylmagnesium Bromides 14a–e: A solution of the ap-

propriate arylmagnesium bromide 13 [prepared from the corres-

ponding aryl bromide (16 mmol) and magnesium turnings (401 mg,

16.5 mmol) in anhydrous Et₂O (13a–d) or THF (13e) (20 mL)] was

added to a 0.3  solution of 2 in Et₂O (60 mL, 18 mmol). The

resulting mixture was stirred under reflux for several days (see

Table 3) with GC monitoring. The solution was then carefully con-

centrated under reduced pressure and, unless otherwise specified,

the residue was taken up in anhydrous Et₂O (15 mL).

1-Chloro-3-(4-propylphenyl)bicyclo[1.1.1]pentane (15bd): To a sus-

pension of N-chlorosuccinimide (950 mg, 7.1 mmol) in anhydrous

THF (5 mL), a solution of 14b [prepared from 4-bromopropylben-

zene (1.195 g, 6 mmol) according to GP 5] in anhydrous THF

(5 mL) was added dropwise. After stirring for 15 h at room temp.

and then for 7 h under reflux, the reaction mixture was diluted with

pentane (30 mL) and washed with 5% aq. HCl, 5% NaOH solution,

and water (20 mL each), dried, and concentrated. Column chroma-

tography of the residue (50 g of silica gel, column 15 ϫ 3 cm, PE)

gave 15ba (277 mg, 24%), R_fϭ 0.50, and 15bd (320 mg, 24%), R_fϭ

1-Phenylbicyclo[1.1.1]pentane (15a): A solution of 14a [prepared

from bromobenzene (1.88 g, 1.26 mL, 12 mmol), Mg turnings

(300 mg, 12.3 mmol), and 2 (13.5 mmol, 40 mL of a 0.3  solution)

according to GP 5] was carefully treated with H₂O (10 mL) at 0

°C. The organic phase was then washed with further H₂O (2 ϫ

10 mL), dried, and concentrated. 15a^[46](1.37 g, 80%) was obtained

after preparative GC separation of the residue.

1

0.34; m.p. 42 °C. – H NMR: δ ϭ 0.93 (t, J ϭ 7.3 Hz, 3 H, CH₃),

1.62 (sext., J ϭ 7.3 Hz, 2 H, CH₂), 2.41 (s, 6 H, 3 CH₂), 2.55 (t,

J ϭ 7.4 Hz, 2 H, CH₂), 7.07–7.14 (m, 4 H, C₆H₄). – ¹³C NMR:

δ ϭ 13.8 (CH₃), 58.9 (3 CH₂), 24.6, 37.7 (CH₂), 126.2, 128.5 (2

CH), 39.8, 48.9, 134.7, 141.5 (C). – MS (EI): m/z (%) ϭ 222/220

(1:3) [M^ϩ], 185 (100) [M^ϩ– Cl], 179/177 (17:54) [M^ϩ– C₃H₇],

144 (56).

1-(4-Propylphenyl)bicyclo[1.1.1]pentane (15ba): This compound was

obtained in analogy to the previous preparation, starting from 14b

[prepared from 4-bromopropylbenzene (1.20 g, 6 mmol) and 2

(6.75 mmol, 22.5 mL of a 0.3  solution) according to GP 5]. Col-

umn chromatography (50 g of silica gel, column 15 ϫ 3 cm, PE)

1

1-Bromo-3-(4-butylphenyl)bicyclo[1.1.1]pentane (15cb): To a solu-

tion of 14c [prepared from 4-bromobutylbenzene (3.197 g, 2.65 mL,

15 mmol) and 2 (16.9 mmol, 56.3 mL of a 0.3  solution) according

to GP 5], a solution of Br₂(2.397 g, 0.77 mL, 15 mmol) in anhyd-

rous THF (10 mL) was added dropwise at 0 °C. After stirring the

reaction mixture for 1 h at room temp., it was treated with satd.

NH₄Cl solution (10 mL). The layers were separated and the organic

phase was washed with 0.1  Na₂S₂O₃solution and water (20 mL

each), dried, and concentrated. Column chromatography (150 g of

silica gel, column 15 ϫ 5 cm, PE) furnished 15cb (1.54 g, 36%) as

gave 15ba (1.11 g, 99%) as an oil, R_fϭ 0.50. – H NMR: δ ϭ 0.93

(t, J ϭ 7.4 Hz, 3 H, CH₃), 1.62 (sext., J ϭ 7.4 Hz, 2 H, CH₂), 2.06

(s, 6 H, 3 CH₂), 2.52 (s, 1 H, CH), 2.55 (t, J ϭ 7.4 Hz, 2 H, CH₂),

7.11 (m, 4 H, C₆H₄). – ¹³C NMR: δ ϭ 13.9 (CH₃), 52.2 (3 CH₂),

24.7, 37.8 (CH₂), 125.8, 128.2 (2 CH), 26.6 (CH), 47.0, 139.0,

140.7 (C).

1-(4-Fluorobenzoyl)-3-(4-propylphenyl)bicyclo[1.1.1]pentane (15bb):

To a solution of 14b [prepared from 4-bromopropylbenzene

(757 mg, 3.8 mmol) and 2 (4.28 mmol, 14.25 mL of a 0.3  solu-

tion) according to GP 5], a solution of 4-fluorobenzonitrile

(484 mg, 4 mmol) in Et₂O (5 mL) was added dropwise at 0 °C.

After stirring the reaction mixture for 48 h under reflux, 5% aq.

HCl (2 mL) was added and stirring was continued for a further

10 h at room temp. The organic phase was washed with 5% aq.

NaHCO₃solution and brine (10 mL each), dried, and concen-

trated. After column chromatography (30 g of silica gel, column 25

1

an oil, R_fϭ 0.26. – H NMR: δ ϭ 0.91 (t, J ϭ 7.5 Hz, 3 H, CH₃),

1.33 (sext., J ϭ 7.8 Hz, 2 H, CH₂), 1.57 (quint, J ϭ 7.8 Hz, 2 H,

CH₂), 2.50 (s, 6 H, 3 CH₂), 2.58 (t, J ϭ 7.7 Hz, 2 H, CH₂), 7.08

(d, J ϭ 8.0 Hz, 2 H, C₆H₄), 7.12 (d, J ϭ 8.0 Hz, 2 H, C₆H₄). – ¹³C

NMR: δ ϭ 13.9 (CH₃), 60.1 (3 CH₂), 22.3, 33.6, 35.2 (CH₂), 126.0,

128.4 (2 CH), 36.8, 43.4, 134.9, 141.7 (C).

ϫ 2 cm, hexane/Et₂O, 9:1), 15bb (362 mg, 31%) was obtained, R_fϭ 1-Allyl-3-(4-fluorophenyl)bicyclo[1.1.1]pentane (15db): At 0 °C, a so-

0.35; m.p. 99 °C. – IR: ν˜ ϭ 3070 cm^–1, 3050, 3030, 2970, 2960,

lution of 14d [prepared from 4-bromofluorobenzene (1.23 g,

2935, 2915, 2875, 1658, 1593, 1503, 1410, 1358, 1306, 1298, 1239,

0.77 mL, 7 mmol) according to GP 5] in Et₂O (10 mL) was added

1226, 1211, 1154, 880, 858, 818, 790, 618. – ¹H NMR: δ ϭ 0.94 (t, dropwise to a solution of allyl bromide (1.21 g, 865 µL, 10 mmol)

J ϭ 7.4 Hz, 3 H, CH₃), 1.64 (sext., J ϭ 7.4 Hz, 2 H, CH₂), 2.53 (s, in anhydrous Et₂O (10 mL). After stirring under reflux for 6 h, the

6 H, 3 CH₂), 2.58 (t, J ϭ 7.2 Hz, 2 H, CH₂), 7.08–7.25 (m, 6 H,

mixture was treated with H₂O (5 mL). The layers were separated

C₆H₄), 8.03–8.14 (m, 2 H, C₆H₄). – ¹³C NMR: δ ϭ 13.7 (CH₃), and the organic phase was washed with 5% aq. HCl, 5% NaHCO₃

55.1 (3 CH₂), 24.5, 37.7 (CH₂), 115.5 (d, J ϭ 22.0 Hz), 125.9, 128.4, solution, and H₂O (10 mL each), dried, and concentrated. Separa-

131.5 (d, J ϭ 9.0 Hz) (2 CH), 42.2, 43.1, 133.0, 136.9, 141.4, 165.5

tion by preparative GC gave 15db (495 mg, 35%) as an oil. – IR:

(d, J ϭ 255.0 Hz), 196.0 (C). – MS (EI): m/z (%) ϭ 308 (23) [M^ϩ], ν˜ ϭ 3075 cm^–1, 3045, 2965, 2905, 2870, 2830, 1643, 1606, 1520,

Eur. J. Org. Chem. 2000, 1137Ϫ1155

1147

M. Messner, S. I. Kozhushkov, A. de Meijere

FULL PAPER

1504, 1410, 1296, 1267, 1220, 1153, 992, 916, 840, 812. – ¹H NMR: 1-(4-Fluorophenyl)-3-phenylbicyclo[1.1.1]pentane (17ab): From 14a

δ ϭ 1.87 (s, 6 H, 3 CH₂), 2.29 (d, J ϭ 7.2 Hz, 2 H, CH₂), 5.02 (d,

[prepared from PhBr (628 mg, 421 µL, 4 mmol) according to GP 5],

J ϭ 10.4 Hz, 1 H, ϭCH₂), 5.03 (d, J ϭ 16.8 Hz, 1 H, ϭCH₂), 5.77 4-bromofluorobenzene (175 mg, 110 µL, 1 mmol), and NiCl₂dppe

(ddt, J ϭ 16.8, 10.4, 7.2 Hz, 1 H, ϭCH), 6.95 (tt, J ϭ 8.8, 2.2 Hz, (59 mg, 0.11 mmol) in Et₂O, 17ab (90 mg, 38%) was obtained ac-

2 H, C₆H₄), 7.14 (ddt, J ϭ 8.8, 5.6, 2.2 Hz, 2 H, C₆H₄). – ¹³C cording to GP 7 and subsequent column chromatography (25 g of

NMR: δ ϭ 52.2 (3 CH₂), 36.6, 115.9 (CH₂), 114.8 (d, J ϭ 21.0 Hz), silica gel, column 16 ϫ 2 cm, PE), R_fϭ 0.25; m.p. 120 °C. – IR:

127.5 (d, J ϭ 8.0 Hz) (2 CH), 135.4 (CH), 37.8, 41.8, 137.3 (d, J ϭ

ν˜ ϭ 3040 cm^–1, 2970, 2915, 2875, 1602, 1505, 1450, 1310, 1220,

3.0 Hz), 161.7 (d, J ϭ 244.0 Hz) (C). – C₁₄H₁₅F (202.26): calcd. C 1192, 1161, 845, 800, 751, 706. – ¹H NMR: δ ϭ 2.31 (s, 6 H, 3

83.13, H 7.48; found C 83.22, H 7.45.

CH₂), 7.00 (tt, J ϭ 8.8, 2.0 Hz, 2 H, C₆H₄), 7.13–7.36 (m, 7 H,

Ar). – ¹³C NMR: δ ϭ 54.1 (3 CH₂), 114.9 (d, J ϭ 21.4 Hz), 126.1,

126.5, 127.0 (d, J ϭ 7.9 Hz) (2 CH), 128.2 (CH), 40.3, 40.7, 136.8,

140.7, 161.7 (d, J ϭ 244.6 Hz) (C). – MS (EI): m/z (%) ϭ 238 (90)

[M^ϩ], 237 (50) [M^ϩ– H], 223 (67) [M^ϩ– H – CH₂], 209 (36), 203

(31), 196 (100), 172 (33), 170 (49). – C₁₇H₂₅F (238.3): calcd. C

85.68, H 6.35; found C 85.83, H 6.39.

1-(4Ј-Ethylbiphenyl-4-yl)bicyclo[1.1.1]pentane (15e): Work-up of the

reaction mixture from the attempted preparation of 14e starting

from 4-bromo-4Ј-ethylbiphenyl (22f) (262 mg, 1 mmol) and 2

(1.13 mmol, 3.8 mL of a 0.3  solution) as described above for 15a

and subsequent column chromatography (20 g of silica gel, column

15 ϫ 2 cm, hexane) gave 15e (32 mg, 13%) as an oil, R_fϭ 0.45. –

¹H NMR: δ ϭ 1.31 (t, J ϭ 7.3 Hz, 3 H, CH₃), 2.11 (s, 6 H, 3 CH₂),

2.45 (s, 1 H, CH), 2.71 (t, J ϭ 7.3 Hz, 2 H, CH₂), 7.20–7.35 (m, 4

H, C₆H₄), 7.35–7.65 (m, 4 H, C₆H₄).

1-Phenyl-3-(p-tolyl)bicyclo[1.1.1]pentane (17ac): From 14a [pre-

pared from PhBr (628 mg, 421 µL, 4 mmol) according to GP 5], 4-

iodotoluene (218 mg, 1 mmol), and NiCl₂dppe (47 mg, 0.09 mmol)

in Et₂O, 17ac (50 mg, 21%) was obtained according to GP 7 and

subsequent column chromatography (50 g of silica gel, column 15

General Procedure (GP 6) for the Preparation of 3-Alkylbicyclo-

[1.1.1]pent-1-ylzinc Chlorides 19: To a solution of the appropriate

lithium derivative 9, prepared from 8 according to GP 4, a 2.0 

solution of ZnCl₂in anhydrous THF (1.2 mL, 2.4 mmol, prepared

from ZnCl₂THF^[21]) was added dropwise at –78 °C. The reaction

mixture was then allowed to warm to room temp. and stirred for

1 h. After careful evaporation of the solvent, the residue was taken

up in anhydrous THF (5 mL) unless specified otherwise.

1

ϫ 3 cm, PE) as an oil, R_fϭ 0.27. – H NMR: δ ϭ 2.31 (s, 6 H, 3

CH₂), 2.35 (s, 3 H, CH₃), 7.10–7.37 (m, 9 H, Ar). – ¹³C NMR: δ ϭ

21.1 (CH₃), 54.0 (3 CH₂), 126.0, 126.1, 126.4, 128.2 (2 CH), 128.9

(CH), 40.6, 40.8, 136.1, 138.0, 141.0 (C).

1-Phenyl-3-(3-pyridyl)bicyclo[1.1.1]pentane (17ad): From 14a [pre-

pared from PhBr (628 mg, 421 µL, 4 mmol) according to GP 5], 3-

iodopyridine (210 mg, 1.02 mmol), and NiCl₂dppe (60 mg,

0.11 mmol) in Et₂O, 17ad (93 mg, 41%) was obtained according to

GP 7 and subsequent column chromatography (20 g of silica gel,

General Procedure (GP 7) for Cross-Coupling under Transition

Metal Catalysis: A solution of the appropriate bicyclo[1.1.1]pen-

tylmagnesium or -zinc halide (14 or 19, respectively; 0.5–4 mmol,

prepared according to GP 5 or GP 6) in Et₂O (THF) was cannu-

lated in one portion into a mixture of the aryl (alkenyl) halide or

triflate (1 mmol) and the catalyst (2–10 mol-%) in anhydrous Et₂O

or THF (5 mL) at ambient temp. A deep-green (sometimes deep-

red) colour appeared immediately. After stirring for 10–60 min, the

colour changed to yellow or brown. The mixture was stirred for a

further 2–72 h at this temp. (see Table 4–7), then treated with H₂O

(1 mL), and filtered through Celite (unless specified otherwise).

After evaporation of the solvent, the residue was separated by col-

umn chromatography. In the preparations of 23ac,ff,fg,aja,ajb, the

solvent (THF) was carefully evaporated under reduced pressure

and replaced by hexane (10 mL) prior to treatment with water.

1

column 15 ϫ 2 cm, PE), R_fϭ 0.22. – H NMR: δ ϭ 2.39 (s, 6 H,

3 CH₂), 7.19–7.39 (m, 6 H, Ar), 7.58 (dt, J ϭ 7.7, 1.8 Hz, 1 H, Ar),

8.49 (m, 1 H, Ar), 8.56 (m, 1 H, Ar). – ¹³C NMR: δ ϭ 54.0 (3

CH₂), 123.0, 126.1, 126.7, 128.2, 133.7, 147.9, 148.1 (CH), 39.0,

41.5, 136.0, 140.4 (C). – MS (EI): m/z (%) ϭ 221 (7) [M^ϩ], 220 (18)

[M^ϩ– H], 206 (13) [M^ϩ– H – CH₂], 103 (28), 91 (25) [C₇H₇^ϩ], 77

(100) [C₆H₅^ϩ].

2-(3-Phenylbicyclo[1.1.1]pent-1-yl)pyrimidine (17ae): From 14a [pre-

pared from PhBr (628 mg, 421 µL, 4 mmol) according to GP 5 and

taken up in THF (4 mL)], 2-bromopyrimidine (318 mg, 2 mmol),

and PdCl₂(dppf) (29 mg, 0.04 mmol) in THF (5 mL), 17ae (271 mg,

61%) was obtained according to GP 7 and subsequent column

chromatography (20 g of silica gel, column 15 ϫ 2 cm, PE/Et₂O,

4:1), R_fϭ 0.18; m.p. 111 °C. – ¹H NMR: δ ϭ 2.50 (s, 6 H, 3 CH₂),

7.18 (t, J ϭ 5.0 Hz, 1 H, Ar), 7.21–7.39 (m, 5 H, Ar), 8.73 (d, J ϭ

5.0 Hz, 2 H, Ar). – ¹³C NMR: δ ϭ 53.9 (3 CH₂), 120.0, 126.2,

126.7, 128.5, 157.1 (CH), 41.3, 42.0, 140.5, 168.1 (C). – MS (EI):

m/z (%) ϭ 222 (28) [M^ϩ], 221 (100) [M^ϩ– H], 207 (42) [M^ϩ– H –

CH₂], 145 (19), 131 (18), 77 (19) [C₆H₅^ϩ]. – C₁₅H₁₄N₂(222.28):

calcd. C 81.05, H 6.35, N 12.60; found C 80.96, H 6.45, N 12.58.

1,3-Diphenylbicyclo[1.1.1]pentane (17aa): To a solution of 14a [pre-

pared from PhBr (628 mg, 421 µL, 4 mmol) according to GP 5], a

2.0  solution of ZnCl₂in THF (3 mL, 6 mmol) was added at 0

°C. After stirring for 1 h at room temp., the suspension was added

to a mixture of PhBr (628 mg, 421 µL, 4 mmol) and Pd(PPh₃)₄

(92 mg, 0.08 mmol) in THF (5 mL) and the resulting mixture was

stirred for a further 24 h. Standard work-up followed by column

chromatography (40 g of silica gel, column 14 ϫ 3 cm, hexane, R_fϭ

0.25) gave 211 mg of a mixture containing 17aa (70%; 15% yield)

and 3,3Ј-diphenyl(bis-1,1Ј-bicyclo[1.1.1]pentyl) (16a) (30%; 13%

yield). A sample of pure 16a^[4a]was obtained by twofold recrystal-

lization from MeOH. Evaporation of the solvent from the mother

liquor followed by twofold recrystallization of the residue from

pentane gave a sample of pure 17aa; m.p. 100 °C. – IR: ν˜ ϭ 3080

cm^–1, 3060, 3030, 2970, 2910, 2870, 1605, 1496, 1448, 1308, 1189,

1030, 758, 702. – ¹H NMR: δ ϭ 2.32 (s, 6 H, 3 CH₂), 7.19–7.39

(m, 10 H, 2 Ph). – ¹³C NMR: δ ϭ 54.0 (3 CH₂), 126.1, 126.5 (4

CH), 128.2 (2 CH), 40.8, 140.9 (2 C). – MS (EI): m/z (%) ϭ 220

(43) [M^ϩ], 219 (100) [M^ϩ– H], 205 (16) [M^ϩ– H – CH₂], 143 (21)

1-(Cycloocten-1-yl)-3-phenylbicyclo[1.1.1]pentane (17af): From 14a

[prepared from PhBr (330 mg, 221 µL, 2.1 mmol) according to GP

5 and taken up in THF (4 mL)], 1-bromocyclooctene (378 mg,

2 mmol), and PdCl₂(dppf) (20 mg, 0.027 mmol) in THF, 17af

(256 mg, 50%) was obtained according to GP 7 and subsequent

column chromatography (20 g of silica gel, column 15 ϫ 2 cm, PE)

1

as an oil, R_fϭ 0.42. – H NMR: δ ϭ 1.39–1.59 (m, 8 H, 4 CH₂),

2.03 (s, 6 H, 3 CH₂), 2.06–2.25 (m, 4 H, 2 CH₂), 5.45 (t, J ϭ 6.1 Hz,

1 H, ϭCH), 7.10–7.32 (m, 5 H, Ph). – ¹³C NMR: δ ϭ 52.7 (3 CH₂),

26.0, 26.1, 26.2, 26.6, 29.3, 29.8 (CH₂), 124.2, 126.2, 126.2, 128.1

(CH), 40.6, 42.7, 139.6, 141.5 (C).

[M^ϩ– C₆H₅], 129 (18), 103 (30), 77 (26) [C₆H₅^ϩ]. – C₁₇H₁₆(220.3): (E)-β-(3-Phenylbicyclo[1.1.1]pent-1-yl)styrene (17ag): From 14a

calcd. C 92.68, H 7.32; found C 92.76, H 7.34.

1148

[prepared from PhBr (330 mg, 221 µL, 2.1 mmol) according to GP

Eur. J. Org. Chem. 2000, 1137Ϫ1155

Nickel- and Palladium-Catalyzed Cross-Coupling Reactions

FULL PAPER

5 and taken up in THF (4 mL)], (E)-2-bromostyrene (366 mg,

2 mmol), and PdCl₂(dppf) (29 mg, 0.04 mmol) in THF, 17ag

(84 mg, 84%) was obtained according to GP 7 and subsequent col-

umn chromatography (20 g of silica gel, column 14 ϫ 2 cm, pent-

1

(376 mg, 76%) was obtained according to GP 7 and subsequent ane) as an oil, R_fϭ 0.53. – H NMR: δ ϭ 0.91 (t, J ϭ 7.0 Hz, 3

column chromatography (20 g of silica gel, column 15 ϫ 2 cm, PE),

H, CH₃), 1.22–1.42 (m, 2 H, CH₂), 1.44–1.53 (m, 2 H, CH₂), 1.84

R_fϭ 0.32; m.p. 65 °C. – H NMR: δ ϭ 2.13 (s, 6 H, 3 CH₂), 6.38 (s, 6 H, 3 CH₂), 2.30 (s, 3 H, CH₃), 7.07 (s, 4 H, C₆H₄). – ¹³C

(m, 2 H, CHϭCH), 7.10–7.39 (m, 10 H, 2 Ph). – ¹³C NMR: δ ϭ

NMR: δ ϭ 14.4, 21.1 (CH₃), 52.2 (3 CH₂), 19.9, 34.0 (CH₂), 125.9,

1

53.7 (3 CH₂), 126.0, 126.1, 126.4, 127.2, 128.1, 128.5, 129.0, 130.5 128.7 (2 CH), 38.9, 41.3, 135.6, 138.7 (C). – MS (EI): m/z (%) ϭ

(CH), 39.8, 41.8, 137.1, 141.0 (C). – MS (EI): m/z (%) ϭ 246 (6) 200 (1) [M^ϩ], 185 (10) [M^ϩ– CH₃], 171 (10) [M^ϩ– C₂H₅], 157

[M^ϩ], 245 (29) [M^ϩ– H], 215 (20), 153 (39), 141 (71), 128 (100). – (100). In an analogous coupling, from 19b (3 mmol), 4-iodotoluene

C₁₉H₁₈(246.3): calcd. C 92.64, H 7.36; found C 92.52, H 7.50.

(438 mg, 2 mmol), and Pd(PPh₃)₄(47 mg, 0.04 mmol) in THF, 20bb

(111 mg, 28%) and 3,3Ј-dipropyl(bis-1,1Ј-bicyclo[1.1.1]pentyl) (16b)

(39 mg, 12%) were obtained according to GP 7 and subsequent

column chromatography (25 g of silica gel, column 18 ϫ 2 cm,

1-(4-Fluorophenyl)-3-(4-propylphenyl)bicyclo[1.1.1]pentane (17ba):

From 14b [prepared from 4-bromopropylbenzene (1.20 g, 6 mmol)

according to GP 5], 4-bromofluorobenzene (1.05 g, 659 µL,

6 mmol), and NiCl₂(PPh₃)₂(196 mg, 0.3 mmol) in Et₂O, 17ba

(157 mg, 9%) was obtained according to GP 7 and subsequent col-

umn chromatography (60 g of silica gel, column 20 ϫ 3 cm, PE)

followed by recrystallization from MeOH, R_fϭ 0.21; m.p. 66 °C. –

IR: ν˜ ϭ 3055 cm^–1, 3030, 2970, 2910, 2875, 1603, 1516, 1307, 1221,

1

pentane), R_fϭ 0.78. – H NMR: δ ϭ 0.88 (t, J ϭ 7.2 Hz, 6 H, 2

CH₃), 1.18–1.43 (m, 8 H, 4 CH₂), 1.37 (s, 12 H, 6 CH₂). – ¹³C

NMR: δ ϭ 14.4 (2 CH₃), 49.0 (6 CH₂), 19.9, 34.4 (2 CH₂), 39.1,

41.0 (2 C). – MS (EI): m/z (%) ϭ 217 (0.2) [M^ϩ– H], 203 (0.6)

[M^ϩ– CH₃], 189 (2) [M^ϩ– C₂H₅], 175 (18) [M^ϩ– C₃H₇], 133 (28),

119 (53), 105 (61), 91 (100).

1

1161, 848, 811. – H NMR: δ ϭ 0.95 (t, J ϭ 7.4 Hz, 3 H, CH₃),

2-(3-Propylbicyclo[1.1.1]pent-1-yl)pyrimidine (20bc): From 19b

(2 mmol), prepared according to GP 6, 2-bromopyrimidine

(159 mg, 1 mmol), and PdCl₂(dppf) (26 mg, 0.035 mmol) in THF,

20bc (142 mg, 75%) was obtained according to GP 7 and sub-

sequent column chromatography (30 g of silica gel, column 25 ϫ

2 cm, Et₂O) as an oil, R_fϭ 0.29. – ¹H NMR: δ ϭ 0.90 (t, J ϭ

7.2 Hz, 3 H, CH₃), 1.28–1.45 (m, 2 H, CH₂), 1.49–1.58 (m, 2 H,

CH₂), 2.05 (s, 6 H, 3 CH₂), 7.15 (t, J ϭ 4.9 Hz, 1 H, Ar), 8.69 (d,

J ϭ 4.9 Hz, 2 H, Ar). – ¹³C NMR: δ ϭ 14.1 (CH₃), 51.9 (3 CH₂),

19.6, 33.5 (CH₂), 156.8 (2 CH), 118.5 (CH), 39.4, 42.6, 168.1 (C).

1.64 (sext., J ϭ 7.4 Hz, 2 H, CH₂), 2.29 (s, 6 H, 3 CH₂), 2.59 (t,

J ϭ 7.4 Hz, 2 H, CH₂), 7.00 (t, J ϭ 8.8 Hz, 2 H, C₆H₄), 7.10–7.26

(m, 6 H, C₆H₄). – ¹³C NMR: δ ϭ 13.8 (CH₃), 54.2 (3 CH₂), 24.6,

37.8 (CH₂), 115.0 (d, J ϭ 21.3 Hz), 126.0, 127.7 (d, J ϭ 8.2 Hz),

128.3 (2 CH), 40.3, 40.6, 137.0 (d, J ϭ 3.0 Hz), 138.1, 141.0, 161.8

(d, J ϭ 244.1 Hz) (C). – MS (EI): m/z (%) ϭ 280 (17) [M^ϩ], 279

(35) [M^ϩ– H], 238 (30), 237 (100) [M^ϩ– C₃H₇], 109 (54), 91 (36)

[C₇H₇^ϩ]. – C₂₀H₂₁F (280.4): calcd. C 85.67, H 7.55; found C 85.79,

H 7.47.

1-(4-Propylphenyl)-3-[4-(trifluoromethyl)phenyl]bicyclo[1.1.1]-

pentane (17bb): From 14b [prepared from 4-bromopropylbenzene

(1.20 g, 6 mmol) according to GP 5], 4-bromobenzotrifluoride

(1.35 g, 840 µL, 6 mmol), and NiCl₂(PPh₃)₂(227 mg, 0.35 mmol)

in Et₂O, 17bb (122 mg, 6%) was obtained according to GP 7 and

subsequent column chromatography (100 g of silica gel, column 20

ϫ 4 cm, PE) followed by recrystallization from MeOH, R_fϭ 0.31;

1-Butyl-3-[4-(trimethylsilyl)phenyl]bicyclo[1.1.1]pentane (20cb):

A

reaction mixture obtained from 19c (44 mmol), prepared according

to GP 6, (4-bromophenyl)trimethylsilane (5.04 g, 22 mmol), and

PdCl₂(dppf) (805 mg, 1.1 mmol) according to GP 7 was poured

into ice-cold satd. NH₄Cl solution (100 mL) and diluted with hex-

ane (200 mL). The layers were separated and the organic phase was

washed with 10% NH₄Cl solution, H₂O, and brine (50 mL each),

dried, and concentrated. Column chromatography of the residue

(180 g of silica gel, column 20 ϫ 7 cm, hexane) gave a fraction with

R_fϭ 0.59, which was distilled under reduced pressure to yield 20cb

1

m.p. 95 °C. – H NMR: δ ϭ 0.96 (t, J ϭ 7.4 Hz, 3 H, CH₃), 1.65

(sext., J ϭ 7.5 Hz, 2 H, CH₂), 2.32 (s, 6 H, 3 CH₂), 2.60 (t, J ϭ

7.6 Hz, 2 H, CH₂), 7.13 (d, J ϭ 8.2 Hz, 2 H, C₆H₄), 7.21 (d, J ϭ

8.2 Hz, 2 H, C₆H₄), 7.28 (d, J ϭ 8.4 Hz, 2 H, C₆H₄), 7.57 (d, J ϭ

8.4 Hz, 2 H, C₆H₄). – ¹³C NMR: δ ϭ 13.9 (CH₃), 54.2 (3 CH₂),

24.7, 37.8 (CH₂), 125.1 (q, J ϭ 3.8 Hz), 126.0, 126.5, 128.4 (2 CH),

40.5, 40.8, 124.3 (q, J ϭ 271.7 Hz), 128.7 (q, J ϭ 32.5 Hz), 137.7,

141.2, 145.0 (q, J ϭ 1.1 Hz) (C). – MS (EI): m/z (%) ϭ 330 (12)

[M^ϩ], 329 (13) [M^ϩ– H], 288 (19), 287 (100) [M^ϩ– C₃H₇], 159

(16), 115 (18), 91 (16) [C₇H₇^ϩ]. – C₂₁H₂₁F₃(330.4): calcd. C 76.34,

H 6.41; found C 76.43, H 6.47.

1

(4.31 g, 72%), b.p. 102–103 °C (0.1 Torr). – H NMR: δ ϭ 0.30 (s,

9 H, 3 CH₃), 0.95 (t, J ϭ 7.0 Hz, 3 H, CH₃), 1.25–1.50 (m, 4 H, 2

CH₂), 1.57 (t, J ϭ 7.0 Hz, 2 H, CH₂), 1.95 (s, 6 H, 3 CH₂), 7.28

(d, J ϭ 7.4 Hz, 2 H, C₆H₄), 7.54 (d, J ϭ 7.4 Hz, 2 H, C₆H₄). – ¹³C

NMR: δ ϭ –1.1 (3 CH₃), 14.2 (CH₃), 52.1 (3 CH₂), 22.9, 28.9, 31.2

(CH₂), 125.5, 133.2 (2 CH), 39.1, 40.9, 137.8, 142.3 (C). – C₁₈H₂₈Si

(271.49): calcd. C 79.34, H 10.36; found C 79.50, H 10.90. – 4,4Ј-

Bis(trimethylsilyl)biphenyl^[47](395 mg, 12%, R_fϭ 0.42) was also

isolated from the reaction mixture by column chromatography.

1-Phenyl-3-propylbicyclo[1.1.1]pentane (20ba): From 19b (1 mmol),

prepared according to GP 6, PhI (204 mg, 112 µL, 1 mmol), and

PdCl₂(dppf) (37 mg, 0.05 mmol) in THF, 20ba (147 mg, 79%) was

obtained according to GP 7 and subsequent column chromato-

graphy (20 g of silica gel, column 15 ϫ 2 cm, pentane) as an oil,

R_fϭ 0.52. – IR: ν˜ ϭ 3075 cm^–1, 3040, 2970, 2920, 2885, 2880,

1620, 1453, 1386, 1304, 1272, 1168, 754, 705. – ¹H NMR: δ ϭ 0.94

(t, J ϭ 7.1 Hz, 3 H, CH₃), 1.25–1.42 (m, 2 H, CH₂), 1.44–1.54 (m,

2 H, CH₂), 1.89 (s, 6 H, 3 CH₂), 7.12–7.32 (m, 5 H, Ph). – ¹³C

NMR: δ ϭ 14.4 (CH₃), 52.2 (3 CH₂), 19.9, 34.0 (CH₂), 126.0, 126.1

(2 CH), 128.0 (CH), 38.9, 41.5, 141.7 (C). – MS (EI): m/z (%) ϭ

186 (2) [M^ϩ], 143 (29) [M^ϩ– C₃H₇], 98 (45), 91 (36), 41 (100).

1-(4-Bromophenyl)-3-butylbicyclo[1.1.1]pentane (20ca): (a) Work-up

of a reaction mixture obtained from 19c (23 mmol), prepared ac-

cording to GP 6, 1,4-dibromobenzene (5.19 g, 22 mmol), and

PdCl₂(dppf) (805 mg, 1.1 mmol) in THF according to GP 7 as in

the preceding coupling and subsequent column chromatography

(200 g of silica gel, column 20 ϫ 7 cm, hexane) gave 20ca (829 mg,

13.5%, R_fϭ 0.53) and 4,4Ј-dibromobiphenyl (1.99 g, 58%, R_fϭ

0.40). (b) To an emulsion of 20cb (17.08 g, 62.7 mmol) in anhydrous

MeOH (660 mL), a solution of Br₂(15.20 g, 4.90 mL, 95.1 mmol)

in MeOH (50 mL) was added over a period of 24 h at room temp.

After stirring for a further 12 h, the mixture was poured into ice-

cold H₂O (1 L) and extracted with pentane (3 ϫ 200 mL). The

combined organic phases were washed with H₂O, 5% NaHCO₃so-

lution, and further H₂O (200 mL each). After evaporation of the

1-Propyl-3-(p-tolyl)bicyclo[1.1.1]pentane

(20bb):

From

19b

(1 mmol), prepared according to GP 6, 4-iodotoluene (109 mg,

0.5 mmol), and PdCl₂(dppf) (8 mg, 0.011 mmol) in THF, 20bb

Eur. J. Org. Chem. 2000, 1137Ϫ1155

1149

M. Messner, S. I. Kozhushkov, A. de Meijere

FULL PAPER

solvent, column chromatography of the residue (200 g of silica gel,

29.6, 29.8, 31.4, 31.8 (CH₂), 130.4, 131.7 (2 CH), 41.0, 44.1, 127.8,

135.4, 197.0 (C).

column 20 ϫ 7 cm, hexane) furnished 20ca (16.87 g, 96%) as an oil,

1

R_fϭ 0.53. – H NMR: δ ϭ 0.95 (t, J ϭ 7.0 Hz, 3 H, CH₃), 1.25–

1-(4Ј-Bromobiphenyl-4-yl)-3-propylbicyclo[1.1.1]pentane

(23ab):

1.45 (m, 4 H, 2 CH₂), 1.52 (t, J ϭ 7.0 Hz, 2 H, CH₂), 1.91 (s, 6 H,

3 CH₂), 7.10 (d, J ϭ 7.6 Hz, 2 H, C₆H₄), 7.43 (d, J ϭ 7.6 Hz, 2 H,

C₆H₄). – ¹³C NMR: δ ϭ 14.1 (CH₃), 52.1 (3 CH₂), 22.9, 28.8, 31.3

(CH₂), 127.8, 131.0 (2 CH), 39.0, 41.0, 120.0, 140.6 (C). – C₁₅H₁₉Br

(279.2): calcd. C 64.52, H 6.86; found C 64.40, H 6.90.

From 19b (5 mmol), prepared according to GP 6, 4,4Ј-dibromobi-

phenyl (22a) (3.12 g, 10 mmol), and PdCl₂(dppf) (73 mg,

0.1 mmol), 23ab (730 mg, 43%) was obtained according to GP 7

with work-up as described above for compound 20cb and sub-

sequent column chromatography (50 g of silica gel, column 15 ϫ

3 cm, PE/Et₂O, 9:1), R_fϭ 0.35; m.p. 156 °C. – IR: ν˜ ϭ 3040 cm^–1,

2960, 2930, 2910, 2875, 2840, 1482, 1390, 1268, 1081, 1006, 811. –

¹H NMR: δ ϭ 0.94 (t, J ϭ 7.0 Hz, 3 H, CH₃), 1.28–1.44 (m, 2 H,

CH₂), 1.50 (t, J ϭ 6.0 Hz, 2 H, CH₂), 1.92 (s, 6 H, 3 CH₂), 7.27

(d, J ϭ 8.0 Hz, 2 H, C₆H₄), 7.45–7.60 (m, 6 H, C₆H₄). – ¹³C NMR:

δ ϭ 14.4 (CH₃), 52.3 (3 CH₂), 19.9, 33.9 (CH₂), 126.6, 126.7, 128.6,

131.8 (2 CH), 39.1, 41.3, 121.3, 137.8, 140.0, 141.2 (C). – MS (EI):

m/z (%) ϭ 342/340 (8:6) [M^ϩ], 299 (9) [M^ϩ– C₃H₇], 91 (29), 73

(100). – C₂₀H₂₁Br (341.3): calcd. C 70.39, H 6.20, Br 23.41; found

C 70.47, H 6.20, Br 23.40.

1-(4-Fluorophenyl)-3-octylbicyclo[1.1.1]pentane (20ea): From 19e

(2.1 mmol), prepared according to GP 6, 4-bromofluorobenzene

(350 mg, 220 µL, 2 mmol), and PdCl₂(dppf) (29 mg, 0.040 mmol)

in THF, 20ea (237 mg, 43%) was obtained according to GP 7 and

subsequent column chromatography (50 g of silica gel, column 15

ϫ 3 cm, PE) as an oil, R_fϭ 0.50. – IR: ν˜ ϭ 3050 cm^–1, 2960, 2930,

2860, 1608, 1523, 1510, 1460, 1276, 1232, 1225, 1158, 842, 816. –

¹H NMR: δ ϭ 0.89 (t, J ϭ 6.6 Hz, 3 H, CH₃), 1.18–1.42 (m, 12 H,

6 CH₂), 1.48–1.56 (m, 2 H, CH₂), 1.86 (s, 6 H, 3 CH₂), 6.96 (tt,

J ϭ 8.8, 2.2 Hz, 2 H, C₆H₄), 7.14 (ddt, J ϭ 8.8, 5.6, 2.2 Hz, 2 H,

C₆H₄). – ¹³C NMR: δ ϭ 14.1 (CH₃), 52.2 (3 CH₂), 22.7, 26.7, 29.4,

29.7, 29.9, 31.6, 32.0 (CH₂), 114.7 (d, J ϭ 21.1 Hz), 127.5 (d, J ϭ

4.0 Hz) (2 CH), 38.9, 41.0, 137.5, 161.6 (d, J ϭ 244.1 Hz) (C). –

MS (EI): m/z (%) ϭ 274 (3) [M^ϩ], 174 (25), 162 (47), 161 (100),

123 (82), 109 (40), 55 (14). – C₁₉H₂₇F (274.4): calcd. C 83.16, H

9.92; found C 83.10, H 10.18

4,4Ј-Bis(3-butylbicyclo[1.1.1]pent-1-yl)biphenyl (23ac): From 19c

(30 mmol), prepared according to GP 6, 4,4Ј-dibromobiphenyl

(22a) (3.12 g, 10 mmol), and PdCl₂(dppf) (73 mg, 0.1 mmol) in

THF, 23ac (3.47 g, 87%) was obtained according to GP 7 under

conditions as those in the preceding preparation and subsequent

column chromatography (100 g of silica gel, column 20 ϫ 5 cm,

hexane), followed by recrystallization from MeOH (500 mL); R_fϭ

1-Octyl-3-[4-(trifluoromethyl)phenyl]bicyclo[1.1.1]pentane

(20eb):

From 19e (2.1 mmol), prepared according to GP 6, 4-bromobenzo-

trifluoride (450 mg, 280 µL, 2 mmol), and PdCl₂(dppf) (29 mg,

0.040 mmol) in THF, 20eb (444 mg, 68%) was obtained according

to GP 7 and subsequent column chromatography (50 g of silica gel,

column 15 ϫ 3 cm, PE) as an oil, R_fϭ 0.59. – IR: ν˜ ϭ 3050

cm^–1, 2960, 2930, 2860, 1622, 1460, 1412, 1328, 1174, 1130, 1070,

1

0.35; m.p. 134–135 °C. – H NMR: δ ϭ 0.91 (t, J ϭ 6.8 Hz, 6 H,

2 CH₃), 1.24–1.43 (m, 8 H, 4 CH₂), 1.48–1.57 (m, 4 H, 2 CH₂),

1.90 (s, 12 H, 6 CH₂), 7.24 (d, J ϭ 8.2 Hz, 4 H, C₆H₄), 7.48 (d,

J ϭ 8.2 Hz, 4 H, C₆H₄). – ¹³C NMR: δ ϭ 14.1 (2 CH₃), 52.2 (6

CH₂), 22.9, 28.9, 31.4 (2 CH₂), 126.5, 126.8 (4 CH), 39.1, 41.3,

139.1, 140.6 (2 C). – MS (EI): m/z (%) ϭ 398 (8) [M^ϩ], 383 (2)

[M^ϩ– CH₃], 355 (9) [M^ϩ– C₃H₇], 341 (100) [M^ϩ– C₄H₉]. – C₃₀H₃₈

(398.6): calcd. C 90.39, H 9.61; found C 90.32, H 9.52.

1

1022, 850, 690. – H NMR: δ ϭ 0.86 (t, J ϭ 6.6 Hz, 3 H, CH₃),

1.18–1.40 (m, 12 H, 6 CH₂), 1.48–1.56 (m, 2 H, CH₂), 1.90 (s, 6 H,

3 CH₂), 7.30 (d, J ϭ 8.4 Hz, 2 H, C₆H₄), 7.53 (d, J ϭ 8.4 Hz, 2 H,

C₆H₄). – ¹³C NMR: δ ϭ 14.1 (CH₃), 52.9 (3 CH₂), 22.7, 26.7, 29.4,

29.7, 29.9, 31.6, 32.0 (CH₂), 125.0 (q, J ϭ 4.0 Hz), 126.4 (2 CH),

39.3, 41.3, 124.4 (q, J ϭ 271.9 Hz), 128.5 (q, J ϭ 32.1 Hz), 145.6

(q, J ϭ 1.3 Hz) (C). – MS (EI): m/z (%) ϭ 324 (4) [M^ϩ], 305 (28)

[M^ϩ– F], 211 (100). – C₂₀H₂₇F₃(324.4): calcd. C 74.04, H 8.39;

found C 73.76, H 8.66.

1-(4Ј-Bromobiphenyl-4-yl)-3-octylbicyclo[1.1.1]pentane (23ae): From

19e (4.7 mmol), prepared according to GP 6, 4,4Ј-dibromobiphenyl

(22a) (3.12 g, 10 mmol), and PdCl₂(dppf) (63 mg, 0.086 mmol) in

Et₂O, 23ae (1.19 g, 62%) was obtained according to GP 7 and sub-

sequent column chromatography (100 g of silica gel, column 20 ϫ

5 cm, hexane), followed by recrystallization from MeOH (500 mL),

R_fϭ 0.35; m.p. 98–103 °C. – IR: ν˜ ϭ 3040 cm^–1, 2960, 2870, 2855,

1482, 1386, 1262, 1080, 1004, 821. – ¹H NMR: δ ϭ 0.90 (t, J ϭ

6.6 Hz, 3 H, CH₃), 1.30 (m, 12 H, 6 CH₂), 1.44–1.56 (m, 2 H, CH₂),

1.90 (s, 6 H, 3 CH₂), 7.27 (d, J ϭ 8.0 Hz, 2 H, C₆H₄), 7.35–7.55

(m, 6 H, C₆H₄). – ¹³C NMR: δ ϭ 14.1 (CH₃), 52.2 (3 CH₂), 22.7,

26.7, 29.3, 29.7, 29.9, 31.7, 31.9 (CH₂), 126.6, 126.7, 128.6, 131.8

(2 CH), 39.1, 41.3, 121.3, 137.9, 140.1, 141.3 (C). – C₂₅H₃₁Br

(411.4): calcd. C 72.98, H 7.60, Br 19.42; found C 72.99, H 7.59,

Br 19.15.

4-(3-Octylbicyclo[1.1.1]pent-1-yl)benzonitrile (20ec): From 19e

(3 mmol), prepared according to GP 6, 4-bromobenzonitrile

(364 mg, 2 mmol), and PdCl₂(dppf) (26 mg, 0.036 mmol) in THF,

20ec (420 mg, 75%) and 4-bromophenyl 3-octylbicyclo[1.1.1]pent-

1-yl ketone (21) (17 mg, 2.5%) were obtained according to GP 7

and subsequent column chromatography (50 g of silica gel, column

15 ϫ 3 cm, PE/Et₂O, 9:1).

20ec: Oil, R_fϭ 0.23. – IR: ν˜ ϭ 2965 cm^–1, 2930, 2875, 2860, 2235,

1670, 1613, 1461, 1276, 1163, 852, 730. – ¹H NMR: δ ϭ 0.89 (t,

J ϭ 6.6 Hz, 3 H, CH₃), 1.18–1.40 (m, 12 H, 6 CH₂), 1.46–1.56 (m,

2 H, CH₂), 1.90 (s, 6 H, 3 CH₂), 7.28 (d, J ϭ 8.0 Hz, 2 H, C₆H₄),

7.56 (d, J ϭ 8.0 Hz, 2 H, C₆H₄). – ¹³C NMR: δ ϭ 14.1 (CH₃), 52.2

(3 CH₂), 22.6, 26.5, 29.3, 29.6, 29.8. 31.4, 31.9 (CH₂), 126.8, 131.9

(2 CH), 39.3, 41.4, 109.8, 119.1, 146.9 (C). – MS (EI): m/z (%) ϭ

281 (1) [M^ϩ], 182 (16), 168 (100), 154 (13), 116 (13). – C₂₀H₂₇N

(281.4): calcd. C 85.35, H 9.67, N 4.98; found C 85.02, H 9.75,

N 4.90.

1-(4Ј-Bromobiphenyl-4-yl)-3-(hex-3-ynyl)bicyclo[1.1.1]pentane

(23aja) and 4,4Ј-Bis[3-(hex-3-ynyl)bicyclo[1.1.1]pent-1-yl]biphenyl

(23ajb): From 19j (41.7 mmol), prepared according to GP 6, 22a

(4.338 g, 13.9 mmol), and PdCl₂(dppf) (400 mg, 0.547 mmol) in

THF, 23aja (2.081 g, 39%) and 23ajb (3.121 g, 50%) were obtained

according to GP 7 and subsequent column chromatography (200 g

of silica gel, column 20 ϫ 7 cm, hexane/benzene, 4:1).

1

23aja: R_fϭ 0.38; m.p. 115–117 °C (MeOH). – H NMR: δ ϭ 1.12

21: R_fϭ 0.28. – ¹H NMR: δ ϭ 0.89 (t, J ϭ 6.6 Hz, 3 H, CH₃), (t, J ϭ 7.4 Hz, 3 H, CH₃), 1.75 (t, J ϭ 7.1 Hz, 2 H, CH₂), 1.96 (s,

1.24 (m, 12 H, 6 CH₂), 1.43–1.55 (m, 2 H, CH₂), 2.12 (s, 6 H, 3

6 H, 3 CH₂), 2.15–2.20 (m, 4 H, 2 H₂), 7.28 (d, J ϭ 9.4 Hz, 2 H,

CH₂), 7.55 (d, J ϭ 8.0 Hz, 2 H, C₆H₄), 7.86 (d, J ϭ 8.0 Hz, 2 H,

C₆H₄), 7.40–7.60 (m, 6 H, C₆H₄). – C₂₃H₂₃Br (379.3): calcd. C

C₆H₄). – ¹³C NMR: δ ϭ 14.1 (CH₃), 53.4 (3 CH₂), 22.7, 26.3, 29.3, 72.82, H 6.11; found C 72.61, H 6.25.

1150

Eur. J. Org. Chem. 2000, 1137Ϫ1155

Nickel- and Palladium-Catalyzed Cross-Coupling Reactions

FULL PAPER

1

23ajb: R_fϭ 0.28; m.p. 136–139 °C (MeOH). – H NMR: δ ϭ 1.04 tyloxypyrimidine-5-yl)phenyl trifluoromethanesulfonate (22e)

(t, J ϭ 7.4 Hz, 6 H, 2 CH₃), 1.69 (t, J ϭ 7.0 Hz, 4 H, 2 CH₂), 1.88 (432 mg, 1 mmol), and PdCl₂(dppf) (43 mg, 0.059 mmol) in THF,

(s, 12 H, 6 CH₂), 2.00–2.15 (m, 8 H, 4 CH₂), 7.20 (d, J ϭ 8.2 Hz,

4 H, C₆H₄), 7.41 (d, J ϭ 8.2 Hz, 4 H, C₆H₄). – ¹³C NMR: δ ϭ

14.3 (2 CH₃), 52.2 (6 CH₂), 12.4, 16.2, 31.1 (2 CH₂), 126.4, 126.8

23ee (365 mg, 79%) was obtained according to GP 7 and sub-

sequent column chromatography (50 g of silica gel, column 15 ϫ

3 cm, PE/Et₂O, 9:1), R_fϭ 0.17; m.p. 85 °C. – IR: ν˜ ϭ 3060 cm^–1,

(4 CH), 38.6, 41.4, 79.4, 81.6, 139.1, 140.2 (2 C). – C₃₄H₃₈(446.7): 2925, 2906, 2855, 1600, 1542, 1455, 1343, 1025, 840, 805. – ¹H

calcd. C 91.42, H 8.58; found C 91.30, H 8.65.

NMR: δ ϭ 0.83–0.98 (m, 6 H, 2 CH₃), 1.29 (m, 22 H, 11 CH₂),

1.42–1.58 (m, 2 H, CH₂), 1.84 (quint, J ϭ 7.4 Hz, 2 H, CH₂), 1.91

(s, 6 H, 3 CH₂), 4.39 (t, J ϭ 6.7 Hz, 2 H, OCH₂), 7.32 (d, J ϭ

8.1 Hz, 2 H, C₆H₄), 7.44 (d, J ϭ 8.1 Hz, 2 H, C₆H₄), 8.68 (s, 2 H,

Ar). – ¹³C NMR: δ ϭ 14.1 (2 CH₃), 52.5 (3 CH₂), 22.7, 22.7, 26.0,

26.7, 28.9, 29.2, 29.3, 29.4, 29.7, 29.9, 31.2, 31.8, 31.9, 67.9 (CH₂),

126.9, 127.0, 147.1 (2 CH), 39.2, 41.3, 128.1, 132.4, 141.8, 164.7

(C). – MS (EI): m/z (%) ϭ 462 (25) [M^ϩ], 349 (100) [M^ϩ– C₈H₁₇],

311 (30), 237 (39), 207 (11), 199 (12), 180 (17), 167 (12), 149 (33),

111 (13), 91 (18), 57 (44). – C₃₁H₄₆N₂O (462.60): calcd. C 80.46,

H 10.02, N 6.06; found C 80.49, H 10.03, N 6.14.

1-Octyl-3-(4Ј-octylbiphenyl-4-yl)bicyclo[1.1.1]pentane (23be): From

19e (2 mmol), prepared according to GP 6, 4-bromo-4Ј-octylbi-

phenyl (22b) (345 mg, 1 mmol), and PdCl₂(dppf) (65 mg,

0.089 mmol) in Et₂O, 23be (357 mg, 80%) was obtained according

to GP 7 and subsequent column chromatography (50 g of silica gel,

column 15 ϫ 3 cm, PE), R_fϭ 0.34; m.p. 89 °C (MeOH). – IR: ν˜ ϭ

3030 cm^–1, 2960, 2925, 2855, 1595, 1460, 1271, 1162, 1009, 822. –

¹H NMR: δ ϭ 0.83–0.98 (m, 6 H, 2 CH₃), 1.19–1.42 (m, 24 H, 12

CH₂), 1.44–1.56 (m, 2 H, CH₂), 1.90 (s, 6 H, 3 CH₂), 2.63 (t, J ϭ

7.7 Hz, 2 H, CH₂), 7.22 (t, J ϭ 8.0 Hz, 4 H, C₆H₄), 7.49 (t, J ϭ

8.0 Hz, 4 H, C₆H₄). – ¹³C NMR: δ ϭ 14.1 (2 CH₃), 52.2 (3 CH₂),

29.3 (2 CH₂), 22.7, 26.7, 29.4, 29.4, 29.5, 29.7, 29.8, 29.9, 31.5,

31.7, 31.9, 35.6 (CH₂), 126.4, 126.7, 126.9, 128.8 (2 CH), 39.1, 41.4,

138.5, 139.1, 140.4, 141.9 (C). – MS (EI): m/z (%) ϭ 444 (0.2) [M^ϩ],

378 (19), 279 (21), 180 (13), 86 (54), 57 (53), 41 (100). – C₃₃H₄₈

(444.7): calcd. C 89.12, H 10.88; found C 89.19, H 10.84.

1-(4Ј-Ethylbiphenyl-4-yl)-3-[2-(tetrahydropyran-2-yloxy)ethyl]-

bicyclo[1.1.1]pentane (23ff): From 19f (89 mmol), prepared accord-

ing to GP 6, 22f (11.38 g, 43.6 mmol), and PdCl₂(dppf) (1.30 g,

1.78 mmol) in THF, 23ff (1.605 g, 10%) and 3,3Ј-bis[2-(tetra-

hydropyran-2-yloxy)ethyl]-1,1Ј-bis(bicyclo[1.1.1]pentyl)

(1.107 g,

6.4%) were obtained according to GP 7 and subsequent column

chromatography (200 g of alumina deactivated with 5% H₂O, col-

umn 30 ϫ 5 cm, hexane/EtOAc, 40:1).

5-Octyl-2-[4-(3-octylbicyclo[1.1.1]pent-1-yl)phenyl]pyrimidine

(23ce): From 19e (1.5 mmol), prepared according to GP 6, 4-(5-

23ff: R_fϭ 0.33; m.p. 30–32 °C. – ¹H NMR: δ ϭ 1.28 (t, J ϭ 7.4 Hz,

3 H, CH₃), 1.48–1.75 (m, 6 H, 3 CH₂), 1.75–1.95 (m, 2 H, CH₂),

2.05 (s, 6 H, 3 CH₂), 2.75 (q, J ϭ 7.4 Hz, 2 H, CH₂), 3.45–3.65 (m,

2 H, OCH₂), 3.80–4.05 (m, 2 H, OCH₂), 4.68 (t, J ϭ 3.2 Hz, 1 H,

OCH), 7.22–7.37 (m, 4 H, C₆H₄), 7.50–7.65 (m, 4 H, C₆H₄). – ¹³C

NMR: δ ϭ 15.6 (CH₃), 52.8 (3 CH₂), 19.6, 25.5, 28.5, 30.8, 31.6,

62.3, 65.8 (CH₂), 126.4, 126.7, 127.0, 128.2 (2 CH), 98.9 (CH), 36.9,

41.8, 138.5, 139.2, 140.1, 143.1 (C).

octylpyrimidine-2-yl)phenyl

trifluoromethanesulfonate

(22c)

(208 mg, 0.5 mmol), and PdCl₂(dppf) (24 mg, 0.033 mmol) in THF,

23ce (140 mg, 63%) was obtained according to GP 7 and sub-

sequent column chromatography (25 g of silica gel, column 20 ϫ

2 cm, PE/Et₂O, 19:1), R_fϭ 0.21; m.p. 34 °C. – ¹H NMR: δ ϭ 0.80–

0.96 (m, 6 H, 2 CH₃), 1.33 (m, 22 H, 11 CH₂), 1.48–1.56 (m, 2 H,

CH₂), 1.56–1.72 (m, 2 H, CH₂), 1.90 (s, 6 H, 3 CH₂), 2.61 (t, J ϭ

7.6 Hz, 2 H, CH₂), 7.32 (d, J ϭ 8.2 Hz, 2 H, C₆H₄), 8.34 (d, J ϭ

8.2 Hz, 2 H, C₆H₄), 8.58 (s, 2 H, Ar). – ¹³C NMR: δ ϭ 14.0 (2

CH₃), 52.2 (3 CH₂), 22.6, 22.7, 26.6, 29.0, 29.2, 29.3, 29.4, 29.6,

29.8, 30.1, 30.7, 31.7, 31.8, 31.9 (CH₂), 126.2, 127.6, 156.9 (2 CH),

39.1, 41.5, 132.6, 135.5, 144.0, 162.5 (C). – MS (EI): m/z (%) ϭ 447

(34) [M^ϩϩ H], 446 (11) [M^ϩ], 432 (16) [M^ϩ– CH₂], 381 (38), 334

(100), 295 (33), 282 (29). – C₃₁H₄₆N₂(446.7): calcd. C 83.35, H

10.38, N 6.27; found C 83.28, H 10.37, N 6.24.

3,3Ј-Bis[2-(tetrahydropyran-2-yloxy)ethyl]-1,1Ј-bis(bicyclo[1.1.1]-

pentyl): Oil, R_fϭ 0.50. – ¹H NMR: δ ϭ 1.48 (s, 12 H, 6 CH₂),

1.40–1.65 (m, 12 H, 6 CH₂), 1.69 (t, J ϭ 7.0 Hz, 4 H, 2 CH₂), 3.30

(dt, J ϭ 9.5, 7.0 Hz, 2 H, OCH₂), 3.35–3.50 (m, 2 H, OCH₂), 3.65

(dt, J ϭ 9.5, 6.9 Hz, 2 H, OCH₂), 3.85 (ddd, J ϭ 11.4, 7.5, 3.7 Hz,

2 H, OCH₂), 4.50 (t, J ϭ 3.2 Hz, 2 H, OCH). – ¹³C NMR: δ ϭ

49.4 (6 CH₂), 19.5, 25.4, 30.1, 31.7, 62.1, 66.1 (2 CH₂), 98.7 (2 CH),

36.3, 39.4 (2 C).

2-[4-(3-Octylbicyclo[1.1.1]pent-1-yl)phenyl]-5-octyloxypyrimidine

(23de): From 19e (1.5 mmol), prepared according to GP 6, 4-(5-

octyloxypyrimidine-2-yl)phenyl trifluoromethanesulfonate (22d)

(400 mg, 0.92 mmol), and PdCl₂(dppf) (36 mg, 0.049 mmol) in

THF, 23de (300 mg, 70%) was obtained according to GP 7 and

subsequent column chromatography (50 g of silica gel, column 15

ϫ 3 cm, PE/Et₂O, 9:1), R_fϭ 0.26; m.p. 45 °C. – IR: ν˜ ϭ 3050

cm^–1, 2960, 2930, 2860, 1613, 1577, 1548, 1442, 1285, 857, 788. –

¹H NMR: δ ϭ 0.89 (t, J ϭ 6.6 Hz, 6 H, 2 CH₃), 1.29 (m, 22 H, 11

CH₂), 1.48–1.58 (m, 2 H, CH₂), 1.83 (quint, J ϭ 6.5 Hz, 2 H, CH₂),

1.91 (s, 6 H, 3 CH₂), 4.08 (t, J ϭ 6.5 Hz, 2 H, OCH₂), 7.31 (d, J ϭ

8.5 Hz, 2 H, C₆H₄), 8.26 (d, J ϭ 8.5 Hz, 2 H, C₆H₄), 8.44 (s, 2 H,

Ar). – ¹³C NMR: δ ϭ 14.0, 14.1 (CH₃), 52.2 (3 CH₂), 22.6, 22.7,

25.8, 26.6, 29.0, 29.1, 29.2, 29.3, 29.6, 29.8, 31.7, 31.7, 31.9, 68.7

(CH₂), 126.2, 127.2, 143.6 (2 CH), 39.1, 41.5, 135.4, 143.2, 151.3,

1-(4Ј-Ethylbiphenyl-4-yl)-3-[3-(tetrahydropyran-2-yloxy)propyl]-

bicyclo[1.1.1]pentane (23fg): From 19g (115 mmol), prepared ac-

cording to GP 6, 22f (7.48 g, 28.6 mmol), and PdCl₂(dppf) (1.40 g,

1.91 mmol) in THF, 23fg (6.82 g, 61%) was obtained according to

GP 7 and subsequent column chromatography (250 g of alumina

deactivated with 5% H₂O, column 30 ϫ 5 cm, hexane/EtOAc, 15:1)

as an oil, R_fϭ 0.31. – ¹H NMR: δ ϭ 1.20 (t, J ϭ 6.9 Hz, 3 H,

CH₃), 1.38–1.65 (m, 8 H, 4 CH₂), 1.68–1.90 (m, 2 H, CH₂), 1.88

(s, 6 H, 3 CH₂), 2.61 (q, J ϭ 6.9 Hz, 2 H, CH₂), 3.28–3.41 (m, 1

H, OCH₂), 3.41–3.55 (m, 1 H, OCH₂), 3.58–3.71 (m, 1 H, OCH₂),

3.75–3.91 (m, 1 H, OCH₂), 4.53 (t, J ϭ 3.2 Hz, 1 H, OCH), 7.11–

7.25 (m, 4 H, C₆H₄), 7.39–7.49 (m, 4 H, C₆H₄). – C₂₇H₃₄O₂(390.6):

calcd. C 83.03, H 8.78; found C 82.71, H 8.99.

1-{4Ј-[2-(Z)-(trans-2-Ethyloxycyclopropyl)vinyl]biphenyl-4-yl}-3-{[4-

(tetrahydropyran-2-yloxy]butyl}bicyclo[1.1.1]pentane (23gh): From

19h (2 mmol), prepared according to GP 6, 22g (170 mg,

0.5 mmol), and PdCl₂(dppf) (24 mg, 0.033 mmol) in THF, 23gh

(115 mg, 48%) was obtained according to GP 7 and subsequent

column chromatography (20 g of silica gel, column 15 ϫ 2 cm, PE/

Et₂O, 4:1) as an oil, R_fϭ 0.25. – ¹H NMR: δ ϭ 0.73 (q, J ϭ

157.5 (C). – MS (EI): m/z (%) ϭ 462 (30) [M^ϩ], 447 (12) [M^ϩ

–

CH₃], 430 (18), 396 (23), 386 (20), 349 (100) [M^ϩ– C₈H₁₇], 311

(20), 256 (16), 237 (17), 186 (15), 57 (72). – C₃₁H₄₆N₂O (462.6):

calcd. C 80.46, H 10.02, N 6.06; found C 80.60, H 10.13, N 6.11.

5-[4-(3-Octylbicyclo[1.1.1]pent-1-yl)phenyl]-2-octyloxypyrimidine

(23ee): From 19e (4 mmol), prepared according to GP 6, 4-(2-oc-

Eur. J. Org. Chem. 2000, 1137Ϫ1155

1151

M. Messner, S. I. Kozhushkov, A. de Meijere

6.4 Hz, 1 H, Cpr), 1.12–1.22 (m, 1 H, Cpr), 1.19 (t, J ϭ 7.0 Hz, 3 H], 446 (11) [M^ϩ], 338 (52), 334 (41), 55 (57). – C₃₀H₄₂N₂O (446.7):

FULL PAPER

H, CH₃), 1.30–1.92 (m, 12 H, 6 CH₂), 1.92 (s, 6 H, 3 CH₂), 2.11

(m, 1 H, Cpr), 3.31 (ddd, J ϭ 6.4, 3.7, 2.6 Hz, 1 H, Cpr), 3.42 (dt,

J ϭ 9.5, 6.6 Hz, 1 H, OCH₂), 3.46–3.56 (m, 1 H, OCH₂), 3.60 (q,

J ϭ 7.0 Hz, 2 H, OCH₂), 3.76 (dt, J ϭ 9.5, 6.6 Hz, 1 H, OCH₂),

3.88 (m, 1 H, OCH₂), 4.59 (t, J ϭ 3.2 Hz, 1 H, OCH), 5.05 (dd,

J ϭ 11.5, 10.0 Hz, 1 H, ϭCH), 6.38 (d, J ϭ 11.5 Hz, 1 H, ϭCH),

7.26–7.32 (m, 2 H, C₆H₄), 7.45–7.58 (m, 6 H, C₆H₄). – ¹³C NMR:

δ ϭ 15.1 (CH₃), 52.2 (3 CH₂), 15.9, 19.7, 23.4, 25.5, 29.9, 30.8,

31.5, 63.4, 66.1, 67.6 (CH₂), 20.0, 61.4, 98.9, 126.5, 126.7, 126.8,

127.8, 129.1, 132.7 (CH), 39.0, 41.4, 136.4, 138.8, 139.3, 140.6 (C).

calcd. C 80.67, H 9.48, N 6.27; found C 80.75, H 9.48, N 6.33.

General Procedure (GP 8) for the Preparation of Triflates 22c–e: To

a solution of the appropriate phenol^[27](1.5 mmol) in anhydrous

pyridine (5 mL), trifluoromethanesulfonic anhydride (460 mg, 274

µL, 1.63 mmol) was added at 0 °C. After stirring for 24 h at room

temp., the mixture was poured into ice-cold water (20 mL) and ex-

tracted with Et₂O (3 ϫ 15 mL). The combined extracts were dried,

the solvent was evaporated, and the residue was purified by column

chromatography (25 g of silica gel, column 15 ϫ 2 cm, CH₂Cl₂).

4-(5-Octylpyrimidine-2-yl)phenyl Trifluoromethanesulfonate (22c):

Compound 22c (593 mg, 95%) was obtained from 2-(4-hydroxy-

phenyl)-5-octylpyrimidine (427 mg, 1.5 mmol) according to GP 8,

{3-[(E)-Pent-3-enyl]bicyclo[1.1.1]pent-1-yl}phenyl

4-Cyano-3,5-di-

fluorobenzoate (23hm): From 19m (23.65 mmol), prepared accord-

ing to GP 6, 4-bromophenyl 4-cyano-3,5-difluorobenzoate (22h)

(5.0 g, 14.79 mmol), and PdCl₂(dppf) (542 mg, 0.74 mmol) in THF,

23hm (2.272 g, 39%) was obtained according to GP 7 and sub-

sequent column chromatography (250 g of silica gel, column 30 ϫ

5 cm, hexane/Et₂O, 10:1), R_fϭ 0.42; m.p. 75–77 °C (MeOH/H₂O,

1

R_fϭ 0.50. – H NMR: δ ϭ 0.89 (t, J ϭ 6.5 Hz, 3 H, CH₃), 1.20–

1.45 (m, 10 H, 5 CH₂), 1.59–1.73 (m, 2 H, CH₂), 2.64 (t, J ϭ

7.7 Hz, 2 H, CH₂), 7.38 (d, J ϭ 9.0 Hz, 2 H, C₆H₄), 8.52 (d, J ϭ

9.0 Hz, 2 H, C₆H₄), 8.63 (s, 2 H, Ar). – ¹³C NMR: δ ϭ 13.9 (CH₃),

22.5, 29.0, 29.1, 29.2, 30.0, 30.6, 31.7 (CH₂), 121.2, 129.8, 150.9 (2

CH), 118.7 (q, J ϭ 320.9 Hz), 133.6, 137.9, 150.9, 160.7 (C).

1

95:5). – H NMR: δ ϭ 1.55–1.70 (m, 5 H, CH₂ϩ CH₃), 1.98 (s, 6

H, 3 CH₂), 1.95–2.05 (m, 2 H, CH₂), 4.88–5.02 (m, 2 H, CHϭCH),

7.05 (d, J ϭ 8.3 Hz, 2 H, C₆H₄), 7.35 (d, J ϭ 8.3 Hz, 2 H, C₆H₄),

8.05 (d, J ϭ 7.5 Hz, 2 H, C₆H₂F₂). – ¹³C NMR: δ ϭ 18.0 (CH₃),

52.3 (3 CH₂), 29.7, 31.3 (CH₂), 107.0 (dd, J ϭ 23.0, 4.0 Hz), 126.6,

130.3 (2 CH), 124.8, 131.1 (CH), 163.5 (dd, J ϭ 261.5, 6.9 Hz) (2

C), 39.2, 41.6, 108.8, 125.4, 148.8, 156.1 (t, J ϭ 21.0 Hz), 163.4,

165.6 (t, J ϭ 6.3 Hz) (C).

4-(5-Octyloxypyrimidine-2-yl)phenyl Trifluoromethanesulfonate

(22d): Compound 22d (496 mg, 77%) was obtained from 2-(4-hy-

droxyphenyl)-5-octyloxypyrimidine (451 mg, 1.5 mmol) according

to GP 8, R_fϭ 0.61. – ¹H NMR: δ ϭ 0.89 (t, J ϭ 6.7 Hz, 3 H,

CH₃), 1.22–1.25 (m, 10 H, 5 CH₂), 1.84 (quint, J ϭ 76.9 Hz, 2 H,

CH₂), 4.11 (t, J ϭ 6.5 Hz, 2 H, OCH₂), 7.36 (dt, J ϭ 8.9, 2.4 Hz,

2 H, C₆H₄), 8.44 (dt, J ϭ 8.9, 2.4 Hz, 2 H, C₆H₄), 8.45 (s, 2 H,

Ar). – ¹³C NMR: δ ϭ 13.5 (CH₃), 22.6, 25.8, 29.0, 29.1, 29.2, 31.7,

68.9 (CH₂), 121.2, 129.3, 143.7 (2 CH), 118.7 (q, J ϭ 320.0 Hz),

137.7, 150.5, 151.9, 155.6 (C).

4-[4-(3-Butylbicyclo[1.1.1]pent-1-yl)-α,α-difluorobenzyloxy]-

2,3Ј,4Ј,6-tetrafluorobiphenyl (23ic): From 19c (42.69 mmol), pre-

pared according to GP 6, (4-bromophenyl)difluoromethyl 3,5,3Ј,4Ј-

tetrafluorobiphenyl-1-yl ether (22i) (7.00 g, 15.65 mmol), and

PdCl₂(dppf) (572 mg, 0.782 mmol) in THF, 23ic (6.508 g, 85%) was

obtained according to GP 7 and subsequent column chromato-

graphy (250 g of silica gel, column 30 ϫ 5 cm, hexane), R_fϭ 0.38;

4-(2-Octyloxypyrimidine-5-yl)phenyl Trifluoromethanesulfonate

(22e): Compound 22e (561 mg, 86%) was obtained from 5-(4-hy-

droxyphenyl)-2-octyloxypyrimidine (451 mg, 1.5 mmol) according

to GP 8, R_fϭ 0.39. – ¹H NMR: δ ϭ 0.89 (t, J ϭ 6.6 Hz, 3 H,

CH₃), 1.22–1.55 (m, 10 H, 5 CH₂), 1.87 (quint, J ϭ 7.1 Hz, 2 H,

CH₂), 4.41 (t, J ϭ 7.7 Hz, 2 H, OCH₂), 7.40 (dt, J ϭ 8.8, 2.5 Hz,

2 H, C₆H₄), 7.59 (dt, J ϭ 8.8, 2.5 Hz, 2 H, C₆H₄), 8.69 (s, 2 H,

Ar). – ¹³C NMR: δ ϭ 13.8 (CH₃), 22.4, 25.8, 28.7, 29.0, 29.1, 31.6,

68.0 (CH₂), 121.1, 128.1, 157.1 (2 CH), 118.6 (q, J ϭ 320.8 Hz),

126.1, 134.95, 149.3, 165.1 (C).

1

m.p. 89–91 °C (MeOH/H₂O, 90:1). – H NMR: δ ϭ 0.95 (t, J ϭ

5.5 Hz, 3 H, CH₃), 1.22–1.45 (m, 4 H, 2 CH₂), 1.55 (t, J ϭ 8.0 Hz,

2 H, CH₂), 1.95 (s, 6 H, 3 CH₂), 6.95 (d, J ϭ 9.2 Hz, 2 H, C₆H₂F₂),

7.15–7.30 (m, 3 H, C₆H₃F₂), 7.35 (d, J ϭ 8.3 Hz, 2 H, C₆H₄), 7.65

(d, J ϭ 8.3 Hz, 2 H, C₆H₄). – ¹³C NMR: δ ϭ 14.1 (CH₃), 52.2 (3

CH₂), 22.9, 28.8, 31.3 (CH₂), 105.3 (d, J ϭ 29.3 Hz), 122.5, 125.3

(t, J ϭ 3.8 Hz) (2 CH), 117.3 (dd, J ϭ 16.2, 4.7 Hz), 119.5 (dd, J ϭ

14.2, 5.0 Hz), 126.7 (t, J ϭ 5.2 Hz) (CH), 159.8 (dd, J ϭ 249.0,

9.1 Hz) (2 C), 39.2, 41.2, 119.3 (t, J ϭ 354.8 Hz), 122.5, 125.9 (t,

J ϭ 21.9 Hz), 125.0 (t, J ϭ 5.4 Hz), 130.5 (t, J ϭ 30.8 Hz), 149.9

(dd, J ϭ 248.6, 14.6 Hz), 150.4 (dd, J ϭ 252.2, 14.8 Hz), 150.8 (t,

J ϭ 14.8 Hz) (C).

General Procedure (GP 9) for the Preparation of Cyanides from

23ab,ae: A mixture of 23ab or 23ae (0.75 mmol) and CuCN

(170 mg, 1.9 mmol) in anhydrous N-methyl-2-pyrrolidone (2 mL)

was stirred at 185 °C for 13 h. After cooling to room temp., the

mixture was treated with a solution of FeCl₃(120 mg, 0.74 mmol)

in 1% aq. HCl (5 mL), stirred for 20 min at 50 °C, and extracted

with Et₂O (3 ϫ 20 mL). The combined extracts were dried, the

solvent was evaporated, and the residue was purified by column

chromatography (25 g of silica gel, column 18 ϫ 2 cm, PE/Et₂O,

9:1).

5-[4-(4-Cyclopropylbutyloxy)phenyl]-2-(3-octylbicyclo[1.1.1]pent-1-

yl)pyrimidine (23je): From 19e (6 mmol), prepared according to GP

6, 5-[4-(4-cyclopropylbutyloxy)phenyl]-2-bromopyrimidine (22j)

(520 mg, 1.5 mmol), and PdCl₂(dppf) (53 mg, 0.072 mmol) in THF,

23je (566 mg, 84%) was obtained according to GP 7 and sub-

sequent column chromatography (50 g of silica gel, column 15 ϫ

3 cm, PE/Et₂O, 19:1), R_fϭ 0.17; m.p. 57 °C. – IR: ν˜ ϭ 3080 cm^–1, 4Ј-(3-Propylbicyclo[1.1.1]pent-1-yl)biphenyl-4-carbonitrile

3005, 2960, 2855, 2625, 1610, 1586, 1432, 1258, 1172, 850, 800. – From 23ab (295 mg, 0.864 mmol), 24ab (191 mg, 77%) was ob-

¹H NMR: δ ϭ 0.03 (m, 2 H, Cpr), 0.41 (m, 2 H, Cpr), 0.61–0.78 tained according to GP 9, R_fϭ 0.20; m.p. 108 °C. – ¹H NMR: δ ϭ

(m, 1 H, Cpr), 0.89 (t, J ϭ 6.5 Hz, 3 H, CH₃), 1.22–1.37 (m, 14 H, 0.95 (t, J ϭ 7.2 Hz, 3 H, CH₃), 1.28–1.44 (m, 2 H, CH₂), 1.46–1.53

(24ab):

7 CH₂), 1.47–1.65 (m, 4 H, 2 CH₂), 1.85 (quint, J ϭ 7.1 Hz, 2 H, (m, 2 H, CH₂), 1.93 (s, 6 H, 3CH₂), 7.32 (dt, J ϭ 8.3, 1.9 Hz, 2 H,

CH₂), 1.96 (s, 6 H, 3 CH₂), 4.03 (t, J ϭ 6.5 Hz, 2 H, OCH₂), 6.97 C₆H₄), 7.52 (dt, J ϭ 8.3, 1.9 Hz, 2 H, C₆H₄), 7.67 (m, 4 H, C₆H₄). –

(d, J ϭ 9.0 Hz, 2 H, C₆H₄), 8.34 (d, J ϭ 9.0 Hz, 2 H, C₆H₄), 8.53 ¹³C NMR: δ ϭ 14.4 (CH₃), 52.3 (3 CH₂), 19.9, 33.9 (CH₂), 126.9,

(s, 2 H, Ar). – ¹³C NMR: δ ϭ 14.1 (CH₃), 52.1 (3 CH₂), 4.4 (2 127.0, 127.6, 132.6 (2 CH), 39.2, 41.3, 110.6, 119.0, 137.0, 142.4,

CH₂), 22.6, 26.0, 26.5, 29.0, 29.2, 29.6, 29.7, 31.5, 31.8, 34.4, 68.0

145.6 (C). – MS (EI): m/z (%) ϭ 287 (4) [M^ϩ], 244 (100) [M^ϩ

–

(CH₂), 114.3, 129.4, 155.0 (2 CH), 10.7 (CH), 34.4, 37.4, 130.1, C₃H₇], 230 (11), 203 (13). – C₂₁H₂₁N (287.4): calcd. C 87.76, H

130.6, 161.1, 162.4 (C). – MS (FAB): m/z (%) ϭ 447 (100) [M^ϩ

ϩ

7.37, N 4.87; found C 87.84, H 7.57, N 4.92.

Eur. J. Org. Chem. 2000, 1137Ϫ1155

1152

Nickel- and Palladium-Catalyzed Cross-Coupling Reactions

FULL PAPER

4Ј-(3-Octylbicyclo[1.1.1]pent-1-yl)biphenyl-4-carbonitrile

(24ae): DMSO (100 mL), compound 26ff or 26fg (10 mmol) was added

From 23ae (309 mg, 0.75 mmol), 24ae (225 mg, 84%) was obtained

portionwise over a period of 40 min such that the temperature was

maintained at 25 °C. After stirring for 12 h at room temp., the

according to GP 9, R_fϭ 0.23; m.p. 80 °C. – IR: ν˜ ϭ 3040 cm^–1,

2960, 2945, 2920, 2910, 2865, 2850, 2840, 2225, 1605, 1492, 1470, mixture was poured into ice-cold water (200 mL) and extracted

1274, 1160, 1006, 837, 823, 801, 733, 729. – ¹H NMR: δ ϭ 0.89 (t, with Et₂O (3 ϫ 50 mL). The combined extracts were washed with

J ϭ 6.6 Hz, 3 H, CH₃), 1.29 (m, 12 H, 6 CH₂), 1.44–1.58 (m, 2 H,

H₂O (3 ϫ 50 mL), dried, and the solvent was evaporated. The res-

CH₂), 1.90 (s, 6 H, 3 CH₂), 7.32 (d, J ϭ 8.2 Hz, 2 H, C₆H₄), 7.51 idue was purified by column chromatography (70 g of silica gel,

(d, J ϭ 8.2 Hz, 2 H, C₆H₄), 7.64 (d, J ϭ 8.5 Hz, 2 H, C₆H₄), 7.70 column 15 ϫ 3 cm, hexane/EtOAc, 30:1).

(d, J ϭ 8.5 Hz, 2 H, C₆H₄). – ¹³C NMR: δ ϭ 14.0 (CH₃), 52.1 (3

1-(4Ј-Ethylbiphenyl-4-yl)-3-vinylbicyclo[1.1.1]pentane (27ff): From

CH₂), 22.6, 26.6, 29.2, 29.6, 29.8, 31.5, 31.8 (CH₂), 126.7, 126.8,

26ff (1.066 g, 3 mmol), 27ff (594 mg, 72%) was obtained according

127.3, 132.4 (2 CH), 39.1, 41.1, 110.5, 118.8, 136.8, 142.2, 145.3

to GP 11, R_fϭ 0.70; m.p. 83–86 °C (MeOH). – ¹H NMR: δ ϭ

(C). – MS (EI): m/z (%) ϭ 357 (7) [M^ϩ], 258 (13), 244 (100) [M^ϩ

–

1.33 (t, J ϭ 7.6 Hz, 3 H, CH₃), 2.16 (s, 6 H, 3 CH₂), 2.70 (q, J ϭ

7.6 Hz, 2 H, CH₂), 5.07 (dd, J ϭ 10.4, 2.1 Hz, 1 H, ϭCH₂), 5.10

(dd, J ϭ 17.2, 2.1 Hz, 1 H, ϭCH₂), 6.02–6.09 (m, 1 H, ϭCH), 7.35

(t, J ϭ 8.4 Hz, 4 H, C₆H₄), 7.57 (dd, J ϭ 8.2, 6.2 Hz, 4 H, C₆H₄). –

¹³C NMR: δ ϭ 15.6 (CH₃), 53.4 (3 CH₂), 28.5, 115.0 (CH₂), 126.5,

126.8, 127.0, 128.2 (2 CH), 137.6 (CH), 40.2, 41.3, 138.4, 139.4,

139.9, 143.2 (C).

C₈H₁₇], 219 (10), 206 (33). – C₂₆H₃₁N (357.52): calcd. C 87.34, H

8.74, N 3.92; found C 87.27, H 8.71, N 4.08.

4-(3-{4Ј-[2-(trans-2-Ethyloxycyclopropyl)vinyl]biphenyl-4-yl}-

bicyclo[1.1.1]pent-1-yl)butan-1-ol (25): A solution of 23gh (115 mg,

0.24 mmol) in MeOH (5 mL) was stirred with the strongly acidic

ion-exchange resin Lewatit SPS 118 (50 mg) for 16 h at room temp.,

filtered through Celite, and the filtrate was concentrated. Column

chromatography of the residue (20 g of silica gel, column 15 ϫ

2 cm, PE/Et₂O, 4:1) furnished 25 (69 mg, 72%) as an oil, R_fϭ

1-(4Ј-Ethylbiphenyl-4-yl)-3-(prop-1-enyl)bicyclo[1.1.1]pentane (27fg)

and 1-(3-tert-Butyloxypropyl)-3-(4Ј-ethylbiphenyl-4-yl)bicyclo-

[1.1.1]pentane (28): From 26fg (8.50 g, 23 mmol), 27fg (3.32 g, 50%,

E/Z ϭ 77:23) and 28 (2.51 g, 30%) were obtained according to

GP 11.

1

0.25. – H NMR: δ ϭ 0.73 (q, J ϭ 6.1 Hz, 1 H, Cpr), 1.12–1.26

(m, 2 H, Cpr, OH), 1.20 (t, J ϭ 7.0 Hz, 3 H, CH₃), 1.33–1.48 (m,

2 H, CH₂), 1.52–1.68 (m, 4 H, 2 CH₂), 1.92 (s, 6 H, 3 CH₂), 2.12

(m, 1 H, Cpr), 3.32 (ddd, J ϭ 6.4, 3.7, 2.6 Hz, 1 H, Cpr), 3.58 (q,

J ϭ 7.0 Hz, 2 H, CH₂), 3.68 (q, J ϭ 5.4 Hz, 2 H, CH₂), 5.06 (dd,

J ϭ 11.5, 10.0 Hz, 1 H, ϭCH), 6.37 (d, J ϭ 11.5 Hz, 1 H, ϭCH),

7.26–7.32 (m, 2 H, C₆H₄), 7.46–7.58 (m, 6 H, C₆H₄). – ¹³C NMR:

δ ϭ 15.1 (CH₃), 52.1 (3 CH₂), 15.9, 22.9, 31.5, 32.9, 62.4, 66.1

(CH₂), 19.6, 61.3, 126.4, 126.6, 126.7, 127.8, 129.0, 132.7 (CH),

38.9, 41.3, 136.4, 138.7, 139.2, 140.5 (C).

1

27fg: R_fϭ 0.63; m.p. 89–92 °C (MeOH). – H NMR: δ ϭ 1.27 (t,

J ϭ 7.6 Hz, 3 H, CH₃), 1.71 (dd, J ϭ 6.0, 1.0 Hz, 3 H, CH₃, E),

1.76 (d, J ϭ 5.3 Hz, 3 H, CH₃, Z), 2.07 (s, 6 H, 3 CH₂), 2.70 (q,

J ϭ 7.6 Hz, 2 H, CH₂), 5.52 (dq, J ϭ 16.5, 6.0 Hz, 1 H, ϭCH, E),

5.67 (dd, J ϭ 16.5, 1.0 Hz, 1 H, ϭCH, E), 7.20–7.30 (m, 4 H,

C₆H₄), 7.45–7.55 (m, 4 H, C₆H₄). – C₂₂H₂₄(288.4): calcd. C 91.61,

H 8.39; found C 91.55, H 8.28.

General Procedure (GP 10) for the Conversion of 23ff,fg to the Cor-

responding Bromides: To a stirred solution of triphenylphosphane

(1.05 g, 4 mmol) in CH₂Cl₂(15 mL), a solution of Br₂(671 mg, 216

µL, 4.2 mmol) in CH₂Cl₂(5 mL) was added at –10 °C. To this

mixture, a solution of 23ff or 23fg (4 mmol) in CH₂Cl₂(5 mL) was

added over a period of 15 min at 0 °C. After stirring for 2 h at

room temp., the mixture was diluted with CH₂Cl₂(30 mL), washed

with brine (20 mL), dried, and the solvent was evaporated. The

residue was purified by column chromatography (50 g of silica gel,

column 15 ϫ 3 cm, hexane/EtOAc, 20:1).

1

28: R_fϭ 0.35; m.p. 85–86 °C (MeOH). – H NMR: δ ϭ 1.21 (s, 9

H, 3 CH₃), 1.27 (t, J ϭ 7.6 Hz, 3 H, CH₃), 1.57 (m, 4 H, 2 CH₂),

1.92 (s, 6 H, 3 CH₂), 2.69 (q, J ϭ 7.6 Hz, 2 H, CH₂), 3.36 (m, 2

H, OCH₂), 7.27 (dd, J ϭ 7.8, 3.4 Hz, 4 H, C₆H₄), 7.50 (dd, J ϭ

7.9, 3.6 Hz, 4 H, C₆H₄). – C₂₆H₃₄O (362.4): calcd. C 86.13, H 9.45;

found C 86.01, H 9.39.

3-Propylbicyclo[1.1.1]pentane-1-carbonyl Chloride (29): To a solu-

tion of 10b (5.40 g, 35.0 mmol) in anhydrous Et₂O, oxalyl chloride

(8.87 g, 6.0 mL, 69.9 mmol) was added dropwise at 20 °C followed

by two drops of DMF. After stirring the solution for 30 min at this

temp., the solvent was evaporated under reduced pressure and the

residue was purified by bulb-to-bulb distillation at 45 °C (0.1 Torr)

to give 29 (5.37 g, 89%) in almost pure form. – ¹H NMR: δ ϭ 0.90

(t, J ϭ 7.5 Hz, 3 H, CH₃), 1.20–1.35 (m, 2 H, CH₂), 1.48 (t, J ϭ

7.4 Hz, 2 H, CH₂), 2.0 (s, 6 H, 3 CH₂). – ¹³C NMR: δ ϭ 14.1

(CH₃), 52.6 (3 CH₂), 19.5, 32.9 (CH₂), 40.0, 45.4, 171.0 (C).

1-(2-Bromoethyl)-3-(4Ј-ethylbiphenyl-4-yl)bicyclo[1.1.1]pentane

(26ff): From 23ff (1.60 g, 4.25 mmol), 26ff (1.25 g, 83%) was ob-

1

tained according to GP 10 as an oil, R_fϭ 0.52. – H NMR: δ ϭ

1.27 (t, J ϭ 7.6 Hz, 3 H, CH₃), 2.01 (s, 6 H, 3 CH₂), 2.16 (t, J ϭ

7.3 Hz, 2 H, CH₂), 2.69 (q, J ϭ 7.6 Hz, 2 H, CH₂), 3.41 (t, J ϭ

7.3 Hz, 2 H, BrCH₂), 7.26 (dd, J ϭ 6.8, 1.6 Hz, 4 H, C₆H₄), 7.51

(dd, J ϭ 8.2, 5.5 Hz, 4 H, C₆H₄). – ¹³C NMR: δ ϭ 15.6 (CH₃),

52.5 (3 CH₂), 28.5, 30.2, 35.0 (CH₂), 126.4, 126.8, 127.0, 128.2 (2

CH), 38.0, 41.9, 138.4, 139.4, 139.6, 143.2 (C). – C₂₁H₂₃Br (355.3):

calcd. C 70.99, H 6.52; found C 70.58, H 6.55.

1-Propyl-3-[4-(3-butylbicyclo[1.1.1]pent-1-yl)benzoyl]bicyclo[1.1.1]-

pentane (30): To a solution of 20ca (2.625 g, 9.40 mmol) in anhyd-

rous Et₂O (100 mL), a 1.7  solution of tBuLi in pentane (11.1 mL,

18.9 mmol) was added dropwise at –78 °C. After stirring for 1 h at

this temp., 29 (2.12 g, 12.28 mmol) was added in a single portion

and the reaction mixture was allowed to warm to room temp. It

was stirred for a further 30 min at this temp. and then poured into

cold 5% NaHCO₃solution (50 mL). The layers were separated and

the organic layer was washed with 5% NaHCO₃solution and brine

(20 mL each), dried, and concentrated. Column chromatography

of the residue (100 g of silica gel, column 20 ϫ 4 cm, hexane/Et₂O,

1-(3-Bromopropyl)-3-(4Ј-ethylbiphenyl-4-yl)bicyclo[1.1.1]pentane

(26fg): From 23fg (11.05 g, 28.29 mmol), 26fg (8.96 g, 86%) was

obtained according to GP 10 as an oil, R_fϭ 0.50. – ¹H NMR: δ ϭ

1.20 (t, J ϭ 7.6 Hz, 3 H, CH₃), 1.58–1.70 (m, 2 H, CH₂), 1.75–1.95

(m, 2 H, CH₂), 1.87 (s, 6 H, 3 CH₂), 2.59 (q, J ϭ 7.6 Hz, 2 H,

CH₂), 3.38 (t, J ϭ 6.8 Hz, 2 H, BrCH₂), 7.20 (dd, J ϭ 8.1, 1.7 Hz,

4 H, C₆H₄), 7.44 (dd, J ϭ 8.3, 1.8 Hz, 4 H, C₆H₄). – C₂₂H₂₅Br

(369.3): calcd. C 71.54, H 6.82; found C 71.31, H 6.76.

1

10:1) gave 30 (2.47 g, 78%) as an oil, R_fϭ 0.48. – H NMR: δ ϭ

General Procedure (GP 11) for the Dehydrobromination of 26ff,fg:

To a solution of sublimed tBuOK (1.23 g, 11 mmol) in anhydrous

0.85–1.00 (m, 6 H, 2 CH₃), 1.25–1.40 (m, 6 H, 3 CH₂), 1.40–1.55

(m, 4 H, 2 CH₂), 1.93 (s, 6 H, 3 CH₂), 2.15 (s, 6 H, 3 CH₂), 7.25

Eur. J. Org. Chem. 2000, 1137Ϫ1155

1153

M. Messner, S. I. Kozhushkov, A. de Meijere

FULL PAPER

(d, J ϭ 7.2 Hz, 2 H, C₆H₄), 7.95 (d, J ϭ 7.2 Hz, 2 H, C₆H₄). – ¹³

C

AG, Chemetall GmbH, Degussa, Hoechst, and Hüls AG. We are

grateful to Dr. Burkhard Knieriem for his careful proofreading of

the manuscript.

NMR: δ ϭ 14.1, 14.3 (CH₃), 52.1, 53.3 (3 CH₂), 19.6, 22.8, 28.7,

31.2, 33.6 (CH₂), 126.0, 128.8 (2 CH), 39.2, 40.7, 41.4, 44.1, 134.6,

146.6, 197.4 (C). – C₂₄H₃₂O (336.5): calcd. C 85.66, H 9.59; found

C 85.92, H 9.43.

[1]

^[1a]J. Michl, in: Applications of Organometallic Chemistry in the

Preparation and Processing of Advanced Materials (Eds.: J. E.

β-Chloro-4-(3-butylbicyclo[1.1.1]pent-1-yl)-α-(3-propylbicyclo[1.1.1]-

pent-1-yl)styrene (31): To a suspension of chloromethyltriphenyl-

phosphonium chloride (4.51 g, 13 mmol) in anhydrous THF

(50 mL), a 2.33  solution of BuLi in hexane (5.6 mL, 13 mmol)

was added over a period of 20 min at –78 °C. After stirring for

30 min at this temp., a solution of 30 (1.88 g, 5.59 mmol) in Et₂O

(20 mL) was added over 30 min and the resulting mixture was

stirred for a further 30 min at –78 °C. It was then allowed to warm

to room temp. and stirred for a further 4 h. Thereafter, H₂O (5 mL)

was added and the resulting mixture was poured into an ice-cold

Et₂O/H₂O mixture (100 mL ϩ 100 mL). After separation of the

layers, the organic layer was washed with H₂O and brine (50 mL

each), dried, and the solvent was evaporated. The residue was then

thoroughly extracted with hexane (100 mL) for 2 h. The resulting

hexane solution was filtered, concentrated, and rapidly filtered

through 60 g of silica gel (column 20 ϫ 4 cm, hexane/Et₂O, 10:1)

to give 31 (1.92 g, 93%, 5:1 mixture of isomers) as an oil, R_fϭ

Harrod, R. M. Laine), Kluwer, Dordrecht, The Netherlands,

[1b]

1995, p. 243 ff. –

R. M. Harrison, T. F. Magnera, J. Vacek,

J. Michl, in: Modular Chemistry (Ed.: J. Michl), Kluwer, Dord-

recht, The Netherlands, 1997, p. 1 ff. –

[1c]

J. Michl, P. Kaszyn-

ski, A. C. Friedli, G. S. Murthy, H.-C. Yang, R. E. Robinson,

N. D. McMurdie, T. Kim, in: Strain and Its Implications in

Organic Chemistry (Eds.: A. de Meijere, S. Blechert), NATO

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0.68. – H NMR (major isomer): δ ϭ 0.88–1.05 (m, 6 H, 2 CH₃),

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(d, J ϭ 7.0 Hz, 2 H, C₆H₄). – ¹³C NMR: δ ϭ 14.2, 14.4 (CH₃),

52.1, 53.3 (3 CH₂), 19.8, 22.9, 28.9, 31.4, 33.6 (CH₂), 125.7, 128.0

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bicyclo[1.1.1]pent-1-yl)acetylene (32) and 4-(3-Butylbicyclo[1.1.1]-

pent-1-yl)-α-(3-propylbicyclo[1.1.1]-pent-1-yl)styrene (33): A solu-

tion of chloroethylene 31 (1.85 g, 5 mmol) in anhydrous THF

(50 mL) was treated with a 2.33  solution of BuLi in hexane

(2.36 mL, 5.5 mmol) and the mixture was stirred at room temp. for

12 h. It was then poured into ice-cold H₂O (30 mL) and the layers

were separated. The organic layer was washed with H₂O and brine

(10 mL each), dried, and the solvent was evaporated. The residue

was separated by column chromatography (60 g of silica gel, col-

umn 20 ϫ 3 cm, hexane) to give 32 (886 mg 53%) and 33

(159 mg, 9%).

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32: R_fϭ 0.42; m.p. 93–95 °C. – ¹H NMR: δ ϭ 0.90 (t, J ϭ 7.1 Hz,

3 H, CH₃), 0.91 (t, J ϭ 6.8 Hz, 3 H, CH₃), 1.20–1.60 (m, 10 H, 5

CH₂), 1.88 (s, 6 H, 3 CH₂), 2.00 (s, 6 H, 3 CH₂), 7.10 (d, J ϭ

6.6 Hz, 2 H, C₆H₄), 7.32 (d, J ϭ 6.6 Hz, 2 H, C₆H₄). – ¹³C NMR:

δ ϭ 14.1, 14.3 (CH₃), 52.1, 54.8 (3 CH₂), 19.8, 22.9, 28.8, 31.3,

33.6 (CH₂), 125.9, 131.4 (2 CH), 38.5, 39.0, 41.4, 42.4, 79.5, 88.9,

121.0, 141.4 (C). – C₂₅H₃₂(332.5): calcd. C 90.30, H 9.70; found C

90.21, H 9.63.

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1.25–1.65 (m, 10 H, 5 CH₂), 1.89 (s, 6 H, 3 CH₂), 1.95 (s, 6 H, 3

CH₂), 5.08 (m, 1 H, ϭCH₂), 5.15 (m, 1 H, ϭCH₂), 7.20 (d, J ϭ

7.0 Hz, 2 H, C₆H₄), 7.35 (d, J ϭ 7.0 Hz, 2 H, C₆H₄). – ¹³C NMR:

δ ϭ 14.2, 14.4 (CH₃), 52.1, 52.2 (3 CH₂), 19.9, 23.0, 28.9, 31.5,

34.0, 112.7 (CH₂), 125.7, 126.8 (2 CH), 39.0, 39.4, 41.4, 42.8, 138.8,

140.5, 148.7 (C).

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Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft

(Project Me 405/15-3), the Fonds der Chemischen Industrie, and,

by generous gifts of chemicals, the companies BASF AG, Bayer

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Received October 8, 1999

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Eur. J. Org. Chem. 2000, 1137Ϫ1155

1155

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