A new highly efficient three-component domino Heck-Diels-Alder reaction with bicyclopropylidene: Rapid access to spiro[2.5]oct-4-ene derivatives

FULL PAPER

A New Highly Efficient Three-Component

Domino Heck Diels Alder Reaction with Bicyclopropylidene:

Rapid Access to Spiro[2.5]oct-4-ene Derivatives**

Hanno N¸ske,^[a]Stefan Br‰se,^[b]Sergei I. Kozhushkov,^[a]Mathias Noltemeyer,^[c]

Mazen Es-Sayed,^[d]and Armin de Meijere*^[a]

Abstract: Bicyclopropylidene (1) was

found to surpass even methyl acrylate

(17a) in its rate of undergoing carbopal-

ladation with aryl- or alkenylpalladium

species, leading to substituted allylide-

necyclopropanes 5, 7 and 10, mostly in

high yields (37 78%). These dienes and

high yields (49 100%). The reaction of

1 with iodobenzene (2-Ph) and 17a gave

18a-Ph in virtually quantitative yield–

of other reaction partners, or could be

trapped by diethyl fumarate (17c) to

give the Diels Alder adduct 18c-H in

45%yield. The coupling of oligoiodo-

benzenes with 1 and subsequent cyclo-

addition could be extended to a multi-

component reaction. In this way, 1,4-

diiodobenzene (37), 1 and an alkyl

acrylate gave the products 38 of a

twofold Heck Diels Alder reaction

in up to 87%yield, 1,3,5-triiodobenzene

(39) reacted in up to 72%yield and

ultimately 1,2,4,5-tetraiodobenzene (41)

gave the fourfold domino Heck Diels

Alder product 42 in 47%isolated yield,

in a single operation in which 12 new

carbon-carbon bonds were formed.

also on

a gram scale–using only

1 mol%of catalyst, and even bromo-

benzene (22) gave 18a-Ph in 59%yield.

Bicyclopropylidene (1), in the presence

of palladium acetate/triphenylphos-

phane underwent rearrangement to al-

lylidenecyclopropane (5-H), which in

turn dimerized (73%) in the absence

cross-conjugated trienes react in

a

Diels Alder mode with dienophiles to

give spiro[2.5]octenes 18a-Ph, 18b-Ph

and 18a-Vin, respectively, in good yields

(89, 69 and 65%). The overall trans-

formation can be achieved as a one-pot

three-component reaction with a variety

of dienophiles to furnish the domino

Heck Diels Alder products 18 regio-

selectively in most cases in good to very

Keywords: bicyclopropylidene

¥

Diels Alder reactions domino

¥

reactions ¥ Heck reaction ¥ multi-

component reactions

found an important place in the tool-box of organic chemists.

Several elegant and facile constructions of highly complex

structures starting from simple molecules in one synthetic

operation make use of these concepts. Especially the need for

highly efficient and flexible synthetic approaches to carbo-

and heterocyclic systems with a combinatorial potential has

led to a dramatic increase in research activities.

Introduction

Domino processes have stirred a steadily increasing interest in

recent years,^[1]and multicomponent reactions have definitely

[a] Prof. Dr. A. de Meijere, Dr. H. N¸ske, Dr. S. I. Kozhushkov

Institut f¸r Organische Chemie

In the context of studying various aspects of intramolecular

Heck reactions,^[2]we also examined domino Heck Heck-^[3a]

and Heck Diels Alder processes^[3b,c]which led to an easy

access to bicyclo[4.3.0]nonene systems. Thus we became

aware that the Heck Diels Alder reaction even proceeds

with 2-bromo-1,m-dienes containing a highly strained meth-

ylenecyclopropane end group or bromomethylenecyclopro-

pane starter to yield a-spirocyclopropane-annelated bicy-

clo[4.3.0]nonene skeletons.^[3c]In this context, the reactions of

certain tetrasubstituted alkenes^[4]were examined, most of

which are generally referred to as being unreactive in the

Heck coupling.^[2]Several methylenecyclopropanes with two

substituents at the methylene terminus, and especially bicy-

clopropylidene (1) were found to be highly reactive alkenes

that underwent palladium-catalyzed cocyclizations with ac-

ceptor-activated and with strained alkenes^[5]as well as Heck-

type carbopalladations, the latter even more rapidly than alkyl

der Georg-August-Universit‰t Gˆttingen

Tammannstrasse 2, 37077 Gˆttingen (Germany)

Fax : (49) 551 399475

E-mail: armin.demeijere@chemie.uni-goettingen.de

[b] Prof. Dr. S. Br‰se

Universit‰t Bonn

¬

Kekule Institut f¸r Organische Chemie und Biochemie

53121 Bonn (Germany)

[c] Dr. M. Noltemeyer

Institut f¸r Anorganische Chemie

der Georg-August-Universit‰t Gˆttingen

Tammannstrasse 4, 37077 Gˆttingen (Germany)

[d] Dr. M. Es-Sayed

Bayer AG, GB Pflanzenschutz

40789 Monheim (Germany)

[**] Part 77 in the series ™Cyclopropyl Building Blocks in Organic

Synthesis∫. For Part 76 see: S. Wiedemann, I. Marek, A. de Meijere,

Synlett 2002, submitted. Part 75: M. W. Nˆtzel, K. Rauch, T. Labahn,

A. de Meijere, Org. Lett. 2002, 4, 839 841.

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Chem. Eur. J. 2002, 8, No. 10

2350 2369

acrylates.^[6]Herein we present the full account of the recently

developed^[6]new three-component domino reaction combin-

ing bicyclopropylidene (1) with aryl or alkenyl halides and a

dienophile. For comparison, some other methylenecycloal-

kanes with tetrasubstituted double bonds were also tested.

nated by b-hydride elimination. The yield of 5-H increased

from 43 to 55%when the reaction was performed in the

presence of a mixture of 10%Et ₃N/HOAc (1:1). This

isomerization was not observed in diethyl ether. In dichloro-

methane the conversion was only 20%after 24 h at ambient

temperature.

Although allylidenecyclopropane (5-H) had been reported

to be unreactive in palladium-catalyzed transformations,^[12d]

prolonged stirring of the mixture of 1 and the catalyst in

benzene at ambient temperature led to slow formation of

oligomers of 5-H. Upon heating at 808C, a mixture of four

bicyclopropylidene dimers 11 14 was formed within 2 h,

apparently by a Pd-catalyzed subsequent reaction of the

initially formed diene 5-H.

This type of transformation turned out to be highly

dependent on the type of catalyst and ligand additive. Thus,

bicyclopropylidene (1) remained unchanged under similar

conditions (heating at 808C in benzene), but with Pd(dba)₂¥

iPr₃P as a catalyst. Yet at 1108C in the absence of any other

activated alkene, one molecule of bicyclopropylidene (1),

after opening of a distal bond, underwent formal [32]

cycloaddition to a second molecule of 1 to give 8-cyclo-

propylidenedispiro[2.0.2.3]nonane (16).^[5]

Results and Discussion

The cross-coupling reaction of bicyclopropylidene (1), a

particularly strained tetrasubstituted alkene, which has re-

cently become easily available,^[7]with iodobenzene (2-Ph)

under typical Heck conditions^[8]gave the 1-phenylallylidene-

cyclopropane (5-Ph) as

a sensitive oil in 78%yield

(Scheme 1).^[9]Besides this product, a significant amount of

polymeric material containing cyclopropane moieties was

Scheme 1. Heck reaction of bicyclopropylidene (1) with aryl (2-Ph) and

alkenyl halides (6, 9) or alkenyl nonaflates (8) and rearrangement to

allylidenecyclopropanes. A: Pd(OAc)₂, PPh₃, Et₃N, DMF, 808C; B:

Pd(PPh₃)₄, Et₃N, MeCN, 808C.

observed.^[6]The mechanism involves carbopalladation of the

double bond in 1 by the initially formed phenylpalladium

iodide, cyclopropylmethyl to homoallyl rearrangement and

subsequent b-hydride elimination to form the diene substruc-

ture. The reaction of 1 with iodoethene (6) gave the unusual

cross-conjugated triene 7-H in up to 37%yield. This

represents a novel access to the so-called dendralenes which

are usually prepared by pyrolysis or elimination reac-

tions.^{[10, 11]}Another [3]dendralene, the hydrocarbon 10, was

obtained in 52%yield by the palladium-catalyzed reaction of

cyclohexenyl nonaflate (8) with 1. Both new dendralenes 7-H

and 10 are prone to undergo polymerization and thus–to

achieve better yields of their cycloadducts–ought to be trapped

with a dienophile immediately after formation or in situ.

Upon treatment of bicyclopropylidene (1) alone with

palladium acetate and triphenylphosphane in benzene at

room temperature, it underwent a slow isomerization to

allylidenecyclopropane (5-H)^[12](Scheme 2), the appearance

Scheme 2. Palladium-catalyzed isomerization of bicyclopropylidene (1)

and further transformations. A: Pd(OAc)₂¥ 2PPh₃, C₆D₆, 808C, 2 h; B:

Pd(dba)₂, P(iPr)₃, toluene, 1108C, 4 h.

The allylidenecyclopropanes 5-Ph, 5-H and 10,^{[13, 14]}when

heated either in isolated form or without isolation after having

been formed in the Heck reaction, with a dienophile gave the

Diels Alder products^[15]18a-Ph, 18c-H, 18a-Vin, 18d-Vin,

19b and 20b in moderate to good yields (Scheme 3).

The constitutions of the Diels Alder products were

determined by extensive NMR studies as well as by X-ray

crystal structure analysis in several cases (Figure 1), and it

turned out that in all reactions with alkyl acrylates only the

quasi-meta product was formed, in accordance with previously

reported observations.^[15]Calculations showed that allylide-

necyclopropane (5-H) has an almost symmetrical highest

occupied molecular orbital (HOMO),^[16]which is in contrast

to other 1-donor-substituted alkenes.^[17]The [3]dendralene 10

1

of which can be monitored by H NMR spectroscopy. The

formation of the diene 5-H is presumably initiated by a

palladium hydride addition to the double bond in 1, followed

by cyclopropylmethyl to homoallyl rearrangement and termi-

Chem. Eur. J. 2002, 8, No. 10

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Scheme 3. Stepwise Heck Diels Alder reactions with bicyclopropyli-

dene (1). A: CDCl₃, D, 12 h; B: Pd(OAc)₂, PPh₃, C₆D₆; C: Pd(OAc)₂, PPh₃,

Et₃N, DMF; D: Pd(PPh₃)₄, Et₃N, DMF.

Scheme 4. Three-component reactions with bicyclopropylidene (1). For

details and conditions see Table 1.

underwent a single Diels Alder reaction with dimethyl

maleate with low regioselectivity to yield both the cyclo-

hexenyl-substituted spiro[2.5]octene 19b and the spirocyclo-

propanated octahydronaphthalene derivative 20b (ratio

1:1.5). Apparently, both 1,3-diene units in the dendralene 10

have about the same reactivity towards the dienophile.

Surprisingly, when the three components bicyclopropyli-

dene (1), iodobenzene (2-Ph) and methyl acrylate (17a), were

mixed with the palladium catalyst system [Pd(OAc)₂, PPh₃,

K₂CO₃/Et₄NCl or Et₃N] in acetonitrile and the mixture heated

in a Pyrex bottle, only a trace of methyl cinnamate, the Heck

coupling product of 2-Ph and 17a, was detected. Best yields of

the domino Heck Diels Alder products 18 were obtained

applying the Jeffery protocol [Pd(OAc)₂, PPh₃, K₂CO₃,

Et₄NCl, MeCN],^[18]and increasing the concentration of all

reactants to 4m finally led to a virtually quantitative formation

of 18a-Ph with 1.0 mol%of precatalyst (Scheme 4). Thus, the

tetrasubstituted alkene 1 is more rapidly carbopalladated than

even methyl acrylate, which is known to be a particularly good

substrate in Heck coupling reactions. This high reactivity of 1

must have to do with its unusual nucleophilicity^[19]which

facilitates the attack of the electrophilic organopalladium

species.

However, only the trans-spiro[2.5]oct-4-ene-7,8-dicarboxy-

late 18 f-Ph was isolated from the one-pot Heck Diels

Alder reaction of bicyclopropylidene 1 and phenyl iodide

(2-Ph) with dimethyl cis-but-2-ene-1,4-dioate (dimethyl mal-

eate) (17b) under Heck as well as under Jeffery conditions

(Table 1, entries 3, 4). The identity of the samples of 18 f-Ph

prepared with dimethyl maleate (17b) (Table 1, entry 3) and

with dimethyl fumarate (17 f) (Table 1, entry 7) was corrobo-

rated by their NMR spectral data and was rigorously proved

by X-ray crystal structure analyses (Figure 1).^[20]Moreover,

excessive 17b isomerized to 17 f (15 to 30%) under the

conditions employed.^[21]Partial isomerization of excessive

dimethyl maleate (17b) (10%) was detected even in the

Diels Alder reaction of 17b with isolated diene 5-Ph

(Scheme 3), yet in this case the major Diels Alder product

was cis-configurated cis-18b-Ph, and the trans-diastereomer

18 f-Ph was formed only in trace quantities. No isomerization

of dimethyl maleate 17b was observed upon heating in the

absence of 1 and 2-Ph under Heck or Jeffery conditions for

extended times (20 24 h). It is not quite clear at this point

whether these findings indicate that the [42] cycloaddition

(at least in some extent) proceeds stepwise under these

conditions and thus partially forms the thermodynamically

more stable trans-isomer. A conceivable alternative mecha-

nism with addition of the homoallylpalladium intermediate 4

onto 17b, followed by 6-endo-trig ring closure in intermedia-

te I is highly unlikely. Just like the cyclopropylcarbinylpalla-

dium intermediate 3, the cyclization product II should rapidly

rearrange to the corresponding ring-opened homoallylpalla-

dium species which would undergo b-hydride elimination to

yield the diene III or its [42] cycloaddition product.

The cross-conjugated triene 7-H formed from bicyclopro-

pylidene (1) and iodoethene (6) is prone to undergo a so-

called transmissive cycloaddition,^[22]that is a domino Diels

Alder reaction in which the diene for the second step is

formed by the first reaction. The three-component reaction of

1, 6 and methyl acrylate (17a) gave the spirocyclopropanated

octahydronaphthalene derivative 21a in 59%isolated yield.

The analogous reaction of 1, 6 and dimethyl fumarate (17 f)

yielded only 35%of the twofold adduct 21 f along with 25%

of the onefold Diels Alder product 18 f-Vin (Scheme 4).

Scope and limitations of this new three-component reaction

were tested with variation of the aryl and alkenyl halide as

well as the dienophile (Scheme 4 and Table 1).

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Domino Heck Diels Alder Reactions

2350 2369

Table 1. Three-component reactions of bicyclopropylidene (1), an aryl 2 or

alkenyl iodide 9 and a dienophile 17. See Scheme 4.

ylate 18 f-Ph, 18 f-Tol and and 18k-Ph (Figure 1), is that the

phenyl ring is perpendicular to the plane of the double bond

which must be caused by steric interaction between the

spirocyclopropane moieties and the ortho hydrogens on the

aromatic rings.

Entry Aryl/

Alkenyl halide

Dienophile Conditions^[a]Product

Yield [%]

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

PhI (2-Ph)

4-TolI (2-Tol) 17a

4-TolI (2-Tol) 17e

4-TolI (2-Tol) 17f

3-PyI (2-Py)

PhI (2-Ph)

9

17a

17b

17e

17f

A

B

A

C

A

C

A

C

18a-Ph

18f-Ph

18e-Ph

18f-Ph

18g-Ph

18a-Tol

18e-Tol

18f-Tol

18a-Py

18e-Py

18f-Py

18 h-Ph

18i-Ph

18j-Ph

100

99

96

98

87

78

97

49

91

87

83

99

80

67

81

63

76

0

17g

A

C

17a

17e

17f

17 h

17i

17j

17a

17e

17k

A

0

19a 20a (1:2) 84

9

19e 20e (1:3) 83

PhI (2-Ph)

18k-Ph

47

[a] A: 5 mol%Pd(OAc) ₂, 15 mol%PPh ₃, K₂CO₃, Et₄NCl, MeCN, 808C, one

step. B: as in A, 1 mol%Pd(OAc) ₂, 3 mol%PPh ₃. C: Pd(OAc)₂, PPh₃, Et₃N,

DMF, 808C, one step.

Excellent results were obtained with iodobenzene (2-Ph),

4-iodotoluene (2-Tol; Table 1, entries 1 7, 9 13) as well as

3-iodopyridine (2-Py; Table 1, entries 14 16) with various

dienophiles 17. The reaction with acrylic acid amide (17g,

entry 8) gave the corresponding spiro[2.5]octene derivative

18g-Ph in moderate yield (49%isolated). With 1-iodocyclo-

hexene (9) instead of cyclohexenyl nonaflate (8) and methyl

(17a) or tert-butyl acrylate (17e) in highly concentrated

solution the products 19 and 20 were also isolated in high

yields (Table 1, entries 20, 21). Even aryl bromides such as

bromobenzene (22) and bromothiophenes (24, 26) underwent

coupling with 1, but in two of these cases significant amounts

of the products arising from direct coupling of the bromides

and the acrylate, were isolated (Scheme 5).

Figure 1. Structures of 18 f-Ph, 18 f-Tol and 18k-Ph in the crystals.^[20]

In the absence of any dienophile and under high pressure

(10 kbar), the dendralene 5-Ph itself acted as the dienophile to

give the spiro[2.5]octene derivative 29 in 28%yield

(Scheme 6).

A special feature of the 8-phenylspiro[2.5]oct-7-ene deriv-

atives 18 prepared, as demonstrated by the X-ray crystal

structure analyses of the dimethyl spiro[2.5]octenedicarbox-

Scheme 6. Dimerization of the allylidenecyclopropane 5-Ph. A:

Pd(OAc)₂, PPh₃, Et₃N, DMF, 10 kbar, 808C, 24 h.

Substituted acrylates were also tested. Whereas methyl a-

methylacrylate 17 h gave the corresponding spiro[2.5]octene

derivative 18 h-Ph in good yield (76%), no products could be

isolated from reactions with the b-substituted 17i and 17j

(Table 1, entries 18, 19).^[13d]

Scheme 5. Heck Diels Alder reactions of bicyclopropylidene (1) with

bromoarenes and methyl acrylate (17a). A: Pd(OAc)₂, PPh₃, K₂CO₃,

Et₄NCl, MeCN, 808C, 48 h; E CO₂Me.

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The lack of reactivity of methyl cinnamate (17j) as a

dienophile in this Heck Diels Alder sequence could be

overcome by the introduction of a strongly electron-with-

drawing substituent. Thus, o-, m- and p-nitrocinnamates 30 all

gave the corresponding cross-coupling cycloadducts, but

interestingly both possible regioisomers 31 as well as 32

(Scheme 7). The reactions required longer heating (up to 4 d).

Scheme 8. Heck Diels Alder reactions of 1 with substituted iodoarenes

33 and methyl (17a) or tert-butyl acrylate (17e). A: Pd(OAc)₂, PPh₃,

K₂CO₃, Et₄NCl, MeCN, 808C, 48 h. For details see Table 2.

Table 2. Heck Diels Alder reactions of 1 with substituted iodoarenes 33. See

Schemes 4 and 8.

ArI R¹

R²

R³

Dienophile Product Yield [%] Isomer

ratio anti/syn

33a Me

33b Bn

H

17a

17e

17a

17e

17a

17e

34aa

34ea

34ab

34eb

34ac

34ec

34ad

99

2.0:1

76^[a]

85

3.0:1

2.0:1

3.0:1

2.5:1

2.7:1

Scheme 7. Heck Diels Alder reactions of 1 and iodobenzene (2-Ph) with

nitro-substituted cinnamic acid esters 30. A: 1, 2-Ph, Pd(OAc)₂, PPh₃,

K₂CO₃, Et₄NCl, MeCN, 808C, 4 d.

39^[a]

98

16^[a]

56^[b]

33c

Me Me

33d Me

H

Me 17a

In the case of p-30 one third (31%isolated) of the product

mixture was the quasi-ortho adduct p-32 as proved by an

X-ray crystal structure analysis (Figure 2).

[a] Along with traces of the corresponding cinnamic acid esters formed by

direct coupling of 33 with 17. [b] Along with 22%of the corresponding

allylidenecyclopropane formed from 1 and 33d.

coupling product of the o,o'-disubstituted iodoarene 33d

underwent [42] cycloaddition only with methyl (17a) and

not with tert-butyl acrylate (17e), and a significant amount

(39%) of the unreacted 1-(2',6'-dimethylphenyl)allylidenecy-

clopropane was isolated.

Eventually, substituted bicyclopropylidenes 35 were used in

the Heck Diels Alder sequence (Scheme 9). In this case,

depending on the regio- and stereochemical differentiation in

the initial attack of the arylpalladium species on 35, up to four

Figure 2. Structures of p-32 and anti-34eb in the crystals.^[20]

The influence of substituents on the aryl iodides was also

examined. An ortho-methyl group on the iodobenzene does

not interfere with the Heck Diels Alder reaction with

methyl acrylate (17a) but does cause a significant decrease

in yield in the reaction with the bulkier tert-butyl acrylate

(17e) (Scheme 8 and Table 2). This steric effect is even more

pronounced in the reaction with the ortho-benzyl substituted

iodide 33b. In all reactions with ortho-substituted phenyl

iodides, two atropisomeric products anti- and syn-34 were

formed due to the hindered rotation around the aryl-

spirooctene bond, with a predominance of the anti-isomer

(with respect to the substituent on the aryl group and the

alkoxycarbonyl group on the spirooctane moiety) of up to 3:1

(¹H NMR), slightly depending on the size of the alkoxycar-

bonyl group. Based on a coalescence temperature between 50

and 758C the rotational barrier is estimated to be in the range

of 75 81 kJmol^À1.^[23]The structure of crystalline anti-34eb

was proved by X-ray crystal structure analysis (Figure 2). The

Scheme 9. Heck Diels Alder reaction with substituted bicyclopropyli-

denes 35. A: Pd(OAc)₂, PPh₃, K₂CO₃, Et₄NCl, MeCN, 808C, 48 h. E

CO₂Me.

different regioisomers are possible.^[24]With the easily acces-

sible^[25]methyl bicyclopropylidenecarboxylate (35a), surpris-

ingly, only two diastereomeric products anti,(Z)-36a and

anti,(E)-36a (36%, 5:4 according to GC) stemming from the

opening of the unsubstituted cyclopropane ring were isolated,

none of the other isomers was detected by NMR spectroscopy

in the crude product. NOESY NMR measurements disclosed

that in both stereoisomers the ester group on the cyclo-

propane ring is orientated towards the phenyl substituent. In

contrast, the reaction of the alkyl-substituted n-pentylbicy-

clopropylidene (35b) led to a complex mixture of isomers and

stereoisomers (29%yield), in this case the NMR spectrum

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Chem. Eur. J. 2002, 8, No. 10

Domino Heck Diels Alder Reactions

2350 2369

showed signals indicating that also the substituted ring had

been opened in the course of the reaction.

The extension of this new domino three-component reac-

tion to oligoiodoarenes was also examined. Treatment of 1,4-

diiodobenzene (37) in the presence of the palladium catalyst

system, with bicyclopropylidene (1) and a dienophile 17, gave

the products 38 of a twofold Heck Diels Alder reaction in

good yields (Scheme 10, Table 3). Under high pressure the

yield of 38a could be raised to 87%. Performing the reaction

at lower concentrations (0.2m) of the starting materials

yielded the mono-coupling-cycloaddition products 18-C₆H₄I

predominantly along with only small amounts of 38. Surpris-

ingly, the product 38a was formed as a single diastereomer, as

proved by an X-ray crystal structure analysis.^[26]Even the

crude product showed only a single set of signals in the

¹³C NMR spectrum.

Scheme 11. Multicomponent domino reactions of 1 with 1,3,5-triiodoben-

zene (39) as well as 1,2,4,5-tetraiodobenzene (41) and dienophiles 17. A:

Pd(OAc)₂, PPh₃, K₂CO₃, Et₄NCl, MeCN, 808C, 2 3 d; E CO₂Me.

Wittig olefinations of the corresponding ketones with in situ

formed cycloalkylidenephosphoranes.^[27]

The reaction of cyclopropylidenecyclohexane (43a) with 2-

Ph under Heck conditions [Pd(OAc)₂, PPh₃, Et₃N, DMF,

808C, 12 h] gave the three isomeric olefins 44, 45 (isolated as

an unseparable 1:1 mixture, 35%yield) and ( Z)-46^[28](53%).

The reaction of isopropylidenecyclopropane (47) with 2-Ph

under the same conditions gave 1-phenyl-1-(2'-propenyl)cy-

clopropane (48) (5%), 4-methyl-3-phenyl-1,3-pentadiene

(49)^[28]and 2-methyl-3-phenyl-1,3-pentadiene [(Z)-50] (ob-

tained as an unseparable 1.7:1 mixture, 60%yield). Cyclo-

butylidenecyclohexane (43b) did not react with 2-Ph under

the applied conditions and could be completely recovered.

The alkene 43b was also left unchanged when it was added to

a reacting mixture of 43a and 2-Ph.

Apparently, these transformations of 43a and 47 start with a

regioselective carbopalladation of the double bond in such a

way that the phenyl group is attached at the less sterically

demanding cyclopropane ring. The resulting cyclopropylmeth-

ylpalladium iodide of type 51 then rapidly rearranges to the

homoallylpalladium iodide of type 52, which, by b-hydride

elimination yields 49. The dienes (Z)-46 and (Z)-50 must arise

by deprotonation of a p-allylpalladium iodide of type 53

(Scheme 12), probably formed by b-dehydropalladation of 52

with rehydridopalladation. Proton abstraction from 53 can

also lead to 49, while 48 is formed by b-dehydropalladation

from 51 without rearrangement.^[29]

Scheme 10. Twofold Heck Diels Alder reaction of bicyclopropylidene

(1) with 1,4-diiodobenzene (37). A: Pd(OAc)₂, PPh₃, K₂CO₃, Et₄NCl,

MeCN, 808C. For details see Table 3.

Table 3. Heck Diels Alder reaction of bicyclopropylidene (1) with 1,4-

diiodobenzene (37) and alkyl acrylates 17a, e, f.

Dienophile

Conditions^[a]

Time [h]

Product

Yield [%]

17a

A

B

C

48

24

21

38a

18a-C₆H₄I

38a

64

87

45

8

17e

A

B

C

48

24

72

38e

18e-C₆H₄I

38e

69

60

50

6

17 f

A

B

48

24

38 f

54

60

[a] A: Pd(OAc)₂, PPh₃, K₂CO₃, Et₄NCl, MeCN, 808C, one step. B:

Pd(OAc)₂, PPh₃, Et₃N, DMF, 808C, 10 kbar, one step. C: As in B, decreased

concentration (0.2m), 1 bar.

Even the reaction of 1 with 1,3,5-triiodobenzene (39) and a

dienophile 17 gave excellent results: In these formal seven-

component reactions yields of up to 60%of the nominally C₃-

symmetrical products 40 were achieved. Finally, with 1,2,4,5-

À

tetraiodobenzene (41) twelve new carbon carbon bonds were

formed in one synthetic operation to give the fourfold cross-

coupling cycloadduct 42 in 47%yield (Scheme 11). This result

shows that this unprecedented assembly of nine highly

reactive small molecules proceeds smoothly and completely

selectively. Nine component all-carbon-carbon bond forming

reactions have been, if at all, scarcely ever been observed.

In order to probe the unique features of bicyclopropylidene

(1), some other tetrasubstituted alkenes with alkylidenecy-

cloalkane units were tested in the palladium-catalyzed

coupling with iodobenzene (2-Ph) (Scheme 12). Such tetra-

substituted alkenes are readily accessible in good yields by

Thus, the domino Heck Diels Alder reaction of bicyclo-

propylidene (1) with a variety of aryl as well as alkenyl halides

and dienophiles is indeed unique in terms of regioselectivity,

achievable yields and versatility. This new three-component

reaction holds a high potential for combinatorial applications,

since various hetero-dienophiles^[30]and acceptor-substituted

bicyclopropylidenes can be employed. Its suitability for solid-

phase synthesis has already been demonstrated.^[25]The

resulting spiro[2.5]octene derivatives can be further elabo-

rated, for example the 4-ethenyl derivative 18-Vin might be

used as a precursor to carotenoid analogues^[31]in which the

Chem. Eur. J. 2002, 8, No. 10

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2355 $ 20.00+.50/0

2355

A. de Meijere et al.

FULL PAPER

aryl or alkenyl halide, triethylamine (202 mg, 2.00 mmol) and 2.00 mmol of

the respective alkene. After the reaction mixture had been stirred for the

given time at the stated temperature, the bottle was cooled to ambient

temperature, the corresponding dienophile (2.00 mmol) added, and then

the mixture was stirred for additional time at the given temperature. The

solution was added to water (10 mL), extracted with diethyl ether (5 Â

20 mL), the combined organic phases washed with water (4 Â 10 mL) and

NaCl solution (10 mL) and dried (MgSO₄). After removal of the solvent in

a rotatory evaporator the residue was subjected to chromatography on

silica gel.

General procedure for the Heck Diels Alder reaction on methylenecy-

clopropane derivatives and bicyclopropylidene (1), one-pot, one step, Heck

conditions (GP 3): A 5 mL sealable bottle with anhydrous DMF (1 mL)

was charged under argon with palladium(ii) acetate (11.2 mg, 49.9 mmol)

and triphenylphosphane (39.3 mg, 150 mmol). Argon was bubbled through

the mixture for 5 min and the mixture was treated with 1.00 mmol of the

respective aryl or alkenyl halide, triethylamine (202 mg, 2.00 mmol),

2.00 mmol of the respective alkene and 2.00 mmol of the respective

dienophile. After having stirred the mixture for the given time at the stated

temperature the mixture was cooled to ambient temperature, the solution

added to water and extracted with diethyl ether (5 Â 20 mL). The combined

organic phases were washed with water (4 Â 10 mL) and NaCl solution

(10 mL) and dried (MgSO₄). After removal of the solvent in a rotatory

evaporator the residue was subjected to chromatography on silica gel.

Scheme 12. Heck reactions with tetrasubstituted alkenes other than

bicyclopropylidene (1). A: Pd(OAc)₂, PPh₃, Et₃N, DMF, 758C.

spirocyclopropane unit mimics a gem-dimethyl group. Spi-

ro[2.5]octene substructures are also present in various natural

products such as the cytotoxic illudines, carcinogenic ptaqui-

losides or the antibiotic leaianafulvene.^[32]Therefore, the

presented chemistry is set for applications in combinatorial

and natural product synthesis.

General procedure for the Heck Diels Alder reaction on methylenecy-

clopropane derivatives and bicyclopropylidene (1), one-pot, two steps,

alkenylsulfonates (GP 4): A 50 mL Pyrex-bottle was charged under argon

with anhydrous acetonitrile (10 mL) and treated with tetrakis(triphenyl-

phosphano)palladium (57.8 mg, 50.0 mmol). Argon was bubbled through

the mixture for 5 min and then it was treated with cyclohexenylnonaflate

(8-ONf, 380 mg, 1.00 mmol), triethylamine (202 mg, 2.00 mmol) and

2.00 mmol of the respective alkene. After having stirred the mixture for

the given time at the stated temperature the bottle was cooled to ambient

temperature, the corresponding dienophile (2.00 mmol) added, and then

the mixture was stirred for additional time at the given temperature. Water

was added and the aqueous phase was extracted with diethyl ether (5 Â

20 mL). The combined organic phases were washed with water (4 Â

10 mL), NaCl solution (10 mL) and dried (MgSO₄). After removal of the

solvent in a rotatory evaporator the residue was subjected to chromatog-

raphy on silica gel.

Experimental Section

General: ¹H and ¹³C NMR spectra were recorded with Bruker AW 250 or

Inova-500 instruments at 250 or 500 MHz and 62.9 or 125.7 MHz,

respectively. Chemical shifts in CDCl₃or [D₆]benzene are reported in d

(ppm) relative to tetramethylsilane (TMS), chloroform or benzene as

internal reference unless otherwise stated. IR spectra were recorded with a

Perkin Elmer 1720 FTIR or a Bruker IFS 66. Low resolution EI mass

spectra were obtained on a Varian MAT 731 with Varian Aerograph 1740

with an ionizing voltage of 70 eV. High resolution MS were obtained with a

VG-70-250S. Elemental analyses were performed by the Mikroanalytisches

Laboratorium der Universit‰t Gˆttingen (Germany). Melting points are

uncorrected. Solvents for extraction and chromatography were technical

grade and distilled before use. Flash chromatography was performed using

Merck silica gel 60 (200 400 mesh). Analytical gas chromatography (GC)

was performed using a Siemens Sichromat 4 equipped with a 25 m capillary

column coated with CP-Sil-55-5B. All reactions were carried out under an

atmosphere of anhydrous nitrogen or argon in oven- and/or flame-dried

glassware. Acetonitrile was dried over phosphorus pentoxide, DMF and

CH₂Cl₂were distilled from CaH₂. Bicyclopropylidene (1) and isopropyli-

denecyclopropane (47) were prepared according to de Meijere et al.^[7]

General procedure for the Heck Diels Alder reaction on bicyclopropy-

lidene (1), one-pot, one step, Jeffery conditions (GP 5): A 5 mL sealable

bottle was charged with anhydrous acetonitrile (1 mL), K₂CO₃(277 mg,

2.00 mmol) and Et₄NCl (166 mg, 1.00 mmol). Argon was bubbled through

the mixture for 5 min. After the reaction mixture was stirred for another

10 min, palladium(ii) acetate (11.2 mg, 49.9 mmol), triphenylphosphane

(39.3 mg, 150 mmol), 1.00 mmol of the respective aryl or alkenyl halide,

bicyclopropylidene (1, 160 mg, 2.00 mmol) and 2.00 mmol of the respective

dienophile were added. After the reaction mixture had been stirred for the

given time at the stated temperature the bottle was cooled to ambient

temperature, diethyl ether (50 mL) was added, the mixture washed with

water (5 Â 25 mL) and dried (MgSO₄). After removal of the solvent in a

rotatory evaporator the residue was subjected to chromatography on silica

gel.

General procedure for the Heck reaction on methylenecyclopropane

derivatives and bicyclopropylidene (1) (GP 1): A 50 mL Pyrex-bottle

containing anhydrous DMF (10 mL) was charged under argon with

palladium(ii) acetate (11.2 mg, 49.9 mmol) and triphenylphosphane

(39.3 mg, 150 mmol). argon was bubbled through the mixture for 5 min

and the mixture was treated with 1.00 mmol of the respective aryl or

alkenyl halide, triethylamine (202 mg, 2.00 mmol) and 2.00 mmol of the

respective alkene. After the reaction mixture had been stirred for the given

time at the stated temperature it was cooled to ambient temperature,

extracted with pentane (5 Â 20 mL); the combined organic phases were

washed with water (15 mL) and dried (MgSO₄). After removal of the

solvent in a rotatory evaporator the residue was subjected to chromatog-

raphy on silica gel eluting with pentane.

General procedure for the Heck Diels Alder reaction on bicyclopropy-

lidene (1), one-pot, one step, high pressure conditions (GP 6): A sealable

Teflon tube with anhydrous DMF (5 mL) was charged under argon with

palladium(ii) acetate (11.2 mg, 49.9 mmol) and triphenylphosphane

(39.3 mg, 150 mmol). Argon was bubbled through the mixture for 5 min

and the mixture was treated with 1.00 mmol of the respective aryl halide,

triethylamine (202 mg, 2.00 mmol), bicyclopropylidene (1, 160 mg,

2.00 mmol) and 2.00 mmol of the respective dienophile. After heating at

the given temperature for the given time at 10 kbar, the solution was cooled

to ambient temperature, added to water (50 mL) and extracted with diethyl

ether (5 Â 20 mL). The combined organic phases were washed with water

(4 Â 10 mL), NaCl solution (10 mL) and being dried (MgSO₄). After

removal of the solvent in a rotatory evaporator the residue was subjected to

chromatography on silica gel.

General procedure for the Heck Diels Alder reaction on methylenecy-

clopropane derivatives and bicyclopropylidene (1), one-pot, two steps

(GP 2): A 50 mL Pyrex-bottle containing anhydrous DMF (10 mL) was

charged under argon with palladium(ii) acetate (11.2 mg, 49.9 mmol) and

triphenylphosphane (39.3 mg, 150 mmol), argon was bubbled through the

mixture for 5 min and the mixture treated with 1.00 mmol of the respective

1-Cyclopropylidene-1-phenylpropene (5-Ph): According to GP 1, bicyclo-

propylidene (1, 160 mg, 2.00 mmol), iodobenzene (2-Ph, 204 mg,

2356

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2356 $ 20.00+.50/0

Chem. Eur. J. 2002, 8, No. 10

Domino Heck Diels Alder Reactions

2350 2369

(, CH), 137.2 (, CH), 136.0 (, CH), 133.6 (, CH), 130.6 (,

1.00 mmol), palladium(ii) acetate (11.2 mg, 49.9 mmol), triphenylphosphane

(39.3 mg, 150 mmol) and triethylamine (202 mg, 2.00 mmol) were heated in

anhydrous DMF (5 mL) for 4 h at 1008C. Work-up and chromatography on

silica gel (column 1 Â 20 cm, pentane) yielded 5-Ph as a colorless oil

(122 mg, 78%), which polymerized upon standing at ambient temperature.

CH), 126.6 (, CH), 116.3 (À, CH₂), 116.0 (À, CH₂), 38.7 (À, C-3'),

21.4 (C_quat, cPr-C), 14.5 (À, cPr-C); the signals of the minor isomers are

covered by the signals of the major diastereomer or are indistinguishable;

MS (EI): m/z (%): 160 (48) [M ], 145 (20) [M À H À CH₂], 132 (10)

R_f 0.42 (pentane); IR (film): nÄ 3111, 3047, 3014, 2951, 2913, 2860,

[M À C₂H₄], 131 (26) [M À H À C₂H₄], 119 (34), 117 (55) [M À H À

À1

1680 (C C), 1513, 1368, 1237, 1078, 911, 831, 762, 737, 704, 649 cm

;

CH₂À C₂H₄], 105 (20) [C₈H₉], 92 (18) [C₇H₈], 91 (100) [C₇H₇], 79 (19)

¹H NMR (250 MHz, C₆D₆): d 7.40 7.20 (m, 5H; Ar-H), 6.25 (dd, ³J

[C₆H₇], 77 (35) [C₆H₅]; HRMS: m/z (%): calcd for C₁₂H₁₆: 160.1252;

17.0, J 10.6 Hz, 1H; CH₂CH), 4.90 (dd, J_AB 2.3, ³J 17.0 Hz, 1H;

found: 160.1252.

3

2

3

CH₂CH), 4.70 (dd, J_AB 2.3, J 10.6 Hz, 1H; CH₂CH), 1.00 0.80 (m,

8-(Cyclopropylidene)dispiro[2.0.2.3]nonane (16): Under argon, a mixture

of bicyclopropylidene (1, 86 mg, 1.07 mmol), Pd(dba)₂(15 mg, 0.026 mmol,

2.4 mol%) and triisopropylphosphane (4.2 mg, 5 mL, 0.026 mmol) was

heated under stirring in anhydrous toluene (1 mL) at 1108C for 4 h, cooled,

concentrated under reduced pressure and purified by column chromatog-

raphy (50 g silica gel, 20 Â 2 cm column, hexane) to give 16 as an oil (41 mg,

48%). R_f 0.62 (hexane); ¹H NMR (250 MHz, CDCl₃): d 2.51 (t, ⁵J

2.2 Hz, 4H; 2CH₂), 1.00 (p, ⁵J 2.2 Hz, 4H; cPr-H), 0.35 0.14 (m,

AA'BB', 8H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃): d 128.9 (C_quat, cPr-

4H; cPr-H); ¹³C NMR (125.7 MHz, CDCl₃): d 139.6 (C_quat), 134.6 (,

CH C), 132.8 (C_quat), 128.8 (, Ar-C), 127.9 (, Ar-C), 127.3 (, Ar-C),

112.4 (C_quat, C C), 111.9 (À, CH₂), 6.4 (À, CH₂), 4.2 (À, CH₂); MS (70 eV,

EI): m/z (%): 156 (82) [M ], 141 (56) [M À CH₃], 128 (66) [M À C₂H₄],

115 [M À C₃H₅]; HRMS: m/z (%): calcd for C₁₂H₁₂: 156.0939; found:

156.0939.

Dimerization of bicyclopropylidene (1)

trans-1-(3''-Cyclopropylidenepropen-1''-yl)-1-(propen-3'-yl)cyclopropane

C), 41.6 (À, 2CH₂), 26.2 (C_quat, 2cPr-C), 8.3 (À, 4cPr-C),

C), 110.8 (C_quat

,

(11),

pane (12), 3-[1'-(propen-3''-yl)cyclopropyl]-1,3,5-hexatriene (13), and

1-[1'-(propen-3''-yl)cyclopropyl]-1,3,5-hexatriene (14): Under argon,

cis-1-(3''-cyclopropylidenepropen-1'-yl)-1-(propen-3'-yl)cyclopro-

2.2 (À, 2cPr-C); MS (EI): m/z (%): 160 (3) [M ], 159 (6) [M À H], 145

(52) [M À H À CH₂], 132 (26) [M À C₂H₄], 131 (52) [M À H À C₂H₄],

a

117 (85) [M À H À CH₂À C₂H₄], 105 (56) [C₈H₉], 92 (40) [C₇H₈], 91

mixture of bicyclopropylidene (1, 400 mg, 469 mL, 5.00 mmol), Pd(OAc)₂

(56 mg, 0.25 mmol, 5 mol%) and PPh₃(131 mg, 0.500 mmol) was heated

under stirring in anhydrous benzene (5 mL) at 808C for 2 h, then cooled

and concentrated under reduced pressure. Column chromatography (50 g

silica gel, 120 Â 2 cm column, hexane, R_f 0.48) gave a mixture of C₁₂H₁₆

hydrocarbons (290 mg, 72.5%) which according to GC analysis contained

11 (48.3%), 12 (15.2%), 13 (19.3%), and 14 (17.2%). This corresponds to

yields of 35, 11, 14, and 12.5%, respectively. The analytical samples were

prepared by preparative gas chromatography (20%SE 30 on Chromosorb

W-AW-DMCS, 2000 mm Â 8.2 mm column, 1358C).

(100) [C₇H₇]; HRMS: m/z (%): calcd for C₁₂H₁₆: 160.1252; found:

160.1252.

Methyl 8-phenylspiro[2.5]oct-7-ene-5-carboxylate (18a-Ph): a) According

to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol), triphenylphosphane

(39.3 mg, 150 mmol), bicyclopropylidene (1, 160 mg, 2.00 mmol), K₂CO₃

(277 mg, 2.00 mmol), Et₄NCl (166 mg, 1.00 mmol) and iodobenzene (2-Ph,

204 mg, 1.00 mmol) were stirred in anhydrous acetonitrile (1 mL) with

methyl acrylate (17a, 172 mg, 2.00 mmol) for 48 h at 808C. After work-up

and being dried over MgSO₄the solvent was removed in a rotatory

evaporator. The residue was subjected to chromatography on 50 g silica gel

(column 2 Â 20 cm, pentane/diethyl ether 10:1) and yielded 18a-Ph as a

yellowish oil (241 mg, 100%). R_f 0.45 (pentane/diethyl ether 30:1); IR

Compound 11: ¹H NMR (250 MHz, CDCl₃): d 6.35 (dm, ³J 11.3 Hz,

3

1H; CH), 6.14 (dd, J 16.1, J 11.3 Hz, 1H; CH), 5.69 5.91 (m, 1H;

3

2

CH), 5.47 (d, J 16.1 Hz, 1H; CH), 5.07 (dd, J 15.2, J 1.0 Hz, 1H;

3

2

3

(film): nÄ 3030, 2990, 1730 (C O), 1650 (C C), 1575, 1510, 1100, 890, 830,

CH₂), 5.02 (dd, J 8.0, J 1.0 Hz, 1H; CH₂), 2.22 (d, J 8.1 Hz, 2H;

750, 730 cm^À1

;

¹H NMR (250 MHz, C₆D₆): d 7.30 7.00 (m, 5H; Ar-H),

CH₂), 1.09 (brs, 4H; cPr-H), 0.65 (brs, 4H; cPr-H); ¹³C NMR (62.9 MHz,

3

5.53 (dd, J_6A-7 6.0, J_6B-7 2.8 Hz, 1H; 7-H), 3.85 (s, 3H; CH₃O), 2.86

CDCl₃): d 138.0 (, C-3''), 136.2 (, C-2''), 126.1 (, C-1''), 123.7 (C_quat

,

3

(dddd, J_4A-5 2.9, J_4B-5 11.6, J_5-6A 6.0, J_5-6B 9.9 Hz, 1H; 5-H), 2.58

cPr-C), 118.9 (, C-2'), 116.2 (À, C-1'), 40.0 (À, C-3'), 21.2 (C_quat, cPr-C),

2

3

2

(ddd, J_AB 17.7, J_5-6B 9.9, J_6B-7 2.8 Hz, 1H; 6-H_B), 2.42 (ddd, J_AB

14.1 (À, 2 cPr-C), 2.5 (À, cPr-C), 2.2 (À, cPr-C); MS (EI): m/z (%): 160 (19)

3

2

3

17.7, J_5-6A 6.0, J_6A-7 6.0 Hz, 1H; 6-H_A), 2.24 (ddd, J_AB 12.9, J_4B-5

[M ], 145 (10) [M À H À CH₂], 132 (9) [M À C₂H₄], 131 (21) [M À H À

4

2

3

4

11.6, J_4B-6B 1.4 Hz, 1H; 4-H_B), 1.36 (ddd, J_AB 12.9, J_4A-5 2.9, J_4A-6

C₂H₄], 117 (36) [M À H À CH₂À C₂H₄], 105 (38) [C₈H₉], 92 (20) [C₇H₈],

2

3

1.0 Hz, 1H; 4-H_A), 0.73 (ddd, J_AB 3.9, J_1A-2B 9.1, J_1B-2B 5.2 Hz, 1H;

91 (100) [C₇H₇], 79 (77) [C₆H₇], 77 (65) [C₆H₅]; HRMS: m/z (%): calcd

2

3

2-H_B), 0.56 (ddd, J_AB 3.5, J_1B-2A 9.8, J_1B-2B 5.2 Hz, 1H; 1-H_B), 0.44

for C₁₂H₁₆: 160.1252; found: 160.1252.

2

3

2

(ddd, J_AB 3.9, J_1A-2A 5.5, J_1B-2A 9.8 Hz, 1H; 2-H_A), 0.30 (ddd, J_AB

Compound 12: ¹H NMR (250 MHz, CDCl₃): d 6.35 (dm, ³J 11.3 Hz,

3.5, J_1A-2A 5.5, J_1A-2B 9.1 Hz, 1H; 1-H_A); ¹³C NMR (62.9 MHz, C₆D₆,

DEPT): d 174.8 (C_quat, CO), 143.0 (C_quat, C-8*), 140.4 (C_quat, Ar-C*),

129.2 (, Ar-C), 128.1 (, Ar-C), 126.6 (, Ar-C), 124.0 (, C-7), 50.8 (,

CH₃O), 39.3 (, C-5), 37.5 (À, C-6), 28.6 (À, C-4), 20.0 (C_quat, C-3), 12.8

3

1H; CH), 6.13 (dd, J 10.5, J 11.3 Hz, 1H; CH), 5.92 5.76 (m, 1H;

3

2

3

CH), 5.55 (d, J 10.5 Hz, 1H; CH), 5.05 (dd, J 1.0, J 17.0 Hz, 1H;

2

3

CH₂), 5.00 (dd, J 1.0, J 8.0 Hz, 1H; CH₂), 2.16 (d, J 7.0 Hz, 2H;

CH₂), 1.13 (dm, J 7.5 Hz, 4H; cPr-H), 0.60 (brs, 4H; cPr-H); ¹³C NMR

3

(À, C-2), 11.6 (À, C-1); MS (70 eV, EI): m/z (%): 242 (25) [M ], 210 (65)

(62.9 MHz, CDCl₃): d 136.4 (, CH), 132.5 (, CH), 129.8 (, CH),

126.8 (C_quat, cPr-C), 115.9 (, C-2'), 115.6 (À, C-1'), 43.4 (À, C-3'), 19.5

(C_quat, cPr-C), 12.9 (À, 2cPr-C), 2.6 (À, cPr-C), 1.8 (À, cPr-C); the mass

spectrum is analogous to the previous one; HRMS: m/z (%): calcd for

C₁₂H₁₆: 160.1252; found: 160.1252.

[M À CH₄O], 183 (100) [M À CO₂CH₃], 91 (49) [C₇H₇]; HRMS: m/z

(%): calcd for C₁₆H₁₈O₂: 242.1307; found: 242.1307.

b) According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol), triphe-

nylphosphane (39.3 mg, 150 mmol), bicyclopropylidene (1, 160 mg,

2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg, 1.00 mmol)

and bromobenzene (22, 157 mg, 1.00 mmol) were stirred in anhydrous

acetonitrile (1 mL) with methyl acrylate (17a, 172 mg, 2.00 mmol) for 48 h

at 808C. After work-up the residue was subjected to chromatography on

50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1) and yielded

18a-Ph as a yellowish oil (144 mg, 59%).

Compound 13 (a 6.2:1 mixture of isomers): Major isomer: ¹H NMR

(250 MHz, CDCl₃): d 6.73 (ddd, ³J 17.0, ³J 12.0, ³J 8.6 Hz, 1H;

3

CH), 6.05 (d, J 12.0, 1H; CH), 5.88 5.72 (m, 1H; CH), 5.65 (dd,

3

J 17.1, J 9.5 Hz, 1H; CH), 5.26 4.76 (m, 6H; 3 CH₂), 2.11 (d, J

7.5 Hz, 2H; CH₂), 0.55 (brs, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃): d

139.0 (C_quat, C-3), 136.5 (, CH), 134.3 (, CH), 132.2 (, CH), 131.7

c) According to GP 3, palladium(ii) acetate (27.0 mg, 120 mmol, 1 mol%),

triphenylphosphane (94.2 mg, 360 mmol, 3 mol%), bicyclopropylidene (1,

1.92 g, 24.0 mmol), K₂CO₃(1.66 g, 12.0 mmol), Et₄NCl (966 mg, 5.8 mmol)

and iodobenzene (2-Ph, 2.45 g, 12.0 mmol) were stirred in anhydrous

acetonitrile (3 mL) with methyl acrylate (17a, 2.07 g, 24.0 mmol) for 48 h at

808C. After work-up, the crude product was subjected to chromatography

on 50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1) and

yielded 18a-Ph as a yellowish oil (2.86 g, 99%).

(, CH), 117.9 (À, CH₂), 116.0 (À, CH₂), 115.7 (À, CH₂), 41.8 (À,

C-3''), 18.8 (C_quat, cPr-C), 11.6 (À, 2cPr-C); the signals of the minor isomer

are covered by the signals of the major diastereomer or are indistinguish-

able; HRMS: m/z (%): calcd for C₁₂H₁₆: 160.1252; found: 160.1252.

Compound 14 (a mixture of isomers): Major (trans,trans-isomer): ¹H NMR

3

(250 MHz, CDCl₃): d 6.55 6.51 (m, 1H; CH), 6.37 (dd, ³J 16.6, J

10.8 Hz, 1H; CH), 6.14 (dd, ³J 16.6, J 8.5 Hz, 1H; CH), 5.99 (dd,

3

³J 15.7, J 8.5 Hz, 1H; CH), 5.86 5.68 (m, 1H; CH), 5.47 (d, ³J

3

15.7 Hz, 1H; CH), 5.19 (dd, J 17.5, J 9.5 Hz, 2H; CH₂), 5.05 (ddd,

d) According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol, 5 mol%),

triphenylphosphane (39.2 mg, 150 mmol, 15 mol%), bicyclopropylidene (1,

160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg,

³J 17.0, J 9.8, J 1.7 Hz, 2H; CH₂), 2.23 (d, ³J 6.5 Hz, 2H; CH₂),

4

0.67 (dm, ³J 8.0 Hz, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃): d 141.4

Chem. Eur. J. 2002, 8, No. 10

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2357 $ 20.00+.50/0

2357

A. de Meijere et al.

FULL PAPER

1.00 mmol) and bromobenzene (22, 157 mg, 1.00 mmol) were stirred in

anhydrous acetonitrile (1 mL) with methyl acrylate (17a, 172 mg,

2.00 mmol) for 48 h at 808C. After work-up, chromatography of the crude

product on 50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1)

gave:

yielded 18a-Tol as a yellow oil (233 mg, 91%). R_f 0.63 (pentane/diethyl

ether 10:1).

Methyl 8-(3'-pyridinyl)spiro[2.5]oct-7-ene-5-carboxylate (18a-Py): Ac-

cording to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol, 5 mol%),

triphenylphosphane (39.2 mg, 150 mmol, 15 mol%), bicyclopropylidene

(1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg,

1.00 mmol) and 3-iodopyridine (2-Py, 205 mg, 1.00 mmol) were stirred in

anhydrous acetonitrile (1 mL) with methyl acrylate (17a, 172 mg,

2.00 mmol) for 24 h at 808C. After work-up, chromatography of the crude

product on 50 g silica gel (column 2 Â 20 cm, diethyl ether) yielded 18a-Py

as a yellowish oil (163 mg, 67%). R_f 0.74 (diethyl ether); IR (film): nÄ

Fraction I: Methyl cinnamate (23) as a colorless oil (26 mg, 16%); R_f 0.58

(pentane/diethyl ether 10:1).

Fraction II: 18a-Ph as a yellowish oil (144 mg, 59%); R_f 0.50 (pentane/

diethyl ether 10:1).

Methyl 8-ethenylspiro[2.5]oct-7-ene-5-carboxylate (18a-Vin): According

to GP 2, iodoethene (6, 154 mg, 1.00 mmol), bicyclopropylidene (1, 320 mg,

3.99 mmol), palladium(ii) acetate (11.2 mg, 49.9 mmol), triphenylphosphane

(39.3 mg, 150 mmol) and triethylamine (202 mg, 2.00 mmol) were heated in

anhydrous DMF (10 mL) at 758C for 20 h. After cooling, methyl acrylate

(17a, 172 mg, 2.00 mmol) was added and stirred for additional 20 h at

ambient temperature. After work-up, chromatography of the crude

product on silica gel (column 2 Â 20 cm, pentane ! pentane/diethyl ether

50:1) gave:

3001, 2950, 2927, 1734 (C O), 1652 (C C), 1636, 1436, 1262, 1195, 1173,

1027, 805, 720 cm^À1; ¹H NMR (250 MHz, CDCl₃): d 8.44 (dd, ³J 4.9, ⁴J

1.9 Hz, 1H; 4'-H), 8.28 (dd, ⁴J 2.0, J 0.6 Hz, 1H; 2'-H), 7.32 (ddd, ³J

5

7.7, ⁴J 2.0, ⁴J 1.9 Hz, 1H; 6'-H), 7.15 (ddd, ³J 7.7, ³J 4.9, ⁵J 0.6 Hz,

1H; 5'-H), 5.54 (t, ³J 3.9 Hz, 1H; 7-H), 3.67 (s, 3H; OCH₃), 2.87 (ddt, ³J

11.6, ³J 8.6, ³J 3.0 Hz, 1H; 5-H), 2.47 (dd, ³J 8.6, ³J 3.9 Hz, 2H;

6-H), 2.15 (dd, ²J 13.0, ³J 11.6 Hz, 1H; 4-H), 1.49 (dd, ²J 13.0, ³J

3.0 Hz, 1H; 4-H), 0.57 0.36 (m, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): d 175.6 (C_quat, CO), 149.7 (, C-6'*), 148.0 (, C-2'*), 139.4

(C_quat, C-3'**), 136.4 (, C-7), 135.5 (C_quat, C-8**), 125.8 (, C-4'*), 122.4

(, C-5'*), 51.6 (, OCH₃), 39.0 (, C-5), 37.1 (À, C-6), 28.3 (À, C-4), 20.0

(C_quat, C-3), 12.4 (À, cPr-C), 11.1 (À, cPr-C); MS (70 eV): m/z (%): 243 (28)

Fraction I:

A mixture (100 mg) of polymers and 7-H, solvents not

completely evaporated; R_f 0.8 0.5 (pentane).

Fraction II: 18a-Vin as a colorless oil (125 mg, 65%); R_f 0.35 (pentane/

diethyl ether 10:1); IR (film): nÄ 2990, 1730 (C O), 1650 (C C), 1100, 890,

[M ], 228 (3) [M À CH₃], 212 (9) [M À OCH₃], 184 (100) [M

À

840, 730 cm^À1; ¹H NMR (250 MHz, C₆D₆): d 5.81 (dd, ³J_6A-7 5.4, ³J_6B-7

CO₂CH₃], 168 (29), 156 (55), 132 (13); elemental analysis calcd (%) for

C₁₅H₁₇NO₂(243.3): C 74.05, H 7.04; found: C 74.34, H 7.32.

3.0 Hz, 1H; 7-H), 5.75 (dd, ³J 10.6, ³J 17.0 Hz, 1H; 1'-H), 5.27 (dd,

²J_AB 2.3, ³J 17.0 Hz, 1H; 2'-H_B), 4.85 (dd, ²J_AB 2.3, ³J 10.6 Hz, 1H; 2'-

Dimethyl cis-8-phenylspiro[2.5]oct-7-ene-4,5-dicarboxylate (18b-Ph): In

an NMR tube, 5-Ph (50.0 mg, 320 mmol), dimethyl maleate (17b, 72.0 mg,

500 mmol) and hydroquinone (2 mg) were heated under nitrogen in CDCl₃

(0.5 mL) at 608C. In certain intervals the probe was cooled and a ¹H NMR

spectrum recorded. After 30 min, a conversion of ca. 50%was determined,

while after 12 h complete conversion to 18b-Ph was detected. The solvent

was removed in vacuo and the residue was subjected to chromatography on

silica gel (column 1 Â 20 cm, hexane/diethyl ether 5:1) to yield 18b-Ph as a

colorless oil (66.5 mg, 69%). R_f 0.13 (hexane/diethyl ether 5:1); IR (film):

3

H_A), 3.85 (s, 3H; OCH₃), 2.71 (dddd, J_4A-5 2.9, J_4B-5 11.6, J_5-6A 5.0,

³J_5-6B 10.0 Hz, 1H; 5-H), 2.52 (ddd, J_AB 17.8, J_5-6B 10.0, J_6B-7

2

3

2

3

3.0 Hz, 1H; 6-H_B), 2.31 (ddd, J_AB 17.8, J_5-6A 5.0, J_6A-7 5.4 Hz, 1H;

2

3

2

6-H_A), 2.11 (dd, J_AB 12.9, J_4B-5 11.6 Hz, 1H; 4-H_B), 1.36 (dd, J_AB

3

2

3

12.9, J_4A-5 2.9 Hz, 1H; 4-H_A), 0.90 (ddd, J_AB 4.6, J_1A-2B 9.4, J_1B-2B

5.9 Hz, 1H; 2-H_B), 0.65 (ddd, ²J_AB 4.3, ³J_1B-2A 10.4, ³J_1B-2B 5.9 Hz, 1H;

1-H_B), 0.40 (ddd, ²J_AB 4.6, J_1A-2A 5.6, J_1B-2A 10.4 Hz, 1H; 2-H_A), 0.25

3

(ddd, J_AB 4.3, J_1A-2A 5.6, J_1A-2B 9.4 Hz, 1H; 1-H_A); ¹³C NMR

2

3

(62.9 MHz, C₆D₆, DEPT): d 174.2 (C_quat, CO), 139.4 (C_quat, C-8), 139.4

nÄ 3030, 2990, 1730 (C O), 1650 (C C), 1575, 1510, 1100, 890, 830, 750,

730 cm^À1; ¹H NMR (250 MHz, CDCl₃): d 7.35 7.15 (m, 3H; Ar-H), 7.08

7.04 (m, 2H; Ar-H), 5.54 (dd, ³J 2.7, ³J 4.6 Hz, 1H; 7-H), 3.75 (s, 3H;

(C_quat, C-8), 134.6 (, CH *), 121.6 (, C-7*), 114.8 (À, CH₂), 51.1 (,

CH₃O), 39.3 (, C-5), 37.7 (À, C-6), 28.9 (À, C-4), 19.5 (C_quat, C-3), 13.5

(À, C-2), 11.3 (À, C-1); MS (70 eV, EI): m/z (%): 192 (20) [M ], 160 (65)

3

OCH₃), 3.73 (s, 3H; OCH₃), 3.14 (ddd, J 3.6, J 6.5, J 11.3 Hz, 1H;

5-H), 2.77 (ddd, ²J 18.5, ³J 2.7, ³J 11.3 Hz, 1H; 6-H), 2.58 (d, ³J

3.6 Hz, 1H; 4-H), 2.56 (ddd, ²J 18.5, ³J 4.6, ³J 6.5 Hz, 1H; 6-H),

1.00 0.87 (m, 2H; cPr-H), 0.60 0.47 (m, 2H; cPr-H); ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): d 173.9 (C_quat, CO₂), 172.6 (C_quat, CO₂),

141.0 (C_quat, Ar-C*), 139.8 (C_quat, C-8*), 129.0 (, 2 Ar-C), 127.5 (, 2 Ar-

C), 126.7 (, Ar_para-C), 124.4 (, C-7*), 51.9 (, OCH₃), 51.7 (, OCH₃),

50.7 (, C-5*), 40.9 (, C-4*), 25.4 (À, C-6), 23.0 (C_quat, C-3), 13.4 (À,

[M À CH₄O], 133 (100) [M À CO₂CH₃]; HRMS: m/z (%): calcd for

C₁₂H₁₆O₂: 192.1150; found: 192.1150.

Methyl 8-(4'-methylphenyl)spiro[2.5]oct-7-ene-5-carboxylate (18a-Tol):

a) According to GP 3, palladium(ii) acetate (11.2 mg, 49.9 mmol,

5 mol%), triphenylphosphane (39.2 mg, 150 mmol, 15 mol%), bicyclopro-

pylidene (1, 160 mg, 2.00 mmol), para-iodotoluene (2-Tol, 218 mg,

1.00 mmol) and triethylamine (204 mg, 2.02 mmol) in anhydrous DMF

(1 mL) were heated with methyl acrylate (17a, 172 mg, 2.00 mmol) for 2 d

at 808C. After work-up, chromatography of the crude product on 50 g silica

gel (column 2 Â 20 cm, pentane/diethyl ether 10:1) yielded 18a-Tol as a

yellow oil (223 mg, 87%). R_f 0.50 (pentane/diethyl ether 10:1); IR (film):

C-2), 13.1 (À, C-1); MS (70 eV, EI): m/z (%): 300 (7) [M ], 268 (15) [M

À

CH₄O], 241 (81) [M À CO₂CH₃], 209 (63) [M À CO₂CH₃À CH₄O], 181

(100) [M À 2CO₂CH₃À H]; HRMS: m/z (%): calcd for C₁₈H₂₀O₄:

300.1362; found: 300.1362.

nÄ 2998, 2949, 1736 (C O), 1636 (C C), 1512, 1435, 1259, 1193, 1168, 1022,

820 cm^À1; ¹H NMR (250 MHz, CDCl₃): d 7.07 (d, ³J 7.9 Hz, 2H; Ar-H),

6.94 (d, ³J 7.9 Hz, 2H; Ar-H), 5.52 (t, ³J 3.8 Hz, 1H; 7-H), 3.72 (s, 3H;

OCH₃), 2.91 (ddt, ³J 11.8, ³J 8.0, ³J 3.0 Hz, 1H; 5-H), 2.48 (dd, ³J

8.0, ³J 3.8 Hz, 2H; 6-H), 2.33 (s, 3H; Ar-CH₃), 2.20 (dd, ²J 12.9, ³J

11.8 Hz, 1H; 4-H), 1.50 (dd, ²J 12.9, ³J 3.0 Hz, 1H; 4-H), 0.69 0.38 (m,

4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 176.0 (C_quat, CO),

142.8 (C_quat, Ar-C*), 137.2 (C_quat, Ar-C*), 136.1 (C_quat, C-8*), 129.0 (, Ar-

C), 128.1 (, Ar-C), 123.6 (, C-7), 51.6 (, OCH₃), 39.3 (, C-5), 37.4 (À,

C-6), 28.5 (À, C-4), 21.1 (, Ar-CH₃), 20.0 (C_quat, C-3), 12.8 (À, cPr-C), 11.5

Diethyl trans-spiro[2.5]oct-7-ene-4,5-dicarboxylate (18c-H): Under argon,

an NMR tube was charged with bicyclopropylidene (1, 86 mg, 1.07 mmol),

Pd(OAc)₂(11 mg, 0.05 mmol, 4.6 mol%), PPh₃(26 mg, 0.10 mmol), AcOH

(6 mg, 5.7 mL, 0.1 mmol) and Et₃N (10.1 mg, 13.9 mL, 0.10 mmol) in C₆D₆

(1 mL) and stirred at ambient temperature. The conversion of starting

1

materials was monitored by H NMR spectroscopy to be complete before

the work-up. After 24 h, when the allylidenecyclopropane 15 had been

formed in 55%yield, the mixture was filtered through a pad of celite,

diethyl fumarate (17c, 100 mg, 95 mL, 0.58 mmol) was added to the filtrate,

and the obtained solution was heated at 808C for 1 h. After cooling and

concentration under reduced pressure, the residue was purified by column

chromatography (50 g silica gel, 15 Â 1.5 cm column, hexane/Et₂O 4:1) to

give the diester 18c-H (66 mg, 45%). R_f 0.20 (hexane/Et₂O 4:1); b.p.

958C (1 Torr); IR (film): nÄ 2982, 1734, 1445, 1373, 1307, 1249, 1186, 1097,

(À, cPr-C); MS (70 eV): m/z (%): 256 (60) [M ], 225 (14) [M À OCH₃],

197 (100) [M À CO₂Me], 181 (88) [M À CH₃À MeOH À CO], 169 (40),

155 (35); elemental analysis calcd (%) for C₁₇H₂₀O₂(256.3): C 79.65, H 7.86;

found: C 79.37, H 8.05.

b) According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol, 5 mol%),

triphenylphosphane (39.2 mg, 150 mmol, 15 mol%), bicyclopropylidene (1,

160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg,

1.00 mmol) and para-iodotoluene (2-Tol, 218 mg, 1.00 mmol) were stirred

in anhydrous acetonitrile (1 mL) with methyl acrylate (17a, 172 mg,

2.00 mmol) for 48 h at 808C. After work-up, chromatography of the crude

product on 50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1)

1036, 975, 717 cm^À1

;

¹H NMR (250 MHz, CDCl₃): d 5.63 (ddd, ³J 9.8,

³J 4.3, ³J 3.2 Hz, 1H; 7-H), 5.00 (dt, ³J 9.8, ⁴J 2.0 Hz, 1H; 8-H),

3

4.17 4.00 (m, 4H; 2 OCH₂), 3.11 (ddd, J 9.0, J 9.0, J 5.5 Hz, 1H;

3

2

3

5-H), 2.97 (d, J 9.0 Hz, 1H; 4-H), 2.43 (dddd, J 17.7, J 5.5, J 4.3,

⁴J 2.0 Hz, 1H; 6-H), 2.28 (dddd, ²J 17.7, ³J 9.0, ³J 3.2, ⁴J 2.0 Hz,

1H; 6-H), 1.24 (t, ³J 7.1 Hz, 3H; CH₃), 1.23 (t, ³J 7.2 Hz, 3H; CH₃),

0.98 0.79 (m, 1H; cPr-H), 0.72 0.69 (m, 1H; cPr-H), 0.58 0.49 (m, 2H;

2358

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2358 $ 20.00+.50/0

Chem. Eur. J. 2002, 8, No. 10

Domino Heck Diels Alder Reactions

2350 2369

cPr-H); ¹³C NMR (62.9 MHz, CDCl₃): d 174.2 (C_quat, CO), 172.3 (C_quat

,

48 h at 808C. After work-up, chromatography of the crude product on 50 g

silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1) yielded 18e-Ph as

a yellowish oil (248 mg, 87%). R_f 0.66 (pentane/diethyl ether 10:1).

CO), 133.8 (, C-8), 122.6 (, C-7), 60.33 (À, CH₂CH₃), 60.25 (À,

CH₂CH₃), 46.8 (, C-5), 41.4 (, C-4), 26.6 (À, C-6), 18.3 (C_quat, cPr-C),

14.0 (, 2 CH₃), 12.9 (À, cPr-C), 11.9 (À, cPr-C); MS (EI): m/z (%): 252 (8)

tert-Butyl 8-(4'-methylphenyl)spiro[2.5]oct-7-ene-5-carboxylate (18e-Tol):

According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol, 5 mol%),

triphenylphosphane (39.2 mg, 150 mmol, 15 mol%), bicyclopropylidene (1,

160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg,

1.00 mmol) and para-iodotoluene (2-Tol, 218 mg, 1.00 mmol) were stirred

in anhydrous acetonitrile (1 mL) with tert-butyl acrylate (17e, 256 mg,

2.00 mmol) for 48 h at 808C. After work-up, chromatography of the crude

product on 50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 20:1)

yielded 18e-Tol as a yellow oil (247 mg, 83%). R_f 0.66 (pentane/diethyl

[M ], 207 (20) [M À OC₂H₅], 206 (11) [M À H À OC₂H₅], 179 (71)

[M À CO₂C₂H₅], 151 (19) [M À C₂H₄À CO₂C₂H₅], 133 (35), 105 (100)

[C₈H₉], 91 (23) [C₇H₇], 79 (20) [C₆H₇]; HRMS: m/z (%): calcd for

C₁₄H₂₀O₄: 252.1361; found: 252.1361; elemental analysis calcd (%) for

C₁₄H₂₀O₄(252.3): C 66.64, H 7.99; found: C 66.92, H 8.29.

[3aS-[(1R*),3aa,6a,7ab]]-1-[(8-Ethenylspiro[2.5]oct-7-en-5-yl)carbonyl]-

8,8-dimethyl-3a,6-methanohexahydro-3H-2,1-benzisothiazole-2,2-dioxide

(18d-Vin): According to GP 2, bicyclopropylidene (1, 320 mg, 3.99 mmol),

iodoethene (6, 154 mg, 1.00 mmol), palladium(ii) acetate (11.2 mg,

49.9 mmol), triphenylphosphane (39.3 mg, 150 mmol) and triethylamine

(202 mg, 2.00 mmol) were heated in DMF (10 mL) for 4 h at 1008C, the

mixture then stirred with (7'R)-1-(10',10'-dimethyl-3'-thia-4'-azatricy-

clo[5.2.1.0^1,5]dec-4'-yl)prop-2-enon (17d, 270 mg, 1.00 mmol) for additional

4.5 h at 758C. Chromatography on silica gel (column 2 Â 20 cm, pentane !

pentane/ethyl acetate 1:1) gave three fractions:

ether 20:1); IR (film): nÄ 3080, 2929, 1727 (C O), 1635 (C C), 1456, 1367,

1259, 1151, 1027, 806 cm^À1

;

¹H NMR (250 MHz, CDCl₃): d 7.07 (d, ³J

7.8 Hz, 2H; Ar-H), 6.93 (d, ³J 7.8 Hz, 2H; Ar-H), 5.51 (t, ³J 3.7 Hz, 1H;

7-H), 2.79 (ddt, ³J 11.7, J 9.7, ³J 2.9 Hz, 1H; 5-H), 2.43 (dd, ³J 9.7,

3

³J 3.7 Hz, 2H; 6-H), 2.32 (s, 3H; Ar-CH₃), 2.16 (dd, ²J 12.8, ³J

11.7 Hz, 1H; 4-H), 1.48 (s, 9H; tBu-H), 1.45 (dd, ²J 12.8, ³J 2.9 Hz,

1H; 4-H), 0.68 0.37 (m, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): d 175.0 (C_quat, CO), 142.9 (C_quat, Ar-C*), 137.4 (C_quat, Ar-C*),

136.0 (C_quat, C-8*), 129.1 (, Ar-C), 128.1 (, Ar-C), 123.8 (, C-7), 80.0

(C_quat, tBu-C), 40.5 (, C-5), 37.4 (À, C-6), 28.7 (À, C-4), 28.1 (, tBu-C),

21.1 (, Ar-CH₃), 20.1 (C_quat, C-3), 12.8 (À, cPr-C), 11.6 (À, cPr-C); MS

Fraction I: Polymers and 7-H, which had not completely evaporated; R_f

0.8 0.5 (pentane).

Fraction II: 18d-Vin as a colorless solid (130 mg, 35%); m.p. 618C; R_f

0.25 (petroleum ether/ethyl acetate 10:1); [a]²_D⁰ À14.9 (c 1.0 in CHCl₃);

(70 eV): m/z (%): 298 (5) [M ], 242 (100) [M À C₄H₈], 225 (22) [M

À

IR (KBr): nÄ 2995, 1715 (C O), 1650 (C C), 1175, 1100, 890, 830, 750,

OtBu], 197 (37) [M À CO₂tBu], 181 (51), 169 (19), 155 (22); elemental

analysis calcd (%) for C₂₀H₂₆O₂(298.4): C 80.50, H 8.78; found: C 80.71, H

8.79.

735 cm^À1

;

¹H NMR (500 MHz, CDCl₃): d 6.08 (dd, ³J 5.4, ³J 3.0 Hz,

1H; CH C), 5.81 (dd, ³J 17.0, J 10.6Hz, 1H; CH CH₂), 5.75 (dd,

3

J_AB 2.3, J 17.0 Hz, 1H; CH CH₂), 5.50 (dd, J_AB 2.3, ³J 10.6 Hz,

2

3

2

tert-Butyl 8-(3'-pyridinyl)spiro[2.5]oct-7-ene-5-carboxylate (18e-Py): Ac-

cording to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol, 5 mol%),

triphenylphosphane (39.2 mg, 150 mmol, 15 mol%), bicyclopropylidene

(1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg,

1.00 mmol) and 3-iodopyridine (2-Py, 205 mg, 1.00 mmol) were stirred in

anhydrous acetonitrile (1 mL) with tert-butyl acrylate (17e, 256 mg,

2.00 mmol) for 24 h at 808C. After work-up, chromatography of the crude

product on 50 g silica gel (column 2 Â 20 cm, diethyl ether) yielded 18e-Py

as a yellowish oil (231 mg, 81%). R_f 0.62 (diethyl ether); IR (film): nÄ

1H; CH CH₂), 3.84 (dd, ³J 6.9, ³J 6.9 Hz, 1H; CHNCH₂), 3.60 3.75

2

(m, 1H; CHCO), 3.50 (d, J_AB 13.9 Hz, 1H; CH₂SO₂), 3.44 (d, J_AB

13.9 Hz, 1H; CH₂SO₂), 2.50 (ddt, ⁴J 1.6, J_AB 17.0, ³J 5.3 Hz, 1H;

2

3

CH₂C ), 2.40 (dd, J_AB 17.0, J 2.5 Hz, 1H; CH₂C ), 2.36 2.30 (m, 1H;

CH₂), 2.10 2.08 (m, 2H; CH₂), 1.90 1.84 (m, 3H; CH₂), 1.45 (d, ³J

9.0 Hz, 1H; CH₂), 1.40 1.35 (m, 2H; CH₂), 1.20 (s, 3H; CH₃), 0.99 (s, 3H;

CH₃), 0.72 0.68 (m, 1H; cPr-H), 0.56 0.55 (m, 2H; cPr-H), 0.48 0.44 (m,

1H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 174.9 (C_quat, CO),

138.6 (C_quat, CH C), 135.2 (, CH C), 120.5 (, CH C), 116.1 (À, CH₂),

64.6 (, CHN), 53.8 (À, CH₂SO₂), 48.4 (C_quat, CCH₂), 46.4 [C_quat, C(CH₃)₂],

45.0 (, CH), 40.8 (, CHCO), 38.6 (À, CH₂), 36.4 (À, CH₂), 32.5 (À,

CH₂), 30.3 (À, CH₂), 27.0 (À, CH₂), 21.6 (, CH₃), 20.9 (, CH₃), 20.6

(C_quat, cPr-C), 13.2 (À, cPr-C), 11.4 (À, cPr-C); MS (70 eV, EI): m/z (%):

3080, 2977, 2931, 1726 (C O), 1641 (C C), 1367, 1263, 1154, 1026, 806,

719 cm^À1

;

¹H NMR (250 MHz, CDCl₃): d 8.47 (dd, ³J 4.8, ⁴J 1.8 Hz,

4

3

1H; 6'-H*), 8.31 (d, J 3.9 Hz, 1H; 2'-H*), 7.19 (dd, J 7.8, J 4.8 Hz,

3

1H; 5'-H), 5.57 (t, J 3.6 Hz, 1H; 7-H), 2.79 (ddt, J 11.6, J 9.5, J

3.5 Hz, 1H; 5-H), 2.45 (dd, ³J 9.5, ³J 3.6 Hz, 2H; 6-H), 2.14 (dd, ²J

12.2, ³J 11.6 Hz, 1H; 4-H), 1.47 (dd, ²J 12.3, ³J 3.5 Hz, 1H; 4-H), 1.46

[s, 9H; C(CH₃)₃], 0.61 0.41 (m, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): d 174.6 (C_quat, CO), 149.8 (, Ar-C), 148.0 (, Ar-C), 139.4

(C_quat, Ar-C**), 136.5 (, Ar-C), 135.8 (C_quat, C-8**), 126.1 (, Ar-C*),

122.4 (, C-7*), 80.2 (C_quat, tBu-C), 40.3 (, C-5), 37.1 (À, C-6), 28.6 (À,

C-4), 28.1 (, tBu-C), 20.0 (C_quat, C-3), 12.4 (À, cPr-C), 11.3 (À, cPr-C); MS

375 (25) [M ], 160 (9) [C₁₁H₁₂O ], 159 (17) [C₁₁H₁₁O ], 132 (100)

[C₁₀H₁₂]; HRMS: m/z (%): calcd for C₂₁H₂₉NO₃S: 375.1868; found:

375.1868.

tert-Butyl 8-phenylspiro[2.5]oct-7-ene-5-carboxylate (18e-Ph): a) Accord-

ing to GP 3, palladium(ii) acetate (11.2 mg, 49.9 mmol), triphenylphosphane

(39.3 mg, 150 mmol), bicyclopropylidene (1, 160 mg, 2.00 mmol), iodoben-

zene (2-Ph, 204 mg, 1.00 mmol) and triethylamine (202 mg, 2.00 mmol)

with tert-butyl acrylate (17e, 256 mg, 2.00 mmol) in anhydrous DMF

(1 mL) were heated at 808C for 2 d. After work-up, chromatography of the

crude product on 50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether

10:1) yielded 18e-Ph as a yellowish oil (222 mg, 78%). R_f 0.59 (pentane/

(70 eV): m/z (%): 285 (1) [M ], 228 (68) [M À C₄H₉], 212 (17) [M

À

C₄H₉O], 184 (100) [M À C₄H₉O À CO], 168 (21), 156 (42), 115 (40), 57

(55) [C₄H₉]; elemental analysis calcd (%) for C₁₈H₂₃NO₂(285.4): C 75.77,

H 8.12; found: C 75.67, H 8.15.

Dimethyl (E)-8-phenylspiro[2.5]oct-7-ene-4,5-dicarboxylate (18 f-Ph):

a) According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol,

5 mol%), triphenylphosphane (39.2 mg, 150 mmol, 15 mol%), bicyclopro-

pylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl

(166 mg, 1.00 mmol) and iodobenzene (2-Ph, 204 mg, 1.00 mmol) were

stirred in anhydrous acetonitrile (5 mL) with dimethyl fumarate (17 f,

288 mg, 2.00 mmol) for 48 h at 808C. After work-up, chromatography of

the crude product on 50 g silica gel (column 2 Â 20 cm, hexane/diethyl ether

5:1) yielded 18 f-Ph as colorless crystals (291 mg, 97%). R_f 0.27 (hexane/

diethyl ether 5:1); m.p. 71 738C (from hexane); IR (film): nÄ 3021, 2951,

diethyl ether 10:1); IR (film): nÄ 3078, 2977, 2930, 1727 (C O), 1642

À1

(C C), 1600, 1492, 1456, 1442, 1367, 1259, 1151, 1023, 849, 703 cm

;

¹H NMR (250 MHz, CDCl₃): d 7.26 7.22 (m, 3H; Ar-H), 7.05 7.01 (m,

2H; Ar-H), 5.52 (t, J 3.6 Hz, 1H; 7-H), 2.79 (ddt, J 11.7, J 9.7, ³J

2.8 Hz, 1H; 5-H), 2.43 (dd, ³J 9.7, ³J 3.6 Hz, 2H; 6-H), 2.15 (dd, ²J

12.8, ³J 11.7 Hz, 1H; 4-H), 1.47 (s, 9H; tBu-H), 1.44 (dd, ²J 12.8, ³J

2.8 Hz, 1H; 4-H), 0.63 0.34 (m, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): d 175.0 (C_quat, CO), 142.9 (C_quat, Ar-C*), 140.4 (C_quat, C-8*),

129.2 (, Ar-C), 127.4 (, Ar-C), 126.5 (, Ar-C), 124.0 (, C-7), 80.0

(C_quat, tBu-C), 40.4 (, C-5), 37.4 (À, C-6), 28.7 (À, C-4), 28.1 (, tBu-C),

20.1 (C_quat, C-3), 12.8 (À, cPr-C), 11.6 (À, cPr-C); MS (70 eV): m/z (%): 284

3

À1

1737 (C O), 1492, 1436, 1259, 1196, 1025, 760, 705 cm

;

¹H NMR

(250 MHz, CDCl₃): d 7.28 7.22 (m, 3H; Ar-H), 7.08 7.05 (m, 2H; Ar-H),

5.53 (dd, ³J 3.8, ³J 3.8 Hz, 1H; 7-H), 3.72 (s, 6H; 2OCH₃), 3.31 (ddd,

³J 6.4, ³J 6.4, ³J 6.4 Hz, 1H; 5-H), 2.97 (d, ³J 6.4 Hz, 1H; 4-H), 2.55

(ddd, ³J 3.8, ³J 6.4, ³J 6.4 Hz, 2H; 6-H), 0.69 0.59 (m, 3H; cPr-H),

0.49 0.43 (m, 1H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 174.5

(C_quat, CO₂), 173.3 (C_quat, CO₂), 141.8 (C_quat, Ar-C*), 139.7 (C_quat, C-8*),

129.2 (, 2 Ar-C), 127.5 (, 2 Ar-C), 126.7 (, Ar_para-C), 123.4 (, C-7*),

51.88 (, OCH₃), 51.84 (, OCH₃), 49.3 (, C-5*), 41.4 (, C-4*), 26.3 (À,

C-6), 20.0 (C_quat, C-3), 11.0 (À, C-2), 10.2 (À, C-1); MS (70 eV, EI): m/z

(2) [M ], 228 (100) [M À C₄H₈], 211 (29), 182 (83) [M À tBuOH À CO],

167 (37), 155 (46), 141 (39), 57 (48) [C₄H₉]; elemental analysis calcd (%)

for C₁₉H₂₄O₂(284.4): C 80.24, H 8.51; found: C 80.07, H 8.48.

b) According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol), triphe-

nylphosphane (39.3 mg, 150 mmol), bicyclopropylidene (1, 160 mg,

2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg, 1.00 mmol)

and iodobenzene (2-Ph, 204 mg, 1.00 mmol) were stirred in anhydrous

acetonitrile (1 mL) with tert-butyl acrylate (17e, 256 mg, 2.00 mmol) for

Chem. Eur. J. 2002, 8, No. 10

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2359 $ 20.00+.50/0

2359

A. de Meijere et al.

FULL PAPER

(%): 300 (18) [M ], 268 (22) [M À CH₄O], 267 (18), 241 (81) [M

À

[M À CO₂Me À MeOH À CO], 167 (29), 154 (7), 128 (4), 77 (4), 59 (9);

elemental analysis calcd (%) for C₁₇H₁₉NO₄(301.3): C 67.76, H 6.36; found:

C 68.61, H 6.69.

CO₂CH₃], 240 (85), 209 (63) [M À CO₂CH₃À CH₄O], 181 (100) [M

2CO₂CH₃À H]; elemental analysis calcd (%) for C₁₈H₂₀O₄(300.4): C 71.98,

H 6.71; found: C 71.76, H 6.68.

8-Phenylspiro[2.5]oct-7-ene-5-carboxylic amide (18g-Ph): According to

GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol), triphenylphosphane

(39.3 mg, 150 mmol), bicyclopropylidene (1, 160 mg, 2.00 mmol), K₂CO₃

(277 mg, 2.00 mmol), Et₄NCl (166 mg, 1.00 mmol) and iodobenzene (2-Ph,

204 mg, 1.00 mmol) were stirred in anhydrous acetonitrile (1 mL) with

acrylic acid amide (17g, 142 mg, 2.00 mmol) for 48 h at 808C. After work-

up, chromatography of the crude product on 50 g silica gel (column 2 Â

20 cm, pentane/diethyl ether 5:1 ! Et₂O/MeOH 10:1) yielded 18g-Ph as

colorless crystals (112 mg, 49%). R_f 0.10 (pentane/diethyl ether 2:1); m.p.

b) From the same quantities of reagents, but dimethyl maleate 17b instead

of dimethyl fumarate 17 f, compound 18 f-Ph (288 mg, 96%) was obtained

according to GP 5 after column chromatography.

c) According to GP 3, palladium(ii) acetate (11.2 mg, 49.9 mmol), triphe-

nylphosphane (39.3 mg, 150 mmol), bicyclopropylidene (1, 160 mg,

2.00 mmol), iodobenzene (2-Ph, 204 mg, 1.00 mmol) and triethylamine

(202 mg, 2.00 mmol) with dimethyl maleate (17b, 288 mg, 2.00 mmol) in

anhydrous DMF (3 mL) were heated at 808C for 20 h. After work-up,

chromatography of the crude product on 50 g silica gel (column 2 Â 20 cm,

pentane/diethyl ether 10:1) yielded 18 f-Ph (294 mg, 98%).

1598C; IR (film): nÄ 3184, 3057, 2991, 2927, 1654 (C O), 1617 (C C), 1437,

1375, 1178, 1120, 748, 722 cm^À1; ¹H NMR (250 MHz, CDCl₃): d 7.70 7.62

(m, 1H; 4'-H), 7.55 7.43 (m, 2H; 3'-H, 5'-H), 7.04 7.0 (m, 2H; 2'-H, 6'-H),

3

Dimethyl

(E)-8-(4'-methylphenyl)spiro[2.5]oct-7-ene-4,5-dicarboxylate

5.84 (brs, 1H; NH₂), 5.74 (brs, 1H; NH₂), 5.54 (d, J 3.5 Hz, 1H; 7-H),

2.78 (ddd, ³J 11.6, ³J 8.9, ³J 2.7 Hz, 1H; 5-H), 2.48 (dd, ³J 8.9, ³J

3.5 Hz, 2H; 6-H), 2.24 (dd, ²J 13.0, ³J 11.6 Hz, 1H; 4-H), 1.43 (dd, ²J

13.0, ³J 2.7 Hz, 1H; 4-H), 0.69 0.37 (m, 4H; cPr-H); ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): d 178.1 (C_quat, CO), 143.3 (C_quat, Ar-C*),

140.1 (C_quat, C-8*), 129.1 (, Ar-C), 127.5 (, Ar-C), 126.6 (, Ar-C), 123.6

(, C-7), 40.7 (À, C-6), 37.9 (, C-5), 29.2 (À, C-4), 20.1 (C_quat, C-3), 12.9

(18 f-Tol): a) According to GP 3, palladium(ii) acetate (11.2 mg, 49.9 mmol,

5 mol%), triphenylphosphane (39.2 mg, 150 mmol, 15 mol%), bicyclopro-

pylidene (1, 160 mg, 2.00 mmol), para-iodotoluene (2-Tol, 218 mg,

1.00 mmol) and triethylamine (204 mg, 2.02 mmol) in anhydrous DMF

(1 mL) were heated with dimethyl fumarate (17 f, 288 mg, 2.00 mmol) for

48 h at 808C. After work-up, chromatography of the crude product on 50 g

silica gel (column 2 Â 20 cm, pentane/diethyl ether 5:1) yielded 18 f-Tol as

colorless crystals (252 mg, 80%). R_f 0.33 (pentane/diethyl ether 5:1); m.p.

(À, cPr-C), 11.6 (À, cPr-C); MS (70 eV): m/z (%): 227 (30) [M ], 183 (100)

[M À CONH₂], 155 (80), 115 (18), 91 (16) [C₇H₇]; elemental analysis

488C; IR (KBr): nÄ 3008, 2953, 2929, 1731 (C O), 1719 (C O), 1652

calcd (%) for C₁₅H₁₇NO (227.3): C 79.26, H 7.54; found: 79.33, H 7.54.

(C C), 1437, 1321, 1179, 1159, 1127, 818 cm^À1; ¹H NMR (250 MHz, CDCl₃):

Methyl 5-methyl-8-phenylspiro[2.5]oct-7-ene-5-carboxylate (18 h-Ph): Ac-

cording to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol, 5 mol%),

triphenylphosphane (39.3 mg, 150 mmol, 15 mol%), bicyclopropylidene

(1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg,

1.00 mmol) and iodobenzene (2-Ph, 204 mg, 1.00 mmol) were stirred in

anhydrous acetonitrile (1 mL) with methyl methylacrylate (17 h, 200 mg,

2.00 mmol) for 48 h at 808C. After work-up, chromatography of the crude

product on 25 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1)

yielded 18 h-Ph as a yellowish oil (195 mg, 76%). R_f 0.58 (pentane/

d 7.06 (d, ³J 7.8 Hz, 2H; Ar-H), 6.95 (d, ³J 7.8 Hz, 2H; Ar-H), 5.50 (t,

³J 3.8 Hz, 1H; 7-H), 3.72 (s, 6H; OCH₃), 3.30 (dt, ³J 6.7, ³J 6.5 Hz,

1H; 5-H), 2.97 (d, ³J 6.7 Hz, 1H; 4-H), 2.53 (dd, ³J 6.5, ³J 3.8 Hz, 2H;

6-H), 2.32 (s, 3H; Ar-CH₃), 0.69 0.59 (m, 3H; cPr-H), 0.50 0.44 (m, 1H;

cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 174.6 (C_quat, CO), 173.4

(C_quat, CO), 141.7 (C_quat, Ar-C*), 136.8 (C_quat, Ar-C*), 136.3 (C_quat, C-8*),

129.1 (, Ar-C), 128.2 (, Ar-C), 123.2 (, C-7), 51.8 (, OCH₃), 49.2 (,

C-4), 41.5 (, C-5), 26.4 (À, C-6), 21.1 (, Ar-CH₃), 20.1 (C_quat, C-3), 10.9

(À, cPr-C), 10.2 (À, cPr-C); MS (70 eV): m/z (%): 314 (21) [M ], 282 (14)

diethyl ether 10:1); IR (film): nÄ 3070, 2998, 2950, 2922, 1736 (C O), 1645

[M À CH₄O], 255 (100) [M À CO₂CH₃], 223 (52) [M À CO₂CH₃À

(C C), 1600, 1435, 1371, 1189, 1019, 823 cm^À1; ¹H NMR (250 MHz, CDCl₃):

CH₄O], 195 (86) [M À CO₂CH₃À CH₄O À CO], 179 (31), 165 (34);

3

d 7.25 7.22 (m, 3H; Ar-H), 7.04 7.01 (m, 2H; Ar-H), 5.50 (dd, J 4.0,

elemental analysis calcd (%) for C₁₉H₂₂O₄(314.4): C 72.59, H 7.05; found:

C 71.94, H 7.30.

³J 3.7 Hz, 1H; 7-H), 3.71 (s, 3H; OCH₃), 2.73 (dd, ²J 17.7, J 3.7 Hz,

3

1H; 6-H), 2.13 (dd, ²J 17.7, ³J 4.0 Hz, 1H; 6-H), 2.04 (d, ²J 13.2 Hz,

1H; 4-H), 1.65 (d, ²J 13.2 Hz, 1H; 4-H), 1.36 (s, 3H; CH₃), 0.54 0.45 (m,

4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 177.9 (C_quat, CO),

141.9 (C_quat, Ar-C*), 140.3 (C_quat, C-8*), 129.3 (, Ar-C), 127.4 (, Ar-C),

b) According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol, 5 mol%),

triphenylphosphane (39.2 mg, 150 mmol, 15 mol%), bicyclopropylidene (1,

160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg,

1.00 mmol) and para-iodotoluene (2-Tol, 218 mg, 1.00 mmol) were stirred

in anhydrous acetonitrile (1 mL) with dimethyl fumarate (17 f, 288 mg,

2.00 mmol) for 48 h at 808C. After work-up, chromatography of the crude

product on 50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1)

yielded 18 f-Tol as a yellow oil (310 mg, 99%). R_f 0.22 (pentane/diethyl

ether 10:1).

126.5 (, Ar-C), 123.4 (, C-7), 51.6 (, OCH₃), 43.1 (À, C-6), 42.1 (C_quat

,

C-5), 35.1 (À, C-4), 24.1 (, CH₃), 18.5 (C_quat, C-3), 11.7 (À, cPr-C), 10.6

(À, cPr-C); MS (70 eV): m/z (%): 256 (28) [M ], 241 (4) [M À CH₃], 225

(8) [M À OCH₃], 197 (100) [M À CO₂Me], 196 (96) [M À CO₂Me À H],

181 (52) [M À HCO₂MeÀ CH₃], 169 (68), 141 (40), 115 (16), 91 (7) [C₇H₇].

Methyl 8-phenyl-5-(methoxycarbonylmethyl)spiro[2.5]oct-7-ene-5-carbox-

ylate (18k-Ph): According to GP 5, palladium(ii) acetate (11.2 mg,

49.9 mmol, 5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%),

bicyclopropylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol),

Et₄NCl (166 mg, 1.00 mmol) and iodobenzene (2-Ph, 204 mg, 1.00 mmol)

were stirred in anhydrous acetonitrile (1 mL) with itaconic dimethyl ester

(17k, 316 mg, 2.00 mmol) for 72 h at 808C. After work-up, chromatography

of the crude product on 25 g silica gel (column 2 Â 20 cm, pentane/diethyl

ether 10:1) yielded 18k-Ph as a colorless oil (149 mg, 47%). R_f 0.18

Dimethyl (E)-8-(3'-pyridinyl)spiro[2.5]oct-7-ene-4,5-dicarboxylate (18 f-

Py): According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol,

5 mol%), triphenylphosphane (39.2 mg, 150 mmol, 15 mol%), bicyclopro-

pylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl

(166 mg, 1.00 mmol) and 3-iodopyridine (2-Py, 205 mg, 1.00 mmol) were

stirred in anhydrous acetonitrile (1 mL) with dimethyl fumarate (17 f,

288 mg, 2.00 mmol) for 48 h at 808C. After work-up, chromatography of

the crude product on 50 g silica gel (column 2 Â 20 cm, diethyl ether)

yielded 18 f-Py as a yellowish oil (190 mg, 63%). R_f 0.54 (diethyl ether);

(pentane/diethyl ether 10:1); IR (film): nÄ 3060, 2997, 2951, 2923, 1734

À1

IR (film): nÄ 3005, 2952, 1734 (C O), 1646 (C C), 1436, 1262, 1197, 1172,

(C O), 1730 (C O), 1635 (C C), 1436, 1371, 1190, 1019 cm

;

¹H NMR

1027, 804, 720 cm^À1; ¹H NMR (250 MHz, CDCl₃): d 8.47 (dd, ³J 4.9, ⁴J

(250 MHz, CDCl₃): d 7.23 7.20 (m, 3H; Ar-H), 7.02 6.08 (m, 2H; Ar-

4

3

4

1.6 Hz, 1H; 2'-H), 8.32 (d, J 2.0 Hz, 1H; 2'-H*), 7.42 (ddd, J 7.7, J

2.0, ⁴J 1.8 Hz, 1H; 4'-H*), 7.19 (dd, ³J 7.7, ³J 4.9 Hz, 1H; 5'-H), 5.58

(dd, ³J 3.9, ³J 3.8 Hz, 1H; 7-H), 3.73 (s, 6H; OCH₃), 3.33 (ddd, ³J 6.4,

³J 6.1, ³J 5.2 Hz, 1H; 5-H), 2.92 (d, ³J 6.1 Hz, 1H; 4-H), 2.63 (ddd,

H), 5.48 (dd, ³J 4.7, ³J 3.1 Hz, 1H; 7-H), 3.71 (s, 3H; OCH₃), 3.66 (s, 3H;

2

OCH₃), 3.01 (d, J 16.5 Hz, 1H; CH₂CO₂Me), 2.80 (d, J 16.5 Hz, 1H;

2

3

2

CH₂CO₂Me), 2.77 (dd, J 17.9, J 3.1 Hz, 1H; 6-H), 2.27 (dd, J 17.9,

³J 4.7 Hz, 1H; 6-H), 2.19 (d, ²J 13.4 Hz, 1H; 4-H), 1.67 (dd, ²J 13.4,

⁵J 1.3 Hz, 1H; 4-H), 0.52 0.39 (m, 4H; cPr-H); ¹³C NMR (62.9 MHz,

CDCl₃, DEPT): d 176.2 (C_quat, CO), 172.0 (C_quat, CO), 142.0 (C_quat, C-8*),

139.8 (C_quat, Ar-C*), 129.2 (, Ar-C), 127.4 (, Ar-C), 126.6 (, Ar-C),

122.6 (, C-7), 51.9 (, OCH₃), 51.5 (, OCH₃), 43.8 (C_quat, C-5), 40.2 (À,

C-6), 39.9 (À, C-4), 33.5 (À, CH₂CO₂Me), 18.0 (C_quat, C-3), 12.0 (À, cPr-C),

3

2

3

²J 18.3, J 5.2, J 3.9 Hz, 1H; 6-H), 2.51 (ddd, J 18.3, J 6.4, J

3.8 Hz, 1H; 6-H), 0.73 0.59 (m, 3H; cPr-H), 0.44 0.39 (m, 1H; cPr-H);

¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 174.2 (C_quat, CO), 173.1 (C_quat

,

CO), 149.8 (, Ar-C), 148.2 (, Ar-C), 138.3 (C_quat, Ar-C*), 136.5 (, Ar-

C*), 135.2 (C_quat, C-8*), 125.6 (, Ar-C*), 122.5 (, C-7*), 52.0 (, OCH₃),

51.9 (, OCH₃), 49.2 (, C-5), 41.1 (, C-4), 25.9 (À, C-6), 19.9 (C_quat

,

9.9 (À, cPr-C); MS (70 eV): m/z (%): 314 (1) [M ], 283 (4) [M À CH₃],

C-3), 10.9 (À, cPr-C), 10.1 (À, cPr-C); MS (70 eV): m/z (%): 301 (8) [M ],

254 (28) [M À CO₂Me À H], 241 (100) [M À CH₂CO₂Me], 195 (24)

242 (100) [M À CO₂Me], 210 (60) [M À CO₂Me À MeOH], 182 (76)

[M À 2CO₂Me À H], 181 (58), 165 (24), 141 (12), 91 (12) [C₇H₇].

0947-6539/02/0810-2360 $ 20.00+.50/0 Chem. Eur. J. 2002, 8, No. 10

2360

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

Domino Heck Diels Alder Reactions

2350 2369

Methyl 8-(1-cyclohex-1-enyl)spiro[2.5]oct-7-ene-5-carboxylate (19a) and

methyl 2-ethenylspiro[cyclopropane-1',3-bicyclo[4.4.0]dec-1-ene]-5-car-

boxylate (20a): According to GP 5, palladium(ii) acetate (11.2 mg,

49.9 mmol, 5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%),

bicyclopropylidene (1, 160 mg, 2.00 mmol), K₂CO₃(278 mg, 2.01 mmol),

Et₄NCl (166 mg, 1.00 mmol) and 1-iodocyclohexene (9, 200 mg, 0.96 mmol)

with methyl acrylate (17a, 172 mg, 2.00 mmol) were heated in acetonitrile

(1 mL) at 808C for 2 d. After work-up, chromatography of the crude

product on 50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1)

yielded a not completely separable mixture of 19a and 20a (1:2, ¹H NMR)

as a clear oil (200 mg, 84%). R_f 0.62 (pentane/diethyl ether 10:1); IR

C(CH₃)₃], 40.5 (, C-5), 37.4 (À, C-6), 31.0 (À, cHex-C), 28.4 (À, cHex-C),

28.0 [, C(CH₃)₃], 25.0 (À, C-4), 22.8 (À, cHex-C), 22.1 (À, cHex-C), 18.8

(C_quat, cPr-C), 13.6 (À, cPr-C), 11.8 (À, cPr-C); 20e: d 175.4 (C_quat, CO),

134.8 (C_quat, C-1), 133.5 (, C-1'), 129.4 (C_quat, C-2), 118.9 (À, C-2'), 79.9

[C_quat, C(CH₃)₃], 48.5 (, C-6), 40.9 (, C-5), 37.3 (À, cHex-C), 34.3 (À,

cHex-C), 31.5 (À, cHex-C), 28.2 [, C(CH₃)₃], 27.8 (À, cHex-C*), 26.2 (À,

C-4*), 18.8 (C_quat, cPr-C), 11.7 (À, cPr-C), 10.4 (À, cPr-C); MS (70 eV): m/z

(%): 288 (4) [M ], 232 (80) [M À C₄H₈], 215 (12) [M À OC₄H₉], 187 (81)

[M À OC₄H₉À CO], 145 (40), 107 (74) [M À OC₄H₉À CO À C₆H₈], 91

(44), 79 (41), 57 (100) [C₄H₉]; elemental analysis calcd (%) for C₁₉H₂₈O₂

(288.4): C 79.12, H 9.78; found: C 78.35, H 9.91.

(film): nÄ 3078, 2997, 2928, 2854, 1736 (C O), 1635 (C C), 1436, 1256,

Dimethyl spiro[cyclopropane-1',2-bicyclo[4.4.0]dec-10-ene]-4,7-dicarbox-

ylate (21a): According to GP 3, iodoethene (6, 154 mg, 1.00 mmol),

bicyclopropylidene (1, 320 mg, 3.99 mmol), methyl acrylate (17a, 344 mg,

4.00 mmol), palladium(ii) acetate (11.2 mg, 49.9 mmol), triphenylphosphane

(39.3 mg, 150 mmol) and triethylamine (202 mg, 2.00 mmol) in anhydrous

DMF (5 mL) were heated at 808C for 24 h. After work-up, chromatog-

raphy of the crude product on silica gel (column 2 Â 20 cm, pentane/diethyl

ether 10:1) gave:

1

1194, 1162, 1026, 920 cm^À1; H NMR (250 MHz, CDCl₃): 19a: d 5.34 (t,

3

³J 3.7 Hz, 1H; 7-H), 5.20 (t, J 3.6 Hz, 1H; 2'-H), 3.67 (s, 3H; OCH₃),

3.01 2.92 (m, 1H; 5-H), 2.35 (dd, ³J 9.7, ³J 3.7 Hz, 1H; 6-H), 2.19 (dd,

²J 13.2, ³J 11.6 Hz, 1H; 4-H), 1.97 1.14 (m, 10H; CH₂), 0.70 0.30 (m,

4H; cPr-H); 20a: d 5.79 (dd, ³J 17.5, ³J 11.1 Hz, 1H; 1''-H), 5.15 (dd,

²J 2.6, ³J 11.1 Hz, 1H; 2''-H), 4.89 (dd, ²J 2.6, ³J 17.5 Hz, 1H; 2''-H),

3.68 (s, 3H; OCH₃), 2.87 2.81 (m, 1H; 5-H), 2.43 2.52 (m, 1H; 6-H),

1.97 1.14 (m, 10H; CH₂), 0.70 0.30 (m, 4H; cPr-H); MS (70 eV): m/z (%):

Fraction I: A mixture of polymers (80 mg); R_f 0.9 (pentane/diethyl ether

246 (31) [M ], 215 (6) [M À OCH₃], 187 (100) [M À OCH₃À CO], 145

(67), 91 (27); elemental analysis calcd (%) for C₁₆H₂₂O₂(246.3): C 78.01, H

9.00; found: C 78.19, H 9.11.

10:1).

Fraction II: 21a as a yellowish oil (164 mg, 59%); R_f 0.17 (pentane/

3

diethyl ether 10:1); IR (film): nÄ 2980, 2920, 1734 (C O), 1653 (C C),

1-(1'-Cyclopropylideneprop-2'-enyl)cyclohex-1-ene

(10),

dimethyl

1

1456, 1436, 1197, 1032 cm^À1; H NMR (250 MHz, CDCl₃): d 5.25 (t, J

9.4 Hz, 1H; 10-H), 3.68 (s, 3H; OCH₃), 3.67 (s, 3H; OCH₃), 2.76 2.69 (m,

1H; 7-H), 2.67 2.52 (m, 1H; 4-H), 2.47 2.25 (m, 2H; 8-H), 2.19 2.13 (m,

2H; 5-H), 2.06 1.97 (m, 2H; 9-H), 1.54 (dt, ³J 13.6, ³J 2.3 Hz, 1H;

6-H), 1.35 1.14 (m, 2H; 3-H), 1.02 0.76 (m, 1H; cPr-H), 0.59 0.32 (m,

2H; cPr-H), 0.29 0.21 (m, 1H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): d 176.4 (C_quat, CO), 175.5 (C_quat, CO), 142.3 (C_quat, C-1), 114.7

(, C-10), 51.6 (, OCH₃), 51.4 (, OCH₃), 40.7 (, C-6*), 39.2 (, C-7*),

37.3 (À, C-9**), 34.4 (À, C-8**), 33.9 (À, C-5**), 33.2 (, C-4*), 28.0 (À,

C-3), 21.3 (C_quat, C-2), 15.5 (À, cPr-C), 8.0 (À, cPr-C); MS (70 eV): m/z

(4S*,5S*)-8-cyclohex-1'-enylspiro[2.5]oct-7-ene-4,5-dicarboxylate (19b)

and dimethyl (3'a,4'a,4'ab)-1'-ethenyl-4',4'a,5',6',7',8'-hexahydrospiro[cy-

clopropane-1,2'(3'H)-naphthalene]-3',4'-dicarboxylate (20b): According

to GP 4, cyclohexenylnonaflate (8, 380 mg, 1.00 mmol), [Pd(PPh₃)₄]

(57.8 mg, 50.0 mmol, 5 mol%), bicyclopropylidene (1, 320 mg, 3.99 mmol),

triethylamine (810 mg, 8.00 mmol) and dimethyl maleate (17b, 288 mg,

2.00 mmol) in anhydrous DMF (10 mL) were heated at 1008C for 18 h.

After work-up, chromatography of the crude product on silica gel (1 Â

20 cm, pentane ! pentane/ethyl acetate 10:1) gave:

Fraction I:

A colorless oil (100 mg), which rapidly polymerizes and

(%): 278 (18) [M ], 246 (16) [M À CH₄O], 218 (44) [M À CH₄O À CO],

according to ¹H NMR and ¹³C NMR contains ca. 10%of 10; R_f 0.8

187 (26) [M À CH₄O À CO À OCH₃], 159 (100) [M À CH₄O À 2CO À

OCH₃], 133 (44), 117 (41), 91 (42); HRMS: m/z (%): calcd for C₁₆H₂₂O₄:

278.1518; found: 278.1518.

(pentane).

Fraction II: A not completely separable mixture of 19b and 20b (130 mg,

43%; 1:1.5 by ¹H NMR). 19b: ¹H NMR (250 MHz, CDCl₃): d 5.3 (t, ³J

4 Hz, 1H; 2'-H), 3.7 (s, 3H; CH₃), 3.6 (s, 3H; CH₃), 3.3 (d, ³J 7 Hz, 2H; 3'-

H), 2.9 2.8 (m, 1H; 4'-H), 2.3 1.0 (m, 10H; CH₂), 0.8 0.5 (m, 4H; cPr-

H); 20b: ¹H NMR (250 MHz, CDCl₃): d 5.85 (dd, ³J 10, ³J 17 Hz, 1H;

Dimethyl (E)-8-ethenylspiro[2.5]oct-7-ene-4,5-dicarboxylate (18 f-Vin)

and

tetramethyl

(3S*,4S*,7R*,8R*)-spiro[cyclopropane-1',2-bicy-

clo[4.4.0]dec-10-ene]-3,4,7,8-tetracarboxylate (21 f): According to GP 3,

iodoethene (6, 154 mg, 1.00 mmol), bicyclopropylidene (1, 320 mg,

3.99 mmol), dimethyl fumarate (17 f, 432 mg, 3.00 mmol), palladium(ii)

acetate (11.2 mg, 49.9 mmol), triphenylphosphane (39.3 mg, 150 mmol) and

triethylamine (202 mg, 2.00 mmol) in anhydrous DMF (10 mL) were

heated at 758C for 20 h. After work-up, chromatography of the crude

product on silica gel (column 2 Â 20 cm, pentane ! pentane/diethyl ether

2:1) gave:

2

3

2

3

CH ), 5.1 (dd, J 2, J 10 Hz, 1H; CH₂ ), 4.9 (dd, J 2, J 17 Hz,

1H; CH₂ ), 3.7 (s, 3H; CH₃), 3.6 (s, 3H; CH₃), 3.2 (d, ³J 7 Hz, 1H; 3'-H),

3.0 2.9 (m, 2H; 4'-H, 5'-H), 2.3 1.0 (m, 8H; CH₂), 0.8 0.5 (m, 4H; cPr-

H); 19b and 20b: clear oil; R_f 0.28 (pentane/diethyl ether 10:1); IR

(film): nÄ 2990, 1730 (C O), 1725 (C O), 1635 (C C), 1110, 890, 840, 750,

730 cm^À1; MS (70 eV, EI): m/z (%): 304 (8) [M ], 272 (9) [M À CH₄O],

244 (68) [M À CH₄O À CO], 213 (40), 185 (100) [M À CH₄O À CO À

CH₃CO₂]; HRMS: m/z (%): calcd for C₁₈H₂₄O₄: 304.1674; 304.1674.

Fraction I: Polymers and 7-H; which had not completely evaporated; R_f

0.8 0.45 (pentane).

tert-Butyl 8-(1-cyclohex-1-enyl)spiro[2.5]oct-7-ene-5-carboxylate (19e)

and tert-butyl 2-ethenylspiro[cyclopropane-1',3-bicyclo[4.4.0]dec-1-ene]-

5-carboxylate (20e): According to GP 5, palladium(ii) acetate (11.2 mg,

49.9 mmol, 5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%),

bicyclopropylidene (1, 160 mg, 2.00 mmol), K₂CO₃(278 mg, 2.01 mmol),

Et₄NCl (166 mg, 1.00 mmol) and 1-iodocyclohexene (9, 200 mg, 0.96 mmol)

with tert-butyl acrylate (17e, 256 mg, 2.00 mmol) were heated in acetoni-

trile (1 mL) at 808C for 2 d. After work-up, chromatography of the crude

product on 50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1)

yielded a not completely separable mixture of 19e and 20e (1:3, ¹H NMR)

as a clear oil (231 mg, 83%). R_f 0.62 (pentane/diethyl ether 10:1); IR

Fraction II: 18 f-Vin as a colorless oil (63.0 mg, 25%); R_f 0.35 (pentane/

diethyl ether 10:1); IR (film): nÄ 2990, 1730 (C O), 1725 (C O), 1650

(C C), 1110, 890, 840, 750, 730 cm^À1; ¹H NMR (250 MHz, CDCl₃): d 6.04

(dd, ³J 5.4, ³J 3.0 Hz, 1H; 7-H), 5.89 (dd, ³J 17.0, ³J 10.6 Hz, 1H;

2

3

CH CH₂), 5.43 (dd, J_AB 2.3, J 17.0 Hz, 1H; CH CH₂), 4.93 (dd,

2

3

J_AB 2.3, J 10.6 Hz, 1H; CH CH₂), 3.95 (s, 3H; OCH₃), 3.85 (s, 3H;

OCH₃), 3.30 (ddd, ³J 6.3, ³J 6.3, ³J 6.4 Hz, 1H; 5-H), 2.95 (d, ³J

6.4 Hz, 1H; 4-H), 2.55 (dd, ³J 6.3, ³J 2.7 Hz, 2H; 6-H), 0.7 0.6 (m, 3H;

cPr-H), 0.55 0.45 (m, 1H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT):

d 174.5 (C_quat, CO₂), 173.1 (C_quat, CO₂), 139.1 (C_quat, CH C), 133.9 (,

CH C), 120.4 (, CH C), 115.8 (À, CH₂), 51.8 (, OCH₃), 51.7 (,

(film): nÄ 3079, 2975, 2929, 1726 (C O), 1652 (C C), 1457, 1368, 1257,

OCH₃), 48.8 (, C-5), 41.3 (, C-4), 26.8 (À, C-6), 19.4 (C_quat, cPr-C), 10.7

1153, 997, 859 cm^À1

;

¹H NMR (250 MHz, CDCl₃): 19e: d 5.33 (t, ³J

(À, cPr-C), 9.9 (À, cPr-C); MS (70 eV, EI): m/z (%): 250 (12) [M ], 218

3

4.0 Hz, 1H; 7-H), 5.21 (t, J 3.5 Hz, 1H; 2'-H), 2.58 2.74 (m, 1H; 5-H),

2.28 (dd, ³J 6.3, ³J 3.2 Hz, 2H; 6-H), 1.97 (dd, ²J 12.7, ³J 11.6 Hz,

1H; 4-H), 1.43 [s, 9H; C(CH₃)₃], 1.77 0.85 (m, 9H; 4-H, cHex-CH₂), 0.68

0.33 (m, 4H; cPr-H); 20e: d 5.80 (dd, ³J 17.5, ³J 11.1 Hz, 1H; 1'-H),

5.14 (dd, ²J 2.5, ³J 11.1 Hz, 1H; 2'-H), 4.86 (dd, ²J 2.5, ³J 17.5 Hz,

1H; 2'-H), 2.91 2.79 (m, 1H; 5-H), 2.26 2.31 (m, 1H; 6-H), 1.43 [s, 9H;

C(CH₃)₃], 1.77 0.85 (m, 10H; 4-H, cHex-CH₂), 0.70 0.30 (m, 4H; cPr-H);

¹³C NMR (62.9 MHz, CDCl₃, DEPT): 19e: d 175.2 (C_quat, CO), 144.8

(22) [M À CH₄O], 191 (65) [M À CO₂CH₃], 159 (41) [M À CO₂CH₃À

CH₄O], 131 (100) [M À CH₄O À CO À CH₃CO₂].

Fraction III: 21 f as a mixture of three diastereomers (138 mg, 35%); R_f

0.11 (pentane/diethyl ether 10:1); IR (film): nÄ 2953, 1734 (C O), 1649

(C C), 1436, 1260, 1200, 1172, 1019, 808 cm^À1; part of the ¹H NMR

(250 MHz, CDCl₃): d 5.06 5.02 (m, 1H; CH C, isomer B, rel. intensity

0.40), 4.83 4.80 (m, 1H; CH C, isomer A, rel. intensity 1.0); MS (70 eV):

(C_quat, C-8), 137.0 (C_quat, C-1'), 124.1 (À, C-2'), 120.7 (, C-7), 79.8 [C_quat

,

m/z (%): 394 (7) [M ], 362 (66) [M À MeOH], 334 (21) [M À MeOH À

Chem. Eur. J. 2002, 8, No. 10 ¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2361 $ 20.00+.50/0

2361

A. de Meijere et al.

FULL PAPER

CO], 302 (76), [M À 2MeOH À CO], 274 (74) [M À 2MeOH À 2CO],

(C_quat, cPr-C*), 141.5 (C_quat, Ar-C*), 140.8 (C_quat, Ar-C*), 131.6 (C_quat, C-4*),

129.3 (, Ar-C), 128.1 (, Ar-C), 127.7 (, Ar-C), 127.4 (, Ar-C), 127.3

(, Ar-C), 126.4 (, Ar-C), 119.4 (, C-5), 40.7 (À, C-6), 38.1 (, C-7),

27.7 (À, C-8), 21.3 (C_quat, C-3), 13.1 (À, C-2), 11.3 (À, C-1), 3.3 (À, cPr-C),

243 (60) [M À 2MeOH À 2CO À OCH₃], 215 (100) [M À 2MeOH À

3CO À OCH₃], 183 (34) [M À 3MeOH À 3CO À OCH₃], 155 (83)

[M À 3MeOH À 4CO À OCH₃]; HRMS: m/z (%): calcd for C₂₀H₂₆O₈:

394.1627; found: 394.1627.

1.7 (À, cPr-C); MS (70 eV): m/z (%): 312 (100) [M ], 284 (61) [M

À

C₂H₄], 255 (72) [M À C₂H₅À C₂H₄], 167 (83); HRMS: m/z (%): calcd for

Methyl 8-(2-thiophenyl)spiro[2.5]oct-7-ene-5-carboxylate (25): According

to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol, 5 mol%), triphenyl-

phosphane (39.3 mg, 150 mmol, 15 mol%), bicyclopropylidene (1, 160 mg,

2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg, 1.00 mmol) and

2-bromothiophene (24, 163 mg, 1.00 mmol) were stirred in anhydrous

acetonitrile (1 mL) with methyl acrylate (17a, 172 mg, 2.00 mmol) for 48 h

at 808C. After work-up, chromatography of the crude product on 50 g silica

gel (column 2 Â 20 cm, pentane/diethyl ether 10:1) yielded 25 as a yellowish

oil (218 mg, 88%). R_f 0.36 (pentane/diethyl ether 10:1); IR (film): nÄ

C₂₄H₂₄(312.4): 312.1878 (correct HRMS); found: 312.1878.

Methyl 4-(4-nitrophenyl)-8-phenylspiro[2.5]oct-7-ene-5-carboxylate (p-31)

and methyl 5-(4-nitrophenyl)-8-phenylspiro[2.5]oct-7-ene-4-carboxylate

(p-32): According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol,

5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%), bicyclopro-

pylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl

(166 mg, 1.00 mmol) and iodobenzene (2-Ph, 204 mg, 1.00 mmol) were

stirred in anhydrous acetonitrile (1 mL) with methyl 3-(4-nitrophenyl)a-

crylate (p-30, 414 mg, 2.00 mmol) for 96 h at 808C. After work-up,

chromatography of the crude product on 25 g silica gel (column 2 Â

20 cm, pentane/diethyl ether 2:1) gave:

3072, 2998, 2948, 1734 (C O), 1653 (C C), 1628, 1436, 1376, 1314, 1260,

1194, 1169, 1023 cm^À1; H NMR (250 MHz, CDCl₃): d 7.13 (dd, J 5.2,

1

3

⁴J 1.2 Hz, 1H; 3'-H), 6.90 (dd, ³J 5.2, ³J 3.5 Hz, 1H; 4'-H), 6.71 (dd,

³J 3.4, J 1.2 Hz, 1H; 5'-H), 5.85 (t, J 3.8 Hz, 1H; 7-H), 3.70 (s, 3H;

4

3

Fraction I: p-32 as a yellowish oil (113 mg, 31%); R_f 0.49 (pentane/

OCH₃), 2.87 (ddt, ³J 11.7, ³J 8.3, ³J 3.1 Hz, 1H; 5-H), 2.49 (dd, ³J 8.3,

diethyl ether 2:1); IR (film): nÄ 3040, 2957, 1732 (C O), 1645 (C C), 1532,

³J 3.8 Hz, 2H; 6-H), 2.17 (dd, J 13.1, J 11.7 Hz, 1H; 4-H), 1.49 (dd,

2

3

1435, 1341, 1261, 1174, 1030, 802 cm^À1

;

¹H NMR (250 MHz, CDCl₃): d

²J 13.0, J 3.1 Hz, 1H; 4-H), 0.96 0.89 (m, 1H; cPr-H), 0.73 0.47 (m,

3

8.20 (d, ³J 8.7 Hz, 2H; 3''-H, 5''-H), 7.62 (d, ³J 8.7 Hz, 2H; 2''-H, 6''-H),

7.34 7.28 (m, 3H; 3'-H, 4'-H, 5'-H), 7.14 7.11 (m, 2H; 2'-H, 6'-H), 5.66 (dd,

³J 4.9, ³J 3.0 Hz, 1H; 7-H), 3.72 (s, 3H; OCH₃), 3.26 (d, ³J 4.4 Hz, 1H;

4-H), 3.09 (ddd, ³J 5.8, ³J 4.9, ³J 4.4 Hz, 1H; 5-H), 2.64 (ddd, ²J 18.0,

³J 5.8, ³J 3.0 Hz, 1H; 6-H), 2.11 (ddd, ²J 18.0, ³J 5.8, ³J 3.0 Hz,

1H; 6-H), 0.76 0.31 (m, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): d 173.8 (C_quat, CO), 150.3 (C_quat, C-4''*), 146.6 (C_quat, C-8*), 141.6

(C_quat, Ar-C*), 139.7 (C_quat, Ar-C*), 129.2 (, Ar-C), 129.2 (, Ar-C), 127.7

(, Ar-C), 127.0 (, C-4'), 124.6 (, C-7), 123.4 (, C-3'', C-5''), 51.8 (,

OCH₃), 49.4 (, C-5), 45.0 (, C-4), 24.4 (À, C-6), 20.9 (C_quat, C-3), 12.9

3H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 175.6 (C_quat, CO),

141.0 (C_quat, C-2'), 135.6 (C_quat, C-8), 127.6 (, C-3'*), 126.3 (, C-4'*),

125.3 (, C-5'*), 124.0 (, C-7*), 51.6 (, OCH₃), 38.9 (, C-5), 37.4 (À,

C-6), 28.6 (À, C-4), 20.0 (C_quat, C-3), 14.0 (À, cPr-C), 12.2 (À, cPr-C); MS

(70 eV): m/z (%): 248 (82) [M ], 217 (10) [M À OCH₃], 189 (100) [M

À

CO₂CH₃], 168 (51), 161 (44), 137 (68); elemental analysis calcd (%) for

C₁₄H₁₆O₂S (248.3): C 67.71, H 6.49; found: C 67.83, H 6.54.

Methyl 8-(3-thiophenyl)spiro[2.5]oct-7-ene-5-carboxylate (27) and methyl

(E)-3-thiophen-3-ylacrylate (28): According to GP 5, palladium(ii) acetate

(11.2 mg, 49.9 mmol), triphenylphosphane (26.3 mg, 100 mmol), bicyclopro-

pylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl

(166 mg, 1.00 mmol) and 3-bromothiophene (26, 163 mg, 1.00 mmol) were

stirred in anhydrous acetonitrile (1 mL) with methyl acrylate (17a, 172 mg,

2.00 mmol) for 72 h at 808C. After work-up, chromatography of the crude

product on 50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1)

gave:

(À, cPr-C), 9.4 (À, cPr-C); MS (70 eV): m/z (%): 363 (16) [M ], 332 (2)

[M À OCH₃], 303 (16) [M À MeOH À CO], 207 (63) [C₁₀H₉NO₄], 176

(100) [C₁₀H₉NO₄À OCH₃], 130 (20), 102 (20); elemental analysis calcd

(%) for C₂₂H₂₁NO₄(363.4): C 72.71, H 5.82; found: C 72.82, H 5.96.

Fraction II: p-31 as yellow crystals (225 mg, 62%); m.p. 1158C; R_f 0.43;

IR (film): nÄ 3040, 2962, 2931, 1735 (C O), 1651 (C C), 1532, 1437, 1259,

1176, 1074, 1027, 800 cm^À1

;

¹H NMR (250 MHz, CDCl₃): d 8.19 (d, ³J

Fraction I: 27 as a yellowish oil (169 mg, 68%); R_f 0.50 (pentane/diethyl

8.8 Hz, 2H; 3''-H, 5''-H), 7.53 (d, ³J 8.8 Hz, 2H; 2''-H, 6''-H), 7.32 7.24

(m, 3H; 3'-H, 4'-H, 5'-H), 7.12 7.08 (m, 2H; 2'-H, 6'-H), 5.69 (t, ³J 3.7 Hz,

1H; 7-H), 3.69 (ddd, ³J 7.1, ³J 6.2, ³J 6.2 Hz, 1H; 5-H), 3.61 (s, 3H;

OCH₃), 2.85 (d, ³J 7.1 Hz, 1H; 4-H), 2.71 (ddd, ²J 18.5, ³J 6.2, ³J

3.7 Hz, 1H; 6-H), 2.48 (ddd, ²J 18.5, ³J 6.2, ³J 3.7 Hz, 1H; 6-H), 0.68

0.56 (m, 2H; cPr-H), 0.43 0.34 (m, 1H; cPr-H), 0.18 0.12 (m, 1H; cPr-H);

ether 10:1); IR (film): nÄ 3064, 2996, 2951, 1736 (C O), 1635 (C C), 1435,

1371, 1259, 1196, 1170, 1021, 971 cm^À1

;

¹H NMR (250 MHz, CDCl₃): d

7.18 (dd, ³J 4.9, ⁴J 3.0 Hz, 1H; 5'-H), 6.90 (dd, ⁴J 3.0, ⁴J 1.2 Hz, 1H;

2'-H), 6.83 (dd, ³J 4.9, ⁴J 1.2 Hz, 1H; 4'-H), 5.64 (t, ³J 3.8 Hz, 1H;

7-H), 3.70 (s, 3H; OCH₃), 2.88 (ddd, ³J 11.8, ³J 8.2, ³J 3.0 Hz, 1H;

5-H), 2.46 (dd, ³J 8.2, ³J 3.8 Hz, 2H; 6-H), 2.17 (dd, ²J 12.9, ³J

11.8 Hz, 1H; 4-H), 1.47 (dd, ²J 12.9, ³J 3.0 Hz, 1H; 4-H), 0.79 0.67

(m, 1H; cPr-H), 0.58 0.42 (m, 3H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): d 175.8 (C_quat, CO), 140.5 (C_quat, C-3'), 138.0 (C_quat, C-8), 128.7

(, C-5'*), 124.7 (, C-2'*), 124.0 (, C-4'*), 122.0 (, C-7), 51.6 (,

OCH₃), 39.1 (, C-5), 37.4 (À, C-6), 28.5 (À, C-4), 20.0 (C_quat, C-3), 13.4

¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 172.92 (C_quat, CO), 152.5 (C_quat

,

C-4''*), 147.7 (C_quat, C-8*), 142.9 (C_quat, Ar-C*), 139.7 (C_quat, Ar-C*), 129.2

(, Ar-C), 128.4 (, Ar-C), 126.91 (, Ar-C), 126.91 (, C-4'), 123.8 (,

C-7), 123.6 (, C-3'', C-5''), 53.7 (, C-5), 51.7 (, OCH₃), 41.7 (, C-4),

30.8 (À, C-6), 20.1 (C_quat, C-3), 11.4 (À, cPr-C), 9.5 (À, cPr-C); MS (70 eV),

m/z (%): 363 (10) [M ], 304 (15) [M À CO₂Me], 279 (36), 167 (44), 149

(À, cPr-C), 11.7 (À, cPr-C); MS (70 eV): m/z (%): 248 (66) [M ], 233 (2)

(100) [M À C₆H₅À C₆H₄NO₂À CH₃], 113 (16); elemental analysis calcd

[M À CH₃], 217 (9) [M À OCH₃], 189 (100) [M À CO₂Me], 161 (44)

(%) for C₂₂H₂₁NO₄(363.4): C 72.71, H 5.82; found: C 72.50, H 5.64.

[M À CO₂Me À C₂H₄], 155 (28); elemental analysis calcd (%) for

Methyl 4-(3-nitrophenyl)-8-phenylspiro[2.5]oct-7-ene-5-carboxylate (m-

31) and methyl 5-(3-nitrophenyl)-8-phenylspiro[2.5]oct-7-ene-4-carboxy-

late (m-32): According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol,

5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%), bicyclopro-

pylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl

(166 mg, 1.00 mmol) and iodobenzene (2-Ph, 204 mg, 1.00 mmol) were

stirred in anhydrous acetonitrile (1 mL) with methyl 3-(3-nitrophenyl)a-

crylate (m-30, 414 mg, 2.00 mmol) for 96 h at 808C. After work-up,

chromatography of the crude product on 25 g silica gel (column 2 Â 20 cm,

pentane/diethyl ether 5:1) gave:

C₁₄H₁₆O₂S (248.4): C 67.71, H 6.49; found: C 66.80, H 6.47.

Fraction II: 28 (30 mg, 18%); R_f 0.34 (pentane/diethyl ether 10:1). The

spectroscopic data are in accordance with the literature.^[33]

7-[Cyclopropylidene(phenyl)methyl]-4-phenylspiro[2.5]oct-4-ene (29): In

a sealable Teflon tube palladium(ii) acetate (22.4 mg, 100 mmol), triphe-

nylphosphane (78.6 mg, 300 mmol), bicyclopropylidene (1, 320 mg,

4.00 mmol), iodobenzene (2-Ph, 408 mg, 2.00 mmol) and triethylamine

(405 mg, 4.00 mmol) in anhydrous DMF (7.5 mL) were heated for 24 h at

808C under a pressure of 10 kbar. After work-up, chromatography of the

crude product on 30 g flash silica gel (column 2 Â 15 cm, pentane) yielded

29 as a clear oil (89 mg, 28%). R_f 0.33 (pentane); IR (film): nÄ 3057,

Fraction I: m-31 as a yellowish oil (139 mg, 38%), R_f 0.24 (pentane/

diethyl ether 5:1); IR (film): nÄ 3042, 2958, 2929, 1734 (C O), 1650 (C C),

2966, 2918, 2849, 1771, 1717, 1675 (C C), 1598, 1491, 1446, 1260, 1095, 1025,

1530, 1437, 1348, 1261, 1200, 1175, 1074, 1027, 805 cm^À^{1 1}H NMR

;

801 cm^À1; ¹H NMR (250 MHz, CDCl₃): d 7.40 7.20 (m, 10H; Ar-H), 5.59

(t, ³J 3.7 Hz, 1H; 5-H), 3.36 (ddt, ³J 11.9, ³J 8.3, ³J 2.9 Hz, 1H; 7-H),

2.49 (dd, ³J 8.3, ³J 3.7 Hz, 2H; 6-H), 2.34 (dd, ²J 12.8, ³J 11.9 Hz,

1H; 8-H), 1.35 (dd, ²J 12.8, ³J 2.9 Hz, 1H; 8-H), 1.40 1.17 (m, 4H; cPr-

H), 0.75 (m, 1H; 2-H), 0.64 0.60 (m, 1H; 2-H), 0.52 0.38 (m, 2H; 1-H);

(250 MHz, CDCl₃): d 8.31 (dd, ⁴J 1.1, ⁴J 0.9 Hz, 1H; 2''-H), 8.09

(ddd, ³J 7.7, ⁴J 1.1, ⁴J 0.8 Hz, 1H; 4''-H), 7.63 (ddd, ³J 7.4, ⁴J 0.9,

⁴J 0.8 Hz, 1H; 6''-H), 7.43 (dd, J 7.7, J 7.4 Hz, 1H; 5''-H), 7.32 7.20

(m, 3H; 3'-H, 4'-H, 5'-H), 7.14 7.08 (m, 2H; 2'-H, 6'-H), 5.71 (t, ³J 3.6 Hz,

1H; 7-H), 3.71 (ddd, ³J 7.2, ³J 6.3, ³J 6.3 Hz, 1H; 5-H), 3.63 (s, 3H;

OCH₃), 2.74 (ddd, ²J 18.4, ³J 6.3, ³J 3.6 Hz, 1H; 6-H), 2.69 (d,

3

¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 153.0 (C_quat, cPr-C CPh*), 142.9

2362

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2362 $ 20.00+.50/0

Chem. Eur. J. 2002, 8, No. 10

Domino Heck Diels Alder Reactions

2350 2369

³J 7.2 Hz, 1H; 4-H), 2.50 (ddd, ²J 18.4, ³J 6.3, ³J 3.6 Hz, 1H; 6-H),

0.97 0.83 (m, 1H; cPr-H), 0.67 0.58 (m, 2H; cPr-H), 0.40 0.30 (m, 1H;

cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 173.8 (C_quat, CO), 166.6

(C_quat, C-3''), 148.2 (C_quat, C-8), 144.8 (C_quat, C-1''), 139.7 (C_quat, C-1'), 133.6

(C_quat, C-4''), 130.0 (, C-2''), 129.3 (, C-2', C-6'), 127.7 (, C-3', C-5'),

124.5 (, C-6''), 122.4 (, C-4'), 120.9 (, C-7), 52.0 (, OCH₃), 44.9 (,

C-4), 39.7 (, C-5), 23.7 (À, C-6), 20.7 (C_quat, C-3), 13.0 (À, cPr-C), 9.6 (À,

Methyl syn-8-(2-methylphenyl)spiro[2.5]oct-7-ene-5-carboxylate (syn-

34aa) and methyl anti-8-(2-methylphenyl)spiro[2.5]oct-7-ene-5-carboxy-

late (anti-34aa): According to GP 5, palladium(ii) acetate (11.2 mg,

49.9 mmol, 5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%),

bicyclopropylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol),

Et₄NCl (166 mg, 1.00 mmol) and ortho-iodotoluene (33a, 218 mg,

1.00 mmol) were stirred in anhydrous acetonitrile (1 mL) with methyl

acrylate (17a, 172 mg, 2.00 mmol) for 48 h at 808C. After work-up,

chromatography of the crude product on 25 g silica gel (column 2 Â 20 cm,

pentane/diethyl ether 10:1) yielded a mixture of two rotamers syn-34aa and

anti-34aa (1:2.0, ¹H NMR) as a yellowish oil (254 mg, 99%). R_f 0.54

(pentane/diethyl ether 10:1); syn-34aa: ¹H NMR (250 MHz, CDCl₃): d

7.29 7.19 (m, 3H; 3'-H, 4'-H, 5'-H), 7.06 (d, ³J 6.5 Hz, 1H; 6'-H), 5.62 (t,

³J 3.6 Hz, 1H; 7-H), 3.85 (s, 3H; OCH₃), 3.11 3.01 (m, 1H; 5-H), 2.64

(dd, ³J 8.1, ³J 3.6 Hz, 2H; 6-H), 2.35 (s, 3H; Ar-CH₃), 2.30 (dd, ²J 13.2,

³J 11.1 Hz, 1H; 4-H), 1.82 (dd, ²J 13.2, ³J 3.1 Hz, 1H; 4-H), 0.70 0.50

(m, 3H; cPr-H), 0.42 0.23 (m, 1H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): d 175.9 (C_quat, CO), 141.1 (C_quat, Ar-C*), 139.2 (C_quat, Ar-C*),

136.9 (C_quat, C-8*), 130.2 (, Ar-C), 129.5 (, Ar-C), 126.7 (, Ar-C), 124.6

(, Ar-C), 123.6 (, C-7), 51.7 (, OCH₃), 39.3 (, C-5), 37.2 (À, C-6),

28.2 (À, C-4), 19.9 (C_quat, C-3), 19.6 (, Ar-CH₃), 12.4 (À, cPr-C), 11.5 (À,

cPr-C); MS (70 eV): m/z (%): 363 (15) [M ], 332 (3) [M À OCH₃], 303

(17) [M À MeOH À CO], 207 (61) [C₁₀H₉NO₄], 176 (100) [C₁₀H₉NO₄

À

OCH₃], 130 (24); elemental analysis calcd (%) for C₂₂H₂₁NO₄(363.4): C

72.71, H 5.82, N 3.85; found: C 72.66, H 5.87, N 3.87.

Fraction II: m-32 as a yellowish oil (46 mg, 13%); R_f 0.22 (pentane/

diethyl ether 5:1); IR (film): nÄ 3041, 2958, 2930, 1735 (C O), 1651 (C C),

1

1529, 1435, 1347, 1260, 1073, 1027, 802 cm^À1; H NMR (250 MHz, CDCl₃):

d 8.37 (dd, ⁴J 1.1, ⁴J 1.0 Hz, 1H; 2''-H), 8.11 (ddd, ³J 7.5, ⁴J 1.1,

⁴J 0.8 Hz, 1H; 4''-H), 7.80 (ddd, J 7.3, J 1.0, J 0.8 Hz, 1H; 6''-H),

7.51 (dd, ³J 7.5, ³J 7.3 Hz, 1H; 5''-H), 7.34 7.2 (m, 3H; 3'-H, 4'-H, 5'-H),

7.19 7.15 (m, 2H; 2'-H, 6'-H), 5.65 (dd, ³J 4.3, ³J 2.8 Hz, 1H; 7-H), 3.74

3

4

3

(s, 3H; OCH₃), 3.22 (d, J 4.4 Hz, 1H; 4-H), 3.10 (ddd, J 5.5, J 4.3,

³J 3.4 Hz, 1H; 5-H), 2.63 (ddd, ²J 18.2, J 4.3, J 3.4 Hz, 1H; 6-H),

2.04 (ddd, ²J 18.2, ³J 5.5, ³J 2.8 Hz, 1H; 6-H), 0.87 0.29 (m, 4H; cPr-

H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 10.9 (À, cPr-C), 14.1 (À, cPr-

C), 20.7 (C_quat, C-3), 23.0 (À, C-6), 38.7 (, C-5), 49.1 (, C-4), 51.8 (,

3

1

cPr-C); anti-34aa: H NMR (250 MHz, CDCl₃): d 7.29 7.19 (m, 3H; 3'-

H, 4'-H, 5'-H), 6.99 (d, ³J 7.2 Hz, 1H; 6'-H), 5.60 (t, ³J 3.6 Hz, 1H; 7-H),

3.85 (s, 3H; OCH₃), 3.11 3.01 (m, 1H; 5-H), 2.64 (dd, ³J 8.1, ³J 3.6 Hz,

2H; 6-H), 2.38 (dd, ²J 12.8, ³J 12.0 Hz, 1H; 4-H), 2.34 (s, 3H; Ar-CH₃),

1.60 (dd, ²J 12.8, ³J 2.9 Hz, 1H; 4-H), 0.70 0.50 (m, 3H; cPr-H), 0.42

0.23 (m, 1H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 176.1

(C_quat, CO), 142.3 (C_quat, Ar-C*), 139.3 (C_quat, Ar-C*), 136.9 (C_quat, C-8*),

129.4 (, Ar-C), 129.3 (, Ar-C), 126.9 (, Ar-C), 124.8 (, Ar-C), 123.0

(, C-7), 51.7 (, OCH₃), 39.4 (, C-5), 37.0 (À, C-6), 28.4 (À, C-4), 20.0

(C_quat, C-3), 19.6 (, Ar-CH₃), 12.7 (À, cPr-C), 11.5 (À, cPr-C); syn-34aa

OCH₃), 173.8 (C_quat, CO), 167.8 (C_quat, C-3''), 148.6 (C_quat, C-8), 141.4 (C_quat

,

C-1''), 136.1 (C_quat, C-1'), 134.4 (, C-4''), 129.2 (, C-2', C-6'), 128.8 (,

C-2''), 126.9 (, C-3', C-5'), 124.8 (, C-6''), 123.2 (, C-4'), 121.6 (, C-7);

MS (70 eV): m/z (%): 363 (9) [M ], 304 (17) [M À CO₂Me], 149 (100)

[M À C₆H₅À C₆H₄NO₂À CH₃], 113 (19); elemental analysis calcd (%) for

C₂₂H₂₁NO₄(363.4): C 72.71, H 5.82, N 3.85; found: C 72.82, H 5.95, N 3.91.

Methyl 4-(2-nitrophenyl)-8-phenylspiro[2.5]oct-7-ene-5-carboxylate (o-31)

and methyl 5-(2-nitrophenyl)-8-phenylspiro[2.5]oct-7-ene-4-carboxylate

(o-32): According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol,

5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%), bicyclopro-

pylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl

(166 mg, 1.00 mmol) and iodobenzene (2-Ph, 204 mg, 1.00 mmol) were

stirred in anhydrous acetonitrile (1 mL) with methyl 3-(2-nitrophenyl)a-

crylate (o-30, 414 mg, 2.00 mmol) for 96 h at 808C. After work-up,

chromatography of the crude product on 25 g silica gel (column 2 Â

20 cm, pentane/diethyl ether 10:1) gave:

and anti-34aa: IR (film): nÄ 3081, 2997, 2949, 2850, 1736 (C O), 1645

(C C), 1489, 1436, 1378, 1259, 1193, 1170, 1025, 760, 731 cm^À1; MS (70 eV):

m/z (%): 256 (40) [M ], 225 (8) [M À OCH₃], 197 (80) [M À CO₂Me],

181 (100) [M À CH₃À CH₄O À CO], 169 (40), 155 (24), 91 (8) [C₇H₇];

elemental analysis calcd (%) for C₁₇H₂₀O₂(256.3): C 79.65, H 7.86; found: C

79.84, H 7.75.

tert-Butyl syn-8-(2-methylphenyl)spiro[2.5]oct-7-ene-5-carboxylate (syn-

34ea) and tert-butyl anti-8-(2-methylphenyl)spiro[2.5]oct-7-ene-5-carbox-

ylate (syn-34ea): According to GP 5, palladium(ii) acetate (11.2 mg,

49.9 mmol, 5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%),

bicyclopropylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol),

Et₄NCl (166 mg, 1.00 mmol) and ortho-iodotoluene (33a, 218 mg,

1.00 mmol) were stirred in anhydrous acetonitrile (1 mL) with tert-butyl

acrylate (17e, 256 mg, 2.00 mmol) for 48 h at 808C. After work-up,

chromatography of the crude product on 25 g silica gel (column 2 Â

20 cm, pentane/diethyl ether 20:1) yielded a mixture of two rotamers

syn-34ea and anti-34ea (1:3.0, ¹H NMR) as a yellowish oil (227 mg, 76%).

R_f 0.54 (pentane/diethyl ether 20:1). syn-34ea: ¹H NMR (250 MHz,

CDCl₃): d 7.12 7.07 (m, 3H; 3'-H, 4'-H, 5'-H), 6.92 (d, ³J 7.1 Hz, 1H; 6'-

Fraction I: 29 as a yellowish oil (83 mg, 27%); R_f 0.86 (pentane/diethyl

ether 10:1).

Fraction II: An unseparable mixture of o-31 and o-32 (3:2, ¹H NMR) as a

yellowish oil (92 mg, 25%). R_f 0.31 (pentane/diethyl ether 10:1); o-32:

¹H NMR (250 MHz, CDCl₃): d 7.75 (d, ³J 8.1 Hz, 1H; 3''-H), 7.65 7.52

(m, 2H; 4''-H, 5''-H), 7.41 (d, ³J 8.0 Hz, 1H; 6''-H), 7.32 7.21 (m, 3H; 3'-

H, 4'-H, 5'-H), 7.14 7.10 (m, 2H; 2'-H, 6'-H), 5.69 (dd, ³J 4.2, ³J 3.4 Hz,

1H; 7-H), 4.01 (ddd, ³J 7.9, ³J 7.1, ³J 5.8 Hz, 1H; 5-H), 3.06 (d, ³J

7.9 Hz, 1H; 4-H), 3.51 (s, 3H; OCH₃), 2.87 (ddd, ²J 18.3, ³J 5.8, ³J

4.2 Hz, 1H; 6-H), 2.43 (ddd, ²J 18.3, ³J 7.1, ³J 3.4 Hz, 1H; 6-H), 0.75

0.27 (m, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 172.6

(C_quat, CO), 142.6 (C_quat, C-2''), 139.7 (C_quat, Ar-C*), 138.9 (C_quat, C-8*),

136.9 (C_quat, Ar-C*), 132.4 (, Ar-C), 129.2 (, Ar-C), 128.8 (, Ar-C),

127.5 (, Ar-C), 127.2 (, Ar-C), 126.8 (, Ar-C), 124.4 (, C-4'), 123.9

(, C-7), 52.8 (, C-5), 51.6 (, OCH₃), 36.3 (, C-4), 31.7 (À, C-6), 20.6

(C_quat, C-3), 11.0 (À, cPr-C), 9.5 (À, cPr-C); o-31: ¹H NMR (250 MHz,

CDCl₃): d 7.95 (d, ³J 7.9 Hz, 1H; 3''-H), 7.80 (d, ³J 8.1 Hz, 1H; 6''-H),

7.65 7.52 (m, 2H; 4''-H, 5''-H), 7.32 7.21 (m, 3H; 3'-H, 4'-H, 5'-H), 7.14

3

H), 5.48 (t, J 3.7 Hz, 1H; 7-H), 2.89 2.77 (m, 1H; 5-H), 2.46 (dd, ³J

7.6, ³J 3.7 Hz, 2H; 6-H), 2.22 (s, 3H; Ar-CH₃), 2.12 (dd, ²J 13.1, ³J

10.9 Hz, 1H; 4-H), 1.64 (dd, ²J 13.1, ³J 3.0 Hz, 1H; 4-H), 1.49 [s, 9H;

C(CH₃)₃], 0.55 0.37 (m, 3H; cPr-H), 0.26 0.20 (m, 1H; cPr-H); ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): d 174.9 (C_quat, CO), 141.1 (C_quat, Ar-C*),

139.4 (C_quat, Ar-C*), 136.9 (C_quat, C-8*), 130.2 (, Ar-C), 129.5 (, Ar-C),

126.6 (, Ar-C), 124.5 (, Ar-C), 123.8 (, C-7), 79.9 [C_quat, C(CH₃)₃], 40.4

(, C-5), 37.2 (À, C-6), 28.3 (À, C-4), 28.1 [, C(CH₃)₃], 19.9 (C_quat, C-3),

19.5 (, Ar-CH₃), 12.4 (À, cPr-C), 11.7 (À, cPr-C); anti-34ea: ¹H NMR

(250 MHz, CDCl₃): d 7.12 7.07 (m, 3H; 3'-H, 4'-H, 5'-H), 6.86 (d, ³J

3

7.11 (m, 2H; 2'-H, 6'-H), 5.69 (dd, ³J 4.2, J 3.4 Hz, 1H; 7-H), 3.71 (s,

3H; OCH₃), 3.70 (d, ³J 9.3 Hz, 1H; 4-H), 3.16 (ddd, ³J 9.3, ³J 5.6, ³J

2

3

4.6 Hz, 1H; 5-H), 2.68 (ddd, J 18.0, J 4.6, J 4.2 Hz, 1H; 6-H), 2.16

2

3

(ddd, J 18.0, J 5.6, J 3.4 Hz, 1H; 6-H), 0.75 0.27 (m, 4H; cPr-H);

7.1 Hz, 1H; 6'-H), 5.47 (t, J 3.7 Hz, 1H; 7-H), 2.89 2.77 (m, 1H; 5-H),

¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 173.6 (C_quat, CO), 150.1 (C_quat

,

2.46 (dd, ³J 7.6, ³J 3.7 Hz, 2H; 6-H), 2.23 (dd, ²J 13.0, ³J 12.0 Hz,

2

C-2''), 142.6 (C_quat, Ar-C*), 139.7 (C_quat, Ar-C*), 136.9 (C_quat, C-8*), 132.4

(, Ar-C), 130.0 (, Ar-C), 129.2 (, Ar-C), 127.6 (, Ar-C), 127.5 (, Ar-

C), 126.9 (, Ar-C), 124.8 (, C-4'), 124.2 (, C-7), 51.7 (, OCH₃), 44.3

(, C-5), 43.8 (, C-4), 24.3 (À, C-6), 21.7 (C_quat, C-3), 14.5 (À, cPr-C), 9.8

1H; 4-H), 2.21 (s, 3H; Ar-CH₃), 1.48 [s, 9H; C(CH₃)₃], 1.43 (dd, J 13.0,

³J 2.8 Hz, 1H; 4-H), 0.55 0.37 (m, 3H; cPr-H), 0.26 0.20 (m, 1H; cPr-

H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 175.0 (C_quat, CO), 142.2

(C_quat, Ar-C*), 139.4 (C_quat, Ar-C*), 136.9 (C_quat, C-8*), 129.4 (, Ar-C),

129.2 (, Ar-C), 126.8 (, Ar-C), 124.8 (, Ar-C), 123.2 (, C-7), 79.9

[C_quat, C(CH₃)₃], 40.5 (, C-5), 36.9 (À, C-6), 28.6 (À, C-4), 28.0 [,

C(CH₃)₃], 20.0 (C_quat, C-3), 19.6 (, Ar-CH₃), 12.6 (À, cPr-C), 11.5 (À, cPr-

(À, cPr-C); o-31 and o-32: IR (film): nÄ 3039, 2956, 2930, 1735 (C O),

1648 (C C), 1531, 1435, 1347, 1260, 1201, 1173, 1075, 1028, 801 cm^À1; MS

(70 eV): m/z (%): 363 (1) [M ], 348 (2) [M À CH₃], 332 (5) [M À OCH₃],

328 (84), 286 (82) [M À OCH₃À NO₂], 268 (100), 254 (42), 115 (42), 91

C); syn-34ea and anti-34ea: IR (film): nÄ 3081, 2977, 2929, 1727 (C O),

1652 (C C), 1486, 1456, 1366, 1258, 1152, 1023, 761, 730 cm^À1; MS (70 eV);

(32) [C₇H₇].

Chem. Eur. J. 2002, 8, No. 10

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2363 $ 20.00+.50/0

2363

A. de Meijere et al.

FULL PAPER

m/z (%): 298 (3) [M ], 242 (100) [M À C₄H₈], 225 (17) [M À OtBu], 197

d_A 3.98, d_B 3.88, ²J 15.3 Hz, 2H; benzyl-CH₂), 2.82 2.77 (m, 1H;

2

3

(39) [M À CO₂tBu], 181 (80), 169 (20), 145 (24); elemental analysis calcd

5-H), 2.45 2.35 (m, 2H; 6-H), 2.24 (dd, J 12.6, J 12.1 Hz, 1H; 4-H),

1.49 [s, 9H; C(CH₃)₃], 1.42 (dd, ²J 12.6, ³J 2.2 Hz, 1H; 4-H), 0.62 0.31

(%) for C₂₀H₂₆O₂(298.4): C 80.50, H 8.78; found: C 80.26, H 8.54.

(m, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 175.0 (C_quat

,

Methyl syn-8-(2-benzylphenyl)spiro[2.5]oct-7-ene-5-carboxylate (syn-

34ab) and methyl anti-8-(2-benzylphenyl)spiro[2.5]oct-7-ene-5-carboxy-

late (anti-34ab): According to GP 5, palladium(ii) acetate (11.2 mg,

49.9 mmol, 5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%),

bicyclopropylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol),

Et₄NCl (166 mg, 1.00 mmol) and ortho-benzyliodobenzene (33b, 294 mg,

1.00 mmol) were stirred in anhydrous acetonitrile (1 mL) with methyl

acrylate (17a, 172 mg, 2.00 mmol) for 48 h at 808C. After work-up,

chromatography of the crude product on 25 g silica gel (column 2 Â 20 cm,

pentane/diethyl), ether 10:1) gave:

CO), 141.4 (C_quat, Ar-C*), 141.3 (C_quat, Ar-C*), 139.9 (C_quat, Ar-C*), 139.2

(C_quat, C-8*), 129.7 (, Ar-C), 129.2 (, Ar-C), 129.1 (, Ar-C), 128.2 (,

Ar-C), 127.1 (, Ar-C), 125.8 (, Ar-C), 125.3 (, Ar-C), 124.6 (, C-7),

80.0 [C_quat, C(CH₃)₃], 40.4 (, C-5), 39.1 (À, benzyl-CH₂), 37.0 (À, C-6),

28.6 (À, C-4), 28.1 [, C(CH₃)₃], 20.4 (C_quat, C-3), 12.7 (À, cPr-C), 11.4 (À,

cPr-C); syn-34eb and anti-34eb: IR (film): nÄ 3062, 3025, 3001, 2976, 2929,

1727 (C O), 1636 (C C), 1453, 1367, 1258, 1153, 738 cm^À1; MS (70 eV): m/z

(%): 374 (1) [M ], 318 (42) [M À C₄H₈], 301 (4) [M À OC₄H₉], 289 (16),

257 (18), 181 (100) [M À HOC₄H₉À CO À C₇H₇], 165 (43), 91 (70)

[C₇H₇]; elemental analysis calcd (%) for C₂₆H₃₀O₂(374.5): C 83.38, H

Fraction I: A mixture of polymers and 18a-H (53 mg). R_f 0.57 (pentane/

8.07; found: C 83.65, H 8.27.

diethyl), ether 10:1).

Methyl syn-8-(2,4-dimethylphenyl)spiro[2.5]oct-7-ene-5-carboxylate (syn-

34ac) and methyl anti-8-(2,4-dimethylphenyl)spiro[2.5]oct-7-ene-5-car-

boxylate (anti-34ac): According to GP 5, palladium(ii) acetate (11.2 mg,

49.9 mmol, 5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%),

bicyclopropylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol),

Et₄NCl (166 mg, 1.00 mmol) and 2,4-dimethyliodobenzene (33c, 232 mg,

1.00 mmol) were stirred in anhydrous acetonitrile (1 mL) with methyl

acrylate (17a, 172 mg, 2.00 mmol) for 48 h at 808C. After work-up,

chromatography of the crude product on 25 g silica gel (column 2 Â 20 cm,

pentane/diethyl ether 10:1) gave a mixture of two rotamers syn-34ac and

anti-34ac (1:2.5, ¹H NMR) as a yellowish oil (265 mg, 98%). R_f 0.48

(pentane/diethyl ether 10:1); syn-34ac: ¹H NMR (250 MHz, CDCl₃): d

6.98 (s, 1H; 3'-H), 6.92 6.77 (m, 2H; 5'-H, 6'-H), 5.49 (t, ³J 3.7 Hz, 1H;

Fraction II: A mixture of two rotamers syn-34ab and anti-34ab (1:2.0,

¹H NMR) as a yellowish oil (282 mg, 85%); R_f 0.43 (pentane/diethyl

ether 10:1); syn-34ab: ¹H NMR (250 MHz, CDCl₃): d 7.32 7.07 (m, 8H;

Ar-H), 7.00 (dd, ³J 6.9, ⁴J 1.9 Hz, 1H; 6'-H), 5.42 (t, ³J 3.7 Hz, 1H;

7-H), 4.05 3.88 (AB system: d_A 4.01, d_B 3.91, ²J 15.3 Hz, 2H; benzyl-

CH₂), 3.73 (s, 3H; OCH₃), 3.02 2.90 (m, 1H; 5-H), 2.50 2.43 (m, 2H;

6-H), 2.15 (dd, ²J 12.9, ³J 10.1 Hz, 1H; 4-H), 1.75 (dd, ²J 12.9, ³J

2.4 Hz, 1H; 4-H), 0.63 0.31 (m, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): d 175.6 (C_quat, CO), 141.6 (C_quat, Ar-C*), 140.2 (C_quat, Ar-C*),

139.2 (C_quat, Ar-C*), 138.7 (C_quat, C-8*), 130.4 (, Ar-C), 129.2 (, Ar-C),

129.0 (, Ar-C), 128.9 (, Ar-C), 128.1 (, Ar-C), 126.9 (, Ar-C), 125.1

(, Ar-C), 124.7 (, C-7), 51.5 (, OCH₃), 39.1 (, C-5), 38.8 (À, benzyl-

CH₂), 37.2 (À, C-6), 28.0 (À, C-4), 19.9 (C_quat, C-3), 12.1 (À, cPr-C), 11.4

(À, cPr-C); anti-34ab: ¹H NMR (250 MHz, CDCl₃): d 7.32 7.07 (m, 8H;

Ar-H), 6.92 (dd, ³J 6.9, ⁴J 1.7 Hz, 1H; 6'-H), 5.41 (t, ³J 3.6 Hz, 1H;

7-H), 4.02 3.85 (AB system: d_A 3.98, d_B 3.89, ²J 15.3 Hz, 2H; benzyl-

CH₂), 3.72 (s, 3H; OCH₃), 3.02 2.90 (m, 1H; 5-H), 2.50 2.43 (m, 2H;

6-H), 2.29 (dd, ²J 12.9, ³J 12.0 Hz, 1H; 4-H), 1.50 (dd, ²J 12.9, ³J

2.4 Hz, 1H; 4-H), 0.63 0.31 (m, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): d 175.9 (C_quat, CO), 141.3 (C_quat, Ar-C*), 141.2 (C_quat, Ar-C*),

139.8 (C_quat, Ar-C*), 138.7 (C_quat, C-8*), 129.6 (, Ar-C), 129.0 (, Ar-C),

128.2 (, Ar-C), 128.1 (, Ar-C), 127.1 (, Ar-C), 125.7 (, Ar-C), 125.3

(, Ar-C), 124.3 (, C-7), 51.6 (, OCH₃), 39.3 (, C-5), 39.1 (À, benzyl-

CH₂), 37.0 (À, C-6), 28.3 (À, C-4), 20.3 (C_quat, C-3), 12.6 (À cPr-C), 11.3 (À,

cPr-C); syn-34ab and anti-34ab: IR (film): nÄ 3061, 3024, 3004, 2948, 2928,

3

7-H), 3.74 (s, 3H; OCH₃), 3.01 2.89 (m, 1H; 5-H), 2.53 (dd, J 8.3, J

3.7 Hz, 2H; 6-H), 2.32 (s, 3H; 4'-CH₃), 2.22 (s, 3H; 2'-CH₃), 2.32 2.18 (m,

1H; 4-H), 1.82 (dd, ²J 13.0, ³J 3.2 Hz, 1H; 4-H), 0.60 0.30 (m, 4H; cPr-

H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 175.5 (C_quat, CO), 140.9

(C_quat, Ar-C*), 136.4 (C_quat, Ar-C*), 136.1 (C_quat, Ar-C*), 135.8 (C_quat, C-8*),

130.1 (, Ar-C), 129.1 (, Ar-C), 125.2 (, Ar-C), 123.4 (, C-7), 51.3 (,

OCH₃), 39.1 (, C-5), 37.1 (À, C-6), 28.0 (À, C-4), 20.8 (, 4'-CH₃), 19.7

(C_quat, C-3), 19.3 (, 2'-CH₃), 12.3 (À, cPr-C), 11.4 (À, cPr-C); anti-34ac:

¹H NMR (250 MHz, CDCl₃): d 6.98 (s, 1H; 3'-H), 6.92 6.77 (m, 2H; 5'-

H, 6'-H), 5.49 (t, ³J 3.7 Hz, 1H; 7-H), 3.74 (s, 3H; OCH₃), 3.01 2.89 (m,

1H; 5-H), 2.53 (dd, ³J 8.3, ³J 3.7 Hz, 2H; 6-H), 2.32 (s, 3H; 4'-H), 2.21

(s, 3H; 2'-CH₃), 2.32 2.18 (m, 1H; 4-H), 1.52 (dd, ²J 12.8, ³J 2.9 Hz,

1H; 4-H), 0.60 0.30 (m, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): d 175.7 (C_quat, CO), 142.1 (C_quat, Ar-C*), 136.4 (C_quat, Ar-C*),

136.1 (C_quat, Ar-C*), 135.9 (C_quat, C-8*), 129.9 (, Ar-C), 129.1 (, Ar-C),

125.3 (, Ar-C), 122.9 (, C-7), 51.3 (, OCH₃), 39.3 (, C-5), 36.9 (À,

C-6), 28.3 (À, C-4), 20.8 (, 4'-CH₃), 19.9 (C_quat, C-3), 19.3 (, 2'-CH₃),

12.5 (À, cPr-C), 11.4 (À, cPr-C); syn-34ac and anti-34ac: IR (film): nÄ

2842, 1735 (C O), 1610 (C C), 1495, 1436, 1377, 1259, 1172, 1029, 762,

699 cm^À1; MS (70 eV): m/z (%): 332 (27) [M ], 304 (8) [M À C₂H₄], 301

(2) [M À OCH₃], 272 (11) [M À MeOH À CO], 205 (38), 181 (100)

[M À MeOH À CO À C₇H₇], 165 (43) [M À C₇H₇À C₆H₄], 129 (26), 91

(70) [C₇H₇]; elemental analysis calcd (%) for C₂₃H₂₄O₂(332.4): C 83.10, H

7.28; found: C 82.90, H 7.56.

3078, 2997, 2949, 2920, 2852, 1737 (C O), 1646 (C C), 1613, 1435, 1377,

tert-Butyl syn-8-(2-benzylphenyl)spiro[2.5]oct-7-ene-5-carboxylate (syn-

34eb) and tert-butyl anti-8-(2-benzylphenyl)spiro[2.5]oct-7-ene-5-carbox-

ylate (anti-34eb): According to GP 5, palladium(ii) acetate (11.2 mg,

49.9 mmol, 5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%),

bicyclopropylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol),

Et₄NCl (166 mg, 1.00 mmol) and ortho-benzyliodobenzene (32b, 294 mg,

1.00 mmol) were stirred in anhydrous acetonitrile (1 mL) with tert-butyl

acrylate (17e, 256 mg, 2.00 mmol) for 48 h at 808C. After work-up,

chromatography of the crude product on 25 g silica gel (column 2 Â

20 cm, pentane/diethyl ether 20:1) yielded a mixture of two rotamers

syn-34eb and anti-34eb (1:3.0, ¹H NMR) as a yellowish oil (146 mg, 39%).

R_f 0.48 (pentane/diethyl ether 20:1); syn-34eb: ¹H NMR (250 MHz,

CDCl₃): d 7.31 7.06 (m, 8H; Ar-H), 6.99 (dd, ³J 6.4, ⁴J 2.6 Hz, 1H; 6'-

H), 5.44 5.39 (m, 1H; 7-H), 4.04 3.86 (AB system: d_A 4.01, d_B 3.90,

²J 15.4 Hz, 2H; benzyl-CH₂), 2.82 2.77 (m, 1H; 5-H), 2.45 2.35 (m, 2H;

6-H), 2.24 (dd, ²J 12.8, ³J 12.1 Hz, 1H; 4-H), 1.68 (dd, ²J 12.8, ³J

3.1 Hz, 1H; 4-H), 1.50 [s, 9H; C(CH₃)₃], 0.62 0.31 (m, 4H; cPr-H);

1316, 1259, 1193, 1170, 1025, 820 cm^À1; MS (70 eV): m/z (%): 270 (35) [M ],

239 (5) [M À OCH₃], 211 (36) [M À OCH₃À CO], 195 (100) [M

À

HOCH₃À CO À CH₃], 165 (15) [M À C₈H₉], 91 (8) [C₇H₇]; elemental

analysis calcd (%) for C₁₈H₂₂O₂(270.4): C 79.96, H 8.20; found: C 79.76, H

8.14.

tert-Butyl

syn-8-(2,4-dimethylphenyl)spiro[2.5]oct-7-ene-5-carboxylate

(syn-34ec) and tert-butyl anti-8-(2,4-dimethylphenyl)spiro[2.5]oct-7-ene-

5-carboxylate (anti-34ec): According to GP 5, palladium(ii) acetate

(11.2 mg, 49.9 mmol, 5 mol%), triphenylphosphane (39.3 mg, 150 mmol,

15 mol%), bicyclopropylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg,

2.00 mmol), Et₄NCl (166 mg, 1.00 mmol) and 2,4-dimethyliodobenzene

(33c, 232 mg, 1.00 mmol) were stirred in anhydrous acetonitrile (1 mL)

with tert-butyl acrylate (17e, 256 mg, 2.00 mmol) for 48 h at 808C. After

work-up, chromatography of the crude product on 25 g silica gel (column

2 Â 20 cm, pentane/diethyl ether 20:1) yielded a mixture of two rotamers

1

syn-34ec and anti-34ec (1:2.7, H NMR) as a yellowish oil (51 mg, 16%).

¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 174.7 (C_quat, CO), 141.7 (C_quat

,

R_f 0.62 (pentane/diethyl ether 20:1); syn-34ec: ¹H NMR (250 MHz,

3

Ar-C*), 140.2 (C_quat, Ar-C*), 139.3 (C_quat, Ar-C*), 138.9 (C_quat, C-8*), 130.5

(, Ar-C), 129.5 (, Ar-C), 129.2 (, Ar-C), 129.0 (, Ar-C), 128.2 (, Ar-

C), 126.9 (, Ar-C), 125.1 (, Ar-C), 124.9 (, C-7), 80.0 [C_quat, C(CH₃)₃],

40.3 (, C-5), 38.8 (À, benzyl-CH₂), 37.3 (À, C-6), 28.3 (À, C-4), 28.1 [,

C(CH₃)₃], 20.1 (C_quat, C-3), 12.2 (À, cPr-C), 11.7 (À, cPr-C); anti-34eb:

CDCl₃): d 7.12 7.06 (m, 2H; 3'-H, 5'-H), 6.93 (d, J 7.1 Hz, 1H; 6'-H),

5.48 (t, ³J 3.6 Hz, 1H; 7-H), 2.87 2.79 (m, 1H; 5-H), 2.45 (dd, ³J 7.7,

³J 3.6 Hz, 2H; 6-H), 2.22 (brs, 3H; 2'-CH₃), 2.16 (brs, 3H; 4'-CH₃), 2.11

(dd, ²J 13.0, ³J 10.9 Hz, 1H; 4-H), 1.64 (dd, ²J 13.0, ³J 3.0 Hz, 1H;

4-H), 1.44 [brs, 9H; C(CH₃)₃], 0.57 0.37 (m, 3H; cPr-H), 0.26 0.20 (m,

1H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 174.9 (C_quat, CO),

3

¹H NMR (250 MHz, CDCl₃): d 7.31 7.07 (m, 8H; Ar-H), 6.90 (dd, J

7.0, ⁴J 1.7 Hz, 1H; 6'-H), 5.44 5.39 (m, 1H; 7-H), 4.01 3.84 (AB system:

142.0 (C_quat, Ar-C*), 136.4 (C_quat, Ar-C*), 136.2 (C_quat, C-8*), 131.5 (C_quat,

2364

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2364 $ 20.00+.50/0

Chem. Eur. J. 2002, 8, No. 10

Domino Heck Diels Alder Reactions

2350 2369

Ar-C), 130.2 (, Ar-C), 129.2 (, Ar-C), 125.2 (, Ar-C), 123.8 (, C-7),

79.9 [C_quat, C(CH₃)₃], 40.4 (, C-5), 37.2 (À, C-6), 28.4 (À, C-4), 28.1 [,

C(CH₃)₃], 20.9 (, 4'-CH₃), 19.9 (C_quat, C-3), 19.4 (, 2'-CH₃), 12.5 (À, cPr-

C), 11.5 (À, cPr-C); anti-34ec: ¹H NMR (250 MHz, CDCl₃): d 7.12 7.06

(m, 2H; 3'-H, 5'-H), 6.86 (d, ³J 7.1 Hz, 1H; 6'-H), 5.47 (t, ³J 3.7 Hz, 1H;

7-H), 2.87 2.79 (m, 1H; 5-H), 2.46 (dd, ³J 7.6, ³J 3.7 Hz, 2H; 6-H), 2.23

(dd, ²J 13.0, ³J 12.0 Hz, 1H; 4-H), 2.21 (brs, 3H; 2'-CH₃), 2.17 (brs, 3H;

4'-CH₃), 1.48 [brs, 9H; C(CH₃)₃], 1.43 (dd, ²J 13.0, ³J 2.9 Hz, 1H; 4-H),

0.57 0.37 (m, 3H; cPr-H), 0.26 0.20 (m, 1H; cPr-H); ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): d 175.0 (C_quat, CO), 142.1 (C_quat, Ar-C*),

136.4 (C_quat, Ar-C*), 136.2 (C_quat, C-8*), 131.5 (C_quat, Ar-C), 130.0 (, Ar-

C), 129.2 (, Ar-C), 125.3 (, Ar-C), 123.2 (, C-7), 79.9 [C_quat, C(CH₃)₃],

40.4 (, C-5), 36.9 (À, C-6), 28.6 (À, C-4), 28.0 [, C(CH₃)₃], 20.9 (, 4'-

CH₃), 19.9 (C_quat, C-3), 19.4 (, 2'-CH₃), 12.6 (À, cPr-C), 11.5 (À, cPr-C);

(C_quat, C-8*), 141.1 (C_quat, Ar-C*), 129.3 (, Ar-C), 127.7 (, Ar-C), 127.4

(, Ar-C*), 126.4 (, C-7*), 51.8 (, OCH₃), 51.1 (, OCH₃), 38.4 (,

C-5), 37.3 (À, C-6), 29.3 (, C-1), 28.8 (C_quat, C-3), 27.1 (À, C-4), 17.9 (À,

cPr-C); isomer 2: ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 175.2 (C_quat

,

CO), 170.5 (C_quat, CO), 140.6 (C_quat, C-8*), 139.0 (C_quat, Ar-C*), 129.6 (,

Ar-C), 127.9 (, Ar-C), 127.3 (, Ar-C*), 126.3 (, C-7*), 51.6 (, OCH₃),

51.2 (, OCH₃), 39.2 (, C-5), 38.7 (À, C-6), 30.4 (, C-1), 30.1 (C_quat

,

1

C-3), 28.6 (À, C-4), 19.7 (À, cPr-C); isomer 1 and 2: H NMR (250 MHz,

CDCl₃): d 7.30 7.06 (m, 5H; Ar-H), 5.87 (dd, ³J 4.9, ³J 4.0 Hz, 1H;

7-H, isomer 1), 5.76 (dd, ³J 3.8, ³J 3.7 Hz, 1H; 7-H, isomer 2), 3.34 (s,

3H; OCH₃), 3.33 (s, 3H; OCH₃), 3.10 3.06 (m, 1H; 5-H, isomer 2), 2.88

2.80 (m, 1H; 1-H, isomer 1), 2.70 2.43 (m, 2H; 6-H), 2.32 2.16 (m, 1H;

cPr-H), 1.91 1.74 (m, 1H; 4-H), 1.68 1.60 (m, 1H; cPr-H), 1.44 1.14 (m,

2H; 4-H; cPr-H); MS (70 eV): m/z (%): 300 (14) [M ], 268 (13) [M

À

syn-34ec and anti-34ec: IR (film): nÄ 3079, 2976, 2924, 1729 (C O), 1635

MeOH], 240 (55) [M À MeOH À CO], 225 (1) [M À MeOH À CH₃À

(C C), 1456, 1366, 1260, 1151, 1023, 820, 736 cm^À1; MS (70 eV): m/z (%):

CO], 209 (19) [M À CO₂Me À MeOH], 181 (100) [M À CO₂Me À

312 (1) [M ], 255 (100) [M À C₄H₉], 239 (18) [M À OC₄H₉], 211 (29)

MeOH À CO], 167 (36), 91 (6) [C₇H₇], 59 (5) [CO₂Me ].

[M À OC₄H₉À CO], 195 (86) [M À HOC₄H₉À CO À CH₃], 169 (19), 91

Methyl 8-(4'-iodophenyl)spiro[2.5]oct-7-ene-5-carboxylate (18a-C₆H₄I)

and 1,4-bis[5'-methoxycarbonylspiro[2.5]oct-7'-ene-8'-yl]benzene (38a):

a) In a 25 mL Pyrex bottle, palladium(ii) acetate (22.4 mg, 100 mmol,

5 mol%), triphenylphosphane (78.6 mg, 300 mmol, 15 mol%), bicyclopro-

pylidene (1, 640 mg, 8.00 mmol), 1,4-diiodobenzene (37, 660 mg,

2.00 mmol) and triethylamine (810 mg, 8.00 mmol) in anhydrous DMF

(10 mL) were heated with methyl acrylate (17a, 689 mg, 8.00 mmol) for

21 h at 808C. After work-up, chromatography of the crude product on silica

gel (50 g, column 2 Â 20 cm, pentane/diethyl ether 5:1 ! diethyl ether) gave:

(9) [C₇H₇].

Methyl 8-(2,6-dimethylphenyl)spiro[2.5]oct-7-ene-5-carboxylate (34ad)

and 1-cyclopropylidene-1-(2,6-dimethylphenyl)-2-propene (5-2,6-Me₂Ph):

According to GP 5, palladium(ii) acetate (22.4 mg, 100 mmol, 5 mol%),

triphenylphosphane (78.7 mg, 300 mmol, 15 mol%), bicyclopropylidene (1,

320 mg, 4.00 mmol), K₂CO₃(553 mg, 4.00 mmol), Et₄NCl (331 mg,

2.00 mmol) and 2,6-dimethyliodobenzene (33d, 464 mg, 2.00 mmol) were

stirred in anhydrous acetonitrile (2 mL) with methyl acrylate (17a, 344 mg,

4.00 mmol) for 48 h at 808C. After work-up, chromatography of the crude

product on 25 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1)

gave:

Fraction I: 18a-C₆H₄I as a colorless oil (330 mg, 45%); R_f 0.45 (pentane/

diethyl ether 10:1); IR (film): nÄ 3079, 2949, 1734 (C O), 1653 (C C),

1635 (C C), 1478, 1434, 1169, 1007, 824 cm^À1; ¹H NMR (250 MHz, CDCl₃):

d 7.56 [d, ³J 8.2 Hz, 2H; 3'(5')-H], 6.77 [d, ³J 8.2 Hz, 2H; 2'(6')-H],

5.50 (t, ³J 3.8 Hz, 1H; 7-H), 3.69 (s, 3H; OCH₃), 2.87 (ddt, ³J 12.0, ³J

8.0, ³J 3.0 Hz, 1H; 5-H), 2.45 (dd, ³J 8.0, ³J 3.8 Hz, 2H; 6-H), 2.15 (dd,

²J 12.9, ³J 12.0 Hz, 1H; 4-H), 1.49 (dd, ²J 12.9, ³J 3.0 Hz, 1H; 4-H),

0.61 0.38 (m, 4H; cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 175.6

(C_quat, CO), 141.8 (C_quat, C-1'*), 139.6 (C_quat, C-8*), 136.5 [, C-2'(6')],

131.1 [, C-3'(5')], 124.3 (, C-7), 92.3 (C_quat, C-4'), 51.6 (, OCH₃), 39.1

(, C-5), 37.2 (À, C-6), 28.3 (À, C-4), 19.9 (C_quat, C-3), 12.7 (À, cPr-C), 11.4

Fraction I: 5-2,6-Me₂Ph as a clear oil (81 mg, 22%); R_f 0.91 (pentane/

diethyl ether 10:1); IR (film): nÄ 3060, 2959, 2930, 1680, 1640 (C C), 1455,

1379, 1035 cm^À1; ¹H NMR (250 MHz, C₆D₆): d 7.13 7.05 (m, 3H; Ar-H),

3

6.77 (dd, ³J 16.9, J 10.3 Hz, 1H; 2-H), 5.08 (d, J 10.3 Hz, 1H; 3-H),

4.65 (d, ³J 16.9 Hz, 1H; 3-H), 2.12 (s, 6H; Ar-CH₃), 1.36 1.02 (m, 4H;

cPr-H); ¹³C NMR (62.9 MHz, C₆D₆, DEPT): d 138.1 (C_quat, C-1), 136.9

(, C-2), 136.7 (C_quat, C-2', C-6'), 129.1 (C_quat, cPr-C), 126.8 (C_quat, C-1'),

126.7 (, C-3', C-5'), 126.7 (, C-4'), 113.1 (À, C-3), 19.7 (, 2 Ar-CH₃), 2.9

(À, cPr-C), 2.7 (À, cPr-C); MS (70 eV): m/z (%): 184 (4) [M ], 169 (56)

(À, cPr-C); MS (70 eV): m/z (%): 368 (40) [M ], 308 (21) [M À MeOH À

[M À CH₃], 154 (100) [M À 2CH₃], 143 (68), 128 (48), 91 (3) [C₇H₇].

Fraction II: 34ad as a yellowish oil (305 mg, 56%); R_f 0.56 (pentane/

CO], 181 (100) [M À MeOH À CO À I], 165 (19) [M À C₆H₄I], 154 (11),

141 (7), 128 (7), 115 (7); elemental analysis calcd (%) for C₁₆H₁₇IO₂(368.2):

C 52.19, H 4.65; found: C 52.31, H 4.83.

diethyl ether 10:1); IR (film): nÄ 3063, 2997, 2949, 2933, 2852, 1734 (C O),

À1

1640 (C C), 1577, 1435, 1376, 1310, 1258, 1170, 1025, 905, 771 cm

;

Fraction II: 38a as a yellowish oil (64 mg, 8%); R_f 0.32 (diethyl ether);

¹H NMR (250 MHz, CDCl₃): d 7.09 6.91 (m, 3H; Ar-H), 5.48 (t, ³J

3.9 Hz, 1H; 7-H), 3.74 (s, 3H; OCH₃), 2.97 (ddd, ³J 11.5, ³J 8.1, ³J

3.1 Hz, 1H; 5-H), 2.53 (dd, ³J 8.1, ³J 3.9 Hz, 2H; 6-H), 2.22 (s, 3H; Ar-

CH₃), 2.19 (s, 3H; Ar-CH₃), 2.22 (dd, ²J 13.0, ³J 11.5 Hz, 1H; 4-H), 1.61

IR (film): nÄ 2927, 1734 (C O), 1653 (C C), 1435, 1169, 1095, 745, 694,

526 cm^À1; ¹H NMR (500 MHz, CDCl₃): d 7.08 (s, 4H; Ar-H), 5.80 (t, ³J

4.0 Hz, 2H; 7'-H), 3.98 (s, 6H; OCH₃), 3.18 (ddd, ³J 11.0, ³J 9.0, ³J

3

2

3.5 Hz, 2H; 5'-H), 2.76 (dd, J 9.0, J 4.0 Hz, 4H; 6'-H), 2.47 (dd, J

13.0, ³J 11.0 Hz, 2H; 4'-H), 1.77 (dd, ²J 13.0, ³J 3.5 Hz, 2H; 4'-H), 0.90

(m, 2H; cPr-H), 0.81 (m, 2H; cPr-H), 0.75 (m, 2H; cPr-H), 0.72 0.68 (m,

2H; cPr-H); ¹³C NMR (125.7 MHz, CDCl₃, APT): d 176.0 (À, CO), 142.7

(À, Ar-C*), 138.5 (À, C-8'*), 128.3 (, Ar-C), 123.8 (, C-7'), 51.6 (,

OCH₃), 39.4 (, C-5'), 37.5 (À, C-6'), 28.5 (À, C-4'), 20.1 (À, C-3'), 12.9 (À,

(dd, ²J 13.0, J 3.1 Hz, 1H; 4-H), 0.60 0.35 (m, 4H; cPr-H); ¹³C NMR

3

(62.9 MHz, CDCl₃, DEPT): d 175.8 (C_quat, CO), 140.2 (C_quat, Ar-C*),

138.2 (C_quat, Ar-C*), 137.1 (C_quat, Ar-C*), 136.1 (C_quat, C-8*), 126.9 (, Ar-

C), 126.8 (, Ar-C), 126.5 (, Ar-C), 123.8 (, C-7), 51.5 (, OCH₃), 39.4

(, C-5), 37.3 (À, C-6), 28.4 (À, C-4), 20.01 (, Ar-CH₃), 19.98 (C_quat, C-3),

19.9 (, Ar-CH₃), 13.3 (À, cPr-C), 12.3 (À, cPr-C); MS (70 eV): m/z (%):

cPr-C), 11.6 (À, cPr-C); MS (70 eV): m/z (%): 406 (31) [M ], 183 (100)

270 (47) [M ], 255 (5) [M À CH₃], 239 (3) [M À OCH₃], 211 (42) [M

À

[C₁₄H₁₅], 152 (6), 108 (14), 84 (14), 77 (6); elemental analysis calcd (%) for

CO₂Me], 195 (100) [M À MeOH À CO À CH₃], 165 (20) [M À C₈H₉];

elemental analysis calcd (%) for C₁₈H₂₂O₂(270.4): C 79.96, H 8.20; found:

C 79.66, H 8.28.

C₂₆H₃₀O₄(406.5): C 76.82, H 7.44; found: C 76.65, H 7.43.

b) According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol, 5 mol%),

triphenylphosphane (39.3 mg, 150 mmol, 15 mol%), bicyclopropylidene (1,

160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg,

1.00 mmol) and 1,4-diiodobenzene (37, 166 mg, 0.500 mmol) were stirred

in anhydrous acetonitrile (1 mL) with methyl acrylate (17a, 172 mg,

2.00 mmol) for 48 h at 808C. After work-up, chromatography of the crude

product on 50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 2:1)

yielded 38a as colorless crystals (130 mg, 64%).

Dimethyl 8-phenylspiro[2.5]oct-7-ene-1,5-dicarboxylate (36a): According

to GP 5, palladium(ii) acetate (22.4 mg, 100 mmol, 5 mol%), triphenyl-

phosphane (52.4 mg, 200 mmol, 10 mol%), methyl bicyclopropylidenecar-

boxylate (35a, 345 mg, 2.50 mmol), K₂CO₃(415 mg, 3.00 mmol), Et₄NCl

(331 mg, 2.00 mmol) and iodobenzene (2-Ph, 408 mg, 2.00 mmol) were

stirred in anhydrous acetonitrile (1 mL) with methyl acrylate (17a, 258 mg,

3.00 mmol) for 24 h at 808C. After work-up, chromatography of the crude

product on 25 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 2:1)

gave:

c) According to GP 6, 1,4-diiodobenzene (37, 330 mg, 1.00 mmol), bicyclo-

propylidene (1, 320 mg, 4.00 mmol), methyl acrylate (17a, 344 mg,

4.00 mmol), palladium(ii) acetate (11.2 mg, 49.9 mmol), triphenylphosphane

(39.3 mg, 150 mmol) and triethylamine (404 mg, 2.00 mmol) were heated in

anhydrous DMF (5 mL) at 808C for 24 h under a pressure of 10 kbar. After

work-up, chromatography of the crude product on silica gel (column 2 Â

20 cm, pentane/diethyl ether 2:1) gave 38a as colorless crystals (354 mg,

87%). R_f 0.72 (pentane/diethyl ether 2:1); m.p. 1248C.

Fraction I: A mixture of polymers (40 mg), R_f 0.82 (pentane/diethyl ether

2:1).

1

Fraction II: 36a as a mixture of two isomers (5:4, H NMR); yellowish oil

(216 mg, 36%); R_f 0.46 (pentane/diethyl ether 2:1); isomer 1: ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): d 175.1 (C_quat, CO), 170.5 (C_quat, CO), 141.3

Chem. Eur. J. 2002, 8, No. 10

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2365 $ 20.00+.50/0

2365

A. de Meijere et al.

FULL PAPER

tert-Butyl 8-(4'-iodophenyl)spiro[2.5]oct-7-ene-5-carboxylate (18e-C₆H₄I)

and 1,4-bis[5'-tert-butoxycarbonylspiro[2.5]oct-7'-ene-8'-yl]benzene (38e):

a) In a 25 mL Pyrex-bottle, palladium(ii) acetate (22.4 mg, 100 mmol,

5 mol%), triphenylphosphane (78.6 mg, 300 mmol, 15 mol%), bicyclopro-

pylidene (1, 640 mg, 8.00 mmol), 1,4-diiodobenzene (37, 660 mg,

2.00 mmol) and triethylamine (810 mg, 8.00 mmol) in anhydrous DMF

(10 mL) were heated with tert-butyl acrylate (17e, 1.03 g, 8.04 mmol) for

3 d at 808C. After work-up, chromatography of the crude product on 50 g

silica gel (column 2 Â 20 cm, pentane/diethyl ether 10:1 ! 2:1) gave:

(62.9 MHz, CDCl₃, DEPT): d 174.5 (C_quat, CO), 173.3 (C_quat, CO),

141.6 (C_quat, Ar-C*), 138.1 (C_quat, C-8'*), 128.3 (, Ar-C), 123.5 (, C-7'),

51.9 (, OCH₃), 51.8 (, OCH₃), 49.3 (, C-5'), 41.4 (, C-4'), 26.3 (À,

C-6'), 20.0 (C_quat, C-3'), 11.0 (À, cPr-C), 10.3 (À, cPr-C); MS (70 eV): m/z

(%): 522 (46) [M ], 491 (24) [M À OCH₃], 463 (50) [M À CO₂CH₃], 431

(43) [M À CO₂CH₃À MeOH], 403 (100) [M À CO₂CH₃À MeOH À CO],

371 (20), 343 (63) [M À CO₂CH₃À 2MeOH À 2CO], 283 (38); elemental

analysis calcd (%) for C₃₀H₃₄O₈(522.6): C 68.95, H 6.56; found: C 69.10, H

6.64.

b) According to GP 6, 1,4-diiodobenzene (37, 330 mg, 1.00 mmol), bicyclo-

propylidene (1, 320 mg, 4.00 mmol), dimethyl fumarate (17 f, 576 mg,

4.00 mmol), palladium(ii) acetate (11.2 mg, 49.9 mmol), triphenylphosphane

(39.3 mg, 150 mmol) and triethylamine (404 mg, 4.00 mmol) were heated in

anhydrous DMF (5 mL) at 808C for 24 h under a pressure of 10 kbar. After

work-up, chromatography of the crude product on silica gel (column 2 Â

20 cm, pentane/diethyl ether 1:1) gave 38 f as colorless crystals (314 mg,

60%). R_f 0.44 (pentane/diethyl ether 1:1); m.p. 1378C.

1,3,5-Tris(5'-methoxycarbonylspiro[2.5]oct-7'-en-8'-yl)benzene (40a): Ac-

cording to GP 5, palladium(ii) acetate (33.7 mg, 150 mmol, 30 mol%),

triphenylphosphane (78.7 mg, 300 mmol, 60 mol%), bicyclopropylidene (1,

480 mg, 6.00 mmol), K₂CO₃(829 mg, 6.00 mmol), Et₄NCl (497 g,

3.00 mmol) and 1,3,5-triiodobenzene (39, 228 mg, 0.50 mmol) were stirred

in anhydrous acetonitrile (1 mL) with methyl acrylate (17a, 517 mg,

6.00 mmol) for 48 h at 808C. After work-up, chromatography of the crude

product on 25 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 2:1) gave:

Fraction I: 18e-C₆H₄I as a yellowish oil (410 mg, 50%); R_f 0.62 (pentane/

diethyl ether 2:1); IR (film): nÄ 3020, 2976, 2930, 1726 (C O), 1653 (C C),

1

1583, 1478, 1367, 1258, 1152, 1007, 824 cm^À1; H NMR (250 MHz, CDCl₃):

d 7.57 (d, ³J 8.3 Hz, 2H; Ar-H), 6.77 (d, ³J 8.3 Hz, 2H; Ar-H), 5.50 (t,

³J 3.7 Hz, 1H; 7-H), 2.76 (ddt, ³J 11.7, ³J 9.8, ³J 3.0 Hz, 1H; 5-H),

2.41 (dd, ³J 9.8, ³J 3.0 Hz, 2H; 6-H), 2.11 (dd, ²J 12.7, ³J 11.7 Hz,

1H; 4-H), 1.46 (s, 9H; tBu-H), 1.44 (dd, ²J 12.7, ³J 3.0 Hz, 1H; 4-H),

0.60 0.50 (m, 2H; cPr-H), 0.46 0.37 (m, 2H; cPr-H); ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): d 174.8 (C_quat, CO), 141.9 (C_quat, C-1'*),

139.9 (C_quat, C-8*), 136.6 (, Ar-C), 131.2 (, Ar-C), 124.6 (, C-7), 92.2

(C_quat, C-4'), 80.1 (C_quat, tBu-C), 40.3 (, C-5), 37.3 (À, C-6), 28.6 (À, C-4),

28.1 (, tBu-C), 19.9 (C_quat, C-3), 12.7 (À, cPr-C), 11.6 (À, cPr-C); MS

(70 eV): m/z (%): 410 (2) [M ], 354 (64) [M À C₄H₈], 309 (12) [M

À

CO₂tBu], 181 (100) [M À CO₂tBu À HI], 57 (25); elemental analysis calcd

(%) for C₁₉H₂₃IO₂(410.3): C 55.62; H 5.65; found: C 55.65, H 5.39.

Fraction II: 38e as colorless crystals (55 mg, 6%); m.p. 1218C; R_f 0.43

Fraction I: Polymeric material as

(pentane/diethyl ether 2:1).

a

yellowish oil (177 mg). R_f 0.82

(pentane/diethyl ether 2:1); IR (KBr): nÄ 3085, 2925, 1716 (C O), 1641

À1

(C C), 1452, 1365, 1257, 1160, 999, 971, 835 cm

;

¹H NMR (250 MHz,

CDCl₃): d 6.89 (s, 4H; Ar-H), 5.50 (t, ³J 3.6 Hz, 2H; 7'-H), 2.77 (ddt,

³J 11.9, ³J 9.7, ³J 2.7 Hz, 2H; 5'-H), 2.41 (dd, ³J 9.7, ³J 3.6 Hz, 4H;

6'-H), 2.13 (dd, ²J 12.6, ³J 11.9 Hz, 2H; 4'-H), 1.46 (s, 18H; tBu-H), 1.42

(dd, ²J 12.6, ³J 2.7 Hz, 2H; 4'-H), 0.60 0.40 (m, 8H; cPr-H); ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): d 174.9 (C_quat, CO), 142.7 (C_quat, Ar-C*),

138.5 (C_quat, C-8'*), 128.2 (, Ar-C), 124.0 (, C-7'), 80.0 (C_quat, tBu-C),

Fraction II: 40a as a yellowish oil (207 mg, 72%); R_f 0.41 (pentane/

diethyl ether 2:1); IR (film): nÄ 3079, 2998, 2949, 2851, 1736 (C O), 1646

(C C), 1436, 1375, 1258, 1193, 1170, 1019, 904, 885, 812, 729 cm^À1; ¹H NMR

3

(250 MHz, CDCl₃): d 6.58 (s, 3H; Ar-H), 5.47 (t, J 3.8 Hz, 3H; 7'-H),

3.69 (s, 9H; OCH₃), 2.82 (ddd, ³J 11.8, ³J 8.1, ³J 2.7 Hz, 3H; 5'-H),

2.44 (dd, ³J 8.1, ³J 3.8 Hz, 6H; 6'-H), 2.11 (dd, ²J 12.8, ³J 11.8 Hz,

2

3

40.4 (, C-5'), 37.4 (À, C-6'), 28.6 (À, C-4'), 28.1 (, tBu-C), 20.1 (C_quat

,

3H; 4'-H), 1.46 (dd, J 12.8, J 2.7 Hz, 3H; 4'-H), 0.57 0.38 (m, 12H;

cPr-H); ¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 175.9 (C_quat, CO), 142.5

(C_quat, C-8'*), 138.5 (C_quat, Ar-C*), 128.3 (, Ar-C), 123.7 (, C-7'), 51.6

(, OCH₃), 39.3 (, C-5'), 37.4 (À, C-6'), 28.4 (À, C-4'), 20.1 (C_quat, C-3'),

C-3'), 12.8 (À, cPr-C), 11.6 (À, cPr-C); MS (70 eV): m/z (%): 490 (13) [M ],

433 (7) [M À C₄H₉], 417 (22) [M À C₄H₉O], 378 (100) [M À 2C₄H₈], 331

(27), 57 (52) [C₄H₉]; elemental analysis calcd (%) for C₃₂H₄₂O₄(490.7): C

78.33, H 8.63; found: C 78.09, H 8.49.

12.8 (À, cPr-C), 11.6 (À, cPr-C); MS (70 eV): m/z (%): 570 (100) [M ], 555

(5) [M À CH₃], 539 (25) [M À OCH₃], 511 (21) [M À CO₂Me], 490 (62),

481 (41), 430 (29), 421 (25), 401 (29), 371 (51), 345 (39), 343 (35), 311 (30),

285 (26), 283 (35), 255 (27).

b) According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol, 5 mol%),

triphenylphosphane (39.3 mg, 150 mmol, 15 mol%), bicyclopropylidene (1,

160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl (166 mg,

1.00 mmol) and 1,4-diiodobenzene (37, 166 mg, 0.500 mmol) were stirred

in anhydrous acetonitrile (1 mL) with tert-butyl acrylate (17e, 256 mg,

2.00 mmol) for 48 h at 808C. After work-up, chromatography of the crude

product on 50 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 4:1)

yielded 38e as colorless crystals (169 mg, 69%).

1,3,5-Tris(5'-tert-butoxycarbonylspiro[2.5]oct-7'-en-8'-yl)benzene

(40e):

According to GP 5, palladium(ii) acetate (33.7 mg, 150 mmol, 30 mol%),

triphenylphosphane (78.7 mg, 300 mmol, 60 mol%), bicyclopropylidene (1,

480 mg, 6.00 mmol), K₂CO₃(829 mg, 6.00 mmol), Et₄NCl (497 g,

3.00 mmol) and 1,3,5-triiodobenzene (39, 228 mg, 0.500 mmol) were stirred

in anhydrous acetonitrile (1 mL) with tert-butyl acrylate (17e, 769 mg,

6.00 mmol) for 72 h at 808C. After work-up, chromatography of the crude

product on 25 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 5:1) gave:

c) According to GP 6, 1,4-diiodobenzene (37, 330 mg, 1.00 mmol), bicyclo-

propylidene (1, 320 mg, 4.00 mmol), tert-butyl acrylate (17e, 512 mg,

4.00 mmol), palladium(ii) acetate (11.2 mg, 49.9 mmol), triphenylphosphane

(39.3 mg, 150 mmol) and triethylamine (404 mg, 4.00 mmol) were heated in

anhydrous DMF (5 mL) at 808C for 24 h under a pressure of 10 kbar. After

work-up, chromatography of the crude product on silica gel (column 2 Â

20 cm, pentane/diethyl ether 4:1) gave 38e as colorless crystals (294 mg,

60%); R_f 0.82 (pentane/diethyl ether 4:1); m.p. 1218C.

Fraction I: Polymeric material as a clear oil (292 mg); R_f 0.88 (pentane/

diethyl ether 5:1).

Fraction II: 40e as a yellowish oil (208 mg, 60%); R_f 0.53 (pentane/

diethyl ether 5:1); IR (film): nÄ 3042, 2977, 2930, 1727 (C O), 1653 (C C),

1

1457, 1367, 1257, 1153, 843 cm^À1; H NMR (250 MHz, CDCl₃): d 6.54 (s,

3H; Ar-H), 5.46 (t, ³J 3.7 Hz, 3H; 7'-H), 2.73 (ddd, ³J 12.1, ³J 9.8, ³J

1,4-Bis(4',5'-dimethoxycarbonylspiro[2.5]oct-7'-ene-8'-yl)benzene (38 f):

a) According to GP 5, palladium(ii) acetate (11.2 mg, 49.9 mmol,

5 mol%), triphenylphosphane (39.3 mg, 150 mmol, 15 mol%), bicyclopro-

pylidene (1, 160 mg, 2.00 mmol), K₂CO₃(277 mg, 2.00 mmol), Et₄NCl

(166 mg, 1.00 mmol) and 1,4-diiodobenzene (37, 166 mg, 0.500 mmol) were

stirred in anhydrous acetonitrile (1 mL) with dimethyl fumarate (17 f,

288 mg, 2.00 mmol) for 48 h at 808C. After work-up, chromatography of

the crude product on silica gel (column 2 Â 20 cm, pentane/diethyl ether

1:1) gave 38 f as colorless crystals (141 mg, 54%). R_f 0.42 (pentane/

3

2

3.0 Hz, 3H; 5'-H), 2.38 (dd, J 9.8, J 3.7 Hz, 6H; 6'-H), 2.08 (dd, J

12.4, ³J 12.1 Hz, 3H; 4'-H), 1.44 [s, 27H; C(CH₃)₃], 1.42 (dd, ²J 12.4,

³J 3.0 Hz, 3H; 4'-H), 0.57 0.38 (m, 12H; cPr-H); ¹³C NMR (62.9 MHz,

CDCl₃, DEPT): d 174.9 (C_quat, CO), 142.5 (C_quat, C-8'), 138.6 (C_quat, Ar-

C), 128.3 (, Ar-C), 123.9 (, C-7'), 80.0 [C_quat, C(CH₃)₃], 40.4 (, C-5'),

37.4 (À, C-6'), 28.6 (À, C-4'), 28.1 [, C(CH₃)₃], 20.1 (C_quat, C-3'), 12.9 (À,

cPr-C), 11.6 (À, cPr-C); MS (70 eV): m/z (%): 697/696 (6/12) [M ], 640/639

(4/8) [M À C₄H₉], 623 (15) [M À OC₄H₉], 528 (98) [M À 3C₄H₈], 481

(21) [M À 2C₄H₉À CO₂C₄H₉], 57 (100) [C₄H₉]; elemental analysis calcd

diethyl ether 1:1); m.p. 1398C; IR (KBr): nÄ 3005, 2950, 1734 (C O), 1653

À1

(%) for C₄₅H₆₀O₆(697.0): C 77.55, H 8.68; found: C 77.66, H 8.74.

(C C), 1432, 1374, 1324, 1259, 1157, 1023, 998, 851 cm

;

¹H NMR

(250 MHz, CDCl₃): d 6.95 (s, 4H; Ar-H), 5.50 (dd, ³J 3.8, ³J 3.7 Hz,

1,3,5-Tris(4',5'-dimethoxycarbonylspiro[2.5]oct-7'-en-8'-yl)benzene (40 f):

According to GP 5, palladium(ii) acetate (33.7 mg, 150 mmol, 30 mol%),

triphenylphosphane (78.7 mg, 300 mmol, 60 mol%), bicyclopropylidene (1,

480 mg, 6.00 mmol), K₂CO₃(829 mg, 6.00 mmol), Et₄NCl (497 g,

3.00 mmol) and 1,3,5-triiodobenzene (39, 228 mg, 0.500 mmol) were stirred

2H; 7'-H), 3.71 (s, 12H; OCH₃), 3.29 (ddd, ³J 12.8, ³J 6.6, J 6.3 Hz,

3

2H; 5'-H), 2.94 (d, ³J 6.6 Hz, 2H; 4'-H), 2.57 (ddd, ²J 18.2, ³J 12.8,

³J 3.8 Hz, 2H; 6'-H), 2.49 (ddd, ²J 18.2, ³J 6.3, ³J 3.7 Hz, 2H; 6'-H),

0.66 0.59 (m, 6H; cPr-H), 0.47 0.43 (m, 2H; cPr-H); ¹³C NMR

2366

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2366 $ 20.00+.50/0

Chem. Eur. J. 2002, 8, No. 10

Domino Heck Diels Alder Reactions

2350 2369

in anhydrous acetonitrile (1 mL) with dimethyl fumarate (17 f, 865 mg,

6.00 mmol) for 72 h at 808C. After work-up, chromatography of the crude

product on 25 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 2:1 !

diethyl ether) gave:

2.00 mmol) were heated in anhydrous DMF (10 mL) at 758C for 20 h.

After work-up, chromatography of the crude product on silica gel (column

2 Â 20 cm, pentane) gave:

Fraction I: 2-Ph, not completely evaporated; R_f 0.85 (pentane).

Fraction I: Polymeric material and 17 f (260 mg overall); R_f 0.77 (pen-

Fraction II: A mixture of (Z)-50 and 49 (1.7:1) as a colorless oil (95 mg,

60%), which could not be separated completely. (Z)-50: ¹H NMR

(250 MHz, C₆D₆): d 7.30 7.00 (m, 5H; Ar-H), 5.83 (q, ³J 7.0 Hz, 1H;

4-H), 5.01 (q, ⁴J 0.5 Hz, 1H; 1-H), 4.77 (q, ⁴J 0.5 Hz, 1H; 1-H), 1.97 (dd,

⁴J 0.5, ⁴J 0.5 Hz, 3H; CH₃), 1.54 (d, ³J 7.0 Hz, 3H; CH₃); ¹³C NMR

(62.9 MHz, C₆D₆, DEPT): d 144.7 (C_quat), 136.0 (C_quat), 132.4 (C_quat), 130.0

(, CH), 128.4 (, CH), 126.8 (, CH), 123.3 (, CH), 115.5 (À, C-1), 20.5

(, CH₃), 15.1 (, CH₃); 49: ¹H NMR (250 MHz, C₆D₆): d 7.30 7.00 (m,

5H; Ar-H), 7.02 (dd, ³J 17, ³J 10 Hz, 1H; 2-H), 5.10 (d, ³J 10 Hz, 1H;

tane/diethyl ether 2:1).

Fraction II: 40 f as a yellowish oil (211 mg, 57%); R_f 0.11 (pentane/

diethyl ether 2:1); IR (film): nÄ 3005, 2952, 1734 (C O), 1653 (C C), 1436,

1374, 1265, 1199, 1171, 1024 cm^À1; ¹H NMR (250 MHz, CDCl₃): d 6.62 (s,

3H; Ar-H), 5.46 (t, ³J 3.9 Hz, 3H; 7'-H), 3.70 (s, 9H; OCH₃), 3.69 (s, 9H;

OCH₃), 3.25 (dd, ³J 7.0, ³J 6.3 Hz, 3H; 5'-H), 2.93 (d, ³J 7.0 Hz, 3H; 4'-

3

H), 2.49 (dd, J 6.3, J 3.9 Hz, 6H; 6'-H), 0.61 0.37 (m, 12H; cPr-H);

¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 174.5 (C_quat, CO), 173.2 (C_quat

,

3

1-H), 4.83 (d, J 17 Hz, 1H; 1-H), 1.97 (s, 3H; CH₃), 1.51 (s, 3H; CH₃);

CO), 141.3 (C_quat, Ar-C*), 138.2 (C_quat, C-8'*), 128.4 (, Ar-C), 123.5 (,

C-7'), 51.8 (, OCH₃), 49.0 (, C-5'), 41.4 (, C-4'), 26.3 (À, C-6'), 19.6

(C_quat, C-3'), 10.9 (À, cPr-C), 10.1 (À, cPr-C); MS (70 eV): m/z (%): 744

¹³C NMR (62.9 MHz, C₆D₆, DEPT): d 144.5 (C_quat), 140.1 (C_quat), 134.3

(C_quat), 130.4 (, CH), 130.2 (, CH), 126.6 (, CH), 124.7 (, CH), 115.3

(À, C-1), 22.7 (, CH₃), 19.4 (, CH₃).

(100) [M ], 684 (72) [M À MeOH À CO], 624 (44) [M À 2MeOH À

Fraction III: 48 as a colorless oil (7.3 mg, 5%); ¹H NMR (250 MHz, C₆D₆):

d 7.23 7.15 (m, 5H; Ar-H), 5.29 (s, 1H; 1'-H), 5.20 (d, ⁴J 0.5 Hz, 1H; 1'-

2CO], 565 (32) [M À CO₂Me À 2MeOH À 2CO], 505 (24) [M

À

CO₂Me À 3MeOH À 3CO], 59 (62) [CO₂Me ].

4

H), 1.90 (d, J 0.5 Hz, 3H; CH₃), 1.0 1.5 (m, 4H; cPr-H).

1,2,4,5-Tetrakis(5'-methoxycarbonylspiro[2.5]oct-7'-en-8'-yl)benzene (42):

According to GP 5, palladium(ii) acetate (44.8 mg, 200 mmol, 20 mol%),

triphenylphosphane (105 mg, 400 mmol, 40 mol%), bicyclopropylidene (1,

641 mg, 8.00 mmol), K₂CO₃(664 mg, 4.80 mmol), Et₄NCl (1.11 g,

6.70 mmol) and 1,2,4,5-tetraiodobenzene (41, 582 mg, 1.00 mmol) were

stirred in anhydrous acetonitrile (2 mL) with methyl acrylate (17a, 689 mg,

8.00 mmol) for 48 h at 808C. After work-up, chromatography of the crude

product on 25 g silica gel (column 2 Â 20 cm, pentane/diethyl ether 1:1)

gave:

Acknowledgements

This work was supported by the Bayer AG and the Fonds der Chemischen

Industrie as well as BASF and Degussa AG (chemicals). S.B. is indebted to

the Fonds der Chemischen Industrie for a graduate student fellowship. The

authors are particularly grateful to Dr. Dmitrii S. Yufit and Professor Dr.

Judith A. K. Howard, University of Durham, for the X-ray crystal structure

analysis of compound 18 f-Ph-1, and to Dr. B. Knieriem, Universit‰t

Gˆttingen, for his careful proofreading of the final manuscript.

Fraction I: Polymeric material (65 mg); R_f 0.71 (pentane/diethyl ether

1:1).

Fraction II: 42 as a grey, semi-solid substance (348 mg, 47%); R_f 0.46

(pentane/diethyl ether 1:1); ¹H NMR (250 MHz, CDCl₃): d 6.34 (brs,

2H; Ar-H), 5.52 5.41 (m, 4H; 7'-H), 3.70 (brs, 12H; OCH₃), 2.96 2.80

(m, 4H; 5'-H), 2.49 2.39 (m, 8H; 6'-H), 2.11 1.93 (m, 4H; 4'-H), 1.38

1.22 (m, 4H; 4'-H), 0.58 0.36 (m, 16H; cPr-H); ¹³C NMR (62.9 MHz,

[1] a) G. H. Posner, Chem. Rev. 1986, 86, 831 844; b) L. F. Tietze, J.

Heterocycl. Chem. 1990, 27, 47 69; c) F. E. Ziegler in Comprehensive

Organic Synthesis, Vol. 5 (Eds.: B. M. Trost, I. Fleming), Pergamon

Press, Oxford, 1991, pp. 875 898; d) T.-L. Ho, Tandem Organic

Reactions, Wiley, New York, 1992; e) E. Negishi, Pure Appl. Chem.

1992, 64, 323 334; f) L. F. Tietze, U. Beifu˚, Angew. Chem. 1993, 105,

137 170; Angew. Chem. Int. Ed. Engl. 1993, 32, 131 163; g) L. F.

Tietze, Chem. Rev. 1996, 96, 115 136; h) P. J. Parsons, C. S. Penkett,

CDCl₃, DEPT): d 175.9 (C_quat, CO), 140.5 (C_quat, Ar-C*), 136.7 (C_quat

,

C-8'*), 126.0 (, Ar-C), 123.7 (, C-7'), 51.6 (, OCH₃), 39.4 (, C-5'), 37.3

(À, C-4'), 28.3 (À, C-6'), 21.3 (C_quat, C-3'), 12.6 (À, cPr-C), 12.4 (À, cPr-C);

MS (70 eV): m/z (%): 734 (86) [M ], 703 (10) [M À OCH₃], 676 (6), 569

(9) [M À C₁₀H₁₃O₂], 311 (80), 206 (78), 183 (88), 105 (100).

1-Cyclohex-1'-enyl-1-phenylcyclopropane (44), 1'-phenylprop-2'-enylide-

necyclohexane (45) and (Z)-(1'-phenylprop-1'-enyl)cyclohex-1-ene [(Z)-

46]: According to GP 1, iodobenzene (2-Ph, 204 mg, 1.00 mmol), cyclo-

propylidenecyclohexane (43a, 490 mg, 4.01 mmol), palladium(ii) acetate

(11.2 mg, 49.9 mmol), triphenylphosphane (39.3 mg, 150 mmol) and triethyl-

amine (202 mg, 2.00 mmol) in anhydrous DMF (10 mL) were heated at

758C for 20 h. After work-up, chromatography of the crude product on

silica gel (column 2 Â 20 cm, pentane) gave:

¬

A. J. Shell, Chem. Rev. 1996, 96, 195 206; i) A. Heumann, M. Reglier,

Tetrahedron 1996, 52, 9289 9346.

[2] For reviews, see: a) R. F. Heck, Acc. Chem. Res. 1979, 12, 146 151;

b) R. F. Heck, Org. React. 1982, 27, 345 390; c) R. F. Heck, Palladium

Reagents in Organic Syntheses, Academic Press, London, 1985;

d) B. M. Trost, T. R. Verhoeven in Comprehensive Organometallic

Chemistry, Vol. 8 (Ed.: G. Wilkinson), Pergamon, Oxford, 1991,

pp. 854 883; e) A. de Meijere, F. E. Meyer, Angew. Chem. 1994,

106, 2473 2506; Angew. Chem. Int. Ed. Engl. 1994, 33, 2379 2411;

f) J. Tsuji, Palladium Reagents and Catalysts? Innovations in Organic

Fraction I: (Z)-46 as a colorless oil (105 mg, 53%); R_f 0.8 (pentane);

¹H NMR (250 MHz, CDCl₃): d 7.45 7.25 (m, 3H; Ar-H), 7.2 7.1 (m, 2H;

3

Ar-H), 5.78 (q, J 7.0 Hz, 1H; 2'-H), 5.25 (brs, 1H; 2-H), 2.30 (brs, 2H;

CH₂), 2.05 (brs, 2H; CH₂), 1.80 1.50 (m, 7H; CH₂, CH₃); ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): d 144.4 (C_quat), 140.2 (C_quat), 127.9 (, Ar-C),

127.8 (, Ar-C), 127.1 (, Ar-C*), 126.2 (, C-2'*), 119.3 (, C-2), 25.9 (À,

C-3, C-6), 23.0 (À, C-5*), 22.4 (À, C-4*), 15.1 (, C-3'); MS (70 eV, EI):

¬

Synthesis, Wiley, Chichester, 1995; g) E. Negishi, C. Coperet, S. M.

Ma, S.-Y. Liou, F. Liu, Chem. Rev. 1996, 96, 365 393; h) T. Jeffery,

Adv. Met.-Org. Chem. 1996, 5, 153 260; i) S. Br‰se, A. de Meijere in

Metal-catalyzed Cross-coupling Reactions (Eds.: F. Diederich, P. J.

Stang), VCH, Weinheim, 1998, pp. 99 166; j) M. Beller, T. H.

Riermeier, G. Stark in Transition Metals in Organic Synthesis (Eds.:

M. Beller, C. Bolm), Wiley-VCH, Weinheim, 1998, pp. 208 240;

k) A. de Meijere, S. Br‰se, J. Organomet. Chem. 1999, 576, 88 110;

l) A. de Meijere, S. Br‰se, in Transition Metal Catalysed Reactions

(Eds.: S.-i. Murahashi, S. G. Davies), Blackwell Science, Oxford, 1999,

pp. 99 131.

m/z (%): 198 (100) [M ], 183 (41) [M À CH₃], 169 (47) [M À C₂H₅], 155

ꢀ

(42) [M À C₃H₇], 141 (46) [M À C₄H₉], 115 (31) [M À C₆H₁₁2-indenyl],

91 (23) [C₇H₇]; HRMS: m/z (%): calcd for C₁₅H₁₈: 198.1408; found:

198.1408.

Fraction II: A mixture of at least three different C₁₅H₁₈isomers (70 mg,

35%), among them 44 and 45 (NMR, MS); R_f 0.65 (pentane); MS (EI,

70 eV): m/z (%): 198 (100) [M ], 183 (53) [M À CH₃], 169 (19) [M

À

C₂H₅], 141 (60), 91 (65) [C₇H₇].

[3] a) S. Br‰se, J. R¸mper, K. Voigt, S. Albecq, G. Thurau, R. Villard, B.

Waegell, A. de Meijere, Eur. J. Org. Chem. 1998, 671 678; b) F. E.

Meyer, K. H. Ang, A. G. Steinig, A. de Meijere, Synlett 1994, 191

193; c) K. H. Ang, S. Br‰se, A. G. Steinig, F. E. Meyer, A. Llebaria, K.

Voigt, A. de Meijere, Tetrahedron 1996, 52, 11503 11528; d) L. Bhat,

A. Steinig, R. Appelbe, A. de Meijere, Eur. J. Org. Chem. 2001, 1673

1680.

Fraction III: Biphenyl (6 mg, 8%); R_f 0.63 (pentane).

1-Phenyl-1-(propen-2'-yl)cyclopropane (48), 4-methyl-3phenyl-1,3-penta-

diene (49) and 2-methyl-3-phenyl-1,3-pentadiene [(Z)-50]: According to

GP 1, iodobenzene (2-Ph, 204 mg, 1.00 mmol), isopropylidenecyclopro-

pane (47, 329 mg, 4.00 mmol), palladium(ii) acetate (11.2 mg, 49.9 mmol),

triphenylphosphane (39.3 mg, 150 mmol) and triethylamine (202 mg,

Chem. Eur. J. 2002, 8, No. 10

¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

0947-6539/02/0810-2367 $ 20.00+.50/0

2367

A. de Meijere et al.

FULL PAPER

[4] For Heck reactions with tetrasubstituted alkenes see: a) R. Grigg, V.

Sridharan, P. Stevenson, T. Worakun, J. Chem. Soc. Chem. Commun.

1986, 1697 1699; b) M. M. Abelman, T. Oh, L. E. Overman, J. Org.

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2312 2313; f) G. Dyker, J. Kˆrning, P. Bubenitschek, P. G. Jones,

Liebigs Ann./Recueil 1997, 203 209.

[5] P. Binger, P. Wedemann, S. I. Kozhushkov, A. de Meijere, Eur. J. Org.

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[6] Preliminary communication: S. Br‰se, A. de Meijere, Angew. Chem.

1995, 107, 2741 2743; Angew. Chem. Int. Ed. Engl. 1995, 34, 2545

2547.

[7] Bicyclopropylidene (1) is readily available in three simple steps: a) A.

de Meijere, S. I. Kozhushkov, T. Sp‰th, N. S. Zefirov, J. Org. Chem.

1993, 58, 502 505; b) A. de Meijere, S. I. Kozhushkov, T. Sp‰th, Org.

Synth. 2000, 78, 142 151.

[8] Typical conditions: 5 mol%Pd(OAc) ₂, 10 mol%PPh ₃, Et₃N, DMF,

808C.

[9] The synthesized allylidenecyclopropanes 5-Ar, 7-R and 10 are volatile,

rapidly polymerizing compounds, which are difficult to isolate in pure

form.

[10] For reviews, see: a) H. Hopf, Angew. Chem. 1984, 96, 947 958;

Angew. Chem. Int. Ed. Engl. 1984, 23, 948 960; b) P. G. Farrell, R.

Grinter, S. F. Mason in Optische Anregung organischer Systeme (Ed.:

W. Foerst), Verlag Chemie, Weinheim, 1966, pp. 88 108; c) H. Hopf,

Angew. Chem. 2001, 113, 727 729; Angew. Chem. Int. Ed. 2001, 40,

705 707.

Kulkarni, B. B. Snider, Org. Prep. Proc. Int. 1986, 18, 7 10; k) G.

Wickham, G. J. Wells, L. Waykole, L. A. Paquette, J. Org. Chem. 1985,

50, 3485 3489; l) L. A. Paquette, G. J. Wells, G. Wickham, J. Org.

Chem. 1984, 49, 3618 3621; m) F. Heinrich, W. L¸ttke, Angew. Chem.

1972, 84, 263 265; Angew. Chem. Int. Ed. Engl. 1972, 11, 234 236;

n) M. F. Semmelhack, R. J. DeFranco, J. Am. Chem. Soc. 1972, 94,

2116 2118; o) W. R. Roth, T. Schmidt, Tetrahedron Lett. 1971, 3639

3642; p) W. R. Dolbier, Jr., D. Lomas, P. Tarrant, J. Am. Chem. Soc.

1968, 90, 3594.

[14] For the synthesis of allylidenecyclopropane derivatives by transition-

metal catalyzed/mediated reactions, see: a) M. Brandl, S. I. Kozhush-

kov, S. Br‰se, A. de Meijere, Eur. J. Org. Chem. 1998, 453 457; b) S. I.

Kozhushkov, M. Brandl, D. S. Yufit, R. Machinek, A. de Meijere,

Liebigs Ann./Recueil 1997, 2197 2204.

[15] For Diels Alder reactions of certain allylidenecyclopropanes see:

a) T. Thiemann, Dissertation, Universit‰t Hamburg, 1992; b) T.

Thiemann, S. Kohlstruk, G. Schw‰r, A. de Meijere in Strain and Its

Implications in Organic Chemistry, NATO ASI Series C, Vol. 273

(Eds.: A. de Meijere, S. Blechert), Kluwer, Dordrecht, 1989, pp. 507

508; c) T. Thiemann, S. Kohlstruk, G. Schw‰r, A. de Meijere,

Tetrahedron Lett. 1991, 32, 3483 3486; d) H. Kigoshi, A. Sawada,

H. Niwa, K. Yamada, Bull. Soc. Chem. Jpn. 1989, 62, 1639 1642; e) F.

Zuttermann, A. Krief, J. Org. Chem. 1983, 48, 1135 1137.

[16] The authors are indebted to Dr. P. R. Schreiner for his assistance with

the calculations which were performed with the program suite

Gaussian 94, Revision D.3, M. J. Frisch, G. W. Trucks, H. B. Schlegel,

P. M. W. Gill, B. G. Johnson, M. A. Robb, J. R. Cheeseman, T. Keith,

G. A. Petersson, J. A. Montgomery, K. Raghavachari, M. A. Al-

Laham, V. G. Zakrzewski, J. V. Ortiz, J. B. Foresman, J. Cioslowski,

B. B. Stefanov, A. Nanayakkara, M. Challacombe, C. Y. Peng, P. Y.

Ayala, W. Chen, M. W. Wong, J. L. Andres, E. S. Replogle, R.

Gomperts, R. L. Martin, D. J. Fox, J. S. Binkley, D. J. Defrees, J.

Baker, J. P. Stewart, M. Head-Gordon, C. Gonzalez, J. A. Pople,

Gaussian, Inc., Pittsburgh PA, 1995.

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Cadogan, I. Gosney, W. J. Henry, J. Chem. Soc. Chem. Commun. 1985,

1785 1786; d) T. Loerzer, R. Gerke, W. L¸ttke, Angew. Chem. 1986,

98, 560 562; Angew. Chem. Int. Ed. Engl. 1986, 25, 278 579; e) D.

[17] a) I. Fleming, Grenzorbitale and Reaktionen organischer Verbindun-

gen, VCH, Weinheim, 1990; b) H. Wollweber in Methoden der

Organischen Chemie (Houben-Weyl), Vol. 5/1c (Ed.: E. M¸ller),

1970, pp. 981 1124.

¬

Djahanbini, B. Cazes, J. Gore, Tetrahedron 1987, 43, 3441 3452; f) M.

Wehbe, Y. Lepage, Bull. Soc. Chim. Fr. 1988, 1027 1031; g) Y. Misaki,

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5289 5292; h) A. G. Griesbeck, K. Peters, E.-M. Peters, H. G.

von Schnering, Angew. Chem. 1990, 102, 801 803; Angew. Chem.

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Gillam, I. Gosney, J. Chem. Soc. Chem. Commun. 1991, 114 115;

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ACS National Meeting (San Francisco), 1997; l) H. Hopf, M. Theurig,

Angew. Chem. 1994, 106, 1173 1174; Angew. Chem. Int. Ed. Engl.

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Jeffery, Tetrahedron Lett. 1985, 26, 2667 2670; c) T. Jeffery, Synthesis

1987, 70 71; d) T. Jeffery, M. David, Tetrahedron Lett. 1998, 39, 5751

5754. However, acetonitrile is not completely inert towards inter-

mediate 4, and the Ritter-type product, N-[(2-cyclopropylidene-1-

methyl-2-phenyl)propyl]acetamide, was isolated in 5%yield in the

reaction of 1 with PhI and 17b under these conditions. ¹H NMR

(250 MHz, CDCl₃): d 7.58 (dd, ³J 7.2, ³J 1.5 Hz, 2H; Ar-H),

3

7.38 7.21 (m, 3H; Ar-H), 6.06 (q, J 7.0 Hz, 1H; CH), 2.05 (s, 3H;

CH₃), 1.50 (d, ³J 7.0 Hz, 3H; CH₃), 1.33 1.27 (m, 4H; cPr-H);

¹³C NMR (62.9 MHz, CDCl₃, DEPT): d 170.3 (C_quat, CO), 138.5

(C_quat, Ar-C), 128.1 (, 2CH, Ar-C), 126.8 (, CH, Ar-C), 126.6 (, 2

CH, Ar-C), 124.2 (C_quat), 72.1 (, CH), 21.2 (, CH₃), 19.4 (, CH₃),

¬

Chem. 1995, 60, 3764 3772; n) V. Gauthier, B. Cazes, J. Gore, Bull.

Chim. Soc. Fr. 1996, 133, 563 579; o) by cross-coupling: H. Kleijn, H.

Westmijze, J. Meijer, P. Vermeer, Recl. Trav. Chim. Pays-Bas 1983,

102, 378 380.

2.7 (À, 2cPr-C); MS (70 eV): m/z (%): 215 (20) [M ], 174 (52) [M

À

C₃H₅], 159 (38) [M À C₄H₉], 141 (100) [C₁₁H₉].

[12] a) U. H. Brinker, L. Kˆnig, Chem. Ber. 1983, 116, 882 893; b) W.

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Gajewski, G. A. Shook, T. Cohen, J. Am. Chem. Soc. 1995, 117, 8495

8501; c) C.-C. Hwu, F.-C. Wang, M.-C. P. Yeh, J.-H. Sheu, J. Organo-

met. Chem. 1994, 474, 123 128; d) F. Kienzle, J. Stadlwieser, I.

Mergelsberg, Helv. Chim. Acta 1989, 72, 348 352; e) J. R. Al

Dulayymi, M. S. Baird, Tetrahedron 1989, 45, 7601 7614; f) J. A.

Stafford, J. E. McMurry, Tetrahedron Lett. 1988, 29, 2531 2534;

g) D. W. McCullough, T. Cohen, Tetrahedron Lett. 1988, 29, 27 30;

h) T. Cohen, S.-H. Jung, M. L. Romberger, D. W. McCullough,

Tetrahedron Lett. 1988, 29, 25 26; i) F. Kienzle, J. Stadlwieser, W.

Rank, I. Mergelsberg, Tetrahedron Lett. 1988, 29, 6479 6482; j) Y. S.

[19] Compare: A. de Meijere, S. I. Kozhushkov, A. F. Khlebnikov, Top.

Curr. Chem. 2000, 207, 89 147, and references therein.

[20] Crystals of the compounds were grown by slow evaporation of a

solution in a hexane/Et₂O mixture (18 f-Ph-1, prepared from 17b) or

by slow cooling of their saturated solutions in Et₂O (18 f-Ph-2,

prepared from 17 f), hexane (18 f-Ph, p-32) or a hexane/Et₂O mixture

(18 f-Tol) and measured on a SMART Bruker CCD 1 K (18 f-Ph-1) or

an STOE AED2 (other compounds) diffractometer using graphite

monochromated Mo_Karadiation. The structure solutions and refine-

ments on F²were performed with the SHELX program suite

(Version 5.10). The hydrogen atoms were located in a difference

Fourier map and refined as riding groups with the 1.2-fold isotropic

displacement parameter of the corresponding C atom. 18 f-Ph-1:

C₁₈H₂₀O₄(300.34), crystal size 0.30 Â 0.18 Â 0.14 mm³, monoclinic, a

11.7145(4), b 6.5412(2), c 20.2856(7) ä, b 101.63(1)8, V

1522.54(9) ä³, Z 4, space group P2₁/c, T 100.0(2) K, 1

1.310 gcm^À3, intensities measured: 13422 (2q_max 61.06), independ-

ent: 4658 (R_int 0.0276), 279 parameters refined, R1 0.0559, wR2

(all data) 0.1156, Gof 1.018, maximum and minimum residual

2368

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Domino Heck Diels Alder Reactions

2350 2369

electron density 0.390 and À0.202 eä^À3. 18 f-Ph-2: C₁₈H₂₀O₄(300.34),

crystal size 0.70 Â 0.25 Â 0.20 mm³, monoclinic, a 11.714(2), b

6.5394(13), c 20.309(4) ä, b 101.47(3)8, V 1524.7(5) ä³, Z 4,

space group P2₁/c, T 133(2) K, 1 1.308 gcm^À3, intensities meas-

ured: 12368 (2q_max 46.5), independent: 2188 (R_int 0.0410), 206

parameters refined, R1 0.0559, wR2 (all data) 0.1081, Gof 1.100,

maximum and minimum residual electron density 0.172 and

À0.195 eä^À3. 18 f-Tol: C₁₉H₂₂O₄(314.37), crystal size 0.80 Â 0.60 Â

0.50 mm³, monoclinic, a 14.543(2), b 5.7066(5), c 20.334(2) ä,

b 92.303(11)8, V 1686.2(3) ä³, Z 4, space group P2₁/c, T

808C, 10 h] 10%of the recovered butene-1,4-dioate in the reaction of

excess dimethyl maleate with phenyl iodide had rearranged to the

trans isomer.

[22] a) O. Tsuge, E. Wada, S. Kanemasa, Chem. Lett. 1983, 239 242; b) O.

Tsuge, E. Wada, S. Kanemasa, Chem. Lett. 1983, 1525 1528; c) E.

Wada, S. Kanemasa, O. Tsuge, Bull. Chem. Soc. Jpn. 1989, 62, 1198

1204; d) C. Spino, G. Liu, N. Tu, S. Girard, J. Org. Chem. 1994, 59,

5596 5608; e) M. M¸hlebach, M. Neuenschwander, Helv. Chim. Acta

1994, 77, 1363 1376; f) O. Tsuge, T. Hatta, H. Yoshitomi, K.

Kurosaka, T. Fujiwara, H. Maeda, A. Kakehi, Heterocycles 1995, 41,

225 228.

[23] The atropisomerism was proved by measuring the ¹H NMR spectrum

of 34ac at 23, 50, 75 and 1008C. At 758C and above only one set of

signals was observable. Compare H. G¸nther, NMR-Spektroskopie,

Thieme, Stuttgart, New York, 1983.

[24] If the Diels Alder reaction were not completely regioselective, eight

isomers could be formed.

[25] A. de Meijere, S. I. Kozhushkov, N. S. Zefirov, Synthesis 1993, 681

683.

[26] A. de Meijere, H. N¸ske, M. Es-Sayed, T. Labahn, M. Schroen, S.

Br‰se, Angew. Chem. 1999, 111, 3881 3884; Angew. Chem. Int. Ed.

1999, 38, 3669 3672.

[27] a) C. J. M. Van den Heuvel, H. Steinberg, T. J. De Boer, Recl. Trav.

Chim. Pays-Bas 1985, 104, 145 152; b) A. A. Frimer, T. Farkash, M.

Sprecher, J. Org. Chem. 1979, 44, 989 995.

150(2) K, 1 1.238 gcm^À3

,

intensities measured: 5415 (2q_max

50.16), independent: 2988 (R_int 0.0197), 211 parameters refined,

R1 0.0533, wR2 (all data) 0.1403, Gof 1.063, maximum and

minimum residual electron density 0.296 and À0.221 eä^À3. 18k-Ph:

C₁₉H₂₂O₄(314.37), crystal size 0.80 Â 0.70 Â 0.40 mm³, monoclinic, a

18.146(4), b 7.0505(10), c 13.313(4) ä, b 99.540(14)8, V

1679.7(6) ä³, Z 4, space group P2₁/c, T 200(2) K, 1

1.243 gcm^À3, intensities measured: 4894 (2q_max 50.04), independent:

2220 (R_int 0.0418), 208 parameters refined, R1 0.0694, wR2 (all

data) 0.1397, Gof 1.048, maximum and minimum residual electron

density 0.296 and À0.221 eä^À3. p-32: C₂₂H₂₁NO₄(363.40), crystal size

0.70 Â 0.60 Â 0.50 mm³, triclinic, a 7.8064(7), b 11.4141(10), c

11.4902(10) ä, a 111.678(5), b 108.215(5), g 91.304(5)8, V

892.58 ä³, Z 2, space group P1, T 133(2) K, 1 1.352 gcm^À3

,

≈

intensities measured: 10902 (2q_max 49.16), independent: 2944

(R_int 0.0594), 245 parameters refined, R1 0.0935, wR2 (all data)

0.1432, Gof 1.271, maximum and minimum residual electron

density 0.218 and À0.217 eä^À3. anti-34eb: C₂₆H₃₀O₂(374.50), crystal

size 1.00 Â 1.00 Â 1.00 mm³, monoclinic, a 12.855(13), b 7.578(8),

c 22.310(2) ä, b 97.420(10)8, V 2155.0(4) ä³, Z 4, space group

[28] The configuration was established by a 400 MHz NOESY NMR

spectrum.

[29] Such a formal rearrangement of a homoallyl- to an arylpalladium

intermediate has literature precedent, cf. a) G. Fournet, G. Balme, J.

Gore, Tetrahedron 1988, 44, 5809 5820; b) G. Fournet, G. Balme, J. J.

Barieux, J. Gore, Tetrahedron 1988, 44, 5821 5832. It has recently

been found for homoallylpalladium intermediates of type 52, cf. c) H.

N¸ske, M. Noltemeyer, A. de Meijere, Angew. Chem. 2001, 113,

3509 3511; Angew. Chem. Int. Ed. 2001, 40, 3411 3413.

[30] H. N¸ske, R. Scheurich, M. Es-Sayed, S. Br‰se, A. de Meijere,

unpublished results.

[31] Such a spirocylopropane analogue of vitamin A has previously been

synthesized: H. Hopf, K. Natsias, Liebigs Ann. Chem. 1988, 705 716.

[32] a) Review: K. Yamada, M. Ojika, H. Kigoshi, Angew. Chem. 1998,

110, 1918 1926; Angew. Chem. Int. Ed. Engl. 1998, 37, 1818 1826;

b) U. Harttig, T. Anke, A. Scherer, W. Steglich, Phytochemistry 1990,

29, 3942 3944.

P2₁/c, T 200(2) K, 1 1.154 gcm^À3

, intensities measured: 4692

(2q_max 50.16), independent: 3739 (R_int 0.0918), 257 parameters

refined, R1 0.1461, wR2 (all data) 0.4298, Gof 1.137, maximum

and minimum residual electron density 0.296 and À0.221 eä^À3

.

CCDC-176378 (18 f-Ph-1), -163615 (18 f-Ph-2), -176661 (18 f-Tol),

-176526 (18k-Ph), -133154 (p-32), -176525 (anti-34eb) contain the

supplementary crystallographic data for this paper. These data can be

obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html

(or from the Cambridge Crystallographic Data Centre, 12 Union

Road, Cambridge CB21EZ, UK; (fax: (44)1223-336-033; or e-mail:

deposit@ccdc.cam.ac.uk).

[21] The isomerization of dimethyl maleate to dimethyl fumarate under

Heck-coupling conditions has previously been documented. Com-

pare: N. A. Cortese, C. B. Ziegler, Jr., B. J. Hrnjes, R. F. Heck, J. Org.

Chem. 1978, 43, 2952 2958. In a control experiment under the

currently employed conditions [Pd(OAc)₂(5 mol%), PPh₃

(15 mol%), PhI, dimethyl maleate (2 equiv), Et₃N (2 equiv), DMF,

[33] a) H. Satonaka, Magn. Reson. Chem. 1986, 24, 265 267; b) J.

Vallgarda, U. Appelberg, L.-E. Arvidsson, S. Hjorth, B. E. Svensson,

U. Hacksell, J. Med. Chem. 1996, 39, 1485 1493.

Received: January 8, 2002 [F3785]

Chem. Eur. J. 2002, 8, No. 10

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A new highly efficient three-component domino Heck-Diels-Alder reaction with bicyclopropylidene: Rapid access to spiro[2.5]oct-4-ene derivatives

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