A major breakthrough in the use of alkoxycarbene complexes of chromium and tungsten for the synthesis of elaborate organic compounds: Dihydropyridine induced reductions and cascade insertion reactions

TETRAHEDRON

Pergamon

Tetrahedron 56 (2000) 5001±5027

A Major Breakthrough in the Use of Alkoxycarbene Complexes of

Chromium and Tungsten for the Synthesis of Elaborate Organic

Compounds: Dihydropyridine Induced Reductions and Cascade

Insertion Reactions

*

Â

H. Rudler, A. Parlier, T. Durand-Reville, B. Martin-Vaca, M. Audouin, E. Garrier, V. Certal and

J. Vaissermann

Á Â Â Â

Laboratoire de Synthese Organique et Organometallique, UMR 7611 and Laboratoire de Chimie Inorganique et Materiaux Moleculaires,

Â

ESA 7071, Universite Pierre et Marie Curie T44-45, 4 place Jussieu 75252, Paris Cedex 5, France

Received 14 December 1999; accepted 31 January 2000

AbstractÐAlkoxy (alkyl)carbene complexes of tungsten and chromium react with dihydropyridine and N-methyldihydropyridine to give

respectively pyridinium ylid complexes and N-methylpyridinium tungstates and chromates. These two types of complexes can be used, for

the former, as cyclopropanation reagents, for the latter, as unprecedented initiators of cascade multiinsertions of ole®ns, alkynes and CO.

Background and Introduction

ef®ciency of these transformations. If one considers the

structure of the starting material, e.g. Cr(CO)₆, and if one

establishes the balance of the various reactions, it appears

clearly that most of the carbon monoxide ligands of the

metal are lost during these transformations. At best, two

CO groups are used, for example one for the formation of

the carbene complex, the other one for the formation of the

phenol in the benzannulation reaction; at worst, only the

CO ligand giving rise to the carbene is incorporated in

the ®nal product, a cyclopropane. Nevertheless, and to the

best of our knowledge, two examples can be found in the

literature which describe the incorporation of three CO

groups for the construction of elaborate molecules.

Fischer carbene complexes continue in an unabated way to

focus the attention of a broad panel of chemists interested in

their structural aspects, their physical properties or their use

as starting material for the construction of new molecules.¹

Their manifold applications as synthons in organic chemis-

try have recently been summarized²and are sketched out in

the general Scheme 1. As can be seen, most of the reactions

deal with the direct interaction of the carbene component

with an external substrate. This is the case for the cyclo-

propanation of ole®ns, the benzannulation reaction of aryl-

containing complexes, the lactam formation reactions. Only

a few examples from the literature are related to a deep

modi®cation of the carbene function before their reaction

with external substrates: this occurs nevertheless during

their interaction with hydrides (Bu₃SnH, KB(OR)₃H,

NaBH₄) which either are able to remove the metal from

the organic moiety, or to modify deeply the complexes

(vide infra).

² the insertion of alkynes into iron alkoxycarbene

complexes³

² the intramolecular insertion of an alkyne into an amino-

carbene complex of chromium.⁴

In the ®rst example, starting from Fe(CO)₅, three carbons

derived from CO can be found in the end products (Eq. (1)).

Whereas two carbons clearly originate from the carbene

complex, it is nevertheless external CO which provides

with the third one.

A second point warrants a comment: the examination of the

general Scheme 1 which depicts the most important trans-

formations of carbene complexes rises the question of the

Keywords: tungsten; chromium; ylids; insertion reactions.

* Corresponding author. Laboratoire de Chimie Organique et Organo-

ꢀ1

Â

metallique, UMR 7611, Universite Pierre et Marie Curie T44-45, 4 place

Jussieu 75252, Paris Cedex 5, France. Tel.: 1331-44-27-61-97; fax: 1331-

44-27-70-89; e-mail: rudler@ccr.jussieu.fr

PII: S0040-4020(00)00214-3

5002

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

Scheme 1.

In the second example, involving an alkynyl aminocarbene

complex and leading to a mixture of 5 and 6, the origin of

two CO groups has again been established. As far as the

third CO group is concerned, the mechanism of its insertion

has not been clearly secured. Since no external CO pressure

was required in order to observe the formation of 6, the third

carbonyl group mandatory originates also from the start-

ing carbene complex either via an intramolecular

reaction, or according to an intermolecular reaction,

free CO being formed upon decomposition of the starting

material.

Analogy between Fischer-type carbene complexes and

carbonyl compounds: ®rst attempts to synthesize

alkylidene complexes of tungsten and chromium

pentacarbonyl

In contrast to high oxidation states of tungsten (and other

metals) for which alkylidene complexes are now well

known and routinely prepared and used for carrying out

ole®n metathesis reactions,^5±8only a few alkylidene

complexes of W(0) and Cr(0) were known despite much

efforts devoted to their synthesis.

Successful attempts were only observed in the case of aryl

substituted carbenes, e.g. diphenyltungstacarbene penta-

carbonyl, which was synthesized by Casey and Fischer as

early as 1975,^9,10and later, phenyltungstacarbene pentacar-

bonyl, isolated by Fischer and Casey.^11±15No alkyl substi-

tuted carbene complexes could be prepared since either

b-elimination reactions, or dimerization reactions took

place instead.^16,17All these approaches were related to the

analogy which emerged between alkoxycarbene complexes

and esters: nucleophiles lead, in general to substitution

products the formation of which is believed to proceed via

a stepwise mechanism involving tetrahedral intermediates

of the type 8.

ꢀ2

The purpose of this paper is to describe reactions related to

the two points mentioned above: on the one hand the inter-

action of dihydropyridines with alkoxycarbene complexes

of chromium and tungsten. This reaction is related to the

analogy which has been established between carbonyl

compounds and carbene complexes. It cleanly leads via

alkyl alkoxy pentacarbonyl pyridinium tungstates and chro-

mates to pyridinium ylid complexes. These new complexes

are stable sources of alkylidene fragments. Their structure

and reactivity will be thoroughly described.

On the second hand, the transformation of three CO ligands

of Cr(CO)₆in the coordination sphere of the metal will be

established: indeed, the intermediate tungstates and

chromates, easily prepared from carbene complexes and

N-methyldihydropyridines undergo multiple insertions of

alkenes, alkynes, together with CO: in the most gratifying

examples which lead to functionalized butenolides, starting

from Cr(CO)₆, a triple bond and three CO ligands were

incorporated.

ꢀ3

This is for example the case for amines: an intermediate

10 is formed which then undergoes a base-catalyzed

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5003

elimination to an aminocarbene complex 9 (NuNRR⁰).

Con®rmation of the involvement of a tetrahedral inter-

mediate came from the work of Fischer who isolated, in

the case of crowded tertiary amines, stable zwitterionic

species 11.^18±22

This complex proved to be stable only below 2208C but

could be further stabilized via its reaction with triphenyl-

phosphine, as a phosphonium ylid complex 21.

To summarize this last approach, the successive reagents

delivered a hydride, then a proton, to give an unstable alkyl-

idene complex, and ®nally, a nucleophilic trapping agent,

e.g. triphenylphosphine, formed a stable complex.

ꢀ4

Herewith we will demonstrate that a single reagent,

dihydropyridine, can ful®l all the three functions:

² it can deliver a hydride (vide infra) to the carbene-carbon

to give a tungstate and pyridinium as the counterion.

² pyridinium once formed can deliver a proton to the

oxygen atom of the ethoxy group to give pyridine and,

by elimination of ethanol from the tungstate, an alkyl-

idene complex.

Aryllithium derivatives reacted along the same lines:

addition of the aryl group to the carbene-carbon of 12,

followed by acid catalyzed elimination of ethanol, led to

diarylcarbene complex 13.^9,15

² ®nally pyridine can interact, as a nucleophile with the

electrophilic carbon of the alkylidene complex to give

a pyridinium ylid complex.

ꢀ5

ꢀ9

However, in the case of methyllithium formation of styrene

15, via the complex 14, was observed, even at low tempera-

ture.¹⁶

Moreover, the transformation is not limited to aryl-substi-

tuted alkoxycarbene complexes: it is of a general scope, and

what appears to be of the highest importance, unlike for

phosphonium ylid complexes of the type 21, which are

very stable, recovery of the properties of the alkylidene

group from the pyridine ylid complexes is easily achieved,

pyridine being less strongly bound to the carbene-carbon

than triphenylphosphine and thus easily eliminated.

ꢀ6

Methylethoxycarbene complex of tungsten 16a reacted also

with methyllithium to afford, after acid treatment, via an

unstable dimethylcarbene complex 17, a dinuclear m-alkyl-

idene complex 18.¹⁷

Dihydropyridines as reducing agents of carbonyl

compounds

Dihydropyridines are the cofactors of enzymes involved in

many biological reductions, e.g. the transformation of

ketones and aldehydes into alcohols. Thus, NADPH

(Nicotinamide adenosine diphosphate), a dihydropyridine,

delivers enantioselectively a hydride to the carbon of

carbonyl groups.^23±25

ꢀ7

Simpler dihydropyridines associated with Lewis acids have

also been used in organic chemistry for the same purpose, to

mimic biological reductions.²⁵

A further analogy between these complexes and esters came

from their behavior towards hydrides: complex hydrides

reacted indeed with complex 12 to afford an intermediate

tungstate 19 which, upon acid treatment, led to the benzyl-

idene complex 20.^11±15

Results and Discussion

Reaction of dihydropyridines with alkoxycarbene

complexes of chromium and tungsten: formation of

pyridinium ylid complexes and pyridinium chromates

and tungstates

ꢀ8

Since alkoxycarbene complexes can be considered as

highly activated esters, we attempted to reduce them

with a series of dihydropyridines. Thus, when a solution

5004

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

Table 1.

No.

Among the noticeable physical data are the shifts of the

signals in the ¹³C NMR spectrum of the former carbene-

carbons (Table 2) from d 333.4 to 57.2 for complex 24a,

whereas in the ¹H NMR spectrum, the C(1)±H appears as a

quartet at d 4.90.

R

Yield No.

R

Yield

24a Me

24b Ph

24c (CH₂)₃±Ph

24d (CH₂)₄±OPh

24e (CH₂)₈±CHvCH₂

41%

43%

48%

50%

48%

24f Cyclopropyl

24g t-Bu

24h (CH₂)₄±CH(OMe)₂

24i (CH₂)₂CHvCH₂

24j (CH₂)₃C;CPh

33%

35%

71%

65%

71%

The bond distances are classical for chromium±carbon and

Ê

tungsten±carbon single bonds, 2.250(6) and 2.32 (2) A

respectively.

of 1,4-dihydropyridine, prepared from pyridine according to

Fowler²⁶was added in excess (2±3 equiv.) to a yellow

ethereal solution of an alkoxycarbene complex of tungsten

or chromium, e.g. 16a, at room temperature, an orange color

developed rapidly. A fast disappearance of the starting

complex was observed. Silica gel chromatography of the

reaction mixture led to the isolation of two complexes, a

complex of low polarity, characterized as the known

M(CO)₅Py (MW, Cr, Pypyridine), in variable amounts,

and a polar, pale yellow, crystalline complex (e.g. 24a) in

33±71% yield (Table 1).^27,28

The reaction is not limited to dihydropyridine itself since

substituted dihydropyridines led to the same type of ylid

complexes.

Formation of 2,5-dihydropyridines from protected 1,2

dihydropyridines: concerted stabilization of two

unstable species: ethylidene tungsten(0) pentacarbonyl

and 2,5-dihydropyridines. A closer examination of the

reaction products provided evidence for the formation of

minor products in variable amounts, depending essentially

on the reaction conditions.

It is known that the reduction of pyridinium chloroformate

25 with NaBH₄leads to protected 1,2-dihydropyridine 26.²⁶

Deprotection of this dihydropyridine by means of MeLi

followed by protonation was assumed to lead to the single

1,2-dihydropyridine 28. The reaction appeared however

more complicated: indeed the interaction of the obtained

dihydropyridine with alkoxycarbene complex 16a led,

besides the expected pyridinium ylid complex 24a, to a

mixture containing two new complexes 33 and 34, the

yield of which was dependent on the amount of MeLi

used for the deprotection reaction.^27,28The structure of

these unexpected complexes could also be established

by NMR spectroscopy and ®nally by X-ray crystal-

lography.

ꢀ10

The new complexes were characterized by their NMR data

and by X-ray crystallography.

The X-ray structures of three of these complexes con®rmed

that indeed a hydride transfer to the carbene-carbon took

place, that the alkoxy group has been eliminated and that

dihydropyridine has been oxidized to pyridine. This is now

bound to the former carbene-carbon, the result being pyri-

dinium ylid complexes and appears clearly on the Cameron

projection of 24g (Fig. 1).

The more polar complex 33 is the result of the interaction of

2,5-dihydropyridine with the unknown ethylidene complex

35 (vide infra), whereas complex 34, is due to the inter-

action of 5-isopropylidene-2,5-dihydropyridine 32 with

Figure 1. Molecular structure of complex 24g.

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5005

1

Table 2. H and ¹³C NMR data, crystallographic data and bond distances (A) and angles (8) for complexes 24a,g, 33 and 34

Ê

Complex

NMR data

X-ray data

C(1)±N(1)

d

¹H H(1)

d

¹³C C(1)

W±C(1)

C(1)±C(2)

W±C(1)±C(2)

W±C(1)±N(1)

34

33

24a

24g

3.86

3.81

4.90

4.47

52.6

54.1

57.2

80.2

2.381(9)

2.34(2)

2.32(2)

2.369(6)

1.51(1)

1.48(2)

1.35(3)

1.550(9)

1.45(1)

1.54(2)

1.49(3)

1.504(8)

113.2(6)

116.6(13)

122.8(16)

124.7(5)

114.1(5)

109.2(11)

112.3(9)

112.0(4)

the same complex.

and possibly also with the two 2,5-dihydropyridines

which, being more stable than 1,2 and 1,4-dihydropyridines,

react rather like simple amines.

ꢀ11

Origin of the 2,5-dihydropyridines. The origin of these

two dihydropyridines was established essentially by label-

ing experiments.^28,29The preparation of 1,2-dihydropyri-

dine is outlined below:

ꢀ13

Finally, the thermal decomposition of the alkylidene

complexes can lead to W(CO)₆which interacts with pyri-

dine to give W(CO)₅Py.

ꢀ14

ꢀ15

ꢀ16

ꢀ12

The protected 1,2-dihydropyridine 26 which is an N,N-

disubstituted carbamate, reacts with MeLi to give the

lithium amide 27 and acetone.^30,31Acetone reacts with

excess MeLi to form t-BuOLi. The negative charge on the

nitrogen atom in 27 can be delocalized on C(3) as in 29 and

upon protonation, a mixture of 1,2- and 2,5-dihydropyri-

dines 28 and 30 can result. The isopropylidene group

originates from acetone, which reacts with the lithium

amide of 2,5-dihydropyridine 29 to give, after elimination

of lithium hydroxide, 3-isopropylidene-2,5-dihydropyridine

32. This in turn can be trapped by the ethylidene complex 35.

Improved synthesis of pyridinium ylid complexes:

lithium aluminum hydride reduction of pyridine to

dihydropyridines and nicotine to dihydronicotines. As

described above, the classical preparation of dihydro-

pyridines from pyridine involves, according to Fowler, a

two-step process: formation of protected dihydropyridines,

followed by a deprotection step Eq. (12).²⁶During the

deprotection step acetone, methanol and t-butanol are

formed which alter the course of the reaction, giving new

but undesired side products. There is nevertheless a way to

avoid such side reactions. Indeed, it has been shown by

Lansbury and Peterson that pyridine could also be reduced

Thus it appears clearly that the role of 1,2-dihydropyridine

is to reduce the alkoxycarbene complexes to the alkylidene

complexes (e.g. 35) with concomitant formation of pyri-

dine; the alkylidene complexes then react with pyridine

5006

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

by LiAlH₄to give inorganically bound derivatives 37 of

dihydropyridines (Eq. (17)).^32,33Later on, Tanner con®rmed

this structure by carrying out NMR experiments on the

hydrolysis products of these complexes.³⁴1,2-, 1,4- and

minor amounts of 2,5-dihydropyridines were detected

together with large amounts of pyridine. We have now

found that this method can be of a preparative use: the

addition of a molar solution of LiAlH₄in THF to pyridine

followed by heating at 708C for 5 h gave a yellow solution.

Careful hydrolysis followed by extraction with diethyl ether

gave solutions of dihydropyridines in this solvent which

were directly used for the reduction of the carbene

complexes.

Conjugated alkoxycarbene complexes react with nucleo-

philes or organometallic compounds to give either 1,4- or

1,2-addition products (or substitution products).^35,36

It was thus of interest to study the reactivity of such

complexes towards dihydropyridines since a 1,2-addition

of a hydride followed by elimination of ethanol would

lead to vinylidene pyridinium ylid complexes.

However, such was not the case: the interaction of solutions

of dihydropyridines with complexes 42 and 43 led, after

silica gel chromatography, to the known enol ether 44

whereas complex 45 gave 46 in 52% yield. A 1,4-addition

of the hydride to the conjugated carbene complexes

followed by protonation clearly can account for this result.

ꢀ17

ꢀ20

The yields of the pyridinium ylid complexes were signi®-

cantly improved: thus, complex 16a gave complex 24a in

94% yield (vs 41%) and complex 38 gave complex 39 in

82% yield (vs 50%)

It is interesting to notice at this point that the borohydride

reduction of conjugated carbene complexes has been

recently shown to give, according to labelling experiments,

enol ethers via a 1,2-addition of the hydride followed by a

1,3-migration of the metal.³⁷

ꢀ18

Pyridinium tungstates and chromates as intermediates

in the formation of pyridinium ylid complexes. As

already mentioned, a plausible mechanism for these reduc-

tion reactions involves the transfer of a hydride to the

carbene-carbon with formation of an intermediate metallate

36. This complex contains now a chiral carbon atom (the

former carbene-carbon) and thus two diastereotopic hydro-

gen atoms giving each a doublet of quartets should be

The same procedure was applied to nicotine: it led to

ethereal solutions of dihydronicotines which reacted with

the carbene complexes 16a and 38 to give the nicotinium

ylid complexes 40 and 41 in respectively 72 and 47% yields

as mixtures of diastereoisomers (de: 10%).

1

detected for the ethoxy group in the H NMR spectrum).

And this was indeed the case and was demonstrated by the

use of N-methyldihydropyridine²⁶as reducing agent.

ꢀ19

The most signi®cant signals in the H NMR spectrum of

1

complex 40, besides those due to the nicotinium group,

appeared at d 4.88 as a quartet for the hydrogen bonded

to the carbene carbon, and at d 2.32 as a doublet for the

methyl group.

ꢀ21

Indeed, if this dihydropyridine is also able to transfer a

hydride to the carbene-carbon, to give a N-methyl pyri-

dinium tungstate, no acid will be available to carry out the

Dihydropyridine induced 1,4 reductions of conjugated

alkoxycarbene complexes: formation of enol ethers.

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5007

second reaction, the protonation of the ethoxy group. The

elimination of ethanol should thus be slower and the

intermediate tungstate detectable. The interaction of

N-methyldihydropyridine with complexes 12 and 16a led

quantitatively to the rather unstable (vide infra) N-methyl-

dihydropyridine tungstates 47 and 48, which could be fully

characterized by NMR spectroscopy.

ꢀ22

ꢀ25

² Reaction of the N-methylpyridinium tungstate 47 with

tri¯uoroacetic acid in the presence of dihydropyran led

to the corresponding isomeric cyclopropanes 52 in 35%

yield.

ꢀ23

Transformation of pyridinium tungstates into pyridi-

nium ylids: alkylidene complexes as intermediates. If

the mechanism outlined above for the transformation of

the intermediate pyridinium tungstates into pyridinium

ylid complexes is correct, then the isolated tungstates

derived from N-methyldihydropyridine should lead to the

same alkylidene complexes and then to ylid complexes upon

treatment with the appropriate acids.

ꢀ26

Several experiments con®rmed this hypothesis

Reactivity of the pyridinium ylid complexes

² Reaction of the tungstate 47 with hydrogen chloride led,

in the presence of triphenylphosphine, to the phospho-

nium ylid complex 21.

Reaction with triphenylphosphine. That external ligands

were able to replace pyridine in the ylid complexes (a funda-

mental aspect as far as their reactivity and use in synthesis

are concerned) came from the reaction of PPh₃, a softer

ligand than pyridine, with complexes 24a,b: whereas the

substitution took place at room temperature for 24b to

give 21, heating in dichloromethane was necessary for the

transformation of 24a into 53. These two complexes are

very stable even in solution.

ꢀ24

ꢀ27

ꢀ28

² Reaction of the tungstate 50 obtained from complex 49a

with pyridinium hydrochloride, in the absence of any

other substrate, led to the pyridinium ylid 24j in 60%

yield.

Reaction with ole®ns: cyclopropanation reactions. Inter-

molecular reactions. The pyridinium ylid complexes

described herein are the result of the interaction of pyridine

with W(0) and Cr(0) alkylidene complexes: one might

5008

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

therefore wonder upon the reversibility of this interaction. If

so, a general access to alkylidene complexes of W(0) and

Cr(0), transferable to ole®ns would be possible: it has

indeed been shown that the benzylidene complex reacted

with ole®ns, at low temperature, to give phenylcyclo-

propanes.^13±15

to 63 as a mixture of cis/trans isomers (54 and 8% yield) and

64 led to 65 in 72% yield. This latter compound was isolated

as white crystals and subjected to an X-ray crystallographic

analysis. The CAMERON projection appears in Fig. 2 and

con®rms the structure of this compound.

Whereas complex 24b did not react with terminal ole®ns,

either at room temperature or in re¯uxing benzene, substi-

tuted ole®ns underwent the cyclopropanation reaction in

re¯uxing methylene chloride (30±50% yield).²⁷

Much better results were observed with electron-rich

ole®ns, such as enol ethers (63±97% yield). And we were

delighted to observe that even pyridinium ylids of tungsten

bearing an alkyl group led to the corresponding cyclo-

propanes (30% yield).^28,38

Even more gratifying were the reactions with the most

nucleophilic ole®ns, such as enamines³⁸and ketene acetals:

high yields of cyclopropylamines and acetals of cyclo-

propanones were obtained.

ꢀ30

Preliminary attempts were also made in order to use the

nicotinium ylid complexes as cyclopropanation reagents:

thus, complex 40 reacted with the enamine of cyclopenta-

none in re¯uxing dichloromethane to give the expected

aminocyclopropane 66 in 54% yield as a mixture of dia-

stereoisomers with seemingly no enantiomeric excess.

ꢀ31

One possible two-step mechanism is given in Eq. (32) and

involves two diastereomeric tungstacyclobutanes. It might

also account for the formation of alkylated ketones via a

zwitterionic intermediate.

ꢀ29

Thus, the cyclopropyl pyridinium ylid complex 24f reacted

with the enamine of cyclopentanone to give quantitatively

the expected dicyclopropylamines 54 as a 58:42 mixture of

exo:endo isomers, as shown by the NMR spectra (see

Experimental). In the case of complex 39, a mixture of

the expected cyclopropylamines 55 was isolated when the

reaction was carried out in re¯uxing benzene (exo: 51%,

endo: 41%), whereas the ring-opened ketone 56 was

obtained in 41% yield in dichloromethane, at room tempera-

ture. Interestingly, indole could be converted, via a two-step

cyclopropanation/rearrangement process, into 57, in 56%

yield.

ꢀ32

Ketene acetals behaved similarly and led in good yields to

the corresponding cyclopropanone mono or bis trimethyl-

silylacetals. Thus, starting from 58, 59 was isolated as a

1:1.8 mixture of isomers and 60 gave 61. Similarly, 62 led

Interaction of the negatively charged metal with the carbon

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5009

Figure 2. Molecular structure of compound 65.

of the iminium would then lead to two diasteromeric

tungstacyclobutanes and ®nally, upon reductive elimination

of the metal, to two cyclopropylamines.

by the double bond took place. However, in the case of

complexes which did not bear a substituent in a to the

carbene-carbon, the corresponding pyridinium ylid com-

plexes could be detected by NMR spectroscopy. But

again, these ylids underwent at room temperature a trans-

formation to the expected cyclopropanation products. (70±

90% yield). Several points warrant a comment:

Intramolecular reactions: direct cyclopropanations without

formation of pyridinium ylid complexes. Intramolecular

cyclopropanation reactions promoted by carbene complexes

are important in the synthesis of natural products. We had

clearly demonstrated, some years ago, that in contrast to

intermolecular cyclopropanations of ole®ns, intramolecular

cyclopropanation in Fischer-type carbene complexes

occurred readily provided that the two functions, the

carbene and the double bond were separated by three or

four carbon atoms.^39,40The N-ylid complexes behaved

similarly.

² the cyclopropanation is highly stereoselective (e.g. 67,

R⁰trans-(CH₂)₄CH₃!70) in that the trans double

bond gave only a trans-substituted cyclopropane and

the cis double bond a cis-substituted cyclopropane.

² in the case of complexes bearing a substituent on the

a-carbon, high stereoselectivity was again observed

since only one isomer could be detected (e.g. 67,

RCH₂Ph R⁰trans-(CH₂)₄CH₃!71), whereas for

R⁰H, a 1:1 mixture of isomers was obtained.

Thus, when a solution of complexes 67 (R±H) was

submitted to an excess of dihydropyridine, a fast consump-

tion of the starting material was again observed. However,

almost no pyridinium ylid complexes could be detected by

NMR spectroscopy: instead, after a few hours at room

temperature, metal-free organic products 68 due to an

intramolecular cyclopropanation reaction could be isolated

in 35±70% yield.²⁸

Reaction with alkynes: insertion of the triple bond and

CO. Intermolecular insertion reactions. In the same way as

the pyridinium ylid complexes react with nucleophilic

ole®ns, they react also with nucleophilic alkynes: thus

ethoxyacetylene and complex 24b gave, yet in low yield

(5%), a new stable alkoxycarbene complex 42: this complex

can indeed be considered as the insertion product of the

alkyne into the metal±carbon double bond of the benzyl-

idene complex 20.⁴¹

ꢀ34

ꢀ33

However, non-activated alkynes did not react in an inter-

molecular way with these ylid complexes.

Intramolecular insertion reactions. Since our efforts to

carry out intramolecular insertions of non-activated ole®ns

into pyridinium ylid complexes were successful (vide

supra), we attempted also to insert intramolecularly triple

bonds in such functions. Thus, when the ylid complex 24j

was heated in re¯uxing benzene for one hour, in the

Thus, direct trapping of the resulting alkylidene complexes

5010

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

presence of methanol, two major esters 72 and 73 were

ylid complexes of tungsten via their N-methylpyridinium

ylides⁴¹(Eq. (37)), trace amounts of aldehydes were

detected by NMR spectroscopy and isolated by silica gel

chromatography. Thus, in the case of complexes 49a,b, the

aldehydes 77a,b were isolated as oils, in 5±10% yields. The

¹³C NMR spectrum of 77b agreed with the presence of a

carbonyl group (d_CO, 204.23 ppm), of carbons s-bonded to

oxygen, at d 83.77 and 66.15 and of those of the unsaturated

alkyl chain at d 138.01, 115.00, 80.55, 79.43, 32.80, 29.04,

obtained in respectively 31 and 28 % yield.⁴¹

ꢀ35

1

28.19, 24.31, 18.52, 18.12, and 15.30; in the H NMR

spectrum, the aldehydic proton appeared as a doublet at d

9.64 whereas the diastereotopic protons of the ethoxy group

gave multiplets at d 3.50 and 3.59.

These esters are the result of the insertion of the triple bond,

of CO, then of methanol with loss of W(CO)₄and pyridine.

On a mechanistic point of view, it is likely that this aldehyde

originates from an intermediate acylium tungstate 76

(Ldihydropyridine or a molecule of solvent) upon proto-

nation, and can be considered as a double CO insertion

product into an alkyltungsten derivative.

When the thermolysis was carried out instead in the

presence of dihydrofuran, two new products which accord-

ing to their physical data resulted from the insertion of the

triple bond, CO and then of dihydrofuran were isolated.

To the major product (20%) was given structure 75, a cyclo-

butanone, to the minor product (8%) structure 74, a substi-

tuted dihydrofuran.

The formation of the different products can be rationalized

in the following way:

² Insertion of the triple bond gives as for ethoxyacetylene,

a new carbene complex. Insertion of CO can then

proceed and lead to a ketene complex (Eq. (36)).

² Methanolysis of this complex, by 1,2 or 1,4 addition of

the alcohol to the ketene would then give the observed

esters. In the presence of dihydrofuran, the intermediate

ketene complex undergoes either a (212) cycloaddition

reaction or a carbon±hydrogen bond activation with

formation of respectively the cyclobutanone 75 and the

substituted dihydrofuran 74.

ꢀ37

Trapping reactions with an a,b-unsaturated ketone, an

ole®n, or an alkyne. In order to shed more light on this

new insertion reaction, the following transformations typical

of known metal acylates (vide infra) were attempted.^42±44

Reaction with cyclopentenone. The interaction of the

carbene complex 23 and N-methylpyridine was carried out

in the absence of any source of proton so as to avoid the

formation of aldehydes. Instead, the reaction was conducted

at 2108C, in the presence of cyclopentenone.⁴⁵After slow

warming to room temperature overnight, work up as usual,

and silica gel chromatography, a 55% yield of 1,4-diketone

78 was obtained as a mixture of diastereomers. The spectro-

scopic data of these compounds agreed fully with this struc-

ture. The ¹³C NMR spectrum con®rmed the presence of two

carbonyl groups (d_CO215.6 and 209.9), of three methylene

groups besides the OCH₂group with its two diastereotopic

hydrogen atoms, and of two methine groups at d 88.2 and

43.9. Thus, a 1,4-addition of the acylmetalate to the conju-

gated ketone took place.

ꢀ36

ꢀ38

Reaction of N-methyldihydropyridine with ethoxycar-

bene complexes of tungsten and chromium: reduction

to N-methylpyridinium tungstates and chromates.

Formation of a-ethoxyacylium tungstates and chromates

upon CO insertion. During the synthesis of pyridinium

Reaction with tethered double bonds. When the same

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5011

reaction was carried out on complex 79,⁴⁶and the mixture

stirred at room temperature for 12 h, an organic product 80

was isolated in 10% yield upon silica gel chromatography.

Its ¹H NMR spectrum agreed with the presence of a cyclo-

propane showing signals at high ®eld, (d 0.95 and

0.43 ppm). The mass spectrum con®rmed the insertion of

a CO group into the organic ligand of the starting carbene

complex. However, according to the ¹³C NMR spectrum, no

carbonyl group was present in the product. Instead, a signal

for a carbon bearing an oxygen atom clearly appeared at d

66.1 ppm. This product resulted thus from an intramolecular

interaction of a hydroxycarbene with the carbon±carbon

double bond of the carbene moiety.

silica gel chromatography in 11% yield, together with a

new product, as an oil, in 10% yield. The mass spectrum

of this latter compound con®rmed the addition of the acylate

complex across the triple bond followed by protonation with

loss of the metal. The ¹H NMR spectrum exhibited, besides

the signals for the aromatic protons and those for the

terminal double bond, a signal for one proton at d 7.74 as

a singlet together with two signals at d 3.53 and 3.34 ppm

for the two diastereotopic protons of the ethoxy group. The

¹³C NMR spectrum con®rmed the presence of two methyl-

ene groups together with a methine group, thus structure 87.

ꢀ42

ꢀ39

Intramolecular alkyne, alkene, and CO cascade inser-

tions: ef®cient formation of functionalized butenolides.

We were able to demonstrate that indeed metal acylates

generated from simple alkoxycarbene complexes and

N-methyldihydropyridines could be trapped either by conju-

gated carbonyl compounds or by alkenes intramolecularly

and alkynes intermolecularly. In relation with our previous

work⁴⁷on the intramolecular insertions of alkynes into

alkoxycarbene complexes and aminocarbene complexes,

we decided to focus our attention on the reactivity of a series

of tungsten and chromium alkoxycarbene complexes

containing a triple bond, or a triple and a double bond,

towards N-methyldihydropyridines in the hope to accede

to functionalized polycyclic compounds.

In the case of the tungsten complex 81a, bearing two double

bonds,⁴⁶the course of the reaction was somewhat different:

the expected hydroxycyclopropane 82 was again observed,

albeit in lower yield (1±7%). Its structure could also be

established by mass spectrometry and by extensive NMR

spectroscopy. Besides 82, two substituted cyclopentanones

83 could be isolated in 54% yield as oils. Their physical data

were also in agreement with such a structure: of signi®cance

were the signals at d 218.9 for the carbonyl group, at d 86.0

for the carbon bearing the ethoxy group, and in the ¹H NMR

spectrum, the signals due to the terminal double bond, to the

methyl group in a to the carbonyl group, as a doublet, to the

two diastereotopic protons of the ethoxy group, at d 3.79

and 3.52, and to the proton in a to the carbonyl, giving a

doublet at d 3.29. The corresponding chromium complex

81b gave only 83 in 83% yield.

Alkynylethoxy carbene complexes of tungsten: insertion of

the alkyne and of one CO group. The various tungsten

complexes 49a, 89, and 91 were prepared according to

classical methods of the literature. Their physical data can

be found in the Experimental section.

ꢀ40

Reactivity of the alkynyl carbene complexes of tungsten 49a

and 89.

In the case of the chromium complex 85 obtained from

complex 84 upon alkylation, no cyclopropane-containing

compound could be detected. The sole product of the reac-

tion was the cyclopentanone 86, obtained as an oil in 73%

yield. Its structure was again assessed thanks to its physical

data (see Experimental).

ꢀ43

When an etheral solution of the carbene complex 49a was

treated at 2108C with a ®vefold excess of N-methyldi-

hydropyridine, a deep red solution formed rapidly. It was

allowed to warm to room temperature and stirred at this

temperature overnight. Evaporation of the solvent followed

by silica gel chromatography led to a single product as an

oil, in 26% yield. The spectroscopic data were all in agree-

ꢀ41

1

ment with structure 88. The H NMR spectrum con®rmed

the presence, besides the aromatic group, of a trisubstituted

double bond, with signals for six protons between d 7.33

and 7.21, for the proton in a to the carbonyl group at d 3.89

as a doublet of doublets and for two diastereotopic protons

of the ethoxy group at d 3.52 and 3.75. The ¹³C NMR

Reaction of complex 79 with diphenylacetylene. Under the

same conditions as above, the interaction of diphenylacetyl-

ene with complex 79 led to the formation of two

compounds: the hydroxy cyclopropane 80 isolated upon

5012

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

spectrum was in agreement with the presence of a carbonyl

group at d 201.3 and of two quaternary carbons at d 137.8

and 135.7. Compound 88 is thus formed via the intramolec-

ular version of the addition of the tungsten acylate to a triple

bond, a reaction which leads to a six-membered ring. This is

followed by the release of the metal upon protonation.

Being aware of this fact, we expected also different products

in going from tungsten complexes of the type 49a to

chromium complexes of the type 94. And this was indeed

con®rmed.

Thus, when complex 94 was treated as above with a solution

of N-methyldihydropyridine, two compounds were isolated

after work up and silica gel chromatography in a 73% over-

all yield. To the more polar compounds, isolated as

two isomers (1:10) were assigned structures 95a,b. The

elemental analysis of the less abundant compound 95a

isolated as white crystals con®rmed the insertion of two

CO groups in the organic ligand of the starting complex.

The ¹³C NMR data were typical of a butenolide (d_CO, 173.3,

d Cq, 161.0, and 125.4, and d_CO, 82.0 76.0 and 67.1). The

¹H NMR spectrum indicated the presence of a methine

group with a doublet (J3.5 Hz) for a hydrogen at d 4.78

and of an ethoxy group with two diastereotopic hydrogens.

The structure of this compound was ®nally con®rmed by

an X-ray analysis which showed indeed the presence of a

butenolide and con®rmed the cis geometry of the two

carbon±oxygen single bonds.⁴⁸

ꢀ44

In the case of complex 89, bearing a benzyl group in a to

the carbene carbon, a mixture of two diastereomeric cyclo-

hexanones 90a,b was obtained in respectively 38 and 19%

yield. Both compounds are substituted cyclohexanones as

indicated by their NMR data: of interest, besides signals for

the carbonyl groups respectively at d 200.7 and 202.0, are

the signals of the protons in a to the carbonyl groups. In

both compounds it appears as a doublet, with J2.9 Hz in

90a, and J10 Hz in 90b: in the former product, the ethoxy

and the benzyl groups are thus cis, whereas in the latter

these two groups are trans. Con®rmation of these stereo-

chemistries was obtained by NOE experiments on both

compounds. The structure, and thus the stereochemical

arrangement of the various substituents in 90b could ®nally

be assessed by an X-ray structure determination.

The physical data of the major product, isolated as an oil,

were in agreement with structure 95b, the coupling constant

between the hydrogen atoms at C-7 and C-7a being equal to

8.4 Hz, thus in agreement with a trans location.

Reactivity of the alkynyl alkenyl carbene complex of

tungsten 91. We have demonstrated above that both double

and triple bonds can insert into the metal±carbon bond of

the new alkoxytungsten acylates. Competition between the

two types of unsaturations might occur in a complex such as

91, although the two are tethered through two different

numbers of carbons. This complex led to a 1:1 mixture of

the two possible compounds 92 and 93 in 36% yield. The

NMR spectra of the two compounds clearly indicated the

presence of a carbon±carbon double bond in 92 and of a

carbon±carbon triple bond in 93.

ꢀ46

A minor, less polar product was also isolated, in 10% yield.

It differed from compounds 95 by the absence of an ethoxy

group, and the presence of a triplet due to a vinylic proton at

d 5.96. Thus structure 96 was assigned to this compound: it

is the result of the elimination of ethanol from compounds

95a,b.

ꢀ47

ꢀ45

The behavior of complex 97 bearing a benzylic substituent

was similar: under the same conditions, only two diastereo-

isomers 98a,b were formed in respectively 15 and 50%

yields. To the minor product, isolated as white crystals

was given structure 98a on the grounds of the elemental

analysis and extensive NMR data. As for the previous

butenolides, the ¹³C NMR spectrum con®rmed the presence

of all the carbons of the unsaturated lactone with signals at d

172.9 (CO), 161.2 and 124.9 for the carbons of the double

bond, 86.5, 86.4 and 68.3 for the carbons linked to oxygen.

The coupling constant between H-7 and H-7a, 8.2 Hz,

con®rmed the trans geometry of these two hydrogens

Reactivity of alkynyl and alkynyl alkenyl chromium

complexes towards N-methyldihydropyridines. The modi®-

cation of the nature of the metal in Fischer type carbene

complexes can deeply alter the course of their reactions

with unsaturated substrates. For example, chromium

carbene complexes usually react at lower temperature

with ole®ns and alkynes than their tungsten counterparts.

Moreover, the nature of the products depends strongly on

the metal: whereas in the case of chromium alkynes are

inserted together with a CO ligand, in the case of tungsten,

only the insertion of the alkyne is observed.

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5013

atoms. The structure and thus the indicated stereochemistry

was again assessed by an X-ray analysis: H-7 is trans with

respect to H-7a and H-6. As far as the major product of the

reaction is concerned, the coupling constant between H-7a

and H-7 is 3 Hz, indicating a cis relationship. NOE experi-

ments were performed on this compound to assess the

stereochemistry of H-7a with respect to H-7 and H-6:

irradiation on H-7a affected both H-7 and H-6, this indicated

clearly an overall cis relationship between these hydrogen

atoms.

the double bond into the intermediate chromium acylate

metal±carbon bond was isolated in 66% yield and fully

characterized by its physical data (see Experimental).

Incorporation of an oxygen atom in the alkynyl chain of

the carbene complexes: direct formation of a tetrahydro-

furopyranone and a tetrahydrofuro oxepinone. A ®nal

yet important modi®cation was introduced in the structure

of the starting carbene complexes: the inclusion of oxygen

in the alkynyl chain. These complexes were easily synthe-

sized by proven methods: indeed, reaction of the tetramethyl

ammonium chromium acylate 105 with two acetylenic

alcohols led to the carbene complexes 106 and 107 which

were fully characterized by their physical data (see Experi-

mental).

A methyl group instead of the benzyl group in the starting

complex did not modify the course of the reaction. Thus,

complex 99 led to a 4:3 mixture of two isomers 100a,b.

Their stereochemistry was ascertained by NMR spectro-

scopy: whereas a cis geometry between H-7 and H-7a was

indicated by a coupling constant of 8.4 Hz in the major

product, a trans geometry appeared between these two

hydrogen atoms in the minor product (J3.4 Hz).

ꢀ51

ꢀ48

When complex 106 was reduced with N-methyldihydro-

pyridine, under the same conditions as above, a single

compound 108 was obtained in 46% yield after work up

and silica gel chromatography as white crystals. Both the

elemental analysis and the NMR data were in agreement

with the insertion of two CO groups in the organic ligand

of the carbene complex. The ¹³C NMR spectrum con®rmed

the formation of a butenolide with signals at d 171.9 for the

carbonyl group, 159.43 and 138.02 for the carbon±carbon

double bond, 85.03, 81.19, and 67.80 for the three carbons

linked to oxygen. In the ¹H NMR spectrum, except for those

of the phenyl groups, all the hydrogen atoms were well

differentiated.

Similarly, neither an alkyl substituent on the triple bond nor

one less methylene group in the alkynyl chain, as in

complex 101 inhibited the insertion reaction: the same

type of butenolide was isolated as a 1:1 mixture of two

isomers 103a,b in a 58% overall yield. The geometry of

the isomers, which could be separated by silica gel chroma-

tography, was again ascertained by NMR spectroscopy.

The structure of this polyinsertion product was ®nally

con®rmed by an X-ray analysis. The CAMERON projection

appears in the Fig. 3.

ꢀ49

Finally, the reduction of complex 107 containing one more

methylene group in the alkyl chain was also carried out:

only a low yield (8%) of the bicyclic lactone 109 was

observed. Its mass spectrum and the NMR data agreed

fully with such a structure.

However, as in the case of the tungsten complexes, a

product 102, a propylidene ethoxycyclopentanone, lacking

thus a CO group, was also isolated in 11% yield. Its mass

spectrum as well as the NMR data con®rmed this structure:

one observes inter alia, a signal at d 6.65 attributable to the

ole®nic proton, and signals for two diastereotopic hydro-

gens of the ethoxy group at d 3.83 and 3.63.

ꢀ50

ꢀ52

Mechanism of the polyinsertion reactions. The formation

of polycyclic butenolides from chromium hexacarbonyl in a

two-step process is complex and unprecedented since it

involves the ef®cient incorporation of a triple bond together

with three CO ligands of the metal without the need of

Surprisingly, when complex 104 containing both a double

and a triple bond was subjected to the N-methyldihydro-

pyridine reduction, no interaction with the triple bond was

observed: a single product 93 resulting from the insertion of

5014

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

Figure 3. Molecular structure of compound 108.

external CO. Three fundamental features can be distin-

guished in the reactions described herein

and nickel tetracarbonyl.^42,43This reaction leads to metal

acylates. The insertion of CO is in general promoted by

an overpressure of CO or by external ligands.

² a key-step, the unexpected and straightforward transfer of

a hydride from dihydropyridines to the carbene-carbon of

alkoxycarbene complexes of chromium and tungsten.

This occurs both with dihydropyridines and N-methyldi-

hydropyridines and leads ®rst to alkoxyalkyl pyridinium

chromates and tungstates then to pyridinium ylid

complexes.

The chemistry of more simple, non-functionalized metal

acylates is well established: they react with ole®ns (e.g.

iron acylates), with alkynes (e.g. chromium and manganese

acylates), with conjugated carbonyl compounds (e.g. nickel,

chromium, and manganese acylates).

Taken altogether, the above known separate reaction path-

ways can explain the following cascade transformations of

the alkoxycarbene complexes of chromium and tungsten:

ꢀ53

² the formation of 1,4-diketones from cyclopentenone

² the formation of substituted a-ethoxycyclopentanones

from butenylethoxycarbene complexes of chromium.

² the formation of a-benzylidene a⁰-ethoxycyclohexa-

nones from phenylhexynylethoxy carbene complexes of

tungsten.

² a second step, the almost quantitative `regeneration' of

the alkylidene group either from the ylid complexes or

from the alkoxyalkyl metalates, a transformation which

is of importance as far as its application to organic synth-

esis is concerned.

The formation of hydroxycyclopropanes is less obvious and

had to the best of our knowledge not been observed up to

now. Intramolecular cyclopropanation reactions have been

well established especially in the chromium and tungsten

carbene chemistry.^39,40One of the resonance forms of the

metal acylates is an oxycarbene complex 112: an intra-

molecular interaction between the double bond and this

carbene might then lead to the observed hydroxycyclopro-

panes 113.

ꢀ54

² the almost quantitative insertion of CO into the alkoxy-

alkyl N-methylpyridinium metalates which leads to

a-alkoxy metal acylates.

ꢀ55

ꢀ56

As far as the mechanism of these and the following reactions

is concerned, insertion of CO into the metal±carbon s bond

of alkyl (carbonyl) metalate is known, the most signi®cant

examples deriving from the chemistry of iron pentacarbonyl

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5015

The formation of butenolides upon successive insertions of

alkynes and CO into metal acylates is related to the

general behavior of Fischer-type carbene complexes

towards alkynes: it involves here again an oxycarbene

complex 112 and takes place according to the following

scheme:

complexes of tungsten and chromium has opened a new

®eld of application of Fischer carbene complexes. Depend-

ing on the nature of the dihydropyridine, either cyclopro-

panation or alkyne insertions reactions can be carried out.

On a synthetic point of view, among the various structural

features which can be achieved, the entry in the butenolide

structure is by far the most gratifying since these

compounds can have interesting pharmacological proper-

ties. On a fundamental point of view, the use of three ligands

of the starting metal carbonyl is also of importance since in

general only up to two CO groups are incorporated in the

end products.

² the interaction of the carbene complex with the alkyne

gives a new carbene complex (117!118)

² this new carbene complex can suffer a CO insertion reac-

tion to give a ketene complex (118!120): this occurs in

the benzannulation reaction, in the insertion of alkynes

into aminocarbene complexes.

² the ketene complex can react intermolecularly with

nucleophiles such as water and alcohols to give acids

or esters and intramolecularly with nucleophiles to give

lactames as in the case of aminocarbene complexes: this

reaction has been thoroughly studied in our Laboratory.⁴⁷

Experimental

General

All reactions were performed under a dry argon atmosphere.

Solvents were distilled from sodium/benzophenone ketyl

(diethyl ether, tetrahydrofurane), phosphorous pentoxide

(dichloromethane) and saturated with argon. Silica gel

(Merck, type 60, 0.063±0.200 mm was used for column

chromatography. ¹H NMR: Bruker AC-200 (200 MHz),

Bruker ARX-400 (400 MHz). ¹³C NMR: AC-200

(50 MHz) and Bruker ARX-400 (100 MHz). All NMR

spectra were recorded in CDCl₃unless stated otherwise

with CHCl₃as internal standard. MS and HRMS: Kratos

MS 50. M.P.: Reichert, the reported melting points are

incorrect. TLC: 0.25 mm Merck silica gel plates 60 F₂₅₄

.

Preparation of the carbene complexes 12, 16a, 16f, 16g

and 38

Complexes 12 and 16a were prepared following the literature

procedures.⁴⁹

Complexes 16f and 38 were prepared by an halogen±metal

exchange reaction.

Typical procedure: to a solution of bromocyclopropane

(0.68 ml, 8.5 mmol) in Et₂O (20 ml) at 2788C, was added

slowly a solution of t-BuLi (10 ml, 1.7 M) in hexane. After

30 min at 2788C, the reaction medium was transferred to a

¯ask containing a suspension of W(CO)₆(3.0 g, 8.5 mmol)

in Et₂O (30 ml) at 08C. After 1 h at room temperature, the

mixture turned brown. The solvent was evaporated in vacuo.

The crude was dissolved with water (60 ml) and petroleum

ether (30 ml). Et₃O¹BF₄²(1.6 g, 8.5 mmol) was then added

in small portions and the organic layer turned instan-

taneously orange.

ꢀ57

It is such an interaction which can explain the formation of

lactones from alkoxycarbene complexes. (120!95) Similar

conclusions have been drawn by Hoye and coworkers to

explain the formation of butenolides from manganese and

chromium acylates.⁴⁴

At the stage preceding the protonation, elimination of the

ethoxy group can also take place: this will lead to a doubly

unsaturated lactone (120!96).

The mixture was extracted with PE. After washing (satu-

rated aqueous NaHCO₃solution, water and brine) and

drying (Na₂SO₄), the solvent was evaporated in vacuo and

the residue puri®ed by column chromatography (PE) to

afford 16g (0.41 g, 11%) as a yellow powder and 16f

(1.38 g, 39%) as a light yellow powder.

Finally, it is known that for tungsten the propensity for CO

insertions is lower than for chromium: the reaction ends

with the formation of 119, the protonation of which

followed by reductive elimination leads to 88.

Conclusion

The complex 38 (60%) was obtained by the same procedure

as a light yellow powder together with 16g in low yield

(5%).

The reaction of dihydropyridines with alkoxycarbene

5016

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

16f: mp348C. ¹H NMR (400 MHz, CDCl₃) d: 4.79 (2H, q,

J7.0 Hz, OCH₂); 3.46 (1H, m, CH); 1.50 (3H, t, J7.0 Hz,

CH₃); 1.38, 1.20 (4H, m, CH₂). ¹³C NMR (100 MHz,

CDCl₃) d: 326.1 (WvC); 203.9 (CO trans); 197.8 (CO

cis); 79.3 (OCH₂); 44.2 (CH); 17.8 (CH₃, CH₂); 14.6

(CH₂). Anal. calcd for C₁₁H₁₀O₆W: C, 31.30; H, 2.39.

Found: C, 31.44; H, 2.22.

W±CH); 2.74 (1H, m, W±C±CHH⁰); 2.30 (1H, m, W±C±

CHH⁰); 1.64±1.41 (7H, m, CH, CH₂); 1.19±1.12 (2H, m,

CH₂). ¹³C NMR (100 MHz, CDCl₃) d: 204.8 (CO trans);

202.0 (CO cis); 140.1, 136.5, 126.8 (CH pyr.); 63.1 (W±C);

50.5 (W±C±CH₂); 39.1, 32.8, 31.8, 25.2, 25.1 (CH, CH₂).

Anal. calcd for C₁₇H₁₇NO₅W: C, 40.88; H, 3.44; N, 2.81.

Found: C: 40.81; H, 3.63 N; 2.97.

1

24f: 48% using method 1. Mp: 838C. H NMR (400 MHz,

16g: mp298C. ¹H NMR (400 MHz, CDCl₃) d: 4.99 (2H, q,

J7.0 Hz, OCH₂); 1.62 (3H, t, J7.0 Hz, O±C±CH₃); 1.23

(9H, s, CH₃). ¹³C NMR (100 MHz, CDCl₃) d: 346.1

(WvC); 202.1 (CO trans); 197.8 (CO cis); 81.2

(OCH₂); 58.7 (C_q); 29.2 (CH₃); 14.7 (O±C±CH₃).

HRMS calcd for C₁₂H₁₄O₆W: 438.0299. Found: 438.0302.

Anal. calcd for C₁₂H₁₄O₆W: C, 32.90; H, 3.22; Found: C,

34.00; H: 3.50.

CDCl₃) d: 8.59 (2H, d, J7.2 Hz, H_opyr.); 7.84 (1H, t,

J7.2 Hz, H_ppyr.); 7.60 (2H, t, J7.2 Hz, H_mpyr.); 3.91

(1H, d, J10.6 Hz, W±CH); 2.01 (1H, m, CH); 1.03 (1H, m,

CH₂); 0.69 (1H, m, CH₂); 0.53 (1H, m, CH₂); 0.10 (1H, m,

CH₂). ¹³C NMR (100 MHz, CDCl₃) d: 204.7 (CO trans);

201.9 (CO cis); 139.5, 136.5, 126.5 (CH pyr.); 70.4 (W±C);

24.9 (CH); 10.4 (CH₂); 10.2 (CH₂). Anal. calcd for

C₁₄H₁₁NO₅W: C, 36.79; H, 2.43; N, 3.06. Found: C,

36.87; H, 2.52; N, 3.06.

38: mp318C. ¹H NMR (400 MHz, CDCl₃) d: 4.89 (2H, q,

J7.0 Hz, OCH₂); 3.24 (2H, d, J5.0 Hz, vC±CH₂); 2.24

(1H, hept, J5.0 Hz, CH); 1.83±1.44, 1.21±1.04 (8H, m,

CH₂); 1.61 (3H, t, J7.0 Hz, CH₃). ¹³C NMR (100 MHz,

CDCl₃) d: 334.6 (WvC); 202.9 (CO trans); 197.5 (CO cis);

80.7 (OCH₂); 71.1 (WvC±CH); 38.0 (CH); 32.5, 24.8

(CH₂); 14.9 (CH₃). Anal. calcd for C₁₄H₁₆O₆W: C, 36.20;

H: 3.47. Found: C, 36.17; H, 3.65.

24g: 49% using method 1. Recrystallization (CH₂Cl₂/

Hexane) mp: 858C. H NMR (400 MHz, CDCl₃) d: 8.86

1

(1H, m, H_opyr.); 8.37 (1H, m, H_opyr.); 7.96 (1H, m, H_p

pyr.); 7.68 (1H, m, H_mpyr.); 7.54 (1H, m, H_mpyr.); 4.47

(1H, s, CH); 1.10 (9H, s, CH₃). ¹³C NMR (100 MHz, CDCl₃)

d: 203.5 (CO trans); 201.9 (CO cis); 144.5, 141.0, 138.5,

126.4, 126.2 (CH pyr.); 82.0 (CH), 39.3 (C_q); 30.9 (CH₃).

Anal. calcd for C₁₅H₁₅NO₅W: C, 38.05; H, 3.20; N, 2.95.

Found: C, 38.01; H, 3.40; N, 2.91.

Preparation of the dihydropyridines 28 and reaction

with the complexes 12, 16a, 16f, 16g and 38

Method 1: This preparation of the dihydropyridines 28 was

described by Fowler.²⁶

Reaction of dihydronicotine with the complexes 16a and

38

Method 2: Typical procedureÐin a ¯ask equipped with a

condenser, pyridine (6 ml) was treated by a solution of

LiAlH₄(4.5 mmol, 1 M) in THF. The yellow solution was

heated at 708C for 5 h and then cooled with an ice-bath.

Saturated aqueous sodium and potassium tartrate solution

was then added slowly. The mixture was extracted with

Et₂O. After washing (water, brine) and drying (Na₂SO₄),

the ether phase containing 28 was added to a solution of

complex 16a, 12 or 38 (3 mmol) in Et₂O (10 ml). The

solution enlighted instantaneously and the solvent was

evaporated in vacuo. The crude mixture was chromato-

graphed on silica gel (40% CH₂Cl₂/PE) to obtain respec-

tively 24a,²⁷24b²⁷or 39 as powders.

In a ¯ask equipped with a condenser, to a solution of

nicotine (4.8 ml, 30 mmol) in THF (18 ml) was added

slowly a solution of LiAlH₄(8.5 ml, 1 M) in THF. Then

the procedure followed the method 2 and a freshly prepared

ether solution of dihydronicotine was added to a solution of

complex 16a or 38 (1.5 mmol) to afford, after chroma-

tography on silica gel (CH₂Cl₂), the complexes 40 (0.55 g,

72%) or 41 (0.41 g, 47%) as orange oils (mixture of dia-

stereoisomers, de%10%).

24a: 94% using method 2. Mp: 1278C. ¹H NMR (400 MHz,

CDCl₃) d: 8.55 (2H, d, J6.0 Hz, H_opyr.); 7.82 (1H, m, H_p

pyr.); 7.59 (2H, m, H_mpyr.); 4.90 (1H, q, J7.0 Hz, CH);

2.53 (3H, d, J7.0 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃)

d: 204.5 (CO trans); 201.9 (CO cis); 139.2, 136.2, 126.6

(CH pyr.); 57.2 (CH); 30.7 (CH₃).

1

40: H NMR (400 MHz, CDCl₃) d: 8.61 (1H, s, H³); 8.45

(1H, d, J6.0 Hz, H⁷); 7.84 (1H, d, J7.8 Hz, H⁵); 7.52

(1H, dd, J6.0, 7.8 Hz, H⁶); 4.88 (1H, q, J7.2 Hz, H¹, 1

dia.); !4.87 (1H, q, J7.2 Hz, H¹, 1 dia.); 3.34 (2H, m, H¹¹);

24b: 88% using method 2. Mp1058C. ¹H NMR (400 MHz,

CDCl₃) d: 8.92 (2H, d, J6.0 Hz, H_opyr.); 7.90 (1H, m, H_p

pyr.); 7.66 (2H, m, H_mpyr.); 7.39±7.25 (5H, m, Ph); 6.03

(1H, s, CH). ¹³C NMR (100 MHz, CDCl₃) d: 203.9 (CO

trans); 201.6 (CO cis); 148.7, 141.9, 138.4 (CH pyr.);

128.7, 127.6, 126.7, 125.7 (Ph), 70.8 (CH).

2.39 (1H, q, J8.9 Hz, H¹⁰); 2.32 (3H, d, J7.2 Hz, H²);

0

2.28 (1H, m, H¹⁰); 2.25 (3H, s, H¹²); 1.97 (1H, m, H⁸); 1.87

0

(1H, m, H⁹); 1.69 (1H, m, H⁹). ¹³C NMR (100 MHz, CDCl₃)

d: 205.0 (CO trans); 202.5 (CO cis); 138.9 (C³); 138.0 (C⁴, 1

dia.); 137.9 (C⁴, 1 dia.); 135.8 (C⁷); 132.4 (C⁵); 126.7 (C⁶);

68.4 (C¹¹); 57.2 (C¹); 57.1 (C⁸); 40.7 (C¹²); 35.8 (C¹⁰); 31.2

(C², 1 dia.); 31.1 (C², 1 dia.); 23.3 (C⁹). HRMS calcd for

C₁₇H₁₈N₂O₅W: 514.0725. Found: 514.0728.

1

39: 82% using method 2. Mp: 1138C. H NMR (400 MHz,

CDCl₃) d: 8.52 (2H, d, J6.0 Hz, H_opyr.); 7.82 (1H, m, H_p

pyr.); 7.58 (2H, m, H_mpyr.); 4.76 (1H, dd, J10.6, 5.0 Hz,

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5017

1

44: Isomer Z. H NMR (400 MHz, CDCl₃) d: 7.36±7.19

(5H, m, Ph); 6.10 (1H, dt, J6.1, 1.5 Hz, O±CHv); 4.61

(1H, dt, J7.4, 6.1 Hz, C±CHv); 3.87 (2H, q, J7.1 Hz,

OCH₂); 3.49 (2H, dd, J7.4, 1.5 Hz, CH₂±Ph); 1.32 (3H, t,

J7.1 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) d: 145.3

(O±Cv); 142.0, 128.4, 125.8 (Ph); 105.6 (C±Cv); 67.8

(OCH₂); 30.3 (CH₂±Ph); 15.4 (CH₃).

1

46: H NMR (400 MHz, CDCl₃) d: 5.77 (1H, m, vCH);

3.69 (2H, q, J6.8 Hz, OCH₂); 2.16 (2H, m, CH₂±Cv);

1.91 (2H, m, CH₂±Cv); 1.47 (6H, m, CH₂); 1.21 (3H, t,

J6.8 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) d: 137.3

(vCH); 118.6 (C_q); 67.2 (OCH₂); 30.7, 28.5, 27.1, 26.9,

25.6 (CH₂); 15.2 (CH₃).

41: ¹H NMR (400 MHz, CDCl₃) d: 8.53 (1H, d, J6.8 Hz,

H⁸); 8.36 (1H, dd, J7.2, 6.8 Hz, H¹²); 7.76 (1H, d,

J7.2 Hz, H¹⁰); 7.49 (1H, m, H¹¹); 4.74 (1H, dd, J10.6,

5.2 Hz, H¹); 3.26 (2H, m, H⁶); 2.73 (1H, m, H²); 2.45±2.20

0

(2H, m, H², H¹⁵); 2.21 (3H, s, H⁷); 1.98±1.79 (2H, m, H¹³,

0

H

¹⁵); 1.72±1.51 (7H, m, H³, H⁴, H⁷, H₀¹⁴); 1.49±1.37 (2H,

0

m, H⁵, H⁶); 1.21±1.08 (2H, m, H⁵, H⁶). ¹³C NMR

(100 MHz, CDCl₃) d: 204.7 (CO trans); 202.1 (CO

cis); 144.9 (C⁹); 139.3 (C⁸); 138.4 (C¹²); 135.8 (C¹⁰);

126.3 (C¹¹); 67.9 (C¹⁶); 62.6 (C¹); 56.8 (C¹³); 50.5 (C²,

1 dia.); 50.4 (C², 1 dia.); 40.4 (C¹⁷); 39.3 (C³); 35.6

(C¹⁵); 32.8 (C⁴); 31.9 (C⁷); 25.3 (C⁵); 25.1 (C⁶); 23.0

(C¹⁴). HRMS calcd for C₂₂H₂₆N₂O₅W: 582.1351. Found:

582.1355.

Cyclopropanation reactions of pyridinium ylid

complexes with enamines

To a solution of 4-cyclopent-1-enyl-morpholine⁵⁰(350 ml,

2.2 mmol) in CH₂Cl₂(10 ml) was added 24f (0.25 g,

0.55 mmol). The solution was stirred for 3 h at room

temperature then the solvent was evaporated in vacuo.

After chromatography column, 54 exo (PE, 66 mg, 58%)

and 54 endo (5% Et₂O/PE, 48 mg, 42%) were obtained as

oils.

Reaction of the dihydropyridines 28 with the conjugated

complexes 42, 43 and 45

The conjugated carbene complexes 42,⁵¹43⁵²and 45⁵⁷were

prepared following the literature procedures.

42: mp: 998C. ¹H NMR (400 MHz, CDCl₃) d: 7.91 (1H, d,

J19.0 Hz, vCH±Ph); 7.65±7.44 (5H, m, Ph); 7.23 (1H, d,

J19.0 Hz, CHvCH±Ph); 4.97 (2H, q, J7.0 Hz, OCH₂);

1.71 (3H, t, J7.0 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃)

d: 305.3 (WvC); 203.9 (CO trans); 197.7 (CO cis); 143.6

(vCH±Ph); 134.7 (CHvCH±Ph); 134.2, 131.0, 129.3,

129.1 (Ph); 79.0 (OCH₂); 15.1 (CH₃).

1

54 exo: H NMR (400 MHz, CDCl₃) d: 3.63 (4H, t, J

5.2 Hz, OCH₂); 2.78 (2H, dt, J11.2, 5.2 Hz, N±CHH⁰);

2.52 (2H, dt, J11.2, 5.2 Hz, N±CHH⁰); 1.86 (1H, m,

0

H⁵); 1.68 (1H, m, H³); 1.56 (3H, m, H³, H⁴, H⁵); 1.06

0

(1H, m, H⁴); 0.97 (1H, t, J4.0 Hz, H²); 0.81 (1H, m,

H⁷); 0.42 (2H, m, H⁸, H⁹); 0.20 (1H, dd, J8.6, 4.0 Hz,

0

43: mp: 888C. ¹H NMR (400 MHz, CDCl₃) d: 7.93 (1H, d,

J15.5 Hz, vCH±Ph); 7.59±7.40 (5H, m, Ph); 6.93 (1H, d,

J15.5 Hz, CHvCH±Ph); 5.12 (2H, q, J7.0 Hz, OCH₂);

1.69 (3H, t, J7.0 Hz, CH₃); ¹³C NMR (100 MHz, CDCl₃)

d: 331.5 (CrvC); 224.4 (CO trans); 216.9 (CO cis); 139.8

(vCH±Ph); 134.6 (CHvCH±Ph); 130.9, 129.8, 129.5,

129.2 (Ph); 76.3 (OCH₂); 15.3 (CH₃).

H⁶); 0.15, 0.07 (2H, m, H⁸, H⁹) ¹³C NMR (100 MHz,

CDCl₃) d: 67.6 (OCH₂), 56.7 (C¹), 50.1 (NCH₂), 31.0

(C⁶), 29.3 (C²), 27.0 (C³), 22.7 (C⁵), 21.7 (C⁴), 8.4 (C⁷),

5.2, 3.9 (C⁸, C⁹).

1

54 endo: H NMR (400 MHz, CDCl₃) d: 3.6 (4H, t, J

4.8 Hz, OCH₂); 2.61 (2H, dt, J12.0, 4.8 Hz, N±CHH⁰);

2.51 (2H, dt, J12.0, 4.8 Hz, N±CHH⁰); 2.00 (1H, m,

0

45: mp: 348C. ¹H NMR (400 MHz, CDCl₃) d: 6.96 (1H, m,

CHv); 4.90 (2H, q, 7.2 Hz, OCH₂); 2.32 (2H, m, CH₂±

CHv); 2.23 (2H, m, CH₂±Cv); 1.62 (4H, m, CH₂); 1.59

(3H, t, J7.2 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) d:

318.5 (WvC); 203.2 (CO trans); 197.9 (CO cis); 156.0

(vC); 147.3 (vCH); 79.4 (OCH₂); 27.0 (CH₂±Cv); 25.3

(CH₂±CHv); 22.1, 21.6 (CH₂); 14.9 (CH₃).

H⁵); 1.90 (1H, m, H³); 1.79 (1H, m, H⁴); 1.65 (2H, m, H³,

0

H⁵); 1.48 (1H, m, H⁴); 1.26 (1H, dd, J9.2, 5.6 Hz, H²);

0.60 (1H, t, J9.2 Hz, H⁶); 0.57 (2H, m, H⁸, H⁹); 0.38 (1H,

0

m, H⁷); 0.19 (2H, m, H⁸, H⁹). ¹³C NMR (100 MHz, CDCl₃)

d: 67.3 (OCH₂); 58.5 (C¹); 49.8 (NCH₂); 34.7 (C⁶); 28.8

(C²); 25.0 (C⁴); 24.7 (C³); 20.7 (C⁵); 5.8, 5.7 (C⁸, C⁹); 5.3

(C⁷). HRMS calcd for C₁₃H₂₁NO: 207.1623. Found:

207.1622.

To a solution of 42, 43 or 45 (2 mmol) in Et₂O (30 ml) was

added a freshly prepared ether solution of 28 (6 mmol). The

solution instantaneously turned from dark red to orange and

the solvent was evaporated in vacuo. After column chroma-

tography (5% Et₂O/PE), 44⁵⁶(70% from 42; 52% from 43)

or 46⁵³(52% from 45) were obtained as colorless oils.

Spectra were identical to those of the literature.

To a solution of 4-cyclopent-1-enyl-morpholine (312 ml,

2.0 mmol) in C₆H₆(10 ml) was added 39 (0.25 g,

0.5 mmol). The solution was stirred for 2 h at 508C and

the solvent was evaporated in vacuo. After chromatography

column, 55 exo (30% CH₂Cl₂/PE, 51%, 63 mg) and 55 endo

(25% Et₂O/PE, 41%, 51 mg) were obtained as oils.

5018

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

57: ¹H NMR (400 MHz, CDCl₃) d: 9.20 (1H, d, J2.4 Hz,

H²); 8.29 (1H, d, J2.4 Hz, H⁴); 8.15 (1H, d, J8.6 Hz, H⁵);

7.87 (1H, d, J8.6 Hz, H⁸); 7.73±7.70 (3H, m); 7.58±7.51

(3H, m); 7.40±7.35 (1H, m). ¹³C NMR (100 MHz, CDCl₃)

d: 150.0 (C²); 147.5 (C⁹); 138.0 (C³); 133.9 (C¹¹); 133.3

(C⁴); 129.5 (C⁷); 129.4, 128.1, 127.5 (C¹², C¹³, C¹⁴, C¹⁵,

C¹⁶); 129.3 (C¹⁰, C⁸); 128.2 (C⁵); 127.1 (C⁶).

55 exo: ¹H NMR (400 MHz, CDCl₃) d: 3.62 (4H, t,

J4.6 Hz, OCH₂); 2.65 (2H, dt, J11.2, 4.6 Hz,

N±CHH⁰); 2.47 (2H, dt, J11.2, 4.6 Hz, N±CHH⁰); 1.84

Cyclopropanation reactions of pyridinium ylid

complexes with enol ethers

(1H, m, H⁵); 1.78±1.71 (3H, m, H⁸, H⁹, H¹²); 1.67 (1H, m,

0

H³); 1.63±1.47 (8H, m, H³, H⁴, H⁵, H⁷₀, H¹⁰,₀H¹¹); 1.32 (1H,

The procedures were identical as those used with the

enamines. The starting pyridinium ylid complex used is

always 24b. After 10 h at room temperature in CH₂Cl₂,

58⁵⁴afforded 59 endo (PE, 55%) and 59 exo (30%

CH₂Cl₂/PE, 31%) as oils.

0

m, H⁷); 1.18±1.06 (3H, m, H⁴, H⁹, H¹²); 0.80 (1H, t,

J4.0 Hz, H²); 0.70 (1H, qn, J4.0 Hz, H⁶). ¹³C NMR

(100 MHz, CDCl₃) d: 67.5 (OCH₂); 56.5 (C¹); 50.2

(NCH₂); 41.0 (C⁸); 32.8 (C⁹, C¹²); 32.6 (C⁷); 29.9 (C²);

27.1 (C³); 26.1 (C⁶); 25.1; 25.0 (C¹⁰, C¹¹); 22.9 (C⁵); 22.0

(C⁴). HRMS (EI¹), calcd for C₁₆H₂₈NO: 249.2171. Found:

250.2171.

55 endo: ¹H NMR (400 MHz, CDCl₃) d: 3.63 (4H, t,

J4.8 Hz, OCH₂); 2.65 (2H, dt, J11.2, 4.8 Hz,

N±CHH⁰); 2.50 (2H, dt, J11.2, 4.8 Hz, N±CHH⁰); 2.00

(1H, m, H⁵); 1.86 (1H, m, H³); 1.84±1.74 (4H, m, H⁴, H⁸,

59 endo: ¹H NMR (400 MHz, CDCl₃) d: 7.28±7.09 (5H, m,

Ph); 4.26 (1H, dt, J8.7, 3.4 Hz, H⁴); 3.68 (1H, q,

0

H⁹, H¹²); 1.59 (₀2H, ₀m, H¹⁰, H¹¹); 1.50 (2H, m, H¹⁰, H¹¹);

0

J8.7 Hz, H⁴); 2.46 (1H, d, J4.7 Hz, H⁵); 2.31 (1H, m,

0

1.42 (2H, m, H³, H⁵); 1.35 (1H, m, H⁴); 1.28±1.15 (3H, m,

0

H³); 2.05±1.82 (2H, m, H², H³); 0.02 (9H, s, SiMe₃). ¹³C

NMR (100 MHz, CDCl₃) d: 141.2, 127.9, 127.45, 125.5

(Ph); 99.1 (C¹); 67.0 (C⁴); 34.6 (C⁵); 28.9 (C²); 28.7 (C³);

0.4 (CH₃).

0

H², H⁷, H⁷); 1.13 (2H, m, H⁹, H¹²); 0.98 (1H, m, H⁶). ¹³

C

NMR (100 MHz, CDCl₃) d: 67.3 (OCH₂); 58.6 (C¹); 49.8

(NCH₂); 40.8 (C⁸); 32.9, 32.6 (C⁹, C¹²); 30.6 (C⁶); 29.7 (C⁷);

29.0 (C²); 26.6 (C⁴); 25.1 (C¹⁰, C¹¹); 24.4 (C³); 20.5 (C⁵).

59 exo: ¹H NMR (400 MHz, CDCl₃) d: 7.36±7.25 (5H, m,

When the same reaction was carried out with CH₂Cl₂instead

of C₆H₆, after 2 days at room temperature, 56 (50% CH₂Cl₂/

PE, 85 mg, 41%) was obtained as an oil. (Isomer E).

Ph); 3.95 (1H, dt, J9.2, 4.0 Hz, H⁴); 2.67 (1H, q,

0

J9.2 Hz, H⁴); 2.62 (1H, d, J10.7 Hz, H⁵); 2.26 (1H, m,

H³); 1.91 (1H, dd, J10.7, 6.0 Hz, H²); 1.65 (1H, ddd,

0

J12.8, 9.2, 4.0 Hz, H³); 0.26 (9H, s, SiMe₃). ¹³C NMR

(100 MHz, CDCl₃) d: 143.6, 130.0, 128.3, 126.5 (Ph); 99.9

(C¹); 69.2 (C⁴); 34.0 (C⁵); 27.2 (C²); 25.8 (C³); 0.8 (CH₃).

HRMS calcd for C₁₄H₂₀O₂Si: 248.1232. Found: 248.1240.

After 2 h at 508C in C₆H₆, 60⁵⁵afforded 61 (PE, 42%) and

61⁰(PE, 22%) as oils.

1

56: Isomer E. H NMR (400 MHz, CDCl₃) d: 6.55 (1H, m,

vCH); 2.55 (2H, tt, J8.0, 7.4 Hz, CH₂±C±Cv); 2.31 (2H,

t, J8.0 Hz, CH₂±CvO); 2.11 (2H, dd, J8.0, 7.2 Hz, CH₂±

CHv); 1.92 (2H, t, J7.4 Hz, CH₂±CvCH); 1.97±1.06

(9H, m, CH, CH₂). ¹³C NMR (100 MHz, CDCl₃) d: 207.4

(CO); 137.3 (C²); 135.8 (C⁶); 39.4 (C⁸); 38.7 (C⁵); 35.9 (C⁷);

32.5 (C⁹, C¹²); 26.9 (C³); 25.1 (C¹⁰, C¹¹); 19.9 (C⁴). HRMS

(EI¹), calcd for C₁₂H₁₉O: 179.1431. Found: 179.1436.

61: ¹H NMR (400 MHz, CDCl₃) d: 7.34±7.15 (5H, m, Ph);

3.90 (1H, dq, J9.2, 7.0 Hz, OCHH⁰); 3.60 (1H, dq, J9.2,

7.0 Hz, OCHH⁰); 1.79 (1H, s, H³); 1.31 (3H, s, H⁵); 1.22

(3H, t, J7.1 Hz, H⁷); 0.88 (3H, s, H⁴); 0.17 (9H, s, SiMe₃).

¹³C NMR (100 MHz, CDCl₃) d: 137.7, 130.1, 127.7, 125.5

(Ph); 94.1 (C¹); 62.2 (C⁶); 36.1 (C³); 29.4 (C²); 22.5 (C⁵);

17.2 (C⁷); 15.2 (C⁴); 0.61 (SiMe₃). HRMS calcd for

C₁₆H₂₆O₂Si: 278.1702. Found: 278.1707.

To a solution of indole (142 ml, 1 mmol) in CH₂Cl₂(15 ml)

was added 24b (0.5 g, 1 mmol). The solution was re¯uxed

for 2 h. After evaporation of the solvent, toluene (20 ml) and

Pd/C (10%) were added. The reaction mixture was then

allowed to re¯ux for 3 days. Silicagel chromatography

(10% AcOEt/PE) gave 57⁵⁸(0.12 g, 56%) as an oil.

61⁰: ¹H NMR (400 MHz, CDCl₃) d: 7.36±7.11 (5H, m, Ph);

3.81 (1H, dq, J9.4, 7.2 Hz, OCHH⁰); 3.41 (1H, dq, J9.4,

7.2 Hz, OCHH⁰); 1.83 (1H, s, H³); 1.31 (3H, s, H⁴); 1.18

(3H, t, J7.2 Hz, H⁷); 0.92 (3H, s, H⁵); 0.21 (9H, s, SiMe₃).

¹³C NMR (100 MHz, CDCl₃) d: 137.7, 130.1, 127.7, 125.5

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5019

0

(Ph); 93.0 (C¹); 61.8 (C⁶); 39.4 (C³); 28.1 (C²); 22.9 (C⁴);

19.1 (C⁷); 15.2 (C⁵); 0.77 (SiMe₃).

(1H, m, H⁴); 1.25 (1H, m, H²); 0.93 (3H, d, J6.8 Hz,

CH₃). ¹³C NMR (100 MHz, CDCl₃) d: 67.4 (OCH₂); 58.4

(C¹); 49.9 (NCH₂); 28.8 (C²); 26.3 (C³); 24.4 (C⁵); 23.9 (C⁴);

20.0 (C⁶); 7.8 (CH₃).

After 5 h at room temperature in C₆H₆, 62⁵⁵afforded 63 cis

(5% CH₂Cl₂/PE, 54%) as white crystals and 63 trans (10%

CH₂Cl₂/PE, 8%) as an oil.

Preparation of the carbene complexes 49a, 94, 84, 101

1

63 cis: Recrystallisation (CH₂Cl₂/Pentane) mp: 358C. H

To a solution of the corresponding iodide compound

(1.0 equiv.) under argon at 2788C in diethyl ether (7 ml/

mmol of iodide) and pentane (10 ml/mmol of iodide) was

added by syringe t-butyllithium (2.0 equiv. of a 1.7 M

hexane solution) over a period of 10 min. This solution

was stirred at 2788C for a period of 15 min and then trans-

ferred by cannula to a suspension of chromium hexa-

carbonyl (or tungsten hexacarbonyl) (1.0 equiv.) in diethyl

ether (15 ml/mmol) at 2788C. This mixture was warmed to

room temperature and was allowed to stir 2.5 h. The solvent

was removed on a rotary evaporator and the reaction

mixture was cooled to 08C. Water (15 ml/mmol), petroleum

ether (15 ml/mmol), then triethyl oxomium tetra¯uoro-

borate (1.1 equiv.) were added. The reaction mixture was

warmed to 258C and was extracted with petroleum ether.

The organic layer was washed with sodium bicarbonate

solution, water, saturated sodium chloride solution and

dried over sodium sulfate. The solvent was removed on a

rotary evaporator and ®nal puri®cation was achieved

through chromatography on silica gel using pure petroleum

ether as eluent.

NMR (400 MHz, CDCl₃) d: 7.35±6.98 (10H, m, Ph); 2.84

(2H, s, CH); 0.37 (9H, s, SiMe₃); 0.03 (9H, s, SiMe₃). ¹³C

NMR (100 MHz, CDCl₃) d: 135.4, 130.5, 127.5, 125.7 (Ph);

87.6 (C±O); 35.1 (CH); 1.2 (SiMe₃); 0.8 (SiMe₃). HRMS

calcd for C₂₁H₃₀O₂Si₂: 371.1863. Found: 371.1863.

1

63 trans: H NMR (400 MHz, CDCl₃) d: 7.32±6.94 (10H,

m, Ph); 2.61 (2H, s, CH); 0.23 (18H, s, SiMe₃). ¹³C NMR

(100 MHz, CDCl₃) d: 137.8, 128.1, 128.0, 126.0 (Ph); 87.6

(C±O), 37.9 (CH); 1.1 (SiMe₃).

After 1 h at room temperature in C₆H₆, 64⁵⁵afforded 65 (1%

Et₂O/PE, 72%) as a white solid.

65: Recrystallization (hexane) mp: 498C. ¹H NMR

(400 MHz, CDCl₃) d: 7.52 (2H, d, J6.8 Hz, H_oPh); 7.28

(2H, t, J6.8 Hz, H_mPh); 7.20 (1H, t, J6.8 Hz, H_pPh);

1.88 (1H, s, CH); 1.78±1.61 (4H, m, CH₂±C_q); 1.55±1.24

(6H, m, CH₂); 0.28 (9H, s, SiMe₃); 0.24 (9H, s, SiMe₃). ¹³

C

NMR (100 MHz, CDCl₃) d: 138.0, 129.8, 127.5, 125.3 (Ph);

91.0 (C±O); 37.7 (CH); 34.1(C_q); 32.7, 26.4, 26.1, 25.1,

23.9 (CH₂); 1.2, 1.1 (SiMe₃). Anal. calcd for C₂₀H₃₄O₂Si₂:

C, 66.24; H, 9.46. Found: C: 66.21 H: 9.59.

Complex 49a

4-cyclopent-1-enyl-morpholine cyclopropanation

reaction with nicotinium ylid complex 40

To a solution of 4-cyclopent-1-enyl-morpholine⁵⁰(311 ml,

1.9 mmol) in CH₂Cl₂(10 ml), 40 (0.25 g, 0.48 mmol) was

added. The solution was re¯uxed for 2 days and after

chromatography column, 66 exo³⁸(1% Et₂O/PE, 31 mg,

36%) and 66 endo³⁸(20% Et₂O/PE, 15 mg, 18%) were

obtained as oils.

General procedure was followed using 5-iodo-1-phenyl-

pent-1-yne (4 g, 14.8 mmol), t-butyllithium (17.4 ml)

tungsten hexacarbonyl (5.2 g, 14.8 mmol) and triethyloxo-

nium tetra¯uoroborate (3.1 g, 16.3 mmol). After chromato-

graphy on silica gel an orange oil identi®ed as complex 49a

was obtained (2.34 g, 34%). ¹H NMR (200 MHz, CDCl₃) d

7.39 (m, 2H, arom ortho); 7.27 (m, 3H, arom para meta)

4.89 (q, 2H, J7 Hz, OCH₂); 3.39 (t, 2H, J7.5Hz, Hz, H²);

2.45 (t, 2H, J7.5 Hz, H⁴); 1.80 (m, 2H, H³); 1.62 (t, 3H,

J7 Hz, CH₃); ¹³C NMR (50 MHz, CDCl₃) d: 334.0 (C¹);

203.3 (trans CO); 197.3 (cis CO); 131.6, 128.3, 127.6

(arom, CH); 123.6 (arom, Cq); 87.7 (C⁶); 81.8 (C⁵); 80.8

(OCH₂); 64.2 (C²); 25.2 (C⁴)); 19.0 (C³); 14.8 (CH₃).

1

66 exo: H NMR (400 MHz, CDCl₃) d: 3.63 (4H, t, J

4.6 Hz, OCH₂); 2.64 (2H, dt, J11.2, 4.6 Hz, N±CHH⁰);

2.49 (2H, dt, J11.2, 4.6 Hz, N±CHH⁰); 1.86 (1H, m,

H⁵); 1.67 (1H, m, H⁴); 1.64±1.59 (2H, m, H³); 1.51 (1H,

Complex 94

0

m, H⁵); 1.14 (1H, m, H⁴); 1.07 (3H, d, J6.0 Hz, CH₃);

0.76 (1H, m, H⁶); 0.73 (1H, m, H²). ¹³C NMR (100 MHz,

CDCl₃) d: 67.6 (OCH₂); 56.1 (C¹); 50.2 (NCH₂); 30.8 (C²);

27.0 (C³); 22.8 (C⁵); 22.0 (C⁴); 20.3 (C⁶); 11.6 (CH₃).

66 endo: ¹H NMR (400 MHz, CDCl₃) d: 3.63 (4H, t,

J4.6 Hz, OCH₂); 2.65 (2H, dt, J11.2, 4.6 Hz, N±

CHH⁰); 2.51 (2H, dt, J11.2, 4.6 Hz, N±CHH⁰); 2.04

General procedure was followed using 5-iodo-1-phenylpent-

1-yne (6 g; 22.2 mmol), terbutyllithium 26.1 ml), chromium

hexacarbonyl (4.9 g, 22.2 mmol) and triethyloxonium

tetra¯uoroborate (4.64 g, 22.2 mmol) and triethyloxonium

(1H, m, H³); 1.90 (1H, m, H⁵); 1.75 (1H, m, H⁴₀); 1.70

0

(1H, m, H³); 1.45 (1H, m, H⁶); 1.42 (1H, m, H⁵); 1.32

5020

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

tetra¯uoroborate (4.64 g, 24.4 mmol) after chromatography

on silica gel an brownish oil identi®ed as complex 94 was

iodide halides. The carbene complex (n mmol) and tetra-

butylammonium bromide (0.1n mmol) in dichloromethane

(15n ml) was treated with 50% aqueous NaOH and the

halide (2±5n mmol). The mixture was stirred at room

temperature under argon until the starting material was

consumed. The reaction mixture was diluted with water,

extracted with dichloromethane, dried, and concentrated

under reduced pressure. The pure product was isolated by

chromatography on silica gel by elution with petroleum

ether.

1

obtained (5.25 g, 60%): H NMR (200 MHz, CDCl₃) d:

7.41±7.24 (m, 5H, arom); 5.08 (q, 2H, J7 Hz, OCH₂);

3.49 (t, 2H, J7.5 Hz, H²); 2.43 (t, 2H, J7.5 Hz, H⁴);

1.77 (qn, 2H, J7.5 Hz, H³); 1.64 (t, 3H, J7 Hz, CH₃).

¹³C NMR (100 MHz, CDCl₃) d: 359.0 (C¹); 223.3 (trans

CO); 216.5 (cis CO); 131.6, 128.3, 127.8 (arom CH);

123.7 (arom Cq); 88.8 (C⁶); 81.8 (C⁵); 78.1 (OCH₂); 62.2

(C²); 25.2 (C⁴); 19.1 (C³); 15.0 (CH₃). Anal. calcd for

C₁₉H₁₆O₆Cr: C, 58.17; H, 4.11. Found: C, 58.21; H, 4.07.

Complex 89

Complex 84

General procedure was followed using carbene complex 49a

(1 g, 1.9 mmol), and benzyl bromide (0.452 ml, 3.8 mmol),

as starting material. After chromatography on silica gel an

orange oil identi®ed as complex 89 was obtained (1.25 g,

General procedure was followed using (3-iodo-propyl)-

benzene (3.5 g, 14.2 mmol), terbutyllithium (16.7 ml),

chromium hexacarbonyl (3.12 g, 14.2 mmol) and triethyl

oxonium tetra¯uoroborate (2.97 g, 15.6 mmol) after

chromatography on silica gel an orange oil identi®ed as

complex 84 was obtained (2.61 g, 50%). ¹H NMR

(200 MHz, CDCl₃) d: 7.36±7.17 (m, 5H, arom); 5.06 (q,

2H, J7 Hz, OCH₂); 3.37 (t, 2H, J7.5 Hz, H²); 2.64 (t,

2H, J7.5 Hz, H⁴); 1.82 (qn, 2H, J7.5 Hz, H³); 1.63 (t,

3H, J7 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) d: 359.6

(C¹); 223.3 (trans CO); 216.5 (cis CO); 141.5 (arom Cq);

128.5, 126.4 (arom CH); 78.0 (OCH₂); 62.8 (C²); 35.5 (C⁴);

28.1 (C³); 15.0 (CH₃). Anal. calcd for C₁₇H₁₆O₆Cr: C, 55.44;

H, 4.38. Found: C, 55.36; H, 4.44.

1

80%). H NMR (200 MHz, CDCl₃) d: 7.43±7.17 (m, 10H,

arom); 4.92 (q, 2H, J7.1 Hz, OCH₂); 4.40 (m, 1H, H²);

2.94 (dd, 1H, J13.4, J6 Hz, H⁷); 2.52 (dd, 1H, J13.4,

J7.9 Hz, H⁷); 2.40 (m, 2H, H³); 1.94 (m, 1H, H⁴); 1.65 (t,

3H, J7.1 Hz, CH₃); 1.55 (m, 1H, H⁴). ¹³C NMR (50 MHz,

CDCl₃) d: 338.3 (C¹); 203.2 (trans CO); 197.2 (cis CO);

138.6 (arom Cq); 131.6, 129.3, 128.6, 128.3, 127.8, 126.6

(arom CH); 123.6 (arom Cq); 89.2 (C⁶); 81.6 (C⁵); 80.7

(OCH₃); 73.3 (C⁴); 37.8 (C²); 30.5 (C⁷); 17.8 (C³); 14.7

(CH₃). HRMS calcd for C₂₆H₂₂O₆W: 614.0926. Found:

614.0930.

Complex 97

Complex 101

General procedure was followed using carbene complex 94

(2.5 g, 6.37 mmol), and benzyl bromide (1.5 ml,

12.74 mmol), as starting material. After chromatography

on silica gel, a brownish oil identi®ed as complex 97 was

General procedure was followed using 4-iodo-1-ethyl but-1-

yne (4.16 g, 20 mmol), terbutyllithium (23.5 ml), chromium

hexacarbonyl (4.4 g, 20 mmol) and triethyl oxonium

tetra¯uoroborate (4.2 g, 22 mmol). After chromatography

on silica gel an orange oil identi®ed as complex 101 was

1

obtained (2.28 g, 74%). H NMR (400 MHz, CDCl₃) d:

7.42±7.21 (m, 10H, arom); 5.16 (q, 2H, J7 Hz, OCH₂);

4.41 (m, 1H, H²); 2.99 (dd, 1H, J13.4, J5.6 Hz, H⁴);

2.50±2.32 (m, 3H, H⁴, H⁷); 1.92 (m, 1H, H³); 1.70 (t, 3H,

J7 Hz, CH₃); 1.58 (m, 1H, H³). ¹³C NMR (100 MHz,

CDCl₃) d: 364.0 (C¹); 223.0 (trans CO); 216.2 (cis CO);

138.7 (arom Cq); 131.6, 129.3, 128.6, 128.3, 127.8 (arom

CH); 123.7 (arom Cq); 89.2 (C⁶); 81.5 (C⁵); 78.0 (OCH₃);

71.8 (C²); 37.8 (C⁷); 30.6 (C⁴); 17.8 (C³); 15.0 (CH₃). Anal.

calcd for C₂₂H₂₂O₆Cr: C, 64.72; H, 4.60. Found: 64.75; H,

4.67.

1

obtained (3.468 g, 52.5%). H NMR (200 MHz, CDCl₃) d:

5.11 (q, 2H, J7 Hz, OCH₂); 3.5 (t, 2H, J6 Hz, H²); 2.30

(t, 2H, J6 Hz, H³); 2.11 (q, 2H, J8 Hz, H⁶); 1.64 (t, 3H,

J7 Hz, CH₃); 1.07 (t, 3H, J8 Hz, H⁷). Anal. calcd for

C₁₄H₁₄O₆Cr: C, 50.90; H, 4.24. Found: C, 50.97; H, 4.50.

Preparation of the carbene complexes 79 and 81a

Complex 79 and 81a were prepared following the literature

procedures.⁴⁶

Complex 91

Preparation of the carbene complexes 89, 97, 91, 104, 99,

85 and 81b

These compounds were prepared by phase transfer catalysed

alkylation of complexes 49a, 84 and 94 with bromide or

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5021

General procedure was followed using carbene complex 49a

Complex 85

(1.4 g, 2.67 mmol), and allylbromide (0.7 ml, 8 mmol), as

starting material. After chromatography on silica gel an

orange oil identi®ed as complex 91 was obtained (1.25 g,

1

80%). H NMR (400 MHz, CDCl₃) d: 7.45±7.20 (m, 5H,

arom); 5.90±5.60 (m, 1H, H⁸); 5.15±4.94 (m, 2H, H⁹); 4.89

(q, 2H, J7.1 Hz, OCH₂); 4.19 (m, 1H, H²); 2.54±2.45 (m,

2H, H⁷); 2.36 (m, 1H, H³); 2.10 (m, 1H, H³); 1.91 (m, 1H,

H⁴); 1.64 (m, 4H, CH₃, H⁴). ¹³C NMR (100 MHz, CDCl₃) d:

338.0 (C¹); 203.3 (trans CO); 197.3 (cis CO); 135.0 (C⁸);

131.6, 128.3, 127.8, (arom, CH); 123.6 (arom Cq); 117.6

(C⁹); 89.2 (C⁶); 80.7 (C⁵); 77.5 (OCH₂); 70.9 (C²); 36.2 (C⁷);

30.4 (C⁴); 17.7 (C³); 14.8 (CH₃).

General procedure was followed using carbene complex 84

(2.3 g, 6.2 mmol), and allyl bromide (1.06 ml, 12.2 mmol),

as starting material. After chromatography on silica gel, an

orange oil identi®ed as complex 85 was obtained (1.9 g,

1

75%). H NMR (400 MHz, CDCl₃) d: 7.34±7.17 (m, 5H,

Complex 104

arom); 5.81 (m, 1H, H⁶); 5.18±5.05 (m, 4H, OCH₂, H⁷);

4.18 (m, 1H, H²); 2.75 (dt, 1H, J12.5 Hz, J5 Hz, H⁴);

2.55 (dt, 1H, J12.5 Hz, J5 Hz H⁴); 2.38 (m, 1H, H⁵);

2.11 (m, 1H, H⁵); 1.85 (m, 1H, H³); 1.66 (t, 3H, J7 Hz,

CH₃); 1.59 (m, 1H, H³). ¹³C NMR (100 MHz, CDCl₃) d:

363.8 (C¹); 223.1 (trans CO); 216.4 (cis CO); 142.0 (arom

Cq); 135.4 (C⁶); 128.6, 128.3, 126.1 (arom); 117.4 (C⁷);

78.1 (OCH₂); 70.3 (C²); 36.4 (C⁴); 34.2, 34.1 (C⁵, C³);

15.1 (CH₃). Anal. calcd for C₂₀H₂₀O₆Cr: C, 58.82; H,

4.94. Found: C, 58.87; H, 5.05.

General procedure was followed using carbene complex 94

(2.45 g, 6.24 mmol), and allyl bromide (1.08 ml,

12.48 mmol), as starting material. After chromatography

on silica gel, a brownish oil identi®ed as complex 104

Complex 81b

1

was obtained (1.65 g, 61%). H NMR (400 MHz, CDCl₃)

d: 7.42±7.28 (m, 5H, arom); 5.80 (m, 1H, H⁸); 5.15±5.06

(m, 4H, OCH₂,H⁹); 4.22 (m, 1H, H²); 2.51 (m, 1H, H⁴);

2.44±2.31 (m, 2H, H⁴, H⁷); 2.07 (m, 1H, H⁷); 1.90 (m,

1H, H³); 1.66 (t, 3H, J7 Hz, CH₃); 1.60 (m, 1H, H³). ¹³C

NMR (100 MHz, CDCl₃) d: 363.4 (C¹); 223.1 (trans CO);

216.3 (cis CO); 135.1 (C⁸); 131.6, 128.3, 127.8, (arom CH);

123.7 (arom Cq); 117.5 (C⁹); 89.1 (C⁶); 81.5 (C⁵); 78.1

(OCH₂); 69.3 (C²); 36.1 (C⁷); 30.5 (C⁴); 17.7 (C³); 15.0

(CH₃). Anal. calcd for C₂₂H₂₀O₆Cr: C, 61.11; H, 4.66.

Found: 61.13; H, 4.71.

General procedure was followed using carbene complex 22

(3.109 g, 11.77 mmol), and allyl bromide (3.05 ml,

35.31 mmol), as starting material. After chromatography

on silica gel, an orange oil identi®ed as complex 81b was

1

obtained (2.797 g, 69%). H NMR (200 MHz, CDCl₃) d:

Complex 99

5.74 (m, 2H, H⁴); 5.14 (q, 2H, J7 Hz, OCH₂); 5.00 (m,

4H, H⁵); 4.12 (qn, 1H, J6.8 Hz, H²); 2.21 (m, 2H, H³);

2.02 (m, 2H, H³); 1.63 (t, 3H, J7 Hz, CH₃). ¹³C NMR

(100 MHz, CDCl₃) d: 364.09 (C¹); 223.23 (trans CO);

216.35 (cis CO); 135.4 (C⁴); 117.27 (C⁵); 78.04 (OCH₂);

69.65 (C²); 36.11 (C³); 15.04 (CH₃).

Preparation of the carbene complexes 106 and 107

General procedure was followed using carbene complex 94

(4.24 g, 10.8 mmol), and methyl iodide (3.18 ml, 51 mmol),

as starting material. After chromatography on silica gel a

deep reed oil identi®ed as complex 99 was obtained

The salt 105 (1.0 mol equivalent) was dissolved in CH₂Cl₂

(20 ml/mmol of 113) under Ar. The ¯ask was covered with

aluminium foil, cooled to 2208C and from an addition

funnel was added a solution of acetyl chloride (1.1 mol

equivalent) in CH₂Cl₂(7 ml/mmol of 113) dropwise over

5 min to give a red solution. After addition, the mixture was

warmed to 2108C and stirred for 10 min.The alkynol

(1.0 mol equivalent) was added as a solution in CH₂Cl₂

(1 ml/mmol) and the solution was stirred at room

temperature for 30 min. The mixture was concentrated

under reduce pressure and the residue was puri®ed by

chromatography to give the carbene complexes as a deep

red oil or solid.

1

(2.825 g, 64%). H NMR (200 MHz, CDCl₃) d: 7.40±7.24

(m, 5H, arom); 5.08 (q, 2H, J7 Hz, OCH₂); 4.17 (m, 1H,

H²); 2.41 (m, 2H, H⁴); 1.88 (m, 1H, H³); 1.60 (t, 3H,

J7 Hz, CH₃); 1.46 (m, 1H, H³); 1.06 (d, 3H, J6.6 Hz,

H⁸). ¹³C NMR (100 MHz, CDCl₃) d: 363.32 (C¹); 223.07

(trans CO); 216.39 (cis CO); 131.64, 128.33, 127.82,

123.81 (arom); 89.06 (C⁵); 81.49 (C⁶); 78.13 (OCH₂);

64.54 (C²); 31.87 (C⁴); 17.57 (C³); 16.12 (CH₃); 14.89 (C³).

HRMS (EI¹), calcd for C₂₀H₁₈O₆Cr: 406.0508. Found:

406.0486.

5022

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

Complex 106

27.6 (C², C⁴, C⁵); 16.02 (CH₃). HRMS (EI¹), calcd for

C₁₅H₁₉O₃: 247.1334. Found: 247.1339.

Reaction of complex 79 with diphenylacetylene

Complex 105 (5 g, 13.7 mmol), acetyl chloride (1.17 g,

15 mmol) and phenyl-4-butyn-1-ol (2 g, 13.7 mmol) were

combined following the general procedure. Complex 106

was obtained as a deep red solid (3.9 g, 67%). Mp: 558C.

¹H NMR (200 MHz, CDCl₃) d: 7.42±7.24 (m, 10H, arom);

4.99 (t, 2H, J6 Hz, H³) 3.14 (t, 2H, J6 Hz, H⁴); ¹³C NMR

(50 MHz, CDCl₃) 349.7 (C¹); 224.3 (trans CO); 216.1 (cis

CO); 131.7±121.2 (arom), 84.4 (C⁶), 77.9 (C³), 71.5 (C⁵),

21.0 (C⁴). Anal. calcd for C₂₂H₁₄O₆Cr: C, 61.97; H, 3.28.

Found: C, 61.80; 3.35.

To a solution of complex 79 (1 g, 2.30 mmol) and diphenyl-

acetylene (0.492 g, 2.76 mmol, 1.2 equiv.) in 60 ml of

CH₂Cl₂at 2258C, under argon, was added dropwise from

an addition funnel a solution of N-methyl dihydropyridine

(0.65 ml, 11.50 mmol) in 15 ml of CH₂Cl₂to give a red

solution. After 20 min, the mixture was warmed to room

temperature and stirred for 1 h 45 min, and ®nally, re¯uxed

for 20 h. The solvent was removed on a rotary evaporator

and the residue was puri®ed by chromatography on silica

gel. Elution with EP/Et₂O (80/20) gave 87 as a yellow oil

(0.065 g, 9%). ¹H NMR (200 MHz, CDCl₃) d: 7.74 (s, 1H,

H¹); 7.41±6.99 (m, 10H, arom); 5.60 (m, 1H, H⁷); 4.98±

4.84 (m, 2H, H⁸); 4.22 (dd, 1H, J7.7 Hz, J4.7 Hz, H⁴);

3.53 (m, 1H, OCH₂); 3.34 (m, 1H, OCH₂); 2.19±1.93 (m,

2H, H⁶); 1.73 (m, 1H, H⁵); 1.22 (m, 1H, H⁵); 1.19 (t, 3H,

J7 Hz, CH₃). HRMS (EI¹), calcd for C₂₂H₂₅O₂: 321.1855.

Found: 321.1860. Further elution with EP/Et₂O (70/30)

gave 80 (0.037 g), 11%).

Complex 107

Complex 105 (4 g, 10.8 mmol), acetyl chloride (0.932 g,

11.88 mmol) and phenyl-5-pentyn-1-ol (1.6 g, 10.8 mmol)

were combined following the general procedure. Complex

1

107 was obtained as a deep red oil (2.1 g, 44%). H NMR

(200 MHz, CDCl₃) d: 7.45±7.10 (m, 10H, arom); 4.96 (t,

2H, J6 Hz, H³) 2.7 (t, 2H, J6 Hz, H⁵); 2.3 (q, 2H,

J6 Hz, H⁴).HMRS (EI¹±CO), calcd for C₂₂H₁₇O₅Cr:

413.0481. Found: 413.0486.

Reaction of N-methyldihydropyridine with carbene

complexes of chromium and tungsten. To a solution of

carbene complex (1 mol equiv.) in CH₂Cl₂(25 ml/mmol of

carbene) at 2108C, under argon was added dropwise from

an additional funnel a solution of N-methyl dihydropyridine

(5 mol equiv.) in CH₂Cl₂(0.5 ml/mmol of amine). After

15 min, the ice bath was taken off and the mixture

allowed to stir at room temperature during 24 h. The

solution turned slowly to dark red. The solvent was

evaporated under vacuum and the residue was puri®ed by

chromatography on silica gel with mixture of EP/Et₂O as

eluent.

Reaction of complex 23 with cyclopentenone

With complex 79: 2-ethoxy-bicyclo [3.1.0] hexan-1-ol 80

N-methyldihydropyridine was prepared following the litera-

ture procedure.²⁶

To a solution of complex 23 (0.782 g, 2.4 mmol) and cyclo-

pentenone (0.77 ml, 9.16 mmol, 4 equiv.) in 80 ml of

CH₂Cl₂at 2108C, under argon, was added dropwise from

an addition funnel a solution of N-methyl dihydropyridine

(1 g, 10.51 mmol) in 15 ml of CH₂Cl₂to give a red solution.

After 15 min, the mixture was warmed to room temperature

and stirred for 15 h. The solvent was removed on a rotary

evaporator and the residue was puri®ed by chromatography

on silica gel to give with Et₂O as eluent compound 78 as a

General procedure was followed using carbene complex 44

(2 g, 4.58 mmol). Elution with EP/EtO₂(80/20) gave 45 as a

yellow liquid (0.065 g, 10%). H NMR (200 MHz, CDCl₃)

1

d: 3.79 (d, 1H, H²); 3.57 (m, 1H, OCH₂); 3.43 (m, 1H,

OCH₂); 3.16 (bs, 1H, OH); 1.97 (m, 1H, H⁴); 1.68 (m, 1H,

H³); 1.46±1.34 (m, 2H, H³, H⁵); 1.17 (t, 3H, CH₃); 1.42 (m,

1H, H⁴); 0.95 (dd, 1H, J9.6 Hz, H⁶); 0.43 (dd, 1H,

J6.4 Hz, H⁶). ¹³C NMR (100 MHz, CDCl₃) d: 82.2 (C²);

66.1 (C¹); 64.4 (OCH₂); 26.3 (C³); 24.7 (C⁴); 23.8 (C⁵); 15.6

(CH₃); 13.7 (C⁶). HRMS (EI¹), calcd for C₈H₁₅O₂:

143.1072. Found: 143.1068.

1

colourless liquid (0.312, 53%). H NMR (200 MHz, C₆D₆)

d: 7.35±7.09 (m, 5H, arom); 4.58 (s, 1H, H⁷); 3.15 (m, 3H,

OCH₂, H³); 2.35±1.36 (m, 6H, H², H⁴, H⁵); 1.01 (t, 3H,

J6.9 Hz, CH₃). ¹³C NMR (100 MHz, C₆D₆) d: 215.6

(C¹); 209.9 (CO); 137.8 (arom Cq); 129.8, 129.5, 127.9

(arom CH); 88.2 (C⁷); 66.3 (OCH₂); 43.9 (C³); 42.2, 38.0,

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5023

With complex 85: 2-ethoxy-5-methyl-3 phenethyl-cyclo-

pentanone 86

137.1 (C⁸); 116.2 (C⁹); 86.3 (C²); 66.1 (C¹); 64.9 (OCH₂);

43.2 (C³); 40.8 (C⁷); 31.2 (C⁴); 25.3 (C⁵); 16.3 (C⁶); 15.6

(CH₃). 82a (trans): ¹H NMR (400 MHz, CDCl₃) d: 5.69 (m,

1H, H⁸); 4.97 (m, 2H, H⁹); 3.64 (m, 2H, OCH₂); 3.63 (d, 1H,

J3.6 Hz, H²); 2.89 (bs, 1H, OH); 2.25 (m, 1H, H⁷); 2.00

(m, 1H, H⁷); 1.59±1.17 (m, 3H, H⁴, H³); 1.34 (m, 1H, H⁵);

1.18 (t, 3H, J7.1 Hz, CH₃); 0.91 (dd, 1H, J6.1 Hz,

0

J9.2 Hz, H⁶); 0.51 (dd, 1H, J6.1 Hz, J4.1 Hz, H⁶).

¹³C NMR (100 MHz, CDCl₃) d: 138.0 (C⁸); 115.6 (C⁹);

83.9 (C²); 68.7 (OCH₂); 65.9 (C¹); 40.3 (C³); 33.8 (C⁷);

31.7 (C⁴); 24.4 (C⁵); 16.2 (CH₃) 14.8 (C⁶).

General procedure was followed using carbene complex 85

(1.33 g, 3.20 mmol). Elution with EP/Et₂O (95/5) gave 86 as

a mixture of two isomers (0.57 g, 73%). 86a: H NMR

1

With complex 81b. General procedure was followed using

carbene complex 81b (2.064 g, 6 mmol). Elution with EP/

Et₂O gave 83 (0.658 g, 83%).

(400 MHz, CDCl₃) d: 7.20±7.11 (m, 5H, arom); 3.66 (m,

1H, OCH₂); 3.41 (m, 1H, H²); 3.36 (m, 1H, OCH₂); 2.59 (m,

2H, H⁸); 2.07 (m, 2H, H⁴H⁵); 1.89 (m, 2H, H⁷, H³); 1.59 (m,

1H, H⁷); 1.44 (m, 1H, H⁴); 1.08 (m, 6H, CH₃). ¹³C NMR

(100 MHz, CDCl₃) d: 216.4 (C¹); 141.2 (arom Cq); 127.3±

124.7 (arom C); 79.1 (C²); 64.1 (OCH₂); 40.7 (C⁵); 38.2

(C³); 33.4 (C⁴); 32.9 (C⁸); 28.9 (C⁷); 14.7 (C⁶); 14.1

(CH₃). HRMS (EI¹) calcd for C₁₆H₂₃O₂: 247.1698. Found:

With complex 49a: 2-benzylidene-6-ethoxy-cyclohexa-

none 88

1

247.1694. 86b: H NMR (400 MHz, CDCl₃) d: 7.24±7.12

(m, 5H, arom); 3.97 (m, 1H, OCH₂); 3.48 (m, 1H, OCH₂);

3.29 (d, 1H, J10.6 Hz, H²); 2.64 (m, 2H, H⁸); 2.26 (m, 1H,

H⁴); 2.10 (m, 1H, H⁵); 2.02 (m, 1H, H⁷); 1.91 (m, 1H, H³);

1.61 (m, 1H, H⁷); 1.16 (t, 3H, CH₃); 1.04 (d, 3H, H⁶); 0.98

(m, 1H, H⁴). ¹³C NMR (100 MHz, CDCl₃) d: 218.3 (CO);

141.1 (arom Cq); 127.3±124.8 (arom CH); 85.7 (C²); 65.8

(OCH₂); 40.9 (C⁵); 39.3 (C³); 34.9 (C⁷); 32.5 (C⁸); 31.6 (C⁴);

14.4, 13. (C⁶, CH₃).

General procedure was followed using carbene complex 49a

(0.525 g, 1 mmol). Elution with EP/Et₂O (92/8) gave 88 as a

yellow liquid (0.060 g, 26%). H NMR (400 MHz, CDCl₃)

1

d: 7.33±7.21 (m, 6H, arom H, H⁷); 3.89 (dd, 1H, J9.2 Hz,

J5.6 Hz, H⁶); 3.75 (dq, 1H, J9.2Hz, J7.1 Hz, OCH₂);

3.52 (dq, 1H, J9.2 Hz, J7.1 Hz, OCH₂); 2.85 (dt, 1H,

J15.8 Hz, J5.1 Hz, H³); 2.60 (m, 1H, H³); 2.20±2.14

(m, 1H, H⁵); 1.94±1.83 (m, 2H, H⁵, H⁴); 1.65±1.56 (m,

1H, H⁴); 1.91 (t, 3H, J7.1 Hz, CH₃). ¹³C NMR

(100 MHz, CDCl₃) d: 201.3 (C¹); 137.8 (Cq); 135.7 (Cq);

135.4 (C⁷); 130.2, 129.5, 128.6, 128.4 (arom CH); 81.7 (C²);

61.1 (OCH₂); 30.7 (C³); 28.6 (C⁵); 21.2 (C⁴); 15.3 (CH₃).

HRMS (EI¹), calcd For C₁₅H₁₉O₂: 231.1749. Found:

231.1748.

With complex 81a: 3-allyl-2-ethoxy-5 methyl-cyclopen-

tanone 83 and 3-allyl-2-ethoxy-bicyclo [3.1.0] hexan-1-ol

82

With complex 89: 3-benzyl-6-benzylidene-2-ethoxy-

cyclohexanone 90

General procedure was followed using carbene complex 81a

(1 g, 2.1 mmol). Elution with EP/Et₂O (95/5) gave 83 as a

colorless liquid (0.136 g, 36%). ¹H NMR (200 MHz,

CDCl₃) d: 5.77 (m, 1H, H⁸); 5.01 (m, 2H, H⁹); 3.97 (dq,

1H, J9.2 Hz, J7.1 Hz, OCH₂); 3.52 (dq, 1H, J9.2 Hz,

J7.1 Hz, OCH₂); 3.29 (d, 1H, J10.7 Hz, H²); 2.44 (m,

1H, H⁷); 2.18 (m, 1H, H⁴); 2.14±2.02 (m, 2H, H⁷, H⁵); 1.95

(m, 1H, H³); 1.16 (t, 3H, J7.1 Hz, CH₃); 1.04 (d, 3H,

J6.6 Hz, H⁶); 0.98 (m, 1H, H⁴). ¹³C NMR (50 MHz,

CDCl₃) d: 218.9 (C¹); 135.9 (C⁸); 117.1 (C⁹); 86.0 (C²);

67.2 (OCH₂); 42.2 (C⁵); 40.9 (C³); 37.6 (C⁷); 32.4 (C⁴);

15.9 (CH₃); 15.2 (C⁶). HRMS (EI¹), calcd for C₁₁H₁₉O₂:

183.1385. Found: 183.1379. Further elution with EP/Et₂O

(90/10) gave 82 as two isomers (0.027 g, 7%). 82a (cis): ¹H

NMR (400 MHz, CDCl₃) d: 5.73 (m, 1H, H⁸); 5.00 (m, 2H,

H⁹); 3.67 (dq, 1H, J9.2 Hz, J7.0 Hz, OCH₂); 3.62 (bs,

1H, H²); 3.50 (dq, 1H, J9.2, J7.1 Hz, OCH₂); 3.25 (s,

1H, OH); 2.32 (m, 1H, H⁴); 2.14 (m, 1H, H³); 1.95 (m, 2H,

H⁷); 1.49 (m, 1H, H⁵); 1.26 (t, 3H, CH₃); 1.17 (m, 1H, H⁴);

1.11 (dd, 1H, J9.2 Hz, J7.0 Hz, OCH₂); 0.42 (dd, 1H,

J6.1 Hz, J9.2 Hz, H⁶). ¹³C NMR (100 MHz, CDCl₃) d:

General procedure was followed using carbene complex 89

(0.823 g, 1.34 mmol). The ketone 90 was obtained as two

isomers: elution with EP/Et₂O (98/2) gave the cis isomer

1

90a as a yellow oil (0.162 g, 38%). H NMR (400 MHz,

CDCl₃) d: 7.41±7.20 (m, 11H, arom H, H⁷); 3.60 (m with

1d, 2H, J2.9 Hz, H², OCH₂); 3.42±3.35 (m, 1H, OCH₂);

2.93 (dtd, 1H, J16.2 Hz, J5.6Hz, J1.7 Hz, H⁵); 2.86

(dd, 1H, J13.6 Hz, J7.2 Hz, H⁸); 2.59±2.51 (m, 2H, H⁸,

H⁵); 2.26±2.19 (m, 1H, H³); 1.83±1.73 (m, 2H, H⁴); 1.61±

1.54 (m, 1H, H⁴); 1.16 (t, 3H, J6.8 Hz, CH₃). ¹³C NMR

(100 MHz, CDCl₃) d: 200.7 (CO); 140.4 (arom Cq); 137.1

(arom Cq); 136.2 (C⁷); 136.0 (Cq); 130.6, 129.4, 128.8,

128.7, 126.5 (arom CH); 82.6 (C²); 65.8 (OCH₂); 42.5

5024

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

(C³); 36.5 (C⁸); 27.1 (C⁵); 24.3 (C⁴); 15.7 (CH₃). Elution

with EP/Et₂O (90/10) gave the trans isomer 90b as a yellow

solid (0.081 g, 19%) mp: 788C. ¹H NMR (400 MHz, CDCl₃)

d: 7.70 (s, 1H, H⁷); 7.30±7.12 (m, 10H, arom H); 4.35±4.27

(dq, 1H, J8.9 Hz, J7.0 Hz, OCH₂); 3.59±3.51 (dq, 1H,

J8.9 Hz, J7.0 Hz, OCH₂); 3.45 (d, 1H, J10.0 Hz, H²);

3.23±3.18 (dd, 1H, J13.3 Hz, J4.1 Hz, H⁸); 2.66±2.59

(dtd, 1H, J16.2 Hz, 4.6 Hz, 1.3 Hz, H⁵); 2.41±2.35 dd, 1H,

J13.3±9.2 Hz, H⁸); 2.24±2.19 (m, 1H, H³); 2.09±2.05 (m,

1H, H⁵); 1.67±1.61 (m, 1H, H⁴); 1.37 (t, 3H, J7.0 Hz,

CH₃); 1.05±0.99 (m, 1H, H⁴). ¹³C NMR (100 MHz,

CDCl₃) d: 202.0 (CO); 139.5 (arom Cq); 137.5 (arom

Cq); 135.1 (C⁷); 130.2, 129.5, 128.6, 128.4, 126.2 (arom

CH); 86.0 (C²); 67.3 (OCH₂); 43.1 (C³); 38.7 (C⁸); 27.2,

26.6 (C⁵, C⁴); 15.5 (CH₃). Anal. calcd for C₂₂H₂₄O₂: C,

82.46; H, 7.55. Found: C, 81.26; H, 7.54.

General procedure was followed using carbene complex 97

(2.02 g, 4.2 mmol). The butenolide 98 was obtained as two

isomers: Elution with EP/Et₂O (30/70) gave 98a as white

solid (0.221 g, 15%) mp 1538C. ¹H NMR (400 MHz,

CDCl₃) d: 7.36±7.07 (m, 10H, arom CH);, 4.74 (d, 1H,

J8.2 Hz, H^7a); 4.10 (m, 1H, OCH₂); 3.59 (m, 1H,

OCH₂); 3.25 (dd, 1H, J13.5Hz, J8 Hz, H⁸); 2.91 (dd,

1H, J10.2 Hz, J8.2 Hz, H⁷); 2.88 (m, 1H, H⁴); 2.25(dd,

1H, J13.5, J9.6 Hz, H⁸); 2.11 (dt, 1H, J 13.7 Hz,

J5 Hz, H⁴); 1.91±1.76 (m, 2H, H⁶, H⁵); 1.23 (t, 3H,

J7.1 Hz, CH₃); 0.98 (m, 1H, H⁵). ¹³C NMR (100 MHz,

CDCl₃) d: 172.9 (C²); 161.2 (C³); 140.1 (arom Cq); 129.9

(arom Cq); 129.7, 129.2, 128.9, 128.7, 126.6 (arom CH);

124.9 (C^3a); 86.5±86.4 (C^7a, C⁷); 68.3 (OCH₂); 43.2 (C⁶);

37.9 (C⁸); 29.4 (C⁵); 25.9 (C⁴); 16.0 (CH₃). Anal. calcd for

C₂₃H₂₄O₃: C, 79.28; H, 6.94. Found: C, 79.24; H, 7.00.

Elution with EP/Et₂O (20/80) gave 98b as a yellow oil

With complex 84: 7-ethoxy-3-phenyl 3, 6, 7, 7a-tetrahydro-

4H-benzofuran-2-one 95 and 3-phenyl-5,6-dihydro-4H-

benzo furan-2-one 96

1

(0.732 g, 50%). H NMR (400 MHz, CDCl₃) d: 7.76±7.42

(m, 10H, arom CH);, 4.96 (d, 1H, J3 Hz, H^7a); 4.06±3.96

(m, 2H, H⁷, OCH₂); 3.80 (m, 1H, OCH₂); 3.18 (m, 1H, H⁴);

2.98 (m, 1H, H⁸); 2.89 (m, 1H, H⁸); 2.50 (m, 1H, H⁴); 2.21

(m, 1H, H⁶); 1.84±1.78 (m, 2H, H⁵); 1.41 (t, 3H, J7 Hz,

CH₃). ¹³C NMR (100 MHz, CDCl₃) d: 173.2 (C²); 161.6

(C³); 140.5 (arom Cq); 130.6 (arom CH); 129.5, 129.3,

128.9, 128.7, 126.7 (arom CH); 125.6 (C^3a); 83.2 (C^7a);

78.8 (C⁷); 69.6 (OCH₂); 41.7 (C⁶); 38.6 (C⁸); 27.0 (C⁵);

26.0 (C⁴); 16.3 (CH₃).

General procedure was followed using carbene complex 84

(1.3 g, 3.30 mmol). Elution with EP/Et₂O (20/80) gave the

butenolide 95 as two isomers. Finally one of them crystal-

lized as a white solid 95a (0.049 g, 6%) mp 908C. ¹H NMR

(400 MHz, CDCl₃) d: 7.50±7.30 (m, 5H, arom) 4.78 (d, 1H

J3.5 Hz, H^7a); 4.10 (m, 1H, H⁷); 3.56 (dq, 2H, J7.1 Hz,

J8 Hz, OCH₂); 3.03 (m, 1H, H⁴); 2.27 (m, 1H, H⁴); 2.05

(m, 1H, H⁶); 1.71 (m, 2H, H⁵); 1.57 (m, 1H, H⁶); 1.09 (t, 3H,

J7 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) d: 173.3 (C²);

161.0 (C³); 130.5 (arom Cq); 129.2, 128.9, 128.8, 128.6

(arom CH); 125.4 (C^3a); 82.0 (C^7a); 76.0 (C⁷);

67.1(OCH₂); 28.4 (C⁶); 26.8 (C⁴); 20.8 (C⁵); 15.9 (CH₃).

Anal. calcd for C₁₆H₁₈O₃: C, 74.40; H, 7.02. Found: C,

73.99; H, 7.06. The second one remained as a colorless

With complex 91: 3-allyl-6-benzylidene-2-ethoxy-cyclo-

hexanone 92 and 2-ethoxy-5-methyl-3-(4-phenyl-but-3-

ynyl)-cyclopentanone 93

1

liquid 95b (0.488 g, 57%). H NMR (200 MHz, CDCl₃) d:

7.47±7.34 (m, 5H, arom H); 4.70 (d, 1H, J8.4 Hz, H^7a);

3.88 (m, 1H, OCH₂); 3.66 (m, 1H, OCH₂); 3.23 (m, 1H, H⁷);

3.03 (m, 1H, H⁴); 2.33±2.11 (m, 2H, H⁴, H⁶); 2.00 (m, 1H,

H⁵); 1.53 (m, 1H, H⁶); 1.37 (m, 1H, H⁵); 1.23 (t, 3H,

J7 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) d: 172.7

(C²); 160.9 (C³); 129.7 (Cq); 129.0±128.6 (arom CH);

125.0 (C^3a); 85.7 (C^7a); 82.8 (C⁷); 66.3 (OCH₂); 29.9 (C⁶);

26.3 (C⁴); 23.6 (C⁵); 15.7 (CH₃). Further elution with EP/

Et₂O (60/40) gave 96 as a yellow oil (0.072 g, 10%) IR

nCO1760cm²¹.¹H NMR (400 MHz, CDCl₃) d: 7.67(d,

General procedure was followed using carbene complex 91

(0.580 g, 1.03 mmol). Elution with EP/Et₂O (95/5) gave 92

as 1/1 mixture of two isomers (0.050 g, 18%). 92a: ¹H NMR

(400 MHz, CDCl₃) d: 7.45±7.25 (m, 6H, H⁷, arom CH);,

5.80 (m, 1H, H⁹); 5.15±5.05 (m, 2H, H¹⁰); 3.81 (d, 1H,

J3.6 Hz, H²); 3.69 (dq, 1H, J9.6 Hz, 7.1 Hz, OCH₂);

3.50 (dq, 1H, J9.6 Hz, 7.1 Hz, OCH₂); 3.00±2.90 (dtd,

1H, J 6.2 Hz, J6.1 Hz, J2.0 Hz, H⁵); 2.75±2.64 (m,

1H, H⁵); 2.45±2.38 (m, 1H, H⁸); 2.20±2.08 (m, 2H, H⁸, H³);

1.92±1.85 (m, 1H, H⁴); 1.74±1.66 (m, 1H, H⁴); 1,24 (t, 3H,

J7.1 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) d: 200.5

(C¹); 136.9 (arom Cq); 136.5 (C⁹); 131.6 (C⁶); 130.4

(arom CH); 128.6 (C⁷); 128.4 (arom CH); 116.6 (C¹⁰);

82.9 (C⁸); 65.7 (OCH₂); 39.8 (C³); 34.0 (C⁷); 26.5 (C⁵);

2H, J8 Hz, arom H ortho); 7.47±7.37 (m, 3H, arom H

7

Â

para, meta); 5.96 (t, 1H, J5.5 Hz, H ); 2.93 (t, 2H,

J5.5 Hz, H⁴); 2.47 (dt, 2H, J5.5 Hz, J5.5 Hz, H⁶);

1.91 (qn, 2H, J5.5 Hz, H⁵). ¹³C NMR (100 MHz,

CDCl₃) d: 169.3 (C²); 149, 147.8.9 (C³, C^7a); 130.1 (arom

Cq); 128.6, 128.5 (arom CH); 121.6 (C^3a); 111.0 (C⁷); 24.4±

23.7 (C⁴, C⁶); 22.8 (C⁵).

With complex 97: 6-benzyl-7-ethoxy-3-phenyl 5, 6, 7, 7a-

tetrahydro-4H-benzofuran-2-one 98

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5025

24.1 (C⁴); 15.3 (CH₃). 92b: ¹H NMR (400 MHz, CDCl₃) d:

7.45±7.27 (m, 6H, H⁷, arom CH);, 5.83 (m, 1H, H⁹); 5.15±

5.08 (m, 2H, H¹⁰); 4.00 (dq, 1H, J9.1 Hz, J7.1 Hz,

OCH₂); 3.59 (d, 1H, J9.7 Hz, H²); 3.52 (dq, 1H, J

9.1 Hz, J7.1 Hz, OCH₂); 3.00 (dt, 1H, J4.6 Hz,

J15.8 Hz, H⁵); 2.65±2.45 (m, 2H, H⁵, H⁸); 2.20±2.00

(m, 3H, H⁸, H³, H⁴); 1.45 (m, 1H, H⁴); 1,29 (t, 3H,

J7.1 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) d: 200.5

(C¹); 136.5 (arom Cq); 135.6 (C⁶); 135.0 (C⁹); 130.2

(arom CH); 128.6 (C⁷); 128.4 (arom CH); 117.3 (C¹⁰);

85.7 (C²); 67.4 (OCH₂); 40.88 (C³); 36.7 (C⁸); 27.15 (C⁵);

26.6 (C⁴); 15.5 (CH₃). HRMS (EI¹), calcd for C₁₈H₂₃O₂:

271.1698. Found: 271.1707. Further elution with EP/Et₂O

(95/5) gave 93 as a yellow liquid (0.050 g, 18%). ¹H NMR

(400 MHz, CDCl₃) d: 7.32±7.19 (m, 5H, arom); 3.98 (m,

1H, OCH₂); 3.52 (m, 1H, OCH₂); 3.32 (d, 1H, J10.5 Hz,

H²); 2.47 (m, 2H, H⁸); 2.30 (m, 1H, H⁴); 2.18±1.96 (m, 3H,

H⁵, H³, H⁷); 1.63 (m, 1H, H⁷); 1,16 (t, 3H, J7 Hz, CH₃);

1,05 (d, 3H, J3.8 Hz, H⁶) 0.99 (m, 1H, H⁴). ¹³C NMR

(100 MHz, CDCl₃) d: 219.3 (C¹); 131.8, 128.6, 128.0

(arom CH); 124.1 (arom Cq); 90.0 (C⁴); 86.9 (C²); 81.2

(C³); 66.9 (OCH₂); 42.3 (C⁵); 40.3 (C³); 33.4 (C¹); 32.7

(C⁴); 17.8 (C²); 15.8 (CH₃); 15.2 (C⁶). HRMS (EI¹), calcd

for C₁₈H₂₃O₂: 271.1698. Found: 271.1696.

With complex 101: 2-ethoxy-5-propylidene-cyclopenta-

none 102 and 6-ethoxy-3 ethyl 4,5,6,6a-tetrahydro-cyclo-

penta[b]furan-2-one 103

General procedure was followed using carbene complex 101

(2.5 g, 7.57 mmol). Elution with EP/Et₂O (90/10) gave the

1

cyclopentanone 102 as an oil (0.142 g, 11%). H NMR

(400 MHz, CDCl₃) d: 6.65 (m, 1H, H⁶); 3.91 (t, 1H,

J8 Hz, H⁵); 3.83 (m, 1H, OCH₂); 3.63 (m, 1H, OCH₂);

2.65 (m, 1H, H³); 2.34 (m, 2H, H³, H⁴); 2.17 (m, 2H, H⁷);

1.77 (m, 1H, H⁴); 1.25 (t, 3H, J8 Hz, CH₃); 1.05 (t, 3H,

J8 Hz, H⁸). ¹³C NMR (100 MHz, CDCl₃) d: 203.69 (CO);

140.14 (C⁶); 133.68 ((C²); 81.69 (C⁵); 65.78 (OCH₂); 27.17

(C⁴); 22.78 (C⁷); 22.38 (C³); 15.44 (CH₃); 12.85(C⁸). The

butenolide 103 was obtained as two isomers in 1/1 ratio

(0.863 g, 58%). Elution with EP/Et₂O (85/15) gave 103a

1

(trans) as a yellow oil). H NMR (200 MHz, CDCl₃) d:

4.66 (d, 1H, J8 Hz, H^6a); 3.77 (m, 1H, OCH₂); 3.56 (m,

2H, OCH₂, H⁶); 2.75±2.00 (m, 6H, H⁴, H⁵, H⁷); 1.20 (t, 3H,

J7 Hz, CH₃); 1.06 (t, 3H, J7.4 Hz, H⁸). ¹³C NMR

(100 MHz, CDCl₃) d: 176.0 (CO); 164.76 (C³); 127.81

With complex 104. General procedure was followed using

carbene complex 104 (1.46 g, 3.38 mmol). Elution with EP/

Et₂O (90/10) gave the cyclopentanone 93 (0.606 g, 66%).

(C^3a); 88.42 (C^6a); 80.72 (C⁶); 66.19 (OCH₂); 31.33 (C⁵);

With complex 99: 6-methyl-7 ethoxy-3-phenyl 5,6,7,7a-

tetrahydro-4H-furan-2-one 100

0

20.86 (C⁴); 18.14 (C⁷); 15.63 (CH₃); 12.62(C⁸). Further

elution with EP/Et₂O (80/20) gave 103b (cis) as a yellow

oil. ¹H NMR (200 MHz, CDCl₃) d: 4.89 (bs, 1H, H^6a); 3.95

(t, 1H, J4 Hz, H⁶); 3.57 (m, 2H, OCH₂); 2.62±2.14 (m,

6H, H⁴, H⁵, H⁷); 1.18 (t, 3H, J7.4 Hz, CH₃); 1,05 (t, 3H,

J7 Hz, H⁸). ¹³C NMR (100 MHz, CDCl₃) d: 177.14 (CO);

166.49 (C³); 133.92 (C^3a); 86.03 (C^6a); 75.48 (C⁶); 67.12

0

(OCH₂); 32.71 (C⁵); 20.44 (C⁴); 18.37 (C⁷); 15.77 (CH₃);

12.57 (C⁸).

With complex 106: 3,7-diphenyl-4,5,7,7a-tetrahydro-

furo[2,3-c]pyran-2-one 108

General procedure was followed using carbene complex 99

(2.03 g, 5 mmol). Elution with EP/Et₂O (70/30) gave 100 as

a 4/3 mixture of two isomers (0.953 g, 70%). 100a (trans):

¹H NMR (200 MHz, CDCl₃) d: 7.49±7.24 (m, 5H, arom);

4.74 (d, 1H, J8.4 Hz, H^7a); 4.06 (m, 1H, OCH₂); 3.60 (m,

1H, OCH₂); 2.81 (dd, 1H, J10.2 Hz, J8.4 Hz, H⁷); 2.32

(m, 1H, H⁴); 1.90 (m, 1H, H⁴); 1.56 (m, 1H, H⁵); 1.75 (m,

1H, H⁶); 1.24 (t, 3H, J7 Hz, CH₃); 1.08 (d, 3H, J6.3 Hz,

H⁸); 0.84 (m, 1H, H⁵). ¹³C NMR (100 MHz, CDCl₃) d:

172.64 (CO); 161.20 (C³); 129.59, 128.84, 128.51, 128.38,

128.16 (arom); 124.45 (C^3a); 87.80 (C^7a); 85.92 (C⁷); 67.99

(OCH₂); 35.97 (C⁶); 32.35 (C⁴); 25.73 (C⁵); 17.44 (C⁸);

General procedure was followed using carbene complex 106

(2 g, 4.69 mmol). Elution with EP/Et₂O (80/20) gave 108 as

a white solid (0.631 g, 46%) mp: 598C. ¹H NMR (200 MHz,

CDCl₃) d: 7.58±7.35 (m, 10H, arom); 4.75 (d, 1H,

J8.8 Hz, H^7a); 4.38 (dd, 1H, J11.4 Hz, J6 Hz, H⁵);

4.15 (d, 1H, J8.8 Hz, H⁷); 3.52 (td, 1H, J11.4 Hz,

1

15.52 (CH₃). 100b (cis): H NMR (200 MHz, CDCl₃) d:

7.49±7.24 (m, 5H, arom);, 4.82 (d, 1H, J3.4 Hz, H^7a);

3.82 (bs, 1H, H⁷); 3.72 (m, 1H, OCH₂); 3.57 (m, 1H,

OCH₂); 3.01 (m, 1H, H⁴); 2.30 (m, 1H, H⁴); 1.80 (m, 1H,

H⁶); 1.58 (m, 2H, H⁵); 1.08 (d, 3H, J6.3 Hz, H⁸); 1,05 (t,

3H, J9 Hz, CH₃). ¹³C NMR (100 MHz, CDCl₃) d: 173.32

(CO); 161.04 (C³); 130.55, 129.26, 128.95, 128.82, 128.61

(arom); 125.78 (C^3a); 83.01 (C^7a); 80.97 (C⁷); 69.85

(OCH₂); 34.53 (C⁶); 26.74 (C⁴); 26.19 (C⁵); 17.88 (C⁸);

15.96 (CH₃). HRMS calcd for C₁₇H₂₁O₃: 273.1491.

Found: 273.1495.

J3 Hz, H⁵); 3.15 (dd, 1H, J2.5 Hz, J14 Hz, H⁴); 2.91

0

(ddd, 1H, J14 Hz, J11.8 Hz, J6 Hz, H⁴). ¹³C NMR

(50 MHz, CDCl₃) d: 171.9 (CO); 159.43 (C³); 138.01

((C^3a); 129.35, 128.93, 128.80, 128.67, 126.36, 124.87

(arom); 85.03 (C⁷); 81.19 (C^7a); 67.80 (C⁵); 29.36 (C⁴).

Anal. calcd for C₁₉H₁₆O₃: C, 78.08; H, 5.49. Found: C,

5026

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

77.93; H, 5.49. HRMS (EI¹), calcd for C₁₉H₁₇O₃: 293.1178.

Found: 293.1174.

11. Fischer, H.; Zeuner, S.; Ackermann, K. J. Chem. Soc., Chem.

Commun. 1984, 684.

12. Casey, C. P.; Polichnowsky, J. W. J. Am. Chem. Soc. 1977, 99,

6097.

With complex 107: 3,8-diphenyl-5,6,8,8a-tetrahydro 4H-

furo[2,3-c]oxepin-2-one 109

13. Casey, C. P.; Polichnowsky, J. W.; Shusterman, A. J.; Jones,

C. R. J. Am. Chem. Soc. 1979, 101, 7282.

14. Fischer, H.; Hofmann, W. J. Chem. Ber. 1991, 124, 981.

15. Fischer, H.; Mauz, E.; Jaeger, M. J. Org. Chem. 1992, 427, 63.

16. Casey, C. P.; Albin, C. P.; Burkhardt, T. J. Am. Chem. Soc.

1977, 99, 2533.

17. Levisalles, J.; Rudler, H.; Jeannin, Y.; Dahan, F. J. Organo-

met. Chem. 1979, 178, C8.

È

18. Dotz, K. H.; Fischer, H.; Hofmann, R.; Kreissel, F. R.;

Schubert, U.; Weiss, K. Transition Metal Carbene Complexes,

Chemie: Deer®eld Beach, FL, 1983.

General procedure was followed using carbene complex 107

(2.1 g, 4.77 mmol). Elution with EP/Et₂O (85/15) gave 109

as an oil (0.112 g, 8%). H NMR (400 MHz, CDCl₃) d:

19. Klabunde, U.; Fischer, E. O. J. Am. Chem. Soc. 1967, 89,

7141.

1

7.44±7.27 (m, 10H, arom); 4.94 (d, 1H, J9.2 Hz, H^8a);

4.21 (ddd, 1H, J12 Hz, J6 Hz, H⁶); 4.10 (d, 1H,

J9.2 Hz, H⁸); 3.64 (ddd, 1H, J12 Hz, J7.6 Hz, J

4 Hz, H⁶); 3.00 (ddd, 1H, J15.8 Hz, J7.6 Hz, J5 Hz,

H⁴); 2.79 (ddd, 1H, J15.8 Hz, J8.1 Hz, J5.1 Hz, H⁴);

2.15 (m, 1H, H⁵); 1.90 (m, 1H, H⁵). ¹³C NMR (100 MHz,

20. Bernasconi, C. F.; Flores, F. X.; Kittredge, K. W. J. Am. Chem.

Soc. 1998, 120, 7983.

21. Bernasconi, C. F.; Stronach, M. W. J. Am. Chem. Soc. 1993,

115, 1341.

22. Kreissel, C. R.; Fischer, E. O.; Kreiter, C. G.; Weiss, K.

Angew. Chem., Int. Ed. Engl. 1973, 12, 563.

23. Eisner, U.; Kuthan J. Chem. Rev. 1972, 72, 1.

24. Stout, D. M.; Meyers, A. I. Chem. Rev. 1982, 82, 223.

25. Zehani, S.; Gelbard New J. Chem. 1986, 10, 511 (and references

cited therein).

CDCl₃) d: 172.41 (CO); 163.80 (C^3a); 139.59 ((C³); 129.34,

0

129.14, 129.01, 128.94, 127.32 (arom); 85.70 (C^8a); 84.30

(C⁸); 71.04 (C⁶); 26.74 (C⁴); 24.92 (C⁵). HRMS (EI¹), calcd

for C₂₀H₁₉O₃: 307.1334. Found: 293.1336.

26. Fowler, W. F. J. Org. Chem. 1972, 37, 132.

27. Rudler, H.; Goumont, R.; Audouin, M.; Parlier, A.; Martin-

Â

Vaca, B.; Durand-Reville, T.; Vaissermann J. Am. Chem. Soc.

1994, 118, 12 045.

The crystal structures of complex 24g, and of compounds 65

and 108 have been deposited at the Cambridge Crystallo-

graphic Data Centre and allocated the deposition numbers

CCDC 137061, 137062, and 137203.

28. Rudler, H.; Martin-Vaca, B.; Nicolas, M.; Audouin, M.;

Vaissermann, J. Organometallics 1998, 27, 361.

29. Martin-Vaca, B.; Rudler, H.; Audouin, M.; Nicholas, M.;

Â

Durand-Reville, T.; Vissiere, B. J. Organomet. Chem. 1998, 567,

Á

References

119±126.

30. Michael, U.; Hornfeldt, A. B. Tetrahedron Lett. 1970, 5219.

È

1. For reviews on the synthetic applications of Fischer carbene

È

31. Scilly, N. F. Synthesis 1973, 160.

32. Lansbury, P. T.; Peterson, J. O. J. Am. Chem. Soc. 1961, 83,

3737.

complexes, see: (a) Dotz, K. H. Angew. Chem., Int. Ed. Engl.

1984, 23, 587. (b) Wulff, W. D. In Comprehensive Organometallic

Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.;

Pergamon Press: Oxford, UK, 1995; Vol. 12. (c) Hegedus, L. S. In

Comprehensive Organometallic Chemistry II; Abel, E. W., Stone,

F. G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford, UK, 1995,

Vol. 12. (d) Doyle, M. In Comprehensive Organometallic

Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.;

Pergamon Press: Oxford, UK, 1995; Vol 12. (e) Harvey, D. F.;

Sigano, D. M. Chem. Rev. 1996, 96, 271. (f) Fischer, E. O.; Maas-

bol, A. Angew. Chem., Int. Ed., Engl. 1964, 3, 580.

33. Lansbury, P. T.; Peterson, J. O. J. Am. Chem. Soc. 1962, 84,

1756.

34. For earlier detection of 2,5-dihydropyridines see Tanner, D. D.;

Chi-Ming Yang J. Org. Chem. 1993, 58, 1840.

35. Fischer, E. O.; Kalbfus, H. J. Organomet. Chem. 1977, 131,

57.

36. Casey, C. P.; Brunsvold, W. R. J. Organomet. Chem. 1974,

77, 345.

37. Mancheno, M. J.; Sierra, M. A.; Gomez-Gallego, M.; Ramirez,

P. Organometallics 1999, 18, 3252.

Â

38. Martin-Vaca, B.; Durand-Reville, T.; Audouin, M.; Rudler, H.

Synthesis 1998, 1534.

2. Wulff, W. D. Organometallics 1998, 17, 3116.

3. Semmelhack, M. F.; Tamura, R.; Schnatter, W.; Springer, J.

J. Am. Chem. Soc. 1984, 106, 5363.

4. Chelain, E.; Parlier, A.; Audouin, M.; Rudler, H.; Daran, J. C.;

Vaissermann, J. J. Am. Chem. Soc. 1993, 115, 10 568.

39. Parlier, A.; Rudler, H.; Platzer, N.; Fontanille, M.; Soum, A.

J. Chem. Soc. Dalton Trans. 1987, 1041.

5. Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413.

6. Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998, 371.

7. Ivin, K. J.; Mol, J. C. Ole®n Metathesis and Metathesis

Polymerization, Academic Press: San Diego, 1997.

40. Alvarez Toledano, C.; Rudler, H.; Daran, J. C.; Jeannin, Y. J.

J. Chem. Soc., Chem. Commun. 1984, 574.

41. Rudler, H.; Martin-Vaca, B. J. Chem. Soc., Perkin Trans.

1997, 3119.

42. Corey, E. J.; Hegedus, L. S. J. Am. Chem. Soc. 1969, 91, 4926.

È

43. Merour, J. Y.; Roustan, J. L.; Charrier, C.; Collins, J.; Benaõm

J. Organomet. Chem. 1973, 51, C24.

8. Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; Robbins, J.;

DiMare, M.; O'Regan, M. J. Am. Chem. Soc. 1990, 112, 3875.

9. Casey, C. P.; Burkhardt, T. J. Am. Chem. Soc. 1973, 95, 5833.

10. Fischer, E. O.; Held, W.; Kneissel, F. R.; Frank, A.; Huttner,

G. Chem. Ber. 1977, 110, 656.

È

44. Soderberg, B. J.; York, D. C.; Hoye, T. R.; Rehberg, G. M.;

Soriano, J. A. Organometallics 1994, 13, 4501.

H. Rudler et al. / Tetrahedron 56 (2000) 5001±5027

5027

45. Rudler, H.; Parlier, A.; Martin-Vaca, B.; Garrier, E.;

Vaissermann J. Chem. Soc., Chem. Commun. 1999, 439.

46. Alvarez, C.; Pacreau, A.; Parlier, A.; Rudler, H.; Daran, J. C.

Organometallics 1987, 6, 1057.

51. Wulff, W. D.; Gilbertson, S. R. J. Am. Chem. Soc. 1985, 107,

503.

52. Aumann, R.; Heinen, H. Chem. Ber. 1987, 120, 537.

53. Gilbert, J. C.; Weerasooriya, U. J. Org. Chem. 1983, 48, 448.

54. Rubottom, G. M.; Gruber, J. M.; Marrero, R.; Juve Jr., H. D.;

Kim, C. W. J. Org. Chem. 1983, 48, 4940.

47. Chelain, E.; Goumont, R.; Hamon, L.; Parlier, A.; Rudler, M.;

Rudler, H.; Daran, J. C.; Vaissermann, J. J. Am. Chem. Soc. 1992,

114, 8088.

55. Ainsworth, C.; Chen, F.; Kuo, Y.-N. J. Organomet. Chem.

1972, 46, 59.

48. For other metal-induced syntheses of butenolides see for

example Alper, H.; Currie, J. K.; Des Abbayes, H. J. Chem.

Soc., Chem. Commun. 1978, 311 and Brandvold, T. A.; Wulff,

W. D.; Rheingold, F. J. Am. Chem. Soc. 1990, 112, 1645 and

references cited therein.

56. Mutterer, F.; Morgen, J. M.; Biedermann, J. M.; Fleury, J. P.;

Weiss, F. Tetrahedron 1970, 26, 477.

57. Wulff, W. D.; Tang, P. C.; Chan, K. S.; McCallum, J. S.; Yang,

D. C.; Gilbertson, S. R. Tetrahedron 1985, 41, 5813.

58. Cacchi, S.; Fabrizi, G.; Marinelli, F.; Moro, L.; Pace, P.

Tetrahedron 1996, 52, 10225.

È

49. Fischer, E. O.; Maasbol, A. Chem. Ber. 1967, 100, 2445.

50. Westheimer, F. H.; Taguchi, K. J. Org. Chem. 1971, 36, 1570.

Article Doi

A major breakthrough in the use of alkoxycarbene complexes of chromium and tungsten for the synthesis of elaborate organic compounds: Dihydropyridine induced reductions and cascade insertion reactions

DOI: 10.1016/S0040-4020(00)00214-3

Source and publish data:

Authors:

Article abstract of DOI:10.1016/S0040-4020(00)00214-3

Full text of DOI:10.1016/S0040-4020(00)00214-3

Products guided by the article

R&D Labs maybe for 19684-50-5

Relevant to this article

Hot Product