The preparation and evaluation of electron poor benzylidene Fischer carbene complexes: Studies toward the total synthesis of (+)-olivin

TETRAHEDRON

Pergamon

Tetrahedron 56 (2000) 10229±10247

The Preparation and Evaluation of Electron Poor Benzylidene

Fischer Carbene Complexes: Studies Toward the Total Synthesis

of (1)-Olivin

*

Vincent P. Liptak and William D. Wulff

Department of Chemistry, Searle Chemistry Laboratory, The University of Chicago, Chicago, IL 60637, USA

Received 8 February 2000; accepted 15 March 2000

AbstractÐThe continued exploration into the fate of the benzannulation reaction is put forth using the electronic nature of substituents on

the aryl ring of benzylidene Fischer carbene complexes as a handle to predict, using s-para values as a guide, the outcome of the reaction

based on the accepted mechanism. The design of this work focuses on evaluation of the synthetic utility of the benzannulation reaction and

the means by which this reaction may be improved to be a better synthetic tool in the preparation of complex natural products as this is

illustrated in our ongoing total synthesis of (1)-olivin which uses the benzannulation reaction as the key convergent synthetic step. To

accomplish these tasks, the preparation of several electron poor benzylidene Fischer carbene complexes was carried out and their reaction

with simple alkyne substrates studied. While much is known about the preparation of electron rich benzylidene Fischer carbene complexes,

little is known about the preparation of their electron poor counterparts. Thus efforts toward developing useful preparative methods of these

elusive targets has also been studied. While the use of both carbon and oxygen based aryl substituents has been explored, to date the

preparation of benzylidene carbene complexes containing oxygen based aryl substituents has been exploited to a greater degree since these

systems carry more immediate synthetic importance. This is so because the skeletal core of many of the natural products that have been

targeted with the benzannulation reaction including (1)-olivin contain a highly oxygenated polycyclic aromatic core. The enhancement in

ef®ciency of the benzannulation reaction using this synthetic methodology is demonstrated by the successful completion of the convergent

synthetic step in the total synthesis of (1)-olivin. q 2000 Published by Elsevier Science Ltd.

Introduction

the benzannulation of aryl complexes to give poly-

oxygenated naphthalene and anthracenes.¹

Since its discovery in 1975, the benzannulation reaction has

been the subject of a great deal of methodological and

mechanistic study.¹Additionally, the benzannulation

reaction has been demonstrated to have signi®cant utility

as a tool for the total synthesis of a variety of natural

products.¹However, the full synthetic potential of the

benzannulation reaction has been not yet realized because

of the inherent inef®ciency and unpredictability which have

plagued the benzannulation reaction to this point. Most of

this unpredictability has been associated with aryl (or

benzylidene) complexes rather than with alkenyl complexes

which tend to give cleaner reaction mixtures over a broader

range of substrates and reaction conditions.²Therefore, the

greatest impact on enhancing the synthetic utility of the

benzannulation reaction would result from improved

predictability in the reactions of aryl or benzylidene

complexes. This is especially the case since a majority of

the applications in natural product synthesis have involved

The chemoselectivity of the product distribution as a func-

tion of the substitution pattern of the carbene complex is

illustrated by the data in Table 1.³While it is clear (entry a,

Table 1) that the reactions of simple aryl Fischer carbene

complex with simple alkynes may give good yields of the

desired phenol product, the complexity of the reaction

mixture quickly increases and/or the overall reaction

ef®ciency decreases as the substitution pattern on the aryl

ring is varied. The data in entries b±f demonstrate quite

clearly this loss of yield and reaction ef®ciency with both

THF and benzene as solvent. It is interesting to note that all

of these examples have the common characteristic of

containing oxygen substituents that can be electron donating

by resonance. The general trend that can be seen from these

and a substantial amount of other data in the literature^1,2a,3is

that more electron rich carbene complexes will tend to give

rise to a more complex reaction pro®le.

The currently accepted mechanism for the formation of

phenol products and for the origin of many of the side-

products observed from the benzannulation reaction is

shown in Scheme 1.^2±12The ®rst branchpoint occurs with

the coupling of the alkyne and the carbene carbon to give the

Keywords: Fischer carbene complexes; benzannulation reaction; s-para;

(1)-olivin.

* Corresponding author. Current address: Department of Chemistry,

Michigan State University, East Lansing, MI 76777, USA;

e-mail: wulff@cem.msu.edu

0040±4020/00/$ - see front matter q 2000 Published by Elsevier Science Ltd.

PII: S0040-4020(00)00867-X

10230

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

Table 1. The benzannulation of benzylidene complexes 1a±1f (RMe) with 1-pentyne (all reactions were run at 0.5 M in carbene complex; N indicates that

1

product was not detected in the 500 MHz H NMR spectrum of the crude reaction mixture; Tr indicates that a trace was observed but the amount was not

determined)

Entry

Complex

R¹

R²

Solvent

Yield 2 (%)

Yield 3 (%)

Yield 4 (%)

a

b

c

d

e

f

1a

1b

1c

1d

1e

1f

H

OCH₃

H

OCH₃

H

OCH₃

H

OAc

OCH₃

OAc

THF

Benzene

THF

Benzene

73

36

60

61

47

51

N

40

N

14

10

N

Tr

N

10

26

diastereomeric h¹, h³-vinyl carbene complexed inter-

mediates 7E and 7Z. Recent evidence shows that these

intermediates are in equilibrium but it is not known if

they isomerize by alkyne de-insertion to intermediate 6 or

by some other mechanism.⁸The Z-isomer of 7 has been

shown to be the origin of the furan product 13^6,13and the

cyclopentenedione product 14.¹⁴From the intermediate 7Z,

the furan product is usually predominate in THF solution

and the cyclopentenedione is predominate in benzene

solution.^2b,3The second branch-point in phenol formation

is intermediate 7E. It is the E-isomer of the h¹, h³-vinyl

carbene complexed intermediate 7 that, after CO insertion

to the h⁴-vinyl ketene complex 8E, has the proper geometry

to cyclize to give the phenol product 10. The major side-

product of the benzannulation reaction that is observed from

the E-manifold is the indene product 12. Given the scores of

other side-products have been observed from the reaction of

alkynes with Fischer carbene complexes under various

conditions it is thus surprising that this reaction is as reliable

as it is for the synthesis of phenols. Signi®cant progress

toward improving the utility of the benzannulation reaction

could be achieved if the side-products shown in Scheme 1

could be eliminated from the reaction of aryl complexes.

It is known from previous studies that the partition between

the E and Z-isomers of the vinyl carbene complexed inter-

mediate 7 is a function of the relative electron density of the

two substituents of the starting carbene complex.⁷The more

electron releasing substituent will preferentially be oriented

trans to the carbon bearing the substituent R_Lof the alkyne.

This explains why for most simple complexes that

intermediate 7E is preferentially formed as a result of the

Scheme 1.

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

10231

Scheme 2.

directing effect of the methoxyl group and why the

benzannulation reaction produces good to excellent yields

of phenol products for simple Fischer carbene complexes. If

the combined electron releasing ability of the substituents of

the carbene carbon is too great then this is also detrimental

to phenol formation since, in this case, CO insertion in 7E is

disfavored relative to direct cyclization and the formation of

indene products.^15a,bThese studies of the effect of

electronics on product distributions suggest that proper

electronic tuning of the carbene complex could potentially

lead to improved chemoselectivity for phenol formation.

However, of the hundreds of benzannulation reactions that

have been reported to date, only a handful have involved

aryl complexes with electron withdrawing substituents on

the aryl group. The two main reasons for this are discussed

below.

current retrosynthetic approach to olivin relies on the

preparation of acylphenol 15 from the benzannulation of

carbene complex 16 with a highly functionalized alkyne

of the type 17 (Scheme 2). Our current synthesis of the

necessary alkyne 17 requires 15 steps and can be achieved

in 6% overall yield.¹⁶The required carbene complex can be

prepared in seven steps and is achieved in 20% overall

yield.³Under this approach then not only is the benzannula-

tion a highly convergent step of the synthesis, but it is also

important because of the value of alkyne 17 which contains

4 of the 5 stereocenters present in the ®nal target.

A second major reason that the benzannulation reaction of

aryl complexes bearing electron-withdrawing groups has

been so sparsely examined is that they are dif®cult to

prepare by existing methods. The Fischer method for the

synthesis of group 6 carbene complexes involving the addi-

tion of an organolithium to the metal hexacarbonyl is almost

exclusively the method that is used in the preparation of aryl

complexes.^15cWhile this method, which necessitates the

generation of aryl lithiums, is compatible with aryllithiums

of the type 18 bearing ether oxygen substituents, it is not

compatible with a variety of arenes bearing electron-with-

drawing groups.

One primary reason for the paucity of examples of the

benzannulation of aryl carbene complexes bearing electron-

withdrawing groups is that all of the natural products whose

syntheses have been pursued with the benzannulation as a

key step in the retrosynthesis have contained oxygenated

aromatic subunits. Depending on the degree of oxygenation

and the substitution pattern, oxygenated aryl carbene

complexes can be unpredictable and inef®cient in the

benzannulation reaction. The ongoing total synthesis of

(1)-olivin in our laboratories is the perfect embodiment

of the dif®culties encountered when attempting to apply

the benzannulation as the convergent step toward the

synthesis of a complex natural product (Scheme 2). The

main skeletal feature of olivin is a highly oxygenated

anthracenone system which under our current approach

would be largely assembled in a single convergent step

using the benzannulation reaction as the source of a highly

oxygenated naphthalene system which, upon further

elaboration, would lead to the desired anthracenone. Our

Given the dif®culties encountered in the benzannulation of

2,4-dioxygenated aryl complexes for the synthesis of olivin

and other natural products in our laboratories (Table 1), we

therefore have embarked on an investigation into the fate of

the benzannulation reaction of electron poor aryl Fischer

carbene complexes and the results of these studies are

reported herein. As a part of this investigation we were

necessarily required to develop new methods for the genera-

tion of electron poor carbene complexes and these results

will also be described in this work. Finally, in conjunction

with the ®rst systematic study of the benzannulation of a

series of aryl carbene complexes with electron withdrawing

substituents on the aryl group, the ®rst systematic study of

the effect of the size of the oxygen heteroatom stabilizing

substituent is reported for a series of methoxy and iso-

propoxy carbene complexes.

Table 2. Substituent s-para values

Substituent

s-para

OCH₃

H

Br

20.27

0.00

0.23

0.31

0.42

0.46

0.50

0.53

0.54

OAc

Results and Discussion

CHO

CO(C₆H₅)

CO(CH₃)

OTf

To begin our investigation, we analyzed the s-para values

of several possible substituents and decided on several

candidates which we felt would be useful for our study

CF₃

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V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

Table 3. Benzannulation of complex 19 with 1-pentyne (unless otherwise speci®ed, all reactions were run with 2 equiv. of 1-pentyne in benzene at 808C and at

0.1 M in carbene complex; N means that this product was not detected in the ¹H NMR of the crude reaction mixture; Quinone 2 and indanone 3 are numbered

after the methoxy carbene complex from which they are derived)

Entry

Carbene complex

R

R₁

R₂

Workup

2/20^a

3/21^b

4

1

2

3

4

5

6

7

8

1b

1g

1a

1h

1l

1i

1j

1d

1k

1l

1m

1n

1c

1o

1p

1q

1r

1s

Me

i-Pr

Me

i-Pr

Me

i-Pr

Me

i-Pr

Me

i-Pr

Me

i-Pr

Me

i-Pr

Me

H

OMe

H

Br

OAc

COCH₃

CF₃

H

CAN

Air

CAN

Air

CAN

Air

CAN

Air

CAN

Air

CAN

Air

36^c

29^c

76

78

82^d

90

72

75

90

91

60

63

96

95

98

60^c

64

60

65^f

66

78^d

67^h

66

49

40

59

1

N

7.5

11

,5

5

1

N

#1

N

4

9

5

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

,5

N

,2

,1

Tr ^e

N

CAN

Air

H

CAN

Air

CAN

Air

OMe

CF₃

Me

i-Pr

N

3^g

H

N

11

CAN

^a20 results from removal of the Cr(CO)₃moiety by stirring in air, and 2 results from CAN oxidation of the crude reaction mixture.

^b21 results from air workup, and 3 results from CAN oxidative workup.

^cReaction performed at 0.5 M and 458C. Reaction of 1b and 1c from ref. 3.

^dReaction performed at 0.005 M.

^eTrace of furan product 13 observed.

^fA 62% yield of phenol and 3% yield of quinone isolated.

^gTentatively identi®ed as furan 13q.

^h48% yield phenol and 19% yield quinone isolated.

(Table 2).¹⁷Our hypothesis based on the previous electronic

studies discussed above, if correct, would predict that as

the para substituent is changed from methoxyl

(s-para20.27) down the list to tri¯uoromethyl

(s-para0.54), the equilibrium between h¹,h³-vinyl-

carbene intermediates 7E and 7Z should be shifted farther

to the 7E and, in addition, the energy barrier for CO

insertion in 7E should be lowered, thus producing an

increased relative yield of phenol product. The reaction of

a number of complexes with two equivalents of 1-pentyne

was examined in benzene (0.1 M in carbene complex) at

808C and the results are presented in Table 3.

error in each case. The high yield of phenol product from

the reaction of the p-tri¯uoromethylphenyl complex 1m is

consistent with the electronic considerations discussed in

Scheme 1 and is an important experimental result. The

benzannulation of para,¹⁸meta¹⁹and ortho-tri¯uoromethyl-

phenyl²⁰carbene complexes have each been reported only

once and in each case have been reported to give lower

yields than the unsubstituted complex 1a. The yield of

benzannulation product from the para-substituted complex

was reported on the unstable chromium tricarbonyl complex

and thus this yield may not re¯ect the real effect of the

p-tri¯uoromethyl group on the reaction.¹⁸The only report

of a bromo-substituted aryl chromium carbene complex was

of a para-substituted complex with an aryl alkyne and the

yield for this reaction was the same as for the unsubstituted

complex as is observed in this work for the reaction 1i with

1-pentyne.²¹

Considering ®rst only those complexes bearing a methoxyl

group as the heteroatom stabilizing group (RMe), an

analysis of the data in Table 3 reveals that there is a correla-

tion between the yield of the phenol product and the s-para

value of substituent on the carbene complex, however, the

correlation is that of a step function and not a linear correla-

tion. The p-methoxyl complex 1b gives a low yield of

phenol (36%, entry 1) and the p-tri¯uoromethyl complex

gives the highest yield (96%, entry 12) and the p-bromo,

p-acetoxy, p-acetyl and the unsubstituted complexes give

between 60 and 78% yield (entries 3, 8, 11 and 19). In

many of the cases both an oxidative and non-oxidative

workup were employed and it was found that the yields of

isolated phenols and quinones were within experimental

As anticipated by the analysis outlined in Scheme 1, the

amounts of side-products in general do decrease with

more electron-poor substituted complexes. For example,

the methoxyl substituted complex 1b gives a 40% yield of

the indenone 3b (entry 1), the unsubstituted complex 1a

gives only a 1% yield of the indenone 3a along with 7.5%

yield of the cyclopentenedione 4a (entry 4) and the tri¯uoro-

methyl complex 1m gives less than 2% yield of 4m (entry

16). However, the mechanism shown in Scheme 1 cannot

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

10233

Scheme 3.

account for all of the products in each of the reactions since

the mass balance is not uniformly high for all substrates. It is

known that one of the many other possible side-process that

occurs during the benzannulation reaction is the oligiomer-

ization of the alkyne.²²This could occur via multiple

insertion of alkyne into the vinyl ketene complex 8Z or

the insertion of alkynes into the vinyl carbene complexed

intermediate 7E or 7Z. That this is occurring to some extent

is suggested by the data in entries 4 and 5. The total mass

balance of the reaction of complex 1a with 1-pentyne

increases from 86.5 to 93% when the concentration is

lowered from 0.1 to 0.005 M which should favor the intra-

molecular processes leading to the products shown in

Scheme 1 over intermolecular reactions with the alkyne.

A similar effect is seen with complex 1g (entries 23 and

24) (Scheme 3).

iso-propoxy group. This effect is overridden by the negative

ortho effect and no difference is seen for the reaction of the

ortho-tri¯uoromethyl and ortho-methyl complexes (entries

20±26). Previously, very little information was available

concerning the effect of size of the oxygen-stabilizing

group on the carbene carbon and the yield of phenol

product. There are two reports²³on the benzannulation of

a Fischer carbene complexes (both alkenyl) where a larger

alkoxy group leads to no change or decreased yields in

phenol products and two reports²⁴(one on an alkenyl

complex and one on an aryl complex) where increased

yields of phenol product are observed with larger alkoxy

groups. The data in Table 3 clearly show that for the

p-substituted aryl complexes with 1-pentyne, that iso-

propoxy groups are superior to methoxy groups in providing

the high ef®ciencies for phenol product. The yields of

phenol product for the p-bromo and unsubstituted phenyl

complexes are increased from 78 to 90% (entries 4 and 6)

and from 75 to 91% (entries 9 and 11) yield, respectively,

upon changing from methoxyl to iso-propoxy complexes.

Curiously, this effect is not seen for the para oxygen substi-

tuted complex (1b vs. 1g and 1d vs. 1k). The effect of

replacement of the methoxyl group with an iso-propoxyl

group on the partition between vinyl carbene complexed

intermediates 7E and 7Z is likely to be electronic rather

than steric. The increase in steric bulk of the alkoxy group

should favor 7Z and not 7E with a resulting increase in furan

or cyclopentenedione product. However, the increased

electron donating ability of an iso-propoxy group would

be expected to electronically favor 7E for reasons discussed

in Scheme 1,⁷and thus to an increase of the yield of phenol

product as observed for the data in Table 3. This could

explain the reason that the yield of phenol from the ortho

methoxy complex 1b does not increase when the methoxyl

group on the carbene carbon is replaced by iso-propoxy. In

this case, the electron donating effect of the para methoxyl

can dominate the increased electronic releasing ability of

iso-propoxy over methoxy. The lack of an effect of an

iso-propoxy group on the para acetoxy complex is not

understood at this time (entries 12 and 13).

The correlation between the electronic nature of the sub-

stituent on the carbene complex and the ef®ciency of phenol

formation does not hold up when the substituent is moved

from the para to the ortho position. It has been shown in our

previous studies that the reaction of several electron rich

ortho substituted aryl carbene complexes with 1-pentyne

resulted in slightly depressed yields from the parent phenyl

carbene complex.³Interestingly, the data in Table 3 reveal

that the yields are depressed for all ortho substituted

complexes examined regardless of their electronic nature.

The ortho-methoxyl, ortho-methyl and ortho-tri¯uoro-

methyl substituted complexes all give yields of phenol

product between 60 and 66%. The suppression of the phenol

product by an ortho substituent in fact has steric origins as

indicated by the reaction of the o-iso-propyl complex 1s

which gives a reduced yield relative to the o-methyl

complex 1q (entries 4, 23 and 27). This becomes signi®cant

when, in a total synthesis application, a highly function-

alized aryl carbene complex is required containing an

ortho substituent. This can be offset to some degree by

lowering the concentration ((entries 23 and 24), however,

this does not work for an o-methoxyl group.³

The data in Table 3 also reveal for the ®rst time that the size

of the oxygen heteroatom stabilizing substituent on the

carbene complex can have a signi®cant effect on the yield

of phenol product. The yield of phenol increases to 90% or

above for most para-substituted complexes in which the

methoxyl group on the carbene carbon is replaced by an

The reaction of the para-acetyl substituted complex 1l with

1-pentyne (Table 3, entry 14) is the ®rst example of the

benzannulation of an aryl carbene complex that bears a

carbonyl functional group.²⁵The synthesis of this complex

was not achieved by the standard Fischer method and

10234

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

Scheme 4.

deserves special comment. Since aldehyde, ketone and ester

functional groups are not compatible with organolithiums,

the preparation of carbene complexes 1l, 1t±1v via the

Fischer method from the aryl bromides 22l, 22t±22v was

not attempted (Scheme 4). We therefore attempted several

direct and indirect methods for preparing these complexes

which are summarized in Scheme 4.

benzoyl chloride did give some 1x, but as a mixture with

several other inseparable products. The anion was also

quenched with acetyl chloride in an attempt to prepare

carbene complex 1y; however, this method proved to

yield only minimal amounts of the desired carbene complex.

Unfortunately, the aldehyde containing complex 1w is not

robust enough to be used in the benzannulation reaction, as

reaction with 1-pentyne under the standard conditions did

not produce any identi®able products.

A modi®ed Semmelheck/Hegedus procedure²⁶applying

dipotassium chromium pentacarbonyl to acyl chloride 23

was also attempted, but failed to give any desired carbene

complex. We were able to achieve moderate success for the

formation of the p-formylphenyl(isopropoxy) carbene

complex 1w by developing a lithium halogen exchange

procedure on the p-bromophenyl carbene complex 1i. The

idea for this approach is that creating enough steric

hindrance around the carbene complex would inhibit

decomposition by attack from the alkyl lithium.²⁷Quench-

ing the anion derived from 1i with DMF gave the desired

carbene complex 1w in 49% yield. This result, while quite

promising, was not indicative of how other electrophiles²⁸

would behave. Attempted quenching of this anion with

Success in preparing the p-acetylphenyl carbene complex 1l

was ®nally realized by the preparation of 25 by the standard

Fischer method from halide 24 in 64% yield, followed by

cleavage of the ethylene acetal by trityl tetra¯uoroborate²⁹

giving the desired carbene complex 1l in 80% yield. The

deprotection of an acetal in the presence of a Fischer

carbene complex cannot be achieved by many of the

commonly used methods and has only been achieved on

one other occasion.³⁰The benzannulation of this novel

carbene complex with 1-pentyne followed by CAN oxida-

tion (Entry 14, Table 3) gave quinone 2l in 63% yield. While

this yield does not perfectly ®t our prediction based on the

Table 4. Benzannulation of complex 1 with 3-hexyne (unless otherwise speci®ed, all reactions were run with 2 equiv. of 3-hexyne in benzene at 808C and at

0.1 M in carbene complex; oxidative workup with CAN was employed; all yields are after isolation by silica gel chromatography; N means that this product

was not detected in the ¹H NMR of the crude reaction mixture)

Entry

Carbene complex

R

R₁

R₂

26

27

28

29

1

2

3

4

5

6

7

8

1b

1a

1h

1i

Me

i-Pr

Me

i-Pr

Me

i-Pr

Me

i-Pr

Me

i-Pr

H

OMe

CF₃

Me

OMe

H

Br

CF₃

H

93^a

96.5^b

97

93

98

D

N

,1

,2

N

,0.7^c

,0.5

,1

N

,0.7^c

N

2

N

26

N

1j

1m

1n

1c

1o

1p

1q

1r

96

N

5

N

20

N

6

99

77^d

74

9

10

11

12

36

58

59

N

^aReaction in THF at 458C and 0.5 M in 1b, Ref. 3.

^bReference 2b.

^cCombined yield of 27 and 28 is ,0.7%.

^dReaction at 458C and 0.5 M in 1c, Ref. 3.

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

10235

Scheme 5.

s-para value of acetyl (in comparison with CF₃) it does

represent a signi®cant advance in Fischer carbene chemistry

in that it demonstrates that very electron de®cient aryl

alkoxy carbene complexes can be prepared and benzannu-

lated to give phenols in reasonable yield.²⁵

the electronic nature of the ortho-substituent had little effect

with the methyl, methoxy and tri¯uoromethyl groups given

between 58 and 77% yield with no correlation with the

electron nature of the group. However, switching to the

isopropoxy carbene complex (entry 10) in this case

produced an unexpected result with the tri¯uoromethyl

substituent. The overall mass balance went up, but the

formation of ®ve membered ring products also went from

essentially zero to a 1.3:1 ratio in favor of the unwanted 5

membered ring products. This may be the result of the

increased steric requirements of the isopropoxy; however,

as yet, we have no supporting evidence for this being the

origin of such a drastic change in product distribution.

A similar set of carbene complexes were also subjected to

reaction, under similar conditions, with 3-hexyne given that

substantial differences in the benzannulation of internal and

terminal alkynes have been observed previously.^1±3The

results of these reactions are summarized in Table 4 and

in general the same trends are seen with the para-substituted

complexes with the only difference being that the starting

point for the electron rich p-methoxyl complex 1b is much

higher (93%, entry 1). In the case of the para-tri¯uoro-

methyl methoxy carbene complex (entry 6, Table 4), the

yield of phenol derived product is once again very high

(96%). Also, in the case of all of the iso-propoxy stabilized

para-substituted carbene complexes (entries 3 5, and 7), all

of the yields are nearly quantitative. These results with

para-substituted systems clearly demonstrate that if

suf®ciently electron poor carbene complexes can be

prepared, then their application to the benzannulation can

produce predictable, high yielding, and ef®cient reactions

(Scheme 5).

While very interesting from an academic perspective, the

above results do not demonstrate what advantages that could

be realized in an actual synthetic application. To achieve

this goal, we choose to examine the key benzannulation step

in the synthesis of (1)-olivin outlined in Scheme 2 and this

required that more synthetically interesting substituted aryl

carbene complexes had to be prepared. For this task, the

starting point chosen was the preparation of the para-

hydroxyphenyl carbene complexes 16a and 16b

(Scheme 6). Our previous preparation of 16a starting from

4-(o-tert-butyldimethylsiloxy)bromobenzene under similar

conditions was accomplished in 43% overall yield.³

However, changing to the tri-isopropylsilyl analog 30, we

were able to prepare the same compound in 73% overall

yield. In a similar manner, the 4-hydroxy-2-methoxyphenyl

carbene complex 16b could be prepared in an improved

As was seen with the reaction with 1-pentyne, an ortho

substituent on the aryl carbene complex leads to depressed

yields and the electron withdrawing ortho-tri¯uoromethyl

group has little effect in improving the reaction. Again,

Scheme 6.

10236

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

Scheme 7.

yield of 70% yield from 31.³The isopropoxy derivative 16c

can be prepared in 47% overall yield via tetramethyl-

ammonium salt 32.³¹

desired product and its intermediate precursor, it is thought

that this product is produced as a function of concentration

and reaction temperature, and thus could be eliminated by

the optimization of these variables.

Benzannulation of these substrates (Scheme 7) produced

desired phenol 33 and compound 34 as the only observable

products. These benzannulation reactions were carried out as

a one-pot sequence of in situ tri¯ation followed immediately

by benzannulation with 1-pentyne. This was done so

because the resulting 4-tri¯atophenyl carbene complexes

were found to be quite sensitive to air oxidation, thus the

one-pot option was the most ef®cient and simple solution.³²

When the para substituent is a tri¯ato group the results

(80% overall yield of phenol from complex 16a; .90%

average yield per step) reveal what appears to be a strong

inductive effect. The yield of phenol formation is much

higher than that observed for the para acetoxy complex

1d (Table 3, 11) and comparable to that of the para tri¯uoro-

methyl complex 1m (Table 3, entry 15). When this same

2-step procedure is applied to the dioxygenated carbene

complex 16b, again the results are quite pleasing. In our

previous studies (Table 1, entries e and f) benzannulation

reactions of this type produced only moderate yield of

phenol and a complex product mixture. In this case

however, the overall yield was 62% (79% average yield

for each of 2 steps) which compares favorably to the 33%

overall yield which results from the previously known simi-

lar 2 step sequence.³Thus, this result shows that even with

highly oxygenated carbene complexes, if the substrate is

made suf®ciently electron poor, good yields for the

benzannulation reaction can result. Compound 34 is thought

to result from a pyridine assisted trapping of ketene inter-

mediate 8E (Scheme 1) by phenoxide ion of the naphthol

product 33. Since this byproduct is actually formed from the

Finally, the convergent step of our synthesis of (1)-olivin

was studied using this new methodology. Aldehyde 38

(Scheme 8) was prepared in 10 steps according to a synthe-

sis that we have previously reported in the literature.¹⁶The

aldehyde 38 was converted to enyne 36 in 66% unoptimized

yield by one-pot one carbon homologation reaction that

produces the alkyne function directly upon with dimethyl-

1-diazo-2-oxopropylphosphonate 39.^33,34Alkyne 36 was

then submitted to conditions similar to those previously

used in our (1)-olivin studies (Scheme 8).¹⁶This three

step, one-pot reaction with of carbene complex 16b with

alkyne 36 and in situ trapping of the phenol with acetic

anhydride to give acetylated phenol 37 occurred in 40%

overall yield (74% average yield).

Conclusions

While the benzannulation has great potential as a synthetic

tool due to the inherent structural features which are present

in the phenol product produced, we believe that it has not

yet been fully exploited because of certain inconsistencies

in the performance of the reaction itself and dif®culties in

the preparation of carbene complexes with the diversity

necessary to tackle many synthetic problems. This work

has provided a demonstration that predictability and high

ef®ciency can be the norm of the benzannulation reaction. It

has also demonstrated that functional constraints imposed

by retrosyntheses for certain complex natural products can

Scheme 8.

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

10237

be accommodated in aryl Fischer carbene complexes with-

out loss of the overall reaction ef®ciency if the groups can be

suf®ciently electronically deactivated. This work, while the

continuation of a long standing theme in the study of Fischer

chromium carbene complex reactivity, has shown that

electron withdrawing groups in the para position of aryl

carbene complexes increase the chemoselectivity for phenol

formation, and has shown that the presence of substituents

in the ortho position are detrimental to phenol formation

regardless of the electronic nature of the ortho substituent

and ®nally, has shown that larger alkyl groups on the

oxygen heteroatom stabilizing substituent of the carbene

carbon give rise to increased yields of the desired phenol

product.

at once as a solid. Stirring at 2788C was continued for

5±10 min and the reaction was allowed to warm to room

temperature and stir for 3±4 h. The resulting dark yellow-

orange carbene lithium acylate solution was concentrated in

vacuo on a rotary evaporator, and allowed to stand under

high vacuum (0.1±0.2 mmHg) for 1±1.5 h. At this time, the

acylate was dissolved in a minimum of distilled water and

®ltered over a Buchner funnel. The acylate solution was

diluted with a few mL of CH₂Cl₂then treated portionwise

with solid trimethyloxonium tetra¯uoroborate under

vigorous stirring until pH 2.0 had been achieved. At this

point, the dark red biphasal solution was stirred for

30 min at room temperature. The reaction was then worked

up by pouring into a separatory funnel containing saturated

NaHCO₃and hexanes. The aqueous layer was extracted 1±2

additional times with hexanes (until all of the red color was

removed from the aqueous layer), the organics were washed

2 times with saturated NaCl solution, and dried over

MgSO₄. The dried solution was ®ltered through a fritted

funnel dry packed with Celite 545. After removal of the

solvent in vacuo, the product was obtained by silica gel

chromatography, and recrystallized from hexanes where

possible.

Experimental

General information

The atmosphere under which synthetic reagents were

combined was argon. Unless otherwise indicated, all

common reagents and solvents were used as obtained

from commercial suppliers without further puri®cation.

Prior to use, tetrahydrofuran and diethyl ether were distilled

from Na/benzophenone ketyl, and methylene chloride and

benzene were distilled from Na. Tri¯ic anhydride was

prepared by distillation from tri¯ic acid and P₂O₅, redistilled

under Ar, and stored under Ar in a sealed Kontes ¯ask with

screw top. Isopropyl tri¯ate was freshly prepared by stirring

i-PrOH and tri¯ic anhydride with pyridine in CH₂Cl₂at 08C

for 1 h, worked up by washing 2£distilled H₂O, drying over

MgSO₄, and concentrating in vacuo. Ceric ammonium

nitrate was prepared as a 0.5 M stock solution in 0.1 M

HNO₃. Carbene complexes 1a,³⁵1d,³1i³⁵and 1q³were

prepared according to their literature procedures using

methyl tri¯ate as alkylating agent. All other reagents

obtained from commercial suppliers were used as received.

Flash chromatography was carried out according to Still³⁶

Pentacarbonyl (methoxy)p-tri¯uoromethylbenzylidene

chromium (0) 1m.³⁵Carbene complex 1m was prepared

according to Procedure I in 73% recrystallized yield.

Compound 1m was obtained as a cranberry red needles;

1

mp100±1018C. R_f0.20 (hexane). H NMR (500 MHz,

CD₂Cl₂): d 4.67 (s, 3H); 7.25 (bd, 2H, J7.8 Hz); 7.65 (d,

2H, J8 Hz). ¹³C NMR (125 MHz, CDCl₃): 67.4, 122.4,

123.5 (q, CF₃, J275 Hz), 125.4, 131.2 (q, CF₃±C,

J25 Hz), 156.2, 215.6, 223.7, 350.5. IR (nujol, cm²¹

)

2065 (m), 1927 (m), 1281 (mw), 1123 (mw), 1066 (mw),

829 (mw), 721 (w), 709 (m). MS (EI) m/z (% rel. intensity):

379.9 M¹(8); 351.9 (15); 314 (27); 295.9 (13); 267.9 (28);

240 (100); 224.9 (14); 196.9 (61); 173 (7); 153 (10); 126

(13); 107 (30); 79.9 (11). HRMS (EI) calcd for C₁₄H₇F₃CrO₆

379.959983, found 379.960080. Anal. calcd for

C₁₄H₇F₃CrO₆: C, 44.23; H, 1.85. Found: C, 44.29; H, 1.86.

1

using 230±240 mesh silica gel. Routine H NMR spectra

were recorded on Bruker 400 and 500 MHz spectrometers

with tetramethylsilane (d 0.0) as an internal reference.

Routine ¹³C NMR spectra were recorded on Bruker 100

and 125 MHz spectrometers with the central peak of the

CDCl₃triplet (d77.0) as an internal reference. Infrared

spectra were recorded on a Nicolet 20SXB FTIR spectro-

meter. Low-resolution and high-resolution mass spectra

were recorded at the University of Illinois UrbanaÐ

Champagne department of chemistry mass spectrometry

laboratory. Elemental Analyses were performed by

Galbraith Inc., Knoxville, TN.

Pentacarbonyl (methoxy)o-tri¯uoromethylbenzylidene

chromium (0) 1o.³⁵Carbene complex 1o was prepared

according to Procedure I in 59% recrystallized yield.

Compound 1o was obtained as strawberry red crystals;

mp54±558C. R_f0.27 (hexane). ¹H NMR (500 MHz,

CDCl₃): d 4.54 (bs, 3H); 7.12 (bs, 1H); 7.44 (t, 1H,

J8 Hz); 7.63 (m, 2H). ¹³C NMR (125 MHz, CD₂Cl₂). d

67.7, 120.4, 122.1, 124.2 (q, ±CF₃, J263 Hz); 127.0,

127.1, 128.9, 132.4, 216.1, 224.6, 351.9. IR (nujol, cm²¹):

2065 (m), 1927 (m), 1281 (mw), 1123 (mw), 1066 (mw),

829 (mw), 721 (w), 709 (m). MS (EI) m/z (% rel. intensity):

380.1 (20, M¹); 352.1 (22); 321.0 (63); 293.1 (46); 268.1

(17); 240.1 (16); 205.1 (46); 185.1 (100); 155.1 (46); 136.1

(25); 107.1 (5). HRMS (FAB) calcd for C₁₄H₇F₃CrO₆

379.959983, found 379.960080. Anal. calcd for

C₁₄H₇F₃CrO₆: C, 44.23; H, 1.85. Found: C, 44.55; H, 2.07.

General procedure for the preparation of methoxy-

benzylidene Fischer chromium carbene complexes

(Procedure I)

To a ¯ame dried round bottom ¯ask, under Ar, was added

1 equiv. of an aryl halide (I or Br) in the volume of THF or

ethyl ether necessary to make the concentration of aryl

halide 0.2±0.5 M. The solution was cooled to 2788C, and

2 equiv. of t-butyl lithium or 1 equiv. of n-butyl lithium

were added dropwise. The resulting solution was stirred at

2788C for 10±15 min, at which time Cr(CO)₆was added all

Pentacarbonyl (methoxy)o-isopropylbenzylidene chro-

mium (0) 1s. Carbene complex 1s was prepared according

to Procedure I in 66% yield. Compound 1s was obtained as

red prisms after recrystallization from pentane/Et₂O (50/1);

mpdec. 102±1058C. R_f0.22 (hexane). ¹H NMR

10238

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

(500 MHz, CDCl₃): d 1.25 (d, 6H, J6.0 Hz); 2.55 (bd, 1H,

J6.5 Hz); 4.34 (bs, 3H); 6.82 (bs, 1H); 7.26±7.30 (m,

3H).). ¹³C NMR (125 MHz, CDCl₃): d 24.1 (±CH(CH₃)₂),

30.5, 66.1, 120.4, 125.9, 126.0, 128.6 (2£Ar), 137.9, 215.9,

224.2, 360.4. IR (thin ®lm, cm²¹): 3064 (w), 2967 (s), 2873

(m), 2062 (vs), 2020 (w), 1960 (vs), 1932 (m), 1596 (w),

1479 (m), 1440 (s), 1252 (s), 1138 (s), 928 (s), 759 (s); MS

(EI) m/z (% rel. intensity): 354 M¹(3), 326 (7), 298 (41),

267 (40), 242 (26), 211 (66), 179 (100), 163 (32), 147 (41),

131 (81), 119 (27), 105 (35), 91 (27), 59 (57). Anal. calcd

for C₁₆H₁₄CrO₆: C, 54.24; H, 3.98. Found: C, 54.35; H, 3.99.

7.67 (d, 2H, J8.5 Hz). IR (nujol, cm²¹): 2890 (w), 2056

(vs), 1960 (vs), 1598 (ms), 1231 (ms), 1163 (ms), 1095 (m).

MS (EI) m/z (% rel. intensity): 370 M¹(4), 342 (11), 314

(21), 298 (9), 286 (10), 258 (30), 230 (100), 188 (30), 172

(30), 159 (85), 135 (50), 91 (21), 77 (30), 63 (25). Anal.

calcd for C₁₆H₁₄CrO₇: C, 51.90; H, 3.81. Found: C, 51.66;

H, 3.91.

Pentacarbonyl (isopropoxy)benzylidene chromium (0)

1h. Carbene complex 1h was prepared according to Pro-

cedure II in 45% recrystallized yield. Compound 1h was

obtained as a bright red solid; mp 45±468C. R_f0.36

(hexane). ¹H NMR (500 MHz, CDCl₃): d 1.7 (d, 6H,

J6.5 Hz); 5.7 (m, 1H); 7.2±7.5 (m, 5H). ¹³C NMR

(125 MHz, CDCl₃): d 22.8, 85.9, 122.6, 128.3, 129.9,

153.9, 216.4, 224.5, 345.3. IR (nujol, cm²¹): 2061 (s),

1924 (s), 1246 (w), 1079 (w), 653 (m). MS (EI) m/z (%

rel. intensity): 312 M¹2CO (3); 284 (11); 256 (3);

230 (1); 228 (18); 200 (90); 178 (20); 158 (41); 157

(30); 129 (75); 118 (22); 105 (30); 86 (62); 84 (100).

Anal. calcd for C₁₅H₁₂CrO₆: C, 52.82; H, 3.55. Found: C,

52.71; H, 3.65.

General procedure for the preparation of isopropoxy-

benzylidene Fischer chromium carbene complexes

(Procedure II)

To a ¯ame dried round bottom ¯ask, under Ar, was added

1 equiv. of an aryl halide (Br or I) in the volume of THF or

ethyl ether necessary to make the concentration of aryl

halide 0.2±0.5 M. The solution was cooled to 2788C, and

2 equiv. of t-butyl lithium or 1 equiv. of n-butyl lithium

were added dropwise. The resulting solution was stirred at

2788C for 10±15 min, at which time Cr(CO)₆was added all

at once as a solid. Stirring at 2788C was continued for

5±10 min and the reaction was allowed to warm to room

temperature and stir for 3±4 h. The resulting dark yellow±

orange carbene lithium acylate solution was concentrated in

vacuo on a rotary evaporator, and allowed to stand under

high vacuum (0.1±0.2 mmHg) for 1±1.5 h. At this time, the

acylate was dissolved in a minimum volume of distilled

water and ®ltered over a Buchner funnel containing

1.5 equiv. of tetramethylammonium bromide dissolved in

a few mL's of distilled water. Upon ®ltration, the vacuum

adapted Erlenmeyer ¯ask was shaken for 1±2 min and

allowed to stand at room temperature for 30±45 min. At

this time, the crude, crystalline, bright yellow±orange

carbene ammonium salt was collected by suction ®ltration

over a Buchner funnel. This crude salt was then dissolved in

CH₂Cl₂and dried over MgSO₄. The methylene chloride

solution was then ®ltered through a fritted funnel dry packed

with Celite 545, and the solvent removed in vacuo. After

pumping under high vacuum (0.1±0.2 mmHg) for 1±2 h,

the crude acylate was dissolved in dry CH₂Cl₂. To the result-

ing solution was added 2±3 equiv. of isopropyltri¯ate as a

concentrated solution in methylene chloride, the reaction

was stirred at room temperature for 30±45 min. The

reaction was then worked up by pouring into a separatory

funnel containing saturated NaHCO₃and hexanes. The

aqueous layer was extracted 1±2 additional times with

hexanes (until all of the red color was removed from the

aqueous layer), the organics were washed 2 times with

saturated NaCl solution, and dried over MgSO₄. The dried

solution was ®ltered through a fritted funnel dry packed

with Celite 545. After removal of the solvent in vacuo, the

product was obtained by silica gel chromatography, and

recrystallized from hexanes where possible.

Pentacarbonyl (isopropoxy)p-bromobenzylidene chro-

mium (0) 1j. Carbene complex 1j was prepared according

to Procedure II in 42% recrystallized yield. Compound 1j

was obtained as dark purple crystals; mp92±938C.

1

R_f0.28 (hexane). H NMR (500 MHz, CDCl₃): d 1.58

(d, 6H, J6 Hz); 5.72 (bs, 1H); 7.11 (bd, 2H, J8 Hz);

7.53 (d, 2H, J8 Hz). ¹³C NMR (125 MHz, CDCl₃): d

22.6, 86.1, 124.5, 131.4 (2 overlapping Ar), 152.3, 216.1,

224.0, 343.3. IR (Nujol): 2060 (s), 1950 (s), 1377 (s), 1232

(m). MS (EI) m/z (% rel. intensity): 420 M¹(12, ⁸¹Br), 418

(12, ⁷⁹Br), 391 (50, ⁸¹Br), 364 (85, ⁸¹Br), 338 (81), 306

(100), 280 (65), 236 (50), 183 (65), 127 (27). HRMS

(FAB) calcd for C₁₅H₁₁⁷⁹BrCrO₆417.914409, found

417.914400. Anal. calcd for C₁₅H₁₄BrCrO₆: C, 42.98; H,

2.65. Found: C, 43.14; H, 2.72.

Pentacarbonyl (isopropoxy)p-acetoxybenzylidene chro-

mium (0) 1k. Carbene complex 1k was prepared according

to Procedure I in 41% yield. Compound 1k was obtained as

red solid. mpdec. 80±838C. ¹H NMR (500 MHz, CDCl₃):

d 2.32 (s, 3H); 4.79 (s, 3H); 7.16 (d, 2H, J8.0 Hz); 7.45 (d,

2H, J8.0 Hz). MS (EI) m/z (% rel. intensity): 398 M¹(6),

370 (40), 342 (60), 314 (25), 286 (49), 258 (100), 216 (20),

187 (7), 121 (4); HRMS (EI) calcd for C₁₇H₁₄CrO₈m/z

398.009327, found. 398.004500. Anal. calcd for

C₁₇H₁₄CrO₈: C, 51.40; H, 3.30. Found: C, 51.51; H, 3.64.

Pentacarbonyl (isopropoxy) p-tri¯uoromethylbenzyl-

idene chromium (0) 1n. Carbene complex 1n was prepared

according to Procedure II in 43% recrystallized yield.

Compound 1n was obtained as a dark violet needles;

mp66±688C. R_f0.29 (hexane). ¹H NMR (400 MHz,

CDCl₃): d 1.59 (d, 6H, J6.0 Hz); 5.64 (bs, 1H); 7.19

(bd, 2H, J8 Hz); 7.67 (d, 2H, J8 Hz). ¹³C NMR

(125 MHz, CDCl₃). d 22.6, 86.4, 121.8, 123.7 (q, ±CF₃,

J275 Hz); 125.4, 130.7, 156.2, 215.8, 223.9, 345.1. IR

(nujol, cm²¹). IR (Nujol): 2063 (s), 1951 (s), 1377 (s),

1312 (m), 1242 (m). MS (EI) m/z (% rel. intensity): 408

M¹(22); 380 (60); 352 (100); 328.1 (84); 296 (61); 268

(74); 226 (42); 186 (40); 167 (84); 127 (63); 107 (73); 89

Pentacarbonyl (isopropoxy)p-methoxybenzylidene chro-

mium (0) 1g. Carbene complex 1g was prepared according

to Procedure I in 41% yield. Compound 1g was obtained as

red solid. mp82±838C. R_f0.10 (hexane). ¹H NMR

(500 MHz, CDCl₃): d 1.62 (d, 6H, J6.0 Hz); 3.88 (s,

3H); 5.98 (bh, 1H, J6.0 Hz); 6.90 (d, 2H, J9.0 Hz);

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

10239

(21). HRMS (FAB) calcd for C₁₆H₁₁F₃CrO₆407.991283,

found 407.991200.

2060 (s), 1945 (s), 1750 (w), 1620 (w), 1452 (m), 1227 (s),

1040 (s), 984 (s), 873 (s). MS (EI) m/z (% rel. intensity): 399

(M¹11, 6), 370 (13), 351 (21), 315 (34), 286 (26), 251 (7),

237 (3), 223 (100), 207 (20), 193 (5), 179 (19), 121 (3), 103

(2), 87 (47), 73 (5); HRMS (FAB) calcd for C₁₇H₁₄CrO₈m/z

398.00930, found 398.14110. Anal. calcd for C₁₇H₁₄CrO₈:

C, 51.27; H, 3.54. Found: C, 51.72; H, 3.85.

Pentacarbonyl (isopropoxy)o-tri¯uoromethylbenzylidene

chromium (0) 1p. Carbene complex 1p was prepared

according to Procedure I in 54% yield. Compound 1p was

obtained as red solid; mp57±588C. R_f0.30 (hexane). ¹H

NMR (500 MHz, CDCl₃): d 1.55 (bs, 6H, ±CHCH₃)₂); 4.5±

6.0 (bs, 1H, ±CH(CH₃)₂); 7.09 (bs, 1H); 7.41 (t, 1H,

J8 Hz); 7.60 (m, 2H). ¹³C NMR (125 MHz, CDCl₃): d

22.7 (±CH(CH₃)₂), 87.8, 120.6, 123.1, 124.2 (q, ±CF₃,

J275 Hz), 127.0, 128.3, 132.0, 216.1, 224.4, 346.3 (one

aryl C not located). IR (nujol, cm²¹): 2066 (s), 1950 (s),

1377 (s), 1310 (m), 1238 (s). MS (EI) m/z (% rel. intensity):

408 M¹(21), 380 (20), 352 (25), 321 (75), 293 (57), 265

(22), 249 (28), 231 (26), 191 (62), 171 (100), 155 (88), 127

(72), 79 (18); HRMS (FAB) calcd for C₁₆H₁₁F₃CrO₆m/z

407.99128, found. 407.99133. Anal. calcd for

C₁₆H₁₁F₃CrO₆: C, 47.07; H, 2.72. Found: C, 47.16; H, 2.81.

Pentacarbonyl (methoxy)p-acetoylbenzylidene chro-

mium (0) 1l. To a ¯ame dried round bottom ¯ask under

Ar was added 25 (0.25 mmoles) in 6 mL CH₂Cl₂. To this

solution was added 2.0 equiv. of Ph₃CBF₄.²⁹The reaction

was stirred at room temperature for 5±10 min. The crude

reaction was poured into 20 mL H₂O. The aqueous layer

was extracted with 1£10 mL CH₂Cl₂, and the organics

dried over MgSO₄. Puri®cation by silica gel chromato-

graphy (2£16 cm, 4/1/1 hex/CH₂Cl₂/Et₂O) gave 70.5 mg

(80%) of the title compound as a dark red oil. Spectral

1

data for 1l: R_f0.36 (4/1/1 hex/CH₂Cl₂/Et₂O). H NMR

(CD₂Cl₂) d 1.59 (d, 6H, J4.0 Hz), 2.29 (s, 3H), 5.79 (bs,

1H), 7.15 (d, 2H, J8.6 Hz), 7.37 (d, 2H, J8.6 Hz). ¹³C

NMR (125 MHz, CDCl₃): d 26.6, 67.2, 122.1, 128.4, 129.8,

137.2, 197.0, 215.7, 223.8, 351.0. IR (thin ®lm, cm²¹): 2958

(w), 2900 (w), 2064 (s), 1950 (s), 1688 (s), 1452 (m), 1265

(s), 1221 (s), 1143 (m), 984 (m). This carbene complex is

too unstable for further characterization.

Pentacarbonyl (isopropoxy)o-methylbenzylidene chro-

mium (0) 1r. Carbene complex 1r was prepared according

to Procedure II in 62% yield. Compound 1r was obtained as

bright orange solid; mp64.5±668C. R_f0.40 (hexane). ¹H

NMR (400 MHz, CDCl₃): d 1.52 (bs, 6H, ±CHCH₃)₂), 2.15

(s, 3H), 4.65 (bs, 1H, ±CH(CH₃)₂); 6.86 (bs, 1H), 7.17±7.25

(m, 3H). ¹³C NMR (100 MHz, CDCl₃): d 18.8, 22.4

(±CH(CH₃)₂), 84.0, 120.3, 125.6, 127.9, 130.5, 135.4,

216.1, 224.6, 360.0 (one aryl C not located). IR (nujol,

cm²¹): 3064w, 2987s, 2935m, 2060vs, 1950vs, 1596w,

1452m, 1376s, 1264vs, 1175vs, 1072vs, 914vs, 893s,

745vs, 766s.

Procedure for the preparation of pentacarbonyl (isopro-

poxy)p-formylbenzylidene chromium (0) 1w. To a ¯ame

dried round bottom ¯ask was added 2.0 mmoles 1j in 30 mL

Et₂O. The solution was cooled to 2788C and 3 equiv.

n-BuLi was added dropwise slowly over 1±2 min. The

resulting solution was stirred for 5 min at which time

4 equiv. DMF was added. The reaction was allowed to

warm to room temperature over ,30 min. The crude reac-

tion was ®ltered over a fritted funnel through silica gel, and

puri®ed by silica gel chromatography (3£12 cm; 20%

EtOAc/hexanes) to give 360 mg (49%) of the desired

carbene complex as a dark red oil. Spectral data for 1w:

Procedure for the preparation of carbene complex 1l.

Compound 24 was formed by ketalization of p-bromo-

phenyl methyl ketone (13.8 mmoles) by re¯uxing for 12 h

in 25 mL of benzene with excess ethylene glycol and

4±5 mol% p-toluenesulfonic acid in a 50 mL round bottom

¯ask attached to a Dean±Stark trap.³⁷The reaction was

washed with 2£10 mL sat. NaHCO₃, 2£10 mL brine, and

dried over Na₂SO₄. The crude product was recrystallized

from pet. ether to give 2.7 g (83%) of the ketalized aryl

halide as a colorless solid. Spectral data of compound 24:

¹H NMR (500 MHz, CDCl₃): d 1.62 (s, 3H); 3.75 (m, 2H);

4.03 (m, 2H); 7.35 (d, 2H, J8 Hz); 7.46 (d, 2H, J8 Hz).

¹³C NMR (125 MHz, CDCl₃): d 27.5, 64.5, 108.4, 121.9,

127.2, 131.3, 142.4. IR (thin ®lm, cm²¹): 3413 (bm), 2983

(m), 2947 (w), 2892 (ms), 1481 (w), 1392 (s), 1370 (m),

1221 (s), 1196 (s), 1144 (m), 1092 (s), 1030 (s), 1009 (m),

941 (m), 869 (ms), 831 (s); MS (EI) m/z (% rel. intensity):

229 (100, M¹±15, ⁸¹Br), 227 (100, M¹±15, ⁷⁹Br), 211 (7,

⁸¹Br), 183 (51, ⁸¹Br), 155 (15, ⁸¹Br), 133 (8), 103 (13), 87

(38), 76 (14), 63 (5). HRMS (FAB) calcd for C₁₀H₁₁O₂⁷⁹Br

m/z 241.99424, found 241.99337. Anal. calcd for

C₁₀H₁₁O₂Br: C, 49.41; H, 4.56. Found: C, 49.42; H, 4.68.

This material was then converted to carbene complex 25 by

procedure I to yield the desired carbene complex in 64%

yield after chromatography as a dark red solid. Spectral data

for 25: ¹H NMR (500 MHz, CDCl₃): d 1.65 (s, 3H); 3.76 (m,

2H); 4.04 (m, 2H); 4.73 (s, 3H); 7.30 (d, 2H, J8.0 Hz);

7.52 (d, 2H, J8 Hz). ¹³C NMR (125 MHz, CDCl₃): d 27.3,

64.6, 67.2, 108.5, 123.5, 125.1, 145.8, 153.2, 216.1, 224.0,

350.3. IR (thin ®lm, cm²¹): 2991 (m), 2959 (m), 2889 (m),

1

R_f0.6 (20% EtOAc/hex). H NMR (500 MHz, CDCl₃): d

1.58 (d, 6H, J7 Hz); 5.65 (bs, 1H); 7.18 (d, 2H, J7.8 Hz);

7.92 (d, 2H, J7.8 Hz); 10.03 (s, 1H).

General procedure for the benzannulation of carbene

complexes 1 with 1-pentyne (Procedure III)

To a 25 mL ¯ame dried Kontes ¯ask equipped with a Te¯on

screw top was added 0.5 mmoles of carbene complex in

5 mL C₆H₆. To this solution was added 2.0 equiv. of

1-pentyne. The system was degassed by running 3 cycles

of freeze±pump±thaw. After the third cycle, the ¯ask was

back-®lled with Ar, and sealed. The reaction was then

heated with stirring to 75±808C for 16 h. At this point, the

reaction was split in half and worked-up using two methods.

Method A: The crude reaction mixture was diluted with

ether and washed with 3£10 mL of brine. The aqueous

layer was then back extracted 1£10 mL ether. The organic

layer was then dried over MgSO₄. The solution was ®ltered

through a fritted funnel dry packed with Celite 545 and the

products were collected by silica gel chromatography

(usually 2£15±20 cm, 5% EtOAc/Hexanes).

10240

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

Method B: The crude reaction mixture was diluted with

ether and treated with 2±3 mL of the above described

CAN solution. The biphasal reaction was stirred for 2±3 h

at room temperature. At this point, the reaction was poured

into a 125 mL separatory funnel and diluted with ether.

15 mL of sat. NaHCO₃was then added to the separatory

funnel to quench the CAN solution, and separated with

out shaking to avoid emulsion. The ether layer was washed

1£10 mL sat. NaHCO₃. The aqueous layer was then back

extracted 2£10 mL ether. The combined organics were then

washed 1£15 mL brine and dried over MgSO₄. The solvent

was removed in vacuo, and the products were collected by

silica gel chromatography (usually 2£15±20 cm, 5%

EtOAc/Hexanes).

Benzannulation of carbene complex 1g with 1-pentyne.

The benzannulation of 1g (0.48 mmoles) with 1-pentyne

following Procedure III, Method B and isolation by silica

gel chromatography (2£18 cm, 5% EtOAc/Hexanes) gave

34 mg (29%) of a yellow solid that was identi®ed as quinone

2b, and 60 mg (59%) of a second yellow solid that was

identi®ed as indanone 3b. Spectral data for 2b and 3b

were identical to that found in the literature.³

Benzannulation of carbene complex 1h with 1-pentyne.

The benzannulation of 1h with 1-pentyne following Pro-

cedure III, Method A and isolation by silica gel chromato-

graphy (2£17 cm, 5% EtOAc/Hexanes) gave 55 mg (90%)

of the desired phenol product 20h as a colorless solid, and

,5% of 4h based on crude NMR data. Spectral data for 20h:

mp110±1118C And R_f0.27 (10% EtOAc/Hex.) ¹H NMR

(500 MHz, CDCl₃): d 1.01 (t, 3H, J7.3 Hz); 1.41 (d, 6H,

J6 Hz); 1.71 (sextet, 2H, J7.5 Hz); 2.70 (t, 2H,

J7.7 Hz); 4.61 (h, 1H, J6 Hz); 4.73 (bs, 1H), 6.65 (s,

1H), 7.42 (t, 1H, J7.8 Hz); 7.46 (t, 1H, J7.4 Hz); 8.05

(d, 1H, J8.4 Hz); 8.18 (d, 1H, J8.3 Hz). ¹³C NMR

(125 MHz, CDCl₃): d 14.0, 22.2 (±CH(CH₃)₂), 23.4, 32.4,

71.2, 110.3, 120.7, 121.3, 122.4, 124.6, 125.6, 125.8, 126.2,

141.8, 147.0. IR (nujol, cm²¹) 3200 (bs, ±OH), 2750 (ms),

1620 (m), 1590 (m). MS (EI) m/z (% rel. intensity): 244.2

M¹(90); 230.1 (6); 202.1 (100); 173.1 (72); 159.1 (3); 145.1

(5); 128.1 (5); 115.1 (8); 105.1 (11); 77 (3). HRMS (EI)

calcd for C₁₆H₂₀O₂244.146330, found 244.145785. Anal.

calcd for C₁₆H₂₀O₂: C, 78.65; H, 8.25. Found: C, 78.36; H,

Benzannulation of carbene complex 1a with 1-pentyne.

The benzannulation of 1a with 1-pentyne following Pro-

cedure III, Method A and isolation by silica gel chromato-

graphy (2£17 cm, 5% EtOAc/Hexanes) gave 41 mg (76%)

of the desired phenol product 20a as a colorless solid, and

7.5% of 4a based on crude NMR data. Spectral data for 20a

was identical to that found in the literature.^{38 1}H NMR

(500 MHz, CDCl₃): d 1.01 (t, 3H, J7.3 Hz); 1.71 (sextet,

2H, J7.5 Hz); 2.70 (t, 2H, J7.7 Hz); 3.93 (s, 3H); 4.70

(bs, 1H), 6.54 (s, 1H), 7.41 (t, 1H, J7.2 Hz); 7.45 (t, 1H,

J7.1 Hz); 8.03 (d, 1H, J8.3 Hz); 8.12 (d, 1H, J8.3 Hz).

¹³C NMR (125 MHz, CDCl₃): d 14.0, 23.4, 32.5, 55.7, 106,

120, 121, 122, 124, 125.6, 125.8, 126, 142, 149. IR (nujol,

cm²¹) 3400 (bs, ±OH), 2950 (ms), 1680 (m), 1590 (m),

1461 (s), 1383 (s), 1270 (m), 1231 (m), 1190 (w), 1167

(w), 1125 (s), 1100 (s), 764 (S). Spectral data for 4a was

identical to that found in the literature:²⁴R_f0.18 (5%

1

8.18. Spectral data for 4h: R_f0.28 (5% EtOAc/hex). H

NMR (500 MHz, CDCl₃): d 0.86 (t, 3H, J7.3 Hz); 1.03

(t, 3H, J7.5 Hz); 1.21 (sextet, 2H, J7.5 Hz); 1.41 (d, 6H,

J6 Hz); 1.68 (sextet, 2H, J7.5 Hz); 1.82 (t, 2H, J8 Hz);

2.50 (t, 2H, J8 Hz); 4.58 (h, 1H, J6 Hz); 4.99 (s, 1H);

6.93 (s, 1H); 7.31 (m, 5H).

1

EtOAc/hex). H NMR (500 MHz, CDCl₃): d 0.86 (t, 3H,

J7.3 Hz); 1.03 (t, 3H, J7.5 Hz); 1.21 (sextet, 2H,

J7.5 Hz); 1.68 (sextet, 2H, J7.5 Hz); 1.82 (t, 2H,

J8 Hz); 2.50 (t, 2H, J8 Hz); 3.17 (s, 3H); 4.99 (s, 1H);

6.93 (s, 1H); 7.31 (m, 5H). ¹³C NMR (125 MHz,

CDCl₃): d 13.8, 14.3, 17.8, 20.4, 27.6, 37.2, 55.0, 56.9,

111.2, 127.1, 128.3, 128.7, 133.7, 142.0, 156.4, 164.2,

205.8, 206.0.

Reaction following Procedure III, Method B and isolation

by silica gel chromatography (2£17 cm, 5% EtOAc/

Hexanes) gave 45 mg (90%) of a yellow solid that was

identi®ed as the quinone 2a, and ,5% of 4h based on

crude NMR data. Spectral data for 2a was identical to that

previously shown in the literature:²⁴R_f0.29 (5% EtOAc/

Hex.) ¹H NMR (500 MHz, CDCl₃): d 1.01 (t, 3H,

J7.35 Hz); 1.62 (q, 2H, J7.4 Hz); 2.55 (t, 2H, J

7.7 Hz); 6.78 (s, 1H); 7.72 (m, 1H); 8.05 (m, 1H); 8.09

(m, 1H). ¹³C NMR (125 MHz, CDCl₃): d 13.8, 21.2, 31.5,

125, 126, 132, 132.2, 133, 134, 151, 185.

Reaction following Procedure III, Method B and isolation

by silica gel chromatography (2£17 cm, 5% EtOAc/

Hexanes) gave 39 mg (78%) of the desired quinone product

2a as a yellow solid, and 7.5% of 4a based on crude NMR

data. Spectral data for 2a was identical to that previously

1

shown in the literature.³⁸R_f0.29 (5% EtOAc/Hex.) H

NMR (500 MHz, CDCl₃): d 1.01 (t, 3H, J7.35 Hz); 1.62

(q, 2H, J7.4 Hz); 2.55 (t, 2H, J7.7 Hz); 6.78 (s, 1H); 7.72

(m, 2H); 8.05 (m, 1H); 8.09 (m, 1H). ¹³C NMR (125 MHz,

CDCl₃): d 13.8, 21.2, 31.5, 125.5, 126.1, 132.0, 132.2,

133.7, 134.0, 151.6, 185.6.

Benzannulation of carbene complex 1i with 1-pentyne.

The benzannulation of 1i with 1-pentyne following Pro-

cedure III, Method A and isolation by silica gel chromato-

graphy (2£20 cm, 5% EtOAc/Hexanes) gave 53 mg (72%)

of the desired phenol product 20i as a colorless solid, and

,5% of 4i based on crude NMR data. Spectral data for 20i:

mp114±1158C; R_f0.16 (5% EtOAc/Hex.) ¹H NMR

(500 MHz, CDCl₃): d 1.01 (t, 3H, J7.3 Hz); 1.70 (s, 2H,

J7.5 Hz); 2.69 (t, 2H, J7.5 Hz); 3.93 (s, 3H); 4.64 (s, 1H,

±OH); 6.56 (s, 1H); 7.48 (d, 1H, J8.8 Hz); 8.02 (d, 1H,

J8.8 Hz); 8.26 (d, 1H, J_meta1.1 Hz). ¹³C NMR

(125 MHz, CDCl₃): d 13.9, 23.3, 32.5, 55.7, 106.4, 120.5,

122.5, 123.4, 123.7, 123.8, 126.9, 128.1, 140.9, 149.6. IR

(nujol, cm²¹) 3300 (bs, ±OH), MS (EI) m/z (% rel. inten-

sity): 296 (100, M¹, ⁸¹Br), 294 (100, M¹, ⁷⁹Br), 281 (41,

Benzannulation of carbene complex 1d with 1-pentyne.

The benzannulation of 1d (0.4 mmoles) with 1-pentyne

following Procedure III, Method A and isolation by silica

gel chromatography (2£13 cm, 7/1/1±4/1/1 hexanes/

CH₂Cl₂/Et₂O) gave 34 mg (60%) of a yellow oil that was

identi®ed as phenol 20d. Phenol 20d was characterized by

oxidation with CAN (Method B from Procedure III) which

gave quinone 20d that was found have spectral data

identical to that reported in the literature for this

compound.³

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

10241

⁸¹Br), 265 (57, ⁷⁹Br), 251 (10, ⁷⁹Br), 237 (15, ⁷⁹Br), 223 (6),

199 (4), 183 (19, ⁷⁹Br), 172 (5), 158 (19), 143 (8), 128 (21),

115 (42), 89 (5), 75 (15), 63 (8). HRMS (EI) calcd for

C₁₄H₁₅⁷⁹BrO₂m/z 294.025541, found 294.024733. Anal.

calcd for C₁₄H₁₅⁷⁹BrO₂: C, 56.97; H, 5.12. Found: C,

57.26; H, 5.26. Spectral data for 4i: R_f0.15 (5% EtOAc/

Hex). ¹H NMR (500 MHz, CDCl₃): d 0.86 (t, 3H,

J7.4 Hz); 1.02 (t, 3H, J7.4 Hz); 1.22 (sextet, 2H,

J7.5 Hz); 1.68 (sextet, 2H, J7.5 Hz); 1.81 (t, 2H,

J7.5 Hz); 2.49 (t, 2H, J7.5 Hz); 3.17 (s, 3H); 4.99 (s,

1H); 6.92 (s, 1H); 7.20 (d, 2H, J8 Hz); 7.44 (d, 2H,

J8 Hz).

crude NMR data. Spectral data for the quinone product

was found to be identical to the quinone obtained above

from the reaction of complex 1i with 1-pentyne.

Benzannulation of carbene complex 1k with 1-pentyne.

The benzannulation of 1k with 1-pentyne following Pro-

cedure III, Method A and isolation by silica gel chromato-

graphy (2£16 cm, 10% EtOAc/Hexanes) gave 93 mg (62%)

of the desired phenol product 20k as a colorless solid.

Phenol 20k was characterized by oxidation with CAN

(Method B of Procedure III) to give quinone 2k which

was found to have spectral data identical to that reported

in the literature for this compound.³Spectral data for 20k:

R_f0.18 (10% EtOAc/Hex.) ¹H NMR (500 MHz, CDCl₃): d

1.00 (t, 3H, J7.6 Hz); 1.40 (d, 6H, ±CH(CH₃)₂, J6 Hz);

1.65 (sextet, 2H, J7.6 Hz); 2.34 (s, 3H); 2.68 (t, 2H,

J7.6 Hz); 4.62 (h, 1H, ±CH(CH₃)₂, J6 Hz); 6.61 (s,

1H), 7.13 (dd, 1H, J₁9, J₂2.2 Hz); 7.77 (d, 1H,

J2.4 Hz); 8.18 (d, 1H, J9.2 Hz).

Reaction following Procedure III, Method B and isolation

by silica gel chromatography (2£17 cm, 5% EtOAc/

Hexanes) gave 52 mg (75%) of the desired quinone product

2i as an orange solid, and ,5% of 4i based on crude NMR

data. Spectral data for 2i: mp66±67^o, R_f0.30 (5%

1

EtOAc/Hex.) H NMR (500 MHz, CDCl₃): d 1.01 (t, 3H,

J7.4 Hz); 1.61 (sextet, 2H, J7.4 Hz); 2.54 (t, 2H,

J7.5 Hz); 6.79 (t, 1H, J1.3 Hz); 7.85 (dd, 1H,

J_ortho8.25, J_meta2.0 Hz); 7.92 (d, 1H, J8.24 Hz); 8.21

(d, 1H, J_meta1.3 Hz). ¹³C NMR (125 MHz, CDCl₃): d 13.8,

21.2, 31.5, 127.7, 129.0, 129.5, 130.6, 133.3, 134.8, 136.6,

151.6, 184.1, 184.3. IR (nujol, cm²¹) 2700 (m), 1670 (s),

1621 (ms), 1584 (mw). MS (EI) m/z (% rel. intensity): 280

(100, M¹, ⁸¹Br), 278 (100, M¹, ⁷⁹Br), 252 (23, ⁸¹Br), 237

(25), 199 (11), 184 (26), 143 (16), 128 (42), 75 (30). HRMS

(EI) calcd for C₁₃H₁₁⁷⁹BrO₂277.994241, found 277.993114.

Anal. calcd for C₁₃H₁₁BrO₂: C, 55.33; H, 3.97. Found: C,

55.28; H, 4.08.

Benzannulation of carbene complex 1l with 1-pentyne.

The benzannulation of 1l (0.48 mmoles) with 1-pentyne

following Procedure III, Method B and isolation by silica

gel chromatography (2£18 cm, 5% EtOAc/Hexanes) gave

31 mg (63% based recovered ester) of the desired quinone

product 2l as a yellow solid, and recovered 14% of air

oxidized carbene complex. Spectral data for 2l: R_f0.17

1

(10% EtOAc/Hex.) H NMR (400 MHz, CDCl₃): d 1.03

(t, 3H, J7.5 Hz); 1.64 (sextet, 2H, J7.5 Hz); 2.59 (t,

2H, J7.5 Hz); 2.72 (s, 3H); 6.86 (s, 1H); 8.16 (d, 1H,

J8 Hz); 8.30 (dd, 1H, J_ortho8, J_meta3.5 Hz); 8.62 (d,

1H, J3 Hz). ¹³C NMR (100 MHz, CDCl₃): d 13.8, 21.2,

27.0, 31.6, 126.6, 126.7, 132.5, 132.6, 134.6, 135.0, 140.7,

152.3, 184.4, 184.5, 196.7. IR (thin ®lm, cm²¹): 2950 (m),

2930 (m), 2869 (m), 1967 (m), 1887 (m), 1680 (s), 1662 (s),

1627 (m), 1603 (m), 1368 (s), 1265 (s), 1248 (m), 1191 (m),

1111 (m), 1060 (w), 828 (w). MS (EI) m/z (% rel. intensity):

243 (M¹11, 75), 224 (100), 215 (16), 201 (20), 185 (7), 171

(16), 159 (8), 147 (30), 128 (15), 115 (22), 97 (10), 71 (18);

HRMS (EI) calcd for C₁₅H₁₄O₃m/z 242.09429, found

242.094702. Anal. calcd for C₁₅H₁₄O₃: C, 74.36; H, 5.82.

Found: C, 74.33; H, 5.92.

Benzannulation of carbene complex 1j with 1-pentyne.

The benzannulation of 1j with 1-pentyne following Pro-

cedure III, Method A and isolation by silica gel chromato-

graphy (2£17 cm, 5% EtOAc/Hexanes) gave 73 mg (90%)

of the desired phenol product 20j as a colorless solid, and

,5% of 4j based on crude NMR data. Spectral data for 20j:

mp117±1188C; R_f0.18 (5% EtOAc/Hex.) ¹H NMR

(500 MHz, CDCl₃): d 1.00 (t, 3H, J7.4 Hz); 1.40 (d, 6H,

±CH(CH₃)₂, J6 Hz); 1.70 (sextet, 2H, J7.4 Hz); 2.68 (t,

2H, J7.7 Hz); 4.61 (h, 1H, ±CH(CH₃)₂, J6 Hz); 4.65 (s,

1H, ±OH); 6.63 (s, 1H), 7.46 (d, 1H, J8.9 Hz); 8.03 (d,

1H, J8.9 Hz); 8.25 (s, 1H). ¹³C NMR (125 MHz, CDCl₃):

d 14.0, 22.1 (±CH(CH₃)₂), 23.3, 32.4, 71.3, 110.3, 120.3,

122.5, 123.7, 124.3, 124.7, 126.9, 128.0, 140.9, 147.6. IR

(nujol, cm²¹) 3250 (bs, ±OH), 2700 (m), 1620 (m), 1592

(m). MS (EI) m/z (% rel. intensity): 324 (10, M¹, ⁸¹Br), 322

(10, M¹, ⁷⁹Br), 282 (100, ⁸¹Br), 251 (56, ⁷⁹Br), 225 (5), 202

(50), 173 (46), 144 (14), 129 (15), 115 (32), 77 (10). HRMS

(EI) calcd for C₁₆H₁₉⁷⁹BrO₂322.056841, found 322.055971.

Anal. calcd for C₁₆H₁₉BrO₂: C, 59.45; H, 5.92. Found: C,

Benzannulation of carbene complex 1m with 1-pentyne.

The benzannulation of 1m with 1-pentyne following Pro-

cedure III, Method A and isolation by silica gel chromato-

graphy (2£20 cm, 5% EtOAc/Hexanes) gave 68 mg (96%)

of the desired phenol product 20m as a colorless solid, and

,2% of 4m based on crude NMR data. Spectral data for

1

20m: mp95±968C; R_f0.30 (5% EtOAc/Hex.) H NMR

(500 MHz, CDCl₃): d 1.02 (t, 3H, J7.3 Hz); 1.72 (sextet,

2H, J7.4 Hz); 2.71 (t, 2H, J7.7 Hz); 3.96 (s, 3H); 4.80 (s,

1H, ±OH); 6.67 (s, 1H); 7.59 (dd, 1H, J_ortho7.25 Hz,

J_meta1.5 Hz); 8.26 (d, 1H, J8.0 Hz); 8.44 (s, 1H). ¹³C

NMR (125 MHz, CDCl₃): d 13.9, 23.3, 32.5, 55.8, 108.1,

119.4, 120.3, 122.3, 123.0, 124.5 (q, ±CF₃, J272 Hz),

124.6, 126.6, 127.6 (q, ±CCF₃, J32 Hz), 142.3, 149.3.

IR (nujol, cm²¹) 3300 (bs, ±OH), 2700 (m), 1620 (m),

1576 (m). MS (EI) m/z (% rel. intensity): 284.1 M¹(100),

269.1 (31), 255.1 (60), 241.1 (10), 227.1 (16), 212.1 (6), 173

(11), 145 (4), 115.1, (11), 93.1 (1), 75 (3). HRMS (EI) calcd

for C₁₅H₁₅F₃O₂284.102415, found 284.101820. Anal. calcd

for C₁₅H₁₅F₃O₂: C, 63.37; H, 5.32. Found: C, 63.21; H, 5.40.

1

59.55; H, 6.01. Spectral data for 4j: H NMR (500 MHz,

CDCl₃): d 0.88 (t, 3H, J7.5 Hz); 1.03 (t, 3H, J7.5 Hz);

1.42 (d, 6H, J6 Hz); 1.24 (sextet, 2H, J7.5 Hz); 1.68

(sextet, 2H, J7.5 Hz); 1.82 (t, 2H, J7.5 Hz); 2.49 (t,

2H, J7.5 Hz); 4.64 (h, 1H, J6 Hz); 6.64 (s, 1H); 6.90

(s, 1H); 7.13 (d, 2H, J8 Hz); 7.49 (d, 2H, J8 Hz).

Reaction following Procedure III, Method B and isolation

by silica gel chromatography (2£17 cm, 5% EtOAc/

Hexanes) gave 63 mg (91%) of an orange solid that was

identi®ed as the quinone 2i, and ,5% of 4j based on

10242

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

Reaction following Procedure III, Method B and isolation

by silica gel chromatography (2£16 cm, 5% EtOAc/

Hexanes) gave 64 mg (95%) of the desired quinone product

2m as an orange solid, and ,2% of 4m based on crude

NMR data. Spectral data for 2m: mp49±508C, R_f0.10

268 (M¹, 45), 253 (6), 240 (1), 225 (15), 199 (9), 177

(100), 144 (13), 128 (5), 113 (72), 89 (4), 78 (48); HRMS

(EI) calcd for C₁₄H₁₁F₃O₂m/z 268.07111, found

268.071769. Anal. calcd for C₁₄H₁₁F₃O₂: C, 62.69; H,

4.13. Found: C, 62.63; H, 4.22.

1

(5% EtOAc/Hex.) H NMR (500 MHz, CDCl₃): d 1.03 (t,

3H, J7.3 Hz); 1.64 (sextet, 2H, J7.5 Hz); 2.59 (t, 2H,

J7.3 Hz); 6.87 (d, 1H, J1.3 Hz); 7.97 (dd, 1H,

J_ortho8.0 Hz, J_meta1.0 Hz); 8.19 (d, 1H, J8.0 Hz); 8.31

(s, 1H). ¹³C NMR (125 MHz, CDCl₃): d 13.8, 21.2, 31.5,

123.1 (q, ±CF₃, J273 Hz), 123.8, 126.8, 130.0, 132.6,

134.1, 134.9, 135.2 (q, ±CCF₃, J34 Hz), 152.3, 183.8,

183.9. IR (nujol, cm²¹) 2700 (m), 1674 (s), 1615 (w). MS

(EI) m/z (% rel. intensity): 268 M¹(100), 253 (31), 225 (36),

197 (14), 173 (22), 144 (31), 115 (20), 94 (5), 75 (16).

HRMS (EI) calcd for C₁₄H₁₁F₃O₂268.071114, found

268.070663. Anal. calcd for C₁₄H₁₁F₃O₂: C, 62.69; H,

4.13. Found: C, 62.72; H, 4.19.

Benzannulation of carbene complex 1p with 1-pentyne.

The benzannulation of 1p with 1-pentyne following Pro-

cedure III, Method B and isolation by silica gel chromato-

graphy (1£22 cm, 10% EtOAc/Hexanes) gave 47 mg (60%)

of a yellow solid that was identi®ed as the quinone 2o. The

spectral data for the quinone product was found to be

identical to the quinone obtained above from the reaction

of complex 1o with 1-pentyne.

Benzannulation of carbene complex 1q with 1-pentyne.

The benzannulation of 1q with 1-pentyne following Pro-

cedure III, Method A and isolation by silica gel chromato-

graphy (2£16 cm, 5% EtOAc/Hexanes) gave 33 mg (62%)

of the desired phenol product 20q as a colorless solid, along

with 1.6 mg (3%) of quinone 2q, and ,3% of 4q based on

crude NMR data. Phenol 20q was characterized by oxida-

tion with CAN (Method B of Procedure III) to give the

corresponding quinone 2q which had spectral data identical

to that reported for this compound.³Spectral data for 20q:

R_f0.33 (5% EtOAc/Hex.) ¹H NMR (500 MHz, CDCl₃): d

1.00 (t, 3H, J7.5 Hz); 1.70 (sextet, 2H, J7 Hz); 2.68 (t,

2H, J6.75 Hz); 2.86 (s, 3H); 3.86 (s, 3H); 4.72 (s, 1H,

±OH); 6.58 (s, 1H); 7.16 (d, 1H, J8 Hz); 7.31 (t, 1H,

J7.5 Hz); 7.94 (d, 1H, J8.5 Hz).

Benzannulation of carbene complex 1n with 1-pentyne.

The benzannulation of 1n with 1-pentyne following Pro-

cedure III, Method A and isolation by silica gel chromato-

graphy (2£20 cm, 5% EtOAc/Hexanes) gave 76 mg (98%)

of the desired phenol product 20n as a colorless solid, and

,1% of 4n based on crude NMR data. Spectral data for 20n:

mp100±1018C; R_f0.30 (5% EtOAc/Hex.) ¹H NMR

(500 MHz, CDCl₃): d 1.01 (t, 3H, J7.3 Hz); 1.41 (d, 6H,

±CH(CH₃)₂, J6 Hz); 1.70 (sextet, 2H, J7.5 Hz); 2.69 (t,

2H, J7.7 Hz); 4.63 (h, 1H, ±CH(CH₃)₂, J6 Hz); 4.81 (s,

1H, ±OH); 6.75 (s, 1H); 7.57 (d, 1H, J8.7 Hz); 8.27 (d,

1H, J8.7 Hz); 8.43 (s, 1H). ¹³C NMR (125 MHz, CDCl₃):

d 13.9, 22.1 (±CH(CH₃)₂), 23.2, 32.4, 71.5, 112.2, 119.4,

120.2, 122.5, 123.4, 124.6 (q, ±CF₃, J272 Hz), 124.7,

127.4, 127.5 (q, ±CCF₃, J32 Hz), 142.5, 147.3. IR

(nujol, cm²¹) 3350 (bs, ±OH), 2730 (m), 1615 (mw),

1518(m). MS (EI) m/z (% rel. intensity): 312.2 M¹(37),

293.2 (5), 270.1 (100), 241.1 (78), 213.1 (6), 173 (11),

145 (5), 115.1 (6), 75 (2). HRMS (EI) calcd for

C₁₇H₁₉F₃O₂312.133715, found 312.133386. Anal. calcd

for C₁₇H₁₉F₃O₂: C, 65.37; H, 6.13. Found: C, 65.06; H, 6.18.

Reaction following Procedure III, Method B and isolation

by silica gel chromatography (2£16 cm, 5% EtOAc/Hex) to

give 36 mg (66%) of an orange solid that was identi®ed as

the quinone 2q, and ,3% of 4q based on crude NMR data.

The spectral data for the quinone product was found to be

identical to the quinone obtained above from the reaction

phenol 20q with CAN.

Benzannulation of carbene complex 1r with 1-pentyne.

The benzannulation of 1r with 1-pentyne following Pro-

cedure III, Method A and isolation by silica gel chromato-

graphy (1.5£28 cm, 5% EtOAc/Hexanes) gave 31 mg

(48%) of the desired phenol product 20r as a colorless

solid, along with 10 mg (19%) of quinone 2r, and ,3% of

4r based on crude NMR data. Phenol 20r was characterized

by oxidation with CAN (Method B of Procedure III) to give

the corresponding quinone 2q which had spectral data

identical to that reported for this compound.³Spectral data

Reaction following Procedure III, Method B and isolation

by silica gel chromatography (2£16 cm, 5% EtOAc/

Hexanes) gave 66 mg (98%) of an orange solid that was

identi®ed as the quinone 2m, and ,1% of 4n based on

crude NMR data. The spectral data for the quinone product

was found to be identical to the quinone obtained above

from the reaction of complex 1m with 1-pentyne.

1

Benzannulation of carbene complex 1o with 1-pentyne.

The benzannulation of 1o with 1-pentyne following Pro-

cedure III, Method B and isolation by silica gel chroma-

tography (1£22 cm, 10% EtOAc/Hexanes) gave 43 mg

(64%) of the desired quinone product 2o as an yellow

solid. Spectral data for 2o: mp74±758C, R_f0.40 (10%

for 20r: R_f0.25 (5% EtOAc/Hex.) H NMR (500 MHz,

CDCl₃):

d

1.02 (t, 3H, J7.5 Hz); 1.45 (d, 6H,

±CH(CH₃)₂, J6 Hz); 1.72 (sextet, 2H, J7.75 Hz); 2.69

(t, 2H, J7.5 Hz); 2.89 (s, 3H), 4.66 (h, 1H, ±CH(CH₃)₂,

J6 Hz); 4.84 (s, 1H, ±OH); 6.67 (s, 1H); 7.60 (d, 1H,

J8 Hz); 7.42 (t, 1H, J8.4 Hz); 7.88 (d, 1H, 8).

1

EtOAc/Hex.) H NMR (500 MHz, CDCl₃): d 1.02 (t, 3H,

J7 Hz); 1.63 (sextet, 2H, J7 Hz); 2.55 (t, 2H, J7 Hz);

6.83 (t, 1H, J1 Hz); 7.83 (t, 1H, J7 Hz); 8.10 (d, 1H,

J8 Hz); 8.39 (d, 1H, J8 Hz). ¹³C NMR (125 MHz,

CDCl₃): d 13.8, 21.1, 31.0, 122.9 (q, ±CF₃, J275 Hz),

128.8 (q, ±CCF₃, J38 Hz), 130.6, 130.7, 132.2, 133.0,

134.6, 136.4, 149.8, 182.9, 184.0. IR (nujol, cm²¹) 2700

(m), 1674 (s), 1615 (w). MS (EI) m/z (% rel. intensity):

Reaction following Procedure III, Method B and isolation

by silica gel chromatography (2£16 cm, 5% EtOAc/Hex) to

give 35 mg (66%) of an orange solid that was identi®ed as

the quinone 2q, and ,3% of 4q based on crude NMR data.

The spectral data for the quinone product was found to be

identical to that of the quinone obtained above from the

reaction phenol 20q with CAN.

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

10243

Benzannulation of carbene complex 1s with 1-pentyne.

The benzannulation of 1s (0.48 mmoles) with 1-pentyne

following Procedure III, Method B and isolation by silica

gel chromatography (2£18 cm, 5% EtOAc/Hexanes) gave

59 mg (49%) of the desired quinone product 2s as a yellow

oil, and 12 mg (11%) of indanone 3s as a yellow oil.

29h based on crude NMR data. Spectral data for 26a was

identical to that found in the literature from the reaction of

1

1a.²⁴mp72±728C; R_f0.27 (10% EtOAc/Hex.) H NMR

(500 MHz, CDCl₃): d 1.16 (t, 6H, J7.5 Hz); 2.66 (q, 4H,

J7.5 Hz); 7.67±7.72 (m, 2H); 8.06±8.09 (m, 2H).

1

Spectral data for 2s: R_f0.50 (5% EtOAc/Hex.) H NMR

Benzannulation of carbene complex 1i with 3-hexyne.

The benzannulation of 1i with 3-hexyne following Pro-

cedure IV and isolation by silica gel chromatography

(2£16 cm, 5% EtOAc/Hexanes) gave 136 mg (93%) of

the desired quinone product 26i as an orange solid, and

,2% of 29i based on crude NMR data. Spectral data for

(500 MHz, CDCl₃): d 1.00 (t, 3H, J7.5 Hz); 1.27 (d, 6H,

J7.0 Hz); 1.61 (sextet, 2H, J7.5 Hz); 2.51 (t, 2H,

J7.0 Hz); 4.39 (h, 1H, J6.5 Hz); 6.69 (s, 1H); 7.64 (t,

1H, J8.0 Hz); 7.73 (dd, 1H, J₁8.0, J₂1.0 Hz); 8.02 (dd,

1H, J₁8.0, J₂1.0 Hz). ¹³C NMR (125 MHz, CDCl₃): d

13.8, 21.1, 23.5 (±CH(CH₃)₂), 28.5, 30.9, 125.2, 128.7,

132.1, 133.0, 133.9, 137.1, 149.1, 151.9, 185.7, 187.6. IR

(neat, cm²¹): 3050 (w), 2966 (s), 2932 (s), 2873 (s), 1650

(s), 1631 (s), 1585 (s), 1464 (s), 1383 (s), 1315 (s), 1260 (s),

1238 (s), 1064 (ms), 978 (m), 913 (m), 782 (s);). MS (EI)

m/z (% rel. intensity): 242 M¹(100), 227 (40), 215 (30), 199

(35), 185 (40), 171 (19), 152 (17), 141 (14), 128 (17), 115

(22), 89 (6), 77 (6), 63 (5);); HRMS (EI) calcd for C₁₆H₁₈O₂

m/z 242.13068, found 242.131306. Anal. calcd for

C₁₆H₁₈O₂: C, 79.31; H, 7.49. Found: C, 79.77; H, 7.45.

1

26i: mp97±988C; R_f0.45 (5% EtOAc/Hex.) H NMR

(500 MHz, CDCl₃): d 1.15 (t, 6H, J7.5 Hz); 2.64 (q, 4H,

J7.5 Hz); 7.80 (dd, 1H, J_ortho8.3 Hz, J_meta2.0 Hz); 7.92

(d, 1H, J8.2 Hz); 8.18 (d, 1H, J2.0 Hz). ¹³C NMR

(125 MHz, CDCl₃): d 13.9 (overlapping ±CH₂CH₃), 20.1,

20.2, 128.0, 128.7, 129.2, 130.8, 133.3, 136.2, 148.0, 148.3,

183.8, 184.2. IR (nujol, cm²¹) 2700 (m), 1670 (s), 1630

(ms), 1575 (m). MS (EI) m/z (% rel. intensity): 294 (100,

M¹, ⁸¹Br), 292 (100, M¹, ⁷⁹Br), 277 (30, ⁷⁹Br), 264 (5), 251

(16, ⁸¹Br), 237 (7, ⁸¹Br), 213 (3), 198 (76), 181 (8), 170 (15),

152 (12), 141 (20, ⁷⁹Br), 128 (25), 115 (14), 86 (5), 75 (32),

63 (10). HRMS (EI) calcd for C₁₄H₁₃⁷⁹BrO₂292.009891,

found 292.008601. Anal. calcd for C₁₄H₁₃BrO₂: C, 57.36;

H, 4.47. Found: C, 57.64; H, 4.70.

1

Spectral data for 3s: R_f0.45 (5% EtOAc/Hex.) H NMR

(500 MHz, CDCl₃): d 0.97 (t, 3H, J7.2 Hz); 1.23 (d, 3H,

J6.5 Hz); 1.24 (d, 3H, J6.5 Hz); 1.41 (m, 3H); 1.88 (m,

1H); 2.34 (dd, 1H, J₁19, J₂3.5 Hz); 2.81 (dd, 1H, J₁19,

J₂7.5 Hz); 3.27 (m, 1H); 4.18 (h, 1H, J6.5 Hz); 7.29 (m,

2H); 7.51 (t, 1H, J8.0 Hz).). ¹³C NMR (125 MHz, CDCl₃):

d 14.1, 20.8, 23.0, 23.2, 27.1, 37.2, 38.6, 43.9, 122.8, 123.9,

132.7, 150.1, 160.1, 207.2; 9 MS (EI) m/z (% rel. intensity):

216 M¹(100), 201 (80), 188 (33), 134 (42), 159 (15), 146

(28), 131 (37), 115 (34), 103 (6), 91 (18), 77 (18).

Benzannulation of carbene complex 1j with 3-hexyne.

The benzannulation of 1j with 3-hexyne following Pro-

cedure IV and isolation by silica gel chromatography

(2£16 cm, 5% EtOAc/Hexanes) gave 143 mg (98%) of

the desired quinone product 26i as an orange solid. No

other products were observed for this reaction.

General procedure for the benzannulation of carbene

complexes 1 with 3-hexyne (Procedure IV)

Benzannulation of carbene complex 1m with 3-hexyne.

The benzannulation of 1m with 3-hexyne following Pro-

cedure IV and isolation by silica gel chromatography

(2£13 cm, 5% EtOAc/Hexanes) gave 135 mg (96%) of

the desired quinone product 26m as a yellow solid. No

other products were observed for this reaction. Spectral

data for 26m: mp57±598C; R_f0.39 (5% EtOAc/Hex.)

¹H NMR (500 MHz, CDCl₃): d 1.17 (t, 6H, J7.5 Hz);

2.69 (q, 2H, J7.5 Hz); 2.70 (q, 2H, J7.5 Hz); 7.92 (d,

1H, J8.0 Hz); 8.21 (d, 1H, J8.0 Hz); 8.36 (s, 1H). ¹³C

NMR (125 MHz, CDCl₃): d 13.8, 13.9, 20.2, 20.3, 123.2 (q,

±CF₃, J272 Hz); 123.5, 127.0, 129.6, 132.5, 134.3, 134.9

(q, ±CCF₃, J33 Hz); 148.5, 148.6, 183.6, 183.9. IR (nujol,

cm²¹) 2700 (m), 1666 (s), 1611 (ms), 1583 (m). MS (EI) m/z

(% rel. intensity): 282.1 M¹(100), 267.1 (54), 239.1 (46),

225.1 (15), 201 (17), 172 (17), 144 (29), 128.1 (17), 115.1

(13), 94 (5), 75 (20). HRMS (EI) calcd for C₁₅H₁₃F₃O₂

282.086765, found 282.087535. Anal. calcd for

C₁₅H₁₃F₃O₂: C, 63.83; H, 4.64. Found: C, 63.72; H, 4.78.

To a 25 mL ¯ame dried Kontes ¯ask equipped with a Te¯on

screw top was added 0.5 mmoles of carbene complex in

5 mL C₆H₆. To this solution was added 2.0 equiv. of

3-hexyne. The system was degassed by running 3 cycles

of freeze±pump±thaw. After the third cycle, the ¯ask was

back-®lled with Ar, and sealed. The reaction was then

heated with stirring to 75±808C for 16 h. At this time, the

reaction was cooled to room temperature, and the crude

reaction mixture was diluted with ether and treated with

2±3 mL of the above described CAN solution. The biphasal

reaction was stirred for 2±3 h at room temperature. At this

point, the reaction was poured into a 125 mL sep funnel and

diluted with ether. 15 mL of sat. NaHCO₃was then added to

the sep funnel to quench the CAN solution, and separated

with out shaking to avoid emulsion. The ether layer was

washed 1£10 mL sat. NaHCO₃. The aqueous layer was

then back extracted 2£10 mL ether. The combined organics

were then washed 1£15 mL brine and dried over MgSO₄.

The solvent was removed in vacuo, and the products were

collected by silica gel chromatography (usually 2£15±

20 cm, 5% EtOAc/Hexanes).

Benzannulation of carbene complex 1n with 3-hexyne.

The benzannulation of 1n with 3-hexyne following Pro-

cedure IV and isolation by silica gel chromatography

(2£13 cm, 5% EtOAc/Hexanes) gave 139 mg (99%) of

the desired quinone product 26m as an orange solid. No

other products were observed for this reaction.

Benzannulation of carbene complex 1h with 3-hexyne.

The benzannulation of 1h with 3-hexyne following Pro-

cedure IV and isolation by silica gel chromatography

(2£17 cm, 5% EtOAc/Hexanes) gave 55 mg (90%) of the

desired quinone product 26a as an orange solid, and ,1% of

Benzannulation of carbene complex 1o with 3-hexyne.

The benzannulation of 1o (0.4 mmoles) with 3-hexyne

10244

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

following Procedure IV and isolation by silica gel chroma-

tography (2£13 cm, 5% EtOAc/Hexanes) gave 84 mg

(74%) of the desired quinone product 26o as a bright yellow

solid. Spectral data for 26o: R_f0.25 (5% EtOAc/hex). H

30. To a 100 mL ¯ame dried round bottom ¯ask under Ar

was added 264 mg (6.6 mmoles) NaH (60% dispersion in

mineral oil). The mineral oil was removed by washing

3£5 mL hexanes. The ¯ask was kept under Ar and 20 mL

of dry THF was added. The stirring suspension was cooled

to 08C, and 1.04 g (6.0 mmoles) of p-bromophenol was

added dropwise slowly over 5±10 min as a solution in

15 mL THF. The reaction was then allowed to stir at 08C

for 30 min then warmed to room temperature and stirred for

1 h. At this time, 1.39 g (7.2 mmoles) of TIPSCl was added

all at once to the reaction, and stirring was continued for

3.5 h. The reaction was then poured onto 50 mL brine and

50 mL of ethyl ether in a sep funnel. The organic layer was

washed 2£50 mL distilled H₂O, 1£50 mL brine, and dried

over MgSO₄. The solvent was removed in vacuo, followed

by silica gel chromatography (3£20 cm, eluant: hexanes) to

give 1.91 g (97%) of 30 as a colorless oil. Spectral data for

30: R_f0.7 (hexanes). ¹H NMR (400 MHz, CDCl₃): d 1.08

(d, 18H, ±CH(CH₃)₂, J7.2 Hz); 1.22 (h, 3H, ±CH(CH₃)₂,

J7.8 Hz); 6.75 (d, 2H, J8.7 Hz); 7.30 (d, 2H, J8.7 Hz).

¹³C NMR (125 MHz, CDCl₃): d 12.6, 17.9, 113.2, 121.7,

132.2, 155.3. IR (neat, cm²¹): 2945 (s), 2927 (s), 2891 (m),

2867 (s), 1585 (s), 1488 (s), 1463 (m), 1384 (w), 1275 (s),

1164 (m), 1094 (m), 1070 (m), 1006 (m), 909 (s), 883 (s),

827 (s), 781 (s). MS (EI) m/z (% rel. intensity): 330 (26, M¹,

⁸¹Br), 328 (26, M¹, ⁷⁹Br), 285 (100, ⁷⁹Br), 259 (56, ⁸¹Br),

243 (16, ⁷⁹Br), 231 (80), 217 (60, ⁸¹Br), 201 (32, ⁸¹Br), 178

(12), 150 (24), 135 (34), 122 (25), 91 (10), 75 (19). HRMS

(EI) calcd for C₁₅H₂₅⁷⁹BrOSi m/z 328.085805, found

328.085264. Anal. calcd for C₁₅H₂₅BrOSi: C, 54.70; H,

7.65. Found: C, 55.08; H, 7.54.

1

NMR (400 MHz, CDCl₃): d 1.17 (m, 6H); 2.65 (m, 4H);

7.79 (t, 1H, J7.5 Hz); 8.08 (d, 1H, J8 Hz); 8.37 (d, 1H, J

8 Hz). ¹³C NMR (100 MHz, CDCl₃): d 11.4 (2£CH₃); 19.9,

20.6, 121.5 (q, ±CF₃, J275 Hz); 130.6, 131.3, 132.7, 134.4,

141.8, 146.9, 150.0, 157.8, 183.4 (2£CO). IR (thin ®lm, cm²¹):

3108 (s), 2981 (s), 2942 (m), 2850 (m), 1672 (s), 1656 (s),

1622 (s), 1587 (s), 1420 (m), 1350 (s), 1314 (s), 1279 (s), 1255

(s), 1225 (m), 1165 (s), 1139 (s), 1103 (s), 1084 (m), 1059 (m),

807 (m); MS (EI) m/z (% rel. intensity): 282 M¹(60), 263 (34),

247 (100), 219 (53), 205 (12), 172 (25), 157 (6), 144 (34), 125

(13), 94 (6), 75 (15); HRMS (EI) calcd for C₁₅H₁₃F₃O₂m/z

282.086765, found 282.086650. Anal. calcd for

C₁₅H₁₃F₃O₂: C, 63.83; H, 4.64. Found: C, 63.63; H, 4.70.

Benzannulation of carbene complex 1p with 3-hexyne.

The benzannulation of 1p (0.4 mmoles) with 3-hexyne

following Procedure IV and isolation by silica gel chroma-

tography (2£13 cm, 2.5% EtOAc/Pentane) gave 40.4 mg

(36%) of the desired quinone product 26o as a bright yellow

solid, 20.7 mg (20%) of indenone 27o as a bright yellow

solid, and 31 mg (26%) of indene 28p as a colorless oil.

Spectral data for 26o was identical to that shown above.

Spectral data for 27o: R_f0.28 (2.5% EtOAc/pent). ¹H

NMR (500 MHz, CDCl₃): d 1.09 (t, 3H, J7.5 Hz); 1.23

(t, 3H, J7.5 Hz); 2.30 (q, 2H, J7.5 Hz); 2.58 (q, 2H,

J7.5 Hz); 7.23 (d, 1H, J7 Hz); 7.39±7.44 (m, 2H). ¹³C

NMR (125 MHz, CDCl₃): d 12.3, 13.8, 16.1, 19.2, 121.5,

122.4 (q, ±CF₃, J275 Hz); 124.5, 128.1, 132.6, 133.2,

136.1, 147.3, 157.3, 194.2. Spectral data for 28p: R_f0.37

(2.5% EtOAc/pent). ¹H NMR (500 MHz, CDCl₃): d 0.50 (t,

3H, J7.5 Hz); 1.15 (t, 3H, J7.5 Hz); 1.28 (d, 3H, J

5 Hz); 1.30 (d, 3H, J5 Hz); 1.88 (m, 1H); 2.09 (m, 1H);

2.20 (sextet, 1H, J7 Hz); 2.71 (sextet, 1H, J7 Hz); 3.42

(t, 1H, J4.5 Hz), 4.53 (h, 1H, J5 Hz); 7.19 (t, 1H, J

8 Hz); 7.45 (d, 1H, J7 Hz); 7.53 (d, 1H, J8 Hz). ¹³C

NMR (125 MHz, CDCl₃): d 8.1, 13.1, 19.3, 21.7, 21.9,

22.2, 46.3, 121.2, 123.7, 124.2 (q, ±CF₃, J275 Hz);

124.3, 125.3, 133.8, 134.5, 146.8, 149.1.

Conversion of 30 to Complex 16a. To 25 mL ¯ame dried

round bottom ¯ask under Ar was added 658 mg

(2.0 mmoles) of 30 in 20 mL of dry THF. The solution

was cooled to 2788C, and 2.38 mL (4 mmoles, 2 equiv.)

of 1.68 M tert-butyllithium was added dropwise over

2±3 min. The reaction was stirred at 2788C for

15±20 min, at which time, 484 mg (2.2 mmoles,

1.1 equiv.) of solid Cr(CO)₆was added all at once. After

stirring an additional 15 min at 2788C, the reaction was

warmed to room temperature over 1 h and stirred at that

temperature for 3 additional hours. The resulting lithium

acylate was concentrated on a rotary evaporator, then

pumped under high vacuum (0.1±0.2 mmHg) for 1±1.5 h.

to remove all THF. The crude acylate was then dissolved in

a minimum of distilled H₂O, diluted with 2±3 mL CH₂Cl₂,

and treated portionwise with small amounts of Meerwein's

salt, until the biphasal reaction has reached a pH of 2±3.

After stirring at room temperature for 30 min, the reaction

was diluted with 20 mL hexanes, and poured into 20 mL

NaHCO₃(sat.) and 20 mL hexanes. The aqueous layer

was extracted 2£15 mL of hexane or until all the dark red

carbene color had been removed. The combined organics

were then washed 1£25 mL brine, and dried over MgSO₄.

The dried solution was then ®ltered over a fritted funnel dry

packed with Celite 545, and the solvent removed in vacuo.

After pumping the crude product under high vacuum for

30 min, the carbene complex was dissolved in 15 mL of

dry THF in a ¯ame dried 100 mL round bottom ¯ask, and

cooled to 08C. To this solution was added, dropwise slowly,

0.5 mL HF^.Pyridine. The reaction was checked by TLC

after 2 min (25% EtOAc/Hex) and showed almost complete

Benzannulation of carbene complex 1q with 3-hexyne.

The benzannulation of 1q (0.5 mmoles) with 3-hexyne

following Procedure IV and isolation by silica gel chroma-

tography (2£20 cm, 2.5% EtOAc/Pentane) gave 66 mg

(58%) of the desired quinone product 26q as a bright yellow

solid. Spectral data for 26q was identical to that reported in

the literature for this compound.³

Benzannulation of carbene complex 1r with 3-hexyne.

The benzannulation of 1r (0.5 mmoles) with 3-hexyne

following Procedure IV and isolation by silica gel chroma-

tography (2£20 cm, 2.5% EtOAc/Pentane) gave 68 mg

(59%) of the desired quinone product 26q as a bright yellow

solid, and 6 mg (6%) of indenone 27q as a yellow oil.

Spectral data for 26q and 27q were identical to that reported

for these compounds.³

Improved preparation of 16a (Procedure V)

Preparation of 4-bromophenyl-triisopropylsilyl ether

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

10245

removal of the TIPS group (R_f,0.7 for TIPS protected

carbene complex and R_f,0.25 for deprotected). After

stirring the reaction for an additional 10 min at room

temperature, ,25 mL of sat. NaHCO₃was added dropwise

via an addition funnel to quench the reaction. The reaction

was then vigorously stirred for ,15 min after complete

addition. The reaction was then poured into 15 mL hexanes.

The organic layer was washed 1£15 mL sat. NaHCO₃. The

combined aqueous washes were then back extracted

2£20 mL hexanes or until all of the red carbene color had

been removed. The combined organics were then washed

1£25 mL brine, and dried over MgSO₄. The solvent was

removed in vacuo, and the product isolated by silica gel

chromatography (3£20 cm, 25% EtOAc hexanes) to give

481 mg (73%) of the desired carbene complex 16a as a

dark red solid. Spectral data was identical to that reported

in the literature.³

of isopropyltri¯ate as a concentrated solution in methylene

chloride, the reaction was stirred at room temperature for

30±45 min. The reaction was then worked up by pouring

into a separatory funnel containing saturated NaHCO₃and

hexanes. The aqueous layer was extracted 1±2 additional

times with hexanes (until all of the red color was removed

from the aqueous layer), the organics were washed 2 times

with saturated NaCl solution, and dried over MgSO₄. The

dried solution was ®ltered through a fritted funnel dry

packed with Celite 545. After removal of the solvent in

vacuo, 670 mg (47%) of the desired product 16c was

obtained after silica gel chromatography as a dark red

solid. Spectral data for 16c: R_f0.08 (25/5/1 hexanes/

1

CH₂Cl₂/Et₂O). H NMR (400 MHz, CDCl₃): d 1.59 (d,

6H, J6.0 Hz); 5.70 (bs, 1H); 6.42 (bs, 1H, ±OH); 7.14

(d, 2H, J8 Hz); 7.46 (d, 2H, J8 Hz). ¹³C NMR

(125 MHz, CDCl₃): d 22.7, 85.6, 114.7, 129.0, 146.7,

159.0, 216.8, 224.0, 336.5. IR (thin ®lm, cm²¹): 3341 (bs,

OH), 2984 (w), 2950 (w), 2057 (s), 1950 (s), 1602 (m), 1210

(m), 920 (m). Anal. calcd for C₁₅H₁₂CrO₇: C, 50.57; H, 3.40.

Found: C, 50.68; H, 3.56.

Improved preparation of 16b

Preparation of 4-bromo-3-methoxyphenyltriisopropyl-

silyl ether 31. Following the same procedure as for the

preparation of 30, 31 was prepared in 92% yield (after

chromatography) from 4-bromo-3-methoxyphenol which

was prepared according to Ref. 3. Spectral data for 31:

In situ preparation and benzannulation of pentacar-

bonyl 4-tri¯ato-benzylidenemethoxy chromium (0) with

1-pentyne (Procedure VI)

1

R_f0.7 (hexanes). H NMR (400 MHz, CDCl₃): d 1.10 (d,

18H, ±CH(CH₃)₂, J7.5 Hz); 1.26 (h, 3H, ±CH(CH₃)₂,

J7.8 Hz); 3.85 (s, 3H), 6.38 (dd, 1H, J_ortho9.0 Hz,

J_meta2.5 Hz); 6.46 (d, 1H, J2.5 Hz) 7.31 (d, 1H,

J8.5 Hz). ¹³C NMR (125 MHz, CDCl₃): d 12.7, 17.9,

56.1, 102.6, 104.9, 113.0, 133.0, 156.5, 156.7. IR (neat,

cm²¹): 2957 (s), 2944 (s), 2892 (m), 2867 (s), 1587 (s),

1580 (s), 1487 (s), 1461 (s), 1447 (s), 1403 (s), 1302 (s),

1206 (s), 1171 (s), 1120 (m), 900 (s). MS (EI) m/z (% rel.

intensity): 360 (42, M¹, ⁸¹Br), 358 (42, M¹, ⁷⁹Br), 317 (100,

⁸¹Br), 289 (53, ⁸¹Br), 273 (15, ⁷⁹Br), 259 (65, ⁷⁹Br), 247 (40,

⁸¹Br), 221 (22), 193 (23), 180 (35), 166 (37), 151 (27), 130

(66), 111 (18), 97 (32), 85 (38), 71 (55). HRMS (EI) calcd

for C₁₆H₂₇⁷⁹BrO₂Si, m/z 358.096370, found 358.096384.

To a 25 mL ¯ame dried Kontes ¯ask equipped with a Te¯on

screw top was added 0.5 mmoles of carbene complex 16a,

and 1.0 mmoles of pyridine in 5 mL dry benzene. The ¯ask

was submitted to 3 cycles of freeze±pump±thaw to remove

all volatiles. At this time, 1.05 equiv. of Tf₂O was added all

at once. The reaction immediately darkened to a blackish-

red was analyzed by TLC (25% EtOAc/Hex) after 1 min to

show that almost complete conversion to the p-tri¯ato-

benzylidene had occurred. After stirring the reaction for 5

additional minutes, 1.0 mmoles of 1-pentyne was added.

The reaction was again degassed by 3 cycles of FPT, and

the reaction was sealed under Ar and stirred at 75±808C for

16 h. After cooling to room temperature, the reaction was

diluted with 15 mL ethyl ether, poured onto 15 mL brine in

a sep funnel, and washed 2 more times with brine and dried

over MgSO₄. The solvent was removed in vacuo and the

reaction puri®ed by silica gel chromatography (2£20 cm,

25/5/1 hexanes/CH₂Cl₂/Et₂O) to give 146 mg (80%) of the

desired phenol 33a as an off white solid, and ,5% of 34a

based on crude NMR data (See compound 34c). Spectral

data for 33a: mp55±568C; R_f0.17 (25/5/1 hexanes/

Conversion of 31 to 16b. Following Procedure V, the

desired carbene complex was prepared from 31 in 73.5%

combined yield of non-chelated and chelated carbene

complex 16b (chelate: 234 mg (25.5%); nonchelate

480 mg (48%)). Spectral data for both the chelated and

non-chelated forms of 16b was identical to that previously

reported in Ref. 3.

1

CH₂Cl₂/Et₂O) H NMR (500 MHz, CDCl₃): d 1.03 (t, 3H,

Preparation of 16c. Following Procedure V starting with

4 mmoles of 30, after the lithium acylate had been pumped

on high vacuum for 1 h, the crude product was dissolved in a

minimum of distilled H₂O, and ®ltered through a Buchner

funnel into a few mL of distilled H₂O containing 1.1 equiv.

of NMe₄Br. The Erlenmeyer ¯ask was shaken for 1±2 min

then allowed to stand at room temperature for 30 min. The

crude orange±yellow ammonium salt was collected by

suction ®ltration over a Buchner funnel. The crude solid

was then dissolved in CH₂Cl₂and dried over MgSO₄. The

methylene chloride solution was the ®ltered through a fritted

funnel dry packed with Celite 545, and the solvent removed

in vacuo. After pumping under high vacuum (0.1±

0.2 mmHg) for 1±2 h, the crude acylate was dissolved in

dry CH₂Cl₂. To the resulting solution was added 2±3 equiv.

J8.0 Hz); 1.72 (sextet, 2H, J7.5 Hz); 2.70 (t, 2H,

J8.0 Hz); 3.96 (s, 3H); 4.75 (s, 1H, ±OH); 6.62 (s, 1H),

7.29 (dd, 1H, J_ortho9.0 Hz, J_meta2.0 Hz); 8.02 (d, 1H,

J2.0 Hz); 8.24 (d, 1H, J9 Hz). ¹³C NMR (125 MHz,

CDCl₃): d 14.0, 23.2, 32.5, 55.8, 107.2, 113.6, 118.1,

118.5 (q, ±CF₃, J325 Hz), 123.3, 123.9, 124.9, 126.1,

141.7, 147.7, 149.4. IR (nujol, cm²¹) 3300 (bs, ±OH),

1620 (m), 1603 (m), 1588 (mw), 1250 (m), 1212 (m),

1115 (w), 1100 (ms), 879 (m), 834 (m), 814 (mw), 718

(m). MS (EI) m/z (% rel. intensity): 364.1 M¹(89), 335

(7), 321 (2), 253 (2), 132.1 (45), 203.1 (100), 188.1 (4),

174.1 (16), 159.1 (5), 145.1 (10), 115.1 (10), 69 (25).

HRMS (EI) calcd for C₁₅H₁₅F₃SO₅364.059230, found

364.058110. Anal. calcd for C₁₅H₁₅F₃SO₅: C, 49.45; H,

4.15. Found: C, 49.49; H, 4.24.

10246

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

In situ preparation and benzannulation of pentacarbonyl

4-tri¯ato-2-methoxybenzylidenemethoxy chromium (0)

with 1-pentyne. Following Procedure VI starting with

0.65 mmoles of carbene complex, the benzannulation of

16b was carried out, and gave 78 mg (62% yield) of the

desired phenol 33b as the only observable product. Spectral

(m, 1H); 4.11 (p, 1H, J7.9 Hz); 5.11±5.17 (m, 2H); 5.82

(m, 1H). ¹³C NMR (125 MHz, CDCl₃): d 23.80, 23.61,

18.3, 20.4 (-SiC(CH₃)₃), 26.1, 27.3, 27.6, 44.6, 60.3, 69.6,

73.7, 75.1, 82.5, 82.8, 83.0, 108.4, 116.4, 138.7. IR (neat,

cm²¹): 3313 (m), 2982 (s), 2954 (s), 2931 (s), 2887 (s), 2857

(s), 2100 (w), 1473 (m), 1463 (m), 1378 (s), 1369 (s), 1252

(s), 1093 (s), 918 (m), 836 (s), 775 (s). MS (CI) m/z (% rel.

intensity): 383 (4, M¹11), 370.2 (2), 367.4 (100), 355.4 (2),

349.4 (3), 338.4 (2). HRMS (CI) calcd For C₂₁H₃₈SiO₄

382.253864, found 382.252600.

1

data for 33b: R_f0.08 (25/5/1 hexanes/CH₂Cl₂/Et₂O). H

NMR (400 MHz, CDCl₃): d 0.99 (t, 3H, J7.0 Hz); 1.69

(sextet, 2H, J7 Hz); 2.66 (t, 2H, J7 Hz); 3.90 (s, 3H);

3.97 (s, 3H); 4.86 (2, 1H, ±OH); 6.65 (d, 1H, J3 Hz); 6.69

(s, 1H); 7.67 (d, 1H, J3 Hz). ¹³C NMR (125 MHz, CDCl₃):

d 13.9, 23.0, 32.2, 56.5, 57.4, 99.4, 105.9, 110.7, 116.1,

118.5 (q, ±CF₃, J310 Hz), 124.0, 127.5, 142.2, 147.3,

150.9, 158.8. IR (nujol, cm²¹) MS (EI) m/z (% rel. inten-

sity): 394 (M1, 40), 335 (8), 321 (2), 253 (1), 231 (48), 203

(100), 188 (4), 174 (17), 159 (5), 145 (11), 115 (12), 69 (25);

HRMS (EI) calcd for C₁₅H₁₅O₅F₃S m/z 364.059230, found

364.058110. Anal. calcd for C₁₆H₁₇F₃SO₆: C, 48.70; H,

4.34. Found: C, 48.60; H, 4.45.

Benzannulation of enyne 36 with pentacarbonyl (2-

methoxy-4-tri¯atobenzylidene)methoxy chromium (0).

To a 50 mL ¯ask equipped with a high vacuum threaded

te¯on stopcock was added a stirring bar and 179 mg

(0.5 mmol) of carbene complex 16b in 3.5 mL of CH₂Cl₂.

After addition of 2.2 equiv. of pyridine, the solution was

deoxygenated by the freeze±thaw method (3 cycles) and

then back®lled with argon at room temperature. Tri¯ic

anhydride (1.05 equiv., 0.525 mmol, 88 mL) was added

and the resulting solution was stirred for 5 min. Enyne 36

(1.05 equiv., 0.525 mmol, 200 mg) was added and the solu-

tion was then deoxygenated by the freeze±thaw method (2

cycles). The ¯ask was back-®lled with argon at room

temperature and then sealed and heated at 458C for 24 h.

Upon cooling to room temperature, 2.0 equiv. of acetic

anhydride (1.0 mmol, 95 mL) was added and the reaction

mixture was stirred for an additional 12 h at room tempera-

ture. The reaction was quenched by addition of 10 mL of

H₂O. The organic layer was washed with brine (10 mL) and

dried over anhydrous magnesium sulfate. The product was

puri®ed by silica gel chromatography with 10% ethyl

acetate in hexane as eluent to give 150 mg (40% yield) of

the desired acetylated phenol 37 (a colorless oil) as the only

observable product. Spectral data for 37: R_f0.14 (10%

In situ preparation and benzannulation of pentacarbonyl

4-tri¯ato-benzylideneisopropoxy chromium (0) with

1-pentyne. Following Procedure VI, the desired phenol

product 33c was obtained in 82% yield as a colorless

solid, and the ketene trapped product 34c was isolated in

6% yield as a colorless oil. Spectral data for 33c: MP50±

518C, R_f0.14 (5% EtOAc/Hex). ¹H NMR (500 MHz,

CDCl₃):

d

1.02 (t, 3H, J7.5 Hz); 1.41 (d, 6H,

±CH(CH₃)₂, J6.0 Hz); 1.71 (sextet, 2H, J7.5 Hz); 2.69

(t, 2H, J7.5 Hz); 4.63 (h, 1H, J6 Hz); 4.72 (s, 1H, ±OH);

6.69 (s, 1H); 7.27 (dd, 1H, J_ortho9.5 Hz, J_meta2.5 Hz);

8.01 (d, 1H, J3 Hz) 8.25 (d, 1H, J9 Hz). ¹³C NMR

(125 MHz, CDCl₃): d 13.9, 22.1 (±CH(CH₃)₂), 23.2, 32.5,

71.3, 110.8, 113.5, 118.1, 118.5, (q, ±CF₃, J312 Hz),

123.3, 125.2, 125.4, 126.2, 141.7, 147.6, 147.7. IR (nujol,

cm²¹) 3210 (bs), 1700 (w), 1680 (w), 1670 (w), 1459 (s),

1380 (s), 1195 (m), 1144 (ms), 1101 (m). MS (EI) m/z (%

rel. intensity): 392 (M¹, 25), 350 (77), 321 (9), 267 (3), 217

(80), 189 (100), 160 (25), 147 (4), 131 (14), 115 (7), 103 (5),

77 (4), 64 (7); HRMS (EI) calcd For C₁₇H₁₉F₃SO₅m/z

392.090531, found, 392.090467. Spectral data for 34c:

1

EtOAc/Hex). H NMR (500 MHz, CDCl₃): d 0.11 (s, 3H);

0.13 (s, 3H); 0.93 (s, 9H); 1.33 (d, 3H, J6.0 Hz); 1.37 (s,

3H); 1.40 (s, 3H); 2.47 (m, 4H); 2.68 (m, 1H); 3.09 (dd, 1H,

J₁13, J₂3 Hz); 3.20 (t, 1H, J5.5 Hz); 3.48 (s, 3H); 3.72

(t, 1H, J6.5 Hz); 3.92±3.97 (m, 7H); 4.14 (p, 1H, J

6.5 Hz); 4.74 (d, 1H, J17 Hz); 4.90 (d, 1H, J12 Hz);

5.68 (m, 1H); 6.65 (d, 1H, J2 Hz); 6.69 (s, 1H); 7.11 (d,

1H, J2 Hz). ¹³C NMR (125 MHz, CDCl₃): d 23.80,

23.61, 18.3, 20.3 (-SiC(CH₃)₃), 20.6, 26.2 (±OC(CH₃)₃),

27.3, 27.5, 47.1, 56.7, 60.9, 73.5, 74.5, 83.0, 84.7, 99.5,

104.9, 108.2, 110.3, 116.0, 116.8, 119.0 (q, ±CF₃,

J325 Hz), 130.0, 132, 138.0, 138.9, 148.2, 154.7, 159.6,

169.5. IR (neat, cm²¹): 3077 (w), 2955 (s), 2933 (s), 2904

(s), 2857 (s), 2752 (w), 1767 (s), 1630 (s), 1610 (m), 1587

(s), 1513 (w), 1456 (s), 1424 (s), 1370 (s), 1244 (s), 1199 (s),

1130 (s), 1107 (s), 1023 (s), 958 (s), 910 (s), 862 (s), 837 (s),

776 (m), 731 (s). MS (EI) m/z (% rel. intensity): 750.4 (9,

M¹), 708.4 (15), 634.3 (29), 603.3 (47), 561.3 (20), 503.3

(10), 471.3 (15), 448.2 (32), 417.2 (80), 356.2 (89), 339.2

(4), 287.3 (10), 232.2 (25), 197.2 (32), 171.2 (20), 145.2

(24), 115.2 (100), 73.1 (97). HRMS (EI) calcd For

C₃₄H₄₉O₁₁F₃SSi m/z 750.271698; found 750.270804.

1

R_f0.31 (5% EtOAc/Hex.). H NMR (400 MHz, CDCl₃):

d 0.95 (t, 3H, J7.5 Hz); 1.05 (t, 3H, J7 Hz); 1.28 (d, 6h,

J7 Hz); 1.45 (d, 6h, J6 Hz); 1.56 (m, 2H); 1.65 (m, 2H);

1.78 (m,1H); 2.05 (m, 1H); 2.58 (bt, 2H, J8 Hz); 4.03 (h,

1H, J6 Hz); 4.15 (m, 1H); 4.74 (h, 1H, J8 Hz); 5.44 (d,

1H, J10 Hz); 6.73 (s, 1H); 7.28 (m, 3H); 7.53 (d, 1H,

J3 Hz); 7.59 (d, 2H, J9 Hz); 8.31 (d, 1H, J9 Hz).

Preparation of enyne 36. To 10 mL ¯ame dried round

bottom ¯ask under Ar, was added 565 mg (1.46 mmoles)

of aldehyde 38¹⁶in 20 mL of dry MeOH. Added

2.0 equiv. of K₂CO₃followed by 1.2 equiv. of dimethyl-1-

diazo-2-oxopropylphosphonate 39^33,34as a solution in 5 mL

of MeOH. The reaction was stirred for 9 h at room tempera-

ture. The crude reaction was ®ltered over Celite 545, and

puri®ed by silica gel chromatography (2£22 cm, 20/1/1

hexanes/CH₂Cl₂/Et₂O) to give 367 mg (66%) of the desired

enyne 36. Spectral data for 36: R_f0.18 (20/1/1 hexanes/

CH₂Cl₂/Et₂O). ¹H NMR (500 MHz, CDCl₃): d 0.10 (s, 3H);

0.12 (s, 3H); 0.91 (s, 9H); 1.33 (d, 3H, J7.6 Hz); 1.37 (s,

3H); 1.40 (s, 3H); 1.97 (t, 1H, J3.3 Hz); 2.44±2.57 (m,

3H); 3.29 (m, 1H); 3.47 (s, 3H); 3.73 (t, 1H, J8.4 Hz); 3.89

Acknowledgements

This work was supported by a grant from the National

Institutes of Health (PHS-GM 33589).

V. P. Liptak, W. D. Wulff / Tetrahedron 56 (2000) 10229±10247

10247

21. Chan, C.-S.; Tse, A. K.-S.; Chan, K. S. J. Org. Chem. 1994, 59,

6084.

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Article Doi

The preparation and evaluation of electron poor benzylidene Fischer carbene complexes: Studies toward the total synthesis of (+)-olivin

DOI: 10.1016/S0040-4020(00)00867-X

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Article abstract of DOI:10.1016/S0040-4020(00)00867-X

Full text of DOI:10.1016/S0040-4020(00)00867-X

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