Alkyne competition in the benzannulation reaction with chromium carbene complexes

Article abstract of DOI:10.1021/jo100433k

(Figure presented) The benzannulation reaction of Fischer carbene complexes is investigated under conditions where the reaction of the carbene complex is occurring in the presence of two different alkynes. A series of competition experiments are examined where the effects of various structural factors are explored by pitting 10 different carbene complexes with 11 different alkynes. Terminal alkynes will react selectively over internal alkynes in all cases examined including both aryl and alkenyl complexes. Aryl carbene complexes with methoxy substituents do not give quite as high selectivity for terminal alkynes over internal alkynes (～95:5) as do isopropoxy substituents (>99:1), whereas most alkenyl complexes give high selectivity with both substituents (>99:1). Competition experiments between two different terminal alkynes or between two different internal alkynes did not result in anything more than very modest selectivities at best (～2:1). Excellent selectivities were realized between two different terminal acetylenes if one of the terminal acetylene was protected with a trimethylsilyl group. Finally, it was demonstrated that the high selectivities between terminal and internal alkynes can be utilized in the reaction with molecules that contain both types of alkyne functions.

Full text of DOI:10.1021/jo100433k

pubs.acs.org/joc
Alkyne Competition in the Benzannulation Reaction
with Chromium Carbene Complexes
Chunrui Wu, Dmytro O. Berbasov, and William D. Wulff*
Department of Chemistry, Michigan State University, East Lansing, Michigan 48824
wulff@chemistry.msu.edu
Received March 21, 2010
The benzannulation reaction of Fischer carbene complexes is investigated under conditions where the
reaction of the carbene complex is occurring in the presence of two different alkynes. A series of
competition experiments are examined where the effects of various structural factors are explored
by pitting 10 different carbene complexes with 11 different alkynes. Terminal alkynes will react
selectively over internal alkynes in all cases examined including both aryl and alkenyl complexes. Aryl
carbene complexes with methoxy substituents do not give quite as high selectivity for terminal
alkynes over internal alkynes (∼95:5) as do isopropoxy substituents (>99:1), whereas most alkenyl
complexes give high selectivity with both substituents (>99:1). Competition experiments between
two different terminal alkynes or between two different internal alkynes did not result in anything
more than very modest selectivities at best (∼2:1). Excellent selectivities were realized between two
different terminal acetylenes if one of the terminal acetylene was protected with a trimethylsilyl
group. Finally, it was demonstrated that the high selectivities between terminal and internal alkynes
can be utilized in the reaction with molecules that contain both types of alkyne functions.
Introduction
other regioisomeric outcome of this reaction (Scheme 1).3
The selectivity was reported to be at least 179:1. Similarly,
the reaction of the o-methoxy complex 4 with 1-pentyne has
been reported to give the quinone 4 with a >111:1 selectivity
over the quinone 5.2a In this case the crude reaction mixture
was submitted to an oxidative workup since the isolation
of the quinone 4 would be more representative of the true
reaction yield than the air-sensitive phenol 6. Unsymmetrical
internal alkynes do not give benzannulated products with
high levels of regioselectivity unless the steric difference
between the two alkynes substituents is large.2 This is illus-
trated by reactions of the complex 4 with the internal alkynes
showninScheme1.2a,4 The regioselectivity is 2.9:1 with n-propyl
methyl acetylene2a and increases to only 4.8:1 with isopropyl
The reaction of chromium carbene complexes with alkynes is
one of the most useful methods for the synthesis of phenols
and quinones.1 One aspect of the utility of this benzannula-
tion reaction is the very high regioselectivity observed in the
reaction with terminal alkynes.2 For example, the reaction of
the phenyl complex 1a with phenylacetylene has been repor-
ted to give the phenol 2 in 87% yield with no detectable
amount of the phenol 3, which would be the result of the
(1) (a) Waters, M. L.; Wulff, W. D. Org. React. 2008, 70, 121–623.
€
(b) Dotz, K. H.; Stendel, J., Jr. Chem. Rev. 2009, 109, 3227.
(2) (a) Wulff, W. D.; Tang, P.-C.; McCallum, J. S. J. Am. Chem. Soc.
€
€
1981, 103, 7677. (b) Dotz, K. H.; Muhlemeier, J.; Schubert, U.; Orama, O.
J. Organomet. Chem. 1983, 247, 187. (c) Wulff, W. D.; Chan, K.-S.; Tang,
P.-C. J. Org. Chem. 1984, 49, 2293. (d) Yamashita, A.; Toy, A. Tetrahedron
Lett. 1986, 27, 3471.
(3) Bao, J.; Wulff, W. D.; Fumo, M. J.; Grant, E. B.; Heller, D. P.;
Whitcomb, M. C.; Yeung, S.-M. J. Am. Chem. Soc. 1996, 118, 2166.
(4) Waters, M. L.; Bos, M. E.; Wulff, W. D. J. Am. Chem. Soc. 1999, 121,
6403.
DOI: 10.1021/jo100433k
r
Published on Web 06/09/2010
J. Org. Chem. 2010, 75, 4441–4452 4441
2010 American Chemical Society

Wu et al.
JOCArticle
SCHEME 1
SCHEME 2
methyl acetylene,2a but with phenyl methyl acetylene4 a 41:1
selectivity is observed. While the regioselectivity can be affec-
ted by sterics, the influence of electronics on the benzannula-
tion reaction is not normally observed to any great extent.5
The source of the regioselectivity is thought to be related to
the relative stability of the isomeric η1,η3-vinyl carbene
complexed intermediates 8A and 8B (Scheme 2).6a Accord-
ing to the best understanding of the mechanism of the ben-
zannulation at this time,1,4,5a,6 these intermediates are gene-
rated by a rate-limiting loss of a carbon monoxide ligand
from the pentacarbonyl carbene complex 7 and then reaction
of the alkyne with the chromium-carbon double bond of the
unsaturated intermediate. Calculations reveal that the sub-
stituent at the 2-position of these intermediates is much
closer to a carbon monoxide ligand than a substituent at
the 1-position. Thus as the steric differential between the
substituents RL and RS increases, intermediate 8A should be
increasingly favored over 8B. Subsequent to the formation of
the η1,η3-vinyl carbene complexed intermediate 8 is the CO
insertion to give the ketene complex 9 and then electrocyclic
ring closure and tautomerization to give the phenol tricar-
bonyl complex 10, which can be isolated but is normally
oxidized to give either a phenol or quinone product.
SCHEME 3
Specifically, if the benzannulation of a carbene complex of
the type 1a was carried out in the presence of a terminal and
an internal alkyne, which product would dominate, the
phenol 13 derived from the terminal alkyne or the phenol
14 derived from the internal alkyne (Scheme 3)? From the
regioselectivity known for this reaction, it might be suspected
that the terminal alkyne would react faster, but this has never
been put to the test in a controlled fashion. In the only study
that gives some insight in the chemoselectivity of the ben-
zannulation reaction for two different alkynes, Finn and co-
workers found that added alkynes could affect the product
distribution from intramolecular benzannulation reactions
without the added alkynes being incorporated into any of the
products.9 This effect was termed the zenochemical effect.
The goal of the present work is to carry out the first systematic
Whereas the regioselectivity of the benzannulation reac-
tion of unsymmetrical alkynes has been studied extensively,
the chemoselectivity of a competition between two different
alkynes has not been examined in any systematic fashion.1,7
(5) (a) Waters, M. L.; Brandvold, T. A.; Isaacs, L.; Wulff, W. D.
Organometallics 1998, 17, 4298. (b) Chamberlin, S.; Waters, M. L.; Wulff,
€
W. D. J. Am. Chem. Soc. 1994, 116, 3113. (c) Dotz, K. H.; Szesni, N.; Nieger,
M.; Nattinen, K. J. Organomet. Chem. 2003, 671, 58. (d) Davies, M. W.;
€
Johnson, C. N.; Harrity, J. P. J. Org. Chem. 2001, 66, 3525. (e) Gordon,
D. M.; Danishefsky, S. J.; Schulte, G. K. J. Org. Chem. 1992, 57, 7052.
€
(6) (a) Hofmann, P.; Hammerle, M.; Unfried, G. Nouv. J. Chim. 1991, 15,
769. (b) Bos, M. E.; Wulff, W. D.; Miller, R. A.; Chamberlin, S.; Brandvold,
T. A. J. Am. Chem. Soc. 1991, 113, 9293. (c) Wulff, W. D.; Bax, B. M.;
Brandvold, T. A.; Chang, K. S.; Gilbert, A. M.; Hsung, R. P. Organometallics
€
1994, 13, 102. (d) Gleichmann, M. M.; Dotz, K. H.; Hess, B. A. J. Am. Chem.
Soc. 1996, 118, 10551. (e) Torrent, M.; Duran, M.; Sola, M. J. Am. Chem. Soc.
1999, 121, 1309. (f) Barluenga, J.; Aznar, F.; Gutierrez, I.; Martin, A.; Garcia-
Granda, S.; Llorca-Baragano, M. A. J. Am. Chem. Soc. 2000, 122, 1314.
(g) Chan, K.-S.; Peterson, G. A.; Brandvold, T. A.; Faron, K. L.; Challener,
C. A.; Hyldahl, C.;Wulff, W. D. J. Organomet. Chem. 1987, 334, 9. (h)Oscar, J.;
Jimenez-Halla, C.; Sola, M. Chem.;Eur. J. 2009, 15, 12503.
(7) The 2-alkyne annulation involves the reaction of alkyl carbene com-
plexes with diynes. The citations in ref 8 contain a few cases where this
reaction has been investigated with unsymmetrical diynes.
(8) (a) Wulff, W. D.; Kaesler, R. W.; Peterson, G. A.; Tang, P. C. J. Am.
Chem. Soc. 1985, 107, 1060. (b) Anderson, B. A.; Bao, J.; Brandvold, T. A.;
Challener, C. A.; Wulff, W. D.; Xu, Y.-C.; Rheingold, A. L. J. Am. Chem.
Soc. 1993, 115, 10671. (C) Mori, M.; Kuriyama, K.; Ochifugi, N.; Watanuki,
S. Chem. Lett. 1995, 615.
(9) Cross, M. F.; Finn, M. G. J. Am. Chem. Soc. 1994, 116, 10921.
4442 J. Org. Chem. Vol. 75, No. 13, 2010

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TABLE 2. Competition Reactions with 1.5 Equiv of Alkynesa
TABLE 1. Temperature and Solvent Effects on the Competition
between 1-Hexyne and 3-Hexynea
entry carbene complex R1 R2 % yield 15b ratio 15:16 or 19c,d
entry carbene complex temp (°C) solvent % yield 15b ratio 15:16c,d
1
2
3
4
1a
1b
1a
1b
Et
Et
Et
Et
78
75
70
85
96:4
>99:1
97:3
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1b
80
80
80
40
40
40
40
80
80
80
40
40
40
40
benzene
THF
MeCN
benzene
THF
MeCN
hexane
benzene
THF
MeCN
benzene
THF
84
42
41
69
35
33
64
84
56
41
74
55
40
79
93:7
94:6
98:2
95:5
98:2
98:2
96:4
94:6
99:1
99:1
>99:1
99:1
98:2
n-Bu Me
n-Bu Me
>99:1
aAll reactions were carried out with 0.3 mmol of 1 in 5 mL of benzene
with 1.5 equiv of 1 -hexyne and 1.5 equiv of 3-hexyne or 2-heptyne.
Reaction time was 22 h at 40 °C. bIsolated yield by silica gel chromatro-
graphy. cDetermined by GC and GC-MS analysis of the crude reaction
mixture. dSmall amounts of 17 and 18 were detected by GC-MS.
9
10
11
12
13
14
observed from the data in Table 1. First, higher chemical
yields are observed in less polar or less coordinating solvents
such as benzene or hexane which more than offset the slightly
higher selectivities observed in THF and acetonitrile. Second,
a clear trend is seen across both the solvent and the nature of
the carbene complex that lower temperatures lead to higher
selectivity. Thus, for each carbene complex the optimal condi-
tions involve performing the reaction in benzene at 40 °C, which
gives a 95:5 selectivity for the methoxy complex 1a (entry 4) and
a >99:1 selectivity for the isopropoxy complex 1b (entry 11).
Although the chemoselectivity between the terminal alkyne
1-hexyne and the internal alkyne 3-hexyne is complete (com-
plex 1b) or nearly complete (complex 1a), the fact that 15 equiv
of both alkynes was used is not synthetically practical (Table 1).
Thus, this competition was repeated with only 1.5 equiv of
each alkyne, and the results are shown in Table 2. Remark-
ably, the selectivities with both carbene complexes in benzene
at 40 °C are essentially the same whether 15 equiv or 1.5 equiv
of the alkynes is used. A competition was also performed
between 1-hexyne and the internal alkyne n-butyl methyl
acetylene (2-heptyne), and in this case the selectivity with the
methoxy carbene complex 1a is about the same (97:3) as it is
with diethyl acetylene (96:4). The isopropoxy complex 1b is
completely selective for 1-hexyne over both internal alkynes,
showing no detectable amount of the quinone 16 or 19 in the
reactions with 3-hexyne or 2-heptyne, respectively.
Like aryl complexes, the benzannulation of alkenyl car-
bene complexes with alkynes is also a very important reac-
tion in the synthesis of phenols and quinones.1 Therefore,
a series of alkenyl complexes shown in Scheme 4 were exami-
ned for their ability to undergo chemoselective reactions with
terminal alkynes in the presence of internal alkynes. The seven
different complexes were subjected to a 1:1 mixture of 1-hexyne
and 3-hexyne (1.5-2 equiv of each) in benzene at 40 °C under
an argon atmosphere. Upon oxidative workup, the crude
reaction mixture was analyzed by GC and/or GC-MS to
determine the ratio of products from each alkyne, and then
subsequently the major product was isolated in pure form by
silica gel chromatography. In each case, the analysis of the
MeCN
hexane
>99:1
aAll reactions were carried out with 0.3-0.5 mmol of 1 in 5 mL of
solvent with 15 equiv of 1-hexyne and 15 equiv of 3-hexyne. Reaction
time was 16 h at 80 °C and 22 h at 40 °C. bIsolated yield by silica gel
chromatrography. cDetermined by GC and GC-MS analysis of the
crude reaction mixture. dTrace amounts of 17 and 18 were detected by
GC-MS.
study of the competition between two different alkynes in
the intermolecular benzannulation of chromium carbene
complexes.
Results
It was deemed important to begin the competition under
conditions where the concentration of each alkyne would not
significantly change even if one of the alkynes were to react in
complete preference. Thus, the first experiments were carried
out with the carbene complex 1a and 15 equiv of 1-hexyne
and 15 equiv of 3-hexyne, and the results are presented in
Table 1. The crude reaction mixtures were oxidized by ceric
ammonium nitrate, and the ratio of the quinones 15 and 16
were determined by GC-MS analysis of the crude reaction
mixture with the aid of authentic samples of each quinone.
Small and varying amounts of the indenone 17 and cyclo-
pentendione 18 were detected by GC-MS but were not quan-
tified. In all cases the major product was the quinone 15
resulting from selective reaction with the terminal alkyne
with selectivities ranging from a minimum of 93:7 up to >99:1.
In each case the yield of quinone 15 was determined by iso-
lation after purification by silica gel chromatography. The
chemoselectivity was examined as a function of the tempera-
ture (40 or 80 °C), the solvent, and the size of the alkyl group
in the alkoxy group of the carbene complex (methyl or isopropyl).
The benzannulations of isopropoxy complexes generally give
higher yields than methoxy complexes.10 Several trends are
(10) Liptak, V. P.; Wulff, W. D. Tetrahedron 2000, 56, 10229.
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SCHEME 4
SCHEME 5
Next it was decided to determine if the very high selecti-
vity of the benzannulation reaction for terminal alkynes over
internal alkynes could be translated into selectivity between
two different terminal alkynes. To maximize the difference in
reactivity, the two terminal alkynes were chosen such that the
steric difference between the substituents on each alkyne was
large. Thus, the reaction of the methoxy phenyl complex 1a
was carried out with a 1: 1 mixture of tert-butyl acetylene and
n-butyl acetylene (1.5 equiv of each), and after oxidative
workup, both quinones 15 and 31 were isolated in a 2:1 ratio
in a total of 74% yield (Scheme 5). The same selectivity was
observed for the alkenyl complex 28. These results suggest
that it will not be possible to chemoselectively react a chro-
mium carbene complex with a terminal alkyne in the pre-
sence of a second terminal alkyne.
While the difference in the rates of reaction of a terminal
acetylene bearing a primary alkyl group and a terminal acety-
lene bearing a tertiary alkyl group are small but real (Scheme 5),
the differences between the rates of an acetylene bearing a
primary alkyl group and an acetylene bearing a phenyl group
are nonexistent (Scheme 6). This was revealed in the competi-
tion of between n-butyl acetylene (1-hexyne) and phenyl acety-
lene which was found to give a 1:1 mixture of quinones 15 and
33 from the phenyl complex 1a and also a 1:1 mixture of qui-
nones 29 and 34 from complex 28. An experiment was also
conducted to test the chemoselectivity between two different
internal alkynes. The phenyl complex 1a was reacted with 1.5
equiv each of 3-hexyne and 2-heptyne and to give a 1:1 mixture
of the quinones 19 and 16. The results in Schemes 5 and 6 taken
together indicate that it will not be possible to chemoselectively
differentiate between two different terminal alkynes or two
different internal alkynes in the benzannulation reaction.
In lieu of a direct discrimination between two different ter-
minal alkynes, it was considered that chemoselection between
two different terminal alkynes may be possible if one of the
terminal alkynes is protected. Thus, the reaction of alkenyl
complex 28 was carried out in the presence of 1-hexyne and
1-octyne and different silylated terminal alkynes (Scheme 7).
Silicon-substituted alkynes are normal substrates for the ben-
zannulation reaction1 but in some cases bulky silyl groups
can lead to the isolation of ketene complexes rather than
the expected benzannulated product.11 We find here that a
product ratio was aided by an authentic sample of the minor
product (22, 27, or 30), which was prepared independently by
the reaction of the appropriate carbene complex and 3-hexyne.
The results reveal that the methoxy alkenyl complexes give a
higher chemoselectivity that the methoxy phenyl complex 1a.
In each case the competition results in a 99:1 selectivity in
favor of the reaction with the terminal alkyne with the excep-
tion of the trans-propenyl complex 23a where a 96:4 ratio is
observed. As with the reactions of the aryl complex 1a, ana-
lysis of the crude reaction mixtures from the reactions with
the alkenyl complexes shown in Scheme 4 by GC-MS reveals
the presence of trace amounts of products analogous to 17
and 18. Interestingly, the reaction of the carbene complex 20a
gave only a single regioisomer of quinone 21. The quinone 24
would have been formed in this reaction if the regiochemistry
of the incorporation of 1-hexyne had been reversed, i.e.,
formed via intermediate 8B in Scheme 2. We had previously
investigated the regioselectivity of complexes 20a and 23a
with 1-pentyne in THF and found that the complex 23a is
completely regioselective (>99:1), whereas complex 20a only
gives a 93:7 selectivity.2c In the present study on the competi-
tion of complex 20a with 1-hexyne and 3-hexyne, we obser-
ved only the quinone 21 and the regioisomeric quinone 24
could not be detected (<1:99). Given the small difference
between 1-pentyne and 1-hexyne, this leads to the conclusion
that the complex 20a is much more regioselective with
terminal alkynes in benzene than in THF.
(11) Moser, W. H.; Sun, L.; Huffman, J. C. Org. Lett. 2001, 3, 3389.
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SCHEME 6
SCHEME 7
silicon substituent provides an excellent method for effecting
chemoselection between two different terminal alkynes. This
is illustrated in Scheme 7 where it was found that both trimethyl-
silyl and tert-butyldimethylsilyl groups are sufficient to lead to
complete chemoselection between 1-hexyne and 1-pentyne in
reaction with the carbene complex 28 when 1-pentyne is pro-
tected with a silyl substitutent.11 Both silyl protecting groups
provide the quinone 29 in >99:1 selectivity over quinone 35.
Under the same conditions, complex 28 will also display com-
plete selection between 1-octyne and trimethylsilyl-1-hexyne
giving >99:1 selectivity in favor of quinone 36 over quinone
37. Again the stereoselectivities were determined by GC-MS
with the aid of authentic samples of the silylated quinone 35, 37,
or 39 that were prepared independently. These competition
experiments were deliberately designed such that the silylated
and nonsilylated terminal alkynes were not the same. This is
because it is possible that the silylated phenol products could
suffer protodesilylation to give the phenols 40-42 prior to oxi-
dative workup. In each case it was determined that the quinones
from these phenols were not formed. For example, quinone 35
(R=H) was not detected in the reaction where quinone 29 was
formed and quinone 29 was not formed in the reaction where 36
was formed. Neither quinone 15 nor quinone 39 was observed in
the reaction where quinone 38 was formed, indicating that both
aryl and alkenyl complexes can be used in the chemoselective
benzannulation of terminal alkynes in the presence of silylated
alkynes.
SCHEME 8
none of the bis-benzannulated product 45 could be detected
1
in the crude reaction mixture by H NMR spectroscopy or
TLC before quinone 44 was purified.
The two-alkyne annulation provides for a synthesis of
phenols starting with an alkyl carbene complex.8 This reac-
tion can be effected either with 2 equiv of an alkyne in an
intermolecular fashion or, more efficiently, with a diyne lead-
ing to an intramolecular process. The reaction of the alkyl
carbene complex with the first equivalent of the alkyne gene-
rates an R,β-unsaturated carbene complex in situ of the type
50 that then undergoes the benzannulation reaction with
the second equivalent of the alkyne (Scheme 9). The penulti-
mate product is a cyclohexadienone of the type 53, which can
be isolated under certain cases but most often is reduced to
a phenol by chromium(0). A few cases are known in which
this reaction has been carried out with unsymmetrical diynes,
and in each case a single product has been reported and is
The fact that high chemoselectivity is seen between term-
inal and internal alkynes with only 1.5 equiv of each alkyne
suggests that it should be possible to achieve chemoselec-
tivity in the reactions of molecules containing two different
alkyne functions. Indeed, the reaction of the phenyl complex
1a with the diyne 43 gave the quinone 44 in which the ter-
minal alkyne was selectively incorporated (Scheme 8). No
evidence for the presence of an isomer of 44 could be detected
in the crude reaction mixture by GC-MS analysis. Also,
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Wu et al.
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SCHEME 9
origins of the selectivity between 1-hexyne and 3-hexyne
must lie either in the kinetic formation of 55 or 8A or, if
the formation of 55 and/or 8A are reversible, in the relative
stability of 8A derived from 1-hexyne and 3-hexyne. Ther-
modynamically, 1-hexyne would be expected to give 8A with
lower energy given the close contacts between RS (H vs Et)
and the carbon monoxide ligand (8B in Scheme 2) and
between RS and the alkoxy substituent (8A in Scheme 10).
The same expectation would pertain to the transition state
for the formation of 8A under kinetic conditions. Therefore,
the reaction with 1-hexyne would be expected to be more
favored and thus much faster.
The chemoselectivity between 1-hexyne and 3-hexyne can
be seen to be a function of the size of the alkoxy group. For
example, the reaction of methoxy substituted complex 1a
gives a 95:5 ratio of quinones 15 to 16 (Table 1, entry 4)
whereas, the isopropoxy substituted complex 1b gives com-
plete selectivity for the quinone 15 (>99:1) as indicated by
entry 11 in Table 1. The bulkier isopropoxy group would be
expected to induce a stronger interaction with the substituent
RS in the η1,η3-vinyl carbene complexes intermediate 8A
than the methoxy group. Thus, differentiation between
1-hexyne (RS = H) and 3-hexyne (RS = Et) in the guise of
intermediate 8A would be expected to be more pronounced
when OR is an isopropoxy group than when it is a methoxy
group.
The solvent and temperature both had an effect on the
competition between the reactions with 1-hexyne and 3-hexyne
as indicated by the data for the reaction with the phenyl
complex 1 (Table 1). Where there was a response to the tem-
perature, not unexpectedly the selectivity decreased with
increasing temperature (entries 8 vs 11). It was interesting
to find that the chemoselectivity increased with the coordi-
nating ability of the solvent, and this was true for both the
methoxy and isopropoxy complexes 1a and 1b. This suggests
that the 16 e- unsaturated species 54 can be intercepted by
solvent to give the saturated intermediate 56. If complex 56
can react with the alkyne in an associative manner to give
the η1,η3-vinyl carbene complexed intermediate 8A, then it
might be expected that this associative process would be
more sensitive to the sterics of the alkyne than a process that
involves direct coordination of an alkyne with 54 to give 8A.13
This could be expected to lead to increased chemoselection
between 1-hexyne and 3-hexyne with coordinating solvents.
The biggest effect of the solvent is the dramatic drop in
yields of the quinone 15 (Table 1). It is well-known that the
yields of the benzannulation reaction are higher in noncoor-
dinating solvents such as benzene and hexane.1,6b,c,g Polar
and/or coordinating solvents lead to the formation of several
different side-products including indenes6b and cyclobute-
nones,6g and this is certainly a possible explanation for the
loss of mass balance in the reactions in THF and MeCN.
Indene products were detected by GC-MS in the crude
reactions mixtures of the reactions indicated in Table 1,
but only the amounts of the quinone 15 were quantified.
Cyclobutenones may not survive the thermal conditions of
GC analysis.
that resulting from reaction of the terminal alkyne in prefe-
rence to the internal alkyne.8 Neither the presence nor absence
of the product resulting from the reaction of the internal
alkyne is indicated in these reports. We decided to examine
the reaction of the methyl complex 47 with the diyne 43 and
determine if, along with the expected phenol 48, we could
obtain any evidence for the isomeric phenol 49 that would
result from reaction of the internal alkyne first. The optimal
solvent for this reaction is THF, and a slightly higher tem-
perature is needed given that CO dissociation from an alkyl
carbene complex is slower than for R,β-unsaturated com-
plexes. The reaction of complex 47 with diyne 43 led to the
isolation of the phenol 48 in 82% yield. Analysis of the crude
reaction mixutre by GC-MS and by 1H NMR with the aid
of the expected shifts for the phenol 49 led to the conclusion
that the phenol 49 is not formed in this reaction or, if it is, the
selectivity for 48 over 49 is at least 50:1.
Discussion
The observations made in the present work can be inter-
preted in terms of the mechanistic scenario outlined in
Scheme 10 that can be taken as our best understanding of
the possibilities and issues associated with the mechanism of
the benzannulation reaction at this point.1,4,5a,6 There seems
to be a consensus that the first and rate-limiting step of the
benzannulation reaction is loss of CO to give the unsaturated
tetracarbonyl complex 54. Although not rate-limiting, the
next step involves a bimolecular reaction of intermediate 54
with an alkyne to give either the alkyne complex 55 by
coordination or, with carbon-carbon bond formation, to
give the η1,η3-vinyl carbene complexed intermediate 8A. It is
not known conclusively whether the formation of 55 and/or
8A from 54 is reversible or irreversible, although some com-
putational studies suggest that it is not reversible.6d The next
step is generally believed to involve an insertion of a carbon
monoxide ligand in vinyl carbene complex 8A to give the
η4-vinyl ketene complex 9A. There is some evidence to
suggest that this CO insertion step is irreversible.4,6d,12 The
(13) A reviewer suggested the interesting possibility that intermediate 56
in Scheme 10 could also react with an alkyne in a dissociative process. If this
involved loss of a CO ligand, then the solvent effect would be expressed in the
differential rates of addition of terminal and internal alkynes to intermediate
54 and to the intermediate generated from 56 by loss of CO.
(12) McCallum, J. S.; Kunng, F.-A.; Gilbertson, S. R.; Wulff, W. D.
Organometallics 1988, 7, 2346.
4446 J. Org. Chem. Vol. 75, No. 13, 2010

Wu et al.
JOCArticle
SCHEME 10
The benzannulation reactions of alkenyl complexes are
well-known1,6c,g to be far less sensitive to solvent than are
the reactions of aryl complexes, and this is one of the reasons
that the competition reactions for the alkenyl complexes
indicated in Scheme 4 were not examined in other solvents.
One interesting feature of the reactions in Scheme 4 is that all
complexes give complete selection for 1-hexyne over 3-hexyne
except for the trans-propenyl complex 23. This may be rela-
ted to the steric interactions associated with the interaction
of an alkyne with intermediate 54 and the expectation that
they would be larger when R1 is non-hydrogen than when it is
hydrogen.
including the aryl complexes 1a14a and 1b,14b the isopropenyl
complex 20a,15 the trans-propenyl complexes 23a16 and 23b,17
the sec-butenyl complex 25a,15b the cyclohexenyl complex 28,18
and the methyl complex 47.19
Preparation of Isopropenyl Isopropoxy Chromium Carbene
Complex 20b. To a flame-dried round-bottom flask filled with
argon was added isopropenyl bromide (1.8 mL, 20 mmol) in
THF (0.1 M). The solution was cooled to -78 °C, and then
1 equiv of n-BuLi was added dropwise. The resulting solution
was stirred at -78 °C for 30 min and then transferred by cannula
to a flask containing 1.1 equiv of Cr(CO)6 in THF (0.05 M) at
room temperature. The solution was allowed to stir at room
temperature for 2 h. The resulting solution of the lithium acylate
was concentrated in vacuo and allowed to stand under high
vacuum for 10 min. The lithium acylate was dissolved in 20 mL
water, and then 1.5 equiv of Me4NBr was added with vigorously
shaking. The solution was stirred at room temperature for 30 min.
After this time, the crude ammonium acylate salt was extrac-
ted three times with CH2Cl2. The organic layer was dried over
MgSO4, and then the solvent was removed in vacuo to give the
ammonium salt (4.14 g, 12.4 mmol) in 62% yield.
Conclusions
This study for the first time gives a quantitative look at the
relative rate of terminal and internal alkynes in the benzan-
nulation reaction of Fischer carbene complexes. While the
alkyne is not under normal conditions involved in the rate-
limiting step of the reaction, the step at which the alkyne is
incorporated is apparently much faster for a terminal alkyne
than for an internal alkyne. This leads to a greater than 99:1
selectivity for incorporation of the terminal alkyne over the
internal alkyne for most of the carbene complexes studied
and the major exception is with aryl methoxy complexes,
which display a 95:5 selectivity. This high selectivity includes
trimethylsilyl substituted internal alkynes that can serve as
surrogates for terminal alkynes since selectivity between
different terminal alkynes is low to nonexistent. Armed with
the information gained from the present work, the synthetic
chemist can proceed with the utmost assurance that the
benzannulation reaction of a Fischer carbene with a mole-
cule containing two alkyne functions will selectively occur at
the terminal alkyne.
A portion of the ammonium acylate salt (0.50 g, 1.4 mmol)
was dissolved in dry CH2Cl2, and 1.5 equiv of freshly prepared
isopropyltriflate20 was added as a concentrated solution in CH2-
Cl2. The reaction was stirred at room temperature for 30 min.
The reaction was quenched by pouring the mixture into a separatory
€
(14) (a) Fischer, E. O.; Kreiter, C. G.; Kollmeier, H. J.; Muller, J.; Fischer,
R. D. J. Organomet. Chem. 1971, 28, 237. (b) Liptak, V. P.; Wulff, W. D.
Tetrahedron 2000, 56, 10229.
(15) (a) Wulff, W. D.; Chan, K.-S.; Tang, P.-C. J. Org. Chem. 1984, 49,
€
2293. (b) Dotz, K. H.; Kuhn, W.; Ackermann, K. Z. Naturforsch. 1983, 38b,
1351.
(16) Wulff, W. D.; Bauta, W. E.; Kaesler, R. W.; Lankford, P. J.; Miller,
R. A.; Murray, C. K.; Yang, D. C. J. Am. Chem. Soc. 1990, 112, 3642.
(17) Wang, S. L. B.; Liu, X.; Ruiz, M. C.; Gopalsamuthiram, V.; Wulff,
W. D. Eur. J. Org. Chem. 2006, 5219.
(18) Chan, K.-S.; Peterson, G. A.; Brandvold, T. A.; Faron, K. L.;
Challener, C. A.; Hyldahl, C.; Wulff, W. D. J. Organomet. Chem. 1987,
334, 9.
Experimental Section
(19) Hegedus, L. S.; McGuire, M. A.; Schultze, L. M. Org. Synth. 1987,
65, 140.
(20) Beard, C. D.; Baum, K.; Grakauskas, V. J. Org. Chem. 1973, 38,
3673.
The preparation and characterization of most of the carbene
complexes employed in this study have been previously described,
J. Org. Chem. Vol. 75, No. 13, 2010 4447

Wu et al.
JOCArticle
funnel containing saturated aq NaHCO3 and pentane. The aque-
ous layer was separated and extracted with pentane until no red
color was seen in the aqueous layer. The combined organic layers
were washed twice with brine, and then dried over MgSO4. The
dried solution was filtered through a fritted funnel dry packed
with Celite 503. The product carbene complex was purified by
silica gel chromatography using pure pentane as eluent to give
carbene complex 20b (0.302 g, 0.99 mmol) in 71% yield. Red
solid, mp 63-64 °C; Rf =0.30 (hexanes). Spectral data for 20b:
1H NMR (CDCl3, 500 MHz) δ 1.49 (d, 6 H, J=5.4 Hz), 1.85 (s,
3 H), 4.83 (br, 1 H), 4.98 (br, 1 H), 5.50 (br, 1 H); 13C NMR
(CDCl3, 125 MHz) δ 19.5, 22.7, 85.2, 157.3, 216.4, 224.1, 349.8
(1 sp2 C not located); IR (neat) 1980s, 1920brs, 1611w cm-1; MS
m/z (% rel intensity) 304 Mþ (3), 276 (14), 248 (10), 164 (100),
122 (42). Anal. Calcd for C12H12CrO6: C, 47.38; H, 3.98. Found:
C, 47.68; H, 4.30.
indene 17 and the cyclopentenedione 18. This reaction was
repeated in THF, MeCN, and hexane as solvents at 40 and at
80 °C and also with the same four solvents for the isopropoxy
complex 1b at both temperatures, and the results are presented
in Table 1. The optimal conditions for the isopropoxy complex
1b was also in benzene at 40 °C and gave quinone 15 in 74% yield
with a greater than 99:1 selectivity for quinone 15 over quinone
16. Spectral data for 2-n-butylnaphthalene-1,4-dione 15: 1H
NMR (CDCl3, 500 MHz) δ 0.93 (t, 3 H, J = 7.3 Hz), 1.38-
1.42 (m, 2 H), 1.52-1.56 (m, 2 H), 2.55 (td, 2 H, J=7.9, 1.3 Hz),
6.77 (t, 1 H, J=1.3 Hz), 7.69-7.71 (m, 2 H), 8.03-8.09 (m, 2 H);
13C NMR (CDCl3, 125 MHz) δ 13.8, 22.5, 29.3, 30.1, 126.0,
126.6, 132.1, 132.3, 133.6, 133.6, 134.7, 152.0, 185.2, 185.3. These
data match those previously reported for this compound.21
Procedure B: Preparation of Authentic Samples of the Minor
Quinones. Illustrated for the synthesis of quinone 16 via the benz-
annulation reaction of carbene complex 1b with 3-hexyne. To a
50 mL flame-dried pear-shaped single-necked flask in which the
14/20 joint was replaced by a high vacuum T-shaped Teflon
valve was added carbene complex 1b (0.153 mg, 0.45 mmol) in
5 mL of benzene. To this was added 2 equiv of 3-hexyne. The
system was deoxygenated by the freeze-thaw method, and after
the third cycle, the flask was backfilled with argon at room
temperature. The flask was sealed by closing the Teflon valve,
and the flask was then heated at 80 °C for 16 h. The crude reac-
tion mixture was diluted with Et2O and treated with 10 equiv of
a 0.5 M ceric ammonium nitrate solution. The two-phase mix-
ture was stirred for 3 h at room temperature. At this point, the
reaction was poured into a 125 mL separatory funnel and dilu-
ted with Et2O. A saturated aq NaHCO3 solution was added to
the funnel and then separated without shaking to avoid an emul-
sion. The combined organic layer was washed with saturated
aq NaHCO3 (2 ꢀ 10 mL). The aqueous layer was then back
extracted with ether (2 ꢀ 10 mL). The combined organic layers
were then washed with brine (15 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The crude product was puri-
fied by silica gel chromatography (2ꢀ25 cm) with 5% EtOAc in
hexanes as eluent to give quinone 16 (0.869 g, 0.406 mmol) in
90% yield as a yellow solid. Spectral data for 2,3-diethyl-
naphthalene-1,4-dione 16: 1H NMR (CDCl3, 500 MHz) δ 1.13
(t, 6 H, J=7.5 Hz), 2.62 (q, 4 H, J=7.5 Hz), 7.66 (dd, 2 H, J=
5.8, 3.3 Hz), 8.04 (dd, 2 H, J=5.7, 3.3 Hz); 13C NMR (CDCl3,
125 MHz) δ 14.0, 20.1, 126.1, 132.2, 133.2, 148.1, 185.0. These
data match those previously reported for this compound.18
Phenyl Carbene Complexes 1a and 1b with 1-Hexyne and
3-Hexyne. This competition experiment was carried out with
carbene complex 1a (0.107 g, 0.34 mmol), 1-hexyne (0.060 mL,
0.52 mmol), and 3-hexyne (0.058 mL, 0.51 mmol) in 5 mL of
benzene at 40 °C for 22 h according to Procedure A to give
quinone 15 (0.0540 g, 0.252 mmol) in 78% isolated yield. The 1H
NMR spectrum of the crude reaction mixture indicated that the
ratio of 15:16 was 96:4. The same reaction with the isopropoxy
complex 1b (0.128 g, 0.38 mmol), 1-hexyne (0.065 mL, 0.57
mmol), and 3-hexyne (0.065 mL, 0.57 mmol) gave 15 (0.0580 g,
0.271 mmol) in 75% yield with a >99:1 ratio of 15:16. The data
for 15 matched that presented in Procedure A above.
Preparation of the sec-Butenyl Isopropoxy Chromium Carbene
Complex 25b. Carbene complex 25b was prepared with the same
procedure described above for the preparation of complex 20b.
The intermediate ammonium acylate salt was obtained in 84%
yield (5.88 g, 16.8 mmol) from (E)-2-bromobut-2-ene (1.85 mL,
20 mmol). The carbene complex 25b was obtained in 94% yield
(0.896 g, 2.81 mmol) from 1.02 g (3.0 mmol) of the ammonium
acylate salt. Red oil; Rf =0.29 (pentane). Spectral data for 25b:
1H NMR (CDCl3, 500 MHz) δ 1.46 (s, 3 H), 1.50 (d, 6 H, J=6.1
Hz), 1.85 (s, 3 H), 4.93 (br, 1 H), 5.09 (br, 1 H); 13C NMR
(CDCl3, 125 MHz) δ 15.0, 20.1, 22.6, 23.03, 83.2, 113.7, 146.1,
216.6, 224.5, 356.3; IR (neat) 2986, 2084, 1991, 1379, 1254, 1178,
1082, 988, 878, 711, 661, 621 cm-1; MS m/z (% rel intensity) 318
M
þ (1), 178 (31), 136 (28), 135 (41), 126 (42), 107 (28), 105 (20),
84 (100), 83 (83), 80 (18), 67 (26), 55 (93). Anal. Calcd for
C13H14CrO6: C, 49.06; H, 4.43. Found: C, 49.01; H, 4.60.
Procedure A. Competitive Benzannulation of Carbene Com-
plexes with Two Different Alkynes. Illustrated for the reaction of
1a in benzene at 40 °C with 15 equiv of 1-hexyne and 15 equiv of
3-hexyne. To a 50 mL flame-dried pear-shaped single-necked
flask in which the 14/20 joint was replaced by a high vacuum
T-shaped Teflon valve was added carbene complex 1a (0.157 g,
0.50 mmol) in 5 mL of benzene. To this were added 1-hexyne
(0.75 mL, 6.5 mmol) and 3-hexyne (0.70 mL, 6.2 mmol). The
system was deoxygenated by the freeze-thaw method, and after
the third cycle the flask was backfilled with argon at room
temperature. The flask was sealed by closing the Teflon valve,
and the flask was then heated at 40 °C for 22 h (or 80 °C for 16 h).
The crude reaction mixture was diluted with Et2O and treated
with 10 equiv of 0.5 M ceric ammonium nitrate solution. The
two phase mixture was stirred for 3 h at room temperature. At
this point, the reaction was poured into a 125 mL separatory
funnel and diluted with Et2O. A saturated aq NaHCO3 solution
was added to the funnel and then separated without shaking to
avoid an emulsion. The organic layer was washed with saturated
NaHCO3 (2ꢀ10 mL). The aqueous layer was then back extrac-
ted with ether (2 ꢀ 10 mL). The combined organic layers were
then washed with brine (15 mL), dried over MgSO4, filtered, and
concentrated in vacuo. The residue was dissolved in 20 mL Et2O,
and 1 mL of this solution was reserved for GC and GC-MS
analysis. The other 95% of the crude reaction mixture was
loaded onto a silica gel chromatography column (2 ꢀ 25 cm)
and eluted with 5% EtOAc in hexanes to give the purified
quinone 15 (0.0703 g, 0.33 mmol) in 69% yield. This isolated
yield was adjusted to account for the 5% that had been removed
as an analytical sample. The ratio of quinone 15 to quinone 16
was determined to be 95:5 by GC analysis on an Alltech
ECONO-CAP SE 54 capillary column (30 m ꢀ 0.53 mm i.d. ꢀ
1.2 μm) with the aid of an authentic sample of quinone 16 that
was prepared as described below. GC-MS analysis confirmed
the presence of 16 and also indicated the presence of trace amounts
of compounds that by molecular weight were consistent with the
Phenyl Carbene Complexes 1a and 1b with 1-Hexyne and
3-Heptyne. This competition experiment was carried out with
carbene complex 1a (0.101 g, 0.32 mmol), 1-hexyne (0.055 mL,
0.48 mmol), and 2-heptyne (0.062 mL, 0.48 mmol) in 5 mL of
benzene at 40 °C for 22 h according to Procedure A to give
quinone 15 (0.0525 g, 0.245 mmol) in 81% isolated yield. The 1H
NMR spectrum of the crude reaction mixture indicated that the
ratio of 15:19 was 97:3, which was determined with the aid of an
authentic sample of 19 prepared as indicated below. The same
reaction with the isopropoxy complex 1b (0.101 g, 0.30 mmol),
(21) Yamashita, M.; Ohishi, T. Bull. Chem. Soc. Jpn. 1993, 66, 1187.
4448 J. Org. Chem. Vol. 75, No. 13, 2010

Wu et al.
JOCArticle
1-hexyne (0.052 mL, 0.45 mmol), and 2-heptyne (0.058 mL, 0.45
mmol) gave 15 (0.0521 g, 0.243 mmol) in 85% yield with a >99:1
ratio of 15:19. The data for 15 matched that presented in Proce-
dure A above.
187.8; IR (neat) 2959, 2932, 2874, 1653, 1614, 1294, 914 cm-1; MS
m/z (% rel intensity) 178 Mþ (79), 163 (63), 135 (100), 121 (11), 107
(26), 91 (22), 79 (12), 77 (11). Anal. Calcd for C11H14O2: C, 74.13;
H, 7.92. Found: C, 74.54, H, 8.29.
Synthesis of Quinone 19 from Phenyl Carbene Complex 1b and
3-Heptyne. Quinone 19 (0.0500 g, 0.22 mmol, 73%) was prepared
from carbene complex 1b (0.102 mg, 0.30 mmol) and 2-heptyne
according to Procedure B. Spectral data for 2-butyl-3-methyl-
trans-sec-Butenyl Carbene Complexes 25a and 25b with 1-Hexyne
and 3-Hexyne. This competition experiment was carried out with
carbene complex 25a (0.38 g, 1.31 mmol), 1-hexyne (0.226 mL, 1.97
mmol), and 3-hexyne (0.223 mL, 1.0 mmol) in 13 mL of benzene at
40 °C for 22 h according to Procedure A to give quinone 26 (0.0136g,
0.708 mmol) in 57% isolated yield. The 1H NMR spectrum of the
crude reaction mixture indicated that the ratio of 26:27 was 99:1,
which was determined with the aid of an authentic sample of 27
prepared as described below. The same reaction with the isopro-
poxy complex 25b (0.268 g, 0.842 mmol), 1-hexyne (0.145 mL, 1.26
mmol), and 3-hexyne (0.143 mL, 1.26 mmol) in 8.4 mL of benzene
gave 26 (0.1270 g, 0.66 mmol) in 83% yield with a >99:1 ratio of
26:27. Spectral data for 5-n-butyl-2,3-dimethylcyclohexa-2,5-
diene-1,4-dione 26: 1H NMR (CDCl3, 300 MHz) δ 0.85 (t, 3 H,
J=7.1 Hz), 1.28-1.43 (m, 4 H), 1.93 (s, 3 H), 1.95 (s, 3 H), 2.33 (t,
2 H, J=7.4 Hz), 6.42 (s, 1 H); 13C NMR (CDCl3, 75 MHz) δ 12.0,
12.3, 13.8, 22.3, 28.7, 29.9, 131.9, 140.3, 140.9, 149.0, 187.4, 187.5.
These data those previously reported for this compound.24
Synthesis of Quinone 27 trans-sec-Butenyl Carbene Complex
25b and 3-Hexyne. Quinone 27 was prepared from carbene com-
plex 25b and 3-hexyne according to Procedure B. Spectral data
for 2,3-diethyl-5,6-dimethylcyclohexa-2,5-diene-1,4-dione 27:
1H NMR (CDCl3, 500 MHz) δ 1.04 (t, 6 H, J = 7.6 Hz), 1.98
(s, 6 H), 2.46 (q, 4 H, J=7.6 Hz); 13C NMR (CDCl3, 125 MHz)
δ 12.3, 14.0, 19.7, 140.4, 145.0, 187.5. These data matched those
previously reported for this compound.25
1
naphthalene-1,4-dione 19: H NMR (CDCl3, 500 MHz) δ 0.93
(t, 3 H, J=7.1 Hz), 1.41-1.46 (m, 4 H), 2.17 (s, 3 H), 2.61-2.64
(m, 2 H), 7.66-7.68 (m, 2 H), 8.05-8.07 (m, 2 H); 13C NMR
(CDCl3, 125 MHz) δ12.6, 13.9, 23.1, 26.8, 30.9, 126.2, 126.3, 132.2,
132.2, 133.3, 133.3, 143.1, 147.6, 184.7, 185.4. These data match
those previously reported for this compound.22
Isopropenyl Carbene Complexes 20a and 20b with 1-Hexyne
and 3-Hexyne. This competition experiment was carried out with
carbene complex 20a (0.170 g, 0.616 mmol), 1-hexyne (0.141 mL,
1.23 mmol), and 3-hexyne (0.1.40 mL, 1.23 mmol) in 6.2 mL of
benzene at 40 °C for 22 h according to Procedure A to give quinone
1
21 (0.0642 g, 0.360 mmol) in 62% isolated yield. The H NMR
spectrum of the crude reaction mixture indicated that the ratio of
21:22 was 99:1, which was determined with the aid of an authentic
sample of 22 prepared as indicated below. The same reaction
with the isopropoxy complex 20b (0.157 g, 0.50 mmol), 1-hexyne
(0.115 mL, 1.0 mmol), and 3-hexyne (0.114 mL, 1.0 mmol) gave 21
(0.0620 g, 0.348 mmol) in 73% yield with a >99:1 ratio of 21:22.
Spectral data for 2-butyl-5-methylcyclohexa-2,5-diene-1,4-dione
1
21: H NMR (CDCl3, 500 MHz) δ 0.91 (t, 3 H, J = 7.2 Hz),
1.33-1.37 (m, 2 H), 1.43-1.48 (m, 2 H), 2.01 (d, 3 H, J=1.6 Hz),
2.36-2.40 (m, 2 H), 6.52 (t, 1 H, J=1.5 Hz), 6.56 (q, 1 H, J=1.6
Hz); 13C NMR (CDCl3, 125 MHz) δ 13.8, 15.4, 22.4, 28.4, 29.9,
132.4, 133.6, 145.5, 149.6, 187.8, 188.3. These data those previously
reported for this compound.23
Cyclohexenyl Carbene Complex 28 with 1-Hexyne and 3-Hexyne.
This competition experiment was carried out with carbene com-
plex 28 (0.16 g, 0.5 mmol), 1-hexyne (0.115 mL, 1.0 mmol), and
3-hexyne (0.114 mL, 1.0 mmol) in 5 mL of benzene at 40 °C for
22 h according to Procedure A to give quinone 29 (0.075 g, 0.344
Synthesis of Quinone 22 from Isopropenyl Carbene Complex
23b and 3-Hexyne. Quinone 22 (0.032 g, 0.18 mmol, 36%) was
prepared from carbene complex 23b (0.152 mg, 0.50 mmol) and
3-hexyne according to Procedure B. Yellow oil, Rf = 0.35 (5%
EtOAc in hexanes). Spectral data for 2,3-diethyl-5-methyl-[1,4]-
benzoquinone 22: 1H NMR (CDCl3, 500 MHz) δ 1.04 (t, 3 H,
J=7.4 Hz), 1.05 (t, 3 H, J=7.4 Hz), 2.00 (d, 3 H, J=1.5 Hz),
2.44 (q, 2 H, J=7.4 Hz), 2.46 (q, 2 H, J=7.4 Hz), 6.52 (q, 1 H,
J=1.5 Hz); 13C NMR (CDCl3, 125 MHz) δ 13.9 (br, 2C), 15.8,
19.4, 19.7, 133.2, 145.3, 145.38, 145.5, 187.7, 188.0; MS m/z
(% rel intensity) 178 Mþ (100), 164 (11), 163 (85), 149 (32), 135
(38), 121 (40), 107 (23), 91 (22), 79 (17), 77 (14), 67 (18), 53 (12).
trans-Propenyl Carbene Complexes 23a and 23b with 1-Hexyne
and 3-Hexyne. This competition experiment was carried out with
carbene complex 23a (0.138 g, 0.50 mmol), 1-hexyne (0.115 mL,
1.0 mmol), and 3-hexyne (0.114 mL, 1.0 mmol) in 5 mL of benzene
at 40 °C for 22 h according to Procedure A to give quinone 24
(0.0350 g, 0.197 mmol) in 41% isolated yield. The 1H NMR
spectrum of the crude reaction mixture indicated that the ratio of
24:22 was 96:4, which was determined with the aid of an authentic
sample of 22 prepared as described above. The same reaction with
the isopropoxy complex 20b (0.152 g, 0.50 mmol), 1-hexyne (0.115
mL, 1.0 mmol), and 3-hexyne (0.114 mL, 1.0 mmol) gave 24
(0.0270 g, 0.152 mmol) in 32% yield with a 98:2 ratio of 24:22.
Yellow oil; Rf = 0.30 (5% EtOAc in hexanes). Spectral data for
1
mmol) in 72% isolated yield. The H NMR spectrum of the
crude reaction mixture indicated that the ratio of 29:30 was 99:1,
which was determined with the aid of an authentic sample of 30
prepared as described below. Spectral data for 2-n-butyl-5,6,7,8-
tetrahydronaphthalene-1,4-dione 29:1HNMR(CDCl3, 500 MHz)
δ 0.90 (td, 3 H, J=7.3, 1.8 Hz), 1.33-1.37 (m, 2 H), 1.44-1.47
(m, 2 H), 1.65-1.67 (m, 4 H), 2.36-2.40 (m, 6 H), 6.44-6.45 (m,
1 H); 13C NMR (CDCl3, 125 MHz) δ 13.7, 20.9, 21.1, 22.2, 22.3,
22.6, 28.5, 29.9, 131.9, 141.9, 142.3, 149.0, 187.5, 187.7. These
data those previously reported for this compound.25
Synthesis of Quinone 30 from Cyclohexenyl Carbene Complex
28 and 3-Hexyne. Quinone 30 was prepared from carbene com-
plex 28 and 3-hexyne according to Procedure B. Spectral data
for 2,3-diethyl-5,6,7,8-tetrahydronaphthalene-1,4-dione 30: 1H
NMR (CDCl3, 500 MHz) δ 1.04 (t, 6 H, J=7.5 Hz), 1.63-1.65
(m, 4 H), 2.37-2.37 (m, 4 H), 2.44 (q, 4 H, J=7.5 Hz); 13C NMR
(CDCl3,125MHz) δ14.0, 19.5, 21.2, 22.5, 141.9, 145.0, 187.5. These
data matched those previously reported for this compound.26
Phenyl Carbene Complex 1a with n-Butyl Acetylene and tert-
Butyl Acetylene. This competition experiment was carried out with
carbene complex 1a (0.247 g, 0.79 mmol), 1-hexyne (0.136 mL, 1.19
mmol), and tert-butyl acetylene (0.142 mL, 1.19 mmol) in 8 mL of
benzene at 40 °C for 22 h according to Procedure A to give quinone
15 (0.079 g, 0.369 mmol) in 49% isolated yield and quinone 31
(0.040 g, 0.187 mmol) in 25% isolated yield. The 1H NMR spec-
trum of the crude reaction mixture indicated that the ratio of 15:31
was 2:1. The data for 15 matched that those presented for 15 in
1
2-butyl-6-methyl-[1,4]-benzoquinone 24: H NMR (CDCl3, 500
MHz) δ 0.91 (t, 3 H, J=7.2 Hz), 1.34-1.38 (m, 2 H), 1.43-1.48
(m, 2 H), 2.03 (d, 3 H, J = 1.5 Hz), 2.40 (t, 2 H, J = 7.7 Hz),
6.47-6.48 (m, 1 H), 6.52-6.53 (m, 1 H); 13C NMR (CDCl3, 125
MHz) δ13.7, 15.9, 22.3, 28.7, 29.8, 132.2, 132.9, 145.8, 149.5, 187.7,
(24) Liebeskind, L. S.; Chidambaram, R. J. Am. Chem. Soc. 1987, 109,
5025.
(22) Liebeskind, L. S.; Granberg, K. L.; Zhang, J. J. Org. Chem. 1992, 57,
4345.
(25) Liebeskind, L. S.; Baysdon, S. L.; South, M. S.; Iyer, S.; Leeds, J. P.
Tetrahedron 1985, 41, 5839.
(26) Xu, Y.-C.; Wulff, W. D. J. Org. Chem. 1987, 52, 3263.
(23) Gayo, L. M.; Winters, M. P.; Moore, H. W. J. Org. Chem. 1992, 57,
6896.
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Wu et al.
JOCArticle
Procedure A above. Spectral data for 2-tert-butylnaphthalene-1,4-
62% combined yield (0.046 g of the mixture). The quinones were
identified in the mixture with the aid of the 1H NMR spectra of
each of the quinones, which were prepared as described above.
Cyclohexenyl Carbene Complex 28 with 1-Hexyne and Trimethyl-
silyl-1-pentyne. This competition experiment was carried out with
carbene complex 28 (0.158 g, 0.50 mmol), 1-hexyne (0.086 mL, 0.75
mmol), and 1-TMS-1-pentyne (0.138 mL, 0.75 mmol) in 5 mL of
benzene at 40 °C for 22 h according to Procedure A to give quinone
29 (0.0884 g, 0.406 mmol) in 81% isolated yield as the only product.
dione 31: 1H NMR (CDCl3, 500 MHz) δ 1.34 (s, 9 H), 6.81 (s, 1 H),
7.66-.769 (m, 2 H), 7.99-8.01 (m, 1 H), 8.04-8.06 (m, 1 H); 13
C
NMR (CDCl3, 125 MHz) δ 29.4, 35.7, 125.6, 126.8, 131.5, 133.2,
133.5, 133.7, 133.8, 158.3, 184.9, 185.9. These data matched those
previously reported for this compound.27
Cyclohexenyl Carbene Complex 28 with n-Butyl Acetylene and
tert-Butyl Acetylene. This competition experiment was carried
out with carbene complex 28 (0.236 g, 0.75 mmol), 1-hexyne
(0.129 mL, 1.12 mmol), and tert-butyl acetylene (0.138 mL, 1.12
mmol) in 7.5 mL of benzene at 40 °C for 22 h according to
Procedure A to give quinone 29 (0.089 g, 0.408 mmol) in 57%
isolated yield and quinone 32 (0.050 g, 0.229 mmol) in 32%
isolated yield. The 1H NMR spectrum of the crude reaction
mixture indicated that the ratio of 29:32 was 2:1. The spectral
data for 29 matched that those presented for 29 above. Spectral
data for 2-tert-butyl-5,6,7,8-tetrahydronaphthalene-1,4-dione
32: 1H NMR (CDCl3, 500 MHz) δ 1.23 (s, 9 H), 1.63-1.65
(m, 4 H), 2.35-2.38 (m, 4 H), 6.48 (s, 1 H); 13C NMR (CDCl3,
125 MHz) δ 20.9, 21.3, 22.1, 22.8, 29.3, 35.1, 131.1, 140.9, 143.9,
155.6, 187.4, 188.4. These data matched those previously repor-
ted for this compound.28
Phenyl Carbene Complex 1a with n-Butyl Acetylene and Phenyl
Acetylene. This competition experiment was carried out with
carbene complex 1a (0.156 g, 0.50 mmol), 1-hexyne (0.086 mL,
0.75 mmol), and phenyl acetylene (0.082 mL, 0.75 mmol) in
5 mL of benzene at 40 °C for 22 h according to Procedure A to
give quinone 15 (0.0397 g, 0.186 mmol) in 39% isolated yield and
quinone 33 (0.0204 g, 0.087 mmol) in 18% isolated yield in a
55:45 isolated ratio. The 1H NMR spectrum of the crude reac-
tion mixture indicated that the ratio of 15:33 was 1:1. The data
for 15 matched that those presented for 15 in Procedure A
above. Spectral data for 2-phenylnaphthalene-1,4-dione 33: 1H
NMR (CDCl3, 500 MHz) δ 7.04 (s, 1 H), 7.43-7.46 (m, 3 H),
7.54-7.56 (m, 2 H), 7.73-7.75 (m, 2 H), 8.07-8.09 (m, 1 H),
8.14-8.15 (m, 1 H); 13C NMR (CDCl3, 125 MHz) δ 125.9, 127.0,
128.4, 129.4, 129.9, 132.0, 132.4, 133.3, 133.7, 133.8, 135.1, 148.0,
184.3, 185.0. These data matched those previously reported for
this compound.18
Cyclohexenyl Carbene Complex 28 with n-Butyl Acetylene and
Phenyl Acetylene. This competition experiment was carried out
with carbene complex 1a (0.158 g, 0.50 mmol), 1-hexyne (0.086
mL, 0.75 mmol), and phenyl acetylene (0.082 mL, 0.75 mmol) in
5 mL of benzene at 40 °C for 22 h according to Procedure A to
give quinone 29 (0.0386 g, 0.180 mmol) in 38% isolated yield and
quinone 34 (0.0333 g, 0.142 mmol) in 30% isolated yield in a 1:1
isolated ratio. The 1H NMR spectrum of the crude reaction
mixture indicated that the ratio of 29:34 was 1:1. The data for 29
match those presented for 29 above. Spectral data for 5,6,7,8-
tetrahydro-2-phenylnaphthalene-1,4-dione 34: 1H NMR (CDCl3,
500 MHz) δ 1.68-1.70 (m, 4 H), 2.43-2.47 (m, 4 H), 6.74 (s,
1 H), 7.37-7.40 (m, 3 H), 7.42-7.44 (m, 2 H); 13C NMR (CDCl3,
125 MHz) δ 20.8, 21.1, 22.3, 22.8, 128.2, 129.1, 129.56, 132.3,
133.1, 142.1, 142.5, 145.5, 186.5, 187.5. These spectral data match
those previously reported for this compound.29
Phenyl Carbene Complex 1a with 3-Hexyne and 2-Heptyne.
This competition experiment was carried out with carbene com-
plex 1a (0.102 g, 0.33 mmol), 2-heptyne (0.076 mL, 0.66 mmol),
and 3-hexyne (0.075 mL, 0.66 mmol) in 5 mL of benzene at 40 °C
for 22 h according to Procedure A. The quinones could not be
separated by chromatography on silica gel, and thus purifica-
tion resulted in the isolation of a 1:1 mixture of 19 and 16 in a
1
The H NMR spectrum of the crude reaction mixture indicated
that the ratio of 29:35a was >99:1 as determined with the aid of an
authentic sample of quinone 35a prepared as described below.
Quinone 35a also could not be detected by GC-MS analysis of the
crude reaction mixture. The data for quinone 29 match those pre-
sented for 29 above.
Synthesis of Quinone 35a from Carbene Complex 28 and Tri-
methylsilyl-1-pentyne. Quinone 35a (45 mg, 0.145 mmol, 44%)
was prepared from carbene complex 28 (103 mg, 0.33 mmol) and
trimethylsilyl-1-pentyne according to Procedure B. Yellow oil;
Rf = 0.51 (20:1:1 hexanes/Et2O/CH2Cl2). Spectral data for
5,6,7,8-tetrahydro-2-(trimethylsilyl)-3-propylnaphthalene-1,4-dione
35a: 1H NMR (CDCl3, 500 MHz) δ 0.26 (s, 9 H), 0.93 (t, 3 H, J=
7.3 Hz), 1.35-1.40 (m, 2 H), 1.62-1.64 (m, 4 H), 2.33-2.37 (m, 4
H), 2.45-2.48 (m, 2 H); 13C NMR (CDCl3, 125 MHz) δ 1.6,
14.3, 21.1, 21.2, 22.5, 22.6, 24.7, 30.7, 141.9, 143.5, 145.5, 156.5,
186.8, 192.0; IR 2942, 2874, 1644, 1273, 868, 844 cm-1; MS m/z
(% rel intensity) 276 Mþ (34), 262 (22), 261 (100), 233 (26).
HRMS (CI) calcd for C16H25O2Si m/z 277.1624, meas 277.1619.
Cyclohexenyl Carbene Complex 28 with 1-Hexyne and tert-
Butyldimethylsilyl-1-pentyne. This competition experiment was
carried out with carbene complex 28 (0.158 g, 0.50 mmol),
1-hexyne (0.086 mL, 0.75 mmol), and 1-TBS-1-pentyne (0.138 g,
0.75 mmol) in 5 mL of benzene at 40 °C for 22 h according to
Procedure A to give quinone 29 (0.0848 g, 0.389 mmol) in 78%
isolated yield as the only product. No evidence for the presence
of quinone 35b could be obtained upon analysis of the crude
1
reaction mixture by GC-MS or H NMR spectroscopy. The
data for quinone 29 match those presented for 29 above.
Cyclohexenyl Carbene Complex 28 with 1-Octyne and Trimethyl-
silyl-1-hexyne. This competition experiment was carried out with
carbene complex 28 (0.0778 g, 0.25 mmol), 1-octyne (0.0404 mL,
0.38 mmol), and 1-TMS-1-hexyne (0.075 mL, 0.38 mmol) in 5 mL
of benzene at 40 °C for 22 h according to Procedure A to give
quinone 36 (0.0492 g, 0.20 mmol) in 80% isolated yield as a yellow
oil; Rf = 0.30 (20:1:1 hexanes/Et2O/CH2Cl2). The 1H NMR
spectrum of the crude reaction mixture indicated the presence of
only a trace of quinone 37 with a ratio of 36:37 of >99:1 as deter-
mined with the aid of an authentic sample of quinone 37 prepared
as described below. Spectral data for 2-n-hexyl-5,6,7,8-tetrahydro-
[1,4]naphthoquinone 36: 1H NMR (CDCl3, 500 MHz) δ 0.86 (t,
3 H, J=6.6 Hz), 1.25-1.34 (m, 6 H), 1.45-1.48 (m, 2 H), 1.66 (m,
4 H), 2.35-2.40 (m, 6 H), 6.44 (t, 1 H, J = 1.5 Hz); 13C NMR
(CDCl3, 125 MHz) δ 13.9, 20.9, 21.1, 22.2, 22.4, 22.6, 27.7, 28.8,
28.9, 31.4, 131.9, 141.9, 142.3, 149.0, 187.5, 187.7; IR (neat) 2932,
2861, 1651, 1616, 1294 cm-1; MS m/z (% rel intensity) 246 Mþ
(50), 203 (38), 178 (24), 177 (100), 176 (33), 175 (21), 161 (26), 149
(15), 148 (23), 147 (15), 91 (16), 79 (16), 77 (16). Anal. Calcd for
C16H22O2: C, 78.01; H, 9.00. Found: C, 77.84; H, 9.14.
Synthesis of Quinone 37 from Carbene Complex 28 and Tri-
methylsilyl-1-hexyne. Quinone 37 (50.1 mg, 0.155 mmol, 47%)
was prepared from carbene complex 28 (103 mg, 0.33 mmol) and
trimethylsilyl-1-hexyne according to Procedure B. Yellow oil;
Rf =0.41 (20:1:1 hexanes/Et2O/CH2Cl2). Spectral data for 2-n-
butyl-3-trimethylsilyl-5,6,7,8-tetrahydro-[1,4] naphthoquinone
(27) Bunge, A.; Hamann, H.-J.; McCalmont, E.; Liebscher, J. Tetrahe-
dron Lett. 2009, 50, 4629.
(28) Kanai, K.; Goto, K.; Kinji, H. Eur. Pat. Appl. EP 254259 A2
19880127 , 1988.
(29) Davies, M. W.; Johnson, C. N.; Harrity, J. P. A. J. Org. Chem. 2001,
66, 3525.
1
37: H NMR (CDCl3, 500 MHz) δ 0.26 (s, 9 H), 0.89 (t, 3 H,
J=7.1 Hz), 1.32-1.35 (m, 4 H), 1.62-1.64 (m, 4 H), 2.34-2.36
(m, 4 H), 2.47-2.49 (m, 2 H); 13C NMR (CDCl3, 125 MHz) δ
1.6, 13.9, 21.1, 21.2, 22.5, 22.6, 23.1, 28.7, 33.5, 141.9, 143.5,
4450 J. Org. Chem. Vol. 75, No. 13, 2010

Wu et al.
JOCArticle
145.4, 156.8, 186.8, 192.0; IR (neat) 2938, 1645, 1273, 868, 847
cm-1; MS m/z (% rel intensity) 290 Mþ (10), 276 (35), 275 (36),
247 (18), 234 (31), 233 (84), 73 (18). HRMS (CI) calcd for
C17H27O 2Si (M þ H)þ m/z 291.1780, meas 291.1782.
(bp 95-102 °C, 15 Torr) to yield 1-trimethylsilyl-1,6-octadiyne
in 89% yield (3.34 g, 18.7 mmol) as a colorless liquid. Spectral
data: 1H NMR (CDCl3, 500 MHz) δ 0.14 (s, 9 H), 1.68 (pent, J=
7 Hz, 2 H), 1.77 (t, J=3 Hz, 3 H), 2.21-2.24 (m, 2 H), 2.34-2.30
(m, 2 H).
Phenyl Carbene Complex 1a with 1-Octyne and Trimethylsilyl-
1-hexyne. This competition experiment was carried out with
carbene complex 1a (0.109 g, 0.35 mmol), 1-octyne (0.0774 mL,
0.52 mmol), and 1-TMS-1-hexyne (0.105 mL, 0.52 mmol) in
6.9 mL of benzene at 40 °C for 22 h according to Procedure A to
give quinone 38 (0.0596 g, 0.246 mmol) in 70% isolated yield.
The 1H NMR spectrum of the crude reaction mixture indicated
the presence of only a trace of quinone 39 with a ratio of 38:39 of
>99:1 as determined with the aid of an authentic sample of qui-
none 39 prepared as described below. Spectral data for 2-hexyl-
naphthalene-1,4-dione 38: 1H NMR (CDCl3, 500 MHz) δ 0.83-
0.86 (m, 3 H), 1.25-1.29 (m, 4 H), 1.34-1.37 (m, 2 H), 1.50-
1.55 (m, 2 H), 2.50-2.53 (m, 2 H), 6.74 (t, 1 H, J = 1.4 Hz),
Preparation of 1,6-Octadiyne 43. 1-Trimethylsilyl-1,6-octa-
diyne (3.34 g, 18.7 mmol) was dissolved in 100 mL of dry THF,
and then 20 mL of 1 M TBAF solution was added via syringe.
The solution turned dark brown immediately. The mixture was
stirred for 1 h at room temperature. Then, 30 mL of a saturated
aqueous ammonium chloride solution was added, and the aque-
ous layer was extracted with diethyl ether. The combined orga-
nic phase was dried with MgSO4 and then filtered. The solvent
was evaporated on rotary evaporator, and then the residue was
passed through silica gel with pentane to remove a brown resi-
due. The pentane was removed under vacuum yielding 1,6-octa-
diyne 43 in 51% yield (1.02 g, 9.6 mmol) as a colorless liquid. The
overall yield from 1,6-heptadiyne was 41% over 3 steps. On
large scale the product can be distilled at bp 65-70 °C (15 Torr).
Spectral data for 43: 1H NMR (CDCl3, 500 MHz) δ 1.65 (pent,
J=7 Hz, 2 H), 1.73 (t, J=2 Hz, 3 H), 1.91 (t, J=3 Hz, 1 H), 2.21
(m, 2 H), 2.27 (m, 2 H); 13C NMR (CDCl3, 125 MHz) δ 3.4, 17.5,
17.8, 27.9, 68.6, 77.0, 77.9, 83.7; IR (KBr) 3420w, 2958s, 2925vs,
2860s, 1456 m. These data matched those previously reported
for this compound.31
Benzannulation of Phenyl Carbene Complex 1a with 1,6-Octa-
diyne 43. The reaction of carbene complex 1a (0.2123 g, 0.68
mmol) and alkyne 43 (0.1083 g, 1.02 mmol) in 10 mL of dry
benzene was carried out following Procedure B described above
at 40 °C for 22 h. After the reaction was done, 10 equiv of a 0.5 M
aqueous solution of ceric ammonium nitrate was added at room
temperature along with 10 mL of diethyl ether, and resulting
mixture was stirred for 6 h. Then, the reaction mixture was
washed with aq NaHCO3, and the aqueous layer was separated
and extracted with Et2O. The combined organic layers were
dried over MgSO4, and the volatiles were removed by rotary
evaporation. Analysis of the crude reaction mixture by GC-MS
and 1H NMR did not provide any evidence for the presence of
quinone 46 or for quinone 45. GC-MS analysis was performed
on an Agilent JW Scientific DB-5 ms column (0.32 mmꢀ30 m)
with an initial temperature of 60 °C with a ramp rate of 10 °C/min.
Quinone 44 had a retention time of 12.48 min, but otherwise the
baseline was flat from 2 to 18 min. Finally, quinone 44 was
purified by preparative TLC (hexane/EtOAc=5:1) on an Anal-
tech 20 ꢀ 20 cm 1000 μm plate to give 0.1182 g of yellow need-
les (0.50 mmol, 73%). Spectral data for 44: 1H NMR (CDCl3,
500 MHz) δ 1.74 (t, J = 2.5 Hz, 3 H), 1.78 (pent, J = 7.5 Hz,
2 H), 2.24 (m, 2 H), 2.69 (dt, J=7.5 Hz, 1 Hz, 2 H), 6.83 (t, J=
1 Hz, 1 H), 7.73 (m, 2 H), 8.07 (m, 1 H), 8.10 (m, 1 H); 13C
NMR (CDCl3, 125 MHz) δ 3.4, 18.4, 27.2, 28.8, 76.8, 78.1, 126.1,
126.6, 132.2, 132.4, 133.6, 133.7, 135.1, 151.2, 185.1, 185.1;
HRMS (ESþ) calcd for (C16H14O2 þ H)þ m/z 239.1072; meas
239.1081. Yellow needles, mp 49-50 °C. Rf =0.59 (5:1 hexane/
EtOAc).
7.66-7.68 (m, 2 H), 7.99-8.01 (m, 1 H), 8.03-8.05 (m, 1 H); 13
C
NMR (CDCl3, 125 MHz) δ 13.9, 22.5, 27.9, 29.0, 29.5, 31.5,
125.9, 126.5, 132.0, 132.3, 133.5, 133.5, 134.6, 151.9, 185.1, 185.2.
These data match those previously reported for this compound.21
Synthesis of Quinone 39 from Phenyl Carbene Complex 1a and
Trimethylsilyl-1-hexyne. Quinone 39 (27.8 mg, 0.087 mmol,
25%) was prepared from carbene complex 1a (107 mg, 0.343
mmol) and trimethylsilyl-1-hexyne according to Procedure B.
The major product of this reaction was tentatively identified as
3-n-butyl-2,3-dihydroinden-1-one (35.3 mg, 0.188), which was
isolated in 55% yield. Spectral data for 2-n-butyl-3-(trimethyl-
silyl)naphthalene-1,4-dione 39: 1H NMR (CDCl3, 500 MHz) δ
0.36 (s, 9 H), 0.93-0.95 (m, 3 H), 1.41-1.45 (m, 4 H), 2.67-2.70
(m, 2 H), 7.64-7.67 (m, 2 H), 7.96-7.98 (m, 1 H), 8.01-8.03 (m,
1 H); 13C NMR (CDCl3, 125 MHz) δ 1.8, 13.9, 23.2, 29.2, 33.5,
126.0, 126.2, 132.2, 133.1, 133.3, 133.3, 148.8, 159.4, 184.6,
189.6. These data match those previously reported for quinone
39.30
Synthesis of 1,6-Octadiyne 43 from 1,6-Heptadiyne. Preparation
of 1-Trimethylsilyl-1,6-heptadiyne. 1,6-Heptadiyne (2.0 g, 21 mmol)
was dissolved in 100 mL of dry THF, cooled to -78 °C, and then
allowed to stir at this temperature for 10 min. A solution of lithium
hexamethyldisilazide (21 mL, 1.0 M) was added, and the resulting
mixture stirred for 45 min at -78 °C. Me3SiCl (2.75 g, 25.2 mmol)
in 5 mL dry THF was then added, and reaction was stirred for 2 h at
the same temperature. Then 20 mL of saturated aqueous solution of
ammonium chloride was added, and the mixture was warmed to
room temperature and stirred for 30 min. The aqueous layer was
extracted twice with 25 mL of Et2O, the combined organic layer was
dried on MgSO4, and the solvent was evaporated under vacuum.
The residue was distilled (bp 72-75 °C, 20 Torr) giving 3.56 g,
20 mmol (95% yield) of 1-trimethylsilyl-1,6-heptadiyne as a color-
less liquid. Spectral data: 1H NMR (CDCl3, 500 MHz) δ 0.15 (s,
9 H), 1.74 (pent, J=7.5 Hz, 2 H), 1.96 (t, J=2.5 Hz, 1 H), 2.29-
2.32 (m, 2 H), 2.33-2.36 (m, 2 H).
Methylation of 1-Trimethylsilyl-1,6-heptadiyne. 1-Trimethyl-
silyl-1,6-heptadiyne (3.56 g, 21 mmol) was dissolved in 100 mL
of dry THF and then cooled to -78 °C. A solution of n-BuLi
(14 mL of 1.6 M solution) in hexane was added via syringe, follo-
wed by 10 mL of HMPA. The reaction turned to a maroon color.
The resulting mixture was stirred for 10 min, and then methyl
iodide (3.64 g, 25.2 mmol) was added; after stirring for 30 min
the color changed and became a pale yellow. The reaction was
allowed to warm to room temperature and was quenched with
30 mL of a saturated aqueous solution of ammonium chloride,
and the aqueous phase was extracted with diethyl ether. After
drying of the combined organic layer with MgSO4 and removal
of the volatiles by a rotary evaporator, the residue was distilled
Two-Alkyne Annulation of Methyl Carbene Complex 47 with
1,6-Octadiyne 43. The reaction of the carbene complex 47
(0.2126 g, 0.85 mmol) and the diyne 43 (0.1062 g, 1.02 mmol)
in 23 mL of dry tetrahydrofuran was carried with Procedure
B indicated above. After 16 h at 70 °C, the reaction was complete,
the solution was transferred to a 50 mL flask, and 10 g of silica
gel was added. The volatiles were removed by rotary evaporator
for 30 min, and then the resulting impregnated silica gel powder
was placed on top of 10 g of silica gel in a column and eluted with
dichloromethane. All fractions were collected and combined,
1
and the H NMR spectrum of the crude reaction mixture was
(30) Liebeskind, L. S.; Baysdon, S. L.; South, M. S.; Iyer, S.; Leeds, J. P.
Tetrahedron 1985, 41, 5839.
(31) Anderson, B. A.; Bao, J.; Brandvold, T. A.; Challener, C. A.; Wulff,
W. D.; Xu, Y.-C.; Rheingold, A. L. J. Am. Chem. Soc. 1993, 115, 10671.
J. Org. Chem. Vol. 75, No. 13, 2010 4451

Wu et al.
JOCArticle
recorded. The 1H NMR spectrum of the crude reaction mixture
without filtering through silica gel is subject to severe signal
broadening due to the presence of paramagnetic Cr(III) species.
The phenol 48 was then purified by silica gel chromatography to
give 48 in 82% yield (0.1142 g, 0.70 mmol). Spectral data for 48:
1H NMR (CDCl3, 500 MHz) δ 2.05 (pent, J=7.5 Hz, 2 H), 2.22
(s, 3 H), 2.80 (t, J=7.5 Hz, 2 H), 2.83 (t, J=7.5 Hz, 2 H), 2.17(s,
3 H), 4.43 (s, 1 H), 6.85 (s, 1 H); 13C NMR (CDCl3, 125 MHz) δ
12.4, 16.1, 25.3, 31.8, 32.6, 119.0, 120.7, 123.4, 135.3, 142.2, 150.4.
HRMS (ES-) calcd for (C11H14O - H)þ m/z 161.0966; meas
161.0970. Yellow needles mp 79 °C. Rf=0.47 (5:1 hexane/EtOAc).
Analysis of the 1H NMR spectrum of the crude reaction
mixture indicates that the phenol 48 is the exclusive product of
the reaction and that the ratio of phenol 48 to phenol 49 is at
pounds 2,3,4,6-tetramethylphenol 70a33 (aryl singlet at 6.78 ppm)
and 2,3,4,5-tetramethylphenol 70b33a (aryl singlet at 6.49 ppm)
and the pair of compounds 2,4-dimethyltetra-2-lol 71a34 (singlet
at 6.62 ppm) and 3,4-dimethyltetra-2-lol 71b32,35 (singlet at
6.33-6.36 ppm) also exhibited shielding effects of the hydroxyl
group in the range of ∼0.3 ppm. Analysis of the 1H NMR spec-
trum of the crude reaction mixture revealed that there were
no absorptions visible in the range of 6.3-6.6 ppm, and thus it
can be concluded that the selectivity for phenol 48 over 49 is at
least 50:1.
Acknowledgment. This work was supported by a grant
from the National Science Foundation (CHE-0750319).
1
Supporting Information Available: H and 13C spectra of the
1
least 50:1. The phenol 49 is a known compound, and the H
compounds discussed in this work. This material is available free
of charge via the Internet at http://pubs.acs.org.
NMR spectrum of 49 is reported to have an aromatic singlet at
6.50 ppm.32 The aryl singlet for the phenol 48 determined in the
present work occurs at 6.85 ppm. This type of chemical shift
difference is typical of what is expected for the shielding effect of
a hydroxy group on a benzene ring. For example, the pair of com-
(33) (a) Baeckstroem, P.; Jacobsson, U.; Koutek, B.; Morin, T. J. Org.
Chem. 1985, 50, 3728. (b) Behera, G. C.; Saha, A.; Ramakrishnan, S.
Marcomolecules 2005, 38, 7695.
(34) Boger, D. L.; Mullican, M. D. J. Org. Chem. 1980, 45, 5002.
(35) Waring, A. J. Z.; Hussain, J.; Pilkington, J. W. J. Chem. Soc., Perkin
Trans. 1 1981, 1454.
(32) Nilsson, J. L. G.; Selander, H.; Sievertsson, H.; Skanberg, I. Acta
Chem. Scand. 1970, 24, 580.
4452 J. Org. Chem. Vol. 75, No. 13, 2010