Approaching ambient temperatures in 1,2-DCE to deliver efficient intermolecular D?tz benzannulation processes

Article abstract of DOI:10.1016/j.tet.2007.09.088

Conditions have been developed that enable intermolecular D?tz benzannulations to be carried out under extremely mild conditions, using 1,2-DCE as the reaction solvent and without the requirement for any additional reaction promoters. The new protocols, at temperatures close to ambient, have been applied successfully to a range of internal and terminal alkynes with a series of aryl and alkenyl carbene complexes, resulting in good to high yields of the benzannulation products. The developed conditions did, however, return lower benzannulation yields when utilised with the traditionally more troublesome 2-furyl carbene complex. It was found that increased reaction temperatures in 1,2-DCE did deliver high yields for the processes with this heteroaryl species.

Full text of DOI:10.1016/j.tet.2007.09.088

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 926e935
www.elsevier.com/locate/tet
Approaching ambient temperatures in 1,2-DCE to deliver efficient
intermolecular Dotz benzannulation processes
¨
*
Stephanie Irvine, William J. Kerr , Allan R. McPherson, Colin M. Pearson
Department of Pure and Applied Chemistry, WestCHEM, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland, UK
Received 19 July 2007; accepted 12 September 2007
Available online 24 October 2007
Abstract
Conditions have been developed that enable intermolecular Dotz benzannulations to be carried out under extremely mild conditions, using
¨
1,2-DCE as the reaction solvent and without the requirement for any additional reaction promoters. The new protocols, at temperatures close to
ambient, have been applied successfully to a range of internal and terminal alkynes with a series of aryl and alkenyl carbene complexes, resulting
in good to high yields of the benzannulation products. The developed conditions did, however, return lower benzannulation yields when utilised
with the traditionally more troublesome 2-furyl carbene complex. It was found that increased reaction temperatures in 1,2-DCE did deliver high
yields for the processes with this heteroaryl species.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Carbene; Chromium; 1,2-Dichloroethane; Dotz benzannulation; Quinone
¨
1. Introduction
cesses are normally performed by heating the substrates in an
ethereal donor solvent,4,5 and high levels of regioselectivity,
with respect to the alkyne insertion, are generally delivered.4,6
Having stated this, there are two common drawbacks associ-
ated with this type of reaction: only moderate yields of prod-
ucts often result, and long reaction times can be required. Due
to these practical issues, considerable work has been devoted
Since their discovery in 1964,1 transition metal carbene
complexes have become widely utilised synthetic tools for the
preparative chemist, delivering a rich array of valuable trans-
formations and desirable product classes.2 Amongst the most
extensively developed and applied methods with Fischer carb-
ene complexes is the Dotz benzannulation process, originally
¨
towards enhancing the efficacy of the Dotz benzannulation
¨
divulged in 1975.3 This annulation, between an a,b-unsatu-
rated Fischer carbene complex and an alkyne, has become an
established synthetic technique for the preparation of highly
functionalised phenols and quinones (Scheme 1).2,4 Such pro-
process. In this regard, studies carried out by Yamashita led
to the serendipitous discovery of a method for promoting these
metal carbene-mediated cyclisations,6e,7 with the use of acetic
anhydride and triethylamine as additives resulting in the pro-
OH
OH
O
O
RL
Cr(CO)3
RS
RL
RS
RL
RS
OMe
[O]
Δ
RL
RS
or
(OC)5Cr
+
OMe
OMe
Scheme 1. Dotz benzannulation process.
¨
* Corresponding author. Tel.: þ44 141 548 2959; fax: þ44 141 548 4246.
E-mail address: w.kerr@strath.ac.uk (W.J. Kerr).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.088

S. Irvine et al. / Tetrahedron 64 (2008) 926e935
927
Table 1
Initial benzannulation reactions probing sulfide additive effects
motion of some reactions which were otherwise unsuccessful
under conventional conditions. Subsequent to this, Boger noted
that certain transformations could be effectively promoted
with acetic anhydride alone.8
Work within our own laboratory has led to the development
of further methods for the promotion of the Dotz annulation
¨
O
O
OMe
1. Solvent, 67 °C,
18 h, additive
2. Ce(IV), HNO3
Ph
(OC)5Cr
H
Ph
+
1
2
3
reaction. In particular, the application of ultrasonication tech-
niques facilitate the benzannulation process and allow reactions
to proceed very rapidly to completion.9 Perhaps more impor-
tantly, we have also exploited the use of dry state adsorption
techniques to considerably enhance the yields obtained in a se-
Entry
Solvent
DodSMe (equiv)
Yielda (%)
1
2
3
4
5
6
THF
THF
0
3
0
3
0
3
80
58
35
22
77
50
n-Bu2O
n-Bu2O
1,2-DCE
1,2-DCE
ries of Dotz reactions.9,10 Additionally, further work within our
¨
laboratory has shown that microwave technology can be applied
as a direct source of thermal energy to successfully promote the
a
Isolated yield.
Dotz benzannulation.11
In common with the PausoneKhand reaction, the first step
¨
studies, 3 equiv of the sulfide promoter was used. As can be seen
from Table 1, in every instance the sulfide additive had a detri-
mental effect on the isolated yield of the naphthoquinone
product.
Despite these disappointing outcomes with the chosen
sulfide additive, the potential for the use of 1,2-DCE as an
effective reaction solvent was noted (Entry 5, Table 1). Conse-
quently, an annulation was attempted at the higher reflux
temperature of 1,2-DCE (83 ꢀC). As shown in Scheme 2, an el-
evated yield of 84% was obtained, which compared favourably
with the equivalent and previously described process in THF.
in the Dotz benzannulation is believed to be decarbonylation
¨
of the transition metal centre.12 Moreover, it has been well
documented in the literature that the addition of alkyl methyl
sulfides can very effectively enhance PausoneKhand cyclisa-
tions, perhaps by promotion of key steps in the reaction
mechanism or by stabilisation of coordinatively unsaturated
intermediates.13 Furthermore, recent work within our own lab-
oratory has now shown that dodecyl methyl sulfide (DodSMe)
can be readily used as an odourless replacement for the more
traditional n-butyl methyl sulfide in PausoneKhand pro-
cesses.14 Based on all of these, we proposed that addition of
alkyl methyl sulfides to Dotz reaction mixtures could lead to
¨
positive promotional effects and we now report on our at-
tempts to formulate further enhanced benzannulation protocols
of this class.
O
OMe
1. 1,2-DCE, 83 °C,
18 h
Ph
(OC)5Cr
H
Ph
+
2. Ce(IV), HNO3
1
2
3
O
2. Results and discussion
84%
Scheme 2. 1,2-DCE as an effective Dotz benzannulation solvent.
¨
2.1. Exploring the use of a sulfide additive in the Do¨tz
benzannulation process
At this stage and undeterred by the results displayed in Ta-
ble 1, a marginally more extended investigation into the sulfide
additive methods was considered appropriate. Based on the
promising use of 1,2-DCE, as shown in Scheme 2, this solvent
was used as the basis for a sulfide additive equivalent study.
From the results displayed in Table 2, it is again clear that
As part of this programme, a model reaction was firstly se-
lected on which to base the initial studies. Due to the robust na-
ture of the phenyl methoxy carbene 1, this complex was chosen
for reaction with commercially available phenylacetylene 2; in
all reactions performed, oxidative work-up, with ceric ammo-
nium nitrate (Ce(IV)) to produce the naphthoquinone product
was applied as standard. As can be seen from Table 1 (Entry 1),
reaction in THF produced a good yield of the benzannulation
product 3; this 80% yield, following standard reflux conditions
in THF under an atmosphere of nitrogen, is in line with that
achieved by Wulff (67%) using optimised conditions in de-
gassed THF under argon at 45 ꢀC.5a,15
Table 2
Benzannulation reactions with increasing sulfide additive levels
O
OMe
1. 1,2-DCE, 83 °C,
18 h, additive
2. Ce(IV), HNO3
Ph
(OC)5Cr
H
Ph
+
1
2
3
O
Investigations into the use of the odourless sulfide, DodSMe,
as an additive were then initiated. This preliminary study was
performed in three different reaction solvents: THF, n-Bu2O
and 1,2-DCE. The ethereal solvents, THF and n-Bu2O, are com-
Entry
DodSMe (equiv)
Yielda (%)
1
2
3
4
5
0
1
2
3
5
84
80
77
53
48
monly utilised to provide optimal yields in Dotz benzannulation
¨
reactions,4,5 whilst 1,2-DCE is the solvent of choice for the
DodSMe-promoted PausoneKhand reaction.14 At the outset,
in each case and in line with that employed in our previous
a
Isolated yield.

928
S. Irvine et al. / Tetrahedron 64 (2008) 926e935
O
O
the sulfide additive has a (progressively) negative impact on
the benzannulation reaction outcomes.
OMe
1.Solvent, 30 °C,
18 h
Ph
(OC)5Cr
H
Ph
+
2. Ce(IV), HNO3
1
2
3
2.2. Probing the potential of 1,2-DCE as a promoting
solvent in Do¨tz benzannulations
1,2-DCE: 83%
THF: 53%
From the results accumulated to this stage, it was apparent
that the use of the sulfide additive was hindering rather than
promoting the desired carbene-mediated cyclisations. Having
stated this, the potential for 1,2-DCE to act as an effective
Scheme 3. Effective Dotz benzannulation at near ambient temperature.
¨
practical advance in this area, with the desired process being
achieved successfully and efficiently at near ambient tempera-
ture without the aid of mechanical promotion.10b
solvent, which could enhance the efficiency of Dotz benzannu-
¨
lations, had started to emerge. In this regard and to probe the
scope of 1,2-DCE as an annulation promoting solvent, lower
temperature processes were explored. Initially and in line with
previously published studies,5a reactions were performed at
45 ꢀC, with THF being used as a comparator. Pleasingly, when
1,2-DCE was used at this lower temperature the efficiency of
the benzannulation process was almost equivalent to that at
83 ꢀC and an excellent 79% yield of the naphthoquinone prod-
uct resulted (Entry 2, Table 3). By comparison, the reaction
performed in THF was considerably less effective (Entry 3).
Somewhat disappointingly, when 1,2-DCE was employed at
room temperature, the reaction yield was significantly reduced
to 32% (Entry 4), with no increase being observed over a
longer reaction period of 72 h in the same solvent (Entry 5).
Despite this, once again, the reaction run in THF at room tem-
perature led to a significantly lower yield (Entry 6) than that
obtained with 1,2-DCE.
At this stage, it should be pointed out that the laboratory
(room) temperature during the studies detailed above was
in the range 14e17 ꢀC, i.e., somewhat lower than the 20e
25 ꢀC commonly regarded as room temperature. Based on
this, it was envisaged that gentle warming of the reaction mix-
ture might be beneficial. In order to investigate this, a simple
study was performed at 30 ꢀC with 1,2-DCE and THF as sol-
vents (Scheme 3). Remarkably, in 1,2-DCE an excellent 83%
yield of benzannulated product 3 was obtained (cf. 53% in
2.3. Establishing the scope of low temperature Do¨tz
benzannulations in 1,2-DCE
To test the more general effectiveness of the developing
low temperature benzannulation protocol in 1,2-DCE, a range
of reactions between a series of carbene complexes and alkyne
substrates were probed. The first set of reactions performed used
the phenyl carbene 1, as shown in Table 4. As can be seen, ex-
cellent yields were obtained from the reactions involving each
of the terminal alkynes (Entries 1 and 3). The moderate yield
of naphthoquinone from diphenylacetylene (Entry 2) could be
attributed to the greater steric hindrance around this alkyne.
The second series of reactions were performed employing
the generally less robust cyclohexenyl carbene 6 (Table 5).
As with complex 1, excellent yields were obtained for the re-
actions involving both terminal alkynes (Entries 1 and 3).
Table 4
Low temperature use of phenyl carbene complex 1 with alkynes in 1,2-DCE
O
OMe
R1
R2
1. 1,2-DCE, 30 °C,
18 h
2. Ce(IV), HNO3
R2
(OC)5Cr
R1
+
1
O
THF). Taking into account that intermolecular Dotz annula-
¨
Entry
R1
R2
Product
Yielda (%)
tions normally require moderate to high temperatures in order
to produce high yields of cyclisation products, this 1,2-DCE
process at 30 ꢀC constitutes an appreciable and encouraging
1
2
3
Ph
Ph
H
3
4
5
83
53
82
Ph
H
n-Bu
a
Isolated yield.
Table 3
Solvent examination over a range of benzannulation reaction temperatures
Table 5
Low temperature use of cyclohexenyl carbene complex 6 with alkynes in 1,2-
DCE
O
OMe
Ph
1. Conditions
2. Ce(IV), HNO3
(OC)5Cr
Ph
H
+
O
1
2
3
OMe
R1
R2
1. 1,2-DCE, 30 °C,
18 h
2. Ce(IV), HNO3
O
R2
(OC)5Cr
R1
+
Entry
Solvent
Temp (ꢀC)
Time (h)
Yielda (%)
6
O
1
2
3
4
5
6
a
1,2-DCE
1,2-DCE
THF
83
45
45
rt
18
18
18
18
72
18
84
79
65
32
32
16
Entry
R1
R2
Product
Yielda (%)
1
2
3
Ph
Ph
H
7
8
9
92
55
80
1,2-DCE
1,2-DCE
THF
Ph
H
rt
n-Bu
rt
a
Isolated yield.
Isolated yield.

S. Irvine et al. / Tetrahedron 64 (2008) 926e935
929
Table 6
Low temperature use of p-tolyl carbene complex 10 with alkynes in 1,2-DCE
O
O
OMe
Ph
1.1,2-DCE, 18 h
2. Ce(IV), HNO3
(OC)5Cr
O
Ph
H
+
OMe
R1
R2
1. 1,2-DCE, 30 °C,
18 h
2. Ce(IV), HNO3
O
O
14
2
15
R2
(OC)5Cr
R1
+
45 °C: 35%
83 °C: 65%
10
O
Scheme 4. Benzannulation with the 2-furyl carbene complex 14 at more
elevated temperatures.
Entry
R1
R2
Product
Yielda (%)
1
2
3
Ph
Ph
H
Ph
11
12
13
65
38
42
Based on these positive outcomes in refluxing 1,2-DCE, re-
actions with the remaining alkynes were performed under sim-
ilar conditions. As shown in Table 8, when compared to the
yields at 30 ꢀC (3e9%), a significant increase in reaction effi-
ciency was recorded with the three alkyne substrates employed
to this stage. In this regard, the outcome of the reaction be-
tween the 2-furyl carbene 14 and the sterically encumbered in-
ternal alkyne (entry 2) was particularly noteworthy. It had
been observed from our studies thus far that, with each of
the previously employed complexes, the lowest yields had
been obtained with diphenylacetylene. In contrast, with com-
plex 14 this alkyne substrate had clearly delivered the most ef-
ficient cyclisation. Interestingly, this reactivity trend with the
2-furyl carbene 14, whereby higher yields are obtained from
more encumbered internal alkynes, has been noted previously
both in seminal studies by Wulff5b and from work within
our own laboratory.11 Overall and from that shown in Table
8, the 2-furyl complex 14 could now be applied effectively
with a series of alkyne substrates with 1,2-DCE as the reaction
solvent.
n-Bu
H
a
Isolated yield.
Once again, a more moderate yield was obtained for the inter-
nal alkyne (Entry 2).
It has previously been shown that Dotz benzannulation reac-
¨
tions carried out with the p-tolyl carbene 10 generally tend to
be lower yielding than reactions carried out with the equivalent
phenyl complex.4,5c,11 This trend was, indeed, observed using
the methodology developed here (Table 6). Despite this, good
to moderate yields of the naphthoquinone products were ob-
tained under what are considered to be remarkably mild condi-
tions for such intermolecular annulations, and with excellent
levels of regioselection.
The results obtained from the reactions involving the phenyl
1, cyclohexenyl 6 and p-tolyl 10 carbene complexes pleasingly
demonstrated that our optimised conditions were successful for
a range of Dotz benzannulations at near ambient temperature.
¨
The next series of reactions to be performed involved the tradi-
tionally less effective 2-furyl carbene 14.4,5b,c,11 Disappoint-
ingly, only very modest yields resulted from the use of this
heteroaryl complex (Table 7), clearly demonstrating that the de-
veloped protocols with 1,2-DCE are not compatible with all
carbenes at such low reaction temperatures.
Undeterred by the poor reactivity of this complex, a further
series of reactions was investigated in order to ascertain
whether an increase in temperature in 1,2-DCE would result in
higher yields with the 2-furyl carbene 14. As shown in Scheme
4, using phenylacetylene as the alkyne substrate, a significantly
increased, yet still moderate, 35% yield was obtained at 45 ꢀC,
whilst a considerably more respectable yield of 65% was
obtained at 83 ꢀC in 1,2-DCE with the same alkyne.
From the results obtained so far, other than with the 2-furyl
carbene complex 14, the yields from reactions involving di-
phenylacetylene had been somewhat lower than those result-
ing from the terminal alkynes which had been investigated.
As mentioned previously, this lowered reactivity profile with
the internal diaryl alkyne is attributed to the increased steric
hindrance around the key triple bond within this substrate.
To investigate this further, a set of reactions using a less en-
cumbered internal alkyne were performed to ascertain if this
would result in an increase in the observed cyclisation yields.
In this regard, 3-hexyne 18 was selected as a less sterically de-
manding internal alkyne and annulations attempted with the
four carbene complexes used to this stage in this study.
Table 8
Dotz benzannulation reactions with 2-furyl carbene complex 14 in 1,2-DCE at
Table 7
Low temperature use of 2-furyl carbene complex 14 with alkynes in 1,2-DCE
¨
83 ꢀC
O
O
OMe
O
OMe
O
R1
R2
R1
R2
1. 1,2-DCE, 30 °C,
18 h
2. Ce(IV), HNO3
1. 1,2-DCE, 83 °C,
18 h
2. Ce(IV), HNO3
R2
R2
(OC)5Cr
R1
R1
+
(OC)5Cr
+
O
O
14
14
O
O
Entry
R1
R2
Product
Yielda (%)
Entry
R1
R2
Product
Yielda (%)
1
2
3
Ph
Ph
H
15
16
17
5
3
9
1
2
3
Ph
Ph
H
15
16
17
65
88
56
Ph
H
Ph
H
n-Bu
n-Bu
a
a
Isolated yield.
Isolated yield.

930
S. Irvine et al. / Tetrahedron 64 (2008) 926e935
Table 9
Dotz benzannulation reactions of internal alkyne 18 in 1,2-DCE
in such carbene-mediated annulation processes. In further sup-
port of (reversible) halide ligation, Guerchais has shown how
chelate chloro coordination stabilises an iron carbene com-
plex, whilst being sufficiently labile to allow further reaction
at the iron centre following ready dissociation.16 In addition,
Nayak and Burkey have described how 1,2-DCE can be em-
ployed in effective CO photodissociation processes with
Cr(CO)6, with the rationalisation being that solvent coordina-
tion with the resulting Cr(CO)5 inhibits re-association of CO,
prior to reaction of the pentacarbonylchromium unit with
added ligand.17 As stated above, loss of CO from the starting
¨
O
OMe
R
1.1,2-DCE, 18 h
2. Ce(IV), HNO3
(OC)5Cr
+
18
O
Entry
R
Temp (ꢀC)
Product
Yielda (%)
1
2
3
4
a
Ph 1
30
30
30
83
19
20
21
22
72
65
69
71
1-Cyclohexenyl 6
p-Tolyl 10
2-Furyl 14
Isolated yield.
carbene complex is believed to be the first step in the Dotz
¨
benzannulation.12
With respect to the lack of success of the sulfide additive in
the benzannulation processes attempted, it has been widely
assumed that the role of such Lewis base promoters in the
PausoneKhand reaction is to facilitate CO ligand loss from
the requisite parent and intermediate cobalt complexes.18
However, a recent publication has proposed that the root of
Lewis base promotion within such PausoneKhand processes
is not centred around the mediation of CO extrusion.19 This
theoretical study has concluded that such Lewis base pro-
moters actually serve to confer irreversibility on the key al-
kene insertion process within PausoneKhand annulations
and, hence, drive the reaction process forward. Based on this
more recent observation and with no directly equivalent olefin
Reactions with phenyl 1, cyclohexenyl 6 and p-tolyl 10 com-
plexes were all carried out at 30 ꢀC; the reaction with 2-furyl
carbene 14 was performed at 83 ꢀC (Table 9). Pleasingly, in
most cases the observed yields were appreciably greater than
those obtained with diphenylacetylene. The 72% yield for
the reaction with phenyl carbene 1 showed a significant im-
provement over the 53% yield previously obtained with diphe-
nylacetylene. This trend was mirrored by the results from the
reactions involving the cyclohexenyl complex 6 (65% cf.
55%), and the p-tolyl carbene 10 (69% cf. 38%). In contrast,
the 71% yield with the 2-furyl complex 14, despite being
more than acceptable for a process with such a heteroaryl
carbene, was lower than the 88% yield obtained with
diphenylacetylene. This result, again, fits with the pattern that
lower yields seem to be obtained with the 2-furyl carbene
when more accessible alkynes are employed.
insertion step present within the Dotz reaction pathway, it is
¨
perhaps not so surprising that Lewis basic sulfide additives
do not serve to promote this class of metal carbene-mediated
benzannulation process.
It should also be noted at this stage that, in attempts to ob-
tain higher yields from the annulation processes involving di-
phenylacetylene and the non-heteroaryl complexes, reactions
were performed with the phenyl carbene 1 and this diaryl al-
kyne at more elevated temperatures. Unfortunately, runs at
50 ꢀC and 83 ꢀC failed to deliver yields that were greater
than the 53% achieved between these substrates at 30 ꢀC
(see, Table 4, Entry 2).
3. Conclusions
The initial proposal, to develop a sulfide-promoted Dotz
¨
benzannulation process, proved to be unsuccessful. However,
it became apparent that 1,2-DCE was acting to promote the
desired cyclisation reactions and, consequently, our focus
turned to developing conditions for use with this readily acces-
sible solvent. Following optimisation, reaction conditions have
2.4. Rationalisation of 1,2-DCE as a promoting solvent
for Do¨tz benzannulation processes
now been formulated which allow intermolecular Dotz benz-
¨
annulations to be performed under remarkably mild low tem-
perature conditions and without the requirement for any
further reaction promoters. This methodology has been ap-
plied to a series of substrates to successfully deliver the prod-
The possibility of using 1,2-DCE as the reaction solvent in
order to perform intermolecular Dotz benzannulations with
¨
such levels of efficiency, especially at relatively low tempera-
tures, was unexpected and intriguing. In this regard, despite
the role of this solvent not currently being well defined, it is
suggested that 1,2-DCE could act as a bidentate ligand within
the reaction manifold and, in turn, could serve to stabilise co-
ordinatively unsaturated chromium species which occur along
the mechanistic pathway, following the initial decarbonylation
step. If 1,2-DCE was to act in this fashion, it is envisaged that
such a ligating species would be readily displaced to allow the
continuation of the desired annulation reaction process. This
rationalisation is analogous to that proposed by Boger,8 who
postulated that acetic anhydride was acting as a similar biden-
tate ligand which serves to stabilise metal-based intermediates
ucts of Dotz annulation in generally good to excellent yields.
¨
4. Experimental
4.1. General experimental methods
All reagents were obtained from commercial suppliers and
used without further purification, unless otherwise stated. Tet-
rahydrofuran and ether were dried by heating to reflux over so-
dium wire, using benzophenone ketyl as an indicator, then
distilled under nitrogen. 1,2-DCE was dried by heating to re-
flux over calcium hydride and then distilled under nitrogen.
Petroleum ether was distilled prior to use and refers to

S. Irvine et al. / Tetrahedron 64 (2008) 926e935
931
fractions boiling between 30 and 40 ꢀC. n-Bu2O, 1-hexyne and
4.3.2. General procedure BdDo¨tz benzannulation reaction
with DodSMe additive
phenylacetylene were purified by distillation under nitrogen.
Fischer carbene complexes 1,20 6,6c,21 1020 and 145b,22 were
readily synthesised by published methods. Flash chromatogra-
phy was carried out using Prolabo silica gel (230e400 mesh).
IR spectra were obtained on a Perkin Elmer Spectrum 1 ma-
To a stirred solution of chromium carbene complex in the
reaction solvent under an atmosphere of N2, were added the
alkyne and DodSMe, sequentially. The reaction vessel was fit-
ted with a reflux condenser, if necessary, and the reaction mix-
ture was warmed to the appropriate temperature for the time
stated. The reaction mixture was then cooled and was added
to a solution of CAN in HNO3 (0.1 M). The resulting solution
was stirred for 30 min before being extracted with ether. The
organic extracts were combined, washed with water, dried
over MgSO4 and concentrated in vacuo. The product was pu-
rified by flash chromatography (eluent: 1:11 ether in petro-
leum ether).
1
chine. H NMR spectra were recorded on a Bruker DPX 400
spectrometer at 400 MHz or a Joel Ex 270 MHz spectrometer
at 270 MHz. 13C NMR spectra were recorded on a Bruker
DPX 400 spectrometer at 100 MHz. Chemical shifts are re-
ported in parts per million. Coupling constants are reported
in hertz and refer to 3JHeH interactions unless otherwise spec-
ified. Accurate mass measurements were performed at the
University of Wales, Swansea using a Finnigan MAT 95XP
high resolution double focusing mass spectrometer.
Following general procedure B, data are reported as (a) al-
kyne, (b) DodSMe, (c) chromium carbene complex, (d) sol-
vent, (e) reaction temperature, (f) reaction time, (g) quantity
of CAN, (h) quantity of HNO3 and (i) product yield.
4.2. Preparation of dodecylmethylsulfide23
To a stirred suspension of K2CO3 (15.01 g, 108.6 mmol)
in DMF (60 mL), cooled to 0 ꢀC in an ice-water bath, was
added a solution of MeI (6.46 mL, 103.8 mmol) and dodeca-
nethiol (23.67 mL, 98.8 mmol) in DMF (20 mL), via cannula.
The resulting mixture was stirred at room temperature for
18 h. The reaction mixture was filtered and HCl (1 M,
50 mL) was slowly added. Distilled water (50 mL) was then
added, followed by EtOAc (50 mL). The organic layer was
separated and washed with water (5ꢁ50 mL). The organic
layer was washed with sodium thiosulfate solution
(1ꢁ30 mL), dried over MgSO4 and concentrated in vacuo.
The crude reaction product was purified by distillation
(bp¼162e164 ꢀC at 18 mmHg) to afford the desired product
as a colourless oil (19.85 g, 93%). FTIR (CH2Cl2): 2927,
4.4. 2-Phenyl-1,4-naphthoquinone, 35a
Following general procedure A:
Reaction carried out in THF at 67 ꢀC: (a) phenylacetylene
2, 55 mL, 0.5 mmol, (b) carbene 1, 100 mg, 0.32 mmol, (c)
THF, 5 mL, (d) 67 ꢀC, (e) 18 h, (f) 1.272 g, 2.32 mmol, (g)
11 mL and (h) 3, 60 mg, 80%.
Reaction carried out in n-Bu2O at 67 ꢀC: (a) phenylacetyl-
ene 2, 138 mL, 1.26 mmol, (b) carbene 1, 250 mg,
0.8 mmol, (c) n-Bu2O, 5 mL, (d) 67 ꢀC, (e) 18 h, (f)
3.180 g, 5.8 mmol, (g) 11 mL and (h) 3, 66 mg, 35%.
Reaction carried out in 1,2-DCE at 67 ꢀC: (a) phenylacetyl-
ene 2, 138 mL, 1.26 mmol, (b) carbene 1, 250 mg,
0.8 mmol, (c) 1,2-DCE, 5 mL, (d) 67 ꢀC, (e) 18 h, (f)
3.180 g, 5.8 mmol, (g) 11 mL and (h) 3, 144 mg, 77%.
Reaction carried out in 1,2-DCE at 83 ꢀC: (a) phenylacetyl-
ene 2, 55 mL, 0.5 mmol, (b) carbene 1, 100 mg, 0.32 mmol,
(c) 1,2-DCE, 5 mL, (d) 83 ꢀC, (e) 18 h, (f) 1.272 g,
2.32 mmol, (g) 11 mL and (h) 3, 63 mg, 84%.
2855 cmꢂ1
. d 2.49 (t,
1H NMR (400 MHz, CDCl3):
J¼7.4 Hz, 2H, SCH2), 2.10 (s, 3H, SCH3), 1.60 (quintet, J¼
7.4 Hz, 2H, CH2), 1.43e1.21 (m, 18H, CH2), 0.89 (t,
J¼6.8 Hz, 3H, CH3).
4.3. General procedures
Reaction carried out in 1,2-DCE at 45 ꢀC: (a) phenylacetyl-
ene 2, 55 mL, 0.5 mmol, (b) carbene 1, 100 mg, 0.32 mmol,
(c) 1,2-DCE, 5 mL, (d) 45 ꢀC, (e) 18 h, (f) 1.272 g,
2.32 mmol, (g) 11 mL and (h) 3, 59 mg, 79%.
Reaction carried out in THF at 45 ꢀC: (a) phenylacetylene
2, 55 mL, 0.5 mmol, (b) carbene 1, 100 mg, 0.32 mmol, (c)
THF, 5 mL, (d) 45 ꢀC, (e) 18 h, (f) 1.272 g, 2.32 mmol, (g)
11 mL and (h) 3, 49 mg, 65%.
Reaction carried out in 1,2-DCE at rt over 18 h: (a) phenyl-
acetylene 2, 55 mL, 0.5 mmol, (b) carbene 1, 100 mg,
0.32 mmol, (c) 1,2-DCE, 5 mL, (d) rt, (e) 18 h, (f)
1.272 g, 2.32 mmol, (g) 11 mL and (h) 3, 24 mg, 32%.
Reaction carried out in 1,2-DCE at rt over 72 h: (a) phenyl-
acetylene 2, 55 mL, 0.5 mmol, (b) carbene 1, 100 mg,
0.32 mmol, (c) 1,2-DCE, 5 mL, (d) rt, (e) 72 h, (f)
1.272 g, 2.32 mmol, (g) 11 mL and (h) 3, 24 mg, 32%.
Reaction carried out in THF at rt: (a) phenylacetylene 2,
55 mL, 0.5 mmol, (b) carbene 1, 100 mg, 0.32 mmol, (c)
4.3.1. General procedure AdDo¨tz benzannulation reaction
To a stirred solution of chromium carbene complex in
the reaction solvent under an atmosphere of N2, was added
the alkyne. The reaction vessel was fitted with a reflux con-
denser, if necessary, and the reaction mixture warmed to the
appropriate temperature for the time stated. The reaction mix-
ture was then cooled and was added to a solution of ceric am-
monium nitrate (CAN) in HNO3 (0.1 M). The resulting
solution was stirred for 30 min before being extracted with
ether. The organic extracts were combined, washed with water,
dried over MgSO4 and concentrated in vacuo. The product was
purified by flash chromatography (eluent: 1:11 ether in petro-
leum ether).
Following general procedure A, data are reported as (a) al-
kyne, (b) chromium carbene complex, (c) solvent, (d) reaction
temperature, (e) reaction time, (f) quantity of CAN, (g) quan-
tity of HNO3 and (h) product yield.

932
S. Irvine et al. / Tetrahedron 64 (2008) 926e935
THF, 5 mL, (d) rt, (e) 18 h, (f) 1.272 g, 2.32 mmol, (g)
11 mL and (h) 3, 12 mg, 16%.
(d) 1,2-DCE, 5 mL, (e) 83 ꢀC, (f) 18 h, (g) 1.272 g,
2.32 mmol, (h) 11 mL and (i) 3, 40 mg, 53%.
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) phenylacetyl-
ene 2, 55 mL, 0.5 mmol, (b) carbene 1, 100 mg, 0.32 mmol,
(c) 1,2-DCE, 5 mL, (d) 30 ꢀC, (e) 18 h, (f) 1.272 g,
2.32 mmol, (g) 11 mL and (h) 3, 62 mg, 83%.
Reaction carried out in THF at 30 ꢀC: (a) phenylacetylene
2, 55 mL, 0.5 mmol, (b) carbene 1, 100 mg, 0.32 mmol, (c)
THF, 5 mL, (d) 30 ꢀC, (e) 18 h, (f) 1.272 g, 2.32 mmol, (g)
11 mL and (h) 3, 40 mg, 53%.
Reaction carried out in 1,2-DCE at 83 ꢀC with 5 equiv of
DodSMe: (a) phenylacetylene 2, 55 mL, 0.5 mmol, (b)
424 mL, 1.6 mmol, (c) carbene 1, 100 mg, 0.32 mmol, (d)
1,2-DCE, 5 mL, (e) 83 ꢀC, (f) 18 h, (g) 1.272 g,
2.32 mmol, (h) 11 mL and (i) 3, 36 mg, 48%.
Yellow solid. Mp 108e110 ꢀC. FTIR (CH2Cl2): 1666,
1
1598 cmꢂ1. H NMR (400 MHz, CDCl3): d 8.22e8.12 (m,
2H), 7.81e7.77 (m, 2H), 7.60e7.57 (m, 2H), 7.50e7.47 (m,
3H), 7.10 (s, 1H).
Following the Wulff-based process5a,b using freezeethaw
degassed THF in a sealed tube at 75 ꢀC; see, Ref. 15.
To a stirred solution of carbene 1 (250 mg. 0.8 mmol) in
dry THF (5 mL) was added phenylacetylene 2 (138 mL,
1.26 mmol). The solution was degassed by the freezeethaw
method (ꢂ196 ꢀC to 25 ꢀC; three cycles). The reaction vessel
was placed under an atmosphere of N2 and heated to 75 ꢀC for
18 h in a one-necked flask fitted with a threaded vacuum stop-
cock. After this time, the reaction mixture was cooled and was
added to a solution of CAN (3.18 g, 5.8 mmol) in HNO3
(0.1 M, 11 mL). The solution was stirred for 30 min and
then extracted with ether (3ꢁ20 mL). The ether extracts
were combined, washed with water (3ꢁ20 mL), dried over
MgSO4 and concentrated in vacuo. The product was purified
by flash chromatography (eluent: 1:11 ether in petroleum
ether) to afford the desired product 3 (133 mg, 71%).
4.5. 2,3-Diphenyl-1,4-naphthoquinone, 45a
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) diphenylace-
tylene, 178 mg, 1 mmol, (b) carbene 1, 200 mg, 0.64 mmol,
(c) 1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f) 2.544 g,
4.64 mmol, (g) 11 mL and (h) 4, 104 mg, 53%.
Reaction carried out in 1,2-DCE at 50 ꢀC: (a) diphenylace-
tylene, 187 mg, 1.05 mmol, (b) carbene 1, 210 mg,
0.67 mmol, (c) 1,2-DCE, 10 mL, (d) 50 ꢀC, (e) 18 h, (f)
2.664 g, 4.86 mmol, (g) 11 mL and (h) 4, 103 mg, 50%.
Reaction carried out in 1,2-DCE at 83 ꢀC: (a) diphenylace-
tylene, 185 mg, 1.04 mmol, (b) carbene 1, 206 mg,
0.66 mmol, (c) 1,2-DCE, 10 mL, (d) 83 ꢀC, (e) 18 h, (f)
2.626 g, 4.79 mmol, (g) 11 mL and (h) 4, 88 mg, 43%.
Following general procedure B:
Reaction carried out in THF at 67 ꢀC with 3 equiv of
DodSMe: (a) phenylacetylene 2, 138 mL, 1.26 mmol, (b)
636 mL, 2.4 mmol, (c) carbene 1, 250 mg, 0.8 mmol, (d)
THF, 5 mL, (e) 67 ꢀC, (f) 18 h, (g) 3.180 g, 5.8 mmol, (h)
11 mL and (i) 3, 108 mg, 58%.
Yellow solid. Mp 134e135 ꢀC. FTIR (CH2Cl2): 1664,
1
1597 cmꢂ1. H NMR (400 MHz, CDCl3): d 8.24e8.19 (m,
2H), 7.82e7.78 (m, 2H,), 7.28e7.21 (m, 6H), 7.14e7.09
(m, 4H).
Reaction carried out in n-Bu2O at 67 ꢀC with 3 equiv of
DodSMe: (a) phenylacetylene 2, 138 mL, 1.26 mmol, (b)
636 mL, 2.4 mmol, (c) carbene 1, 250 mg, 0.8 mmol, (d)
n-Bu2O, 5 mL, (e) 67 ꢀC, (f) 18 h, (g) 3.180 g, 5.8 mmol,
(h) 11 mL and (i) 3, 41 mg, 22%.
Reaction carried out in 1,2-DCE at 67 ꢀC with 3 equiv of
DodSMe: (a) phenylacetylene 2, 138 mL, 1.26 mmol, (b)
636 mL, 2.4 mmol, (c) carbene 1, 250 mg, 0.8 mmol, (d)
1,2-DCE, 5 mL, (e) 67 ꢀC, (f) 18 h, (g) CAN, 3.180 g,
5.8 mmol, (h) 11 mL and (i) 3, 94 mg, 50%.
Reaction carried out in 1,2-DCE at 83 ꢀC with 1 equiv of
DodSMe: (a) phenylacetylene 2, 55 mL, 0.5 mmol, (b)
85 mL, 0.32 mmol, (c) carbene 1, 100 mg, 0.32 mmol, (d)
1,2-DCE, 5 mL, (e) 83 ꢀC, (f) 18 h, (g) 1.272 g,
2.32 mmol, (h) 11 mL and (i) 3, 60 mg, 80%.
4.6. 2-Butyl-1,4-naphthoquinone, 524
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) 1-hexyne,
115 mL, 1 mmol, (b) carbene 1, 200 mg, 0.64 mmol, (c)
1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f) 2.544 g,
4.64 mmol, (g) 11 mL and (h) 5, 98 mg, 82%.
Yellow oil. FTIR (CH2Cl2): 1664, 1596 cmꢂ1. H NMR
(400 MHz, CDCl3): d 8.13e8.04 (m, 2H), 7.76e7.71 (m,
1
2H), 6.80 (t, 4JHeH¼1.2 Hz, 1H), 2.59 (td, J¼7.6 Hz, 4JHeH
¼
1.2 Hz, 2H), 1.58 (quintet, J¼7.6 Hz, 2H), 1.44 (sextet,
J¼7.3 Hz, 2H), 0.97 (t, J¼7.3 Hz, 3H).
Reaction carried out in 1,2-DCE at 83 ꢀC with 2 equiv of
DodSMe: (a) phenylacetylene 2, 55 mL, 0.5 mmol, (b)
170 mL, 0.64 mmol, (c) carbene 1, 100 mg, 0.32 mmol,
(d) 1,2-DCE, 5 mL, (e) 83 ꢀC, (f) 18 h, (g) 1.272 g,
2.32 mmol, (h) 11 mL and (i) 3, 58 mg, 77%.
Reaction carried out in 1,2-DCE at 83 ꢀC with 3 equiv of
DodSMe: (a) phenylacetylene 2, 55 mL, 0.5 mmol, (b)
254 mL, 0.96 mmol, (c) carbene 1, 100 mg, 0.32 mmol,
4.7. 5,6,7,8-Tetrahydro-2-phenyl-1,4-naphthoquinone, 711
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) phenylacetyl-
ene 2, 122 mL, 1.11 mmol, (b) carbene 6, 224 mg,
0.71 mmol, (c) 1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f)
2.878 g, 5.15 mmol, (g) 11 mL and (h) 7, 155 mg, 92%.

S. Irvine et al. / Tetrahedron 64 (2008) 926e935
933
Yellow solid. Mp 57e58 ꢀC. FTIR (CH2Cl2): 1651,
Yellow solid. Mp 107e109 ꢀC. FTIR (CH2Cl2): 1664,
1
1
1605 cmꢂ1. H NMR (400 MHz, CDCl3): d 7.48e7.42 (m,
5H), 6.79 (s, 1H), 2.51e2.49 (m, 4H), 1.77e1.73 (m, 4H).
1603 cmꢂ1. H NMR (270 MHz, CDCl3): d 8.11e7.06 (m,
13H), 2.55 (s, 3H).
4.12. 2-Butyl-7-methyl-1,4-naphthoquinone, 1327
4.8. 5,6,7,8-Tetrahydro-2,3-diphenyl-1,4-
naphthoquinone, 8
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) 1-hexyne,
110 mL, 0.96 mmol, (b) carbene 10, 200 mg, 0.61 mmol,
(c) 1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f) 2.423 g,
4.42 mmol, (g) 11 mL and (h) 13, 58 mg, 42%.
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) diphenylace-
tylene, 196 mg, 1.1 mmol, (b) carbene 6, 220 mg,
0.70 mmol, (c) 1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f)
2.785 g, 5.08 mmol, (g) 11 mL and (h) 8, 120 mg, 55%.
1
Brown oil. FTIR (CH2Cl2): 1664, 1603 cmꢂ1. H NMR
(270 MHz, CDCl3): d 7.95 (d, J¼7.8 Hz, 1H), 7.89 (s, 1H),
Yellow/orange solid. Mp 166e168 ꢀC. FTIR (CH2Cl2):
4
4
7.52 (dd, J¼7.9 Hz, JHeH¼1.0 Hz, 1H), 6.75 (t, JHeH
¼
1
1650, 1606 cmꢂ1. H NMR (400 MHz, CDCl3): d 7.30e7.25
4
1.3 Hz, 1H), 2.56 (td, J¼7.6 Hz, JHeH¼1.2 Hz, 2H), 2.50
(s, 3H), 1.62e1.51 (m, 2H), 1.49e1.35 (m, 2H), 0.96 (t,
J¼7.2 Hz, 3H).
(m, 6H), 7.09e7.06 (m, 4H), 2.63e2.60 (m, 4H), 1.86e1.82
(m, 4H). 13C NMR (100 MHz, CDCl3): d 187.3, 143.2,
142.5, 133.3, 130.8, 128.3, 127.8, 23.1, 21.4. Anal. Calcd
for C22H18O2: C, 84.05; H, 5.77%. Found: C, 84.05; H,
5.54%. High resolution mass spectrum (EI) m/z: 314.1298;
C22H18O2 ([M]þ) requires 314.1301.
4.13. 5-Phenylbenzo[b]furan-4,7-dione, 156i
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) phenylacetyl-
ene 2, 114 mL, 1.04 mmol, (b) carbene 14, 200 mg,
0.66 mmol, (c) 1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f)
2.626 g, 4.79 mmol, (g) 11 mL and (h) 15, 7 mg, 5%.
Reaction carried out in 1,2-DCE at 45 ꢀC: (a) phenylacetyl-
ene 2, 57 mL, 0.52 mmol, (b) carbene 14, 100 mg,
0.33 mmol, (c) 1,2-DCE, 5 mL, (d) 45 ꢀC, (e) 18 h, (f)
1.311 g, 2.39 mmol, (g) 11 mL and (h) 15, 26 mg, 35%.
Reaction carried out in 1,2-DCE at 83 ꢀC: (a) phenylacetyl-
ene 2, 57 mL, 0.52 mmol, (b) carbene 14, 100 mg,
0.33 mmol, (c) 1,2-DCE, 5 mL, (d) 83 ꢀC, (e) 18 h, (f)
1.311 g, 2.39 mmol, (g) 11 mL and (h) 15, 48 mg, 65%.
4.9. 2-Butyl-5,6,7,8-tetrahydro-1,4-naphthoquinone, 925
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) 1-hexyne,
132 mL, 1.15 mmol, (b) carbene 6, 230 mg, 0.73 mmol,
(c) 1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f) 2.9 g,
5.29 mmol, (g) 11 mL and (h) 9, 125 mg, 80%.
1
Brown oil. FTIR (CH2Cl2): 1650, 1615 cmꢂ1. H NMR
4
(400 MHz, CDCl3): d 6.47 (t, JHeH¼1.4 Hz, 1H), 2.42e
2.38 (m, 6H), 1.69e1.68 (m, 4H), 1.51e1.44 (m, 2H),
1.42e1.33 (m, 2H), 0.93 (t, J¼7.2 Hz, 3H).
Yellow/orange solid. Mp 145e147 ꢀC. FTIR (CH2Cl2):
1
1670, 1567, 1371 cmꢂ1. H NMR (400 MHz, CDCl3): d 7.74
4.10. 7-Methyl-2-phenyl-1,4-naphthoquinone, 1126
(d, J¼1.8 Hz, 1H), 7.52e7.44 (m, 5H), 6.94 (d, J¼1.8 Hz,
1H), 6.81 (s, 1H).
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) phenylacetyl-
ene 2, 105 mL, 0.96 mmol, (b) carbene 10, 200 mg,
0.61 mmol, (c) 1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f)
2.423 g, 4.42 mmol, (g) 11 mL and (h) 11, 98 mg, 65%.
4.14. 5,6-Diphenylbenzo[b]furan-4,7-dione, 169a
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) diphenylace-
tylene, 185 mg, 1.04 mmol, (b) carbene 14, 200 mg,
0.66 mmol, (c) 1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f)
2.626 g, 4.79 mmol, (g) 11 mL and (h) 16, 6 mg, 3%.
Reaction carried out in 1,2-DCE at 83 ꢀC: (a) diphenylace-
tylene, 185 mg, 1.04 mmol, (b) carbene 14, 200 mg,
0.66 mmol, (c) 1,2-DCE, 10 mL, (d) 83 ꢀC, (e) 18 h, (f)
2.626 g, 4.79 mmol, (g) 11 mL and (h) 16, 175 mg, 88%.
Yellow solid. Mp 101e102 ꢀC. FTIR (CH2Cl2): 1659,
1
1603 cmꢂ1. H NMR (270 MHz, CDCl3): d 8.08e7.47 (m,
8H), 7.03 (s, 1H), 2.52 (s, 3H).
4.11. 6-Methyl-2,3-diphenyl-1,4-naphthoquinone, 129a
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) diphenylace-
tylene, 171 mg, 0.96 mmol, (b) carbene 10, 200 mg,
0.61 mmol, (c) 1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f)
2.423 g, 4.42 mmol, (g) 11 mL and (h) 12, 75 mg, 38%.
Orange solid. Mp 170e171 ꢀC. FTIR (CH2Cl2): 1670,
1
1598, 1360 cmꢂ1. H NMR (400 MHz, CDCl3): d 7.77 (d,
J¼1.7 Hz, 1H), 7.23e7.21 (m, 6H), 7.05e7.02 (td,
4
J¼6.8 Hz, JHeH¼1.9 Hz, 4H), 6.96 (d, J¼1.7 Hz, 1H).

934
S. Irvine et al. / Tetrahedron 64 (2008) 926e935
4.15. 5-Butylbenzo[b]furan-4,7-dione, 1728
4.19. 5,6-Diethylbenzo[b]furan-4,7-dione, 225b
Following general procedure A:
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) 1-hexyne,
119 mL, 1.04 mmol, (b) carbene 14, 200 mg, 0.66 mmol,
(c) 1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f) 2.626 g,
4.79 mmol, (g) 11 mL and (h) 17, 12 mg, 9%.
Reaction carried out in 1,2-DCE at 83 ꢀC: (a) 3-hexyne 18,
131 mL, 1.15 mmol, (b) carbene 14, 220 mg, 0.73 mmol, (c)
1,2-DCE, 10 mL, (d) 83 ꢀC, (e) 18 h, (f) 2.9 g, 5.29 mmol,
(g) 11 mL and (h) 22, 106 mg, 71%.
Reaction carried out in 1,2-DCE at 83 ꢀC: (a) 1-hexyne,
119 mL, 1.04 mmol, (b) carbene 14, 200 mg, 0.66 mmol,
(c) 1,2-DCE, 10 mL, (d) 83 ꢀC, (e) 18 h, (f) 2.626 g,
4.79 mmol, (g) 11 mL and (h) 17, 75 mg, 56%.
Yellow solid. Mp 62e63 ꢀC. FTIR (CH2Cl2): 1663, 1578,
1364 cmꢂ1
. d 7.64 (d,
1H NMR (400 MHz, CDCl3):
J¼1.8 Hz, 1H), 6.82 (d, J¼1.8 Hz, 1H), 2.62e2.54 (m, 4H),
1.15e1.10 (m, 6H).
1
Yellow oil. FTIR (CH2Cl2): 1659, 1608, 1370 cmꢂ1. H
NMR (400 MHz, CDCl3): d 7.67 (d, J¼1.8 Hz, 1H), 6.84 (d,
Acknowledgements
4
J¼1.8 Hz, 1H), 6.49 (t, JHeH¼1.3 Hz, 1H), 2.50 (td,
4
J¼7.6 Hz, JHeH¼1.3 Hz, 2H), 1.57e1.49 (m, 2H), 1.45e
We would like to thank the C.K. Marr Trust for a fully
funded studentship (C.M.P.), and also AstraZeneca, R&D
Molndal for studentship support (S.I.). We are also grateful
¨
to the EPSRC Mass Spectrometry Service, University of
Wales, Swansea for analyses and to Majbrit and Co, Denmark
for further encouragement and support.
1.36 (m, 2H), 0.95 (t, J¼7.3 Hz, 3H).
4.16. 2,3-Diethyl-1,4-naphthoquinone, 195a
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) 3-hexyne 18,
115 mL, 1 mmol, (b) carbene 1, 200 mg, 0.64 mmol, (c)
1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f) 2.544 g,
4.64 mmol, (g) 11 mL and (h) 19, 112 mg, 72%.
References and notes
1. Fischer, E. O.; Maasbol, A. Angew. Chem., Int. Ed. Engl. 1964, 3, 580.
¨
2. de Meijere, A.; Schirmer, H.; Duetsch, M. Angew. Chem., Int. Ed. 2000,
39, 3964.
Yellow solid. Mp 64e66 ꢀC. FTIR (CH2Cl2): 1659,
1
1596 cmꢂ1. H NMR (400 MHz, CDCl3): d 8.11e8.07 (m,
3. Dotz, K. H. Angew. Chem., Int. Ed. Engl. 1975, 14, 644.
¨
4. (a) Dotz, K. H.; Tomuschat, P. Chem. Soc. Rev. 1999, 28, 187; (b) Dotz,
¨
¨
2H), 7.72e7.68 (m, 2H), 2.66 (q, J¼7.5 Hz, 4H), 1.17 (t,
K. H. Angew. Chem., Int. Ed. Engl. 1984, 23, 587.
J¼7.5 Hz, 6H).
5. (a) 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; (b)
Wulff, W. D.; McCallum, J. S.; Kunng, F.-A. J. Am. Chem. Soc. 1988, 110,
7419; (c) Dotz, K. H.; Dietz, R. Chem. Ber. 1978, 111, 2517.
¨
6. (a) Wulff, W. D.; Tang, P.-C.; McCallum, J. S. J. Am. Chem. Soc. 1981,
4.17. 2,3-Diethyl-5,6,7,8-tetrahydro-1,4-
naphthoquinone, 2029
103, 7677; (b) Dotz, K. H.; Muhlemeier, J.; Schubert, U.; Orama, O.
¨
¨
Following general procedure A:
J. Organomet. Chem. 1983, 247, 187; (c) Wulff, W. D.; Chan, K.-S.;
Tang, P.-C. J. Org. Chem. 1984, 49, 2293; (d) Wulff, W. D.; Yang,
D. C. J. Am. Chem. Soc. 1984, 106, 7565; (e) Yamashita, A.; Toy, A.
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) 3-hexyne 18,
113 mL, 0.99 mmol, (b) carbene 6, 200 mg, 0.63 mmol, (c)
1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f) 2.505 g,
4.57 mmol, (g) 11 mL and (h) 20, 89 mg, 65%.
Tetrahedron Lett. 1986, 27, 3471; (f) Dotz, K. H. Chem. Ber. 1977,
¨
110, 78; (g) Chamberlin, S.; Waters, M. L.; Wulff, W. D. J. Am. Chem.
Soc. 1994, 116, 3113; (h) Davies, M. W.; Johnson, C. N.; Harrity,
J. P. A. Chem. Commun. 1999, 2107; (i) Davies, M. W.; Johnson, C. N.;
Harrity, J. P. A. J. Org. Chem. 2001, 66, 3525; (j) Waters, M. L.; Bos,
M. E.; Wulff, W. D. J. Am. Chem. Soc. 1999, 121, 6403; (k) Hoffmann,
Yellow solid. Mp 78e80 ꢀC. FTIR (CH2Cl2): 1635 cmꢂ1
.
1H NMR (400 MHz, CDCl3): d 2.49 (q, J¼7.5 Hz, 4H),
2.44e2.41 (m, 4H), 1.70e1.67 (m, 4H), 1.08 (t, J¼7.5 Hz,
6H).
P.; Hammerle, M.; Unfried, G. New J. Chem. 1991, 15, 769.
¨
7. (a) Yamashita, A. J. Am. Chem. Soc. 1985, 107, 5823; (b) Yamashita, A.;
Scahill, T. A.; Toy, A. Tetrahedron Lett. 1985, 26, 2969; (c) Yamashita,
A.; Toy, A.; Scahill, T. A. J. Org. Chem. 1989, 54, 3625; (d) Flitsch,
W.; Lauterwein, J.; Micke, W. Tetrahedron Lett. 1989, 30, 1633.
8. (a) Boger, D. L.; Jacobsen, I. C. J. Org. Chem. 1990, 55, 1919; (b) Boger,
D. L.; Jacobsen, I. C. J. Org. Chem. 1991, 56, 2115; (c) Boger, D. L.;
Jacobsen, I. C. Tetrahedron Lett. 1989, 30, 2037.
4.18. 2,3-Diethyl-6-methyl-1,4-naphthoquinone, 2127
Following general procedure A:
Reaction carried out in 1,2-DCE at 30 ꢀC: (a) 3-hexyne 18,
109 mL, 0.96 mmol, (b) carbene 10, 200 mg, 0.61 mmol, (c)
1,2-DCE, 10 mL, (d) 30 ꢀC, (e) 18 h, (f) 2.423 g,
4.42 mmol, (g) 11 mL and (h) 21, 96 mg, 69%.
9. (a) Harrity, J. P. A.; Kerr, W. J.; Middlemiss, D. Tetrahedron 1993, 49,
5565; (b) Harrity, J. P. A.; Kerr, W. J.; Middlemiss, D.; Scott, J. S.
J. Organomet. Chem. 1997, 532, 219.
10. (a) Harrity, J. P. A.; Kerr, W. J.; Middlemiss, D. Tetrahedron Lett. 1993,
34, 2995; (b) Caldwell, J. J.; Colman, R.; Kerr, W. J.; Magennis, E. J.
Synlett 2001, 1428.
Yellow solid. Mp 58e59 ꢀC. FTIR (CH2Cl2): 1648,
11. Hutchinson, E. J.; Kerr, W. J.; Magennis, E. J. Chem. Commun. 2002, 2262.
1606 cmꢂ1
.
1H NMR (400 MHz, CDCl3): d 7.97 (d,
12. (a) Fischer, H.; Muhlemeier, J.; Markl, R.; Dotz, K. H. Chem. Ber. 1982,
¨
¨
¨
J¼7.9 Hz, 1H), 7.87 (s, 1H), 7.48 (d, J¼7.9 Hz, 1H), 2.67e
115, 1355; (b) Casey, C. P.; Cesa, M. C. Organometallics 1982, 1, 87.
13. Sugihara, T.; Yamada, M.;Yamaguchi, M.;Nishizawa, M. Synlett 1999, 771.
2.62 (m, 4H), 2.48 (s, 3H), 1.17e1.13 (m, 6H).

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935
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2005, 3, 2396.
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15. It should be noted that, as part of this programme and by following
a Wulff-based process,5a,b a 71% yield of naphthoquinone 3 was obtained
from reaction of carbene complex 1 and phenylacetylene 2 at 75 ꢀC in
a sealed tube under nitrogen with degassed THF (freezeethaw method;
ꢂ196 ꢀC to 25 ꢀC; three cycles), and following Ce(IV) work-up. Accord-
ingly, all further reactions within this programme were performed under
more standard inert (nitrogen) gas conditions in routinely dried THF
(Na, benzophenone ketyl).
20. Fischer, E. O.; Kreiter, C. G.; Kollmeier, H. J.; Muller, J.; Fischer, R. D.
J. Organomet. Chem. 1971, 28, 237.
21. King, J. D.; Quayle, P. Tetrahedron Lett. 1991, 32, 7759.
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J. A.; Jones, E. M. J. Chem. Soc. A 1971, 3368.
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Chem. 1998, 1387; (b) Poignant, G.; Nlate, S.; Guerchais, V.; Edwards,
A. J.; Raithby, P. R. Organometallics 1997, 16, 124.
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18. (a) Sugihara, T.; Yamaguchi, M.; Nishizawa, M. Chem.dEur. J. 2001, 7,
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28. Dotz, K. H.; Larbig, H. Bull. Soc. Chim. Fr. 1992, 6, 579.
¨
29. Xu, Y.-C.; Wulff, W. D. J. Org. Chem. 1987, 52, 3263.