Palladium-catalyzed carbonylative annulation of terminal alkynes: Synthesis of coumarins and 2-quinolones

Article abstract of DOI:10.1016/S0022-328X(03)00786-1

o-Iodophenols and o-iodoaniline derivatives react with terminal alkynes under 1 atm of CO in the presence of pyridine and catalytic amounts of Pd(OAc)₂ to generate coumarins and 2-quinolones, respectively, as the only products. Terminal alkynes bearing alkyl, aryl, silyl, hydroxyl, ester and cyano substituents are effective in these processes affording the desired products in moderate yields. The formation of coumarins and 2-quinolones in this process is in stark contrast with all previously described palladium-catalyzed reactions of o-iodophenols or o-iodoanilines with terminal alkynes and CO, which have afforded chromones and 4-quinolones. Moreover, under our reaction conditions terminal alkynes insert into the carbon-palladium bond instead of undergoing a Sonogashira-type coupling as confirmed by an isotope labeling experiment.

Full text of DOI:10.1016/S0022-328X(03)00786-1

Journal of Organometallic Chemistry 687 (2003) 425ꢀ435
/
www.elsevier.com/locate/jorganchem
Palladium-catalyzed carbonylative annulation of terminal alkynes:
synthesis of coumarins and 2-quinolones
Dmitry V. Kadnikov, Richard C. Larock *
Department of Chemistry, Iowa State University, Ames IA 50011, USA
Received 5 June 2003; received in revised form 17 July 2003; accepted 25 July 2003
Dedicated to Professor Jean-Pierre Geneˆt on the occasion of his 60th birthday
Abstract
o-Iodophenols and o-iodoaniline derivatives react with terminal alkynes under 1 atm of CO in the presence of pyridine and
catalytic amounts of Pd(OAc)2 to generate coumarins and 2-quinolones, respectively, as the only products. Terminal alkynes
bearing alkyl, aryl, silyl, hydroxyl, ester and cyano substituents are effective in these processes affording the desired products in
moderate yields. The formation of coumarins and 2-quinolones in this process is in stark contrast with all previously described
palladium-catalyzed reactions of o-iodophenols or o-iodoanilines with terminal alkynes and CO, which have afforded chromones
and 4-quinolones. Moreover, under our reaction conditions terminal alkynes insert into the carbonÃ/palladium bond instead of
undergoing a Sonogashira-type coupling as confirmed by an isotope labeling experiment.
# 2003 Elsevier B.V. All rights reserved.
Keywords: Palladium; Terminal alkyne; Carbon monoxide; Annulation
1. Introduction
is insertion into the transition metalÃ/carbon bond, while
most of the reactions involving terminal alkynes proceed
through the formation of alkynyl-transition metal com-
plexes [1].
Both internal and terminal alkynes have been utilized
in a variety of transition metal-catalyzed reactions for
the construction of new carbonÃ
/
carbon and carbonÃ
/
The palladium-catalyzed annulation of internal al-
kynes by ortho-substituted aryl iodides developed in our
laboratories in the last 15 years [4,5] generally proceeds
heteroatom bonds [1,2]. However, the reactivity of
terminal and internal alkynes is generally quite different.
The reactions of alkynes catalyzed by transition-metal
complexes can be roughly divided into three categories:
(1) reactions involving attack of various nucleophiles on
the triple bond coordinated to the transition metal; (2)
reactions involving insertion of the triple bond into the
by insertion of an alkyne into a carbonÃ
/palladium
bond. Terminal alkynes are generally ineffective in those
processes. Analogous methods for the synthesis of
benzofurans [6], indoles [7,8], isocoumarins [9], quino-
lines [10], pyridines [10] and carbolines [11] from
terminal alkynes and related ortho-substituted aryl
iodides always require the use of a copper co-catalyst
and undoubtedly involve the initial formation of an
ortho-substituted alkynylbenzene by a Sonogashira
coupling [12], followed by cyclization to form the
desired heterocycle. Quite often it is necessary to use
reagents other than palladium complexes, such as
NaOEt [7], n-Bu4NF [8], ZnCl2 [9] or CuI [10], to affect
cyclization.
transition metalÃ
/
carbon bond; and (3) reactions pro-
ceeding through the formation of transition metalꢀ
/
alkynyl complexes (Scheme 1). Both terminal and
internal alkynes have been utilized in processes in which
a nucleophile attacks the triple bond activated by
coordination to a transition-metal complex [3]. The
main reaction pathway for internal alkynes, however,
We have recently developed general and efficient
syntheses of 3,4-disubstituted coumarins [13] and 2-
* Corresponding author.
E-mail address: larock@iastate.edu (R.C. Larock).
0022-328X/03/$ - see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0022-328X(03)00786-1

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D.V. Kadnikov, R.C. Larock / Journal of Organometallic Chemistry 687 (2003) 425ꢀ435
/
Scheme 2.
Scheme 1.
The unusual alkyne/CO insertion selectivity of the
carbonylative annulation of internal alkynes developed
by us has prompted us to examine analogous reactions
of terminal alkynes. Herein, we wish to report that,
under our conditions for the palladium-catalyzed car-
bonylative annulation of internal alkynes, terminal
quinolones [14] by three-component processes involving
an ortho-functionalized aryl iodide, an internal alkyne,
and CO (Scheme 2). One of the interesting features of
these processes is the fact that insertion of the carbonÃ
/
carbon triple bond into the carbonÃpalladium bond
/
occurs in preference to insertion of CO, while all
previous alkyne/CO reactions have afforded products
in which CO inserts first.
alkynes undergo insertion into the carbonÃ
bond in preference to the insertion of CO, thus affording
coumarins or 2-quinolones (Eq. (4)).
/
palladium
Analogous palladium-catalyzed reactions of terminal
alkynes with o-iodophenols or o-iodoanilines and CO
are well known. The reaction of o-iodophenol, a
terminal alkyne and CO affords either aurones [15ꢀ
/17]
(Eq. (1)) or chromones [17ꢀ19] (Eq. (2)) depending on
/
ð4Þ
the reaction conditions employed. Alternatively, chro-
mones can be obtained as the sole products under mild
conditions by using o-iodophenyl acetates as annulating
agents [20]. The analogous reaction employing o-iodoa-
nilines is also known and affords exclusively 6-mem-
bered ring 4-quinolones (Eq. (3)) [19,21].
2. Results and discussion
2.1. Synthesis of coumarins
ð1Þ
ð2Þ
ð3Þ
The reaction of o-iodophenol with phenylacetylene in
the presence of 1 atm of CO under our standard reaction
conditions for the synthesis of coumarins from internal
alkynes [13] afforded 3-phenylcoumarin (1) in a 23%
yield (Eq. (5)). This is the product that would be
expected if the terminal alkyne reacted in the same
manner as an internal alkyne. None of the other
annulation products we might have reasonably ex-
pected, namely 2-phenylchromone or 2-phenylbenzo-
furan, were detected. The reaction, however, was very
messy, and a significant amount of a low polarity
viscous purple oil was isolated. This oil most likely
results from polymerization of phenylacetylene. Since
studies of the palladium-catalyzed dimerization of
terminal alkynes have shown that phenylacetylene is
by far the most reactive acetylene [22], we have
examined a number of different alkynes in order to
identify a more suitable alkyne for our optimization
studies (Eq. (6)). The results are summarized in Table 1.
Thus, the outcome of these reactions is quite different
from the carbonylative annulation of internal alkynes
developed by us. These processes clearly involve initial
formation of an ynone, which cyclizes to either 5- or 6-
membered rings depending on the base used (Scheme 3).

D.V. Kadnikov, R.C. Larock / Journal of Organometallic Chemistry 687 (2003) 425ꢀ
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435
427
Scheme 3.
Table 1
Palladium-catalyzed carbonylative annulation of terminal alkynes by
o-iodophenol (Eq. (6)) a
ð6Þ
The reaction of trimethylsilylacetylene (entry 2) was
significantly cleaner, and only the product and o-
iodophenol were observed by Thin-layer chromatogra-
phy (TLC) analysis. The yield of the desired product,
however, was very low, and the reaction was not
complete even after 24 h. The low yield might be
attributed to the high volatility of this acetylene (b.p.
53 8C). Therefore, two other silyl acetylenes with higher
boiling points have been examined (entries 3 and 4). In
both cases a higher yield of the desired coumarin was
obtained, and the starting material was almost comple-
tely consumed. The slight decrease in the yield in the
reaction of triisopropylsilylacetylene relative to the yield
in the reaction of triethylsilylacetylene is most likely due
to the increased steric hindrance about the triple bond.
The alkyl acetylene, 1-decyne, was examined next (entry
5). Surprisingly, both 3- and 4-n-octylcoumarins were
isolated from the reaction mixture in an ca. 2:1 ratio.
The combined yield of the coumarins was the highest
observed so far (36%). However, it should be noted that
a small amount of apparent polymeric product is
present in the isolated coumarin, as evidenced by the
alkyl portion of the 1H-NMR spectrum. Indeed, a
significant amount of polymeric product was also
isolated from the reaction mixture. To minimize the
amount of polymerization, the reaction was run at lower
temperatures (entries 6 and 7). Unfortunately, the
decrease in the reaction temperature led to incomplete
reactions and significantly lower yields of the coumar-
ins. None of the desired product was formed in the
reaction run at 80 8C.
a
Typical reaction conditions: o-iodophenol (0.5 mmol); the alkyne
(2.5 mmol); pyridine (1.0 mmol); n-Bu4NCl (0.5 mmol); and Pd(OAc)2
(5 mol%, 0.025 mmol) under 1 atm of CO in DMF (5 ml) was stirred at
120 8C for 24 h.
bThree equivalents of alkyne were used.
ð5Þ
The experiments conducted with N-substituted o-
anilines (see below) showed that the use of a lower
amount of the alkyne improves the yield of the desired

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/
product. Higher yields were also obtained using 1-
hexyne instead of 1-decyne. Therefore, two experiments
were conducted to determine if the same changes would
be observed in the reactions of o-iodophenol (Table 1,
entries 8 and 9). However, no improvement in the yield
was observed in either case. The use of three equivalents
of 1-decyne (entry 8) led to a small decrease in the yield
of the coumarins. The reaction of 1-hexyne (entry 9) was
significantly cleaner than the reaction of 1-decyne, and a
much lower amount of the polymeric products was
formed. However, the yield of the coumarins did not
increase.
Our initial experiments have established that the
carbonylative annulation of terminal alkynes under
our reaction conditions follows a different mechanism
than under previously developed conditions and leads to
the formation of different products. The formation of 4-
n-octylcoumarin (6) in the reaction with 1-decyne
strongly suggests that the triple bond of the terminal
the reaction afforded 3- and 4-n-octyl-2-quinolones
(Rꢁn-Oct) in a 73:27 ratio and an overall 29% yield.
/
Although the yield is slightly lower than the yield of the
corresponding reaction with o-iodophenol (Table 1,
entry 5), the quinolones were much purer than the
1
coumarins (as judged by their H-NMR spectra). The
significantly higher polarity of 2-quinolones allows more
efficient separation from the polymeric by-products by
column chromatography. As is the case with internal
alkynes, treatment of the crude reaction mixture with
ethanolic NaOH is required to achieve complete re-
moval of the ethoxycarbonyl group from the quinolone
products. When the reaction was run without such
treatment, all four possible products with NÃ
/
H and NÃ
/
CO2Et groups were observed.
alkyne does insert into the carbonÃ
/
palladium bond,
ð7Þ
since no mechanism involving a Sonogashira-like cou-
pling between o-iodophenol and a terminal alkyne can
account for the formation of such a product.
Lowering the temperature to 100 8C and shortening
the reaction time to 12 h did not significantly affect the
yield of the desired quinolones (compare entries 1 and
2). Since a decrease in the temperature did not lead to a
decrease in the reaction yield, 1-hexyne was examined as
a model substrate (entry 3). Despite the fact that the
However, the results of the experiments shown in
Table 1, as well as the reactivity patterns established for
the carbonylative annulation of internal alkynes [13,14],
indicate that the number of reaction parameters that can
be varied to improve the yield of the process is very
limited. Therefore, we decided to switch to N-substi-
tuted o-iodoanilines, which in many cases have proven
to be more reactive than o-iodophenols.
boiling point of 1-hexyne is only 71ꢀ72 8C, the yield of
/
the 2-quinolone actually increased to 44%. Moreover,
both quinolone isomers were essentially pure, as judged
by 1H-NMR spectroscopy. Therefore, 1-hexyne was
used as a model substrate for optimization from this
point on. Further variation of the reaction temperature
and time (entries 4 and 5) showed that this terminal
alkyne behaves under our reaction conditions quite
similar to internal alkynes. The annulation reaction is
complete after 6 h at 100 8C (entry 4). A further decrease
2.2. Synthesis of 2-quinolones*/optimization of the
reaction conditions
Ethyl N-(2-iodophenyl)carbamate and 1-decyne were
chosen as model substrates (Eq. (7)). Under the stan-
dard coumarin reaction conditions (Table 2, entry 1),
Table 2
The effect of the reaction temperature and stoichiometry on the palladium-catalyzed carbonylative annulation of terminal alkynes with ethyl N-(2-
iodophenyl)carbamate (Eq. (7)) a
Entry
R
Equivalents
Temperature (8C)
Time (h)
% Yield
Ratio of isomers b
1
2
3
4
5
6
7
8
9
n-C8H17
3
3
120
100
100
100
80
24
12
12
6
29
32
44
43
31
33
44
55
47
73:27
76:24
73:27
70:30
74:26
73:27
73:27
70:30
70:30
n-C4H9
3
3
3
24
24
24
24
24
10
5
100
100
100
100
3
2
a
Typical reaction conditions: ethyl N-(2-iodophenyl)carbamate (0.5 mmol), the alkyne, pyridine (1.0 mmol), n-Bu4NCl (0.5 mmol), and
Pd(OAc)2 (5 mol%, 0.025 mmol) under 1 atm of CO in DMF (5 ml) were stirred at 100 8C for 12 h, then the crude product was treated with 1 M
ethanolic NaOH (5 ml) at room temperature for 30 min.
b
The ratio of 3-alkyl- to 4-alkyl-2-quinolones.

D.V. Kadnikov, R.C. Larock / Journal of Organometallic Chemistry 687 (2003) 425ꢀ
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435
429
Table 3
Synthesis of 2(1H)-quinolones via palladium-catalyzed annulation of terminal alkynes (Eq. (7)) a
in the reaction temperature to 80 8C results in a very
slow reaction, and a lower yield even after 24 h (entry 5).
Since oligomerization of the alkyne is presumed to be
the major competing process, the amount of the alkyne
in the reaction mixture was varied to establish the
optimal aryl iodide to alkyne ratio (entries 6ꢀ9).
Increasing the amount of 1-hexyne to 10 equivalents
/
(entry 6) led to a significant decline in the yield of the

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/
desired product, while the use of lesser amounts of 1-
hexyne (entries 8 and 9) resulted in higher yields. The
highest yield was obtained using three equivalents of 1-
hexyne (entry 8). It is noteworthy, that even the use of
only two equivalents of the alkyne afforded a higher
yield of the quinolones than the use of five equivalents.
These results are in contrast with the carbonylative
annulation of internal alkynes, in which the yield of the
product increased with an increase in the amount of
alkyne up to a certain point and then remained constant.
We have subsequently examined the effect of a
number of other reaction parameters on the yield of 2-
quinolones. No significant change in the yield of 2-
quinolone was observed when a different Pd(II) catalyst,
PdCl2(PhCN)2, or a Pd(0) catalyst, Pd(dba)2, were
employed. However, the yield dropped to 26%, when
10 mol% of PPh3 was added. It is noteworthy, that the
regioselectivity of the reaction is not at all affected by
the choice of the palladium catalyst, suggesting that in
all cases the reaction proceeds through the same
arylpalladium intermediate. Similarly, change of the
yield of 13 is only slightly lower than the yields of 2-
quinolones from alkyl acetylenes. Still, a significantly
greater amount of polymeric by-products is formed in
the reaction with phenylacetylene. In fact, the reaction
mixture turns purple at room temperature immediately
upon mixing the reagents in the reaction vial. Unfortu-
nately, an attempt to improve the yield of 13 by adding
phenylacetylene to the reaction mixture at 100 8C failed
(entry 4). Excellent regioselectivity is the other interest-
ing feature of this phenylacetylene reaction. The carbo-
nylative annulation of cyclohexylacetylene afforded a
ca. 4:1 mixture of isomers (entry 2), although the size of
a cyclohexyl and a phenyl group are almost the same.
Therefore, it is likely that the steric bulk of the
substituents on the triple bond is a major, but not the
only, factor determining the regioselectivity of the
process. The electronic effects of the substituents on
the carbonÃ
/
carbon triple bond should favor alkyne
insertion when it affords a vinylpalladium complex with
the palladium atom next to a substituent better able to
stabilize a negative charge. Since a phenyl group is much
more effective in stabilizing a negative charge than a
cyclohexyl group is, this would account for the better
regioselectivity observed in the reaction of phenylacety-
lene.
base
(pyridine,
2,4,6-collidine,
3-cyanopyridine,
DMAP, NEt3), removal of n-Bu4NCl, or an increase
in the amount of the catalyst did not raise the yield of 2-
quinolone. The ratio of regioisomers varied only slightly
from a low of 61:39 to a high of 80:20.
The carbonylative annulation of terminal alkynes
bearing various functional groups was examined next.
Triethylsilylacetylene afforded the desired product 14 in
a 38% yield with excellent regioselectivity (entry 5). The
carbonylative annulation of terminal alkynes bearing
hydroxyl, ester and cyano groups shows that the
outcome of the process strongly depends on the
Thus, at this point, the optimized reaction conditions
are actually the same as the reaction conditions used for
the carbonylative annulation of internal alkynes: 0.5
mmol of ethyl N-(2-iodophenyl)carbamate, three
equivalents of alkyne, two equivalents of pyridine, one
equivalent of n-Bu4NCl, 5 mol% of Pd(OAc)2 in 5 ml of
DMF. The reactions are run at 100 8C for 12 h, and the
crude reaction products are treated with 5 ml of 1 M
ethanolic NaOH at room temperature for 30 min to
remove the carbamate protecting group. The carbony-
lative annulation of other terminal alkynes was investi-
gated next using these reaction conditions.
proximity of the group to the carbonÃ/carbon triple
bond. The carbonylative annulations of propargyl
alcohol (entry 6) and ethyl propiolate (entry 7) afforded
very messy reactions, producing significant amounts of
polymeric products. None of the desired 2-quinolones
1
were detected by H-NMR spectroscopy.
The carbonylative annulation of terminal alkynes in
2.3. Synthesis of 2-quinolones*scope and limitations
/
which the same functional groups are 3ꢀ4 carbon atoms
/
removed from the triple bond affords 2-quinolone
products. Although the yield in the reaction with 5-
hexyn-1-ol remains low (entry 8) perhaps due to
carbonylation of the alcohol group, the yield obtained
Alkyl-substituted terminal alkynes afford the desired
2-quinolones as mixtures of regioisomers in 50ꢀ55%
/
yields (Table 3, entries 1 and 2). The regioselectivity of
the reaction improves with an increase in the size of the
substituent on the triple bond. These results support our
hypothesis that the terminal alkynes behave in this
process just like the internal alkynes in our earlier
annulation chemistry [4,5]. Namely, they undergo inser-
tion into the carbonÃ
/
palladium bond, and the regios-
electivity of the insertion is governed by steric factors.
The carbonylative annulation of phenylacetylene
gives rise to 3-phenyl-2-quinolone (13) as the sole
product in a 42% yield (entry 3). Despite the fact that
phenylacetylene is significantly more reactive in the
palladium-catalyzed homocoupling reaction [22], the
Scheme 4.

D.V. Kadnikov, R.C. Larock / Journal of Organometallic Chemistry 687 (2003) 425ꢀ
/
435
431
Scheme 5.
employing methyl 5-hexynoate (entry 9) is only slightly
lower than the yield of the reaction with 1-hexyne. The
carbonylative annulation of 5-hexynenitrile also af-
forded the desired products in a 41% yield (entry 10).
The surprising feature of these reactions is an evident
improvement in the regioselectivity. The ratio of isomers
is around 4 to 1 when functionalized acetylenes are used,
compared to the 2.2 to 1 ratio obtained in most of the
reactions with 1-hexyne (entry 1, see also entry 11). It is
conceivable that additional coordination of the palla-
dium atom by the functional group of the alkyne
stabilizes the palladium complex from which the major
isomer arises upon insertion (Scheme 4). It is surprising,
however, that the nature of the functional group does
not affect the regioselectivity, since a cyano group and
an hydroxyl group are expected to have significantly
different affinities towards palladium.
The carbonylative annulation of 1-hexyne with an
iodoaniline bearing a methoxy group in the para
position to the carbamate group afforded the desired
product in a 53% yield as a 69:31 mixture of regioi-
somers (entry 11). Thus, an electron-donating group on
the aromatic ring affects neither the yield nor the
regioselectivity of the process.
complex. Nucleophilic attack of the carbamate nitrogen
on the carbonyl group of the acylpalladium complex
leads to formation of the N-protected 2-quinolone with
regeneration of the Pd(0) catalyst. Subsequent hydro-
lysis of the carbamate group affords the desired product.
Thus, our process differs from the previously reported
palladium-catalyzed reaction of o-iodoanilines with
terminal alkynes and CO in two aspects [19]. First, the
terminal alkyne inserts into the carbonÃ
/palladium
bond, instead of undergoing a Sonogashira-type cou-
pling. Second, this insertion of the alkyne occurs prior to
the insertion of CO, thus leading to 2- and not 4-
quinolone derivatives.
The insertion of a carbonÃ
terminal alkyne into the carbonÃ
unprecedented [23ꢀ26], although it is certainly very rare.
/carbon triple bond of a
/palladium bond is not
/
The Sonogashira-type coupling prevails in almost all
cases, and even in those cases where insertion apparently
occurs, it sometimes competes with coupling [25].
However, in our case, invoking such a coupling as the
first step of the process could hardly account for the
formation of 3-substituted 2-quinolones, and no reason-
able mechanism for the formation of the 4-substituted
isomer from the coupling product can be envisioned.
Indeed, the formation of both regioisomers and the fact
that the regioselectivity is apparently governed by steric
factors, just as in the annulation of internal alkynes,
provides the strongest support for the idea that alkyne
insertion does occur.
2.4. Mechanism
Since the carbonylative annulation of terminal al-
kynes closely resembles the carbonylative annulation of
internal alkynes in all major features (the nature of the
products, the regioselectivity, etc.), we believe that the
mechanisms of these two processes must be similar.
Thus, for the carbonylative annulation of terminal
alkynes we propose the mechanism shown in Scheme
5. The in situ reduction of Pd(OAc)2 to Pd(0) generates
the active catalyst. Oxidative addition of the aryl iodide
to Pd(0) leads to formation of an arylpalladium com-
plex, which in turn reacts with the terminal alkyne to
generate a vinylpalladium intermediate. Insertion of CO
into the vinylpalladium bond produces an acylpalladium
Still, we sought more direct evidence for the insertion
step. Therefore, the carbonylative annulation of deuter-
ated phenylacetylene has been examined (Eq. (8)). To
our delight, the reaction afforded 3-phenyl-4-deutero-2-
quinolone with better than 90% deuterium incorpora-
1
tion, as determined by H-NMR spectroscopic and MS
analysis. This result proves unambiguously that inser-
tion of the terminal alkyne does indeed occur under our
reaction conditions. It also shows that relatively little
exchange of the acetylenic proton occurs under our
reaction conditions, even with phenylacetylene, and,

432
D.V. Kadnikov, R.C. Larock / Journal of Organometallic Chemistry 687 (2003) 425ꢀ435
/
therefore, the formation of alkynylpalladium complexes
is irreversible. It is also remarkable that phenylacetylene
survives long enough to participate in the annulation,
even though it has been reported that the dimerization
of phenylacetylene proceeds in a 63% yield after just 40
min at room temperature in the presence of just 2 mol%
of an appropriate palladium catalyst [22].
meter (Finnigan MAT, San Jose, CA). High resolution
mass spectra were recorded on a Kratos MS50TC
double focusing magnetic sector mass spectrometer
using EI at 70 eV.
4.2. Reagents
All reagents were used directly as obtained commer-
cially unless otherwise noted. DMF, hexanes, and ethyl
acetate were purchased from Fisher Scientific Co.
Pyridine was purchased from Fisher Scientific Co. and
purified by distillation from CaH2. Et3N, 2,4,6-collidine,
3-cyanopyridine and DMAP were purchased from
Aldrich Chemical Co. n-Bu4NCl was purchased from
Lancaster Synthesis, Inc. 1-Hexyne, 1-octyne, phenyla-
cetylene, d-phenylacetylene, trimethylsilylacetylene,
triethylsilylacetylene, triisopropylsilylacetylene, propar-
gyl alcohol, 5-hexyn-1-ol and ethyl propiolate were
purchased from Aldrich Chemical Co. Methyl 5-hex-
ynoate and 5-hexynenitrile were purchased from GFS
Chemicals Co. Cyclohexylacetylene was purchased from
Farchan Chemical Co. Ethyl N-(2-iodophenyl)carba-
mate [14] and tert-butyl N-(2-iodo-4-methoxyphe-
nyl)carbamate [27] were prepared following literature
procedures. All palladium salts were donated by John-
son Matthey Inc. and Kawaken Fine Chemicals Co.
Ltd. Triphenylphosphine was donated by Kawaken
Fine Chemicals Co. Ltd.
ð8Þ
3. Conclusions
The reaction of o-iodophenol or ethyl N-(2-iodophe-
nyl)carbamate with terminal alkynes and CO under our
standard
carbonylative
annulation
conditions
(Pd(OAc)2/pyridine) affords exclusively coumarins or
2-quinolones. This is the first example of such chemos-
electivity. All previous work has reported the formation
of chromones or 4-quinolones from these starting
materials, respectively. Terminal alkynes with alkyl,
phenyl, silyl, hydroxyl, ester, and cyano substituents
react with ethyl N-(2-iodophenyl)carbamate to afford 2-
quinolones in modest yields. Both 3- and 4-substituted
2-quinolones are obtained in the reactions with terminal
alkynes bearing long alkyl chains. Such unusual beha-
vior for terminal alkynes indicates that the key step in
this process is insertion of the terminal alkyne into the
4.3. General procedure for the synthesis of coumarins
o-Iodophenol (0.5 mmol), the alkyne (2.5 mmol),
pyridine (79 mg, 1.0 mmol), n-Bu4NCl (139 mg, 0.5
mmol), Pd(OAc)2 (5.6 mg, 5 mol%, 0.025 mmol) and
DMF (5 ml) were placed in a 4 dram vial. The vial was
purged with CO for 2 min and then connected to a
balloon of CO. The reaction mixture was stirred at
120 8C for 24 h, then allowed to cool to room
temperature (r.t.), diluted with EtOAc, washed with
water, dried over anhydrous MgSO4, and concentrated
under reduced pressure. The product was isolated by
column chromatography on silica gel. The following
coumarins were prepared using this procedure.
carbonÃ
/
palladium bond and not the Sonogashira-type
coupling. This reactivity pattern is unambiguously
proven by an isotope labeling experiment. The annula-
tion of d-phenylacetylene affords 4-deutero-3-phenyl-2-
quinolone in a 40% yield with better than 90% deuter-
ium incorporation.
4. Experimental
4.3.1. 3-Phenyl-2H-1-benzopyran-2-one (1)
The compound was identified by comparing its H-
4.1. General
1
and 13C-NMR spectral properties with the literature
data [28].
1
All H- and 13C-NMR spectra were recorded at 400
and 100.5 MHz, respectively. TLC was performed using
commercially prepared 60-mesh silica gel plates (Scien-
tific Adsorbents Co.), and visualization was effected
with short wavelength UV light (254 nm) or a basic
KMnO4 solution (3 g KMnO4ꢂ
NaOH (5%)ꢂ300 ml of H2O). All melting points are
4.3.2. 3-Trimethylsilyl-2H-1-benzopyran-2-one (2)
Yellowish solid, m.p. 85ꢀ
7.79 (s, 1H), 7.45ꢀ7.52 (m, 2H), 7.22ꢀ
(s, 9H); 13C-NMR (CDCl3): d 163.0, 154.9, 150.1, 131.6,
130.1, 127.8, 124.2, 119.5, 116.8, ꢃ1.8; MS m/z
(relative intensity): 218 (27, Mꢂ), 203 (100), 175 (52),
/
88 8C; 1H-NMR (CDCl3): d
/
20 g K2CO3ꢂ
/
5 ml
/
/7.31 (m, 2H), 0.33
/
uncorrected. Low resolution mass spectra were recorded
on a Finnigan TSQ700 triple quadrupole mass spectro-
/

D.V. Kadnikov, R.C. Larock / Journal of Organometallic Chemistry 687 (2003) 425ꢀ
/
435
433
145 (16), 135 (17), 94 (16); HRMS Calc. for C12H14O2Si:
218.0763, Found: 218.0770.
4.4. General procedure for the synthesis of 2-quinolones
Ethyl N-(2-iodophenyl)carbamate (0.5 mmol), the
alkyne (1.5 mmol), pyridine (79 mg, 1 mmol), n-Bu4NCl
(139 mg, 0.5 mmol), and Pd(OAc)2 (5.6 mg, 5 mol%,
0.025 mmol) were placed in a 4 dram vial and dissolved
in 5 ml of DMF. The vial was purged with CO for 2 min,
and then connected to a balloon of CO. The reaction
mixture was stirred at 100 8C for 12 h, then allowed to
cool to r.t., diluted with EtOAc, washed with water, and
concentrated under reduced pressure. The residue was
treated with 5 ml of 1 M ethanolic NaOH at r.t. for 30
min. Then 15 ml of satd aq. NH4Cl were added, and the
resulting mixture was extracted with EtOAc. The
organic extracts were combined, washed with satd aq.
NH4Cl and water, dried over anhydrous MgSO4, and
concentrated under reduced pressure. The residue was
separated by column chromatography on silica gel. The
following 2-quinolones were prepared using this proce-
dure.
4.3.3. 3-Triethylsilyl-2H-1-benzopyran-2-one (3)
White solid, m.p. 80ꢀ
7.77 (s, 1H), 7.45ꢀ7.52 (m, 2H), 7.22ꢀ
0.96ꢀ1.01 (m, 9H), 0.84ꢀ
0.90 (m, 6H); 13C-NMR
/
83 8C; 1H-NMR (CDCl3): d
/
/
7.31 (m, 2H),
/
/
(CDCl3): d 163.0, 154.9, 151.4, 131.8, 127.8, 127.6,
124.2, 119.5, 116.8, 7.6, 2.7; IR (neat, cmꢃ1): 2954,
2918, 2873; MS m/z (relative intensity): 230 (100, [MÃ
/
C2H5]ꢂ), 203 (22), 175 (21).
4.3.4. 3-Triisopropylsilyl-2H-1-benzopyran-2-one (4)
Off-white solid, m.p. 113ꢀ
d 7.82 (s, 1H), 7.46ꢀ7.51 (m, 2H), 7.25ꢀ
1.53 (septet, Jꢁ7.6 Hz, 3H), 1.13 (d, Jꢁ
/
118 8C; 1H-NMR (CDCl3):
/
/
7.31 (m, 2H),
/
/7.6 Hz, 18H);
13C-NMR (CDCl3): d 163.2, 154.9, 152.3, 131.9, 127.8,
126.1, 124.1, 119.4, 116.7, 18.9, 11.3; IR (neat, cmꢃ1):
2943, 2868, 1701; MS m/z (relative intensity): 259 (100,
[MÃ
/
C3H7]ꢂ), 69 (29); HRMS (MÃ
/
C3H7)ꢂ Calc. for
4.4.1. 3-n-Butyl-2(1H)-quinolinone (9)
C15H19O2Si: 259.1154, Found: 259.1159.
1
White solid, m.p. 145ꢀ
7.60 (s, 1H), 7.50 (d, Jꢁ
7.18 (ddd, Jꢁ8.0, 6.4, 2.0 Hz, 1H), 2.70 (t, Jꢁ
2H), 1.66ꢀ1.74 (m, 2H), 1.41ꢀ1.51 (m, 2H), 0.99 (t, Jꢁ
/
147 8C; H-NMR (CDCl3): d
/
7.6 Hz, 1H), 7.40ꢀ
/
7.47 (m, 2H),
4.3.5. 3-Octyl-2H-1-benzopyran-2-one (5)
/
/7.8 Hz,
1
White solid, m.p. 59ꢀ
NMR (CDCl3): d 7.48 (s, 1H), 7.42ꢀ
(d, Jꢁ8.0 Hz, 1H), 7.25 (ddd, Jꢁ1.0, 7.2, 8.0 Hz, 1H),
2.56 (t, Jꢁ7.4 Hz, 2H), 1.60ꢀ1.66 (m, 2H), 1.20ꢀ1.40
(m, 10H), 0.87 (t, Jꢁ
7.6 Hz, 3H); 13C-NMR (CDCl3): d
/
62 8C (lit. [29] m.p. 64 8C); H-
/
/
/
/
7.46 (m, 2H), 7.31
7.4 Hz, 3H); 13C-NMR (CDCl3): d 164.7, 137.7, 136.6,
134.5, 129.4, 127.1, 122.5, 120.5, 115.9, 30.8, 30.1, 22.8,
14.2; IR (CDCl3, cmꢃ1): 2958, 2859, 1656, 1566; MS m/
z (relative intensity): 201 (26, Mꢂ), 172 (25), 159 (100),
158(51), 130 (40); HRMS Calc. for C13H15NO:
201.1154, Found: 201.1158.
/
/
/
/
/
/
162.1, 153.3, 138.5, 130.6, 130.3, 127.3, 124.4, 119.8,
116.6, 32.0, 31.0, 29.6, 29.5, 29.4, 28.2, 22.8, 14.3. All
spectral properties are identical to those reported in the
literature [29].
4.4.2. 4-n-Butyl-2(1H)-quinolinone (10)
1
White solid, m.p. 140ꢀ
7.73 (d, Jꢁ8.0 Hz, 1H), 7.48ꢀ
(m, 1H), 6.61 (s, 1H), 2.87 (t, Jꢁ
(m, 2H), 1.43ꢀ
/
142 8C; H-NMR (CDCl3): d
/
/
7.50 (m, 2H), 7.21ꢀ
7.6 Hz, 2H), 1.68ꢀ
1.52 (m, 2H), 0.98 (t, Jꢁ
/7.27
4.3.6. 4-Octyl-2H-1-benzopyran-2-one (6)
/
/1.76
Off-white solid, m.p. 60ꢀ
7.64 (dd, Jꢁ1.2, 8.0 Hz, 1H), 7.53 (ddd, Jꢁ
Hz, 1H), 7.27ꢀ7.36 (m, 2H), 6.29 (s, 1H), 2.77 (t, Jꢁ
Hz, 1H), 1.66ꢀ1.74 (m, 2H), 1.20ꢀ1.40 (m, 10H), 0.89 (t,
Jꢁ
6.8 Hz, 3H); 13C-NMR (CDCl3): d 161.3, 156.6,
/
63 8C; 1H-NMR (CDCl3): d
/
/7.2 Hz, 3H);
13C-NMR (CDCl3): d 164.8, 153.6, 138.8, 130.5, 124.3,
122.6, 120.1, 119.6, 117.1, 32.2, 31.1, 22.8, 14.1; IR
(neat, cmꢃ1): 2963, 1646, 1556; MS m/z (relative
intensity): 201 (28, Mꢂ), 159 (78), 130 (100); HRMS
Calc. for C13H15NO: 201.1154, Found: 201.1158.
/
/1.6, 7.0, 8.6
/
/7.8
/
/
/
154.0, 131.8, 124.5, 124.3, 119.6, 117.5, 114.1, 32.01,
31.97, 29.7, 29.5, 29.4, 28.3, 22.8, 14.3; MS m/z (relative
intensity): 258 (27, Mꢂ), 173 (19), 160 (100), 132 (37);
HRMS Calc. for C17H22O2: 258.1620, Found: 258.1623.
4.4.3. 3-Cyclohexyl-2(1H)-quinolinone (11)
1
White solid, m.p. 229ꢀ
7.58 (s, 1H), 7.52 (d, Jꢁ
7.0, 8.2 Hz, 1H), 7.38 (d, Jꢁ
1.2, 7.2, 8.0 Hz, 1H), 3.00ꢀ3.06 (m, 1H), 2.01ꢀ
2H), 1.79ꢀ1.89 (m, 3H), 1.48ꢀ1.58 (m, 3H), 1.27ꢀ
/
231 8C; H-NMR (CDCl3): d
/
7.6 Hz, 1H), 7.45 (ddd, Jꢁ
8.0 Hz, 1H), 7.18 (ddd, Jꢁ
2.04 (m,
1.40
/1.2,
/
/
4.3.7. 3-Butyl-2H-1-benzopyran-2-one (7)
/
/
White solid, m.p. 60ꢀ63 8C (lit. [28] m.p. 64 8C). The
/
/
/
/
spectral properties are identical to those reported in the
literature [28].
(m, 3H); 13C-NMR (CDCl3): d 164.2, 139.4, 137.3,
134.5, 129.4, 127.4, 122.5, 120.6, 115.7, 37.3, 32.8, 27.0,
26.6; IR (neat, cmꢃ1): 2933, 2853, 1651, 1566; MS m/z
(relative intensity): 227 (32, Mꢂ), 198 (44), 183 (54), 170
(100), 154 (64), 128 (44); HRMS Calc. for C15H17NO:
227.1310, Found: 227.1316.
4.3.8. 4-Butyl-2H-1-benzopyran-2-one (8)
Yellow oil, the spectral properties are identical to
those reported in the literature [30].

434
D.V. Kadnikov, R.C. Larock / Journal of Organometallic Chemistry 687 (2003) 425ꢀ435
/
4.4.4. 4-Cyclohexyl-2(1H)-quinolinone (12)
Off-white solid, m.p. 233ꢀ
235 8C; 1H-NMR (CDCl3):
d 7.78 (d, Jꢁ8.0 Hz, 1H), 7.50 (ddd, Jꢁ1.2, 7.2, 8.2
Hz, 1H), 7.40 (dd, Jꢁ0.8, 8.0 Hz, 1H), 7.24 (ddd, Jꢁ
1.2, 6.8, 8.0 Hz, 1H), 6.62 (s, 1H), 3.00ꢀ3.05 (m, 1H),
1.82ꢀ2.02 (m, 5H), 1.25ꢀ
1.54 (m, 5H); 13C-NMR
(CDCl3): d 164.5, 158.2, 138.7, 130.4, 124.0, 122.6,
120.0, 117.3, 117.0, 39.4, 33.3, 27.0, 26.5; IR (neat,
cmꢃ1): 2928, 2853, 1656, 1556; MS m/z (relative
intensity): 227 (100, Mꢂ), 198 (16), 184 (20), 172 (14),
170(14), 159 (16); HRMS Calc. for C15H17NO:
227.1310, Found: 227.1314.
other spectral data have been obtained; MS m/z
(relative intensity): 217 (40, Mꢂ), 159 (42), 130 (100),
102 (44); HRMS Calc. for C13H15NO2: 217.1103,
Found: 217.1107.
/
/
/
/
/
/
/
/
4.4.9. Methyl 4-(2(1H)-oxoquinolin-3-yl)butanoate
(17)
1
Colorless solid, m.p. 145ꢀ
d 7.65 (s, 1H), 7.52 (d, Jꢁ
1.4, 7.0, 8.4 Hz, 1H), 7.39 (d, Jꢁ
Jꢁ1.0, 7.0, 8.0 Hz, 1H), 3.69 (s, 1H), 2.74 (t, Jꢁ
2H), 2.46 (t, Jꢁ7.4 Hz, 2H), 2.04ꢀ
2.11 (m, 2H); 13C-
/
148 8C; H-NMR (CDCl3):
/
8.0 Hz, 1H), 7.47 (ddd, Jꢁ
8.0 Hz, 1H), 7.20 (ddd,
7.6 Hz,
/
/
/
/
/
/
NMR (CDCl3): d 174.2, 164.4, 137.8, 137.4, 133.2,
129.8, 127.4, 122.7, 120.4, 115.8, 51.8, 33.8, 29.9, 23.9;
IR (neat, cmꢃ1): 3003, 2953, 2848, 1736, 1661, 1576; MS
m/z (relative intensity): 245 (32, Mꢂ), 244 (19), 172
(100), 171 (55), 159 (38), 158 (25); HRMS Calc. for
C14H15NO3: 245.1052, Found: 245.1056.
4.4.5. 3-Phenyl-2(1H)-quinolinone (13)
White solid, m.p. 230ꢀ
/
231 8C (lit. [31] m.p. 231ꢀ
232 8C); H-NMR (d6-DMSO): d 8.10 (s, 1H), 7.72ꢀ
7.77 (m, 2H), 7.50 (ddd, Jꢁ1.2, 7.2, 8.4 Hz, 1H),
7.32ꢀ7.45 (m, 4H), 7.19 (dd, Jꢁ
7.2, 7.6 Hz, 1H); 13C-
/
1
/
/
/
/
NMR (d6-DMSO): d 161.0, 138.4, 137.6, 136.3, 131.5,
130.2, 128.7, 128.1, 127.9, 127.8, 121.9, 119.5, 114.7; MS
m/z (relative intensity): 221 (49, Mꢂ), 220 (100), 165
(39); HRMS Calc. for C15H11NO: 221.0841, Found:
221.0846.
4.4.10. Methyl 4-(2(1H)-oxoquinolin-4-yl)butanoate
(18)
Brown solid, m.p. 164ꢀ
7.78 (d, Jꢁ8.0 Hz, 1H), 7.52 (dd, Jꢁ
7.43 (d, Jꢁ8.0 Hz, 1H), 7.26 (dd, Jꢁ
3.71 (s, 3H), 2.92 (t, Jꢁ
2H), 2.05ꢀ
2.11 (m, 2H); 13C-NMR (CDCl3): d 173.7,
/
167 8C; 1 H-NMR (CDCl3): d
/
/
7.2, 8.0 Hz, 1H),
4.4.6. 3-Triethylsilyl-2(1H)-quinolinone (14)
/
/
7.2, 8.0 Hz, 1H),
1
White solid, m.p. 138ꢀ
7.88 (s, 1H), 7.53 (dd, Jꢁ
Jꢁ1.2, 7.2, 8.4 Hz, 1H), 7.33 (d, Jꢁ
(ddd, Jꢁ1.0, 7.0, 8.0 Hz, 1H), 1.00ꢀ
/
140 8C; H-NMR (CDCl3): d
/
7.8 Hz, 2H), 2.48 (t, Jꢁ7.0 Hz,
/
/
1.2, 8.4 Hz, 1H), 7.48 (ddd,
8.0 Hz, 1H), 7.17
1.05 (m, 9H), 0.92ꢀ
/
/
/
164.3, 152.3, 138.7, 130.7, 124.4, 122.8, 120.0, 119.8,
116.9, 51.9, 33.5, 31.8, 24.2; IR (neat, cmꢃ1): 3013,
2953, 2853, 1736, 1651, 1435, 1171; MS m/z (relative
intensity): 245 (100, Mꢂ), 172 (81), 130 (59); HRMS
Calc. for C14H15NO3: 245.1052, Found: 245.1058.
/
/
/
0.98 (m, 6H); 13C-NMR (CDCl3): d 167.4, 148.8, 139.7,
131.7, 130.7, 127.8, 122.2, 120.4, 115.9, 7.8, 3.1; IR
(neat, cmꢃ1): 2953, 2868, 1636, 1596, 1546; MS m/z
(relative intensity): 259 (10, Mꢂ), 230 (100), 174 (30),
172 (48), 144 (43); HRMS Calc. for C15H21NOSi:
259.1392, Found: 259.1397.
4.4.11. 4-(2(1H)-Oxoquinolin-3-yl)butanenitrile (19)
Solid, m.p. 164ꢀ
1H), 7.55 (d, Jꢁ8.0 Hz, 1H), 7.50 (ddd, Jꢁ
Hz, 1H), 7.41 (d, Jꢁ8.4 Hz, 1H), 7.23 (ddd, Jꢁ
8.0 Hz, 1H), 2.86 (t, Jꢁ7.2 Hz, 2H), 2.45 (t, Jꢁ
2H), 2.08ꢀ
2.16 (m, 2H); 13C-NMR (CDCl3): d 164.2,
/
167 8C; 1H-NMR (CDCl3): d 7.70 (s,
/
/
1.2, 7.2, 8.4
1.0, 7.0,
7.2 Hz,
4.4.7. 3-(4-Hydroxybutyl)-2(1H)-quinolinone (15)
/
/
1
White solid, m.p. 148ꢀ
7.64 (s, 1H), 7.52 (d, Jꢁ
7.0, 8.4 Hz, 1H), 7.38 (d, Jꢁ
1.0, 7.0, 8.0 Hz, 1H), 3.78 (t, Jꢁ
Jꢁ7.6 Hz, 2H), 1.99 (br s, 1H), 1.77ꢀ
1.67ꢀ
1.74 (m, 2H); 13C-NMR (CDCl3): d 164.3, 137.5,
/
150 8C; H-NMR (CDCl3): d
/
/
/
7.6 Hz, 1H), 7.47 (ddd, Jꢁ
8.0 Hz, 1H), 7.20 (ddd, Jꢁ
6.2 Hz, 2H), 2.73 (t,
1.84 (m, 2H),
/
1.4,
/
/
/
138.3, 137.9, 131.6, 130.2, 127.5, 122.9, 120.2, 119.8,
115.9, 30.0, 24.4, 17.0; IR (neat, cmꢃ1): 2953, 2856,
2238, 1655; MS m/z (relative intensity): 212 (Mꢂ, 28),
172 (50), 159 (100); HRMS Calc. for C13H12N2O:
212.0950, Found: 212.0953.
/
/
/
/
137.1, 134.1, 129.7, 127.3, 122.8, 120.5, 115.7, 62.7, 32.2,
30.0, 25.0; IR (neat, cmꢃ1): 2923, 2848, 1656; MS m/z
(relative intensity): 217 (33, Mꢂ), 199 (50), 172 (100),
159 (65), 158 (71), 130 (60); HRMS Calc. for
C13H15NO2: 217.1103, Found: 217.1108.
4.4.12. 4-(2(1H)-Oxoquinolin-4-yl)butanenitrile (20)
1
Brown oil; H-NMR (CDCl3): d 7.71 (d, Jꢁ
/8.0 Hz,
1H), 7.55 (dd, Jꢁ
1H), 7.28 (dd, Jꢁ
2H), 2.50 (t, Jꢁ6.8 Hz, 2H), 2.08ꢀ2.16 (m, 2H), only a
small amount of 20 was isolated; therefore, no other
spectral data have been obtained; MS m/z (relative
intensity): 212 (Mꢂ, 39), 159 (41), 143 (100), 130 (72),
115 (53); HRMS Calc. for C13H12N2O: 212.0950,
Found: 212.0953.
/
7.2, 8.0 Hz, 1H), 7.43 (d, Jꢁ
/
8.4 Hz,
4.4.8. 4-(4-Hydroxybutyl)-2(1H)-quinolinone (16)
/
7.2, 8.0 Hz, 1H), 3.06 (t, Jꢁ
/
7.6 Hz,
1
White solid, m.p. 147ꢀ
7.74 (d, Jꢁ
1H), 7.37 (d, Jꢁ
Hz, 1H), 6.59 (s, 1H), 3.73 (t, Jꢁ
Jꢁ7.4 Hz, 2H), 1.80ꢀ1.88 (m, 2H), 1.68ꢀ
only a small amount of 16 was isolated; therefore, no
/
150 8C; H-NMR (CDCl3): d
/
/
/
8.0 Hz, 1H), 7.51 (ddd, Jꢁ
8.0 Hz, 1H), 7.24 (ddd, Jꢁ
6.4 Hz, 2H), 2.91 (t,
1.79 (m, 2H),
/
0.8, 7.2, 8.0 Hz,
/
/1.2, 7.2, 8.4
/
/
/
/

D.V. Kadnikov, R.C. Larock / Journal of Organometallic Chemistry 687 (2003) 425ꢀ
/
435
435
4.4.13. 3-n-Butyl-6-methoxy-2(1H)-quinolinone(21)
Acknowledgements
1
White solid, m.p. 165ꢀ
7.56 (s, 1H), 7.32 (d, Jꢁ8.8 Hz, 1H), 7.09 (dd, Jꢁ
8.8 Hz, 1H), 6.95 (d, Jꢁ2.8 Hz, 1H), 3.85 (s, 3H), 2.69
(t, Jꢁ7.6 Hz, 2H), 1.65ꢀ1.73 (m, 2H), 1.41ꢀ1.51 (m,
2H), 0.98 (t, Jꢁ
7.2 Hz, 3H); 13C-NMR (CDCl3): d
/
168 8C; H-NMR (CDCl3): d
/
/2.8,
We gratefully acknowledge the donors of the Petro-
leum Research Fund, administered by the American
Chemical Society, for partial support of this research,
and Kawaken Fine Chemicals Co., Ltd. and Johnson
Matthey, Inc. for donating Pd(OAc)2.
/
/
/
/
/
164.1, 155.2, 136.2, 135.0, 132.2, 121.1, 118.8, 117.1,
108.5, 55.9, 30.8, 30.2, 22.8, 14.3; IR (neat, cmꢃ1): 2933,
2834, 1651, 1621, 1501; MS m/z (relative intensity): 231
(38, Mꢂ), 202 (61), 189 (86), 188 (56), 174 (100); HRMS
Calc. for C14H17NO2: 231.1259, Found: 231.1263.
References
4.4.14. 4-n-Butyl-6-methoxy-2(1H)-quinolinone (22)
[1] J. Tsuji, Palladium Reagents and Catalysts: Innovations in
Organic Synthesis, John Wiley & Sons, Ltd, Chichester, 1995.
[2] N.E. Schore, Chem. Rev. 88 (1988) 1081.
1
White solid, m.p. 195ꢀ
7.42 (d, Jꢁ8.4 Hz, 1H), 7.13ꢀ
2.83 (t, Jꢁ7.6 Hz, 2H), 1.69ꢀ
(m, 2H), 0.99 (t, Jꢁ
7.4 Hz, 3H); 13C-NMR (CDCl3): d
/
198 8C; H-NMR (CDCl3): d
/
/7.16 (m, 2H), 3.87 (s, 1H),
[3] S. Cacchi, J. Organomet. Chem. 576 (1999) 42.
[4] R.C. Larock, J. Organomet. Chem. 576 (1999) 111.
[5] R.C. Larock, Pure Appl. Chem. 71 (1999) 1435.
[6] A. Arcadi, F. Marinelli, S. Cacchi, Synthesis (1986) 749.
[7] T. Sakamoto, Y. Kondo, H. Yamanaka, Heterocyles 24 (1986) 31.
[8] A. Yasuhara, Y. Kanamori, M. Kaneko, A. Numata, Y. Kondo,
T. Sakamoto, J. Chem. Soc., Perkin Trans. 1 (1999) 529.
[9] H.-Y. Liao, C.-H. Cheng, J. Org. Chem. 60 (1995) 3711.
[10] K.R. Roesch, R.C. Larock, J. Org. Chem. 67 (2002) 86.
[11] H. Zhang, R.C. Larock, Tetrahedron Lett. 43 (2002) 1359.
[12] K. Sonogashira, in: F. Diederich, P.J. Stang (Eds.), Metal-
catalyzed Cross-coupling Reactions, Wiley-VCH, Weinheim,
1998, p. 203.
/
/
1.76 (m, 2H), 1.44ꢀ1.51
/
/
164.2, 155.2, 152.8, 133.4, 120.8, 120.0, 119.2, 118.2,
106.6, 56.0, 32.2, 30.9, 22.8, 14.1; IR (neat, cmꢃ1): 2963,
1651; MS m/z (relative intensity): 231 (27, Mꢂ), 189
(21), 41 (100); HRMS Calc. for C14H17NO2: 231.1259,
Found: 231.1262.
4.5. Isotope labeling experiment
Ethyl N-(2-iodophenyl)carbamate (146 mg, 0.5
mmol), d-phenylacetylene (98% D, 155 mg, 1.5 mmol),
pyridine (79 mg, 1.0 mmol), n-Bu4NCl (139 mg, 0.5
mmol), and Pd(OAc)2 (5.6 mg, 5 mol%, 0.025 mmol)
were placed in a 4 dram vial and dissolved in 5 ml of
DMF. The vial was purged with CO for 2 min, and then
connected to a balloon of CO. The reaction mixture was
stirred at 100 8C for 12 h, then allowed to cool to r.t.,
diluted with EtOAc, washed with water, and concen-
trated under reduced pressure. The residue was treated
with 5 ml of 1 M ethanolic NaOH at r.t. for 30 min.
Then 15 ml of satd aq. NH4Cl were added, and the
resulting mixture was extracted with EtOAc. The
organic extracts were combined, washed with satd aq.
NH4Cl and water, dried over anhydrous MgSO4, and
concentrated under reduced pressure. Column chroma-
tography on silica gel using 1:1 hexane/ethyl acetate as
an eluent afforded 46 mg (40%) of 4-deutero-3-phenyl-
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9773.
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¨
Am. Chem. Soc. 119 (1997) 698.
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355.
2(1H)-quinolinone: colorless solid, m.p. 239ꢀ
1H-NMR (d6-DMSO): d 8.10 (s, 0.11H), 7.72ꢀ
(m, 2H), 7.50 (ddd, Jꢁ1.2, 7.2, 8.4 Hz, 1H), 7.32ꢀ
7.45 (m, 4H), 7.19 (dd, Jꢁ
7.2, 7.6 Hz, 1H); 13C-NMR
/
240 8C;
[26] E. Rossi, A. Arcadi, G. Abbiati, O.A. Attanasi, L.D. Crescentini,
Angew. Chem. Int. Ed. 41 (2002) 1400.
/
7.77
/
/
[27] Y. Kondo, S. Kojima, T. Sakamoto, J. Org. Chem. 62 (1997)
6507.
/
(d6-DMSO): d 161.0, 138.4, 136.3, 131.5, 130.2, 128.7,
128.1, 127.9, 127.8, 121.9, 119.5, 114.7 (the signal of the
carbon bound to the deuterium is not observed); MS m/
z (relative intensity): 222 (43, Mꢂ), 221 (100), 192 (17),
191 (14), 166 (22), 165 (23); HRMS Calc. for
C15H10DNO: 222.0903, Found: 222.0906.
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