A new protocol for the consecutive α- and β-activation of propiolates towards electrophiles, involving conjugate addition of tertiary amines and intramolecular silyl migration

Article abstract of DOI:10.1002/chem.200500175

Herein, we present a novel approach for the consecutive α- and β-activation of conjugated alkynes and demonstrate the application of this methodology towards the C-C bond-forming reactions of propiolates. This new concept is based on the 1,4-addition of a

Full text of DOI:10.1002/chem.200500175

A New Protocol for the Consecutive a- and b-Activation of Propiolates
towards Electrophiles, Involving Conjugate Addition of Tertiary Amines and
Intramolecular Silyl Migration
Yuji Matsuya, Kousuke Hayashi, and Hideo Nemoto*[a]
Abstract: Herein, we present a novel
approach for the consecutive a- and b-
activation of conjugated alkynes and
demonstrate the application of this
combination of methyl 3-trimethylsilyl-
propiolate, 1,4-diazobicyclo-
[2.2.2]octane (DABCO), and aromatic
aldehydes brought about domino-type
manding aromatic aldehyde, 2,6-dime-
thylbenzaldehyde, produced alkyne de-
rivatives as the sole products from the
reaction, presumably, by the reaction
pathway common to the first cases. The
intramolecular version of the reaction
was successfully applied to the cycliza-
tion of trimethylsilylpropiolic esters de-
rived from salicylaldehydes, leading to
a new formylcoumarin synthesis. Stud-
ies of the reaction mechanisms are also
described.
À
À
methodology towards the C C bond-
C C bond formations to afford highly
forming reactions of propiolates. This
new concept is based on the 1,4-addi-
tion of a tertiary amine to a conjugated
alkyne, followed by an aldol-type addi-
tion to an aldehyde and subsequent in-
tramolecular silyl migration. This se-
quential process is generally applicable
for 3-trimethylsilylpropiolates. The
functionalized olefins as the major
products. On the other hand, aliphatic
aldehydes, including the sterically de-
Keywords: alkynes
reactions formylcoumarins
silyl-migration · tertiary amines
·
domino
·
·
Introduction
philes can be achieved at both the a- and b-positions de-
pending upon the reaction conditions (Scheme 1).
Alkynes conjugated with an electron-withdrawing group or
groups (EWG) have been recognized as very versatile tools
in organic synthesis, because of their ability to undergo a va-
riety of carbon–carbon or carbon–heteroatom bond-forming
reactions.[1] The ability of these compounds to act as Mi-
chael acceptors towards nucleophiles has been well-docu-
mented,[2] and this type of conjugate addition reaction has
often been catalyzed by trialkylphosphines or tertiary
amines.[3] In particular cases, the phosphine-catalyzed system
has been reported to bring about “umpolung”, which facili-
tates an abnormal nucleophilic attack at the a-position to
form a phosphonium ylide. This unique reaction pattern has
been applied to the synthesis of dehydroamino acids[4] and
several substituted furan derivatives.[5] Consequently, the
catalytic activation of conjugated alkynes toward nucleo-
Scheme 1. Phosphine-catalyzed a- or b-activation of alkynes towards nu-
cleophiles.
Anionic b-activation of terminal alkynes has been conven-
tionally achieved by direct deprotonation; this method takes
advantage of the relatively low pKa value of the proton at-
tached to the sp carbon. However, the formation of these
acetylides requires the use of a stoichiometric amount of a
strong metal base.[1,6] Recently, methods for the mild and
metal-free catalytic b-activation of conjugated terminal al-
kynes by indirect deprotonation using tertiary amines or
phosphines have been reported; these methods provide effi-
cient syntheses for propargylic alcohol,[7] 1,3-dioxolane,[7]
and tetronic acid derivatives.[8] Anionic a-activation of con-
jugated alkynes is based upon the formation of an allene–
[a] Dr. Y. Matsuya, K. Hayashi, Prof. H. Nemoto
Faculty of Pharmaceutical Sciences
Toyama Medical and Pharmaceutical University
2630 Sugitani, Toyama 930–0194 (Japan)
Fax : (+81)76-434-5047
E-mail: nemotoh@ms.toyama-mpu.ac.jp
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
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DOI: 10.1002/chem.200500175
Chem. Eur. J. 2005, 11, 5408 –5418

FULL PAPER
enolate, which is produced either by the Michael-type addi-
tion of particular nucleophiles[9] or by hydrometalation[10]
followed by reaction with electrophiles. A Lewis acid medi-
ated Chalcogeno–Morita–Baylis–Hillman reaction,[11] an
amine-catalyzed reaction of acetylenedicarboxylates with al-
dehydes or imines,[12] and a phosphine-assisted intramolecu-
lar cycloaddition reaction[13] have been also reported. Thus,
various activation methods are applicable for conjugated al-
kynes, increasing their versatility as a synthetic tool.
Results and Discussion
The intermolecular reaction: After taking both the silyl
groupꢁs migrating ability and its affinity to oxygen into con-
sideration, we chose 3-silylated propiolates as potential sub-
strates for the reaction (Scheme 2) The simplest one, methyl
3-trimethylsilylpropiolate (1a) was treated with the tertiary
amine 1,4-diazobicyclo[2.2.2]octane (DABCO) in refluxing
benzene. After five hours under these conditions the propio-
late 1a was completely recovered (Table 1, entry 1). In the
As mentioned previously, treatment of conjugated termi-
nal alkynes with tertiary amines brings about self-dimeriza-
tion[14] or a domino process in the presence of aldehydes
under suitable reaction conditions.[7] Since these reactions
are triggered by anionic b-activation through indirect depro-
tonation of the terminal alkynes, the introduction of an ap-
propriate substituent at the b-position would prevent such
reactions and enable simple a-activation to occur, by the
conjugate addition of a tertiary amine. Although such
amine-catalyzed processes, including subsequent reactions
with aldehydes, relate to the Morita–Baylis–Hillman reac-
tion of conjugated alkenes, which involves b-elimination for
regeneration of the amine catalysts,[15] conjugated alkynes
cannot participate in the b-elimination process owing to the
lack of an a-proton. However, we envisaged that b-activa-
tion might be possible, provided that the substituent at the
b-position was able to migrate onto the alkoxide group in an
intramolecular fashion. If this did prove possible, novel con-
secutive a- and b-activation of conjugated alkynes toward
electrophiles could be realized (Scheme 2).
Table 1. Reaction of silylated propiolates 1 with DABCO in the presence
(or absence) of an aromatic aldehyde.[a]
Entry
Substrate
t [h]
Yield [%][b]
Ratio (2:3)
1[c]
2
3
1a
1a
1b
1c
5
0.666
18
complete recovery of 1a
–
78
41
78:22
37:63
–
4
24
no reaction
[a] The reaction was carried out using the selected aldehyde (0.5 mmol),
propiolate (1 mmol), and DABCO (1 mmol) under an Ar atmosphere.
[b] Isolated yields (2 + 3) based on the aldehyde. [c] In the absence of
aldehyde (control experiment).
presence of an aromatic aldehyde, however, rapid consump-
tion of the aldehyde was observed and two products were
produced (entry 2); these were separated and purified by
column chromatography. The NMR spectra of these prod-
ucts clearly showed the presence of one methyl ester and
two aromatic constituents, suggesting that the products were
composed of the propiolate and the aldehyde in a 1:2
manner. The structure of the major product 2 was confirmed
by the spectral data, which included a 2D NMR spectrum,[17]
and the geometry of the olefin was determined by an NOE
experiment between the olefinic proton and the methyne
proton. More sterically demanding substrates (1b and 1c)
were also utilized, but a considerable decrease in the reac-
tion rate was observed in these cases as shown by entries 3
and 4. Although 1b produced the corresponding products 2
and 3, the product ratio was reversed as a result of the pro-
longed reaction time.
Scheme 2. Our new concept for the consecutive a- and b- activation of al-
kynes towards electrophiles.
The experiment shown in Scheme 3 verified that product
3 arose from product 2. Exposure of the isolated sample of
Based on this concept, we have found a new domino-type
À
C C bond forming reaction between propiolates and alde-
hydes, which is mediated by tertiary amines (metal-free and
traceless activators).[16] Herein we describe, details of our
studies into these reactions, and their application towards
the synthesis of formylcoumarin.
Scheme 3. Conversion of product 2 into product 3.
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H. Nemoto et al.
Table 2. Investigation into the optimum reaction conditions required for
the synthesis of 2.
compound 2 to DABCO in refluxing benzene resulted in its
gradual conversion to compound 3. This transformation can
be explained by base-induced isomerization of the double
bond followed by hydrolysis of the resulting silyl enol ether.
Thus, this new reaction, involving the simultaneous forma-
À
tion of two C C bonds, potentially provides a new general
method for preparing multifunctionalized olefins 2 by con-
trolling the reaction time.
Entry Amine
Solvent Conditions
Yield [%] Ratio (2:3)
1
2
Et3N
DBU
benzene reflux, 2 h
benzene reflux, 2 h
benzene reflux, 3 h
0
–
With these findings in our hands, we focused on optimiz-
ing the reaction conditions. Various trigger nucleophiles and
solvents were tested with the propiolate 1a and benzalde-
hyde (Table 2). As a nucleophile, triethylamine was inert
under the reaction conditions and 1,8-diazabicyclo-
[5.4.0]undec-7-ene (DBU) produced a poor result (entries 1
and 2). Although quinuclidine and 3-quinuclidinol afforded
moderate to good yields, the saturated product 3 was also
formed as a result of the relatively slow reaction rate (en-
tries 3 and 4). DABCO, with its bicyclo[2.2.2]octane skele-
ton, was the most promising nucleophile among the tertiary
amines (entry 5). Heating was
11
68
43
73
0
100:0
21:79
37:63
74:26
–
3
quinuclidine
4
3-quinuclidinol benzene reflux, 2 h
5
6
7
8
9
10
DABCO
DABCO
DABCO[a]
DABCO
DABCO
DABCO
benzene reflux, 40 min
benzene RT, 24 h
benzene reflux, 4 h
62
24
4
63:37
100:0
100:0
100:0
THF
DCE[b] reflux, 40 min
DMF RT, 2 h
reflux, 40 min
10
[a] A catalytic amount (10 mol% to aldehyde) of DABCO was used. All
other experiments were carried out using 2 equiv of amine. [b] 1,2-di-
chloroethane.
found to be required for suffi-
Table 3. Reaction of propiolate 1a with various aldehydes under the optimum conditions.[a]
cient progress of the reaction
(entry 6). By using 10 mol% of
DABCO (entry 7), a compara-
ble yield to entry 5 was ob-
tained, implying that DABCO
participated in the reaction in a
Entry
R
t [min]
Yield [%] of (2+3)
Ratio (2:3)[b]
Yield [%] of 4
catalytic fashion; although
a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
Ph
40
40
50
40
40
45
50
30
120
30
73
56
64
74:26
100:0
78:22
78:22
100:0
76:24
83:17
100:0
100:0
63:37
37:63
–
0
0
0
0
0
0
0
0
0
prolonged reaction time caused
a decrease in the amount of the
olefin product 2 isolated. Sever-
al other solvents such as THF,
1,2-dichloroethane, and DMF
were also utilized, but were
found to be ineffective for the
reaction (entries 8–10).
For the next step in our
study, these reactions were per-
formed under optimum condi-
tions with a variety of different
aldehydes in order to evaluate
the generality of the synthetic
process. Various aromatic alde-
hydes were observed to proceed
in a similar manner through the
2-Me-C6H4
3-Me-C6H4
4-Me-C6H4
2-MeO-C6H4
3-MeO-C6H4
4-MeO-C6H4
2-Br-4,5-(MeO)2-C6H2
1-naphthyl
2-naphthyl
4-Cl-C6H4
4-NO2-C6H4
pentafluorophenyl
2,6-(Me)2-C6H3
nPr
78
quant.[c]
50
83
51
44
72
0
0
40
43
120
120
60
50
40
0[d]
0[d]
0
0[d]
0[d]
–
–73
–63
–78
0
0
0
iPr
tBu
30
–94
[a] The reactions were carried out using the selected aldehyde (0.5 mmol), propiolate (1 mmol), and DABCO
(1 mmol) in benzene (1 mL) under an Ar atmosphere. [b] These products could be separated by column chro-
matography. [c] Isolated in a desilylated form. [d] Afforded a complex mixture.
À
successive C C bond-forming
processes, yielding highly func-
tionalized olefins 2 as a major products with exclusive ster-
eoselectivity (Table 3, entries 1–10). One notable feature
was that ortho-substituted benzaldehydes did not produce
compound 3, presumably because of the inefficiency of the
isomerization due to steric repulsion between the ortho and
allylic substituents. 4-Chlorobenzaldehyde, a slightly elec-
tron-deficient substrate, afforded predominantly product 3k
on a comparable timescale (entry 11), probably due to the
higher acidity of the benzylic methyne proton in the initial
product 2k. Highly electron-deficient aromatic aldehydes
such as 4-nitro and perfluoro derivatives did not produce
any of the products already identified, despite the fact that
the aldehydes were completely consumed in the reaction
(entries 12 and 13). A notable change in the course of the
reaction was observed upon the use of 2,6-dimethylbenzal-
dehyde (entry 14). The products 2n and 3n were not detect-
ed in the reaction, and instead the alkyne 4n was produced
as the sole product from the reaction in high yield. Similarly,
aliphatic aldehydes were found to afford only the alkyne
products 4o–q (entries 15–17). This dramatic change, which
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À
Domino C C Bond Formations
FULL PAPER
depends upon the structure of aldehydes, has provided us
with a greater insight into the reaction mechanism (vide
infra).
We propose the following reaction mechanism (Scheme 4)
for this new domino-type process on the basis of several of
our experimental results. The reaction of ethyl 2-butynoate
to the olefin carbon may have affected the equilibrium
could not be ruled out. However, the alkylidenecarbene 8
seems to be an important potential precursor for the alkyne
products 4, as such 1,2-rearrangement reactions (path A)
are well-established processes and have significant prece-
dents.[20,21] When the alkyne 4d (R=pTol)[22] was reacted
with p-tolualdehyde and DABCO, immediate decomposition
occurred to form a complicated mixture, the NMR spectrum
of which showed no existence of the olefin product 2d;
whereas the alkyne 4q (R=tBu) was recovered unchanged
under the same conditions (Scheme 6). These results clearly
Scheme 6. Reactivity of alkynes 4 d and 4 q.
suggest that the alkyne 4 is not a precursor of the olefin 2,
but is a dead end product of the reaction, although the sta-
bility of this compound depends upon the nature of the sub-
stituent R. One possible explanation to account for the for-
À
mation of the olefin 2 is that a direct C H insertion of the
aldehyde onto the alkylidenecarbene 8 (path B) occurs. In
general, the reaction of carbenes and aldehydes has been re-
ported to result in the formation of oxirane or dioxorane de-
rivatives via carbonium ylides;[23] this is also the case for al-
kylidenecarbenes,[20] and such direct insertion processes of
aldehydes have not yet been observed. In addition, we can
provide no explanation for the complete change of the reac-
tion course (path A or B), via the common carbene inter-
mediate 8, with the structure of the aldehydes. It is not clear
from the available data whether path B is a good model for
the present reaction or not. Thus, we propose the more
plausible reaction pathway, path C, which includes nucleo-
philic addition of the anion center of the ylide 7 to the alde-
hyde, followed by an intramolecular 1,2-hydride shift to pro-
duce the olefin 2. Path C would have an advantage over
path A, provided that the equilibrium between 7 and 8 is
fully biased towards the ylide form 7, and the hydride shift
would result in the extrusion of the tertiary amine through
an addition–elimination process in a 1,4-fashion. It is impor-
tant to note that we regard all of the transformations men-
tioned above (from 1a to 8 or 9) as a sequence of reversible
processes, as this assumption allows us to rationalize that
the susceptibility of the intermediate 9 to the irreversible
1,2-hydride shift may control the direction of the reaction
towards either product 2 or 4, respectively. As shown in
Table 3, relatively electron-rich aromatic aldehydes afforded
product 2 (and in some cases product 3) in good overall
yields, whereas highly electron-poor aldehydes produced
neither products 2 or 4 and instead afforded complicated
mixtures. These results imply that the former substrates
have considerably faster reaction rates for the hydride shift
compared to the latter, presumably, because the transition
states are effectively stabilized by donation from the p-elec-
Scheme 4. Proposed reaction mechanism.
or 1-trimethylsilyl-1-propyne with benzaldehyde and
DABCO under identical conditions resulted in the complete
recovery of all of the substrates (Scheme 5). This fact indi-
Scheme 5. Other alkyne reactions.
cates that both the TMS and electron-withdrawing carbonyl
groups are essential for the progress of the reaction. Thus,
the sequence starting with the 1,4-addition of the trigger nu-
cleophile, followed by an aldol-type addition to the alde-
hyde and subsequent silyl migration is a plausible proposal
for the initial process. This process also includes the consec-
utive a- and b-activation of the propiolate as expected. The
ammonium ylide intermediate 7, thus formed, possibly equi-
librates with the a-silyloxy alkylidenecarbene 8,[18] which
arises from a net a-elimination of the tertiary amine. With
regard to the ammonium ylide/alkylidenecarbene equilibri-
um, it has been reported that the large polarization value
and the high dissociation energy barrier of the ammonium
ylide, estimated by the MOPAC program with 2-propylide-
necarbene and trimethylamine as simplified model mole-
cules, make the ylide form much more stable than the corre-
sponding carbene.[19] Accordingly, we presumed that the
equilibrium between 7 and 8 lay mostly to the ylide form 7,
although the possibility that the functional groups attached
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H. Nemoto et al.
tron system of the p orbital on the aromatic ring into the
the two reaction sites for the cyclization, the formyl group
and the alkyne part. The substrates (10a–f) were prepared
from substituted salicylaldehydes and 3-trimethylsilylpro-
piolic acid in moderate to good yields (52–88%) using 1-(3-
s*CÀ orbital at the benzylic position. Otherwise, especially
H
in the case of the latter substrates, the reaction would favor
path A producing the alkyne 4, which may decompose due
to its inherent instability under the reaction conditions to
afford the complex mixtures observed. The fact that the ali-
phatic aldehydes produced alkynes 4 exclusively might also
have been explained in the same manner, except that the al-
kynes 4, thus formed, are stable under the reaction condi-
tions. In the case of 2,6-dimethylbenzaldehyde, exclusive for-
mation of 4 was also observed;[24] this can be rationalized by
postulating that the effective p–s* interaction in the hy-
dride-shift transition state may have been impeded by di-
minished coplanarity of the aromatic plane with the plane of
the conjugated olefin (hydride acceptor); this would be en-
forced by the steric repulsion of the two ortho-substituents.
Alternatively, there is a possibility that the intermediate 7
could not react with the sterically congested 2,6-dimeth-
ylbenzaldehyde to afford the alkyne product 4 through
path A.
Recently, an acylation reaction of a vinylselenonium ylide
with an aromatic aldehyde has been reported.[25] The overall
process involved in this reaction is similar to the last step of
our reaction (from 7 to 2). The mechanism proposed in this
report involves the intermediacy of an allenoate anion origi-
nating from a betaine (corresponding to 9) produced by b-
elimination of selenide through base-induced deprotonation.
This mechanism was deduced from the observation that no
deuterium was incorporated in the product of the reaction
when using benz[D]aldehyde as a substrate. However, when
our reaction was performed using benz[D]aldehyde, com-
plete incorporation of deuterium into the products 2 and 3
was observed (Scheme 7). This deuterium was entirely re-
dimethylaminopropyl)-3-ethylcarbodiimide
hydrochloride
(EDCI) and 4-dimethylaminopyridine (DMAP).[26] When
the parent substrate 10a was allowed to react with two
equivalents of DABCO in refluxing benzene, the cyclization
produced the 3-formylcoumarin 11a in
a 63% yield
(Table 4, entry 1). Unlike the intermolecular reaction, when
Table 4. Formylcoumarin-forming reactions.
Entry
R[a]
Amine
Solvent
t [h]
Yield
[%][b]
1
2
3
4
5
6
7
8
9
a
a
a
a
a
b
c
d
e
f
H
H
H
H
DABCO
DABCO
DABCO
DABCO
quinuclidine
DABCO
DABCO
DABCO
quinuclidine
DABCO
benzene
DCE[c]
DMF[d]
THF
THF
THF
benzene
THF
THF
8
5
63
62
39
64
64
81
47
46
50
26
0.5
3
0.666
2.5
7
H
5-Me
5-MeO
4-MeO
5,6-benzo
5-Cl
1
0.333
1
10
THF
[a] The numbering on the aromatic ring starts from the carbon bearing
the formyl group and proceeds clockwise. [b] Isolated yields. [c] 1,2-Di-
chloroethane. [d] The reaction was performed at 808C.
other solvents were used for the reaction comparable yields
were obtained (entries 2–4), with the combination of THF
and quinuclidine bringing about a superior result with re-
gards to reaction rate (entry 5). The results of the coumarin-
forming reactions for variously substituted compounds
under optimum conditions are summarized in Table 4 (en-
tries 5–10). In all cases the 3-formylcoumarin derivatives
were produced in moderate to good yields with the excep-
tion of the chloro-substituted compound 10 f, which afforded
product 11 f in a low yield as a result of the competitive
cleavage of the ester bond.
The coumarin nucleus is widely found in nature, and bio-
logically significant activities of coumarin derivatives have
made the development of new methodologies for the mild
and concise construction of the coumarin nucleus impor-
tant.[27] Although there are well-established methods based
on Pechmann condensation or Knoevenagel condensation,
the harsh reaction conditions involved limit the scope of
these reactions and the functional group compatibility.
Recent reports on coumarin formation utilizing the Morita–
Baylis–Hillman reactions of salicylaldehydes with acrylates
suffer from a lack of regiocontrol in the cyclization step
(coumarins or chromenes) and produce low yields of target
compounds.[28] In particular, efficient approaches for the syn-
Scheme 7. Experiments using benz[D]aldehyde.
tained in product 2 even in the presence of an excess
amount of a proton source, such as MeOH, in the reaction
medium. In addition, the use of electron-rich aromatic alde-
hydes has been reported to decrease the acylation efficiency
of the vinylselenonium ylide, which is opposite to the ten-
dency found in our reaction. These contrasts strongly indi-
cate that our reaction involves the hydride shift mechanism,
instead of deprotonation.
The intramolecular reaction: Following studies on this
domino-type reaction focused on the intramolecular varia-
tion. For this purpose, trimethylsilylpropiolic esters derived
from salicylaldehydes were chosen as substrates on the basis
of their ready availability and the suitable distance between
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À
Domino C C Bond Formations
FULL PAPER
thesis of 3-formylcoumarins are quite limited.[29] The reac-
tion described here may provide a new and general method-
ology for the synthesis of 3-formylcoumarins.
and subsequent transformation would afford the formylcou-
marin 11 via the acylsilane 17.[30] Additionally, there is a pos-
sibility that the products 11a–f arise from an intramolecular
À
A
similar reaction mechanism to that depicted in
C H insertion reaction (formation of 18) followed by a rear-
À
Scheme 4 is proposed for the coumarin-forming reaction
(Scheme 8). After the cyclization, subsequent silyl migration
rangement, as the intramolecular C H insertion of alkylide-
necarbenes is a well-known process.[31]
However, these possibilities were excluded by the follow-
ing experiments. Firstly, the acylsilane 17[32] was exposed to
the coumarin forming conditions (DABCO, benzene,
reflux), but was recovered unchanged by the reaction condi-
tions (Scheme 10). Secondly, deuterated salicylaldehyde[33]
Scheme 8. A plausible reaction mechanism for the formation of the for-
mylcoumarins.
gives the ammonium ylide 14 (or the carbene 15), which
reacts with water to form the formylcoumarin concomitant
with silanol elimination. The ylide 14 did not participate in
the reaction with another aldehyde, even when an equimolar
amount of benzaldehyde was present in the reaction mix-
ture. The decreased flexibility in the conformation of the
ylide 14 compared to ylide 7 is the most likely explanation
for this distinct difference between the intra- and the inter-
molecular reactions.
Scheme 10. Experiments conducted to clarify the reaction mechanism of
formylcoumarin formation.
was transformed into the substrate [D]10a (60% D-incorpo-
ration), which upon treatment with DABCO in refluxing
benzene generated the formylcoumarin [Da]11a, the deuteri-
um in which was retained on the same carbon as the sub-
strate. These results unambiguously verified that the formyl-
coumarin-forming reaction did not involve the pathways
shown in Scheme 9.
The fact that the formyl hydrogen in the products 11a–f
originated from an external proton sources was confirmed
by the experiment shown in Scheme 11. When the reaction
Other possible reaction pathways leading to the formyl-
coumarins 11 are illustrated in Scheme 9. A bond-insertion
process is one of the principal features of alkylidenecarbene
Scheme 11. Coumarin-forming reaction in the presence of [D4]MeOH.
Scheme 9. Alternative reaction pathways for formylcoumarin formation.
was performed in the presence of a small amount of
[D4]MeOH, the deuterium was incorporated into the formyl
group of the product.[34] Although we initially expected that
a deuterated enol ether product 19 would be formed, we
could not trap it because of its immediate hydrolysis in the
workup process. The mechanism above suggests that water
is essential to regenerate the tertiary amine. In fact, the re-
action using 10 mol% of the amine was very sluggish in the
absence of water, while addition of water into the reaction
reactions, and is a feature that is attributed to their strongly
electrophilic nature.[20] For example, the O Si insertion reac-
À
tions of several b-silyloxy alkylidenecarbenes to form silylat-
ed dihydrofurans has been reported.[18] If a similar insertion
reaction occurs in our case, the alkylidenecarbene 15 may
be transformed into an oxetene intermediate 16, which can
be also derived from the betaine 13 by an addition–elimina-
tion process. Electrocyclic ring-opening of the oxetene 16
Chem. Eur. J. 2005, 11, 5408 –5418
www.chemeurj.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5413

H. Nemoto et al.
(10%), and a color change noted from brown to pale yellow. The organic
layer was then washed with brine and dried over MgSO4. After evapora-
tion of the solvent the residue was purified by silica-gel column chroma-
tography (CH2Cl2 then 10% AcOEt/CH2Cl2), which afforded the prod-
ucts 2, 3, or 4 as a colorless oils. The yields from these reactions are
listed in Table 3.
medium improved the yield of the 3-formylcoumarin by up
to 50% (Table 5).
Table 5. The effect of water on the catalytic activity of amines.
Methyl
(Z)-4-oxo-4-phenyl-2-[phenyl(trimethylsilyloxy)methyl]but-2-
enoate (2a): 1H NMR (CDCl3): d=À0.03 (s, 9H), 3.41 (s, 3H), 5.56 (d,
J=1.7 Hz, 1H), 6.12 (d, J=1.7 Hz, 1H), 7.17–7.31 (m, 7H), 7.43 (t, J=
7.3 Hz, 1H), 7.66 ppm (d, J=8.1 Hz, 2H); 13C NMR (CDCl3): d=À0.31,
51.55, 75.48, 117.55, 126.86, 128.11, 128.17, 128.38, 128.47, 132.88, 136.31,
139.68, 159.82, 165.55, 197.13 ppm; IR (neat): n˜ =1724, 1669 cmÀ1; MS
(EI): m/z: 368 [M]+; HRMS: calcd for C21H24O4Si: 368.1444 [M]+;
found: 368.1443.
Methyl 2-benzoyl-4-oxo-4-phenylbutyrate (3a): 1H NMR (CDCl3): d=
3.10 (d, J=6.4 Hz, 2H), 3.70 (s, 3H), 5.80 (t, J=6.4 Hz, 1H), 7.46 (t, J=
7.3 Hz, 4H), 7.58 (t, J=7.3 Hz, 2H), 7.97 ppm (d, J=7.3 Hz, 4H);
13C NMR (CDCl3): d=33.18, 52.25, 52.28, 128.64, 128.94, 133.77, 135.34,
171.82, 195.11 ppm; IR (neat): n˜ =1729, 1686 cmÀ1; MS (EI): m/z: 296
[M]+; HRMS: calcd for C18H16O4: 296.1049 [M]+; found: 296.1046.
Entry
Amine
Additive
t [h]
Yield [%]
1
2
3
4
DABCO
DABCO
DABCO
MS4Š
none
H2O (1 equiv)
H2O (1 equiv)
24
24
24
2
8
24
43
50
quinuclidine
Conclusion
Methyl (Z)-4-oxo-4-(2-methylphenyl)-2-[(2-methylphenyl)(trimethylsilyl-
oxy)methyl]but-2-enoate (2b): 1H NMR (CDCl3): d=À0.07 (s, 9H), 2.29
(s, 3H), 2.61 (s, 3H), 3.41 (s, 3H), 5.82 (brs, 1H), 5.83 (d, J=1.3 Hz,
1H), 7.06–7.22 (m, 5H), 7.32 (t, J=7.3 Hz, 1H), 7.44 (d, J=7.7 Hz, 1H),
7.52 ppm (d, J=7.7 Hz, 1H); 13C NMR (CDCl3): d=À0.40, 19.05, 21.54,
51.45, 72.72, 118.43, 125.09, 126.15, 127.78, 128.00, 130.52, 131.56, 131.59,
131.75, 135.25, 135.57, 137.88, 139.83, 159.85, 165.67, 198.56 ppm; IR
(neat): n˜ =1725, 1667 cmÀ1; MS (EI): m/z: 396 [M]+; HRMS: calcd for
C23H28O4Si: 396.1757 [M]+; found: 396.1759.
In this paper, we described the novel consecutive activation
of conjugated alkynes mediated by tertiary amines. The key
step in these reactions involves an intramolecular migration
of the silyl group. Our intended application of these reac-
tions is in the preparation of multifunctionalized olefins
À
through domino-type C C bond formations by using aro-
matic aldehydes. In addition, it was found that the reaction
was applicable to an intramolecular version, which has lead
to a new 3-formylcoumarin synthesis. However, it is worth
noting that the second reaction partner in this synthesis was
not an aldehyde but water. As a result of our studies it has
been shown that the silylated propiolates have great poten-
tial as a versatile tool in organic synthesis. The concept de-
scribed here could, we believe, open new possibilities for
the chemistry of conjugated alkynes. Further synthetic appli-
cations of the reaction provided by this work are currently
underway in our laboratory, and will be reported in due
course.
Methyl (Z)-4-oxo-4-(3-methylphenyl)-2-[(3-methylphenyl)(trimethylsilyl-
oxy)methyl]but-2-enoate (2c): 1H NMR (CDCl3): d=À0.01 (s, 9H), 2.25
(s, 3H), 2.29 (s, 3H), 3.45 (s, 3H), 5.51 (d, J=1.7 Hz, 1H), 6.15 (d, J=
1.7 Hz, 1H), 6.99 (d, J=7.3 Hz, 1H), 7.04–7.12 (m, 3H), 7.18 (t, J=
7.7 Hz, 1H), 7.24 (d, J=7.3 Hz, 1H), 7.45–7.47 ppm (m, 2H); 13C NMR
(CDCl3): d=À0.27, 21.17, 21.27, 51.54, 75.48, 117.15, 123.95, 125.84,
127.47, 127.92, 128.17, 128.83, 128.92, 133.68, 136.26, 137.73, 137.94,
139.57, 160.27, 165.63, 197.27 ppm; IR (neat): n˜ =1725, 1668 cmÀ1; MS
(EI): m/z: 396 [M]+; HRMS: calcd for C23H28O4Si: 396.1757 [M]+;
found: 396.1759.
Methyl
2-(3-methylbenzoyl)-4-oxo-4-(3-methylphenyl)butyrate
(3c):
1H NMR (CDCl3): d=2.38 (s, 6H), 3.08 (d, J=6.8 Hz, 2H), 3.70 (s, 3H),
5.77 (t, J=6.8 Hz, 1H), 7.33 (t, J=7.7 Hz, 2H), 7.39 (d, J=7.7 Hz, 2H),
7.76 (d, J=7.7 Hz, 2H), 7.79 ppm (s, 2H); 13C NMR (CDCl3): d=21.33,
33.27, 52.19, 52.42, 125.83, 128.74, 129.16, 134.49, 134.52, 135.45, 138.81,
171.90, 195.33 ppm; IR (neat): n˜ =1738, 1695 cmÀ1; MS (EI): m/z: 324
[M]+; HRMS: calcd for C20H20O4: 324.1361 [M]+; found: 324.1360.
Experimental Section
Methyl (Z)-4-oxo-4-(4-methylphenyl)-2-[(4-methylphenyl)(trimethylsilyl-
oxy)methyl]but-2-enoate (2d): 1H NMR (CDCl3): d=À0.04 (s, 9H), 2.28
(s, 3H), 2.35 (s, 3H), 3.43 (s, 3H), 5.52 (d, J=1.7 Hz, 1H), 6.09 (d, J=
1.7 Hz, 1H), 7.05 (d, J=8.1 Hz, 2H), 7.12 (d, J=8.1 Hz, 2H), 7.15 (d, J=
8.1 Hz, 2H), 7.60 ppm (d, J=8.1 Hz, 2H); 13C NMR (CDCl3): d=0.00,
21.37, 21.92, 51.79, 75.58, 117.61, 127.10, 128.93, 129.15, 129.29, 134.29,
137.02, 138.07, 143.91, 160.45, 165.92, 197.00 ppm; IR (neat): n˜ =1725,
General remarks: All nonaqueous reactions were carried out under an
Ar atmosphere. Reagents were purchased from commercial sources and
used as received. Anhydrous solvents were prepared by distillation over
1
CaH2 or purchased as high-grade reagents. H and 13C NMR spectra were
obtained on a Varian Gemini 300 (300 MHz for 1H and 75.46 MHz for
13C NMR spectra) instrument or a Varian UNITY plus 500 (500 MHz for
1H and 125 MHz for 13C) instrument, using tetramethylsilane or chloro-
form as an internal reference. Mass spectra were recorded on a JEOL D-
200 or a JEOL AX 505 mass spectrometer, and the ionization method
was electron impact (EI, 70 eV). IR spectra were recorded on a Perkin–
Elmer 1600 spectrometer. Melting points were taken using a Yanagimoto
micro melting point apparatus and are uncorrected. Column chromatog-
raphy was carried out by employing Cica Silica Gel 60N (spherical, neu-
tral, 40–50 mm or 63–210 mm).
1667 cmÀ1 MS (EI): m/z: 396 [M]+; HRMS: calcd for C23H28O4Si:
;
396.1757 [M]+; found: 396.1756.
Methyl 2-(4-methylbenzoyl)-4-oxo-4-(4-methylphenyl)butyrate (3d):
1H NMR (CDCl3): d=2.40 (s, 6H), 3.08 (d, J=6.9 Hz, 2H), 3.69 (s, 3H),
5.75 (t, J=6.9 Hz, 1H), 7.25 (d, J=8.2 Hz, 4H), 7.88 ppm (d, J=8.2 Hz,
4H); 13C NMR (CDCl3): d=21.63, 33.25, 52.14, 128.74, 129.56, 132.86,
144.68, 171.90, 194.74 ppm; IR (neat): n˜ =1737, 1692 cmÀ1; MS (EI): m/z:
324 [M]+; HRMS: calcd for C20H20O4: 324.1361 [M]+; found: 324.1361.
Methyl (Z)-4-oxo-4-(2-methoxyphenyl)-2-[hydroxy-(2-methoxyphenyl)-
methyl]but-2-enoate (2e): 1H NMR (CDCl3): d=3.47 (s, 3H), 3.73 (s,
3H), 3.76 (s, 3H), 5.82 (d, J=1.3 Hz, 1H), 5.90 (d, J=1.3 Hz, 1H), 6.81
(d, J=7.7 Hz, 1H), 6.88–6.98 (m, 3H), 7.22–7.30 (m, 2H), 7.44 (ddd, J=
9.0, 7.3, 2.1 Hz, 1H), 7.82 ppm (dd, J=7.7, 1.7 Hz, 1H); 13C NMR
(CDCl3): d=51.41, 55.12, 55.59, 71.39, 110.44, 112.02, 115.89, 120.56,
General procedure for the reaction of propiolate 1a with aldehydes: A
solution of methyl 3-trimethylsilylpropiolate (156 mg, 1 mmol),[35] alde-
hyde (0.5 mmol), and DABCO (112 mg, 1 mmol) in anhydrous benzene
(1 mL) was refluxed for 0.5–2 h. After this time, the reaction mixture was
cooled to room temperature and diluted with CH2Cl2 (20 mL) producing
a
brown solution. This solution was washed with hydrochloric acid
5414
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 5408 –5418

À
Domino C C Bond Formations
FULL PAPER
120.76, 125.91, 127.57, 128.13, 129.26, 131.20, 134.50, 156.48, 159.07,
161.56, 165.89, 194.82 ppm; IR (neat): n˜ =3485, 1722, 1655 cmÀ1; MS
(EI): m/z: 356 [M]+; HRMS: calcd for C20H20O6: 356.1260 [M]+; found:
356.1261.
J=8.5, 1.7 Hz, 2H), 8.58 ppm (s, 2H); 13C NMR (CDCl3): d=33.53,
52.30, 52.58, 124.07, 126.97, 127.76, 128.92, 128.94, 129.71, 130.59, 132.43,
132.77, 135.80, 172.01, 195.09 ppm; IR (neat): n˜ =1735, 1692 cmÀ1; MS
(EI): m/z: 396 [M]+; HRMS: calcd for C26H20O4: 396.1362 [M]+; found:
396.1353.
Methyl (Z)-4-oxo-4-(3-methoxyphenyl)-2-[(3-methoxyphenyl)(trimethyl-
silyloxy)methyl]but-2-enoate (2 f): 1H NMR (CDCl3): d=0.00 (s, 9H),
3.42 (s, 3H), 3.71 (s, 3H), 3.74 (s, 3H), 5.55 (d, J=1.6 Hz, 1H), 6.15 (d,
J=1.6 Hz, 1H), 6.73 (dt, J=7.4, 1.6 Hz, 1H), 6.83–6.86 (m, 2H), 6.99 (dt,
J=6.6, 2.7 Hz, 1H), 7.10–7.25 ppm (m, 4H); 13C NMR (CDCl3): d=
À0.23, 51.62, 55.17, 55.27, 75.33, 111.81, 112.20, 113.75, 117.61, 119.20,
119.96, 121.62, 129.13, 129.43, 137.65, 141.33, 159.38, 159.58, 159.70,
165.59, 196.84 ppm; IR (neat): n˜ =1725, 1671 cmÀ1; MS (EI): m/z: 428
[M]+; HRMS: calcd for C23H28O6Si: 428.1656 [M]+; found: 428.1652.
Methyl (Z)-4-oxo-4-(4-chlorophenyl)-2-[(4-chlorophenyl)(trimethylsilyl-
oxy)methyl]but-2-enoate (2k): 1H NMR (CDCl3): d=À0.03 (s, 9H), 3.47
(s, 3H), 5.52 (d, J=1.7 Hz, 1H), 6.06 (d, J=1.7 Hz, 1H), 7.21 (d, J=
9.0 Hz, 2H), 7.25 (d, J=8.5 Hz, 2H), 7.35 (d, J=9.0 Hz, 2H), 7.62 ppm
(d, J=8.5 Hz, 2H); 13C NMR (CDCl3): d=À0.32, 51.79, 74.79, 118.12,
128.14, 128.64, 128.73, 129.79, 134.13, 134.73, 138.21, 139.52, 158.95,
165.29, 195.83 ppm; IR (neat): n˜ =1725, 1673 cmÀ1; MS (EI): m/z: 436
[M]+; HRMS: calcd for C21H22Cl2O4Si: 436.0664 [M]+; found: 436.0664.
Methyl 2-(3-methoxybenzoyl)-4-oxo-4-(3-methoxyphenyl)butyrate (3 f):
1H NMR (CDCl3): d=3.09 (d, J=6.9 Hz, 2H), 3.70 (s, 3H), 3.80 (s, 6H),
5.76 (t, J=6.9 Hz, 1H), 7.12 (ddd, J=8.2, 2.4, 0.8 Hz, 2H), 7.36 (t, J=
8.2 Hz, 2H), 7.49 (t, J=2.4 Hz, 2H), 7.55 ppm (ddd, J=8.2, 2.4, 0.8 Hz,
2H); 13C NMR (CDCl3): d=33.24, 52.18, 52.37, 55.32, 112.60, 120.51,
121.07, 129.87, 136.61, 159.97, 171.72, 194.81 ppm; IR (neat): 1738,
1696 cmÀ1; MS (EI): m/z: 356 [M]+; HRMS: calcd for C20H20O6: 356.1260
[M]+; found: 356.1252.
Methyl
2-(4-chlorobenzoyl)-4-oxo-4-(4-chlorophenyl)butyrate
(3k):
1H NMR (CDCl3): d=3.09 (d, J=6.8 Hz, 2H), 3.70 (s, 3H), 5.67 (t, J=
6.8 Hz, 1H), 7.43 (d, J=8.5 Hz, 4H), 7.89 ppm (d, J=8.5 Hz, 4H);
13C NMR (CDCl3): d=33.10, 52.33, 52.35, 129.32, 129.97, 133.55, 140.48,
171.61, 193.70 ppm; IR (neat): n˜ =1734, 1697 cmÀ1; MS (EI): m/z: 364
[M]+; HRMS: calcd for C18H14Cl2O4: 364.0269 [M]+; found: 364.0271.
Methyl 4-(2,6-dimethylphenyl)-4-trimethylsilyloxy-2-butynoate (4n):
1H NMR (CDCl3): d=0.18 (s, 9H), 2.51 (s, 6H), 3.76 (s, 3H), 5.96 (s,
1H), 7.02 (d, J=7.7 Hz, 2H), 7.12 ppm (t, J=7.7 Hz, 1H); 13C NMR
(CDCl3): d=À0.11, 20.26, 52.58, 60.22, 76.18, 87.31, 128.25, 129.10,
135.31, 136.45, 153.81 ppm; IR (neat): n˜ =2233, 1718, 1253 cmÀ1; MS
(EI): m/z: 290 [M]+; HRMS: calcd for C16H22O3Si: 290.1338 [M]+;
found: 290.1332.
Methyl (Z)-4-oxo-4-(4-methoxyphenyl)-2-[(4-methoxyphenyl)-(trimethyl-
silyloxy)methyl]but-2-enoate (2g): 1H NMR (CDCl3): d=À0.03 (s, 9H),
3.45 (s, 3H), 3.74 (s, 3H), 3.82 (s, 3H), 5.50 (d, J=1.7 Hz, 1H), 6.11 (d,
J=1.7 Hz, 1H), 6.76 (d, J=9.0 Hz, 2H), 6.79 (d, J=9.0 Hz, 2H), 7.18 (d,
J=8.5 Hz, 2H), 7.65 ppm (d, J=8.5 Hz, 2H); 13C NMR (CDCl3): d=
À0.23, 51.56, 55.18, 55.35, 75.08, 113.42, 113.72, 116.90, 128.14, 129.67,
130.88, 131.93, 159.32, 160.24, 163.30, 165.73, 195.71 ppm; IR (neat): n˜ =
1724, 1659 cmÀ1; MS (EI): m/z: 428 [M]+; HRMS: calcd for C23H28O6Si:
428.1656 [M]+; found: 428.1652.
1
Methyl 4-trimethylsilyloxy-2-heptynoate (4o): H NMR (CDCl3): d=0.17
(s, 9H), 0.92 (t, J=7.2 Hz, 3H), 1.39–1.48 (m, 2H), 1.65–1.72 (m, 2H),
3.76 (s, 3H), 4.43 ppm (t, J=6.6 Hz, 1H); 13C NMR (CDCl3): d=À0.05,
13.57, 18.29, 39.70, 52.66, 61.99, 75.67, 88.91, 153.88 ppm; IR (neat): n˜ =
Methyl 2-(4-methoxybenzoyl)-4-oxo-4-(4-methoxyphenyl)butyrate (3g):
1H NMR (CDCl3): d=3.07 (d, J=6.8 Hz, 2H), 3.69 (s, 3H), 3.85 (s, 6H),
5.67 (t, J=6.8 Hz, 1H), 6.92 (d, J=9.0 Hz, 4H). 7.96 ppm (d, J=9.0 Hz,
4H); 13C NMR (CDCl3): d=33.40, 52.06, 52.17, 55.51, 114.08, 128.38,
131.04, 163.93, 172.08, 193.69 ppm; IR (neat): n˜ =1735, 1686 cmÀ1; MS
(EI): m/z: 356 [M]+; HRMS: calcd for C20H20O6: 356.1260 [M]+; found:
356.1258.
2361, 1722, 1253 cmÀ1
C11H20O3Si: 228.1182 [M]+; found: 228.1177.
Methyl 5-methyl-4-trimethylsilyloxy-2-hexynoate
;
MS (EI): m/z: 228 [M]+; HRMS: calcd for
(4p):
1H NMR
(CDCl3): d=0.16 (s, 9H), 0.96 (d, J=6.8 Hz, 3H), 0.97 (d, J=6.8 Hz,
3H), 1.84–1.89 (m, 1H), 3.76 (s, 3H), 4.18 ppm (d, J=6.0 Hz, 1H);
13C NMR (CDCl3): d=À0.10, 17.65, 17.94, 34.82, 52.64, 67.71, 76.38,
88.09, 153.88 ppm; IR (neat): n˜ =2235, 1721, 1252 cmÀ1; MS (EI): m/z:
228 [M]+; HRMS: calcd for C11H20O3Si: 228.1182 [M]+; found: 228.1163.
Methyl 5,5-dimethyl-4-trimethylsilyloxy-2-hexynoate (4q): 1H NMR
(CDCl3): d=0.16 (s, 9H), 0.96 (s, 9H), 3.76 (s, 3H), 4.03 ppm (s, 1H);
13C NMR (CDCl3): d=À0.18, 25.26, 36.37, 52.59, 71.07, 76.63, 88.14,
153.88 ppm; IR (neat): n˜ =2235, 1721, 1254 cmÀ1; MS (EI): m/z: 242 [M]+
; HRMS: calcd for C12H22O3Si: 242.1338 [M]+; found: 242.1378.
Methyl (Z)-4-oxo-4-(2-bromo-4,5-dimethoxyphenyl)-2-[(2-bromo-4,5-di-
methoxyphenyl)(trimethylsilyloxy)methyl]but-2-enoate (2h): 1H NMR
(CDCl3): d=À0.03 (s, 9H), 3.54 (s, 3H), 3.77 (s, 3H), 3.84 (s, 3H), 3.86
(s, 3H), 3.91 (s, 3H), 5.93 (s, 1H), 5.97 (s, 1H), 6.89 (s, 1H), 7.00 (s, 1H),
7.09 (s, 1H), 7.15 ppm (s, 1H); 13C NMR (CDCl3): d=À0.20, 51.95, 55.98,
56.05, 56.11, 56.31, 74.02, 111.38, 112.66, 114.12, 114.64, 114.71, 117.20,
119.27, 128.55, 131.33, 147.44, 148.83, 149.45, 152.09, 165.58, 193.07 ppm;
IR (neat): n˜ =1724, 1675 cmÀ1; MS (EI): m/z: 644 [M]+; HRMS: calcd
for C25H30Br2O8Si: 644.0077 [M]+; found: 644.0049.
Preparation of Methyl 4-(4-methylphenyl)-4-trimethylsilyloxy-2-buty-
noate (4d): A solution of methyl propiolate (840 mg, 10 mmol) in THF
(5 mL) was added at À788C to a solution of lithium diisopropylamide
(LDA) (10 mmol) in THF (15 mL), prepared from diisopropylamine and
n-butyllithium, and the mixture was stirred for 20 min at the same tem-
perature. After the addition of p-tolualdehyde (1.179 mL, 10 mmol) and
further stirring for 0.5 h, chlorotrimethylsilane (1.4 mL, 11 mmol) was
added dropwise. The mixture was then gradually warmed to room tem-
perature, and continuously stirred for 0.5 h. After this time, the reaction
was quenched with saturated NH4Cl, extracted with CH2Cl2, and dried
over MgSO4. Finally, the solvent was evaporated to leave a residue,
which was purified by chromatography on silica gel (CH2Cl2) to afford
4d as a pale yellow oil (2.267 g, 82%). 1H NMR (CDCl3): d=0.20 (s,
9H), 2.35 (s, 3H), 3.76 (s, 3H), 5.53 (s, 1H), 7.18 (d, J=8.1 Hz, 2H),
7.35 ppm (d, J=8.1 Hz, 2H); 13C NMR (CDCl3): d=0.04, 21.10, 52.66,
64.19, 76.74, 87.60, 126.34, 129.23, 136.44, 138.23, 153.77 ppm; IR (neat):
n˜ =2237, 1719, 1253 cmÀ1; MS (EI): m/z: 276 [M]+; HRMS: calcd for
C15H20O3Si: 276.1182 [M]+; found: 276.1170.
Methyl
(Z)-4-oxo-4-(1-naphthyl)-2-[(1-naphthyl)(trimethylsilyloxy)me-
1
thyl]but-2-enoate (2i): H NMR (CDCl3): d=À0.08 (s, 9H), 3.15 (s, 3H),
5.87 (brs, 1H), 6.44 (brs, 1H), 7.26 (brs, 1H), 7.42–7.58 (m, 4H), 7.62–
7.91 (m, 7H), 8.30 (brs, 1H), 9.08 ppm (d, J=8.5 Hz, 1H); 13C NMR
(CDCl3): d=À0.37, 51.55, 119.88, 123.88, 125.13, 125.70, 125.90, 126.06,
126.15, 126.34, 126.42, 128.21, 128.31, 128.69, 128.93, 130.41, 130.61,
131.72, 133.56, 133.70, 135.30, 159.64, 165.62, 198.66 ppm; IR (neat): n˜ =
1725, 1658 cmÀ1; MS (EI): m/z: 468 [M]+; HRMS: calcd for C29H28O4Si:
468.1757 [M]+; found: 468.1758.
Methyl (Z)-4-oxo-4-(2-naphthyl)-2-[(2-naphthyl)(trimethylsilyloxy)meth-
yl]but-2-enoate (2j): 1H NMR (CDCl3): d=À0.03 (s, 9H), 3.40 (s, 3H),
5.82 (d, J=1.7 Hz, 1H), 6.23 (d, J=1.7 Hz, 1H), 7.40–7.46 (m, 3H), 7.50–
7.55 (m, 2H), 7.71–7.88 (m, 7H), 7.90 (dd, J=8.5, 1.7 Hz, 1H), 8.08 ppm
(s, 1H); 13C NMR (CDCl3): d=À0.22, 51.64, 75.70, 118.19, 123.71, 124.56,
126.09, 126.13, 126.15, 126.40, 127.61, 127.91, 128.10, 128.29, 128.44,
129.54, 130.85, 132.19, 132.96, 133.17, 133.90, 135.46, 137.19, 159.96,
165.55, 197.07 ppm; IR (neat): n˜ =1724, 1664 cmÀ1; MS (EI): m/z: 468
[M]+; HRMS: calcd for C29H28O4Si: 468.1757 [M]+; found: 468.1767.
Reaction of propiolate (1a) with benz[D]aldehyde: Benz[D]aldehyde
was purchased from Aldrich (98 atom% D) and used as received. A so-
lution of methyl 3-trimethylsilylpropiolate (156 mg, 1 mmol), benz[D]al-
dehyde (54 mg, 0.5 mmol), and DABCO (112 mg, 1 mmol) in anhydrous
benzene (1 mL) was refluxed for 40 min. After this time, the mixture was
cooled to room temperature and diluted with CH2Cl2 (20 mL). This solu-
Methyl 2-(2-naphthyloyl)-4-oxo-4-(2-naphthyl)butyrate (3j): 1H NMR
(CDCl3): d=3.24 (d, J=6.8 Hz, 2H), 3.74 (s, 3H), 6.11 (t, J=6.8 Hz,
1H), 7.52–7.55 (m, 2H), 7.59–7.62 (m, 2H), 7.85–7.90 (m, 6H), 8.04 (dd,
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H. Nemoto et al.
tion was then washed with hydrochloric acid (10%) and brine successive-
ly, and dried over MgSO4. After evaporation of the solvent, the residue
was purified by silica-gel column chromatography (CH2Cl2) to afford
compound [D]2a (57 mg, 62%). Only a trace amount of the product
2-Formyl-4-methoxyphenyl 3-trimethylsilylpropiolate (10c): Yield 56%;
1H NMR (CDCl3): d=0.29 (s, 9H), 3.84 (s, 3H), 7.14 (d, J=9.0 Hz, 1H),
7.16 (dd, J=2.6, 9.0 Hz, 1H), 7.36 (d, J=2.6 Hz, 1H), 10.14 ppm (s, 1H);
13C NMR (CDCl3): d=À0.99, 55.81, 93.16, 98.19, 112.17, 122.21, 124.15,
128.20, 144.91, 151.15, 157.93, 187.79 ppm; IR (neat): n˜ =2178, 1733 cmÀ1
;
[D]3a could be detected by TLC.
A solution of [D]2a (40 mg,
MS (EI): m/z: 276 [M]+; HRMS: calcd for C14H16O4Si: 276.0818 [M]+;
found: 276.0825.
0.11 mmol) and DABCO (24 mg, 0.22 mmol) in anhydrous benzene
(0.5 mL) was refluxed for 14 h. After this time, the same workup proce-
dure as that described above was utilized and compound [D]3a (11 mg,
34%) and the starting material [D]2a (24 mg, 60%) were isolated.
2-Formyl-5-methoxyphenyl 3-trimethylsilylpropiolate (10d): Yield 88%;
1H NMR (CDCl3): d=0.31 (s, 9H), 3.88 (s, 3H), 6.71 (d, J=2.2 Hz, 1H),
6.91 (dd, J=2.2, 8.8 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 10.02 ppm (s, 1H);
13C NMR (CDCl3): d=À0.66, 56.13, 93.32, 98.21, 108.53, 112.99, 121.39,
132.42, 150.51, 152.50, 165.20, 186.96 ppm; IR (neat): n˜ =2179, 1735,
The experiment in the presence of MeOH was performed as follows: A
solution of methyl 3-trimethylsilylpropiolate (156 mg, 1 mmol), benz[-
D]aldehyde (54 mg, 0.5 mmol), DABCO (112 mg, 1 mmol), and MeOH
(100 ml) in anhydrous benzene (1 mL) was refluxed for 40 min. After this
time, the mixture was cooled to room temperature and diluted with
CH2Cl2 (20 mL). This solution was then washed with hydrochloric acid
(10%) and brine successively, and dried over MgSO4. After evaporation
of the solvent, the residue was purified by silica-gel column chromatogra-
phy (CH2Cl2) to afford compound [D]2a (48 mg, 52%). The 1H NMR
spectrum showed that 100% of the deuterium was incorporated into the
product.
Product [D]2a: 1H NMR (CDCl3): d=À0.01 (s, 9H), 3.45 (s, 3H), 7.17–
7.31 (m, 7H), 7.46 (t, J=7.3 Hz, 1H), 7.68 ppm (d, J=8.1 Hz, 2H); MS
(EI) m/z: 370 [M]+; HRMS calcd for C21H22D2O4Si: 370.1567 [M]+;
found: 370.1578. In the 1H NMR spectrum, the peaks d=5.56 (d, J=
1.7 Hz, 1H) and d=6.12 ppm (d, J=1.7 Hz, 1H), which were observed in
the 1H NMR spectrum of compound 2a, were found to have disap-
peared.
1693 cmÀ1 MS (EI): m/z: 276 [M]+; HRMS: calcd for C14H16O4Si:
;
276.0818 [M]+; found: 276.0788.
1-Formyl-2-naphthyl 3-trimethylsilylpropiolate (10e): Yield 69%;
1H NMR (CDCl3): d=0.32 (s, 9H), 7.31 (d, J=8.8 Hz, 1H), 7.58 (ddd,
J=1.1, 6.9, 8.2 Hz, 1H), 7.70 (ddd, J=1.3, 6.9, 8.5 Hz, 1H), 7.88 (d, J=
8.2 Hz, 1H), 8.12 (d, J=8.8 Hz, 1H), 9.18 (d, J=8.5 Hz, 1H), 10.73 ppm
(s, 1H); 13C NMR (CDCl3): d=À0.66, 93.19, 98.95, 121.08, 121.36, 125.40,
126.99, 128.49, 129.87, 130.97, 132.02, 136.66, 150.72, 153.60, 189.84 ppm;
IR (neat): n˜ =2172, 1728, 1684 cmÀ1; MS (EI): m/z: 296 [M]+; HRMS:
calcd for C17H16O3Si: 296.0869 [M]+; found: 296.0858.
4-Chloro-2-formylphenyl 3-trimethylsilylpropiolate (10 f): Yield 64%;
1H NMR (CDCl3): d=0.31 (s, 9H), 7.22 (d, J=8.8 Hz, 1H), 7.60 (dd, J=
2.2, 8.8 Hz, 1H), 7.88 (d, J=2.2 Hz, 1H), 10.13 ppm (s, 1H); 13C NMR
(CDCl3): d=À0.66, 92.98, 99.15, 124.76, 128.85, 129.74, 133.04, 135.19,
149.43, 150.37, 186.70 ppm; IR (neat): n˜ =2178, 1736 cmÀ1; MS (EI): m/z:
280 [M]+; HRMS: calcd for C13H13ClO3Si: 280.0323 [M]+; found:
280.0274.
Product [D]3a: 1H NMR (CDCl3): d=3.70 (s, 3H), 5.79 (s, 1H), 7.46 (t,
J=7.3 Hz, 4H), 7.58 (t, J=7.3 Hz, 2H), 7.97 (d, J=7.3 Hz, 4H); MS (EI)
m/z: 298 [M]+; HRMS calcd for C18H14D2O4: 298.1174 [M]+; found:
298.1183. In the 1H NMR spectrum, the peak d=3.10 ppm (d, J=6.4 Hz,
General procedure for the formation of the 3-formylcoumarins 11a–f: A
mixture of the propiolic ester 10 (0.125 mmol), and DABCO (28 mg,
0.25 mmol) or quinuclidine (28 mg, 0.25 mmol) in a suitable solvent
(1 mL) was refluxed under an Ar atmosphere. After completion of the
reaction, the mixture was diluted with CH2Cl2, washed with HCl (10%)
and brine, and dried over MgSO4. The solvent was evaporated to leave a
residue, which was purified by silica-gel chromatography (CH2Cl2) to
afford the 3-formylcoumarin as a colorless solid. The yields from all
these reactions are listed in Table 4.
3-Formylcoumarin (11a): Yield 64%; m.p. 134–1358C (lit.[36] m.p. 132–
1338C); 1H NMR (CDCl3): d=7.36–7.42 (m, 2H), 7.68–7.72 (m, 2H),
8.43 (s, 1H), 10.27 ppm (s, 1H); 13C NMR (CDCl3): d=117.15, 118.13,
121.69, 125.33, 130.81, 135.06, 145.67, 155.50, 160.14, 187.78 ppm.
1
2H), which was observed in the H NMR spectrum of compound 3a, was
found to have disappeared, and the peak d=5.80 (t, J=6.4 Hz, 1H) in
3a was simplified to a singlet.
General procedure for the preparation of the 3-trimethylsilylpropiolic
esters of salicylaldehydes 10a–f: 4-Dimethylaminopyridine (24 mg,
0.2 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydro-
chloride (575 mg, 3 mmol) were added successively to a solution of salicy-
laldehyde (2 mmol) and 3-trimethylsilylpropiolic acid (284 mg, 2 mmol)
in anhydrous CH2Cl2 (10 mL) at room temperature. The resulting mix-
ture was then stirred for 1 h at room temperature. The order of the addi-
tion of the reagents, the concentration of the solution, and the reaction
time were very important factors for the reproducibility of the reaction.
Alternative procedures or a prolonged reaction time resulted in the for-
mation of salicylaldehyde trimethylsilyl ethers, which could not be re-
moved from the desired esters. The reaction mixture was concentrated to
about 4 mL, which was directly purified by silica-gel column chromatog-
raphy (CH2Cl2) to afford a mixture of the ester 10 and the starting salicy-
laldehyde. After evaporation of the solvent, the residue was dissolved in
Et2O (50 mL), washed with K2CO3 (10%, 4”30 mL), and dried over
MgSO4. The aqueous layer was then acidified with HCl (10%), and ex-
tracted with CH2Cl2 to give the recovered salicylaldehyde (20–40%).
Evaporation of the organic layer afforded the pure ester as a colorless oil
in 52–88% yield based on the consumed salicylaldehyde.
3-Formyl-6-methylcoumarin (11b): Yield 81%; m.p. 123–1248C;
1H NMR (CDCl3): d=2.44 (s, 3H), 7.30 (d, J=8.6 Hz, 1H), 7.46–7.51 (m,
2H), 8.37 (s, 1H), 10.26 ppm (s, 1H); 13C NMR (CDCl3): d=20.69,
116.86, 117.89, 121.55, 130.37, 135.23, 136.27, 145.66, 153.72, 160.40,
187.94 ppm; IR (KBr): n˜ =1733, 1691 cmÀ1; MS (EI): m/z: 188 [M]+;
HRMS: calcd for C11H8O3: 188.0474 [M]+; found: 188.0448.
3-Formyl-6-methoxycoumarin (11c): Yield 47%; m.p. 176–1788C (lit.[37]
1
m.p. 1708C); H NMR (CDCl3): d=3.87 (s, 3H), 7.07 (d, J=2.7 Hz, 1H),
7.25–7.35 (m, 2H), 8.37 (s, 1H), 10.25 ppm (s, 1H); 13C NMR (CDCl3):
d=56.15, 111.68, 118.33, 118.53, 121.88, 123.64, 145.48, 150.19, 156.58,
187.88 ppm; MS (EI): m/z: 204 [M]+; HRMS: calcd for C11H8O4:
204.0423 [M]+; found: 204.0378.
2-Formylphenyl 3-trimethylsilylpropiolate (10a): Yield 52%; 1H NMR
(CDCl3): d=0.30 (s, 9H), 7.24 (dd, J=1.3, 8.1 Hz, 1H), 7.43 (t, J=
7.7 Hz, 1H), 7.65 (ddd, J=1.3, 7.7, 8.1 Hz, 1H), 7.92 (dd, J=1.3, 7.7 Hz,
1H), 10.18 ppm (s, 1H); 13C NMR (CDCl3): d=À0.62, 93.33, 98.36,
123.23, 127.10, 127.89, 130.53, 135.46, 150.70, 150.91, 188.13 ppm; IR
(neat): n˜ =2178, 1734, 1703 cmÀ1; MS (EI): m/z: 246 [M]+; HRMS: calcd
for C13H14O3Si: 246.0712 [M]+; found: 246.0688.
3-Formyl-7-methoxycoumarin (11d): Yield 46%; m.p. 236–2388C (lit.[37]
m.p. 2388C); 1H NMR ([D6]DMSO): d=3.92 (s, 3H), 7.05 (dd, J=2.6,
8.5 Hz, 1H), 7.11 (d, J=2.6 Hz, 1H), 7.92 (d, J=8.5 Hz, 1H), 8.65 (s,
1H), 9.99 ppm (s, 1H); 13C NMR ([D6]DMSO): d=56.03, 111.64, 113.18,
113.53, 117.99, 132.48, 146.98, 157.16, 159.07, 165.20, 186.59 ppm; MS
(EI): m/z: 204 [M]+; HRMS: calcd for C11H8O4: 204.0423 [M]+; found:
204.0387.
3-Formylbenzo[d]coumarin (11e): Yield 50%; m.p. 226–2288C; 1H NMR
(CDCl3): d=7.50 (d, J=9.1 Hz, 1H), 7.64 (ddd, J=1.1, 7.1, 8.0 Hz, 1H),
7.78 (ddd, J=1.4, 7.1, 8.5 Hz, 1H), 7.95 (d, J=8.0 Hz, 1H), 8.15 (d, J=
9.1 Hz, 1H), 8.36 (d, J=8.5 Hz, 1H), 9.20 (s, 1H), 10.33 ppm (s, 1H);
13C NMR (CDCl3): d=112.93, 116.86, 120.03, 121.70, 126.99, 129.42,
129.58, 130.03, 130.34, 137.07, 141.16, 156.64, 160.30, 187.80 ppm; IR
2-Formyl-4-methylphenyl 3-trimethylsilylpropiolate (10b): Yield 59%;
1H NMR (CDCl3): d=0.30 (s, 9H), 2.41 (s, 3H), 7.12 (d, J=8.2 Hz, 1H),
7.44 (dd, J=2.2, 8.2 Hz, 1H), 7.70 (d, J=2.2 Hz, 1H), 10.14 ppm (s, 1H);
13C NMR (CDCl3): d=À0.66, 20.99, 93.40, 98.08, 122.93, 127.43, 130.63,
136.08, 137.10, 148.76, 150.93, 188.27 ppm; IR (neat): n˜ =2177, 1728,
1697 cmÀ1 MS (EI): m/z: 260 [M]+; HRMS: calcd for C14H16O3Si:
;
260.0868 [M]+; found: 260.0853.
5416
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Chem. Eur. J. 2005, 11, 5408 –5418

À
Domino C C Bond Formations
FULL PAPER
1
(KBr): n˜ =1724 cmÀ1
;
MS (EI): m/z: 224 [M]+; HRMS: calcd for
solid (9 mg, 41%). The H NMR spectrum was identical to that obtained
for 11a with one exception. The integration value for the proton at C-4
on the coumarin nucleus (d=8.43 ppm) suggested 60% D incorporation.
C14H8O3: 224.0473 [M]+; found: 224.0405.
6-Chloro-3-formylcoumarin (11 f): Yield 26%; m.p. 180–1828C (lit.[37]
1
Formation of compound [Db]11a: A mixture of the propiolic ester 10a
(31 mg, 0.125 mmol), DABCO (28 mg, 0.25 mmol), and [D4]MeOH (1
drop) in benzene (1 mL) was refluxed for 1 h. After this time, the mix-
ture was diluted with CH2Cl2, washed with HCl (10%) and brine, and
dried over MgSO4. The solvent was then removed by evaporation, and
the residue produced was purified by silica-gel chromatography (CH2Cl2)
affording 3-formylcoumarin [Db]11a as a colorless solid (3 mg, 14%).
The other major product obtained was salicylaldehyde, which was proba-
m.p. 1798C); H NMR (CDCl3): d=7.36 (d, J=8.8 Hz, 1H), 7.64 (dd, J=
2.5, 8.8 Hz, 1H), 7.68 (d, J=2.5 Hz, 1H), 8.34 (s, 1H), 10.25 ppm (s, 1H);
13C NMR (CDCl3): d=118.71, 119.17, 122.57, 129.72, 130.76, 134.92,
144.28, 153.84, 159.80, 187.30 ppm; MS (EI): m/z: 208 [M]+; HRMS:
calcd for C10H5ClO3: 207.9927 [M]+; found: 207.9905.
Preparation of compound 17: A mixture of allylpalladium chloride dimer
(27 mg, 0.15 mmol), triethyl phosphite (50 mg, 0.3 mmol), and hexame-
thyldisilane (0.64 mL, 3.2 mmol) was stirred at room temperature for
5 min. Coumarin 3-carboxylic acid chloride (314 mg, 1.5 mmol) in anhy-
drous toluene (0.5 mL) was then added to this solution, and the resulting
reaction mixture was refluxed for 16 h (coumarin 3-carboxylic acid chlo-
ride was prepared by the treatment of coumarin 3-carboxylic acid with
thionyl chloride). After this time, the reaction mixture was diluted with
CH2Cl2, washed with saturated NaHCO3, dried over MgSO4, and then
the solvent removed by evaporation. Purification of the residue was ach-
ieved by silica-gel chromatography (20% AcOEt/hexane) affording com-
pound 17 (17 mg, 5%) as a pale yellow solid. M.p. 117–1198C; 1H NMR
(CDCl3): d=0.32 (s, 9H), 7.33 (dt, J=1.3, 7.7 Hz, 1H), 7.38 (d, J=
8.1 Hz, 1H), 7.61–7.66 (m, 2H), 8.04 ppm (s, 1H); 13C NMR (CDCl3): d=
À2.39, 116.80, 118.58, 124.96, 128.53, 130.51, 133.75, 142.06, 155.04,
160.71 ppm; IR (KBr): n˜ =1719, 1631, 1608, 1554 cmÀ1; MS (EI): m/z:
246 [M]+; HRMS: calcd for C13H14O3Si: 246.0712 [M]+; found: 246.0740.
1
bly formed by methanolysis. The H NMR spectrum of [Db]11a was iden-
tical to that obtained for 11a, with the exception of the integration value
of the formyl proton (10.27 ppm), which suggested 60% D incorporation.
[1] a) The Chemistry of Functional Groups. The Chemistry of the
Carbon–Carbon Triple Bond (Ed.: S. Patai), Wiley, Chichester, 1978;
b) Modern Acetylene Chemistry (Eds.: P. J. Stang, F. Diederich),
VCH, Weinheim, 1995.
[2] a) P. Perlmutter, Conjugate Addition Reactions in Organic Synthesis,
Pergamon, Oxford, 1992; b) M. E. Jung in Comprehensive Organic
Synthesis (Eds.: B. M. Trost, I. Fleming, M. F. Semmelhack), Perga-
mon, Oxford, 1991.
[3] a) X. Lu, C. Zhang, Z. Xu, Acc. Chem. Res. 2001, 34, 535; b) J. Ina-
naga, Y. Baba, T. Hanamoto, Chem. Lett. 1993, 241; c) G. T. Crisp,
M. J. Millan, Tetrahedron 1998, 54, 637; d) M. Wende, R. Meier,
J. A. Gladysz, J. Am. Chem. Soc. 2001, 123, 11490; e) E. Winterfeldt,
H. Preuss, Chem. Ber. 1966, 99, 450.
[4] B. M. Trost, G. R. Dake, J. Am. Chem. Soc. 1997, 119, 7595.
[5] I. Yavari, M. Anary-Abbasinejad, A. Alizadeh, Tetrahedron Lett.
2002, 43, 4503.
[6] L. Brandsmen, Preparative Acetylene Chemistry 2nd ed., Elsevier,
Amsterdam, 1988.
[7] a) P. de Armas, F. Garcia-Tellado, J. J. Marrero-Tellado, D. Tejedor,
M. A. Maestro, J. Gonzalez-Platas, Org. Lett. 2001, 3, 1905; b) D. Te-
jedor, F. Garcia-Tellado, J. J. Marrero-Tellado, P. de Armas, Chem.
Eur. J. 2003, 9, 3122.
[8] D. T. Aragon, G. V. Lopez, F. Garcia-Tellado, J. J. Marrero-Tellado,
P. de Armas, D. Terrero, J. Org. Chem. 2003, 68, 3363.
[9] a) J. P. Marino, H. N. Nguyen, J. Org. Chem. 2002, 67, 6291; b) H.-X.
Wei, J. J. Gao, G. Li, Tetrahedron Lett. 2001, 42, 9119; c) H.-X. Wei,
J. Hu, D. W. Purkiss, P. W. Pare, Tetrahedron Lett. 2003, 44, 949.
[10] a) T. Tsuda, T. Yoshida, T. Kawamoto, T. Saegusa, J. Org. Chem.
1987, 52, 1624; b) T. Tsuda, T. Yoshida, T. Saegusa, J. Org. Chem.
1988, 53, 1037; c) G. Li, H.-X. Wei, S. Willis, Tetrahedron Lett. 1998,
39, 4607; d) P. V. Ramachandran, M. V. R. Reddy, M. T. Rudd,
Chem. Commun. 1999, 1979.
[11] T. Kataoka, H. Kinoshita, S. Kinoshita, T. Iwamura, S. Watanabe,
Angew. Chem. Int. Ed. 2000, 39, 2358.
[12] a) V. Nair, A. R. Sreekanth, N. Abhilash, A. T. Biju, B. Rema Devi,
R. S. Menon, N. P. Rath, R. Srinivas, Synthesis 2003, 1895; b) C.-Q.
Li, M. Shi, Org. Lett. 2003, 5, 4273; c) A. A. Esmaili, A. Bodaghi,
Tetrahedron 2003, 59, 1169.
[13] J.-C. Wang, S.-S. Ng, M. J. Krische, J. Am. Chem. Soc. 2003, 125,
3682.
[14] a) E. Winterfeldt, Chem. Ber. 1964, 97, 1952; b) R. M. Acheson, P. J.
Ansell, J. R. Murray, J. Chem. Res. Synop. 1986, 378; c) M. Medion-
Simon, U. Pindur, Helv. Chim. Acta 1991, 74, 430.
[15] a) K. Morita, Z. Suzuki, H. Hirose, Bull. Chem. Soc. Jpn. 1968, 41,
2815; b) A. B. Baylis, M. E. D. Hillman, German Patent 2155113,
1972 [Chem. Abstr. 1972, 77, 34179q]; c) For a recent review see: E.
Ciganek, Org. React. 1997, 51, 201; d) D. Basavaiah, P. D. Rao, R. S.
Hyma, Tetrahedron 1996, 52, 8001.
[16] For a preliminary communication see: Y. Matsuya, K. Hayashi, H.
Nemoto, J. Am. Chem. Soc. 2003, 125, 646.
[17] The 2D NMR spectra (HMQC and HMBC) were measured for the
product 2 f (Table 3), and peak assignments were unambiguously
carried out for the compound.
Preparation of the deuterated substrate [D]10a: Following the reported
procedure,[38] salicylaldehyde was protected as a methoxymethyl ether.
This compound was then transformed into a cyanohydrin trimethylsilyl
ether as follows (see reference [39]). Trimethylsilyl cyanide (104 mg,
1 mmol) and triethylamine (1 drop) were added to a solution of the me-
thoxymethyl ether (166 mg, 1 mmol) in anhydrous CH2Cl2 (4 mL). After
continuous stirring at room temperature for 4 h the reaction mixture was
evaporated and dried under reduced pressure by a vacuum pump to
afford the cyanohydrin trimethylsilyl ether (254 mg, 96%) in an almost
entirely pure form (this was determined from the 1H NMR spectrum).
1H NMR (CDCl3): d=0.25 (s, 9H), 3.51 (s, 3H), 5.24 (d, J=6.8 Hz, 1H),
5.29 (d, J=6.8 Hz, 1H), 5.81 (s, 1H), 7.07 (dt, J=1.3, 7.7 Hz, 1H), 7.14
(dd, J=1.3, 7.7 Hz, 1H), 7.33 (dt, J=1.7, 7.7 Hz, 1H), 7.60 ppm (dd, J=
1.7, 7.7 Hz, 1H).
The deuterium-rich salicylaldehyde and the propiolic ester [D]10a were
prepared by the following procedure: The cyanohydrin trimethylsilyl
ether (254 mg, 0.96 mmol) was dissolved in THF (2 mL) and added to an
equimolar amount of LDA in THF (2 mL) at À788C. The mixture was
then stirred at À788C for 15 min and D2O (1 mL) was added. The mix-
ture was then diluted with aqueous NH4Cl, extracted with CH2Cl2, and
dried over MgSO4. Evaporation of the solvent produced a residue, which
was dissolved in MeOH (3 mL), treated with K2CO3 (138 mg, 1 mmol),
and then stirred at room temperature for 0.5 h. After this time, the reac-
tion mixture was diluted with H2O, extracted with CH2Cl2, and then
dried over MgSO4. Evaporation of the solvent afforded the deuterium-
rich salicylaldehyde methoxymethyl ether. The deuterium incorporation
of this compound was estimated as approximately 60% from the
1H NMR spectrum. Aqueous H2SO4 (5 mol%, 1 mL) was then added to
a solution of this crude product in MeOH (5 mL), and the resulting mix-
ture was heated at 608C for 12 h. After dilution with H2O, the aqueous
solution was extracted with CH2Cl2 and dried over MgSO4. Finally, the
solvent was evaporated to leave a residue, which was purified by silica-
gel chromatography (CH2Cl2) affording salicyl[D]aldehyde (71 mg,
60%). The deuterium-rich propiolic ester [D]10a was synthesized accord-
ing to the general procedure mentioned above. The 60% D incorporation
1
of these products was confirmed by their H NMR spectra.
The coumarin-forming reaction of compound [D]10a: A mixture of the
propiolic ester [D]10a (30 mg, 0.125 mmol) and DABCO (28 mg,
0.25 mmol) in benzene (1 mL) was refluxed for 8 h. After completion of
the reaction, the mixture was diluted with CH2Cl2, washed with HCl
(10%) and brine, and dried over MgSO4. Removal of the solvent by
evaporation produced a residue, which was purified by silica-gel chroma-
tography (CH2Cl2) affording the 3-formylcoumarin [Da]11a as a colorless
Chem. Eur. J. 2005, 11, 5408 –5418
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ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5417

H. Nemoto et al.
[18] For recent reports on the generation and subsequent reaction of b-
silyloxyalkylidenecarbenes: a) L. R. Reddy, H.-J. Gais, C.-W. Woo,
G. Raabe, J. Am. Chem. Soc. 2004, 126, 4859; b) K. S. Feldman,
M. L. Wrobleski, J. Org. Chem. 2000, 65, 8659; c) S. Kim, C. M.
Cho, Tetrahedron Lett. 1995, 36, 4845.
[28] a) S. E. Drewes, O. L. Njamela, N. D. Emslie, N. Ramesar, J. S. Field,
Synth. Commun. 1993, 23, 2807; b) P. T. Kaye, R. S. Robinson,
Synth. Commun. 1996, 26, 2085; c) P. T. Kaye, X. W. Nocanda, J.
Chem. Soc. Perkin Trans. 1 2000, 1331.
[29] For example: a) L. Rene, A. Lefebvre, G. Auzou, Synthesis 1986,
567; b) S. Padmanabhan, R. Peri, D. J. Triggle, Synth. Commun.
1996, 26, 827.
[19] T. Sueda, T. Nagaoka, S. Goto, M. Ochiai, J. Am. Chem. Soc. 1996,
118, 10141.
[30] Conversion of acylsilanes into silyloxycarbenes by thermal rear-
rangement, and subsequent transformations have been reported see:
A. R. Bassindale, A. G. Brook, J. Harris, J. Organomet. Chem. 1975,
90, C6.
[31] Recent representative examples on this subject: a) K. S. Feldman,
J. C. Saunders, M. L. Wrobleski, J. Org. Chem. 2002, 67, 7096;
b) K. S. Feldman, A. L. Perkins, Tetrahedron Lett. 2001, 42, 6031;
c) S. Ohira, K. Yamasaki, H. Nozaki, M. Yamato, M. Nakayama,
Tetrahedron Lett. 1995, 36, 8843; d) S. Ohira, K. Okai, T. Moritani,
J. Chem. Soc. Chem. Commun. 1992, 721.
[32] Compound 17 was synthesized from coumarin-3-carboxylic acid by
the Pd-catalyzed reaction according to the reported procedure: K.
Yamamoto, S. Suzuki, J. Tsuji, Tetrahedron Lett. 1980, 21, 1653.
[33] The preparative method for the deuterated salicylaldehyde was de-
scribed in the Experimental Section.
[20] Reviews on the nature and reactivity of alkylidenecarbenes: a) P. J.
Stang, Acc. Chem. Res. 1982, 15, 348; b) P. J. Stang, Chem. Rev.
1978, 78, 383.
[21] Several recent examples on the 1,2-rearrangement of alkylidenecar-
benes: a) M. Ochiai, M. Kunishima, S. Tani, Y. Nagao, J. Am. Chem.
Soc. 1991, 113, 3135; b) Y. Tobe, N. Iwasa, R. Umeda, M. Sonoda,
Tetrahedron Lett. 2001, 42, 5485; c) E. T. Chernick, S. Eisler, R. R.
Tykwinski, Tetrahedron Lett. 2001, 42, 8575.
[22] This compound was prepared by a different method (see the Experi-
mental Section).
[23] a) R. Huisgen, P. de March, J. Am. Chem. Soc. 1982, 104, 4953;
b) R. P. LꢁEsperance, T. M. Ford, M. Jones Jr., J. Am. Chem. Soc.
1988, 110, 209.
[24] We confirmed the stability of the alkyne 4n under the reaction con-
ditions. The instability of 4d under basic conditions may be attribut-
ed to the relatively high acidity of the benzylic proton. In case of
4n, on the other hand, such deprotonation–decomposition reactions
would be impeded by the influence of the two ortho substituents.
[25] S.-I. Watanabe, T. Kusumoto, C. Yoshida, T. Kataoka, Chem.
Commun. 2001, 839.
[26] The yields were calculated based on the amount of consumed salicy-
laldehyde. Remaining salicylaldehyde could be removed simply by
alkaline extraction: see the Experimental Section.
[34] Deuterium incorporation was determined as about 60% by
1H NMR spectroscopy.
[35] R. F. Cunico, H. M. Lee, J. Am. Chem. Soc. 1977, 99, 7613.
[36] K. Ito, K. Nakajima, J. Heterocycl. Chem. 1988, 25, 511.
[37] L. Rene, A. Lefebvre, G. Auzou, Synthesis 1986, 567.
[38] R. D. Youssefyeh, H. F. Campbell, S. Klein, J. E. Airey, P. Darkes,
M. Powers, M. Schnapper, K. Neuenschwander, L. R. Fitzpatrick,
C. E. Pendley, G. E. Martin, J. Med. Chem. 1992, 35, 895.
[39] S. Kobayashi, Y. Tsuchiya, T. Mukaiyama, Chem. Lett. 1991, 537.
[27] A recent report on the syntheses of coumarins using propiolates:
B. M. Trost, F. D. Toste, K. Greenman, J. Am. Chem. Soc. 2003, 125,
4518.
Received: February 18, 2005
Published online: July 8, 2005
5418
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 5408 –5418