Carbonylative addition of arylboronic acids to terminal alkynes: A new catalytic access to α,β-unsaturated ketones

Article abstract of DOI:10.1002/adsc.200700141

The carbonylative addition of arylboronic acids to terminal alkynes under mild conditions affords (E)-α,β-unsaturated ketones with good yields. The reaction was achieved with chloro(1,5-cyclooctadiene)rhodium(I) dimer or chlorodicarbonylrhodium(I) dimer a

Full text of DOI:10.1002/adsc.200700141

FULL PAPERS
DOI: 10.1002/adsc.200700141
Carbonylative Addition of Arylboronic Acids to Terminal
Alkynes: A New Catalytic Access to a,b-Unsaturated Ketones
Julien Dheur,a Mathieu Sauthier,a,* Yves Castanet,a,* and AndrØ Mortreuxa
a
UnitØ de Catalyse et Chimie du Solide – UMR, CNRS 8181 – USTL – ENSCL, BP 90108, 59652 Villeneuve d’Ascq,
France
Fax : (+33)-3-2043-6585; e-mail: mathieu.sauthier@univ-lille1.fr or yves.castanet@ensc-lille.fr
Abstract: The carbonylative addition of arylboronic catalytic cycle involving a 1,2-insertion of the termi-
acids to terminal alkynes under mild conditions af- nal alkyne in a rhodium-acyl bond is proposed. This
fords (E)-a,b-unsaturated ketones with good yields. new reaction represents the first example of the hy-
The reaction was achieved with chloro(1,5-cycloocta- droacylation of terminal alkynes involving rhodium-
diene)rhodium(I) dimer or chlorodicarbonylrhodi- acyl reagents generated under CO pressure and
um(I) dimer as catalytic precursor without additional promises a wide field of interest.
phosphine as their use inhibits the reaction. Experi-
ments using deuterated 1-hexyne discarded the possi- Keywords: alkynes; carbonylation; C C bond forma-
bility of a rhodium-vinylidene intermediate, thus a tion; rhodium; a,b-unsaturated carbonyl compounds
À
Introduction
The rhodium-catalysed 1,4-addition of arylboronic
acids to a,b-unsaturated ketones has opened a new
À
a,b-Unsaturated ketones are important key reagents area of investigation for the development of new C C
in organic synthesis. As typical examples, they are bond forming reactions.[8] The key step of that reac-
widely used as Michael acceptors in numerous cata- tion involves a transmetalation of the aryl moiety
lysed 1,4-addition reactions,[1] or as activated olefins from a boron species to the rhodium centre and leads
in Heck-type couplings[2] or in epoxidation reactions.[3] to suitable metal-carbon-containing catalytic inter-
They are commonly synthesised through an aldol con- mediates.[9] This reactivity has been more recently ex-
densation reaction between one equivalent of ketone ploited for the development of other rhodium-cata-
and one equivalent of an aldehyde derivative fol- lysed reactions like the addition of arylboronic acids
lowed by a dehydration step.[4] The reaction is ex- to alkynes.[10] Rhodium complexes containing Rh C
À
tremely efficient when acetophenone derivatives are bonds are otherwise well-known to readily insert
used for chalcone synthesis. Nevertheless, it shows carbon monoxide and yield metal-acyl complexes.[11]
limitations when the aldehyde has an a-hydrogen and These are known to react with olefins[12] for ketones
leads to the synthesis of a,b-unsaturated ketones synthesis although they are not easily obtained
À
being less straightforward. Alternative strategies are through the activation of the C H bond in aldehydes.
also available to access this latter family and among With these two concepts in mind, we recently investi-
them, the most efficient ones appear to be the selec- gated the possibility of performing the carbonylative
tive oxidation of an allylic alcohol[5] and Friedel– 1,4-addition of arylboronic acids to enones [Scheme 1,
Crafts acylation reaction of arenes using a,b-unsatu- Eq.(1)].[13]
rated acyl chlorides.[6] In that context, only a limited
This new transformation efficiently yields 1,4-dike-
number of reactions involve a carbonylation step and tones and offers a fast access to 2,5-disubstituted pyr-
most of them, such as the Pauson–Khand reaction, roles or furans when the carbonylation reaction is fol-
give access to cyclic-a,b-unsaturated ketones.[7]
lowed by cyclisation.[14] This reaction is one of the
Molecules obtained from cascade-like reactions rare examples of a nucleophilic acylating reagent cat-
where carbon monoxide is the only source of carbonyl alytically generated from carbon monoxide.[15] As con-
function would be an interesting catalytic process. tinuation of this work, we thus anticipated that this
This procedure would not only be economically reactivity could be enlarged to alkynes. We now
viable in terms of atomic yield, but also valuable from report that arylboronic acids react with terminal al-
an environmental point of view, as this insertion does kynes under carbon monoxide pressure to yield selec-
not yield any by-product.
tively a,b-unsaturated ketones if appropriate condi-
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Julien Dheur et al.
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Scheme 1. Carbonylative addition of arylboronic acid to enones and alkynes.
Scheme 2. Products obtained through carbonylative addition of phenylboronic acid to a terminal alkyne, 1-hexyne.
tions are used [Scheme 1, Eq. (2)]. This transforma- a,b-unsaturated ketone is accompanied by the forma-
tion is formally a hydroacylation of alkynes and is a tion of side products in low yields. The analysis of the
very rare example of a reaction involving carbon mixture by gas chromatography/mass spectrometry
monoxide as the carbonyl source.[16] However, in the (GC/MS) with electron impact and chemical ionisa-
course of our work, the catalytic carbonylative addi- tion, evidenced the formation of less than 5% of de-
tion reaction of phenylboronic acids on internal al- rivatives having the same molecular weight as the
kynes yielding 5-aryl-2(5H)-furanones was reported main product 3aa (m/z=188, [M+]). These com-
[Scheme 1, Eq. (3)]. Even thought this reaction does pounds, obtained in low yields, can be attributed to
not yield a,b-unsaturated ketones, it likely involves an the isomers of 3aa with a Z double bond configura-
acylation step before the cyclisation yielding the 5- tion or the branched derivative. GC-MS analysis also
aryl-2(5H)-furanones.[17]
show the presence of three higher molecular weight
derivatives in less than 10% yield which have the
same molecular weight (m/z=270, [M+]). Actually,
this molecular weight fits with the mass of compounds
including one phenyl moiety, a CO unit and two
Results and Discussion
The reaction between one equivalent of phenylboron- hexyne units. Various attempts to separate these iso-
1
ic acid and one equivalent of 1-hexyne in methanol at mers were only successful with compound 4aa. H and
808C under 5 bar CO in the presence of 0.5 % of 13C NMR analysis of this product allowed us to deter-
[Rh
the formation of a,b-unsaturated ketone 3aa as the is noteworthy that in all the experiments run in the
major product in 41% yield (Scheme 2). course of this study, neither the corresponding furan-
(COD)Cl]2 (COD=1,5-cyclooctadiene) showed mine its configuration as represented in Scheme 2. It
The structure of the obtained compound was con- one, nor hex-1-enylbenzene (the product of direct ad-
1
firmed by H and 13C NMR spectroscopy. Moreover, dition of the phenylboronic acid to 1-hexyne without
the coupling constant between the two olefinic pro- CO insertion) were observed.
tons is consistent with an E configuration of the
The formation of all these side products in low
double bond (3JH,H =15 Hz). The formation of the amounts does not account for the mass balance. Since
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Adv. Synth. Catal. 2007, 349, 2499 – 2506

Carbonylative Addition of Arylboronic Acids to Terminal Alkynes
Table 1. Carbonylative addition of phenylboronic acid to 1-hexyne 2a, effect of the reaction conditions on the yield in 3aa.[a]
FULL PAPERS
Entry
1a (mmol)
methanol
Solvent
T [8C]
P(CO) [bar]
1-Hexyne conversion [%]
3aa [%][b]
.5
11
2
3
4
5
6
7
8
9
80
5
>90
>90
>90
>90
46
>90
>90
10
41
57
52
32
16
46
10
traces
traces
1
2.3
2.3
2.3
2.3
2.3
2.3
2.3
2.3
2.3
2.3
methanol
methanol
methanol
methanol
methanol
1-propanol
CF3CH2OH
toluene
80
80
80
60
100
80
80
80
80
80
5
10
20
5
5
5
5
5
5
5
>90
>90
>90
10
11
DMF
THF
traces
[a]
The reactions were performed in 10 mL of solvent with 0.5% of [Rh
ACHTREUNG
[b]
Table 2. 1,4-Carbonylative addition of phenylboronic acid to
1-hexyne, influence of the catalyst precursor on the yield in
3aa.[a]
the GC analysis of the crude shows the complete dis-
appearance of 1-hexyne, the moderate yield of 3aa
can likely be attributed to polymerisation of the
alkyne in the presence of the rhodium-based cata-
lyst.[18] This competitive reaction led us to perform
the reaction using an excess of 1-hexyne (2.3 mmol of
1-hexyne vs. 1.5 mmol of phenylboronic acid). Under
these new conditions, the yield calculated from phe-
nylboronic acid increased from 41% to 57% and the
starting 1-hexyne once again completely disappeared
(Table 1, entries 1 and 2). Additional experiments
showed that the use of much higher quantities of
starting 1-hexyne does not improve the global yield in
3aa. The influence of the reaction conditions on the
yield in a,b-unsaturated ketone was also studied with
phenylboronic acid and 1-hexyne as model substrates
(Table 1).
The CO pressure needs to be well tuned to achieve
the highest yield of 3aa. When the pressure was in-
creased from 5 to 20 bar, the yield of the expected
a,b-unsaturated ketone gradually decreased from
57% to 32% (entries 2–4). On the other hand, if a
lower pressure was used, the formation of higher mo-
lecular weight derivatives 4 increased and the overall
yield of 3aa decreased once more. 808C proved to be
the optimal reaction temperature. Higher or lower
Entry
Catalyst
3aa [%][b]
10.5% [Rh
A
0
2
0.5% [Rh
A
0
3
A
0
4
5
1
1
G
0
0
U
A
2
6
7
8
1% RhCl3, 3 H2O
0.5% [Rh(C2H4)2Cl]2
0.5% [Rh(CO)2Cl]2
3
8
A
57
43
39
11
17
16
16
<2
9
0.5% [Rh
0.5% [Rh
ACHTREUNG
10
11
12
13
14
15
ACHTREUNG
1% ClRh
ACHTREUNG
0.5% [Rh
0.5% [Rh
1% ClRh(CO)dppp
0.25% Rh4(CO)12
G
A
AHCTREUNG
[a]
The reactions were performed with 1.5 mmol arylboronic
acid, 2.3 mmol 1-alkyne and 1% of rhodium catalyst in
10 mL of MeOH under 5 b CO at 808C for 1 8 h.
Yields were determined by GC using undecane as inter-
nal standard and based on phenylboronic acid.
[b]
temperatures led to markedly lower yields (entries 2, reactions were carried out starting from 2.3 mmol of
5, 6). At 608C, the reaction rate was probably too 1-hexyne, 1.5 mmol of phenylboronic acid in 10 mL
slow to achieve a high yield within 18 h. At this tem- MeOH under 5 bar CO pressure, using the same
perature, even the polymerisation process was limited amount of rhodium in all the experiments (1% of
to a 46% conversion. Methanol allowed much higher rhodium).
yields than any other organic solvents and appears to
In contrast with the reaction involving methyl vinyl
be the medium of choice to perform the reaction (en- ketone[13,14], most of the rhodium precursors were in-
tries 2, 7–10). Other alcohols such as 1-propanol or efficient and led to inactive catalysts (entries 1–6).
trifluorethanol gave much lower yields. Using THF or The best precursors were rhodium chloride dimers
DMF, as well as non-polar solvents like toluene, gave containing carbon monoxide (CO) or 1,5-cycloocta-
only traces of ketone 3aa.
diene (COD). To the best of our knowledge, the
Other rhodium complexes have been evaluated to COD is easily replaced by CO under pressure.[19] The
determine the best catalyst precursor (Table 2). The use of an excess of COD (in order to stabilize Rh-
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Scheme 3. Proposed catalytic cycle for the carbonylative addition of an arylboronic acid to a terminal alkyne.
COD complexes by shifting the equilibrium toward aged. Alternatively, the reaction between a rhodium
these compounds[20]) did not give rise to a better reac- complex C and a terminal alkyne can lead to a rhodi-
tivity (entries 8–10). All rhodium complexes with um vinylidene intermediate E as suggested by Lee
phosphines were much less efficient and afforded lim- et al. in a reaction involving an addition step of an
ited yields of 3aa from 11% to 17% (entries 11–14). aryl to a terminal alkyne.[17d] The a-migration of the
We investigated the use of Rh4(CO)12, as simple, com- acyl moiety to the vinylidene ligand yields the inter-
mercially available cluster, but this precursor was mediate F. Finally, compound D or F can be directly
completely ineffective.
protonated leading to the same product 3. In order to
Scheme 3 depicts two proposed catalytic cycles for determine which pathway is involved in our transfor-
this transformation. Starting from derivative A, a first mation, a standard reaction has been performed be-
step would involve the transmetallation of the aryl tween phenylboronic acid and deuterated 1-hexyne
from the boron to the rhodium centre giving a rhodi- (95% D) in MeOH (Scheme 4).
um-aryl species (compound B).
After one overnight reaction the product was puri-
B can insert a CO moiety yielding a metal-acyl fied by silica gel column chromatography and ana-
1
1
complex C as the key intermediate for this family of lysed by H NMR spectroscopy. The H NMR spec-
reactions. As usual for this type of insertion, the phe- trum of the resulting a,b-unsaturated ketone clearly
nomenon is likely reversible and the decarbonylation evidenced the exclusive deuterium incorporation at
step is moreover well documented.[21] One would the a-position of the carbonyl group (70% D). Al-
expect under these reaction conditions that the rhodi- though the recovery of deuterium to this position was
um-aryl complex B will directly react with the alkyne
and thus generate an aryl-substituted alkyne. This re-
action which has been only described with internal al-
kynes[22] was never observed in our case. In a further
step, two different pathways can be envisaged from C
to yield 3. The newly generated rhodium-acyl com-
plex C can react with the alkyne, giving a new rhodi-
um intermediate D. Depending on the insertion type
of the alkyne (head to head, head to tail and tail to
tail), several isomeric structures of D can be envis- deuterated terminal alkyne.
Scheme 4. Carbonylative addition of phenylboronic acid to a
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Carbonylative Addition of Arylboronic Acids to Terminal Alkynes
FULL PAPERS
incomplete, probably due to an MeOH-hexyne proton the reaction. A 57% yield of 3aa is obtained if phe-
exchange in the course of the reaction, this observa- nylboronic acid is reacted with 1-hexyne compared to
tion clearly discards a pathway involving a rhodium 41% yield of 3ab with 1-heptyne.[23] A similar trend is
vinylidene intermediate in favour of a 1,2-migration observed with p-tolylboronic acid, 1-hexyne or 1-hep-
process. The protonation thus occurs at the b-position tyne, yielding enones 3ba and 3bb in 69% and 47%
of the enone and several proton donors may be in- yields, respectively. The nature of the substituents on
volved in this final step.[15] The arylboronic acid itself the phenyl group also has an important impact on the
or the water generated via the dehydration of arylbor- yield of enones 3. Electron-donating substituents lead
onic acid in the cyclic trimer anhydride can act as to the highest yields in compounds 3. The enones 3ba
good proton donors. Another possibility arises from and 3ca obtained from the p-tolylboronic acid or p-
the protic nature of methanol which would favour this methoxyphenylboronic acid were isolated in, respec-
last step; this would be consistent with the fact that tively, 69% and 70% yields compared to 57% with
other solvents induce lower yields in 3aa.
phenylboronic acid. In contrast, using aryl groups
On the other hand, the detection by GC-MS of bearing electron-withdrawing substituents gave lower
higher molecular weight derivatives 4 is related to a yields. Enones 3da and 3fa synthesised from p-chloro-
side reaction involving intermediate B. Further 1- phenylboronic acid or p-fluorophenylboronic acid are
alkyne insertion remains, however, limited as no obtained in 45% and 51% yield. The meta-substitu-
other higher oligomers were detected by GC-MS tion of the chloride on the phenyl ring led to a poor
analysis.
reactivity since derivative 3ea is only obtained in
Finally, in order to delineate the scope and limita- 27% yield. A similar trend concerning the aryl sub-
tions of this reaction, various 1-alkynes and arylbor- stituents effect was reported in the case of the carbon-
onic acids were allowed to react using the standard ylative 1,4-addition reaction of arylboronic acids to
procedure (Scheme 5 and Table 3). The reaction prod- internal alkynes or methyl vinyl ketone.[14,18] In the
ucts were purified by silica gel column chromatogra- case of the reactivity of methyl vinyl ketone, this
phy with the appropriate eluent.
effect could be correlated to the lower selectivity of
The results obtained show that the chain size of the carbonylated versus non-carbonylated reaction prod-
alkyne plays an important role on the efficiency of ucts. Such a comparison cannot be made in this case
since no non-carbonylated product are observed but
this likely comes from the well established lower abili-
ty of carbon monoxide to insert into the metal-aryl
bond when the aryl moieties are substituted with elec-
tron-withdrawing groups.[24]
Conclusions
We have developed a new reaction, namely the rhodi-
um-catalysed carbonylative addition reaction of aryl-
boronic acids to terminal alkynes. The reaction ena-
bles the synthesis of a,b-unsaturated ketones 3, rather
than 5-aryl-2(5H)-furanones, with carbon monoxide
as carbonyl source. This catalytic reaction is a further
example of the use of a metal-acyl intermediate gen-
erated from carbon monoxide and an organoboron
derivative for organic synthesis. Further studies are in
progress aimed at both mechanistic aspects of the re-
action and applications of carbonylation reactions
using arylboronic acids and other co-reactants as sub-
strates.
Scheme 5. Carbonylative addition of various arylboronic
acids to terminal alkynes.
Table 3. 1,4-Carbonylative addition of various arylboronic
acids to terminal alkynes.[a]
Entry
Ar
R
3 (%)[b]
1
2
3
4
5
6
7
8
C6H5
p-CH3-C6H4
C6H5
p-CH3-C6H4
p-CH3O-C6H4
p-Cl-C6H4
m-Cl-C6H4
p-F-C6H4
C4H9
C4H9
C5H11
C5H11
C4H9
C4H9
C4H9
C4H9
3aa (57)
3ba (69)
3ab (41)
3bb (47)
3ca (70)
3da (45)
3ea (27)
3fa (51)
Experimental Section
General Remarks
[a]
Conditions: same as in Table 2, using 1mol% [Rh-
(COD)Cl]2 as catalyst precursor.
Isolated yields based on arylboronic acid.
A
All reactions were performed under a dry carbon monoxide
and nitrogen atmosphere. Methanol was distilled from Mg
[b]
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Julien Dheur et al.
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and stored under nitrogen prior to use. Terminal alkynes
and arylboronic acids were purchased from Sigma–Aldrich.
The alkynes were distilled from CaH2 prior to use. H and
3ab: 1-phenyl-oct-2-en-1-one: 1H NMR (300 MHz,
CDCl3): d=7.85 (d, 3JH,H =7.2 Hz, 2H, CHarom), 7.47 (t,
3JH,H =7.3 Hz, 1H, CHarom), 7.38 (t, 3JH,H =7.7 Hz, 2H,
1
13C NMR spectra were recorded in CDCl3 at room tempera-
ture on a Bruker AV300 spectrometer at 300 MHz. Chemi-
cal shifts were determined relative to internal standard
peaks and deuterated solvents (TMS at d=0 ppm for pro-
tons, CDCl3 at d=77.23 ppm for carbon atoms). GC analy-
ses for yield determinations were performed on a Varian
3900 chromatograph. Flash chromatography for product pu-
rifications was performed using silica gel (Macherey–Nagel,
60 Š, 230–400 mesh). Deuterated hexyne was prepared by
D2O–1-hexyne proton/deuterium exchange according to a
literature procedure.[25]]
3
CHarom), 6.99 (dt, JH,H =15.4 and 6.9 Hz, 1H, CH=CHCO),
3
6.79 (d, 3JH,H =15.5 Hz, 1H, CH=CHCO), 2.23 (q, JH,H
=
3
7.7 Hz, 2H, CH2), 1.44 (t, JH,H =7.2 Hz, 2H, CH2), 1.25 (m,
4H, CH2), 0.82 (t, JH,H =6.9 Hz, 3H); 13C NMR (75 MHz,
3
CDCl3): d=190.9, 150.2, 138, 132.6, 128.5, 128.1, 125.8, 32.8,
31.4, 27.9, 22.5, 14
3ba: 1-p-tolyl-hept-2-en-1-one: 1H NMR (300 MHz,
CDCl3): d=7.84 (d, 3JH,H =8.1Hz, 2H, CH arom), 7.26 (d,
3JH,H =7.8 Hz, 2H, CHarom), 7.05 (m, 1H, CH=CHCO), 6.88
3
(d, JH,H =15.5 Hz, 1H, CH=CHCO), 2.41(s, 1H, CH 3), 2.31
3
(q, JH,H =7.1Hz, 2H, COC H2CH2), 1.44 (m, 4H, CH2), 0.93
3
(t, JH,H =7.1Hz, 3H, CH 3); 13C NMR (75 MHz, CDCl3): d=
GC/MS Analysis
GC/MS, using both electron impact (EI) and chemical
ionisation (CI) techniques was used to analyse the crude of
reaction involving phenylboronic acid and 1-hexyne. CI was
used in order to confirm the molecular mass of those com-
pounds detected using EI/MS.
GC conditions: Gas chromatography was performed on a
Trace GC (Thermoelectron, San Jose, USA). A RTx-5MS
(Restek, Evry, France) column 30 m”0.25 mm i.d”0.25 mm
df was used for the analysis with a helium carrier gas flow of
1mLmin À1. The GC oven initial temperature was 808C and
temperature was ramped first at 108CminÀ1 to 2308C and
then at 58CminÀ1 to 2808C where it was held for 15 min. A
1 mL injection with a 1:100 split was used, the injector tem-
perature was fixed at 2808C.
MS conditions: MS analysis were performed on a Polaris
Q from Thermoelectron (San Jose, USA).The instrument
was calibrated using FC43 (perfluorotributylamine) as refer-
ence. The chemical ionisation (CI) reagent gas was methane
with a 2 mLminÀ1 flow rate. Mass spectra were acquired
over the range m/z 40 to 450 in positive ionisation mode.
The source temperature is 2008C.
190.4, 149.5, 143.3, 135.4, 129.2, 128.7, 125.8, 32.5, 30.3, 22.3,
21.6, 13.9; MS: m/z (%)=203 (12) [M+1]+, 202 (24) [M]+,
187 (35), 173 (14), 159 (20), 148 (29), 145 (28), 131 (17), 119
(100), 91(54), 81(7), 65 (15), 55 (8).
3bb: 1-p-tolyl-oct-2-en-1-one: 1H NMR (300 MHz,
CDCl3): d=7.77 (d, 3JH,H =8.2 Hz, 2H, CHarom), 7.18 (d,
3
3JH,H =7.9 Hz, 2H, CHarom), 6.98 (dt, JH,H =15.5 and 6.7 Hz,
3
1H, CH=CHCO), 6.80 (d, JH,H =15.4 Hz, 1H, CH=CHCO),
3
2.33 (s, 3H, CH3), 2.22 (q, JH,H =7 Hz, 2H, COCH2CH2),
3
1.4 (qt, JH,H =7.3 Hz, 2H, CH2), 1.25 (m, 4H, CH2), 0.82 (t,
3JH,H =6.7 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3): d=
189.1, 148.2, 142.2, 133.5, 127.4, 126.9, 123.9, 30.8, 29.7, 26.2,
20.6, 18.8, 11.5.
3ca:
1-p-chlorophenyl-hept-2-en-1-one:
1H NMR
3
(300 MHz, CDCl3): d=7.87 (d, JH,H =8.6 Hz, 2H, CHarom),
7.43 (d, JH,H =8.5 Hz, 2H, CHarom), 7.08 (dt, JH,H =15.5 Hz
and 6.3 Hz, 1H, CH=CHCO), 6.84 (d, JH,H =15.4 Hz, 1H,
3
3
3
3
CH=CHCO), 2.32 (q, JH,H =6.7 Hz, 2H, COCH2CH2), 1.25–
1.56 (m, 4H, CH2), 0.93 (t, 3JH,H =7.2 Hz, 3H, CH3);
13C NMR (75 MHz, CDCl3): d=189.6, 150.8, 139, 136.3,
129.9, 128.8, 125.4, 32.6, 30.3, 22.3, 13.9 MS: m/z (%)=223
(13) [M+1]+, 222 (26) [M]+, 207 (21), 193 (26), 187 (16),
179 (14), 168 (23), 154 (19), 141 (36), 139 (100), 115 (15),
111 (32), 81 (16), 75 (22), 55 (17).
General Procedure of Carbonylative Addition of
Arylboronic Acids to Terminal Alkynes
3da:
1 p-m-ethoxyphenyl-hept-2-en-1-one:
1H NMR
3
(300 MHz, CDCl3): d=7.86 (d, JH,H =6.9 Hz, 2H, CHarom),
6.96 (m, 1H, CH=CHCO), 6.85 (d, 3JH,H =7 Hz, 2H,
CHarom), 6.80 (d, 3JH,H =17 Hz, 1H, CH=CHCO), 3.77 (s,
Arylboronic acid (1.5 mmol) and rhodium catalyst (1%)
were introduced in a 100-mL stainless steel autoclave with a
glass insert tube and purged three times with nitrogen. In a
Schlenk tube flushed with nitrogen, the terminal alkyne
(2.3 mmol) and the internal standard (142 mL) were dis-
solved in methanol (10 mL). The solution was transferred
with a syringe into the autoclave, which was then pressurised
with 5 bar of carbon monoxide and heated at 808C with a
water bath. After 18 h, the autoclave was cooled to room
temperature and depressurised. The pure products were iso-
lated by flash chromatography (n-hexane/diethyl ether: 95/
5).
3
3H, OCH3), 2.22 (q, JH,H =6.7 Hz, 2H, COCH2CH2), 1.35
(m, 4H, CH2), 0.84 (t, JH,H =5.2 Hz, 3H, CH3); 13C NMR
3
(75 MHz, CDCl3): d=189.1, 163.2, 149, 130.83, 130.79, 125.5,
113.7, 55.4, 32.5, 30.3, 22.3, 13.9; MS: m/z (%)=219 (6)
[M+1]+, 218 (22) [M]+, 189 (10), 175 (23), 164 (37), 150
(14), 135 (100), 121 (4), 107 (10), 92 (7), 77 (19), 63 (4), 55
(3).
3ea:
1-(3-chlorophenyl)-hept-2-en-1-one:
1H NMR
3
(300 MHz, CDCl3): d=7.79 (s, 1H, CHarom), 7.70 (d, JH,H
=
3
3aa: 1-phenyl-hept-2-en-1-one: 1H NMR (300 MHz,
CDCl3): d=7.92 (d, 3JH,H =7.3 Hz, 2H, CHarom), 7.55 (t,
7.5 Hz, 1H, CHarom), 7.40 (t, JH,H =7.7 Hz, 1H, CHarom), 7.3
(t, 3JH,H =7.09 Hz, 1H), 7.09 (dt, 3JH,H =15.2 and 4.8 Hz,
1H), 6.72 (d, 3JH,H =15.4 Hz, 1H), 2.32 (q, 3JH,H =6.9 Hz,
3JH,H =7.3 Hz, 1H,), 7.46 (t, J=7.7 Hz, 2H, CHarom), 7.07 (dt,
3
3
2H, COCH2CH2), 1.42 (m, 4H, CH2), 0.94 (t, JH,H =5.3 Hz,
J=7.0 and 15.3 Hz, 1H, CH=CHCO), 6.87 (d, JH,H
15.3 Hz, 1H, CH=CHCO), 2.31(q,
=
3H, CH3); 13C NMR (75 MHz, CDCl3): d=189.4, 151.1,
139.6, 134.8, 132.5, 129.8, 128.6, 126.6, 125.4, 32.6, 30.2, 22.3,
13.8; MS: m/z (%)=223 (12) [M+1]+, 222 (34) [M]+, 207
(24), 193 (31), 187 (29), 179 (16), 168 (19), 158 (13), 154
(19), 145 (20), 141 (34), 139 (100), 131 (13), 115 (20), 111
(38), 81(12), 75 (22), 55 (30).
3JH,H =7.0 Hz, 2H,
3
COCH2CH2), 1.44 (m, 4H, CH2), 0.93 (t, JH,H =7.1Hz, 3H,
CH3); 13C NMR (75 MHz, CDCl3): d=190.9, 150.1, 138.0,
132.6, 128.5, 125.9, 32.6, 30.3, 22.3, 13.9; MS: m/z (%)=189
(11) [M+1]+, 188 (35) [M]+, 173 (35), 159 (34), 145 (44),
131 (44), 117 (23), 105 (100), 91 (19), 77 (63), 65 (2), 55 (21).
2504
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2499 – 2506

Carbonylative Addition of Arylboronic Acids to Terminal Alkynes
FULL PAPERS
3fa:
1-(4-fluorophenyl)-hept-2-en-1-one:
1H NMR
[5] a) M. Shibuya, S. Ito, M. Takahashi, Y. Iwabuchi, Org.
Lett. 2004, 6, 23, 4303; b) M. Jurado-Gonzalez, A. C.
Sullivan, J. R. H. Wilson, Tetrahedron Lett. 2004, 45,
4465; c) U. Bora, M. K. Chaudhuri, D. Dey, D. Kalita,
W. Kharmawphlang, G. C. Mandal, Tetrahedron 2001,
57, 2445.
3
(300 MHz, CDCl3): d=7.96 (t, JH,H =5.6 Hz, 2H, CHarom),
3
7.09 (m, 3H, CHarom and CH=CHCO), 6.85 (d, JH,H
=
15.4 Hz, 1H, CH=CHCO), 2.31(q, 3JH,H =6.8 Hz, 2H), 1.43
(m, 4H), 0.93 (t, 3JH,H =7.1Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=189.0, 165.4 (1JC,F =254 Hz), 150.2, 134.2 (4JC,F
=
13 Hz), 131.0 (3JC,F =37 Hz), 125.3, 115.5 (2JC,F =87 Hz), 32.5,
30.2, 22.3, 13.8; MS: m/z (%)=207 (10) [M+1]+, 206 (20)
[M]+, 191 (20), 177 (22), 163 (18), 152 (13), 149 (14), 138
(16), 123 (100), 109 (12), 95 (33), 81 (10), 75 (15), 55 (9).
4aa: 3,4-dibutyl-4-phenylcyclopent-2-enone: 1H NMR
(300 MHz, CDCl3): d=7.18 (m, 5H, CHarom), 5.88 (s, 1H,
CH2C=CH-CO), 2.90 and 2.76 (AB system, 2H, CHAHB,
2J=18.8 Hz), 2.37 (t, 2H, 3JH,H =7.6 Hz),1.83 [m, 2H,
[6] a) W. Yin, Y. Ma, J. Xu, Y. Zhao, J. Org. Chem. 2006,
71, 4312; b) M. S. Taylor, D. N. Zalatan, A. M. Lerch-
ner, E. N. Jacobsen, J. Am. Chem. Soc. 2005, 127, 1313.
[7] For the Pauson–Khand reaction: a) K. M. Brummond,
J. L. Kent, Tetrahedron 2000, 56, 3263; b) Y. K. Chung,
Coord. Chem. Rev. 1999, 188, 297; starting with a stoi-
chiometric nickeltetracarbonyl complex: c) J. R. Her-
manson, J. W. Hershberger, A. R. Pinhas, Organometal-
lics 1995, 14, 5426; carbonylation of a zirconacyclopen-
tadiene complex: d) Z. Xi, H.-T. Fan, S. Mito, T. Taka-
hashi J. Organomet. Chem. 2003, 682, 108.
[8] a) T. Hayashi, K. Yamasaki, Chem. Rev. 2003, 103,
2829; b) T. Hayashi, Synlett 2001, 879; c) M. Sakai, H.
Hayashi, N. Miyaura, Organometallics 1997, 16, 4229;
d) K. Fagnou, M. Lautens, Chem. Rev. 2003, 103, 169.
[9] T. Hayashi, M. Takahashi, Y. Takaya, M. Ogasawara, J.
Am. Chem. Soc. 2002, 124, 5052.
3
CH2C(Ph)], 1.02–1.38 (m, 10H), 0.87 (t, 3H, JH,H =7.3 Hz),
0.78 (t, 3H, 3JH,H =7.3 Hz); 13C NMR (300 MHz, CDCl3):
d=211.2, 180.9, 143.2, 128.4, 127.9, 126.4, 126.3, 55.5, 46.5,
38.1, 33.1, 29.2, 26.8, 23.2, 22.5, 13.9, 13.8; MS: m/z (%)=
270 (5) [M]+, 214 (100), 172 (72).
Acknowledgements
[10] H. O. Chang, H. J. Hyung, S. K. Ki, K. Nakjoong,
Angew. Chem. Int. Ed. 2003, 42, 7, 805.
The authors thank Adeline Page for Mass Spectrometry ex-
periments made at the Centre Commun de SpectromØtrie de
Masse, UniversitØ des Sciences et Technologies de Lille
(France).
[11] a) M. P. García, A. P. Martínez , M. V. JimØnez, C. Siur-
ana, L. A. Oro, F. J. Lahoz, A. Tiripicchio, Inorganica
Chimica Acta 2000, 308, 51; b) P. J. Stang, L. Song, Q.
Lu, B. Halton, Organometallics 1990, 9, 2149.
[12] a) M. C. Willis, H. E. Randell-Sly, R. L. Woodward,
G. S. Currie, Org. Lett. 2005, 7, 11, 2250; b) M. Imai,
M. Tanaka, K. Tanaka, Y. Yamamoto, N. Imai-Ogata,
M. Shimowatari, S. Nagumo, N. Kawahara, H. Sue-
mune, J. Org. Chem. 2004, 69, 1144; c) C. P. Lenges,
P. S. White, M. Brookhart, J. Am. Chem. Soc. 1998, 120,
6965; d) T. Kondo, N. Hiraishi, Y. Morisaki, K. Wada,
Y. Watanabe, T.-a. Mitsudo, Organometallics 1998, 17,
2131.
[13] M. Sauthier, Y. Castanet, A. Mortreux, Chem.
Commun. 2004, 1520.
[14] H. Chochois, M. Sauthier, E. Maerten, Y. Castanet, A.
Mortreux, Tetrahedron 2006, 62, 11740.
[15] With organozinc reagents: M. Yuguchi, M. Tokuda, K.
Orito, J. Org. Chem. 2004, 69, 908.
[16] Metal-catalysed hydroacylations of alkynes involving
an aldehyde as acylating reagent: a) X. YµÇez Rueda,
S. Castillón, J. Organomet. Chem. 2007, 692, 1628;
b) M. C. Willis, H. E. Randell-Sly, R. L. Woodward,
S. J. McNally, G. S. Curie, J. Org. Chem. 2006, 71, 5291;
c) T. Tsuda, T. Kiyoi, T. Saegusa, J. Org. Chem. 1990, 5,
2554; d) C.-H. Jun, H. Lee, J.-B. Hong, B.-I. Kwon,
Angew. Chem. Int. Ed. 2002, 41, 12, 2146; e) K. Tanaka,
G. C. Fu, J. Am. Chem. Soc. 2002, 124, 10296; f) K.
Takeishi, K. Sugishima, K. Sasaki, K. Tanaka, Chem.
Eur. J. 2004, 10, 5681; g) M. C. Willis, H. E. Randley-
Sly, R. L. Woodward, G. S. Currie, Org. Lett. 2005, 7,
11, 2250; h) K. Tanaka, G. C. Fu, J. Am. Chem. Soc.
2001, 123, 11492; reactions involving a stoichiometric
metal-acyl reagent: i) A. Saito, Y. Oka, Y. Nozawa, Y.
Hanzawa, Tetrahedron Lett. 2006, 47, 2201; j) Z. Huan,
T. Fujioka, S.-I. Usugi, H. Yorimitsu, H. Shinokubo, K.
Oshima, Org. Biomol. Chem. 2005, 3, 1622.
References
[1] Several reagents are used in those selected examples:
dialkylzinc: a) S. V. Malhotra, Y. Wang, Tetrahedron:
Asymmetry 2006, 1032; b) O. Knopf, A. Alexakis, Org.
Lett. 2002, 4, 3835; c) A. Alexakis, J. Burton, J. Vastra,
C. Benhaim, X. Fournioux, A. van den Heuvel, J.-M.
LevÞque, F. MazØ, S. Rosset, Eur. J. Org. Chem. 2000,
4011; Grignard reagents: d) S. R. Harutyunyan, F.
López, W. R. Browne, A. Corea, D. PeÇa, R. Badorrey,
A. Meetsma, A. J. Minaard, B. L. Feringa, J. Am.
Chem. Soc. 2006, 128, 9103; e) D. Martin, S. Kehrli, M.
dꢁAugustin, H. Clavier, M. Mauduit, A. Alexakis, J.
Am. Chem. Soc. 2006, 128, 8416; ketones, amines, and
thiols using a base in catalytic amount: f) R. Shankar,
A. K. Jha, U. S. Singh, K. Hajela, Tetrahedron Lett.
2006, 47, 3077; nitroalkanes: g) D. Y. Park, S. Gowri-
sankar, J. N. Kim, Tetrahedron Lett. 2006, 47, 6641 ;
indole with Lewis acids: h) M. Shi, S.-C. Cui, Q.-J. Li,
Tetrahedron 2004, 60, 6679.
[2] a) I. Kondolff, H. Doucet, M. Santelli, Tetrahedron
Lett. 2003, 44, 8487; b) A. Bianco, C. Cavarischia, M.
Guiso, Eur. J. Org. Chem. 2004, 2894.
[3] Chalcone epoxidation: M. Hinch, O. Jacques, C. Drago,
L. Caggiano, R. F. W. Jackson, C. Dexter, M. S. Anson,
S. J. F. Macdonald, J. Mol. Catal. A : Chem. 2006, 251,
123.
[4] The reaction is also called Claisen–Schmidt reaction:
M. Smith, J. March, Marchꢀs Advanced Organic
Chemistry : Reactions, Mechanisms, and Atructure, 6th
edn., Wiley-Interscience, New York, 2006.
Adv. Synth. Catal. 2007, 349, 2499 – 2506
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2505

Julien Dheur et al.
FULL PAPERS
[17] Ö. Aksun, N. Dege, L. Artok, H. Türkmen, B. C¸ etin-
kaya, Chem. Commun. 2006, 3187–3189.
c) G. R. Clark, W. R. Roper, L. J. Wright, V. P. D. Yap,
Organometallics 1997, 16, 51 35.
[18] Recent publications for rhodium-catalysed terminal
acetylene polymerisation: a) Y. Kishimoto, M. Itou, T.
Miyatake, T. Ikariya, R. Noyori, Macromolecules 1995,
28, 6662; b) M. Tabata, T. Sone, Y. Sadahiro, Macro-
mol. Chem. Phys. 1999, 200, 265; c) A. Nakazato, I.
Saeed, T. Katsumata, T. Masuda, J. Zednik, J. Vohlidal,
J. Polym. Sci. Part A: Polym. Chem. 2002, 40, 1689.
[19] T. Kobayashi, Y. Koga, K. Narasaka, J. Organomet.
Chem. 2001, 624, 73.
[22] a) T. Hayashi, K. Inoue, N. Taniguhi, M. Ogasawara, J.
Am. Chem. Soc. 2001, 123, 9918; b) M. Lautens, M.
Yoshida, Org. Lett. 2002, 4, 123; c) E. Genin, V. Mi-
chelet, J.-P. GenÞt, J. Organomet. Chem. 2004, 689,
3820; d) R. Shintani, A. Tsurusaki, K. Okamoto, T.
Hayashi, Angew. Chem. Int. Ed. 2005, 44, 3909.
[23] Complementary experiment carried out using 1-hep-
tyne and triphenylboroxine led to a slightly better yield
(51% based on phenyl moiety of the boron derivative).
[24] a) N. Sugita, J. V. Minkiewicz, R. F. Heck, Inorg. Chem.
1978, 17, 2809; b) G. R. Clark, W. R. Roper, L. J.
Wright, V. P. D. Yap, Organometallics 1997, 16, 5135.
[25] L. J. Goossen, M. Blanchot, C. Brinkmann, K. Goossen,
R. Karch, A. Rivas-Nass, J. Org. Chem. 2006, 71, 950.
[20] R. Itooka, Y. Iguchi, N. Miyaura, J. Org. Chem. 2003,
68, 6000.
[21] a) H. M. Colquhoun, D. J. Thompson, M. V. Twigg, Car-
bonylation, Direct Synthesis of Carbonyl Compounds,
1991, Plenum Press, New York; b) N. Sugita, J. V. Min-
kiewicz, R. F. Heck, Inorg. Chem. 1978, 17, 2809;
2506
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2499 – 2506