[(NHC)AuCl]-catalyzed Meyer-Schuster rearrangement: scope and limitations

Article abstract of DOI:10.1016/j.tet.2008.10.111

An efficient catalytic system allowing for the synthesis of a variety of α,β-unsaturated ketones has been developed. [(NHC)AuCl] (NHC{double bond, long}N-heterocyclic carbene) in the presence of a silver(I) salt was found to catalyze the Meyer-Schuster rearrangement, leading to α,β-unsaturated ketones from easily accessible propargylic alcohols in high yields. Catalysis was performed in a 2:1 mixture of methanol and water at 60 °C and afforded good yields even for tertiary alcohols and sterically demanding substrates. Thorough evaluation of the present catalytic system uncovered that it was unsuitable for terminal alkynes and primary alcohols. In these cases low yields of the target molecules were obtained due to the formation of unexpected by-products.

Full text of DOI:10.1016/j.tet.2008.10.111

Tetrahedron 65 (2009) 1767–1773
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
[(NHC)AuCl]-catalyzed Meyer–Schuster rearrangement: scope and limitations
y
z
,
y
*
´
´
Ruben S. Ramon , Nicolas Marion , Steven P. Nolan
Institute of Chemical Research of Catalonia (ICIQ), Av. Pa¨ısos Catalans 16, 43007 Tarragona, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 July 2008
Received in revised form 21 October 2008
Accepted 22 October 2008
Available online 24 December 2008
An efficient catalytic system allowing for the synthesis of a variety of a,b-unsaturated ketones has been
developed. [(NHC)AuCl] (NHC]N-heterocyclic carbene) in the presence of a silver(I) salt was found to
catalyze the Meyer–Schuster rearrangement, leading to -unsaturated ketones from easily accessible
a,b
propargylic alcohols in high yields. Catalysis was performed in a 2:1 mixture of methanol and water at
60 ꢀC and afforded good yields even for tertiary alcohols and sterically demanding substrates. Thorough
evaluation of the present catalytic system uncovered that it was unsuitable for terminal alkynes and
primary alcohols. In these cases low yields of the target molecules were obtained due to the formation of
unexpected by-products.
Keywords:
Meyer–Schuster rearrangement
Gold
NHC
Ó 2008 Elsevier Ltd. All rights reserved.
Propargylic alcohol
Enones
1. Introduction
rearrangement,11 this transformation can be catalyzed by several
transition metals.12
The interest for
a
,
b
-unsaturated carbonyl compounds is linked
Recently, gold has shown to be useful in catalysis. The activation
to their general importance in synthesis. Such compounds are
useful building blocks, e.g., in total synthesis of natural products,1
display biological activities2 and are notably used as substrates in
cyclopropanation,3 Michael-additions4 and cycloadditions such as
the Diels–Alder reaction.5 Hence, efficient procedures leading to
of alkynes by AuI,III leading to a manifold of new structures and
reactivity highlights the use of gold as an excellent activator of
p-
systems.13 The Lewis acidity of gold complexes and their ability to
activate alkynes as well as allenes for inter- or intramolecular nu-
cleophilic attack has prompted intensive research, notably in-
volving oxo-nucleophiles.
these substrates are of interest. Typical approaches to
a,b-un-
saturated ketones are the aldol condensation,6 including the
Knoevenagel reaction,7 and the Horner–Wadsworth–Emmons
(HWE) reaction which produces unsaturated esters.8 These classical
reactions have proved to be very useful and are well established as
standard procedures. Nevertheless, for synthetic chemists there is
still an interest in developing new routes to unsaturated carbonyl
compounds as in some cases standard procedures fail to provide
expected results. Furthermore, some of these methods generate
considerable amount of waste and do not meet the standards of
modern and environmentally friendly chemistry. In this context,
Gold-catalyzed formation of a,b-unsaturated enones can be
performed using readily accessible propargylic acetates as sub-
strates.14 Zhang et al. recently reported the formation of un-
saturated ketones catalyzed by [(PPh3)AuNTf2].15 Concomitantly,
our group reported the [(NHC)AuI]-catalyzed formation of enones
as well as enals from propargylic acetates (Scheme 1).16 Compu-
tational studies on the mechanism of this reaction led us to propose
the unexpected activation of water by gold(I) instead of activation
of the p-system. Formation of conjugated enones from propargylic
alcohols in the presence of gold is also known. The AuIII-catalyzed
rearrangement of propargylic alcohols was notably observed by
Campagne et al., when using 5 mol % of NaAuCl4 as catalyst in the
the isomerization of propargylic alcohols into a,b-unsaturated ke-
tones and aldehydes allows total atom economy9 and represents
an attractive alternative. As the Rupe10 and the Meyer–Schuster
presence of ethanol.17 Dudley reported the preparation of
a,b-un-
saturated esters, aiming to find an alternative methodology to the
HWE olefination of hindered ketones by using electron-rich
* Corresponding author. Fax: þ44 1334 463808.
E-mail address: sn17@st-andrews.ac.uk (S.P. Nolan).
Present address: School of Chemistry, University of St-Andrews, St-Andrews,
OAc
O
[(NHC)AuCl]/AgX
y
R1
R1
R2
- AcOH
R2
KY16 9ST U.K.
z
Present address: Department of Chemistry, Massachusetts Institute of Tech-
Scheme 1. Formation of
a,
b-unsaturated enones from propargylic acetates.
nology, Cambridge, MA 02139, USA.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.10.111

1768
R.S. Ramo´n et al. / Tetrahedron 65 (2009) 1767–1773
R2 OH
R1
R2
O
AuCl3 (5 mol %)
1,2 = alkyl, aryl
A
N
N
R
R1
Ts
OEt
R
R
R =
OEt
OH
Au
Cl
O
[(NHC)AuCl]
NHC =
IMes
ItBu
IPr
[(PPh3)AuCl] (5 mol %)
B
N
Ts
N
n
Scheme 4. Gold–NHC complexes used.
n
Scheme 2. Meyer–Schuster rearrangements reported by Dudley and Chung.
Lowering the catalyst loading from 2 mol % to 0.1 mol % only led to
minor conversion despite prolonged reaction time.
Having an efficient catalytic system in hand, we explored the
scope of this transformation. It should be noted that the reaction
time and the temperature necessary to reach full conversion were
found highly dependent of the substrates. So, in order to ensure
complete conversion of all substrates, reactions were heated
overnight. To examine the influence of substituents on the aryl
moiety, different aryl derivatives with a butyl chain in the acety-
lenic position were first screened. As illustrated in Table 2, good to
excellent yields were obtained for a variety of substrates. Sub-
stitution of the aromatic ring with electron-withdrawing groups
(entries 2 and 3) furnished slightly lower yields compared to 1a. On
the other hand, electron-donating substituents (entries 4 and 5) as
well as the tertiary alcohol 1f (entry 6) afforded excellent results. Of
note, 1a–1e were selectively converted into the (E)-isomers. This
result is in line with the stereoselective conversion of propargylic
acetates we previously reported.16 Furthermore, the present cata-
lytic system equals or outperforms other catalytic systems for the
Meyer–Schuster rearrangement of propargylic alcohols.18–21
Next, the effect of the acetylenic substituent was examined
while keeping an unsubstituted phenyl ring at the propargylic
position (Table 3). When the acetylenic substituent was modified
from n-butyl to tert-butyl, a good conversion into the correspond-
ing product was observed (entry 1). This is remarkable since the
corresponding propargylic acetate failed to react with our previous
catalytic system.16 Using activating substituents such as a phenyl
group (entry 2) provided excellent conversion. Interestingly, with
1i, transesterified methoxyester 2ia was obtained quantitatively
when using MeOH as solvent (entry 3). In order to avoid this
transesterification, the same reaction was performed in dioxane.
With a yield of up to 97%, an E/Z ratio of 5:1 was observed. This
represents a slightly better stereoselectivity for compound 2ib than
reported previously by Dudley et al.12i Changing from ethoxy al-
kyne 1i to ethoxy propiolate 1j, reactivity was clearly switched,
leading to the unexpected product 2j in 69% yield (entry 5).
ethoxyacetylene and tertiary propargylic alcohols (Scheme 2, A).
While a tertiary alcohol should facilitate the proposed ionization of
the C–O bond, the use of electron-rich alkynes enforces alkyne
activation by a soft Lewis-acid catalyst such as AuCl3.18 An advan-
tage of activating the alkyne instead of the alcohol function is the
elimination of the concurring Rupe rearrangement.10 Dudley et al.
later reported an improved catalytic system with expanded scope
using AuI instead of AuIII.19 AuI-catalyzed Meyer–Schuster rear-
rangement of propargylic alcohols was also reported by Chung et al.
in 2007 using [(PPh3)AuCl] (Scheme 2, B),20 but only moderate to
good yields were obtained for specific substrates. Recently, Akai
et al. disclosed a promising catalytic system applicable to primary
alcohols but requiring [MoO2(acac)2] in addition to [(PPh3)AuCl]
and AgOTf.21
In this contribution, we present a general procedure to produce
a,b-unsaturated ketones and esters in good yields and high ster-
eocontrol with a [(NHC)AuCl]-catalyst under mild reaction condi-
tions. The scope and a proposed mechanism will be discussed as
well as the limitations of the present catalytic system.
2. Results and discussion
As gold behaves as an excellent catalyst for p-activation, our aim
is to explore the scope of gold–NHC complexes in catalysis.22
Amongst others, we reported in this context the formation of
indenes using propargylic acetates as substrates under anhydrous
conditions23 as well as the formation of enones in the presence of
water (Scheme 3).16 Our interest in propargylic alcohols lies in the
fact that they are readily available, presenting a more straightfor-
ward synthesis, usually in one step from addition of an acetylide
onto a ketone or an aldehyde. As a starting point, we used com-
pound 1a with 2 mol % of [(IPr)AuCl] in the presence of AgSbF6 in
DCM. While there was no conversion under anhydrous conditions,
we observed the formation of remarkable amounts of the Meyer–
Schuster product 2a when using technical grade DCM. After testing
a broad spectrum of solvents, we decided to use MeOH for further
reactions. We made a brief screening of commonly used gold–NHC
complexes (Scheme 4). Noteworthy, [(IPr)AuCl] was found to be by
far the best catalyst in comparison to [(IMes)AuCl] and [(ItBu)AuCl]
(Table 1, entries 1–6). [(IPr)AuCl] and silver tetrafluoroborate were
independently tested as catalyst, in both cases the starting material
was recovered unchanged (entries 7 and 8). Concerning the nature
of the silver salts, AgBF4 gave similar results compared to AgSbF6.
Table 1
Catalyst screening for Meyer–Schuster rearrangementa
OH
O
[(NHC)AuCl]/AgSbF6 (2 mol %)
MeOH/H2O, rt
Bu
Bu
1a
2a
Entry
Catalyst
Time
Conv.b (%)
1
2
3
4
5
6
7
8
[(IPr)AuCl]
70 min
70 min
70 min
4 h
4 h
4 h
80
27
37
99
42
70
0
[(IMes)AuCl]
[(ItBu)AuCl]
[(IPr)AuCl]
[(IMes)AuCl]
[(ItBu)AuCl]
Only AgSbF6
Only [(IPr)AuCl]
anh.
[(NHC)AuCl]
AgX
OAc
OAc
O
Bu
DCM, rt
3 h
3 h
Bu
H2O
0
Bu
a
Reaction conditions: 1a (0.27 mmol) in MeOH (2 mL), water (0.3 mL),
[(NHC)AuCl]/AgSbF6(2 mol %), rt.
b
Conversion determined by GC.
Scheme 3. [(NHC)AuCl]-catalyzed formation of indenes and enones.

R.S. Ramo´n et al. / Tetrahedron 65 (2009) 1767–1773
1769
Table 2
Effect of aryl derivatives in propargylic position
R2
O
R2
OH
[(IPr)AuCl]/AgSbF6 (2 mol %)
Bu
MeOH/H2O, 60 °C, overnight
Bu
R1
R1
1
2
Entry
1
Propargylic alcohol
1
Enone
2
Yielda (%)
96
OH
O
1a
2a
Bu
Bu
OH
O
2
1b
Bu
2b
81b
Bu
F3C
F3C
NC
OH
OH
O
O
3
4
1c
2c
74b
81b
Bu
Bu
Bu
Bu
NC
O
O
O
O
1d
2d
OH
O
5
1e
1f
2e
2f
92b
Bu
Bu
OH
O
6
96
Bu
Bu
a
NMR yields with respect to benzaldehyde as internal standard are average of two runs.
Isolated yield.
b
Table 3
Effect of acetylenic substituents
OH
O
[(IPr)AuCl]/AgSbF6 (2 mol %)
MeOH/H2O, 60 °C, overnight
R1
R1
2
1
Entry
1
Propargylic alcohol
OH
1
Enone
2
Yielda (%)
86
O
1g
2g
2h
OH
O
2
1h
95
OH
OH
O
3
1i
1i
2ia
2ib
81 E/Z 1.5:1
71 E/Z 5:1
O
O
O
O
O
4b
O
OH
5
1j
2j
69c
O
O
MeO
O
a
NMR yields with respect to benzaldehyde as internal standard are average of two runs.
Reaction performed in dioxane to avoid transesterification.
Isolated yield.
b
c

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R.S. Ramo´n et al. / Tetrahedron 65 (2009) 1767–1773
Table 4
Screening of substrates with varied substitution patterns
R2
R1
R2
OH
O
[(IPr)AuCl]/AgSbF6 (2 mol %)
MeOH/H2O, 60 °C, overnight
R1
R3
R3
2
1
Entry
1b
Propargylic alcohol
1
Enone
2
Yielda (%)
OH
O
1k
2k
86 E/Z 5:1
O
O
Bu
O
O
OH
Bu
2
1l
2l
86 E/Z 1:1
HO
3
4
1m
1n
2m
2n
96
28
HO
O
OH
O
5
1o
1p
2o
2p
58
O
HO
6
89c
F
F
a
NMR yields with respect to benzaldehyde as internal standard are average of two runs.
Reaction performed in dioxane to avoid transesterification.
Isolated yield.
b
c
Remarkably, when using 1,4-dioxane as solvent neither the Meyer–
Schuster rearrangement nor the formation of a lactone was
observed. Instead, the hydration of the alkyne leading to the cor-
1r showed low reactivity towards the Meyer–Schuster rearrange-
ment and AuI-catalyzed hydration of the triple bond was observed
instead.24 Finally, we would like to point out the formation of 3-
responding a-hydroxy ketone was obtained.
Finally, Table 4 shows an extended scope of the reaction. As with
the results in Table 3, when using the ethoxy alkyne 1k good yields
and stereoselectivity (Table 4, entry 1) were achieved. Entries 4 and
5 illustrate poor to moderate yields. Obviously, the absence of an
aryl substituent decreases the conversion of propargylic alcohols
into the corresponding enones. Entries 3 and 6 present examples
for ‘switched’ substitution compared to Tables 2 and 3. Conversion
of substrates having the aryl moiety in the acetylenic position while
there is an alkyl substituent in a propargylic position, was com-
parable to results for other substrates. The conversion of the ter-
tiary propargylic alcohol 1l (entry 2), gave as expected a 1:1
mixture of the two diastereomers of 2l as the butyl and the ethyl
chain can hardly be differentiated structurally.
Table 5
Substrates exhibiting low reactivitya
R2 OH
R1
[(IPr)AuCl]/AgSbF6 (2 mol %)
complex mixture
MeOH/H2O, 60 °C, overnight
R3
1
2
Entry
1b
Propargylic alcohol
1
Product, yield (%)
O
O
OMe
OH
Ph
1q
Ph
Ph
2qa, 5%
2qb, 35%
HO
HO
Ph
O
As shown in Tables 2–4, [(IPr)AuCl] in the presence of AgSbF6
represents an adequate and fairly stereoselective catalytic system
for the substrates tested so far. Except for compound 1j (Table 3,
entry 5) showing a different but interesting reactivity.
2
3
1r
1s
H
Ph
2ra, 32%
O
Ph
2rb, 8%
HO
TMS
In spite of the remarkable scope of this catalytic system it is
limited to substrates substituted in the acetylenic and propargylic
positions. Experiments using either primary alcohols or terminal
alkynes gave complex product mixtures. More specifically, the
formation of the enone or enal was always observed, but yields
were minor due to the important formation of by-products. Similar
results were achieved when using alkynes with a trimethylsilyl
group (TMS) in the acetylenic position (Table 5, entry 3). A com-
pilation of substrates not suitable, under these conditions, for the
Meyer–Schuster rearrangement is presented in Table 5. Compound
Complex mixture
O
OH
Ph
Ph
4
1t
Ph
2t, 9%
a
NMR yields with respect to benzaldehyde as internal standard are average of
two runs.
b
Reaction performed at room temperature.

R.S. Ramo´n et al. / Tetrahedron 65 (2009) 1767–1773
1771
R
N
R
N
N
OH
N
R
R
HO
R1
Au
Au
O
R2
H
R1
H
HO
R1
O
R2
R2
I
II
N
N
N
N
R
R
AgX,H2O
R
R
Au
OH
Au
Cl
H2O
N
R
N
•
N
R
R
N
R
H
O
O
Au
Au
R1
R2
H
O
O
•
R2
R2
R1
R1
IV
Scheme 5. Proposed mechanism for the [(NHC)AuCl] catalyzed Meyer–Schuster rearrangement.
III
phenyl-indanone from alkynol 1t, isolated with a poor yield of 9%.
In the literature, the conversion of a propargylic alcohol into an
indanone derivative has been achieved by rhodium-catalyzed
isomerization,25 whereas no AuI-catalyzed process has been
reported so far to the best of our knowledge. We propose a mech-
anism with the initial conversion of the propargylic alcohol into the
enal, followed by a AuI-activation of either the aryl or more likely
the aldehyde moiety leading to an allyl alcohol that can isomerize
into 2t.26 Since both types of activation are unusual for gold(I)
complexes, investigations on this reactivity are being pursued.
For the Meyer–Schuster rearrangement, Dudley postulated
a mechanism catalyzed by gold(I) as well as a revised one for
scandium(III).12i Even if the mechanism was supported by experi-
mental results, we suppose, due to noteworthy differences between
both systems, that a different reaction pathway is involved. Dudley
postulated the initial attack of the solvent, ethanol, followed by the
attack of a water molecule to form an intermediate, shown in
Scheme 6, that can convert into the conjugated ester. Using
methanol instead of ethanol lead to a 1:1 mixture of unsaturated
ethoxy and methoxyester, supporting their mechanistic proposal.
In contrast to Dudley, we observed with 1i (Table 3, entry 3) as well
as with 1k (Table 4, entry 1) quantitative transesterification to
unsaturated methoxyester when using MeOH as solvent. Note-
worthy, 2ib was recovered when subjected to standard reaction
conditions in MeOH. This excludes the possibility of a Meyer–
previously postulated based on DFT calculations.16 This
[(NHC)AuOH] species could then attack the triple bond to give I.
Transition state II should facilitate elimination of water leading to
the activated allenolate III. The gold–hydroxo complex could finally
be regenerated through interaction with another water molecule
with release of the reaction product as illustrated in IV. Neverthe-
less, a straightforward mechanism with the triple bond activated by
gold involving a water attack to form an allenol that tautomerizes
into the product cannot be excluded at this time.
Regarding the formation of furanone 2j we suggest a different
pathway in which MeOH attacks the gold-activated triple bond
leading to a vinylether A. If the (E)-isomer is formed, the hydroxy
group is spacially close enough to attack the ester leading to the
furanone derivative (Scheme 7). In the case of the formation of the
OH
OH
EtO
OH
[Au]+
OEt
O
H
[Au]+
MeOH
Ph
Ph
OEt
Ph
O
O
OMe
1j
(E)-A
MeOH
Schuster rearrangement followed by
a gold-catalyzed trans-
OH
H
Ph
MeO
O
O
esterification and suggests another reaction pathway. On the other
hand, 2ib (Table 3, entry 4) and 2k (Table 4, entry 1) were formed in
high yields in 1,4-dioxane as solvent. Chung et al. proposed another
mechanism, which involves a cumulene intermediate (Scheme 6).20
As all compounds presented in Table 4 do not bear the proton
needed in the propargylic position to form such a cumulene in-
termediate, we can exclude such a reaction pathway. Hence, we
propose the mechanism shown in Scheme 5. Instead of activating
the triple bond, we propose that the catalyst could ‘activate’
a molecule of water to form a gold–hydroxo complex as we
O
Ph
OMe OEt
(Z)-A
2j
Scheme 7. Proposed mechanism for the conversion of 1j into 2j.
(Z)-isomer we suggest that under the reaction conditions the (Z)-
isomer could isomerize into the (E)-isomer. At this time we are
a-hydroxy propiolates with
[(NHC)AuCl] in order to obtain further mechanistic insights.
investigating the reactivity of
R2
R1
[Au]
OH
OEt
OEt
3. Conclusion
•
•
R
R3
We have presented an NHC–gold(I) based catalytic system en-
Chung
Dudley
abling the conversion of propargylic alcohols into
a,b-unsaturated
Scheme 6. Key intermediates in the proposed mechanisms by Chung and Dudley.
ketones and esters. Under optimized conditions, high conversion

1772
R.S. Ramo´n et al. / Tetrahedron 65 (2009) 1767–1773
for a broad range of substrates was achieved. While being able to
accommodate sterically demanding and deactivating substituents,
the present catalytic system proved to be inappropriate for primary
alcohols and terminal alkynes. On the other hand, stereoselectivity
was found to range from good to excellent. A mechanism was
proposed, suggesting activation of a water molecule instead of the
C^C triple bond. Furthermore, we observed formation of a fur-
anone and an indanone derivative. These species raise interesting
mechanistic issues in the context of gold(I)-catalysis. Due to the
ease of preparation of propargylic alcohols, the gold(I)-catalyzed
Meyer–Schuster rearrangement appears to be a promising tool to
4.4. (E)-4-(3-Oxohept-1-enyl)benzonitrile (2c)
The compound was prepared as described in the general pro-
cedure (74% isolated yield). 1H NMR (400 MHz, CDCl3):
d 7.70–7.60
(m, 4H, HAr), 7.51 (d, J¼16.2 Hz, 1H, CAr–CH]), 6.79 (d, J¼16.2 Hz,
1H, ]CH–C]O), 2.67 (t, J¼7.4 Hz, 2H, C]O–CH2), 1.66 (m, 2H, CH2–
CH2–CH2), 1.39 (m, 2H, CH2–CH3), 0.94 (t, J¼7.3 Hz, 3H, CH3). 13C
NMR (100 MHz, CDCl3): d 200.0 (C),139.7 (CH),139.1 (C),132.8 (CH),
129.1 (CH), 128.7 (CH), 118.5 (C), 113.5 (C), 41.3 (CH2), 26.3 (CH2),
22.5 (CH2), 14.0 (CH3). HRMS (ESI) calcd for C14H16NO ([MþH]þ)
214.1232. Found 214.1243.
access a,b-unsaturated carbonyl compounds.
4.5. (E)-1-(Benzo[d][1,3]dioxol-5-yl)hept-1-en-3-one (2d)
4. Experimental section
4.1. General information
The compound was prepared as described in the general pro-
cedure (81% isolated yield). 1H NMR (400 MHz, CDCl3):
d 7.46 (d,
J¼16.0 Hz, 1H, CAr–CH]), 7.05 (d, J¼1.4 Hz, 1H, HAr), 7.03 (dd,
J¼7.9 Hz, J¼1.5 Hz, HAr), 6.82 (d, J¼8 Hz, 1H, HAr), 6.58 (d, J¼16.0 Hz,
1H, ]CH–C]O), 6.01 (s, 2H, CH2O2), 2.63 (t, J¼7.5 Hz, 2H, C]O–
CH2), 1.65 (m, 2H, CH2–CH2–CH2), 1.37 (m, 2H, CH2–CH3), 0.94 (t,
All reagents were used as received. Reactions were performed
under ambient atmosphere. Technical grade solvents were used.
[(NHC)AuCl] complexes were synthesized as described in the lit-
erature.27 Propargylic alcohols were synthesized as described in the
literature16 and purified by flash chromatography (silica 60 Å, Sili-
cycle 230–400 mesh). 1H and 13C NMR spectra were recorded on
a Bruker Avance 400 ULTRASHIELD NMR spectrometer at ambient
temperature in CDCl3 containing 0.03% TMS. Chemical shifts are
given in parts per million (ppm) relative to CDCl3 (1H: 7.26 ppm,
13C: 77.16 ppm). Coupling constants are given in hertz (Hz). High
resolution mass spectra (HRMS) were recorded by the HRMS unit of
the ICIQ (Tarragona) using ESI (Electron Spray Ionization). Gas
chromatography (GC) was performed on an Agilent 6890N Gas
Chromatograph.
J¼7.3 Hz, 3H, CH3). 13C NMR (100 MHz, CDCl3):
d 200.7 (C),149.9 (C),
148.5 (C), 142.2 (CH), 129.2 (C), 124.9 (CH), 124.6 (CH), 108.8 (CH),
106.7 (CH),101.7 (CH2), 40.9 (CH2), 26.7 (CH2), 22.6 (CH2),14.1 (CH3).
HRMS (ESI) calcd for C14H17O3 ([MþH]þ) 233.1178. Found 233.1173.
4.6. (E)-1-(Naphthalen-1-yl)hept-1-en-3-one (2e)
The compound was prepared as described in the general pro-
cedure (92% isolated yield). 1H NMR (400 MHz, CDCl3):
d 8.41 (d,
J¼15.9 Hz, 1H, CAr–CH]), 8.20 (d, J¼8.3 Hz, 1H, HAr), 7.90 (t,
J¼5.3 Hz, 2H, HAr), 7.78 (d, J¼7.2 Hz,1H, HAr), 7.62–7.46 (m, 3H, HAr),
6.85 (d, J¼15.9 Hz, 1H, ]CH–C]O), 2.74 (t, J¼7.4 Hz, 2H, C]O–
CH2), 1.73 (tt, 2H, CH2–CH2–CH2), 1.43 (tq, 2H, CH2–CH3), 0.98 (t,
J¼7.3 Hz, 3H, CH3). 13C NMR (100 MHz, CDCl3):
d 200.6 (C), 139.2
4.2. General procedure
(CH), 133.8 (C), 132.1 (C), 131.7 (C), 130.7 (CH), 128.9 (CH), 128.8
(CH), 127.0 (CH), 126.4 (CH), 125.6 (CH), 125.1 (CH), 123.4 (CH), 41.2
(CH2), 26.6 (CH2), 22.6 (CH2), 14.1 (CH3). HRMS (ESI) calcd for
C17H19O ([MþH]þ) 239.1436. Found 239.1443.
In a 4 mL vial equipped with a magnetic stirring bar [(IPr)AuCl]
(3.1 mg, 5
AgSbF6 (1.7 mg, 5
stirred for 1 min. The propargylic alcohol 1 (0.25 mmol, 1 equiv)
was added, followed by addition of distilled H2O (300 L). The re-
m
mol, 0.02 equiv) was dissolved in MeOH (1.70 mL).
mmol, 0.02 equiv) was added and the solution was
m
4.7. 4-Methoxy-5-phenylfuran-2(5H)-one (2j)
action mixture was heated overnight at 60 ꢀC. Volatile components
were then removed under reduced pressure and the residue was
dissolved in a 1:1 mixture of pentane and Et2O. The solution was
filtered over a plug of silica (w1 cm) and solvents were removed
under reduced pressure. NMR yields were determined as follow: A
defined amount (w0.2 mmol) of benzaldehyde was added as in-
ternal standard to the crude product. Reported yields are average of
two runs. New compounds were additionally prepared in 0.5 mmol
scale and purified by flash chromatography for complete charac-
terization and isolated yields.
The compound was prepared as described in the general pro-
cedure (69% isolated yield). 1H NMR (400 MHz, CDCl3):
d
7.42–7.36
(m, 3H, HAr), 7.35–7.29 (m, 2H, HAr), 5.69 (s, 1H, Ph–CH), 5.16 (s, 1H,
CH–C]O), 3.85 (s, 3H, OCH3). 13C NMR (100 MHz, CDCl3):
181.8
d
(C), 172.7 (C), 134.1 (C), 129.6 (CH), 129.0 (CH), 126.8 (CH), 88.4 (CH),
80.4 (CH), 59.7 (CH3).
4.8. (E)-1-(3-Fluorophenyl)hex-2-en-1-one (2p)
Compounds 2a,16 2f,16 2h,16 2l,16 2n,16 2o16 and 2rb,16 2ia,28 2ib,29
2g,30 2k,31 2m,32 2qa,33 2qb,34 2ra35 and 2t36 were characterized by
comparing their NMR spectra with the literature data.
The compound was prepared as described in the general pro-
cedure (89% isolated yield). 1H NMR (400 MHz, CDCl3):
d 7.70 (m,
1H, HAr), 7.61 (m, 1H, HAr), 7.44 (m, 1H, HAr), 7.24 (m, 1H, HAr), 7.09
(td, 3J1¼15.4 Hz 3J2¼7.0 Hz, 1H, CH2–CH]CH), 6.83 (td, 3J¼15.4 Hz,
4J¼1.5 Hz, 1H, CH2]CH–C]O), 2.30 (m, 2H, CH2–CH]), 1.56 (m,
2H, CH2–CH3), 0.98 (t, J¼7.4 Hz, 3H, CH3). 13C NMR (100 MHz,
4.3. (E)-1-(4-(Trifluoromethyl)phenyl)hept-1-en-3-one (2b)
The compound was prepared as described in the general pro-
CDCl3):
d
189.6 (d, J¼2.2 Hz, C), 162.9 (d, J¼247.6 Hz, C), 150.8 (CH),
cedure (81% isolated yield). 1H NMR (400 MHz, CDCl3):
d
7.65 (s, 4H,
140.2 (d, J¼6.3 Hz, C), 130.2 (d, J¼7.8 Hz, CH), 125.7 (CH), 124.3 (d,
J¼2.9 Hz, CH), 119.6 (d, J¼21.6 Hz, CH), 115.4 (d, J¼22.3 Hz, CH), 34.9
(CH2), 21.5 (CH2), 13.8 (CH3). HRMS (ESI) calcd for C12H14FO
([MþH]þ) 193.1029. Found 193.1039.
H
Ar), 7.55 (d, J¼16.2 Hz, 1H, CAr–CH]), 6.79 (d, J¼16.2 Hz, 1H,
]CH–C]O), 2.68 (t, J¼7.4 Hz, 2H, C]O–CH2), 1.67 (m, 2H, CH2–
CH2–CH2), 1.39 (m, 2H, CH2–CH3), 0.95 (t, J¼7.3 Hz, 3H, CH3). 13C
NMR (100 MHz, CDCl3):
d 200.3 (C), 140.4 (CH), 138.2 (C), 131.9 (q,
J¼32.52 Hz, C–CF3), 128.5 (CH), 128.4 (CH), 126.0 (q, J¼3.8 Hz, CH),
123.9 (q, J¼272.2 Hz, CF3), 41.2 (CH2), 26.4 (CH2), 22.6 (CH2), 14.0
(CH3). HRMS (ESI) calcd for C14H16F3O ([MþH]þ) 257.1153. Found
257.1166.
Acknowledgements
This work was supported in part by the ACS/PRF, the ICIQ
Foundation and the Ministerio de Educacion y Ciencia (Spain). SPN
´

R.S. Ramo´n et al. / Tetrahedron 65 (2009) 1767–1773
1773
Commun. 2006, 2048–2050; (c) Correa, A.; Marion, N.; Fensterbank, L.; Mal-
acria, M.; Nolan, S. P.; Cavallo, L. Angew. Chem., Int. Ed. 2008, 47, 718–721; (d) de
Fre´mont, P.; Marion, N.; Nolan, S. P. J. Organomet. Chem. 2009, 694. doi:10.1016/
j.jorganchem.2008.10.047; (e) Gourlaouen, C.; Marion, N.; Nolan, S. P.; Maseras,
F. Org. Lett. 2009, 11, 81–84; (f) Marion, N.; Lemie`re, G.; Correa, A.; Costabile, C.;
Ramo´n, R. S.; Moreau, X.; de Fre´mont, P.; Dahmane, R.; Hours, A.; Lesage, D.;
Tabet, J.-C.; Goddard, J.-P.; Gandon, V.; Cavallo, L.; Fensterbank, L.; Malacria, M.;
Nolan, S. P. Chem.dEur. J. 2009, 15. doi:10.1002/chem.200801387
is an ICREA Research Professor. NM (2007FI_A 01466) and RSR
(2008FI 01047) received pre-doctoral fellowships by the AGAUR.
NM thanks Umicore for a Ph.D. award.
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