New elements in the gold(I)-catalyzed cycloisomerization of enynyl ester derivatives embedding a cyclohexane template

Article abstract of DOI:10.1016/j.jorganchem.2010.10.016

The gold-catalyzed cycloisomerization of enynyl esters bearing a cyclohexyl template has been studied and has been shown to lead to two types of products arising from 1,2- vs. 1,3-O-acyl-migration. Results have shown to be dependent on the nature of the s

Full text of DOI:10.1016/j.jorganchem.2010.10.016

Journal of Organometallic Chemistry 696 (2011) 388e399
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
New elements in the gold(I)-catalyzed cycloisomerization of enynyl ester
derivatives embedding a cyclohexane template
Youssef Harrak, Malika Makhlouf, Stéphane Azzaro, Emily Mainetti, Juan Manuel Lopez Romero,
*
*
Kevin Cariou, Vincent Gandon, Jean-Philippe Goddard, Max Malacria , Louis Fensterbank
Institut Parisien de Chimie Moléculaire (UMR CNRS 7201), FR 2769 UPMC univ Paris 06, C. 229, 4 place Jussieu, 75005 Paris, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The gold-catalyzed cycloisomerization of enynyl esters bearing a cyclohexyl template has been studied
and has been shown to lead to two types of products arising from 1,2- vs. 1,3-O-acyl-migration. Results
have shown to be dependent on the nature of the solvent, the catalysts, the migrating group, the
stereochemistry of the starting diastereomer as well as the alkene partner. This set of findings confirms
the intricate nature of the “golden carousel” of propargylic acetates.
Received 21 July 2010
Received in revised form
4 October 2010
Accepted 5 October 2010
Available online 13 October 2010
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
Gold catalysis
Golden carousel
Propargyl acetate
Cycloisomerization
1. Introduction
exploited by the groups of Fürstner [7] and Fehr [8] for the total
synthesis of cubebol.
Connecting an alkyne to an alkene and submitting the resulting
enyne to a transition metal catalytic species has been at the origin
of a very vast array of versatile transformations [1]. Constraints in
the systems (tether length, substitution of the unsaturated
partners.) as well as the choice of the metal are key parameters
which have been used on a reliable basis in order to favor a mech-
anistic pathway (metallacycle or other) and thus direct the reac-
tivity of the system. For the last decade, we have concentrated on
skeletal rearrangement types of transformations [2] based on the
use of electrophilic gold and platinum complexes, [3] and have
notably focussed on the use of enynols and derived substrates [4].
These transformations have allowed expedient access to
molecular complexity even from structurally simple precursors.
Incorporating a cycle in the reacting system can further increase the
molecular complexity as shown by the transformation of a to b and
c to d (Scheme 1) [5]. In this series, the nature of the oxygenated
function is determinant for the outcome of the reaction as the c to
d transformation features a now well-known Ohloff-Rautenstrauch
rearrangement step [6]. Related substrates were judisciouly
Formally, these transformations feature an intriguing function-
alization of an alkyne, consisting in the first case as a double
alkylation and a hydrogenation giving an enol which tautomerizes
to b, and in the second case as a double alkylation concomitant with
an oxygenation (product d).
We also surmised that precursors incorporating a ring in the
tether and prefiguring an O-acyl migration, more precisely
substrates of type I could yield valuable carbocylic platforms II
(Scheme 2). Our initial study involving various cyclic substrates
confirmed that assumption [9a]. Interestingly, among this series
from cyclobutyl to cyclohexyl based precursors I, the latter
(precursors 1) offered highly contrasted results depending on the
nature of the catalyst used and that required further examination.
Notably, in the course of this study, we have evidenced different
formal modes of catalytic additions to the alkyne motif, which
differ from the modes described in Scheme 1. We herein report on
the behavior of this peculiar system.
2. Results and discussions
2.1. Cycloisomerizations of precursors 1
* Corresponding authors. Tel.: þ33 (0)1 44 27 70 68; fax: þ33 (0) 44 27 73 60.
E-mail addresses: max.malacria@upmc.fr (M. Malacria), louis.fensterbank@
upmc.fr (L. Fensterbank).
While initial test reaction with PtCl2 smoothly provided the
expected tricyclic structure 2a (Scheme 2) as a single diastereomer
0022-328X/$ e see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.10.016

Y. Harrak et al. / Journal of Organometallic Chemistry 696 (2011) 388e399
389
Scheme 1. PtCl2-catalyzed cycloisomerization of 1,5-cyclohexenynol derivatives.
from the diastereomeric mixture 1a [9a], switching to gold catalysts
gave birth to more complex mixtures in which the type and the
relative amount of the various products obtained proved to be
dependent from the starting diastereomers. These can be obtained
separately and an X-ray structure determination of diastereomer
1a-trans (relative to the stereochemical relationship between the
pendant unsaturated chains) could be accomplished (Fig. 1) (see
Supplementary material). Results for 1a-cis with AuCl3, PPh3AuCl/
AgSbF6 (AuDI) and Echavarren’s catalyst bi-Ph(t-Bu)2AuSbF6
(AuDII) [10] are now summarized in Table 1.
Simple gold(III) catalyst AuCl3 gave a mixture of 2a and allenic
product 3a as minor component (Table 1, entries 1 & 2). In contrast,
the use of toluene marked a strongly reversed ratio of product 3a vs.
2a (entry 3). Sharp differences of reactivity have already been
observed in gold-catalyzed cycloisomerization reactions when
switching from CH2Cl2 to toluene [11]. Cationic gold(I) catalyst
resulted in even more complex mixtures featuring in some cases
products 4a and 5a (entries 4e5). Stereochemical assignment of 5a
was done by analogy of the NMR spectra with 5a-NO2 for which an
X-ray structure determination was carried out (see Fig. 2). Formally,
product 5a is a product of the intramolecular addition of a CeH
bond of the alkene partner onto the alkyne (Scheme 3).
with gold catalysts, is well-known in the literature [4b,13]. We
could confirm our assumption by submitting 3a to the Echavarren
complex and observed the smooth formation of 5a (Scheme 3). In
order to rationalize the formation of 5a, we propose an initial
electrophilic activation of the allenylester 3a. Subsequent 6-exo-dig
cyclization to give homoallylic stabilized carbocationic species 7
followed by proton loss and protodeauration would provide diene
intermediate 8. The latter would undergo a diastereoselective
allylic isomerization which has some precedent in gold catalysis
[14], and that is here probably driven by the need to relieve the 1,3-
allylic strain. Presumably, subsequent acetic acid elimination from
5a would lead to 4a.
We also examined the behavior of the trans diastereomer 1a-
trans (see Fig.1). This one proved to be even more selective towards
allenyl substrate 3a and allenyl intermediate derived products 4a
and 5a, especially upon gold(I) catalysis (entries 3 to 6, see Table 2).
The case of the p-nitrobenzoate analog of 1a-trans established
this trend further, as the reaction with Echavarren’s catalyst gave
a mixture of the corresponding allenylester product 3a-NO2 and
the bicyclic product 5a-NO2 as the major one (i.e. a C : A ratio of 0 : 1
!) whose structure could be secured by an X-ray analysis (Fig. 2, see
Supplementary material).
We suspected that the latter would originate from allenylester
3a for several reasons. First, while the formation of dienic product
of type 5 is well-precedented upon gold catalysis, [12] here any
transformation from 1a-cis would imply the inversion of configu-
ration of one stereogenic center and we could not hypothesize any
reasonable pathway for that. Moreover, products such as 2a have
generally shown to be stable in the reaction conditions. For
instance, 2a can be exposed to AuDI for 24 h with no alteration.
Finally, noble metal-triggered activation of allenyl esters, especially
It should be mentioned that, at that stage, we cannot discard the
fact that 5a and 5a-NO2 can also be formed from the corresponding
trans precursors 1a through the regular mechanism [12a,b]
involving intermediates C (see below, Scheme 5).
AcO
AcO
( )n'
[M]
( )n'
H
( )n
I
II
( )n
[M] = PtCl2, AuCl3, Au+
ref. [9a]
AcO
AcO
5 mol% PtCl2
Tol., 80°C, 3 h
H
2a, 95%
1a
Scheme 2. Polycyclic platforms from cyclohexyl tethered enynes.
Fig. 1. X-ray structure of 1a-trans.

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Y. Harrak et al. / Journal of Organometallic Chemistry 696 (2011) 388e399
Table 1
Gold-catalyzed cycloisomerizations of 1a-cis.
AcO
AcO
[Au]
AcO
AcO
+
+
+
H
H
1a-cis
2a
3a
4a
5a
Catalysts:
Au+I: AuClPPh3+AgSbF6
Au+II:
CH3-CN, Au P
t-Bu
t-Bu
SbF6
Entry
Catalyst
AuCl3 (5%)
Conditionsa
Yield (%)
2a:3a:4a:5a ratiob
C : Ac
1
2
3
4
5
CH2Cl2, 24 h
CH2Cl2, 3 h
PhMe, 3 h
CH2Cl2, 1 h
CH2Cl2, 24 h
60
84
91
90
89
1 : 0.6 : traces : 0
1 : 0.7 : 0 : 0
1 : 5 : 0 : 0
1 : 1.4 : 0 : 0
1 : 0.9 : traces : 0.75
1 : 0.6
1 : 0.7
1 : 5
1 : 1.4
1 : 1.7
AuCl3 (10%)
AuCl3 (10%)
AuþI (2%)
AuþII (2%)
a
All reactions run at rt on a 1 mmol scale at 0.025 M (CH2Cl2: dichloromethane, PhMe: toluene).
Ratio determined on the 1H NMR of the crude product.
C: cycloisomerization product 2a, A: allene 3a þ products 4a and 5a originating from 3a.
b
c
2.2. DFT calculations for the formation of 2a
with the 6-31G* (H, C, O, P) and LANL2DZ þ ECP basis sets (Au). All
calculations were performed with the Gaussian series of programs
[16]. All relative energies presented herein are free energies in
kilocalories per mole.
DFT computations were carried out to shed light on some
mechanistic issues. We concentrated on the experimental results
obtained using cationic gold(I) complexes, Au(PH3)þ being taken as
model catalyst. The facile equilibrium between the three types of
From the computational data available in the literature [17],
assuming that gold rather activates the triple CeC bond towards
nucleophilic attack, several pathways can be envisaged (Scheme 5):
(i) the gold complex A transforms into the vinylgold species B; (ii) A
or B undergoes 5-exo cyclization to give the cyclopropylcarbene C;
(iii) A or B undergoes 6-endo cyclization to give carbene D; (iv)
intermediate B gives rise to carbene E (1,2-O-acyl shift from A) [18].
Although the formation of 2 from D after 1,2-O-acyl shift, or from E
via electrophilic cyclopropanation, appears feasible, a rearrange-
ment of C into such framework seems quite unlikely.
gold complexes of propargylic esters, namely a
p-coordinated
alkyne, a carbene, and an allene, also coined as the "golden car-
ousel » has been theoretically studied by Cavallo et al. Our aim was
not to reproduce it herein [15]. Instead, we rather decided to focus
on “non-allenic” cyclization pathways leading to species of type 2
and the related intriguing diastereoselectivity.
The geometry optimizations and thermodynamic corrections
were performed with hybrid density functional theory (B3LYP)
The bulk of the computations on that matter is displayed on
Scheme 6. From A-cis and A-trans, we could model the concerted
formation of the cyclopropycarbenes C1-cis and C1-trans. The other
two diastereomers, C2-cis and C2-trans respectively, could not be
directly connected to A type complexes, but to the corresponding
vinylgold species B-cis and B-trans. Similarly, the formation of the
four possible complexes D was computationally achieved in a step-
wise fashion from B type species. They converged as O-stabilized
carbenoids rather than carbene intermediates. No transition states
directly connecting A to D could be found which a priori eliminates
a preliminary 6-endo-dig cyclization.[7], [17deh] As expected,
transition states between B-cis and B-trans and gold carbene E
could be located. In terms of free energy of activation, the formation
of C1 cyclopropylcarbenes only just wins over that of vinylgold
species B (
the former is only slightlyexothermic (
and can thus be considered reversible. Besides, manifold efforts
failed to generate the framework of 2 from species of type C1. On the
other hand, species B are formed in an appreciably exothermic
D
Gz ¼ 9.6; 6.0 kcal/mol vs 10.4; 7.1 kcal/mol). However,
298
D
G298 ¼ ꢀ3.6; ꢀ4.7 kcal/mol)
fashion (
D
G298 ¼ ꢀ9.2; ꢀ12.5 kcal/mol), making the way back more
difficult. From there, the formation of C2-cis and C2-trans is quite
slow, especially in the trans series (
the thermodynamics of the reaction appears quite unfavorable as
D
Gz ¼ 14.5; 21.9 kcal/mol), and
298
well (
fashion (
D
G298 ¼ 4.0; 6.7 kcal/mol). Although formed in an exothermic
Fig. 2. X-ray structure of 5a-NO2.
D
G298 ¼ w e13e17 kcal/mol), it is even more difficult to

Y. Harrak et al. / Journal of Organometallic Chemistry 696 (2011) 388e399
391
AcO
C
H
AcO
Au+II
H
rt, 12 h
[M]
5a, 62%
3a
1,3-allylic
isomerization
AcO
[Au+]
[Au] H
6-exo
-dig
AcO
AcO
1. proton loss
2. protodeauration
6
7
8
Scheme 3. Mechanism proposal for the formation of 5a.
Table 2
Gold-catalyzed cycloisomerizations of 1a-trans.
AcO
AcO
AcO
[Au]
AcO
+
+
+
H
H
1a-trans
2a
3a
4a
5a
Entry
Catalyst
Conditionsa
Yield (%)
2a:3a:4a:5a ratiob
C : Ac
1
2
3
4
5
6
AuCl3 (10%)
AuCl3 (10%)
AuþI (2%)
CH2Cl2, 3 h
PhMe, 3 h
CH2Cl2, 1 h
CH2Cl2, 1 h
CH2Cl2, 1 h
CH2Cl2, 24 h
77
79
89
91
83
80
1 : 1.7 : traces : 0
1 : 10 : 0 : 0
1 : 3.5 : 0 : 5
1 : 0 : 10 : 0
1 : 1.7 : 0.4 : 2.2
as above
1 : 1.7
1 : 10
1 : 8.5
1 : 10
1 : 4.3
AuþI (5%)
AuþII (2%)
AuþII (2%)
a
All reactions run at rt on a 1 mmol scale at 0.025 M (CH2Cl2: dichloromethane, PhMe: toluene).
Ratio determined on the 1H NMR of the crude product.
C: cycloisomerization product 2a, A: allene 3a þ products 4a and 5a originating from 3a.
b
c
PNBO
O
O
PNBO
Au+II
+
H
O2N
1a-trans-NO2
3a-NO2, 19%
5a-NO2, 63%
Scheme 4. Cycloisomerization of a p-nitrobenzoate derivative.
(ii)
[Au]+
[Au]+
[Au]+
AcO
O
or
(iii)
AcO
OAc
OAc
O
[Au]+
(i)
or
[Au]
A
B
C
D
1
(iv)
OAc
OAc
[Au]+
2
E
Scheme 5. Potential intermediates on route to 2.

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Y. Harrak et al. / Journal of Organometallic Chemistry 696 (2011) 388e399
[Au]+
H
[Au]+
AcO
AcO
[Au]+
H
[Au]+
OAc
OAc
O
O
O
O
[Au]
[Au]
H
H
H
C1-cis (-3.6)
C2-cis (-5.2)
H
H
H
9.6
5.3
D1-cis (-16.9) D2-cis (-17.6)
G1
G2
[Au]+
OAc
13.4
10.0
O
O
10.4
7.1
[Au]
1.2
OAc
OAc
OAc
H
H
[Au]+
[Au]+
[Au]+
0.9
7.4
A-cis (4.2)
B-cis (-9.2)
[Au]+
OAc
O
O
H
H
H
F2 (-20.9)
E (-2.3)
F1 (-22.0)
observed
1.5
[Au]
H
H
14.3
15.0
A-trans (0.0)
B-trans (-12.5)
O
O
O
O
6.0
9.4
[Au]
[Au]
[Au]+
AcO
[Au]+
AcO
G1 or G2
H
H
H
H
D1-trans (-16.3)
D2-trans (-13.2)
H
H
C1-trans (-4.7)
C2-trans (-5.8)
Scheme 6. Free energies (kcal/mol) relative to A-trans (in parentheses for minima, over an arrow for transition states).
reach the 6-endo transition states leading to the four diastereomeric
D type complexes (
Gz
¼ w19e28 kcal/mol). In fact, the kineti-
2.3. Cycloisomerizations of precursors 1b
D
298
cally favored pathway is the one converting B-cis or B-trans into
It was also interesting to look at prenyl derived precursors, since
the expected cycloisomerization products (2a-type products)
would bear a gem-dimethylated cyclopropane moiety which is
a common motif in natural products. Our initial findings also drove
us to study separately both diastereomers of the starting product
and these results are given below (Scheme 7). Here also, 1b-trans
could be crystallized and its structure solved by X-ray crystallog-
raphy (Fig. 3, see Supplementary material).
Cycloisomerization of the cis and the trans precursor 1b with
PtCl2 proved to be more troublesome than in previous cases, since
even more complex mixtures were obtained from which the
expected cycloisomerization product 2b was isolated as the same
single diastereomer in moderate yield (Scheme 7, 50e60%). Minor
amounts (5e10%) of a side product ascribed to diene 9b (present as
carbene E (
stable than B (
D
Gz ¼ 10.4; 14.0 kcal/mol). That species is clearly less
298
DG298 ¼ 6.9; 10.2 kcal/mol), however, it can reach
another close-lying transition state leading to complex F1
(
D
Gz ¼ 3.2 kcal/mol), in which the cyclopropyl ligand corre-
298
sponds to the experimentally observed product 2a. The other
possible diastereomer F2 is actually more difficult to obtain
(D
Gz ¼ 9.7 kcal/mol), the corresponding transition state lying
298
6.5 kcal/mol higher than the one leading to F1. The E/F1 trans-
formation is appreciably exothermic by 19.7 kcal/mol.
Thus, from these calculations,
a diastereoselective intra-
molecular cyclopropanation involving a gold carbene intermediate
appears as the most probable pathway.
AcO
AcO
5 mol% PtCl2
H
1b-cis
2b, 60%
AcO
AcO
5 mol% PtCl2
H
1b-trans
2b, 53%
Fig. 3. X-ray structure of 1b-trans.
Scheme 7. PtCl2-catalyzed cycloisomerizations of prenyl precursors 1b.

Y. Harrak et al. / Journal of Organometallic Chemistry 696 (2011) 388e399
393
Fig. 4. X-ray structure of 9b-NO2.
Table 3
Gold-catalyzed cycloisomerizations of 1b-cis.
AcO
AcO
AcO
OAc
+
H
[Au]
+
+
1b-cis
H
H
1b-cis
2b
3b
9b
Entry
Catalyst
Conditionsa
Yield (%)
2b:3b:9b:1b-cis ratiob
C : Ac
1
2
3
AuCl3 (10%)
AuCl3 (10%)
AuþI (2 or 5%)
CH2Cl2, 24 h
PhMe, 1 h
CH2Cl2, 1 h
30
65
0
1 : 0 : 0.18 : 2.5
1 : 2.5 : 0.5 : 1
degradation
1 : 0.18
1 : 3
a
All reactions run at rt on a 1 mmol scale at 0.025 M (CH2Cl2: dichloromethane, PhMe: toluene).
Ratio determined on the 1H NMR of the crude product.
C: cycloisomerization product 2b, A: allene 3b þ product 9b originating from 3b.
b
c
O
O
O
O
1. proton loss -
acetate migration
[Au]
H
6-endo-trig
[Au]
9b
2. protodeauration
3b
H
Scheme 8. Mechanism proposal for the formation of 9b.
AcO
AcO
AcO
Au+II
+
H
H
10b, 21.5%
2b, 8.5%
1b-cis
O2N
O2N
+
O
O
O
O
Au+II
O
O
H
O2N
1b-cis-NO2
10b-NO2, 23%
11, 45%
Scheme 9. Cycloisomerizations of precursors 1b-cis and 1b-cis-NO2.
a very major isomer) were observed in these reactions. Structure of
9b was ascertained by obtaining an X-ray structure of the p-
nitrobenzoate derivative (Scheme 4) (9b-NO2) which originated
from the saponification of 9b followed by acylation with the
correspond acyl chloride (Fig. 4, see Supplementary material).
We then examined the behavior of each diastereomer with gold
catalysts. The cis-diastereomer 1b-cis proved to be little reactive
with AuCl3 leading in all cases to a significant amount of unreacted
starting material (Table 3). It should be mentioned that no epi-
merization of 1b-cis was observed. Here too, the use of toluene

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Y. Harrak et al. / Journal of Organometallic Chemistry 696 (2011) 388e399
a mixture of 2b and what we interpreted as being a diastereomer of
O
Y
2b, cyclopropyl derivative 10b was obtained. In all these studies, it
would be the first time that we were able to isolate another dia-
stereomer of the cyclopropyl type of product 2. Because we wanted
to ascertain the structure of 10b, we examined the behavior of the
para-nitrobenzoate analog 1b-cis-NO2.
The p-nitrobenzoate analog of 10b (10b-NO2) was isolated but in
similar yield and unfortunately did not lend itself to cristallization
in order to get an X-ray analysis. Another type of dienic product was
formed as a single regioisomer, in good yield (45%) and based on
NMR spectra, we proposed structure 11. Mechanistic considerations
will be discussed below (Scheme 11). In contrast, the trans diaste-
reomer 1b-trans proved to be more reactive, resulting generally in
the full consumption of starting material with AuCl3 (entries 1e3,
Table 4). Consistently, the use of toluene as a solvent led to a much
higher yield of allene 3b and allene-derived diene 9b.
Precursor 1b-trans and p-nitrobenzoate analog 1b-trans-NO2
provided high yielding reactions leading selectively to the classical
cycloadduct of type 2b (Scheme 10), thus marking a sharp contrast
with the behavior of 1b-cis and 1b-cis-NO2 (Scheme 9). The
determination of the relative chemistry of 2b-NO2 was accom-
plished by an X-ray diffraction analysis on DNP- hydrazone 13, see
Supplementary material (Fig. 5).
One of the important findings in this study is the observation of
the sharp difference of behavior between both diastereomers of 1b
in the presence of the highly reactive Echavarren’s catalyst, as
illustrated in Schemes 9 and 10. To someextent, this is reminiscentof
the seminal studies by Fürstner [7] and Fehr [8] on 1,5-enynyl
acetates systems who evidenced that “the configuration of the
stereogenic center carrying the acetate unit translates into the
stereochemistry of the product” [7]. In our case, in the acetate series,
precursor 1b-cis leads to a non-stereoselective cycloisomerization
Y
O
O
2 mol % Au+II
DCM, 2 min.
O
H
1b-trans, Y = Me
1b-trans-NO2,
2b, 80%
2b-NO2, 80%
NO2
NO
Y =
2
NO2
N
H
O
N
H
DNPH
APTS cat.
K2CO3
2b-NO2
MeOH
H
H
12, 80%
13, 91%
Scheme 10. Cycloisomerization of precursors 1b-trans.
resulted in an increase of the amount of allene-derived products,
accompanied here by a better overall yield (entry 2).
Diene 9b is another type of formal CeH addition onto the
alkyne. Presumably, it originates from allene 3b via the mechanism
depicted in Scheme 8. Activation of the allenylester moiety would
trigger a 6-endo-trig cyclization. The resulting intermediate H
would then undergo proton loss accompanied by O-acyl migration
on the carbocationic intermediate. A final protodeauration would
deliver 9b.
The reaction with cationic gold catalysts gave contrasted results.
While the traditional “AuPPh3þ” catalyst gave intractable materials
(Table 3), Echavarren’s catalyst resulted in a particularly intriguing
outcome despite a low overall yield (30%) (Scheme 9). Indeed
1. proton loss
X
2. protodeauration
[Au]
11
O
3. isomerization
O
X
O
H
[Au]
O
2b and
2b-NO2
10b and
10b-NO2
cyclopropanation
+
I
B
via carbene E
Scheme 11. Mechanism proposals for the formation 11.
Table 4
Gold-catalyzed cycloisomerizations of 1b-trans.
AcO
AcO
AcO
OAc
H
[Au]
+
+
H
H
1b-trans
2b
9b
3b
Entry
Catalyst
Conditionsa
Yield (%)
2b:3b:9b ratiob
C : Ac
1
2
3
4
AuCl3 (10%)
AuCl3 (10%)
AuCl3 (10%)
AuþI (2 or 5%)
CH2Cl2, 10 min
PhMe, 2 h, rt
PhMe, 2 h, 60 ꢁ
CH2Cl2, 1 h
68
70
70
0
1 : 0 : 0.6
1 : 4 : 2
1 : 2 : 1
1 : 0.6
1 : 6
1 : 4
e
C
degradation
a
All reactions run at on a 1 mmol scale at 0.025 M.
b
c
Ratio determined on the 1H NMR of the crude product.
C: cycloisomerization product 2b, A: allene 3b þ product 9b originating from 3b.

Y. Harrak et al. / Journal of Organometallic Chemistry 696 (2011) 388e399
395
1,3-migration products. A lot of parameters intervene which direct
the golden carousel of the propargyl acetate reactivity. It is worthy
of note that the AuCl3/toluene combination, as well as the use of
cationic gold catalysts, and to some extent the trans configuration
of the starting materials favors the allenylester product or allene-
derived products. No obvious rationalization is available at that
time. But one can hypothesize that gold cationic catalysts, because
of their linear coordination mode and their bulky ligand have more
steric interactions with the cylohexyl template in the 1,2-O-acyl
migration, and that the 1,3-migration would allow to relieve them.
Another element of interest in this study is the strong difference of
behavior between the two diastereomers of the allyl and of the
prenyl precursors, when Echavarren’s catalyst is used. The higher
nucleophilicity of the prenyl group would be at play at an earlier
stage in the golden carousel. This set of findings confirms the high
synthetic potential of the “golden carousel” of propargylic acetates,
but also its intricate nature which so far thwarts predictability.
Fig. 5. X-ray structure of hydrazone 13.
reaction since the two diastereomers of products of type 2 have been
observed for the first time in all these studies, while 1b-trans yields
very efficiently and selectively to the expected product 2b. In the
p-nitrobenzoate series (1b-cis-NO2), in addition to the new diaste-
reomeric product 10b, a previously unobserved dienic product (11)
is isolated as the major compound. Similarly to 1b-trans, 1b-trans-
NO2 gives a high yield of the expected product 2b-NO2. This differs
significantly from the allyl precursors reactivity 1a while structur-
ally, the only distinction between precursors 1a and 1b is the alkene
partner, i. e. allyl vs. prenyl. In the allyl case, one would be under the
golden carousel regime featuring 1,2-migration to give cyclopropyl
adduct 2a evolving as an intermediate carbene E, as suggested by the
DFT calculations, and 1,3- or possibly double 1,2-migration to give
allenylester 3a and allenyl derived products 4a and 5a. For the prenyl
derivatives 1b, and byextension of the mechanism proposed by Fehr
[8] to the 1,6-enyne system, one could speculate that a bifurcation of
the carousel takes place through the intervention of the more
nucleophilic double bond of the prenyl moiety on the vinylmetal
oxonium B providing intermediates I. The latter could then evolve to
diene 11 through elimination, protolysis and isomerization, or by
cylopropanation to diastereomers 2b and 10b and to 10b-NO2. The
trans diastereomers could also possibly react through carbene E as in
the allyl series and provide products 2b [19] (Scheme 11).
4. Experimental
4.1. General Remarks
Reactions were carried out under argon, with magnetic stirring
and distilled solvents. THF and Et2O were distilled from Na/
benzophenone. DMSO, benzene, dichloromethane and toluene
were distilled from CaH2. Thin layer chromatography (TLC) was
performed on Merck 60 F254 silica gel. Merck Geduran SI 60 A silica
gel (35ꢀ70 mm) was used for column chromatography. The
melting points reported were measured with a Reichert hot stage
apparatus and are uncorrected. IR spectra were recorded with
a Bruker Tensor 27 ATR diamant PIKE spectrometer. 1H, 13C spectra
were recorded at 400 and 100 MHz respectively, using a Bruker
AVANCE spectrometer fitted with a BBFO probehead. Chemical
shifts are given in ppm using the CDCl3 signal as reference
(1H ¼ 7.26 ppm, 13C ¼ 77.16 ppm). Unless noted, NMR spectra were
recorded in CDCl3 at 293 K. The terms m, s, d, t and q stand for
multiplet, singlet, doublet, triplet and quadruplet respectively, and
the term bs means a broad signal. Exact masses were recorded by
the plateforme de spectrométrie de masse (IPCM UMR7201) of
Université Pierre et Marie Curie (electrospray source). The catalysts
were purchased from Strem and SigmaeAldrich and used without
further purification.
3. Conclusion
This study shed some new light on the reactivity of 1,6-enynes
flanked with an O-acyl group at the propargylic position with
electrophilic complexes. When using precursors with a cyclohexyl
template, platinum catalysis favors products from the 1,2-O-acyl
group migration, while gold catalysis results in mixtures of 1,2- and
4.2. General procedure for the preparation of propargylic esters 1
TMS
R
R
R1OCO
HO
1) Desilylation
R
R
2) Acylation
R = H, Ba-trans
R = Me, Bb-trans
TMS
R=H, R1=Ac, 1a-trans
R=H, R1=PNB, 1a-trans-NO2
R=CH3, R1=Ac, 1b-trans
R
HO
Separation
R
R=CH3, R1=PNB, 1b-trans-NO2
TMS
R
R
R = H, Aa
R = Me, Ab
HO
R1OCO
1) Desilylation
2) Acylation
R
R
R = H, Ba-cis
R = Me, Bb-cis
R=H, R1=Ac, 1a-cis
R=H, R1=PNB, 1a-cis-NO2
R=CH3, R1=Ac, 1b-cis
R=CH3, R1=PNB, 1b-cis-NO2

396
Y. Harrak et al. / Journal of Organometallic Chemistry 696 (2011) 388e399
4.2.1. Preparation and separation of propargylic alcohols B
The diastereomeric mixtures of propargylic alcohols Aa and Ab
were obtained according to the reported procedure [9a]. The two
isomers were separated by flash chromatography on silica gel
(petroleum ether/diethyl ether 8/2).
NMR (100 MHz, CDCl3) d 162.6, 150.5, 136.8, 136.3, 130.6 (2C), 123.6
(2C), 116.5, 83.0, 78.7, 74.9, 46.2, 35.2, 34.9, 26.3, 24.3, 21.2. HRMS
calcd. for C18H19NO4 ([M þ H]þ): 314.1388; found: 314.1391.
O2N
4.2.2. General procedure for the desilylation of substrates B
O
The compound B (1 mmol, 1 equiv.) was diluted in DMSO (5 mL)
and stirred with KF (232 mg, 4 mmol, 4 equiv.) and few drops of
water. After 1 h at rt, the reaction was completed. The mixture was
quenched with saturated NH4Cl aqueous solution and extracted
with diethylether. The combined organic layers were washed with
brine, dried over MgSO4 and evaporated to give the crude alcohol,
which is used in the next step without further purification.
O
4.2.4.4. 1a-cis-NO2. White solid (73%). Mp ¼ 119e121 ꢁC IR (neat):
n
¼ 3299, 2931, 2857,1721,1521,1319.1119 cmꢀ1. 1H NMR (400 MHz,
CDCl3)
d
8.27 (d, J ¼ 8.4 Hz, 2H), 8.16 (d, J ¼ 8.4 Hz, 2H), 5.83 (m, 1H),
4.2.3. General procedure for the esterification of propargylic
alcohols
5.05 (m, 2H), 2.88 (m, 1H), 2.79 (m, 1H), 2.73 (s, 1H), 2.66 (m, 1H),
2.07e1.86 (m, 3H), 1.73e1.60 (m, 3H), 1.36 (m, 1H), 1.25 (m, 1H). 13C
To a stirred solution of the corresponding alcohol (1 mmol,
1.0 equiv.), Et3N (0.4 mL, 3 mmol, 3 equiv.) and DMAP (12 mg,
0.1 mmol, 0.1 equiv.) in CH2Cl2 (10 mL) was added acetic anhydride
(0.189 mL, 2 mmol, 2 equiv.) or 4-nitrobenzoyl chloride (371 mg,
2 mmol, 2 equiv.) at rt. The solution was refluxed for 24 h,
quenched with saturated NH4Cl aqueous solution and extracted
with CH2Cl2. The combined organic layers were washed with brine,
dried over anhydrous Na2SO4, filtered and evaporated in vacuo to
give the crude ester. Purification was achieved by flash chroma-
tography on silica gel (PE/Et2O gradient) to afford acetate or
p-nitrobenzoate 1.
NMR (100 MHz, CDCl3) d 162.7, 150.5, 136.8, 136.4, 130.6 (2C), 123.5
(2C), 116.5, 81.7, 80.0, 77.5, 45.9, 36.3, 35.1, 28.2, 24.8, 23.4. HRMS
calcd. for C18H19NO4 ([M þ H]þ): 314.1388; found: 314.1392.
O2N
O
O
4.2.4.5. 1b-trans. White solid (79%). Mp ¼ 89e91 ꢁC. IR (neat):
4.2.4. Characterization of propargylic esters 1
n
¼ 3274, 2931, 2859, 1743, 1365, 1226 cmꢀ1
.
1H NMR (400 MHz,
CDCl3)
d
5.08 (m, 1H), 2.74 (d, J ¼ 13.6 Hz, 1H), 2.54 (s, 1H), 2.46 (m,
1H), 2.03 (s, 3H), 1.94 (m, 1H), 1.70e1.50 (m, 11H), 1.28 (m, 3H). 13C
NMR (100 MHz, CDCl3) 169.1, 132.5, 122.8, 84.0, 76.7, 73.6, 46.7,
O
O
d
34.6, 28.5, 25.9, 25.7, 24.3, 21.6, 21.2, 17.7. HRMS calcd. for C15H22O2
([M þ H]þ): 235.1693; found: 235.1697.
4.2.4.1. 1a-trans. White solid (81%). Mp ¼ 73e75 ꢁC. IR (neat):
O
O
n
¼ 3274, 2934, 2860, 1742, 1366, 1224 cmꢀ1
.
1H NMR (400 MHz,
CDCl3)
d
5.73 (m, 1H), 5.00 (m, 2H), 2.71 (d, J ¼ 13.6 Hz,1H), 2.64 (m,
1H), 2.57 (s, 1H), 2.04 (s, 3H), 2.01 (m, 1H), 1.77e1.51 (m, 6H), 1.30
(m, 2H).13C NMR (100 MHz, CDCl3)
d
169.1, 137.2, 116.0, 83.8, 76.6,
73.8, 45.7, 34.6 (2C), 25.8, 24.2, 21.6, 21.1. HRMS calcd. for C13H18O2
([M þ H]þ): 207.1381; found: 207.1379.
4.2.4.6. 1b-cis. Colorless oil (81%). IR (neat):
n
¼ 3273, 2933, 2857,
6.06 (m, 1H),
1743, 1366, 1224 cmꢀ1 1H NMR (400 MHz, CDCl3)
.
d
2.67 (m, 1H), 2.59 (s, 1H), 2.36 (m, 1H), 1.96 (s, 3H), 1.86 (m, 1H), 1.70
(m, 1H), 1.65e1.52 (m, 9H), 1.45 (m, 1H), 1.30e1.10 (m, 3H). 13C NMR
O
O
(100 MHz, CDCl3)
d 169.0, 132.4, 122.6, 80.6, 79.6, 76.2, 46.4, 36.0,
28.6, 28.0, 25.6, 24.9, 23.3, 21.7, 17.6. HRMS calcd. for C15H22O2
([M þ H]þ): 235.1693; found: 235.1697.
O
O
4.2.4.2. 1a-cis. Colorless oil (85%). IR (neat):
n
¼ 3273, 2934, 2859,
5.69 (m, 1H),
1745, 1368, 1221 cmꢀ1 1H NMR (400 MHz, CDCl3)
.
d
4.97 (m, 2H), 2.71 (d, J ¼ 12.0 Hz, 1H), 2.60 (s, 1H), 2.53 (m, 1H), 1.99
(s, 3H), 1.89 (m, 1H), 1.80e1.43 (m, 6H), 1.20 (m, 2H).13C NMR
(100 MHz, CDCl3)
d 169.0, 137.0, 115.9, 80.5, 79.5, 76.4, 45.5, 36.0,
4.2.4.7. 1b-trans-NO2. White solid (63%). mp ¼ 131e133 ꢁC. IR
34.7, 27.8, 24.8, 23.2, 21.8. HRMS calcd. for C13H18O2 ([M þ H]þ):
(neat):
n
¼ 3269, 2901, 2859, 1739, 1360, 1199 cmꢀ1
.
1H NMR
207.1381; found: 207.1383.
(400 MHz, CDCl3)
d
8.29(d, J ¼ 8.8 Hz,2H), 8.19 (d, J ¼ 8.8 Hz, 2H), 5.17
4.2.4.3. 1a-trans-NO2. White solid (69%). Mp ¼ 121e123 ꢁC. IR
(t, J ¼ 6.8 Hz, 1H), 2.87 (d, J ¼ 13.6 Hz, 1H), 2.79 (m, 1H), 2.67 (s, 1H),
2.63 (m, 1H), 2.11 (m, 1H), 1.89e1.59 (m, 10H), 1.48e1.31 (m, 3H). 13C
(neat):
(400 MHz, CDCl3)
n
¼ 3298, 2935, 2858, 1723, 1521, 1321. 1116 cmꢀ1
.
1H NMR
NMR (100 MHz, CDCl3)
d 162.6, 150.5, 136.4, 133.1, 130.6 (2C), 123.6
d
8.29 (d, J ¼ 9.2 Hz, 2H), 8.18 (d, J ¼ 9.2 Hz, 2H),
(2C), 122.5, 83.2, 78.9, 74.7, 47.2, 34.9, 29.1, 26.5, 25.8, 24.4, 21.3, 17.8.
5.79 (m, 1H), 5.06 (m, 2H), 2.95 (d br, J ¼ 14.0 Hz, 1H), 2.79 (m, 1H),
HRMS calcd. for C20H23NO4 ([M þ H]þ): 342.1701; found: 342.1698.
2.68 (s, 1H), 2.12 (m, 1H), 1.90e1.56 (m, 5H), 1.50e1.30 (m, 3H). 13C

Y. Harrak et al. / Journal of Organometallic Chemistry 696 (2011) 388e399
397
O2N
O
O
4.3.2.3. 5a. White solid. Mp ¼ 69e71 ꢁC. IR (neat):
n
¼ 2935, 2863,
1718, 1507, 1314, 1222 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d 6.03 (dd,
4.2.4.8. 1b-cis-NO2. White solid (66%). mp ¼ 134e136 ꢁC. IR (neat):
n
¼ 3267, 2919, 2860, 1743, 1359, 1211 cmꢀ1
.
1H NMR (400 MHz,
J ¼ 10, 2.4 Hz, 1H), 5.73 (m, 1H), 5.36 (s, 1H), 5.13 (s, 1H), 3.25 (m,
1H), 2.10 (m, 1H), 1.93 (m, 4H), 1.69 (m, 2H), 1.51 (m, 3H), 1.36 (m,
CDCl3)
d
8.26 (d, J ¼ 8.8 Hz, 2H), 8.17 (d, J ¼ 8.8 Hz, 2H), 5.19 (t,
3H). 13C NMR (100 MHz, CDCl3)
d 169.9, 142.1, 127.9, 127.8, 115.1,
J ¼ 6.8 Hz, 1H), 2.87 (m, 1H), 2.74 (s, 1H), 2.53 (m, 1H), 2.03 (m, 1H),
1.88 (m, 2H), 1.75e1.59 (m, 10H), 1.37 (m, 1H), 1.25 (m, 1H). 13C NMR
79.3, 41.9, 29.8, 29.7, 28.6, 25.4, 22.1, 21.7. HRMS calcd. for C13H18O2
([M þ H]þ): 207.1381; found: 207.1384.
(100 MHz, CDCl3)
d 162.7, 150.4, 136.5, 132.9, 130.6 (2C), 123.4 (2C),
122.6, 82.0, 80.2, 77.4, 46.8, 36.3, 29.2, 28.5, 25.8, 24.9, 23.5, 17.9.
HRMS calcd. for C20H23NO4 ([M þ H]þ): 342.1701; found: 342.1706.
O
H
O
O2N
O
O
4.3.2.4. 5a-NO2. White solid. Mp ¼ 141e143 ꢁC. IR (neat):
n
¼ 2931, 2858, 1715, 1520, 1332, 1119 cmꢀ1
.
1H NMR (400 MHz,
CDCl3)
d
8.25 (d, J ¼ 8.8 Hz, 2H), 8.10 (d, J ¼ 8.8 Hz, 2H), 6.07 (dd,
J ¼ 10, 2.3 Hz, 1H), 5.79 (m, 1H), 5.52 (s, 1H), 5.24 (s, 1H), 3.42 (d,
J ¼ 12.4 Hz, 1H), 2.29 (m, 1H), 2.15 (m, 1H), 1.62 (m, 5H), 1.51 (m,
4.3. General procedure for cycloisomerization reactions
1H), 1.38 (m, 2H). 13C NMR (100 MHz, CDCl3)
d 163.0, 150.3, 141.6,
4.3.1. General procedure for AuCl3 and Echavarren gold complex
catalyzed reactions
137.5, 130.3 (2C), 128.0, 127.9, 123.5 (2C), 115.9, 81.8, 42.2, 30.3,
30.0, 29.2, 25.3, 21.8. HRMS calcd. for C18H19NO4 ([M þ H]þ):
314.1388; found: 314.1393.
The catalyst was added to a solution of the substrate in anhy-
drous CH2Cl2 or toluene (0.025 M). The reaction progress was
monitored by TLC. When the reaction was complete, the mixture
was filtered through a short pad of silica. The solvent was removed
under vacuum, and purification by flash chromatography afforded
the cycloisomerization products.
O2N
O
H
O
4.3.2. General procedure for PPh3Auþ catalyzed reaction
AuClPPh3 (2 mol%) was added to a solution of AgSbF6 (2 mol%) in
anhydrous CH2Cl2 (corresponding volume to have a final substrate
concentration of 0.025 M). The mixture was stirred for 5 min and
the substrate was added neat. The reaction progress was monitored
by TLC. When the reaction was complete, the mixture was filtered
through a short pad of silica. The solvent was removed under
vacuum, and purification by flash chromatography over silica
afforded the cycloisomerization product.
4.3.2.5. 3a. Colorless oil (mixture of diastreoisomers). IR (neat):
n
¼ 3074, 2928, 2853, 1979, 1727, 1360, 1279 cmꢀ1
.
1H NMR
(400 MHz, CDCl3) d 7.33 (m, 1H), 5.79 (m, 1H), 4.99 (m, 2H), 2.38 (m,
2H), 2.12e1.80 (m, 9H), 1.77 (m, 2H), 1.28 (m, 1H). 13C NMR
(100 MHz, CDCl3) 186.2 (2C), 168.8 (2C), 136.9 (2C), 122.7 (2C),
d
116.0 (2C), 110.4 (2C), 41.0, 40.1, 38.1, 37.8, 33.2 (2C), 33.0 (2C), 27.4
(2C), 25.5 (2C), 21.0 (2C). HRMS calcd. for C13H18O2 ([M þ H]þ):
207.1381; found: 207.1389.
4.3.2.1. 2a. Colorless oil, IR (neat):
n
¼ 2923, 2852, 1744, 1677, 1366,
2.45 (m, 1H), 2.25 (m, 1H),
1213 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d
2.20 (m,1H), 2.16 (s, 3H),1.67 (m, 3H),1.52 (m,1H),1.40 (m,1H),1.23
O
(m, 4H), 1.02 (m, 1H), 0.88 (dt, J ¼ 8, 4 Hz, 1H), 0.40 (m, 1H). 13C NMR
(100 MHz, CDCl3)
d 169.6, 141.5, 124.1, 38.2, 36.0, 27.9, 27.1, 26.8,
O
•
26.5, 20.9, 18.5, 12.4, 12.0. HRMS calcd. for C13H18O2 ([M þ H]þ):
207.1381; found: 207.1379.
O
O
4.3.2.6. 3a-NO2. Colorless oil (mixture of diastreoisomers). IR
(neat):
¼ 3075, 2931, 2854, 1978, 1718, 1527, 1360, 1237,
1093 cmꢀ1. 1H NMR (400 MHz, CDCl3)
8.27 (m, 4H), 7.55 (m, 1H),
5.78 (m, 1H), 5.00 (m, 2H), 2.33 (m, 1H), 2.16e1.80 (m, 7H), 1.45 (m,
2H),1.24 (m, 1H). 13C NMR (100 MHz, CDCl3)
187.0 (2C), 162.6 (2C),
150.1 (2C), 136.8 (2C), 135.0 (2C), 130 (6C), 123.6 (4C), 116.1 (2C),
110.8 (2C), 41.2, 41.0, 38.0, 37.8, 33.4, 33.2, 33.0 (2C), 27.5 (2C), 25.5,
25.4. HRMS calcd. for C18H19NO4 ([M þ H]þ): 314.1388; found:
314.1397.
H
n
d
d
4.3.2.2. 4a. Colorless oil. 1H NMR (400 MHz, CDCl3)
3H), 2.81 (t, J ¼ 5.9 Hz, 2H), 2.67 (t, J ¼ 5.9 Hz, 2H), 2.25 (s, 3H)
1.92e1.87 (m, 2H), 1.86e1.78 (m, 2H). Spectral data are in agree-
ment with the literature [20].
d
7.07e6.96 (m,

398
Y. Harrak et al. / Journal of Organometallic Chemistry 696 (2011) 388e399
O2N
O2N
O
O
O
•
O
H
4.3.2.11. 10b-NO2. White solid. Mp ¼ 124e126 ꢁC IR (neat):
¼ 2937, 2858, 1743, 1520, 1256, 1110 cmꢀ1
.
1H NMR (400 MHz,
4.3.2.7. 3b. Colorless oil (mixture of diastreoisomers). IR (neat):
n
n
¼ 3072, 2931, 2851,1980,1723,1355,1276 cmꢀ1.1HNMR (400 MHz,
CDCl3)
d 8.29 (m, 4H), 2.55 (m, 1H), 2.05 (m, 1H), 1.87 (m, 2H), 1.70
(m, 3H), 1.48 (m, 1H), 1.29e1.05 (m, 11 H). 13C NMR (100 MHz,
CDCl3) 162.8, 150.6, 140.1, 135.7, 131.0 (2C), 123.5 (2C), 123.0, 35.7,
CDCl3) d 7.30 (m, 1H), 5.17 (m, 1H), 2.40 (m, 1H), 2.16e2.05 (m, 6H),
1.92 (m, 3H), 1.79 (m, 2H), 1.69 (s, 3H), 1.57 (s, 3H), 1.40 (m, 2H). 13C
NMR (100 MHz, CDCl3) 186.3, 186.2, 168.7 (2C), 132.3, 132.2, 123.0
d
d
35.5, 28.2, 25.9 (2C), 25.8, 25.7, 25.4, 25.1, 23.7, 15.9. HRMS calcd. for
C20H23NO4 ([M þ Na]þ): 364.1519; found: 364.1519.
(2C), 122.8 (2C), 110.2 (2C), 41.9 (2C), 33.4, 33.3, 33.1 (2C), 32.3, 31.9,
27.5 (2C), 25.8 (2C), 25.6, 25.5, 21.0, 20.9, 17.8 (2C). HRMS calcd. for
C15H22O2 ([M þ H]þ): 235.1693; found: 235.1701.
O2N
O
O
O
O
•
H
4.3.2.12. 11. Yellow solid. Mp ¼ 133e135 ꢁC. IR (neat):
n
¼ 2929,
2864, 1747, 1536, 1277 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d
8.29 (m,
4.3.2.8. 2b. Colorless oil, IR (neat):
1213 cmꢀ1. 1H NMR (400 MHz, CDCl3)
2.14 (s, 3H), 2.01 (m, 1H), 1.63 (m, 4H), 1.23e0.88 (m, 12 H). 13C NMR
(100 MHz, CDCl3) 169.3, 139.6, 125.5, 35.3, 34.9, 27.2, 25.7, 25.6,
n
¼ 2931, 2849, 1721, 1640, 1317,
d
2.53 (m, 1H), 2.37 (m, 1H),
4H), 5.45 (s, 1H), 2.51 (m, 1H), 2.30 (m, 2H), 2.00 (m, 2H), 1.76 (m,
3H), 1.26 (m, 4H) 1.04 (d, J ¼ 8 Hz, 6H). 13C NMR (100 MHz, CDCl3)
d
d
162.9, 150.7, 145.5, 139.2, 135.3, 131.0 (2C), 123.6, 123.5 (2C), 114.2,
25.2, 25.1, 23.9, 23.8, 20.9, 20.8, 15.5. HRMS calcd. for C15H22O2
36.0, 34.9, 34.1, 33.4, 25.5, 25.5 (2C), 20.9, 20.8. HRMS calcd. for
([M þ H]þ): 235.1693; found: 235.1696.
C20H23NO4 ([M þ Na]þ): 364.1519; found: 364.1517.
O2N
O
O
O
O
H
4.3.2.13. 9b. Colorless oil. IR (neat)
n
¼ 2950, 1730, 1460, 1370,
4.3.2.9. 10b. Colorless oil. IR (neat):
n
¼ 2930, 2850, 1729, 1647,
1250 cmꢀ1 1H NMR (400 MHz, CDCl3)
.
d
6.10 (dd, J ¼ 9.8, 2.5 Hz,
1235 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d 2.51 (m, 1H), 2.14 (s, 3H),
1H),5.60 (d, J ¼ 9.8 Hz, 1 H), 5.52 (bs, 1H), 3.03 (m, 1H), 2.18e2.13 (m, 2H), 2.02 (s,
1.98 (dd, J ¼ 14.4, 8.8 Hz,1H), 1.80 (m, 2H), 1.65 (m, 3H),1.41 (m,1H),
1.28e1.03 (m, 5H), 1.04 (s, 3H), 0.95 (s, 3H). 13C NMR (100 MHz,
3H), 1.89e1.78 (m, 4H), 1.68e1.54 (m, 1H), 1.45 (s, 3H), 1.41 (s, 3H),
1.21 (m, 1H), 1.07 (m, 1H). 13C NMR (100 MHz, CDCl3)
d 170.5, 137.2,
CDCl3)
d 169.1, 139.8, 122.3, 35.6, 35.5, 28.2, 26.0, 25.7 (2C), 25.5,
25.3, 24.8, 23.7, 20.9, 15.7. HRMS calcd. for C15H22O2 ([M þ H]þ):
130.5, 127.1, 124.1, 84.6, 45.0, 35.0, 32.0, 30.6, 25.8, 23.5, 22.9, 22.6,
22.3.
235.1693; found: 235.1701.
O
O
O
H
O
H
H
4.3.2.14. 9b-NO2. White solid. Mp 143e145 ꢁC. IR (neat)
1730, 1554, 1459, 1369, 1147 cmꢀ1 1H NMR (400 MHz, CDCl3)
n
¼ 2950,
4.3.2.10. 2b-NO2. White solid. Mp ¼ 129e131 ꢁC IR (neat):
.
n
¼ 2934, 2852, 1739, 1519, 1255, 1106 cmꢀ1
.
1H NMR (400 MHz,
d
8.27 (m, 2H), 8.15 (m, 2H), 6.12 (dd, J ¼ 10.0, 2.5 Hz, 1H), 5.66 (d,
CDCl3)
d
8.29 (m, 4H), 2.54 (d br, J ¼ 15.2 Hz, 1H), 2.42 (m, 1H), 2.08
J ¼ 10 Hz, 1H), 5.53 (bs, 1H), 3.14 (d, J ¼ 10 Hz, 1H), 2.26 (m, 1H),
(m, 1H), 1.70 (m, 4H), 1.10 (m, 12 H). 13C NMR (100 MHz, CDCl3)
162.9, 150.6, 139.8, 135.7, 131.1 (2C), 126.2, 123.5 (2C), 35.6, 34.8,
2.13 (m, 2H), 1.87 (m, 3H), 1.62 (m, 7H), 1.16 (m, 2H). 13C NMR
d
(100 MHz, CDCl3) d 163.6, 150.3, 137.3, 136.9, 131.2, 130.6 (2C),
27.2, 25.7 (2C), 25.2 (2C), 24.3, 23.7, 21.2, 15.7. HRMS calcd. for
126.4, 124.7, 123.5 (2C), 87.0, 45.5, 35.0, 32.2, 30.6, 25.9, 23.7, 22.9,
22.4.
C20H23NO4 ([M þ Na]þ): 364.1519; found: 364.1518.

Y. Harrak et al. / Journal of Organometallic Chemistry 696 (2011) 388e399
[3] (a) A. Fürstner, Chem. Soc. Rev. 38 (2009) 3208;
399
O
(b) E. Jiménez-Núñez, A.M. Echavarren, Chem. Rev. 108 (2008) 3326;
(c) A.S.K. Hashmi, Chem. Rev. 107 (2007) 3181;
O
(d) D.J. Gorin, D.F. Toste, Nature 446 (2007) 395;
(e) P. Belmont, E. Parker, Eur. J. Org. Chem. (2009) 6075.
H
NO2
[4] For recent contributions from our group, see: (a) Y. Harrak, A. Simonneau,
M. Malacria, V. Gandon, L. Fensterbank, Chem. Commun. (2010) 865;
(b) N. Marion, G. Lemière, A. Correa, C. Costabile, R.S. Ramón, X. Moreau, P. de
Frémont, R. Dahmane, A. Hours, D. Lesage, J.C. Tabet, J.-P. Goddard, V. Gandon,
L. Cavallo, L. Fensterbank, M. Malacria, S.P. Nolan, Chem. Eur. J. 15 (2009) 3243;
(c) G. Lemière, V. Gandon, K. Cariou, A. Hours, T. Fukuyama, A.-L. Dhimane,
L. Fensterbank, M. Malacria, J. Am. Chem. Soc. 131 (2009) 2993;
(d) X. Moreau, A. Hours, L. Fensterbank, J.-P. Goddard, M. Malacria,
S. Thorimbert, J. Organometal. Chem. 694 (2009) 561.
[5] C. Blaszykowski, Y. Harrak, C. Brancour, K. Nakama, A.L. Dhimane,
L. Fensterbank, M. Malacria, Synthesis (2007) 2037.
[6] For seminal articles, see: (a) H. Strickler, J.B. Davis, G. Ohloff, Helv. Chim. Acta
59 (1976) 1328;
H
4.3.2.15. Formation of ketone 12. To a solution of 2b-NO2 (341 mg,
1 mmol, 1 equiv.) in MeOH (20 mL) was added K2CO3 (1.1 g,
8 mmol, 8 equiv.) and stirring was maintained at rt for 24 h. Then,
the reaction was diluted with Et2O, quenched with saturated NH4Cl
aqueous solution and the resulting aqueous layer was extracted
with Et2O. The combined organic layers were washed with brine,
dried over anhydrous Na2SO4, filtered and evaporated in vacuo. The
crude was purified by flash column chromatography on silica gel
(PE/Et2O 100/0 to 9/1) to afford 12 as a colorless oil (154 mg, 80%).
(b) V. Rautenstrauch, J. Org. Chem. 49 (1984) 950;
(c) E. Mainetti, V. Mouriès, L. Fensterbank, M. Malacria, J. Marco-Contelles,
Angew. Chem. Int. Ed. 41 (2002) 2132;
(d) For reviews, see: N. Marion, S.P. Nolan Angew. Chem. Int. Ed. 46 (2007)
2750;
IR (neat)
d
n
¼ 2977, 1689, 1312, 1087 cmꢀ1. 1H NMR (400 MHz, C6D6)
(e) J. Marco-Contelles, E. Soriano, Chem. Eur. J. 13 (2007) 1350;
(f) For a recent carbonylative version, see: C. Brancour, T. Fukuyama, Y. Ohta,
I. Ryu, A.-L. Dhimane, L. Fensterbank, M. Malacria Chem. Comm. (2010) 5470.
[7] A. Fürstner, P. Hannen, Chem. Eur. J. 12 (2006) 3006.
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E. Mainetti, N. Marion, V. Mouriés, S. Thorimbert, L. Fensterbank, M. Malacria,
Adv. Synth. Cat. 350 (2008) 43;
(b) For an aromatic linker in asymmetric version, see: I.D.G. Watson, S. Ritter,
F.D. Toste J. Am. Chem. Soc. 131 (2009) 2056.
[10] P. Pérez-Gálan, N. Delpont, E. Herrero-Gómez, F. Maseras, A.M. Echavarren,
Chem. Eur. J. 16 (2010) 5324 (and references therein).
2.60 (m, 1H), 1.76 (m, 1H), 1.60 (m, 2H), 1.48 (m, 1H), 1.26 (m, 4H),
1.04e0.82 (m, 11H). 13C NMR (100 MHz, C6D6)
d 210.2, 53.4, 44.4,
35.8, 34.8, 30.8, 30.1, 28.0 (2C), 27.7, 27.1, 26.6, 17.5.
4.3.2.16. Formation of hydrazone 13. To a stirred solution of ketone
12 (108 mg, 0.56 mmol, 1 equiv.), 2,4 dinitrophenylhydrazine
(166 mg, 0.84 mmol, 1.5 equiv.) in toluene (10 mL) was added TSOH
(5 mg, 0.026 mmol, 0.05 equiv.) at rt. The reaction mixture was
refluxed for 3 h. The solvent was evaporated under vacuum and the
residue was purified by flash chromatography on silica gel (PE/Et2O
100/0 to 95/05) to afford 13 as an orange solid. (190 mg, 91%).
[11] (a) For solvent effects in gold-catalyzed cycloisomerizations, see: R. Zriba,
V. Gandon, C. Aubert, L. Fensterbank, M. Malacria Chem. Eur. J. 14 (2008)
1482;
mp ¼ 153e155 ꢁC, IR (neat):
n
¼ 3295, 2924, 2839, 1613, 1588, 1422,
(b) See also A.S. Dudnik, Y. Xia, Y. Li, V. Gevorgyan, J. Am. Chem. Soc. 132
(2010) 7645 (and references therein).
1296 cmꢀ1 1H NMR (400 MHz, CD2Cl2)
. d 11.36 (s, 1H), 9.06 (d,
J ¼ 2.4 Hz, 1H), 8.24 (dd, J ¼ 9.6 Hz, 2.0, 1H), 7.90 (d, J ¼ 9.6 Hz, 1H),
2.59 (m,1H),1.96 (ddd, J ¼ 14.0, 9.6, 3.6 Hz,1H),1.74 (m, 3H),1.50 (m,
2H), 1.39 (s, 3H) 1.31e1.11 (m, 5H), 1.05e0.89 (m, 5H). 13C NMR
[12] (a) C. Nieto-Oberhuber, M.P. Muñoz, S. López, E. Jiménez-Núñez, C. Nevado,
E. Herrero-Gómez, M. Raducan, A.M. Echavarren, Chem. Eur. J. 12 (2006) 1677;
(b) N. Cabello, E. Jiménez-Núñez, E. Buñuel, D.J. Cárdenas, A.M. Echavarren, Eur. J.
Org. Chem. (2006) 4217;
(100 MHz, CD2Cl2)
d 162.3, 145.3, 137.3, 129.7, 128.9, 123.5, 116.4,
(c) J. Marco-Contelles, N. Arroyo, S. Anjum, E. Mainetti, N. Marion, K. Cariou,
G. Lemière, V. Mouriès, L. Fensterbank, M. Malacria, Eur. J. Org. Chem. (2006)
4618.
46.8, 40.4, 33.5, 29.7, 27.8, 26.9, 26.8, 26.5, 25.8, 25.0, 22.4, 16.5.
HRMS calcd. for C19H24N4O4 ([M þ Na]þ): 395.1691; found: 395.1697.
[13] (a) L. Zhang, S. Wang, J. Am. Chem. Soc. 128 (2006) 1442;
(b) P. Mauleón, J.L. Krinsky, F.D. Toste, J. Am. Chem. Soc. 131 (2009) 4513;
(c) D. Garayalde, E. Gómez-Bengoa, X. Huang, A. Goeke, C. Nevado, J. Am.
Chem. Soc. 132 (2010) 4720 (and references therein).
Acknowledgments
[14] (a) N. Marion, R. Gealageas, S.P. Nolan, Org. Lett. 9 (2007) 2653;
(b) C. Gourlaouen, N. Marion, S.P. Nolan, F. Maseras, Org. Lett. 11 (2009) 81.
[15] A. Correa, N. Marion, L. Fensterbank, M. Malacria, S.P. Nolan, Angew. Chem.
Int. Ed. 47 (2008) 718.
[16] M.J. Frisch, et al., Gaussian 03, Revision C.02. Gaussian, Inc., Pittsburgh, PA,
2004.
We thank the MRES, the CNRS, the IUF and the ANR Blan 0302
“Allènes” for financial support. Calculations were performed at
CRIHAN, plan interrégional du bassin parisien (project 2006-013).
Special thanks to Lise-Marie Chamoreau (UPMC) for the X-ray
structure determination of 1a-trans, 1b-trans, 9b-NO2 and 13 and
Michel Giorgi (U. Aix-Marseille III) for the X-ray structure deter-
mination of 5a-NO2.
[17] (See inter alia): (a) C. Nieto-Oberhuber, S. López, E. Jiménez-Núñez,
A.M. Echavarren, Chem. Eur. J. 12 (2006) 5916;
(b) N. Cabello, E. Jiménez-Núñez, E. Buñuel, D.J. Cárdenas, A.M. Echavarren,
Eur. J. Org. Chem. (2007) 4217;
(c) C. Nieto-Oberhuber, P. Pérez-Galán, E. Herrero-Gómez, T. Lauterbach,
C. Rodríguez, S. López, C. Bour, A. Rosellón, D.J. Cárdenas, A.M. Echavarren, J.
Am. Chem. Soc. 130 (2008) 269;
Appendix A. Supplementary material
(d) E. Soriano, P. Ballesteros, J. Marco-Contelles, Organometallics 24 (2005)
3182;
CCDC 784467; 783123; 784468; 784466 and 784469 contain
the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
(e) E. Soriano, J. Marco-Contelles, Chem. Eur. J. 14 (2008) 6771;
(f) E. Soriano, J. Marco-Contelles, J. Org. Chem. 72 (2007) 1443;
(g) E. Soriano, J. Marco-Contelles, J. Org. Chem. 72 (2007) 2651;
(h) E. Soriano, J. Marco-Contelles, J. Org. Chem. 70 (2005) 9345;
(i) S. Baumgarten, D. Lesage, V. Gandon, J.-P. Goddard, M. Malacria, J.-C. Tabet,
Y. Gimbert, L. Fensterbank, Chem. Cat. Chem. 1 (2009) 138;
(j) O. Nieto Faza, C. Silva Lopez, R. Alvarez, A.R. de Lera, J. Am. Chem. Soc. 128
(2006) 2434.
Appendix. Supplementary data
[18] For a clarification, see: Because cyclopropanes are formed, we decided to use
the carbene rendition of the intermediates. However, the true nature of these
species can be rather cationic. (a) A. Fürstner, Chem. Soc. Rev. 38 (2009) 3208;
(b) A.M. Echavarren, Nat. Chem. 1 (2009) 431.
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.jorganchem.2010.10.016.
[19] A 6- endo- dig/1,2-O-acyl migration tandem (see Refs. [7] and [17deh]) might
also be invoked in order to explain the formation of cyclopropyl products 2b
and 10b. We thank a referee for this suggestion.
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