Regioselective Synthesis of Indene from 3-Aryl Propargylic gem-Dipivalates Catalyzed by N-Heterocyclic Carbene Gold(I) Complexes

Article abstract of DOI:10.1002/adsc.201800305

1-Aryl-3,3-bis(pivaloyloxy)propynes can be converted in good to high yields into either 1,3- or 1,2-bis(pivaloyloxy)indenes, depending on the N-heterocyclic carbene (NHC) gold(I) hexafluoroantimonate catalyst used. Almost exclusive formation of 1,3-di(oxycarbonyl)indene derivatives was achieved with cationic gold complexes containing the embracing N,N′-1,3-bis(9-butylfluorenyl)benzimidazolylidene ligand (^nBuFNHC). The regioselective issue of the reaction was rationalized by the specific spatial distribution of the steric bulk in the ^nBuFNHC ligand. In contrast, only modest selectivities in favor of 1,2-disubstituted indenes were observed with more classical NHC gold complexes, the best selectivity being then obtained with N,N′-1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolylidene gold chloride (SIPrAuCl) as precatalyst. (Figure presented.).

Full text of DOI:10.1002/adsc.201800305

Title: Regioselective Synthesis of Indene from 3-Aryl Propargylic
gem-Dipivalates Catalyzed by N-Heterocyclic Carbene Gold(I)
Complexes
Authors: Damien Hueber, Matthieu Teci, Eric Brenner, Dominique Matt,
Jean-Marc Weibel, Patrick Pale, and Aurelien Blanc
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800305
Link to VoR: http://dx.doi.org/10.1002/adsc.201800305

10.1002/adsc.201800305
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Regioselective Synthesis of Indene from 3-Aryl Propargylic
gem-Dipivalates Catalyzed by N-Heterocyclic Carbene Gold(I)
Complexes
Damien Hueber,a Matthieu Teci,b Eric Brenner,b Dominique Matt,b Jean-Marc Weibel,a
Patrick Pale,a,* and Aurélien Blanca,*
a
Laboratoire de Synthèse, Réactivité Organiques, et Catalyse, Institut de Chimie, UMR 7177 CNRS, Université de
Strasbourg, 4 rue Blaise Pascal, 67070 Strasbourg, France.
E-mail: ppale@unistra.fr; ablanc@unistra.fr
Laboratoire de Chimie Inorganique Moléculaire et Catalyse, Institut de Chimie, UMR 7177 CNRS, Université de
b
Strasbourg, 4 rue Blaise Pascal, 67070 Strasbourg, France.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
coordinated allene (A in Scheme 1) or to a gold
carbene (B in Scheme 1), which can further evolve.
All these intermediates seem to be in equilibrium and
of close energy,[5] and the selectivity towards one or
the other pathway seems to be dictated by the R1-3
substituents of the propargylic ester.[6]
Furthermore, it has been shown that alkenyl or aryl
propargylic esters (R1 = alkenyl or aryl) lead under
gold catalysis to valuable cyclized products upon
participation of the unsaturated group to further
reactions with intermediates A or B.[7] It was also
shown that the outcome of such reactions could be
adjusted towards one or another product depending
on the presence or not of water, of silver salt, and on
the ligand nature.[8]
Abstract. 1-Aryl-3,3-bis(pivaloyloxy)propynes can
be converted in good to high yields into either 1,3- or
1,2-bis(pivaloyloxy)indenes, depending on the N-
heterocyclic
carbene
(NHC)
gold(I)
hexafluoroantimonate catalyst used. Almost exclusive
formation of 1,3-di(oxycarbonyl)indene derivatives
was achieved with cationic gold complexes containing
the
embracing
N,N'-1,3-bis(9-
butylfluorenyl)benzimidazolylidene ligand (nBuFNHC).
The regioselective issue of the reaction was
rationalized by the specific spatial distribution of the
steric bulk in the nBuFNHC ligand. In contrast, only
modest selectivities in favor of 1,2-disubstituted
indenes were observed with more classical NHC gold
complexes, the best selectivity being then obtained
with
N,N’-1,3-bis(2,6-diisopropylphenyl)-4,5-
dihydroimidazolylidene gold chloride (SIPrAuCl) as
precatalyst.
Keywords: Gold(I); N-heterocyclic carbenes;
Homogeneous catalysis; Indenes; Rearrangement
Homogeneous gold catalysis has emerged at the turn
of the XXIst century, and has rapidly grown through a
kind of new “gold rush”,[1] providing access to
numerous compounds under (very) mild conditions,
but also offering to the chemical community various
new reactions, especially rearrangements.[2] Among
the latter, gold-catalyzed 1,2- and 1,3-acyl migrations
of propargylic esters have been a milestone,[3]
considering the various applications,[4] the complexity
associated to decipher the exact mechanism[5] and the
difficulty to tune the selectivity of the 1,2- or 1,3 shift
(Scheme 1). This rearrangement is initiated by endo-
or exo-dig cyclization of the carboxylate group upon
gold coordination to the alkyne moiety, followed by
1,3- or 1,2-migration, leading respectively to a gold
Scheme 1. Gold(I) Catalyzed Rearrangements of
Propargylic Esters.
Indenes are recurrent motifs in many
pharmaceuticals and natural products (Scheme 2)
such as Sulindac, an efficient non-steroidal anti-
inflammatory drug, Coixinden A, an antimicrobial
substance or Indriline, an antidepressant agent.[9]
Considering the potent biological activities of this
1
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10.1002/adsc.201800305
Advanced Synthesis & Catalysis
Scheme 2. Selected Natural or Bioactive Products Containing Indene Motifs and Mechanistic Hypothesis for Gold-
Catalyzed Transformation of Propargylic gem-Diester 1.
class of molecules, various synthetic methods number of steps as short as possible within a scalable
dedicated to the preparation of indene derivatives sequence.
have been reported in the literature, including gold
catalysis.[8a,10] We thus wondered if alkenyl or aryl
propargylic gem-diesters 1 could be engaged in 1,2-
or 1,3-migration processes catalyzed by gold, leading
to polyfunctionalized building blocks such as indenes
3 or 4 in only one step (Scheme 2).
In this context, we started investigating the
behavior of propargylic gem-diesters (1) under Au-
catalysis and we have already demonstrated that such
diesters highly selectively provide (E)-3-carbonyloxy
enones 2 in good to high yields in the presence of
[(triphenylphosphino)]gold(I) silicotungstate as non-
conventional and recyclable catalyst (Scheme 3).[11]
Scheme 4. Three Step Synthesis of Propargyl gem-
Dipivalates 1a-h.
The reaction optimization was performed with one
Scheme
3.
Polyoxometalate-Gold(I)
Catalyzed of the simplest of these propargylic gem-diesters, i.e.
Stereoselective Rearrangement of Propargylic gem-Diesters the 1-phenyl-3,3-bis(pivaloyloxy)propyne (1a). The
1 into (E)-Enones.10
latter was submitted to various gold catalysts,
activated or not by silver salt, in dichloromethane at
room temperature. These reactions were performed in
In the present work, we show that certain NHC- the presence of anhydrous molecular sieves to trap
gold complexes catalyze the almost exclusive any adventitious water and thus limiting hydration or
formation of 1,3-di(carbonyloxy)indene derivatives (3 hydrolysis side-reactions (Table 1). Despite these
in Scheme 2) from 3-arylpropargylic gem-diesters.
precautions, the common (triphenylphosphino)gold
The starting 3-arylpropargylic gem-dipivalates 1a- catalyst mostly gave mainly the (E)-1-phenyl-3-
h were conveniently produced through a three-step pivaloyloxyprop-2-en-1-one (2a), (Table 1, entry
sequence from propargyl alcohol and iodo aryl 1).[11,13] The same trend also occurred with less
derivatives (Scheme 4). From the latter,
a
donating phosphite ligand on gold, although with a
Sonogashira coupling followed by a Swern oxidation diminished reactivity (Table 1, entry 2 vs 1).
allowed the formation of various 3-arylprop-2-yn-1- Interestingly, shifting to more donating o-
als. These aldehydes could be converted to their ester biarylphosphines reversed this selectivity in favor of
acetals in the presence of an excess of anhydride and the 1,3-di(pivaloyloxy)indene 3a, but to the detriment
sulfuric acid as catalyst.[12] This strategy allows of the kinetic of the reaction (Table 1, entry 3).
readily varying the aryl moiety, while keeping the Rewardingly, gold catalysts carrying even more
2
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10.1002/adsc.201800305
Advanced Synthesis & Catalysis
donating NHC-type ligand[14] restored the reactivity,
with reaction times mostly below 1 h (Table 1, entries
4-9). Furthermore, depending on NHC substitution,
the selectivity towards 3a could be reinforced, up to
the almost exclusive formation of this compound
(Table 1, entry 9). NHC ligands also allowed the
formation of the 1,2-di(pivaloyloxy)indene 4a, more
or less selectively depending on their nature (Table 1,
entries 5-7).[15]
SIPr and IPr ligands with a high hindrance,
measured as the percentage of buried volume (%VBur),
seem to favour the formation of the 1,2-
di(pivaloyloxy)indene 4a (Table 1, entries 6 and 7).
However, using this factor, no clear correlation
between ligand size and product yields could be found.
In contrast, the formation of enone 2a is almost
constant, whatever the NHC used, although with large
variations (16±12%). The latter could be due to the
more or less important presence of water, brought by
the silver salt used to activate the gold chloride
catalyst. It is worth noticing here that the highly
hygroscopic silver hexafluoroantimonate alone
promoted the sole formation of 2a to an extent of 20%
(Table 1, entry 11).
Figure 1. Structures and topographic steric maps (TSM)[17]
of
SIPrAuCl,
N,N'-bis(9-butylfluorenyl)
benzimidazolylidene gold(I) chloride and triflimide
complexes 6 and 7.
The N,N'-bis(9-butylfluorenyl)benzimidazolylidene
ligand[19] nBuFNHC) outperformed all the evaluated
(
ligands, providing a very high selectivity in favour of
the 1,3-disubstituted indene 3a (Table 1, entry 9 vs 4-
8). As already observed for other reactions,[18b] the
strong embracing character of this ligand is likely
responsible for the observed selectivity. Indeed, TSM
of the gold complex 6 shows that the two butyl chains
of the ligand are facing the metal, creating a pocket,
which is clearly not the case for the [1,2]-selective
SIPr ligand (Figure 1 and Table 1, entry 6 vs 9). The
Table
1.
Optimization
of
Gold(I)-Catalyzed
Rearrangement of Propargylic gem-Dipivalate 1a in Indene
Derivatives 2a or 3a.
Entry Gold Complex
(%VBur for NHC)
Time Yield Yield Yield in situ formed cationic [AuL]+ complex can thus bind
(h)
3aa
4aa
2aa
the alkyne bond of 1a between these two chains, in an
orthogonal position relative to the benzimidazole
moiety (complex C in Scheme 5). It is worth
reminding here that  coordination is largely
controlled by steric factors.[20] The coordination
induces the subsequent formation of cyclic
intermediates D or/and F (Scheme 5). The latter can
easily evolve towards the complex A' allene and
subsequently to product 3. In contrast, intermediate D
already suffered from strong steric interactions
between the oxolanium moiety and one butyl side
chain, limiting its evolution towards the carbenic
intermediate E, which is not the case on the
intermediate F.[21] Even if formed, intermediate E
does not have the right conformation to proceed
through a Nazarov-type cyclization to the final
product. To reach this conformation (intermediate
B’), a rotation around the C-C bond adjacent to the
newly created carbene is required; however, this
rotation seems hampered by severe clashes with the
butyl side chains. The difficulties to form both
intermediates D and B’ are factors that may prevent
the formation of the corresponding 1,2-disubstituted
product, explaining the high selectivity in favor of the
1,3 disubstituted product.
1
2
3
4
5
6
7
8
9
Ph3PAuCl
0.5
5
24
0.25
0.25
1
0.75
0.25
8
9
-
-
-
5
28
42
55
2
33
18
17
28
10
16
18
3
PhosphiteAuCl 5b
JohnPhosAuCl
IMesAuCl (36.5)
ItBuAuCl (39.3)
IPrAuCl (46.6)
SIPrAuCl (47.4)
IAdAuCl (39.8)
32
10
45
25
20
41
85
nBuFNHC-AuCl 6c 0.5
(39.4)
6
-
10
nBuFNHC-AuNTf2 3.5
7d (42.6)
70
15
-
11
AgSbF6
24
-
-
20
a) Calculated yields from 1H NMR integration relative to an
b)
internal standard (hexamethylbenzene). 5 = tris(2,4-di-
tert-butylphenyl)phosphite.
fluoren-9-yl)benzimidazol-2-ylidene)gold(I) chloride.
Reaction run without AgSbF6, 7 = (1,3-bis(9-butyl-9H-
fluoren-9-yl)benzimidazol-2-ylidene) gold(I) triflimide.[16]
c)
6 = (1,3-bis(9-butyl-9H-
d)
For NHC ligands, the spatial distribution of the
steric bulk can easily be depicted by a topographic
steric map (TSM).[17] Recently, this parameter proved
to be a more accurate criterion than the buried volume
to rationalize results and selectivity in gold catalysis
(Figure 1).[18]
Of note, the slightly lower selectivity observed
using the nBuFNHC gold(I) triflimide 7 could be
attributed to the presence of the large NTf2 counter
3
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10.1002/adsc.201800305
Advanced Synthesis & Catalysis
anion, distorting the clamp formed around gold atom while the latter quantitatively gave the corresponding
(Figure 1, TMS of 6 vs 7).
indenes 3d-e (Table 2, entries 4-5 vs 1). With a better
electron-donating group, such as in the methoxylated
1c, the 1,3-regioselectivity slightly decreased, leading
to an inseparable mixture of 3c and 4c in a ratio of
83:17, but with a steady overall yield of 75% (Table 2,
entry 3 vs 1).
Table 2. Scope of N,N'-bis(9-Butyl)fluorenyl-NHC
Gold(I)-Complex 6 in Catalyzed Transformation of
Propargylic gem-Diester 1 in 1,3-Di(pivaloyloxy)indene
Derivatives 3.
Scheme 5. Simplified view of the developed interactions
during the formation of 1,2- or 1,3-disusbtituted products
within the N,N'-bis(9-butylfluorenyl)benzimidazolylidene
gold(I)-complex (E = OCOR).
a) Isolated yield. b) No reaction, starting material recovered.
c)
Reaction run at 45 °C. d) Isolated with 12% of 1,2-
di(carbonyloxy)indene derivative 4c (See SI). e) Along with
Having identified the best gold catalyst and best
conditions to provide 1,3-di(pivaloyloxy)indene 3, we
then explored the scope and limitations of this
transformation. Various propargylic gem-dipivalates
1a-h were submitted to the conditions set above
(Table 2).
The coordination of the alkynyl moiety to the
metal will probably be influenced by the electronic
properties of the substituent on the aryl group
adjacent to the insaturation. This phenomenon was
clearly observed by comparing the para-chlorophenyl
derivative 1b and the methylphenyl derivatives 1d-e.
The former proved to be unreactive (Table 2, entry 2
vs 1) due to its electron-withdrawing substituent,
74% of unreacted starting material.
To tackle the hindrance issue discussed above, we
screened the effect of the substituent position (Table 2,
entries 4-6). In the methyl series, the para derivative
1d readily reacted, as expected (Table 2, entry 4),
while the meta derivative 1e reacted as efficiently but
provided two regioisomers 3e/3e’ in, respectively, a
ratio of 89:11 (Table 2, entry 5). As suspected from
our model and hindrance developed in Scheme 5, the
ortho derivative 1f reacted only very slowly, probably
because of the steric hindrance generated by the
methyl group located close to the insaturation, giving
4
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10.1002/adsc.201800305
Advanced Synthesis & Catalysis
butylfluorenyl)NHCAuCl[18b] 6 (5 mol%) and MS 4Å in
dry dichloromethane. The resulting mixture was stirred at
room temperature for 1 hour. The gem-dipivalates (≈ 0.3
mmol) were added to the catalytic solution and stirred at
room temperature until completion (NMR monitoring). The
reaction mixture was then evaporated, and the crude
residue was purified by flash column chromatography over
silica gel (Cyclohexane/EA 5%) to afford the desired
products.
only 22% of the expected product along with the
remaining starting material, even after extended
reaction time and heating (Table 2, entry 6). These
results reasonably fit with our hypothesis: in para
position, the substituent probably does not feel any
constraint, while in ortho position, steric interactions
with the NHC butyl chain are highly probable. In the
meta position, less interactions should apply, but in
one rotamer the methyl substituent may experience
some clash with one butyl chain, thus leading
preferentially to one regiosiomer.
For the same reason, we also examined the
behaviour of the 1- or 2-naphthyl substituted
propargylic gem-diesters 1g-h (Table 2, entries 7-8).
As expected, both electron rich naphthyl derivatives
lead to the formation of two indenes 3g and 3h in
high yields. It is noteworthy to mention that the 2-
naphthyl derivative 1h affords exclusively the
regioisomer 3h resulting from selective addition of
the naphthyl group in position one.
In summary, we have demonstrated that the spatial
repartition of hindrance imparted by nBuFNHC ligand
around the gold atom is a key factor in the
regioselective conversion in good to high yields of 1-
aryl-3,3-bis(pivaloyloxy)-propynes (1) into 1,3-
di(oxycarbonyl)indene derivatives (3). In contrast,
only modest selectivity in favor of 1,2-disubstituted
indenes 4 was observed with more classical NHC
1H-Indene-1,3-diyl bis(2,2-dimethyl-propanoate) 3a:
Prepared according General procedure 1 from 0.316 mmol
of 1a; yield: 75% (75.2 mg, 0.238 mmol); yellow oil; TLC
Rf 0.65 (Cyclohexane/EA 20%); 1H NMR (400 MHz,
CDCl3) δ 1.23 (s, 9H), 1.38 (s, 9H), 6.26 (d, J = 2.3 Hz,
1H), 6.30 (d, J = 2.3 Hz, 1H), 7.22−7.29 (m, 2H),
7.30−7.37 (m, 1H), 7.38−7.41 (m, 1H); 13C NMR (126
MHz, CDCl3) δ 27.2, 39.0, 39.7, 74.6, 113.9, 118.5, 124.3,
127.3, 128.7, 138.5, 141.0, 151.3, 175.1, 179.0; HR-MS
[M+Na]+ 339.1540 [C19H24O4Na], calculated 339.1567.
6-Methoxy-1H-indene-1,3-diyl
bis(2,2-dimethyl-
propanoate) 3c: Prepared according General procedure 1
from 0.1 mmol of 1c; yield: 63% (26 mg, 0.075 mmol as an
inseparable mixture with 4c 12%); colorless oil; TLC Rf
1
0.53 (Cyclohexane/EA 20%); H NMR (400 MHz, CDCl3)
δ 1.23 (s, 9H), 1.37 (s, 9H), 3.81 (s, 3H), 6.13 (d, J = 2.4
Hz, 1H), 6.24 (d, J = 2.4 Hz, 1H), 6.84 (dd, J = 8.3, 2.4 Hz,
1H), 6.99 (d, J = 2.4 Hz, 1H), 7.12 (d, J = 8.3 Hz, 1H); 13
C
NMR (126 MHz, CDCl3) δ 27.2, 27.2, 39.0, 39.6, 55.7,
74.4, 111.5, 111.9, 113.3, 131.1, 143.0, 151.3, 159.7, 175.1,
179.0; HR-MS [M+Na]+ 369.1624 [C20H26O5Na],
calculated 369.1672.
6-Methyl-1H-indene-1,3-diyl
bis(2,2-dimethyl-
gold complexes, the best selectivity in this series propanoate) 3d: Prepared according General procedure 1
from 0.272 mmol of 1d; yield: 98%, 88.8 mg, 0.269 mmol;
being then achieved with SIPrAuCl/AgSbF6 as
catalyst.
Further works on the improvement of the [1,2]-
migration selectivity as well as on the development of
chiral version of N-alkylfluorenyl NHC ligands are
ongoing in our laboratories.
1
yellow oil; TLC Rf 0.63 (Cyclohexane/EA 20%); H NMR
(400 MHz, CDCl3) δ 1.27 (s, 9H), 1.37 (s, 9H), 2.38 (s, 3H),
6.18 (d, J = 2.4 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H),
7.10−7.16 (m, 2H), 7.21 (s, 1H); 13C NMR (126 MHz,
CDCl3) δ 21.6, 27.2, 27.2, 39.0, 39.6, 74.6, 113.0, 118.1,
125.3, 129.2, 135.8, 137.4, 141.2, 151.4, 175.2, 179.1; HR-
MS [M+Na]+ 353.1769 [C20H26O4Na], calculated 353.1723.
5-Methyl-1H-indene-1,3-diyl
bis(2,2-dimethyl-
propanoate) 3e: Prepared according General procedure 1
from 0.303 mmol of 1e, in mixture with 11 mg of 7-
methyl-1H-indene-1,3-diyl bis(2,2-dimethyl-propanoate)
2c’: 11%); yield: 87% (87 mg, 0.297 mmol; yellow oil;
Experimental Section
General Information. Proton (1H NMR) and carbon (13C
NMR) nuclear magnetic resonance spectra were recorded
on 300, 400 or 500 MHz instruments. Chemical shifts are
given in part per million (ppm) on the delta scale. The
1
TLC Rf 0.63 (Cyclohexane/EA 20%); H NMR (400 MHz,
CDCl3) δ 1.22 (s, 9H), 1.38 (s, 9H), 2.39 (s, 3H), 6.24 (d, J
= 2.4 Hz, 1H), 6.26 (d, J = 2.4 Hz, 1H), 7.03 (brs, 1H),
7.04−7.09 (m, 1H), 7.28 (d, J = 7.6 Hz, 1H); 13C NMR
(126 MHz, CDCl3) δ 21.6, 27.2, 27.2, 39.0, 39.7, 74.4,
114.1, 119.2, 124.1, 127.9, 138.1, 138.7, 151.3, 175.2,
179.0; HR-MS [M+Na]+ 353.1711 [C20H26O4Na],
calculated 353.1723.
1
solvent peak was used as reference value. For H NMR:
CHCl3 = 7.26 ppm. For 13C NMR: CHCl3= 77.16 ppm.
High resolution mass spectra (HRMS) data were recorded
on a microTOF spectrometer equipped with orthogonal
electrospray interface (ESI). The parent ions [M]+.,
[M+H]+. [M+Li]+. or [M+Na]+. are quoted. Analytical thin
,
layer chromatography (TLC) was carried out on silica gel
60 F254 plates or basic alumina (63−200 µm) with
visualization by ultraviolet light or potassium
permanganate dip. Flash column chromatography was
carried out using silica gel 60 (40−63 µm) or basic Al2O3
(63−200 µm) and the procedure included the subsequent
evaporation of solvents in vacuo. Reagents and solvents
were purified using standard means. Dichloromethane
(CH2Cl2), acetonitrile (CH3CN), tetrahydrofuran (THF) and
diethyl ether (Et2O) were dried over activated alumina
column (DryStation). All other chemicals were used as
received, and all extractive procedures were performed
using non-distilled solvents and all aqueous solutions used
were saturated unless details are given.
4-methyl-1H-indene-1,3-diyl
bis(2,2-dimethyl-
propanoate) 3f: Prepared according General procedure 1
from 0.303 mmol of 1f; yield: 22% (22 mg, 0.067 mmol);
1
yellow oil; TLC Rf 0.64 (Cyclohexane/EA 20%); H NMR
(400 MHz, CDCl3) δ 1.23 (s, 9H), 1.36 (s, 9H), 2.52 (s, 3H),
6.24 (d, J = 2.4 Hz, 1H), 6.30 (d, J = 2.4 Hz, 1H), 7.06–
7.10 (m, 1H), 7.14 (t, J = 7.5 Hz, 1H), 7.20−7.23 (m, 1H,
H5); 13C NMR (126 MHz, CDCl3) δ 19.4, 27.1, 27.2, 39.0,
39.4, 74.0, 114.1, 121.9, 127.2, 130.6, 131.5, 136.0, 141.6,
153.1, 175.5, 179.0. HR-MS [M+Na]+ 353.1720
[C20H26O4Na], calculated 353.1723.
3H-Cyclopenta[a]naphthalene-1,3-diyl
bis(2,2-
dimethylpropanoate) 3g: Prepared according General
procedure 1 from 0.273 mmol of 1g; yield: 92% (91.7 mg,
0.25 mmol); yellow oil; TLC Rf 0.64 (Cyclohexane/EA
General Procedure
1
for the gold-catalyzed
rearrangement of propargylic gem-dipivalates 2 in 1,3-
dipivoyloxyindene derivatives 3: AgSbF6 (5 mol%) was
1
20%); H NMR (400 MHz, CDCl3) δ 1.26 (s, 9H), 1.48 (s,
9H), 6.37 (d, J = 2.3 Hz, 1H), 6.52 (d, J = 2.3 Hz, 1H),
7.46−7.55 (m, 3H), 7.78 (d, J = 8.3 Hz, 1H), 7.86−7.90 (m,
added
to
a
solution
of
N,N'-bis(9-
5
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10.1002/adsc.201800305
Advanced Synthesis & Catalysis
1H), 8.62 (d, J = 8.5 Hz, 1H); 13C NMR (126 MHz, CDCl3)
δ 27.3, 27.3, 39.1, 39.7, 74.3, 114.5, 121.6, 123.9, 125.9,
126.4, 127.3, 128.0, 128.8, 133.5, 134.3, 139.9, 153.2,
175.3, 179.1; HR-MS [M+Na]+ 389.1732 [C23H26O4Na],
calculated 389.1723.
Harrak, C. Blaszykowski, M. Bernard, K. Cariou, E.
Mainetti, V. Mouries, A.-L. Dhimane, L. Fensterbank,
M. Malacria J. Am. Chem. Soc. 2004, 126, 8656-8657.
[4] For reviews, see: a) N. Marion, S. P. Nolan, Angew.
Chem. Int. Ed. 2007, 46, 2750-2752; b) R. K. Shiroodi,
V. Gevorgyan, Chem. Soc. Rev. 2013, 42, 4991-5001.
1H-Cyclopenta[a]naphthalene-1,3-diyl
bis(2,2-
dimethylpropanoate) 3h: Prepared according General
procedure 1 from 0.330 mmol of 1h; yield: 85% (102.4 mg,
0.279 mmol); yellow oil; TLC Rf 0.64 (Cyclohexane/EA
[5] A. Correa, N. Marion, L. Fensterbank, M. Malacria, S.
P. Nolan, L. Cavallo, Angew. Chem. Int. Ed. 2008, 47,
718-721.
1
20%); H NMR (400 MHz, CDCl3) δ 1.27 (s, 9H), 1.42 (s,
9H), 6.39 (d, J = 2.3 Hz, 1H), 6.64 (d, J = 2.3 Hz, 1H),
7.41−7.54 (m, 3H), 7.77−7.82 (m, 1H), 7.86−7.92 (m, 2H);
13C NMR (126 MHz, CDCl3) δ 27.2, 27.3, 39.2, 39.7, 74.2,
113.5, 117.0, 123.4, 125.6, 127.0, 129.0, 129.3, 129.8,
133.1, 136.4, 136.7, 151.4, 175.2, 178.7; HR-MS [M+Na]+
389.1683 [C23H26O4Na], calculated 389.1723.
[6] J. Jiang, Y. Liu, C. Hou, Y. Li, Z. Luan, C. Zhao, Z. Ke
Org. Biomol. Chem. 2016, 14, 3558-3563.
[7] For selected examples see: a) L. Zhang, S. Wang J. Am.
Chem. Soc., 2006, 128, 1442-1443. b) J. Zhao, C. O.
Hughes, F. D. Toste, J. Am. Chem. Soc. 2006, 128,
7436-7437; c) A. Buzas, F. Gagosz, J. Am. Chem. Soc.
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Schwier, A. W. Sromek, D. M. L. Yap, D. Chernyak, V.
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e) D. Leboeuf, A. Simonneau, C. Aubert, M. Malacria,
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2011, 51, 6868-6871.
1H-indene-1,2-diyl bis(2,2-dimethylpropanoate) (4a):
By-product obtained during the optimization study (table
1
1); yellow oil; TLC Rf 0.70 (Cyclohexane/EA 20%); H
NMR (500 MHz, CDCl3) δ 1.30 (s, 9H), 6.81 (d, J = 12.3
Hz, 1H), 7.44−7.50 (m, 2H), 7.54−7.59 (m, 1H), 7.90−7.94
(m, 2H), 8.41 (d, J = 12.3 Hz, 1H); 13C NMR (126 MHz,
CDCl3) δ 26.8, 39.0, 109.9, 128.4, 128.7, 133.0, 138.0,
151.0, 174.6, 190.5; HR-MS [M+Na]+ 255.0980
[C14H16O3Na], calculated 255.0992.
(E)-3-Oxo-3-phenylprop-1-en-1-yl pivalate (2a):[11a] By-
product obtained during the optimization study (table 1);
1
yellow oil; TLC Rf 0.45 (Cyclohexane/EA 20%); H NMR
[8] a) N. Marion, S. Diez-Gonzalez, P. de Frémont, A. R.
Noble, S. P. Nolan, Angew. Chem. Int. Ed. 2006, 45,
3647-3650; b) N. Marion, P. Carlqvist, R. Gealagas, P.
de Frémont, F. Maseras, S. P. Nolan, Chem. Eur. J.
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Slawin, S. P. Nolan, Chem. Commun. 2010, 46, 9113-
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M. Z. Slawin, C. S. J. Cazin, S. P. Nolan,
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(500 MHz, CDCl3) δ 1.30 (s, 9H), 6.81 (d, J = 12.3 Hz, 1H),
7.44−7.50 (m, 2H), 7.54−7.59 (m, 1H), 7.90−7.94 (m, 2H),
8.41 (d, J = 12.3 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ
26.8, 39.0, 109.9, 128.4, 128.7, 133.0, 138.0, 151.0, 174.6,
190.5; HR-MS [M+Na]+ 255.0980 [C14H16O3Na],
calculated 255.0992.
Acknowledgements
We gratefully acknowledge the CNRS and the French Ministry of
Research. D.H. thanks the Agence Nationale de la Recherche
(Grant ANR-11-JS07-001-01 SyntHetAu) for a PhD fellowship.
[9] a) H. Buschmann, T. Christoph, in Analgesics; H.
Buschmann, T. Christoph, E. Friderichs, C. Maul, B.
Sundermann, Eds.; Wiley-VCH: Weinheim, 2002, 106
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Okamoto, H. Sakamoto, Y. Sonoda, Nippon Nogei
Kagaku Kaishi 1993, 67, 1405-1410; c) M. P. Young,
O. C. Idowu, P. McKeown, (e-Therapeutics Ple, UK),
US Patent 20110212173, A1 20110901, 2011.
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6
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10.1002/adsc.201800305
Advanced Synthesis & Catalysis
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7
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10.1002/adsc.201800305
Advanced Synthesis & Catalysis
COMMUNICATION
Regioselective Synthesis of Indene from 3-Aryl
Propargylic gem-Dipivalates Catalyzed by N-
Heterocyclic Carbene Gold(I) Complexes
Adv. Synth. Catal. Year, Volume, Page – Page
Damien Hueber,a Matthieu Teci,b Eric Brenner,b
Dominique Matt,b Jean-Marc Weibel,a Patrick
Pale,a,* and Aurélien Blanca,*
8
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