Synthesis of benzofulvenes through chemoselective Sonogashira and Barluenga couplings of ortho ethynyl-N-tosylhydrazones and cycloisomerization

Article abstract of DOI:10.1039/c5ra14459k

Chemoselective synthesis of ortho ethynylhydrazones 7 derived from 2-iodoacetophenone via a Sonogashira coupling is reported for the first time. In this challenging transformation, a site-selective coupling in the presence of a hydrazone function was developed. These compounds represent useful intermediates for the synthesis of benzofulvenes through a sequence of palladium-catalyzed cross-coupling and palladium-catalyzed 5-exo-dig cyclization.

Full text of DOI:10.1039/c5ra14459k

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O
I
CH3
This work (3steps)
5-exo-dig cyclization
TsNHNH2
R1
Ar2
N-NHTs
N-NHTs
CH3
R2
Ar1-X/[Pd]
CH3
[Pd/Cu]
I
R1
R2
R2
5
not isolated
Site-selective coupling
Sequential synthesis of benzofulvenes

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Journal Name
RSCPublishing
ARTICLE
Synthesis of Benzofulvenes through Chemoselective
Sonogashira, Barluenga Couplings of ortho Ethynyl-
N-Tosylhydrazones and Cycloisomerization
Cite this: DOI: 10.1039/x0xx00000x
Jessy Aziz,a JeanꢀDaniel Brion,a Mouad Alami*a and Abdallah Hamze*a
Received 00th January 2012,
Accepted 00th January 2012
Chemoselective synthesis of ortho ethynylhydrazones 7, derived from 2ꢀiodoacetophenone via
DOI: 10.1039/x0xx00000x
www.rsc.org/
a Sonogashira coupling is reported for the first time. In this challenging transformation, a siteꢀ
selective coupling in the presence of a hydrazone function was developed. These compounds
represent useful intermediates for the synthesis of benzofulvenes through a sequence of
palladiumꢀcatalyzed crossꢀcoupling and palladiumꢀcatalyzed 5ꢀexoꢀdig cyclization.
One of the major research topics of our laboratory includes
Introduction
developing synthetic methods using
readily available starting materials for the C
bonds formation. Recently, we disclosed an excellent approach
to the synthesis of benzofulvenes through a selective
palladiumꢀcatalyzed 5ꢀexo dig cyclization of aromatic 1,5ꢀ
enynes 4.5 These latter were prepared from 2ꢀiodoacetophenone
in six steps sequence using as intermediate
tosylhydrazone having a trimethylsilylethynyl group at the C2
position (Scheme 1).
N
ꢀtosylhydrazones as
Multiꢀfunctionalized building blocks have become an
appealing tool in organic synthesis. In fact, they can be
involved in cascade reactions, which became highly
recommended for chemists due to their simple, inexpensive and
timeꢀsaving character along with facile addition of complexity
−
C3 and C N4
−
5
ꢀ
to the final structures. Among these new scaffolds,
Nꢀ
1
a
Nꢀ
tosylhydrazones have emerged as precursors for the inꢀsitu
generation of nonꢀstabilized diazo compounds.1 When these
2
compounds are properly functionalized, multiple C
heteroatom bonds are created in a oneꢀpot fashion.2
−C and
C−
Scheme 1.Reactivity of ortho-substituted hydrazones and in situ synthesis of enynes 4, precursors of benzofulvenes 5
In our continuing attempts to discover new reactivity of
Nꢀ
improve two aspects of this sequence. First, we sought to
tosylhydrazones, and to increase the interest of our synthetic shorten the synthetic scheme exploring the unprecedented site
approach in the formation of benzofulvenes 5, we decided to selective Sonogashira coupling of 2ꢀiodoꢀNꢀtosylhydrazone 6
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DOI: 10.1039/C5RA14459K
with terminal aromatic alkynes while maintaining intact the tedious. For these reasons, we turned our attention to the
hydrazone function.6 Second, because the Barluenga coupling alternative synthetic route path b (Scheme 2). The first step
of
presence of a palladium catalyst and a base under heating, we worked well, providing the
tried to explore the ability of ꢀtosylhydrazone intermediates yield (95%) as a mixture of Eꢀ and Z
7
and the 5ꢀexo
ꢀ
dig cyclization of
4
both required the consisting in the condensation of
ꢀtosylhydrazone
ꢀisomers in a 75/25 ratio.8
1
with sulfonylhydrazide
N
6
in an excellent
N
7
to achieve the sequential Barluenga coupling and the aromatic The next step consists in installing an ethynyl group at position
1,5ꢀenynes cycloisomerization without prior isolation of 2 by a Sonogashira reaction. To our knowledge, this siteꢀ
compound
we wish to disclose our full results that extended the scope of hydrazone function.
our earlier work.5 This strategy provides
convenient Initially, ꢀtosylhydrazone 6 and 4ꢀethynylanisole were
4. Each of these goals was met with success; herein selective coupling has never been described in the presence of a
a
N
challenging and site selective approach to a variety of chosen as coupling partners to optimize the Sonogashira
benzofulvenes, which are not readily available by other reaction. When conventional Sonogashira reaction conditions
methods.
were applied (PdCl2(PPh3)2 (10 mol%), CuI (20 mol%), Et3N
(2equiv),THF, rt), the desired coupling product 7a was formed
with only a 33% isolated yield (Scheme 3).
Results and discussion
As outlined in Scheme 2, 2ꢀethynylhydrazones
7 can be
obtained according two routes starting from readily available 2ꢀ
iodoacetophenone . The first one will involve a Sonogashira
coupling with a terminal aryl alkyne, followed by the
tosylhydrazones formation (compound 7, path a). The second
one, more challenging, will consist in tosylhydrazone
formation from and then its site selective Sonogashira
1
Nꢀ
6
1
coupling with an aryl alkyne under palladiumꢀcopper catalysis
while keeping intact the hydrazine function (path b). In order to
achieve this transformation selectively, fineꢀtuning of the
palladium catalyst, the ligand and the base employed will be
necessary to assure high reaction selectivity, thus avoiding the
formation of indazole byꢀproducts as has been reported by
Inamoto et al.7
Scheme 3.Chemoselectivity issue during the coupling of N-tosylhydrazone
6
As expected from Inamoto report,7 another product was formed
simultaneously, the 3ꢀmethylꢀ1ꢀtosylꢀ1 ꢀindazole in a 35%
yield through an intramolecular BuchwaldꢀHartwig coupling of
H
9
9
the hydrazone(
possible isomerisation of hydrazone
storage or under the reaction conditions of the coupling; which
explains the yield of indazole
Z)ꢀ
6
isomer.7, It should be noticed that a
E
/
Z
6
can occur during
9
.
As a consequence, the main challenge of this work is to
determine chemoselective coupling conditions preserving the
Nꢀtosylhydrazone function, and favoring the intermolecular
Sonogashira reaction over the intramolecular Buchwaldꢀ
Hartwig coupling. The optimization assays for the Sonogashira
coupling between
depicted in Table 1.10
We started screening different bases (entries 1ꢀ3),
diisopropylamine gave the best result with complete
conversion of the hydrazone and the formation of the desired
product 7a in a 45% yield (entry 3). Several solvents were also
tested (entries 3ꢀ6) and dimethylsulfoxide permitted a full
conversion of the starting material in just 8 hours, furnishing 7a
in a 55% yield (entry 6). It should be noticed that all the assays
were conducted at room temperature. At higher temperatures,
Nꢀtosylhydrazone 6 and 4ꢀethynylanisole are
Scheme 2.Synthesis ofN’-(2-alkynylbenzilidene)hydrazides
acetophenones.
7, derived from
According to path a, the Sonogashira coupling of 2ꢀ
iodoacetephenone under standard conditions (PdCl2(PPh3)2
(10 mol%), CuI (20 mol%), Et3N (2equiv), THF, rt) took place
with a good yield for the electronꢀrich alkyne (8a: R = ꢀOMe)
but with a low yield for the electronꢀpoor alkyne (6b: R =
CN). The major drawback of this path is the condensation step
with ꢀtoluenesulfonylhydrazide because very low yields were
a
1
6
p
p
ꢀ
p
obtained for hydrazone 7a formation, and we never succeeded
in isolating the hydrazone 7b despite the use of many protocols
by changing the solvent (MeOH, EtOH), the temperature (rt or
reflux) and additives (MgSO4, PTSA). In all cases, the 1H NMR
of the crude mixture was very complicated and separation was
decomposition of the
Nꢀtosylhydrazone 6 occurred leading to
the BamfordꢀStevens product.11Then, we turned our attention to
the catalytic system. Different copper catalysts were tested
(entries 6ꢀ9), however, no significant increase in the yield of 7a
was observed. Copper (I) iodide was maintained as the copper
2 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C5RA14459K
source in this coupling. Changing the palladium source enabled Electronꢀdeficient alkynes were also effective, albeit affording
the reduction of the reaction time to 3 hours (entries 10ꢀ12).
the coupling product 7h with a slightly diminished yield.
Table 1. Optimization assays for the Sonogashira coupling between Nꢀ
tosylhydrazone 6 and 4ꢀethynylanisolea
Table 2. Synthesis of 7 from Nꢀtosylhydrazone 6 and terminal arylalkynesa
CH3
N-NHTs
CH3
N-NHTs
CH3
N
[Pd], [Ligand],
[Cu], [Base]
OMe
N
Ts
Solvant, 20 °C,
Argon
I
OMe
9
7a
6
CH3
N-NHTs
P
P
P
n P
P
Fe
i-Pr
P
CH3
P
i-Pr
i-Pr
n = 1 dppm
n = 4 dppb
Xphos
Binap
dppf
7a 76%
7b 82%
7c 65%
Yieldb
Entry
Pd
Ligand
Cu
Base
Solvent
7a
9
1c,d
2c,d
3c
CuI
CuI
CuI
CuI
CuI
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
Pd(OAc)2
Pd(acac)2
Pd(PPh3)4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Et3N
THF
THF
THF
33
31
45
40
42
55
54
46
51
55
44
55
55
63
45
58
76
35
26
32
31
32
37
40
36
36
39
42
44
44
37
50
41
19
Piperidine
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
4c
Toluene
MeCN
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
5d
6c
CuI
7d 63%
7e 82%
7f 81%
7c
CuBr
CuCl2
CuTc
CuI
CuI
CuI
CuI
CuI
CuI
CuI
8c
9c
ꢀ
ꢀ
ꢀ
10
11
12
13
14
15
16
ꢀ
Dppf
Dppm
Dppb
XPhos
Rac-Binap
7g 68%
7h 58%
7i 60%
aReaction conditions: Nꢀtosylhydrazone6 (0.48 mmol), alkyne (2 equiv),
Pd(OAc)2 (10 mol%), rac. Binap (20 mol%), CuI (20 mol%), iPr2NH (3
equiv), DMSO (3 mL) at 20 °C for 3 hours, under argon inlet.
17
CuI
a
Unless otherwise noted, reaction conditions: Nꢀtosylhydrazone6 (0.48
mmol), 4ꢀethynylanisole (2 eq), Pd (10 mol%), Ligand (20 mol%), CuI
(20 mol%), Base (3 equiv), Solvent (3 mL) at 20 °C for 3 hours, under
argon inlet. b Yields of isolated product. Reaction time = 6ꢀ24h. 10ꢀ
c
d
15% of 6 was recovered.
We were pleased to find that heterocyclic 3ꢀthienylthiophene
was successfully coupled with hydrazone
6 to access compound
Among several palladium source examined, Pd(OAc)2 afforded 7i in a 60% yield. Unfortunately, our conditions were not
7a in the highest yield of 55% (entry 10). Finally, the ligands compatible with aryl alkynes having electronꢀwithdrawing
had the most notable effect on the yield of 7a (entries 10 and substituents (CN, NO2) on the aromatic nucleus as no coupling
13ꢀ17). The chemoselectivity for the Sonogashira coupling was products were isolated. It should be noticed that all hydrazones
enhanced in the presence of a bidendate phosphine ligand (racꢀ
Binap, entry 17), affording the desired product 7a in a 76% NOESY experiment.12 This diastereoselectivity is in
yield and limiting the formation of indazole to 19%.
accordance with the above statement that only the isomer of
hydrazone gives indazole via intramolecular amination
Once the optimized conditions were established, the scope while the
isomer reacts with the terminal alkyne and gives
for the Sonogashira coupling between hydrazone and hydrazones 7, with retention of the configuration, via
7 were obtained as a single (E)ꢀisomer as determined by
9
Z
6
9
E
6
a
different terminal alkynes was examined (Table 2). Electronꢀ Sonogashira coupling.
enriched alkynes allow the coupling to proceed with good
isolated yields ranging from 63 to 82% (compounds 7a
tolylacetylene gave also the desired coupling product 7c with a catalyzed
good yield, indicating that there no influence of steric hindrance ethynylhydrazones 7a and aryl halides (Scheme 4). Thus, when
ꢀ
f
).
O
ꢀ
Next, we tested the formation of enynes
4
through a palladiumꢀ
crossꢀcoupling reaction
between
orthoꢀ
of the alkyne partner on the coupling.
using the following conditions: PdCl2(MeCN)2, dppp, Cs2CO3,
dioxane 90 °C, 4 h in a sealed tube,13 we noticed the formation
This new protocol worked also well with electronꢀneutral
alkynes, giving the desired products 7f and 7g in good yields.
of benzofulvenes 5a and 5b via in situ 5ꢀexo
ꢀ
dig cyclisation
and
alongside the expected enynes 4a and 4b. Enynes
4
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benzofulvenes
5 were obtained as a mixture in a ratio of about
60/40 determined by 1H NMR (Scheme 4).
In order to avoid any tedious separation of compounds
4 and 5,
these results prompted us to consider the sequential synthesis of
benzofulvenes starting from orthoꢀethynylhydrazones and
without prior isolation of
5d 60%b
5e 40%b
5
7
4
.
a Reaction conditions for the palladiumꢀcatalyzed crossꢀcoupling reaction: Nꢀ
tosylhydrazone 7 (0.48 mmol), aryl iodide (0.80 eq), PdCl2(MeCN)2(10
mol%), XPhos (20 mol%), NaOtBu (3 eq), PhF (3 ml) at 100 °C for 3 hours,
sealed tube. bNꢀtosylhydrazone 7 (0.48 mmol), aryl iodide (0.80 eq),
PdCl2(MeCN)2(10 mol%), Dppp (20 mol%), Cs2CO3 (3 eq), dioxane (3 ml) at
100 °C for 3 hours, sealed tube.
Scheme 4.Synthesis of enynes
4
from N-tosylhydrazones 7a.
Reaction conditions: N-tosylhydrazone 7a (0.24 mmol), aryle iodide (1 equiv),
Conclusions
PdCl2(MeCN)2 (10 mol%), Dppp (20 mol%), Cs2CO3 (3 equiv), Dioxane (3 mL) at 90
In summary,
successfully performed on a
2ꢀiodoacetophenone, leading to
ethynylhydrazones . These compounds were further used for
a
siteꢀselective Sonogashira coupling was
ꢀtosylhydrazone derived from
variety of ortho
a
°C for 4 hours in a sealed tube. Values between brackets refers to isolated
yields.
N
6
a
ꢀ
7
Indeed, enynes
coupling between hydrazones
subjected, without prior isolation, to a 5ꢀexo
giving rise to benzofulvene derivatives
4
, formed in situ by a palladiumꢀcatalyzed
and aryl iodides,3b, 3c were then
dig cyclization
the formation of aromatic 1,5ꢀenynes and their in situ
cyclisation to provide benzofulvene derivatives. This represents
an original and practical synthetic method of benzofulvenes
7
ꢀ
5
.
starting from functionalized Nꢀtosylhydrazones.
Table 3 shows unoptimized results for the sequential two steps
synthesis of benzofulvenes 5 10
We succeeded preparing a
Experimental section
.
General method
variety of benzofulvenes with electronꢀpoor (5a) and electronꢀ
rich substituents (compounds 5b and 5c). Likewise, the reaction
conditions were compatible with the thiophene moiety and
benzofulvene 5e was formed in a 40% yield. Despite the
moderate yields observed, this method represents a short
approach for the synthesis of a variety of benzofulvene
Melting points (mp) were recorded on a Büchi Bꢀ450 apparatus
and were uncorrected. NMR spectra were performed on a
Bruker AMX 200 (1H, 200 MHz; 13C, 50 MHz), Bruker
AVANCE 300 or Bruker AVANCE 400 (1H, 400 MHz; 13C,
100 MHz). Solvent peaks were used as reference values: CDCl3
at 7.26 ppm for H NMR and 77.16 ppm for 13C NMR; DMSO
1
derivatives 5.
at 2.50 ppm for 1H NMR and 39.52 ppm for 13C NMR; Acetone
at 2.05 ppm for H NMR and 29.84 ppm for 13C NMR; MeOD
1
at 3.31 ppm for 1H NMR and 49.00 ppm for 13C NMR.
Table 3.Sequential synthesis of benzofulvenes 5.
Chemical shifts
δ are given in ppm, and the following
abbreviations are used: singlet (s), doublet (d), doublet of
doublet (dd), triplet (t), quadruplet (q), multiplet (m) and broad
singlet (bs). Infrared spectra (IR) were measured on a Bruker
Vector 22 spectrophotometer and were recorded neat (neat, cmꢀ
1). High resolution mass spectra were recorded on
a
MicrotofQBrukerDaltonics. Reaction courses and product
mixtures were routinely monitored by TLC on silica gel
(precoated F254 Merck plates), and compounds were visualized
under a UVP Mineralight UVGLꢀ58 lamp (254 nm) and with
phosphomolybdic acid/ꢀ. Flash chromatography was performed
using silica gel 60 (40–63 mm, 230–400 mesh ASTM) at
medium pressure (200 mbar). Dimethylsulfoxide was used as
received, dioxane, cyclohexane and tetrahydrofuran were dried
using the procedures described in D. Perrin Purification of
Laboratory Chemicals.14NꢀTosylhydrazones were prepared
according to literature procedure described by Creary, X. et
5a 45%a
5b 62%a
5c 55%b
1
al.15 All products reported showed H and 13C NMR spectra in
agreement with the assigned structures.
4 | J. Name., 2012, 00, 1-3
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Experimental procedure for the preparation of N-
tosylhydrazone 6
1605, 1511, 1340, 1307, 1288, 1248, 1165, 1080, 1051, 1030,
906; 1H NMR (300 MHz, CDCl3) δ (ppm) 8.02 (s, 1H), 7.90 (d,
J
(d,
= 8.3 Hz, 2H), 7.53 – 7.45 (m, 1H), 7.39 – 7.21 (m, 7H), 6.85
J
To a rapidly stirred suspension of pꢀtoluenesulfonylhydrazide
= 8.9 Hz, 2H), 3.81 (s, 3H), 2.37 (s, 3H), 2.33 (s, 3H); 13C
(5.5 mmol) in dry methanol (10 mL) was added the carbonyl
substrate (5 mmol) in portion wise. The reaction mixture was
refluxed for 12 hours. The mixture was allowed to cool to room
temperature and the tosylhydrazone began to precipitate. After
approximately 30 min, the mixture was cooled to 0 °C and the
product removed by filtration, washed with a small quantity of
methanol and then dried under vacuum.
NMR (75 MHz, CDCl3) δ 160.0 (C), 155.4 (C), 144.2 (C),
141.2 (C), 135.6 (C), 133.0 (2CH), 132.8 (CH), 129.7 (2CH),
128.8 (CH), 128.7 (CH), 128.2 (2CH), 128.1 (CH), 121.8 (C),
115.1 (C), 114.2 (2CH), 94.6 (C), 86.9 (C), 55.5 (OCH3), 21.7
(CH3), 17.3 (CH3); HRMS (ESI) (M + H)+ calculated for
C24H23N2O3S 419.1418 found 419.1424.
N
’-(1-(2-iodophenyl)ethylidene)-4-methylbenzene-
sulfonohydrazide 6. Hydrazone ( ) precipitated as a white
solid (yield 95%) as a mixture of and Z isomers (75/25); M =
414.26 g.molꢀ1; m.p.: 146ꢀ148 °C; Rf
0.46
(
E
)-4-methyl-
N’-(1-(p-tolylethynyl)phenyl)ethylidene)-
6
benzenesulfonohydrazide 7b. Grey solid; Yield 82%; M=
E
402.14 g.molꢀ1; m.p.: 142ꢀ144 oC; Rf
=
0.33
=
(Cyclohexane/EtOAc 80/20); IR (film, cmꢀ1): 3459, 2214, 2040,
2006, 1971, 1950, 1597, 1511, 1405, 1341, 1309, 1166, 1081,
1052, 1019, 912; 1H NMR (400 MHz, CDCl3,) δ (ppm) 7.89 (d,
(Cyclohexane/EtOAc 70/30); IR (film, cmꢀ1): 3444, 3426, 3376,
3302, 3264, 3245, 3190, 3169, 3123, 3086, 3040, 3014, 2961,
2835, 2723, 2666, 2535, 2364, 2340, 2263, 2212, 2160, 2142,
2107, 1995, 1970, 1698, 1424, 1339, 1291, 1244, 1167, 1091,
1032, 1010; Major isomer: (
(ppm) 8.45 (s, 1H), 7.87 (d,
Hz, 1H), 7.29 (d, = 8.7 Hz, 2H), 7.27 (td,
7.07 (dd, = 8.2, 1.7 Hz, 1H), 6.97 (td,
2.40 (s, 3H), 2.14 (s, 3H) ; 13C NMR (75 MHz, CDCl3) δ (ppm)
156.5 (C), 144.2 (C), 144.1 (C), 139.4 (CH), 135.7 (C), 130.0
(CH), 129.7 (2CH), 129.3 (CH), 128.2 (2CH), 128.1 (CH), 95.2
J
= 8.2 Hz, 2H), 7.82 (s, 1H), 7.51 (d,
J = 7.3 Hz, 1H), 7.29 (m,
7H), 7.13 (d, = 7.9 Hz, 2H), 2.37 (s, 3H), 2.37 (d, 3H), 2.32
J
E
J
)ꢀ: 1H NMR (400 MHz, CDCl3)
= 8.7 Hz, 2H), 7.74 (dd, = 8.2, 1
= 8.2, 1 Hz, 1H),
= 8.2, 1.7 Hz, 1H),
δ
(s, 3H); 13C NMR (101 MHz, CDCl3) δ (ppm) 155.1 (C), 144.2
(C), 141.3 (C), 139.0 (C), 135.6 (C), 133.0 (CH), 131.4 (2CH),
129.7 (2CH), 129.3 (2CH), 128.9 (CH), 128.8 (CH), 128.3
(CH), 128.2 (2CH), 121.7 (C), 120.0 (C), 94.7 (C), 87.6 (C),
21.7 (CH3), 21.7 (CH3), 17.2 (CH3); HRMS (ESI) (M + H)+
calculated for C24H23N2O2S 403.1464 found 403.1475.
J
J
J
J
J
(
E)-4-methyl-
N’-(1-(o-tolylethynyl)phenyl)ethylidene)-
(C), 21.7 (CH3), 18.1 (CH3); Minor isomer: (
MHz, CDCl3) δ (ppm) 7.84 (d, = 8.7 Hz, 2H), 7.79 (dd,
= 8.2, 1 Hz, 1H), 7.33 (s, 1H), 7.31
= 8.2, 1.7 Hz, 1H), 6.92 (dd, = 8.2,
Z
)ꢀ: 1H NMR (400
benzenesulfonohydrazide 7c. Green solid; Yield 65%; M =
J
J =
402.14 g.molꢀ1; m.p.: 78ꢀ80 C; Rf = 0.33 (Cyclohexane/EtOAc
o
8.2, 1 Hz, 1H), 7.38 (td,
(d, = 8.7, 2H), 7.05 (td,
J
J
80/20); IR (film, cmꢀ1): 3060, 2212, 2196, 2155, 2118, 2045,
2001, 1597, 1492, 1455, 1403, 1381, 1341, 1308, 1266, 1166,
J
J
1.7 Hz, 1H), 2.41 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ (ppm) 155.6 (C), 144.1 (C), 139.9 (CH), 139.6 (C),
135.5 (C), 131.2 (CH), 129.6 (2CH), 129.5 (CH), 128.1 (2CH),
127.7 (CH), 93.2 (C), 24.0 (CH3), 21.7 (CH3); HRMS (ESI) (M
+ H)+ calculated for C15H16IN2O2S 414.9959 found 414.9972.
1
1081, 1049, 920, 913, 814; H NMR (300 MHz, DMSO) δ
(ppm) 10.63 (s, 1H), 7.75 (d,
1H), 7.42 (d, = 6.8 Hz, 2H), 7.40 – 7.37 (m, 1H), 7.28 (d,
8.2 Hz, 4H), 7.23 (dd, = 6.8, 2.3 Hz, 2H), 2.35 (s, 3H), 2.31
(s, 3H), 2.28 (s, 3H);13C NMR (75 MHz, DMSO) δ 155.2 (C),
J = 8.2 Hz, 2H), 7.59 – 7.54 (m,
J
J =
J
Typical procedure for the Sonogashira coupling between 143.2 (C), 141.6 (C), 139.6 (C), 136.3 (C), 132.6 (CH), 131.6
hydrazone 6 and terminal alkynes
(CH), 129.6 (CH), 129.3 (2CH), 128.9 (CH), 128.7 (CH), 128.7
(CH), 128.1 (CH), 127.3 (2CH), 125.8 (CH), 121.9 (C), 120.5
(C), 92.5 (C), 91.6 (C), 20.9 (CH3), 20.2 (CH3), 18.4 (CH3);
HRMS (ESI) (M + H)+ calculated for C24H23N2O2S 403.1468
found 403.1475.
To 1 equivalent of ꢀtosylhydrazone (0.48 mmol) in 3 ml of
N
anhydrous DMSO under argon inlet, 0.1 eq of Pd(OAc)2 (0.048
mmol), 0.2 eq of racꢀBINAP (0.097 mmol) and 0.2 eq of CuI
(0.097 mmol) were respectively added. The reaction mixture
was stirred at room temperature for 3 minutes. Then, 3
(E)-N’-(1-(2-((4-(dimethylamino)phenyl)ethynyl)phenyl)-
ethylidene)-4-methylbenzene- sulfonehydrazide 7d.
equivalents of the distilled base iPr2NH (1.45 mmol) were
Green solid; Yield 63%; M = 431.17 g.molꢀ1; m.p.: 148ꢀ150 oC;
Rf = 0.19 (Cyclohexane/EtOAc 80/20); IR (film, cmꢀ1): 3259,
3235, 2855, 2206, 2192, 2158, 2098, 2044, 2011, 1987, 1913,
1605, 1524, 1444, 1402, 1365, 1340, 1309, 1265, 1166, 1084,
slowly added and the mixture stirred for about 1 minute before
adding 2 equivalents of the terminal alkyne (0.97 mmol). The
reaction mixture was stirred for 3 hours at 20 °C, than quenched
with a saturated solution of NH4Cl and washed with ethyl
acetate. The organic layers were washed with a saturated
solution of NaCl, dried with Na2SO4 and concentrated under
pressure. Column chromatography (Cyclohexane/EtOAc 90/10)
afforded the final products.
1
1052; H NMR (300 MHz, CDCl3) δ (ppm) 7.95 (s, 1H), 7.91
(d,
J
= 8.3 Hz, 2H), 7.47 (d,
J = 7.7 Hz, 1H), 7.36 – 7.17 (m,
7H), 6.62 (d,
J
= 8.9 Hz, 2H), 2.98 (s, 6H), 2.37 (s, 3H), 2.34 (s,
3H); 13C NMR (75 MHz, DMSO) δ (ppm) 155.9 (C), 150.3 (C),
143.2 (C), 141.2 (C), 136.3 (C), 132.3 (2CH), 131.9 (CH),
129.4 (2CH), 128.7 (CH), 128.1 (CH), 127.7 (CH), 127.4
(2CH), 121.3 (C), 111.8 (2CH), 108.2 (C), 95.6 (C), 85.9 (C),
39.7 (2CH3), 21.0 (CH3), 18.2 (CH3); HRMS (ESI) (M + H)+
calculated for C25H26N3O2S 432.1732 found 432.1740.
(E)-N’-(1-(2-((4-methoxyphenyl)ethynyl)phenyl)ethylidene)-
4-methylbenzenesulfono- hydrazide 7a. Brown solid; Yield
76%; M = 418.14 g.molꢀ1; m.p.: 141ꢀ144 °C; Rf = 0.36
(Cyclohexane/EtOAc 70/30); IR (film, cmꢀ1): 2214, 2168,
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 5

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VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C5RA14459K
(
E
)-
N
’-(1-(2-((6-methoxynaphtalen-2-yl)ethynyl)phenyl)-
1599, 1508, 1405, 1342, 1308, 1229, 1168, 1093, 1048, 920; 1H
NMR (300 MHz, DMSO) δ (ppm) 10.59 (s, 1H), 7.75 (d,
ethylidene)-4-methylbenzene- sulfonohydrazide 7e.
J
=
Brown solid; Yield 82%; M = 468.15 g.molꢀ1; m.p.: 152ꢀ154 8.3 Hz, 2H), 7.59 – 7.46 (m, 3H), 7.44 – 7.34 (m, 2H), 7.34 –
oC; Rf = 0.17 (Cyclohexane/EtOAc 80/20); IR (film, cmꢀ1): 7.15 (m, 5H), 2.30 (s, 3H), 2.28 (s, 3H); 13C NMR (75 MHz,
1
3368, 2214, 2199, 2038, 2017, 1985, 1627, 1601, 1499, 1477, DMSO) δ (ppm) 162.1 (C, JCꢀF = 234.0 Hz), 155.4 (C), 143.2
1437, 1390, 1339, 1309, 1261, 1211, 1165, 1121, 1094, 1080, (C), 141.8 (C), 136.3 (C), 133.6 (2CH, JCꢀF = 8.6.0 Hz), 132.5
1052, 1030, 968, 909, 856, 814, 763, 733; H NMR (300 MHz, (CH), 129.4 (2CH), 128.7 (2CH), 128.1 (CH), 127.4 (2CH),
DMSO) δ (ppm) 10.60 (s, 1H), 7.99 (s, 1H), 7.85 (d,
Hz, 2H), 7.76 (d,
= 8.2 Hz, 2H), 7.62 – 7.55 (m, 1H), 7.50 – Hz), 92.4 (C), 87.6 (C), 20.9 (CH3), 18.2 (CH3); 19F NMR (188
7.34 (m, 4H), 7.24 (dd,
= 12.2, 5.6 Hz, 4H), 3.90 (s, 3H), 2.36 MHz, DMSO) δ (ppm) ꢀ108.42; HRMS (ESI) (M + H)+
(s, 3H), 2.22 (s, 3H); 13C NMR (75 MHz, DMSO) δ (ppm) calculated for C23H20FN2O2S 407.1230 found 407.1216.
158.2 (C), 155.6 (C), 143.1 (C), 141.7 (C), 136.3 (C), 134.1 )- ’-(1-(2-(thiophen-3-ylethynyl)phenyl)ethylidene)-4-
3
1
4
2
J = 8.2 120.2 (C), 118.6 (C, JCꢀF = 3.0 Hz), 115.9 (2CH, JCꢀF = 22.2
J
J
(
E N
(C), 132.4 (CH), 130.9 (CH), 129.3 (3CH), 128.8 (CH), 128.6 methylbenzenesulfonohydrazide 7i. yellow oil; Yield 60%; M
(CH), 128.3 (CH), 128.1 (CH), 127.9 (C), 127.3 (2CH), 127.1 = 394.51 g.molꢀ1; Rf = 0.29 (Cyclohexane/EtOAc 80/20); IR
(CH), 120.5 (C), 119.4 (CH), 116.9 (C), 106.1 (CH), 94.3 (C), (film, cmꢀ1): 3215, 1597, 1439, 1401, 1385, 1339, 1309, 1246,
1
87.5 (C), 55.3 (OCH3), 20.9 (CH3), 18.3 (CH3); HRMS (ESI) 1187, 1165, 1080, 1050, 1018; H NMR (300 MHz, CDCl3) δ
(M
469.1580.
)-4-methyl-
+
H)+ calculated for C28H25N2O3S 469.1567 found (ppm)8.29 (bs, 1H), 7.89 (d,
J
= 8.3 Hz, 2H), 7.52 – 7.44 (m,
= 3.0, 1.1 Hz, 1H), 7.25 (dd, = 8.3, 6.3 Hz,
= 5.0, 1.1 Hz, 1H), 2.35 (s, 3H), 2.31 (s, 3H);
1H), 7.42 (dd,
J
J
J
(
E
N
’-(1-(2-phenylethynyl)phenyl)ethylidene)- 6H), 7.08 (dd,
benzenesulfonohydrazide 7f. Green solid; Yield 81%; M= 13C NMR (75 MHz, CDCl3) δ (ppm)155.3 (C), 144.2 (C), 141.4
388.12 g.molꢀ1;m.p.: 80ꢀ82 C; Rf = 0.33 (Cyclohexane/EtOAc (C), 135.5 (C), 132.8 (CH), 129.7 (3CH), 128.9 (CH), 128.7
o
80/20); IR (film, cmꢀ1): 3057, 2245, 2190, 2085, 2038, 2022, (CH), 128.7 (CH), 128.3 (CH), 128.1 (2CH), 125.6 (CH), 122.0
1597, 1492, 1456, 1437, 1399, 1341, 1308, 1266, 1166, 1120, (C), 121.4 (C), 89.6 (C), 87.7 (C), 21.7 (CH3), 17.34 (CH3);
1081, 1050, 1017, 916; H NMR (300 MHz, MeOD) δ (ppm) HRMS (ESI) (M + H)+ calculated for C21H19N2O2S2 395.0888
1
7.82 (d,
7.25 (d,
J
J
= 8.2 Hz, 2H), 7.54 – 7.45 (m, 1H), 7.33 (m, 7H), found 395.0888.
= 8.0 Hz, 3H), 2.30 (s, 3H), 2.29 (s, 3H); 13C NMR
General procedure for the sequential synthesis of
benzofulvenes 5
(75 MHz, MeOD)δ (ppm) 157.5 (C), 145.2 (C), 143.4 (C),
137.5 (C), 133.6 (2CH), 132.4 (2CH), 130.4 (2CH), 129.7
(2CH), 129.5 (2CH), 129.3 (CH), 129.0 (2CH), 124.2 (C), Condition
122.5 (C), 94.8 (C), 88.7 (C), 21.5 (CH3), 18.3 (CH3);HRMS alkynylbenzilidene)hydrazide (
(ESI) (M + H)+ calculated for C23H21N2O2S 389.1306 found (0.05 mmol, 10 mol%), 2ꢀdicyclohexylphosphinoꢀ2′,4′,6′ꢀ
A:
In
a
sealed
tube,
N’ꢀ(2ꢀ
7
) (0.48 mmol), PdCl2(MeCN)2
389.1318.
triisopropylbiphenyl (XPhos) (0.1 mmol, 20 mol %), and 3 mL
of fluorobenzene (PhF) were mixed under argon for 5 minutes
(
E)-4-methyl-
N
’-(1-(2-(naphtalen-1-ylethynyl)phenyl)- at rt. NaO
tBu (1.44 mmol, 3 eq) was then added, the reaction
ethylidene)benzenesulfonohydrazide 7g.
mixture is stirred for 1 minute and aryl halide (0.38 mmol, 0.80
Grey solid; Yield 68%; M = 438.14 g.molꢀ1; m.p.: 134ꢀ136 C; eq) is added. The reaction vessel was then capped with a
Rf = 0.33 (Cyclohexane/EtOAc 80/20); IR (film, cmꢀ1): 2836, pressure screw cap and the reaction mixture was stirred at 100
1603, 1583, 1498, 1484, 1466, 1453, 1414, 1394, 1336, 1311, °C for 3 h. After cooling to room temperature, EtOAc was
1225, 1204, 1161, 1124, 1081, 1051, 1037, 1007, 950; 1H NMR added to the mixture, which was filtered through celite. The
o
(300 MHz, CDCl3) δ (ppm) 8.26 (d,
1H), 7.89 (d, = 8.3 Hz, 2H), 7.83 (d,
7.59 (m, 3H), 7.57 – 7.53 (m, 1H), 7.53 – 7.48 (m, 1H), 7.44 (d, inlet,
= 7.3 Hz, 1H), 7.39 (dd, = 4.8, 3.0 Hz, 1H), 7.35 (d, = 1.0 Bis(diphenylphosphino)propane (Dppp) (0.1 mmol, 20 mol%)
Hz, 2H), 7.17 (d, = 8.1 Hz, 2H), 2.39 (s, 3H), 2.26 (s, 3H); and Cs2CO3 (0.48 mmol, 1 eq) were mixed in 3 mL of dioxane.
J
= 8.3 Hz, 1H), 8.18 (s, solvents were evaporated under reduced pressure. The crude
= 6.5 Hz, 1H), 7.68 – residue was transferred in a sealed tube, where under argon
PdI2 (0.05 mmol, 10 mol%), 1,3ꢀ
J
J
J
J
J
J
13C NMR (75 MHz, MeOD)δ (ppm)157.2 (C), 145.0 (C), 143.4 The reaction vessel was then capped with a pressure screw cap
(C), 137.4 (C), 134.6 (C), 134.2 (C), 133.7 (CH), 131.4 (CH), and the reaction mixture was stirred at 150 °C for 12 hours. The
130.3 (2CH), 130.1 (CH), 129.8 (CH), 129.6 (CH), 129.4 (CH), crude reaction mixture was allowed to cool to room
129.3 (CH), 128.9 (2CH), 128.2 (CH), 127.6 (CH), 126.8 (CH), temperature. EtOAc was added to the mixture, which was
126.3 (CH), 122.5 (C), 121.5 (C), 93.6 (C), 92.9 (C), 21.4 filtered through celite. The solvents were evaporated under
(CH3), 18.6 (CH3); HRMS (ESI) (M + H)+ calculated for reduced pressure and the crude residue purified by flash
C27H23N2O2S 439.1459 found 439.1475.
)- ’-(1-(2-((4-fluorophenyl)ethynyl)phenyl)ethylidene)-4-
methylbenzenesulfono- hydrazide 7h. Green solid; Yield alkynylbenzilidene)hydrazide (
chromatography on silica gel.
Condition B: In
(
E
N
a
7
sealed
tube,
N’ꢀ(2ꢀ
) (0.48 mmol), PdCl2(MeCN)2
58%; M = 406.11 g.molꢀ1; m.p.: 134ꢀ136 oC; Rf = 0.32 (0.05 mmol, 10 mol%), 1,3ꢀBis(diphenylphosphino)propane
(Cyclohexane/EtOAc 80/20); IR (film, cmꢀ1): 3470, 3380, 3364, (Dppp) (0.1 mmol, 20 mol%) and 3 mL of dioxane were mixed
3196, 3130, 3100, 3071, 2209,2158, 2108, 2045, 1987, 1958, under argon for 5 minutes at rt. Cs2CO3 (1.44 mmol, 3 eq) was
6 | J. Name., 2012, 00, 1-3
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ARTICLE
DOI: 10.1039/C5RA14459K
then added, the reaction mixture is stirred for 1 minute and aryl 7.29 (m, 2H), 7.10 (s, 1H), 7.05 – 6.98 (m, 2H), 3.88 (s, 3H);
halide (0.38 mmol, 0.80 eq) is added. The reaction vessel was 13C NMR (75 MHz, CDCl3) δ (ppm) 159.8 (C), 147.2 (C),
then capped with a pressure screw cap and the reaction mixture 141.1 (C), 139.4 (C), 137.4 (C), 136.0 (C), 130.3 (2CH), 129.0
was stirred at 100 °C for 3 h. After cooling to room (2CH), 128.9 (2CH), 128.4 (C), 128.3 (CH), 127.60 (CH),
temperature, EtOAc was added to the mixture, which was 125.6 (CH), 124.9 (CH), 122.2 (CH), 120.5 (CH), 119.4 (CH),
filtered through celite. The solvents were evaporated under 114.2 (2CH), 55.5 (OCH3); HRMS (ESI) (M + H)+ calculated
reduced pressure. The crude residue was transferred in a sealed for C23H19O 311.1436 found 311.1432.
tube, where under argon inlet, PdI2 (0.05 mmol, 10 mol%), 1,3ꢀ
E)-3-((3-(4-methoxyphenyl)-1H-inden-1-ylidene)methyl)-
Bis(diphenylphosphino)propane (Dppp) (0.1 mmol, 20 mol%) thiophene 5e.
and Cs2CO3 (0.48 mmol, 1 eq) were mixed in 3 mL of dioxane. Condition B: Yellow oil; Yield 40%; M = 316.42 g.molꢀ1; Rf =
The reaction vessel was then capped with a pressure screw cap 0.67 (Cyclohexane/EtOAc 80/20); IR (film, cmꢀ1): 2958, 2927,
and the reaction mixture was stirred at 150 °C for 15 hours. The 2834, 1621, 1606, 1501, 1448, 1415, 1361, 1330, 1303, 1286,
1
crude reaction mixture was allowed to cool to room 1250, 1177, 1033; H NMR (300 MHz, CDCl3) δ (ppm)7.78 –
temperature. EtOAc was added to the mixture, which was 7.70 (m, 1H), 7.67 (d,
filtered through celite. The solvents were evaporated under 7.49 (dd, = 5.0, 1.2 Hz, 1H), 7.43 (s, 1H), 7.41 (dd,
reduced pressure and the crude residue purified by flash 2.9 Hz, 1H), 7.32 – 7.27 (m, 2H), 7.09 (s, 1H), 7.02 (d,
J = 8.8 Hz, 2H), 7.62 – 7.55 (m, 2H),
J
J
J
= 5.0,
= 8.8
chromatography on silica gel.
)-4-(1-(4-methoxybenzylidene)-1
5a.
Hz, 2H), 3.88 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
-inden-3-yl)benzonitrile (ppm)159.8 (C), 146.6 (C), 141.0 (C), 139.3 (C), 139.1 (C),
138.0 (C), 129.0 (2CH), 128.7 (CH), 128.4 (C), 127.2 (CH),
(
E
H
Conditions A. For a complete description, see reference 5.
)-1-(4-methoxybenzylidene)-3-( -tolyl)-1 -indene
127.0 (CH), 126.6 (CH), 125.5 (CH), 122.0 (CH), 121.2 (CH),
5b. 120.6 (CH), 119.3 (CH), 114.3 (2CH), 55.5 (OCH3); HRMS
Condition A: Yellow oil; Yield 62%; M = 324.42 g.molꢀ1; Rf = (ESI) (M + H)+ calculated for C21H17OS 317.1000 found
0.85 (Cyclohexane/EtOAc 70/30); IR (film, cmꢀ1): 3068, 2957, 317.1002.
2923, 2854, 2835, 1730, 1601, 1569, 1510, 1464, 1446, 1377,
(
E
p
H
1342, 1303, 1256, 1174, 1141, 1112, 1052; 1H NMR (300
MHz, CDCl3) δ (ppm) 7.80 – 7.75 (m, 1H), 7.64 (m, 5H), 7.47
(s, 1H), 7.35 – 7.26 (m, 4H), 7.15 (s, 1H), 6.99 (d, = 8.8 Hz,
Acknowledgements
J
We gratefully acknowledge the support of this project by
CNRS, University Paris Sud, and by La Ligue Contre le Cancer
throughout an Equipe Labellisee 2014 grant. The BioCIS UMR
8076 laboratory is a member of the Laboratory of Excellence
LERMIT supported by a grant from ANR (ANRꢀ10ꢀLABXꢀ
33).
2H), 3.87 (s, 3H), 2.44 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
(ppm) 160.1 (C), 146.9 (C), 140.7 (C), 139.3 (C), 138.1 (C),
137.5 (C), 133.2 (C), 131.9 (2CH), 130.1 (C), 129.5 (2CH),
127.9 (CH), 127.7 (2CH), 127.1 (CH), 125.4 (CH), 122.7 (CH),
120.4 (CH), 119.2 (CH), 114.5 (2CH), 55.5 (OCH3), 21.5
(CH3); HRMS (ESI) (M + H)+ calculated for C24H21O 325.1592
found 325.1596.
Notes and references
(
E)-1-(4-methoxybenzylidene)-3-(4-methoxyphenyl)-1
H-
aUniv Paris Sud, CNRS, BioCISꢀUMR 8076, Laboratoire de Chimie
Thérapeutique, Equipe Labellisée Ligue Contre le Cancer, LabEx
LERMIT, Faculté de Pharmacie, 5 rue JꢀB Clément, ChâtenayꢀMalabry,
Fꢀ92296, France, Eꢀmail: mouad.alami@uꢀpsud.fr, abdallah.hamze@uꢀ
psud.fr, Phone: (+33)ꢀ1ꢀ4683ꢀ5498; Fax: (+33)ꢀ1ꢀ46835498
indene 5c.
Condition B: Yellow oil; Yield 55%; M = 340.41 g.molꢀ1; Rf =
0.8 (Cyclohexane/EtOAc 70/30); IR (film, cmꢀ1): 3000, 2958,
2835, 1731, 1599, 1569, 1510, 1498, 1462, 1441, 1418, 1378,
1342, 1302, 1284, 1246, 1172, 1111, 1052, 1028; 1H NMR
(300 MHz, CDCl3) δ (ppm) 7.81 – 7.73 (m, 1H), 7.70 – 7.57
(m, 5H), 7.45 (s, 1H), 7.33 – 7.27 (m, 2H), 7.11 (s, 1H), 7.00
†Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/b000000x/
(dd,
J
= 9.9, 8.9 Hz, 4H), 3.88 (s, 3H), 3.87 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ (ppm) 160.0 (C), 159.7 (C), 146.5 (C),
140.7 (C), 139.4 (C), 137.5 (C), 131.9 (2CH), 130.1 (C), 129.0
(2CH), 128.6 (C), 127.6 (CH), 127.1 (CH), 125.4 (CH), 122.1
(CH), 120.4 (CH), 119.2 (CH), 114.5 (2CH), 114.2 (2CH), 55.5
(2OCH3); HRMS (ESI) (M + H)+ calculated for C24H21O2
341.1542 found 341.1537.
1
Citations here in the format A. Name, B. Name and C. Name,
Journal Title, 2000, 35, 3523; A. Name, B. Name and C. Name,
Journal Title, 2000, 35, 3523.
1.
2.
For reviews, see (a) J. Barluenga and C. Valdés, Angew. Chem.
Int. Ed., 2011, 50, 7486;(b) Z. Liu and J. Wang, J. Org. Chem.,
2013, 78, 10024;(c) Z. Shao and H. Zhang, Chem. Soc. Rev.,
2012, 41, 560;(d) Q. Xiao, Y. Zhang and J. Wang, Acc. Chem.
Res., 2012, 46, 236.
(a) J. Barluenga, N. Quiñones, M.ꢀP. Cabal, F. Aznar and C.
Valdés, Angew. Chem. Int. Ed., 2011, 50, 2350;(b) Z. Huang, Y.
Yang, Q. Xiao, Y. Zhang and J. Wang, Eur. J. Org. Chem., 2012,
6586;(c) L. Zhou, Y. Shi, Q. Xiao, Y. Liu, F. Ye, Y. Zhang and J.
(E)-1-benzylidene-3-(4-methoxyphenyl)-1H-indene 5d.
Condition B: Yellow oil; Yield 60%; M = 310.39 g.molꢀ1; Rf =
0.67 (Cyclohexane/EtOAc 80/20); IR (film, cmꢀ1): 2956, 2923,
2852, 1732, 1606, 1502, 1465, 1453, 1438, 1343, 1303, 1286,
1
1249, 1177, 1157; H NMR (300 MHz, CDCl3) δ (ppm) 7.82 –
7.74 (m, 1H), 7.71 – 7.64 (m, 4H), 7.63 – 7.57 (m, 1H), 7.47
(dd, J = 14.7, 7.5 Hz, 3H), 7.37 (dd, J = 5.0, 3.7 Hz, 1H), 7.35 –
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 7

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RSC Advances
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C5RA14459K
Wang, Org. Lett., 2011, 13, 968;(d) Y. Xia, Y. Zhang and J.
Wang, ACS Catal., 2013, 3, 2586.
3.
4.
(a) B. Tréguier, A. Hamze, O. Provot, J.ꢀD. Brion and M. Alami,
Tetrahedron Lett., 2009, 50, 6549;(b) E. Brachet, A. Hamze, J.ꢀF.
o. Peyrat, J.ꢀD. Brion and M. Alami, Org. Lett., 2010, 12, 4042;(c)
M. Roche, A. Hamze, O. Provot, J.ꢀD. Brion and M. Alami, J.
Org. Chem., 2013, 78, 445;(d) M. Lawson, A. Hamze, J.ꢀF.
Peyrat, J. Bignon, J. Dubois, J.ꢀD. Brion and M. Alami, Org.
Biomol. Chem., 2013, 11, 3664.
(a) J. Aziz, G. Frison, M. Gómez, J.ꢀD. Brion, A. Hamze and M.
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8 | J. Name., 2012, 00, 1-3
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