Cascade reactions: A multicomponent approach to functionalized indane derivatives by a tandem palladium-catalyzed carbamoylation/carbocylization process

Article abstract of DOI:10.1002/adsc.201301051

A novel, multicomponent and stereoselective approach to functionalized indane derivatives is reported. It is based on a tandem process consisting of Pd-catalyzed oxidative carbamoylation of 2-(2-ethynylbenzyl)malonates with carbon monoxide, a secondary am

Full text of DOI:10.1002/adsc.201301051

FULL PAPERS
DOI: 10.1002/adsc.201301051
Cascade Reactions: A Multicomponent Approach to
Functionalized Indane Derivatives by a Tandem Palladium-
Catalyzed Carbamoylation/Carbocylization Process
Bartolo Gabriele,a,* Lucia Veltri,a Raffaella Mancuso,a and Carla Carfagnab
a
Dipartimento di Chimica e Tecnologie Chimiche, Universitꢀ della Calabria, Via P. Bucci 12/C, 87036 Arcavacata di
Rende, Cosenza, Italy
Fax : (+39)-0984-49-2044; phone: (+39)-0984-492813; e-mail: bartolo.gabriele@unical.it
Dipartimento di Scienze Biomolecolari, Universitꢀ di Urbino, 61029 Urbino, Italy
b
Received: November 24, 2013; Revised: May 4, 2014; Published online: July 30, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201301051.
Abstract: A novel, multicomponent and stereoselec-
ACHTUNGTRENcNUGN lization, occurring through intramolecular addition
tive approach to functionalized indane derivatives is of an in situ formed carbanion to the propiolamide
reported. It is based on a tandem process consisting moiety.
of Pd-catalyzed oxidative carbamoylation of 2-(2-
ethynylbenzyl)malonates with carbon monoxide, Keywords: carbamoylation; carbonylation; cascade
a secondary amine, and oxygen (with formation of reactions; indanes; multicomponent reactions; palla-
a propiolamide intermediate), followed by carbocy- dium
Introduction
the alkyne substrate bears a suitably placed nucleo-
philic group.[5,6] In this case, in fact, the initially
“Cascade”, “tandem”, or “domino” reactions are pro- formed propiolamide intermediate can undergo a sub-
cesses in which two or more chemical transformations sequent intramolecular conjugate addition with for-
take place under identical conditions, with the prod- mation of
a
cyclic carbonylated derivative
uct obtained in the first transformation becoming the (Scheme 2).[5,6]
substrate of the subsequent transformation(s), eventu-
Although several applications of this concept have
ally leading to the final product.[1] These processes are been described, leading to a variety of heterocyclic
of particular importance in synthesis, since they avoid derivatives,[4,5] no example of a tandem triple bond
the isolation and purification of the intermediate(s) carbamoylation–carbocyclization process has been re-
and allow the formation in one step of the desired ported so far. In this paper, we wish to report such
product starting from simple building blocks, with evi- a process, which allows the direct and multicompo-
dent practical advantages, in terms of efficiency, selec- nent synthesis[7] of functionalized indanes 3 starting
tivity, and atom, step and energy economy.[1–3]
from readily available 2-(2-ethynylbenzyl)malonates
The PdI2/KI-catalyzed oxidative carbamoylation of
terminal alkynes, disclosed by our research group
some years ago,[4] is a multicomponent reaction in
which 1-alkynes, CO, a secondary amine, and oxygen
react to selectively afford propiolamides, through the
formation of an alkynylpalladium iodide species fol-
lowed by carbon monoxide insertion and nucleophilic
displacement by the amine. The active catalyst is the
2À
PdI4 anion, formed in situ from the reaction be-
tween PdI2 and an excess of iodide ligands. Scheme 1
shows the process, with anionic iodide ligands being
omitted for clarity.
This kind of reactivity can be successfully exploited
Scheme 1. PdI2/KI-catalyzed oxidative carbamoylation of
for the development of useful cascade reactions, when terminal alkynes.[4]
Adv. Synth. Catal. 2014, 356, 2547 – 2558
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2547

FULL PAPERS
Bartolo Gabriele et al.
Scheme 2. Application of PdI2-catalyzed oxidative carba-
moylation of the terminal triple bond to the synthesis of car-
bonylated heterocycles. The oxidative carbonylation process
is followed, in situ, by an intramolecular conjugate addi-
tion.[5,6]
and analogs (1), CO, O2, and a secondary amine
R2NH (2), according to Scheme 3.
Scheme 3. This work: formation of carbonylated indane de-
rivatives 3 by tandem oxidative carbamoylation of 2-(2-eth-
AHCTUNGTREGyNNNU nylbenzyl)malonates and analogs 1, to give propiolamide
intermediates I, followed by carbocyclization.
Results and Discussion
Our working hypothesis was based on the use of 2-(2-
ethynylbenzyl)malonates and analogs (1), which,
The first substrate we tested was dimethyl 2-(2-
under the basic conditions employed to promote the ethynylbenzyl)malonate 1a, which was used as crude
triple bond oxidative carbamoylation leading to the product deriving from deprotection of the corre-
propiolamide species I, could ensure a sufficient con- sponding TMS-protected precursor 1a’.[8] Substrate 1a
centration of a carbanion intermediate to cause car- was initially allowed to react in DME (substrate con-
bocyclization. The carbocyclization may be promoted centration=0.2 mmol of 1a per mL of DME) at
by the electrophilic activation of the triple bond of I 1008C in the presence of PdI2 (1 mol%), KI
by PdI2, as shown in Scheme 4. In path a, the intramo- (10 mol%) and 2 equiv. of morpholine (2a), under
lecular nucleophilic attack occurs in an anti fashion, 20 atm (at 258C) of a 4/1 mixture of CO and air.
with formation, after protonolysis, of the Z isomer of After 3 h, analysis of the reaction mixture revealed
indane 3 (3-Z); in path b, palladation of the carbanion the formation of two carbonylation products, corre-
with simultaneous chelation by the triple bond takes sponding to the E and Z isomers of the desired di-
place, followed by syn insertion and protonolysis, to methyl 1-(2-morpholino-2-oxoethyliden)indan-2,2-di-
give the E isomer of indane 3 (3-E).
carboxylate (3aa-E and 3aa-Z, respectively). The
Scheme 4. Cascade oxidative carbamoylation–carbocyclization leading to carbonylated indane derivatives 3. The PdI2-cata-
lyzed oxidative carbamoylation of the triple bond of 2-(2-ethynylbenzyl)malonates and analogs 1 leads to propiolamide inter-
mediates I, which then undergo carbocyclization to give 3.
2548
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 2547 – 2558

FULL PAPERS
Cascade Reactions: A Multicomponent Approach to Functionalized Indane Derivatives
Table 1. PdI2-catalyzed oxidative carbamoylation of 2-(2-ethynylbenzyl)malonate 1a under different conditions.[a]
Entry Solvent 2a:KI:PdI2
Concentration
T
PCO
Pair
Conversion
Yield of
Yield of
Total
molar ratio
of 1a[b]
[8C][c] [atm] [atm] of 1a [%][c]
3aa-E [%][c] 3aa-Z [%][c] yield
[%][c]
1
2
3
4
5
6
7
8
DME
DME
DME
DME
DME
DME
DME
DME
200:10:1
200:10:1
200:5:1
200:20:1
100:10:1
200:10:1
200:10:1
200:10:1
0.22
0.22
0.22
0.22
0.22
0.10
0.05
0.22
0.22
0.22
0.22
0.22
100
80
16
16
16
16
16
16
16
32
16
16
16
16
4
4
4
4
4
4
4
8
4
4
4
4
100
100
100
100
95
37
33
33
32
33
42
35
45
53
41
57
12
6
7
8
7
5
8
7
11
10
23
11
3
43
40
41
39
38
50
42
56
63
64
68
15
100
100
100
100
100
100
100
100
100
100
100
75
100
100
100
100
80
9
dioxane 200:10:1
MeOH 200:10:1
MeCN 200:10:1
10
11
12
DMA
200:10:1
[a]
All reactions were carried out in the presence of 1 mol% of PdI2 in conjunction with an excess of KI for 3 h. Substrate
1a, derived from desilylation of dimethyl 2-{2-[2-(trimethylsilyl)ethynyl]benzyl}malonate 1a’, was used as the crude mate-
rial, without further purification, in the carbonylation reaction.
Given as mmol of crude 1a per mL of solvent.
Based on starting 1a’, by GLC. The formation of unidentified heavy products (chromatographically immobile materials)
accounted for the difference between substrate conversion and product yield in all cases.
[b]
[c]
main product (37% isolated yield, Table 1, entry 1) ture CO and air. Under these conditions, after 3 h,
turned out to be the E stereoisomer, which was fully carbonylated indane 3aa-E was obtained in 65% iso-
characterized by spectroscopic techniques, including lated yield (based on starting dimethyl 2-{2-[2-(trime-
2D COSY and NOESY NMR experiments.
In order to improve this initial result, we screened only a 3% yield of 3aa-Z (Table 2, entry 1).
the reaction parameters to find the optimal conditions To assess the generality of the method, we then ap-
thylsilyl)ethynyl]benzyl}malonate 1a’), together with
for the formation of 3aa-E. The results obtained by plied the optimized conditions to other differently
changing the reaction temperature, 2a:KI:PdI2 molar substituted substrates 1b–g, bearing either p-donating
ratio, substrate concentration, total pressure, and sol- or electron-withdrawing groups on the aromatic ring
vent are shown in Table 1, entries 2–12. The product (such as a methoxy or nitro group, respectively) as
yield was lower when working at 808C (entry 2) or well as different electron-withdrawing groups on the
with a KI/PdI2 molar ratio of 5 or 20 rather that 10 homobenzylic carbon. We also changed the nature of
(entries 3 and 4). A lower yield was also observed on the amine, by testing the reactivity of other cyclic and
using 1 equiv. of the amine 2a rather than 2 equiv. acyclic secondary amines 2a–f. The results obtained
(entry 5). On the other hand, an improvement in are shown in Table 2, entries 2–12. As can be seen,
product yield was observed when the substrate con- good yields of the corresponding carbonylated in-
centration was lowered to 0.1 mmol of 1a per mL of danes were consistently obtained, even employing
DME (entry 6) and the total pressure was raised to a hindered amine such as diisopropylamine 2f. In
40 atm (entry 8). Among the other solvents tested (di- some cases, better results in terms of product selectiv-
oxane, MeOH, MeCN, and DMA), acetonitrile pro- ity were observed by working at a lower substrate
vided the highest product yield (entry 11). On the concentration (0.05 mmol per mL of solvent rather
basis of these results, the final optimized conditions than 0.1, Table 2, entries 5, 7–9). The reaction consis-
corresponded to the use of MeCN as the solvent (sub- tently showed high diastereoselectivity, the E isomer
strate concentration=0.1 mmol of 1a per mL of being formed predominantly or exclusively.
MeCN), with
a
1a:2a:KI:PdI2 molar ratio of
Several pieces of experimental evidence support
100:200:10:1, at 1008C and under 40 atm of a 4:1 mix- the proposed mechanism for the formation of prod-
Adv. Synth. Catal. 2014, 356, 2547 – 2558
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2549

FULL PAPERS
Bartolo Gabriele et al.
Table 2. Stereoselective synthesis of functionalized indane derivatives 3 by tandem PdI2-catalyzed oxida-
tive carbamoylation of 2-(2-ethynylbenzyl)malonates and analogs (1)/carbocyclization.[a]
2550
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 2547 – 2558

FULL PAPERS
Cascade Reactions: A Multicomponent Approach to Functionalized Indane Derivatives
Table 2. (Continued)
[a]
All reactions were carried out in MeCN at 1008C and under 40 atm (at 258C) of a 4:1 mixture of CO
and air, in the presence of 1 mol% of PdI2 in conjunction with an excess of KI (KI:PdI2 molar ratio=
10). Substrates 1, derived from desilylation of the corresponding TMS-protected precursors 1’, were
used as crude materials, without further purification, in the tandem reaction The 2:1 molar ratio was
2. Conversion of 1 was quantitative in all cases. The formation of unidentified heavy products (chro-
matographically immobile materials) accounted for the difference between substrate conversion and
product yield in all cases.
Given as mmol of crude 1 per mL of MeCN.
Isolated yield based on starting 1’.
The reaction also led to the formation of small amounts of the Z isomer (3% GLC yield).
The reaction also led to the formation of small amounts of the Z isomer (2% GLC yield).
The reaction also led to the formation of small amounts of the Z isomer (6% GLC yield).
The reaction also led to the formation of small amounts of the Z isomer (7% isolated yield).
[b]
[c]
[d]
[e]
[f]
[g]
ucts 3 (Scheme 4). First of all, the reaction did not Conclusions
take place with substrates bearing an internal triple
bond, since an alkynylpalladium intermediate could In conclusion, we have reported a novel multicompo-
not be formed in this case. Also, no reaction occurred nent carbonylative approach to functionalized indane
when a tertiary amine, such as triethylamine, was derivatives 3 starting from simple and readily avail-
used instead of a secondary amine (partial decompo- able substrates [2-(2-ethynylbenzyl)malonates and an-
sition of the substrate with the formation of a mixture alogs (1), CO, a secondary amine (2), and O2]
of unidentified products was observed). Finally, for- (Scheme 3).
mation of indane 3ad-E in 56% yield was observed
The cascade process leading to 3 occurs through
from the Sonogashira coupling between dimethyl 2- the concatenation of two chemical transformations,
(2-iodobenzyl)malonate and N,N-diethylpropiolamide, the Pd-catalyzed oxidative carbamoylation of the
carried out with PdACHTNUGTRNEUNG(PPh3)4 and CuI as catalysts and triple bond of 1, with formation of a propiolamide in-
NaOAc as the base, as shown in Scheme 5. This latter termediate
I,
followed
by
carbocyclization
result demonstrates that propiolamide I can indeed (Scheme 4).
be the intermediate for the formation of indanes 3
The process takes place under relatively mild condi-
under basic conditions and in the presence of palladi- tions (MeCN as the solvent at 1008C and under
um, according to the mechanism shown in Scheme 4. 40 atm of a 4:1 mixture of CO and air) and shows
Adv. Synth. Catal. 2014, 356, 2547 – 2558
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2551

FULL PAPERS
Bartolo Gabriele et al.
General Procedure for the Preparation of Dimethyl
2-Halobenzylmalonates
The 2-halobenzyl bromide derivative (11 mmol) [2-iodoben-
zyl bromide (commercially available): 3.27 g; 2-iodo-4,5-di-
methoxybenzyl bromide:[12] 3.93 g; 2-iodo-4,5-dimethylben-
zyl bromide:[12] 3.57 g; 2-iodo-5-methoxybenzyl bromide:[12]
3.60 g; 2-bromo-4-nitrobenzyl bromide:[13] 3.24 g] was added
under nitrogen to a stirred suspension of NaH (95% purity,
0.45 g, 15 mmol,) and dimethyl malonate (17 mmol, 2.25 g,
1.94 mL) in anhydrous THF (30 mL). The reaction mixture
was allowed to reflux for 6 h under stirring. After cooling,
the mixture was poured into 10% HCl (15 mL). The two
phases were separated and the aqueous phase was extracted
with ether (20 mLꢂ3). The collected organic phases were
washed with brine to neutral pH, dried over MgSO4 and
evaporated to dryness. After filtration and evaporation of
the solvent, products were purified by column chromatogra-
phy on silica gel using the following mixtures as eluent: 8:2
hexane-acetone for the dimethyl 2-(2-iodo-4,5-dimethoxy-
benzyl)malonate, dimethyl 2-(2-iodo-4,5-dimethylbenzyl)-
malonate and dimethyl 2-(2-iodo-5-methoxybenzyl)malo-
Scheme 5. Formation of dimethyl (E)-1-(diethylcarbamoyl-
methylene)indane-2,2-dicarboxylate (3ad-E) by in situ cycli-
zation of the propiolamide intermediate derived from Sono-
gashira coupling between N,N-diethylpropiolamide and di-
methyl 2-(2-iodobenzyl)malonate.
high diastereoselectivity toward the formation of the
E isomer. The products obtained belong to a particu-
larly important class of carbocycles, which have nate; 95:5 hexane-AcOEt for dimethyl 2-(2-bromo-4-nitro-
benzyl)malonate.
shown several interesting pharmacological activi-
ties.[9,10]
Dimethyl 2-(2-iodo-4,5-dimethoxybenzyl)malonate: Yield:
2.11 g, starting from 3.93 g of 1-bromomethyl-2-iodo-4,5-di-
methoxybenzene (47%); colorless solid; mp 86–878C; IR
(KBr): n=3001 (m), 2944 (m), 2846 (m), 1731 (s), 1596 (m),
1504 (m), 1353 (m), 1255 (m), 1218 (m), 1167 (m), 1032 (m),
Experimental Section
949 (w), 869 (m), 793 (m) cmÀ1
;
1H NMR (300 MHz,
General Remarks
CDCl3): d=7.21 (s, 1H), 6.77 (s, 1H), 3.84 (s, 3H), 3.83 (s,
3H), 3.81 (t, J=7.8 Hz, 1H), 3.71 (s, 6H), 3.27 (d, J=
7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=169.0, 149.2,
148.5, 132.5, 121.9, 113.5, 88.1, 56.14, 55.97, 52.6, 51.9, 39.0;
GC-MS (EI, 70 eV): m/z=408 (45) [M+], 345 (2), 307 (3),
281 (100), 277 (74), 250 (12), 221 (23), 207 (13), 191 (11),
150 (7), 105 (5), 77 (7); anal. calcd. for C14H17IO6 (408.19):
C 41.19, H 4.20, I 31.09; found: C 41.03, H 4.21, I 31.10.
Dimethyl 2-(2-iodo-4,5-dimethylbenzyl)malonate: Yield:
2.52 g, starting from 3.57 g of 1-bromomethyl-2-iodo-4,5-di-
methylbenzene (61%); yellow solid; mp 83–858C; IR (KBr):
n=1730 (s), 1636 (m), 1434 (m), 1345 (m), 1233 (m), 1154
Solvent and chemicals were of reagent grade and were used
without further purification. All reactions were analyzed by
TLC on silica gel 60 F254 or on neutral alumina and by GLC
using a gas chromatograph and capillary columns with poly-
methylsilicone+5% phenylsilicone as the stationary phase.
Column chromatography was performed on silica gel 60
(70–230 mesh). Evaporation refers to the removal of solvent
under reduced pressure.
Melting points are uncorrected. 1H NMR and 13C NMR
spectra were recorded at 258C on a Bruker DPX Avance
300 spectrometer or on a Bruker DPX Avance 500 spec-
trometer in CDCl3 solutions at 300 or 500 MHz and 75 or
126 MHz, respectively, with Me4Si as internal standard.
Chemical shifts (d) and coupling constants (J) are given in
ppm and in Hz, respectively. IR spectra were taken with
a JASCO FT-IR 4200 spectrometer. Mass spectra were ob-
tained using a Shimadzu QP-2010 GC-MS apparatus at
70 eV ionization voltage. Microanalyses were carried out
with a Carlo Erba Elemental Analyzer Mod. 1106.
1
(m) cmÀ1; H NMR (300 MHz, CDCl3): d=7.57 (s, 1H), 6.97
(s, 1H), 3.82 (t, J=7.8 Hz, 1H), 3.71 (s, 6H), 3.25 (d, J=
7.8 Hz, 2H), 2.16 (s, 3H), 2.16 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=169.0, 140.2, 137.6, 137.3, 137.0, 131.6, 96.5, 52.5,
51.8, 38.7, 19.3, 18.8; GC-MS (EI, 70 eV): m/z=376 (3)
[M+], 345 (2), 313 (8), 275 (3), 249 (100), 245 (17), 217 (5),
189 (27), 175 (8), 159 (8), 115 (13), 91 (8); anal. calcd. for
C14H17IO4 (376.19): C 44.70, H 4.55, I 33.73; found: C 44.86,
H 4.56, I 33.64.
Dimethyl 2-(2-iodo-5-methoxybenzyl)malonate: Yield:
2.41 g, starting from 3.60 g of 1-bromomethyl-2-iodo-4-me-
thoxybenzene (58%); colorless oil. IR (film): n=1736 (s),
1593 (m), 1469 (m), 1436 (m), 1343 (m), 1294 (m), 1238 (m),
Preparation of Substrate Precursors
Substrate precursors dimethyl 2-(2-iodobenzyl)malonate and
methyl 2-(2-iodobenzyl)-3-oxobutyrate were prepared as re-
ported in the literature.[11] Dimethyl 2-(2-iodo-4,5-dimeth-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
dimethyl 2-(2-bromo-4-nitrobenzyl)malonate and methyl 2-
cyano-3-(2-iodophenyl)propionate were prepared as de-
scribed below.
1
1154 (m), 1042 (m) cmÀ1; H NMR (300 MHz, CDCl3): d=
7.66 (d, J=8.7 Hz, 1H), 6.80 (d, J=3.0 Hz, 1H), 6.53 (dd,
J=8.7, 3.0 Hz, 1H), 3.84 (t, J=7.8 Hz, 1H), 3.75 (s, 3H),
3.72 (s, 6H), 3.29 (d, J=7.8 Hz, 2H); 13C NMR (75 MHz,
CDCl3): d=168.9, 160.0, 141.2, 140.1, 116.5, 114.9, 88.7, 55.4,
52.6, 51.6, 39.5; GC-MS (EI, 70 eV): m/z=378 (11) [M+],
347 (2), 315 (7), 277 (3), 251 (100), 191 (17), 176 (8), 161
2552
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 2547 – 2558

FULL PAPERS
Cascade Reactions: A Multicomponent Approach to Functionalized Indane Derivatives
(12), 133 (5), 118 (4), 89 (6), 77 (5); anal. calcd. for
C13H15IO5 (378.16): C 41.29, H 4.00, I 33.56; found: C 41.40,
H 4.39, I 33.62.
methyl 2-(2-iodo-4,5-dimethoxybenzyl)malonate: 3.29 g; di-
methyl 2-(2-iodo-4,5-dimethylbenzyl)malonate: 3.03 g; di-
methyl 2-(2-iodo-5-methoxybenzyl)malonate: 3.05 g; di-
methyl 2-(2-bromo-4-nitrobenzyl)malonate: 2.79 g; methyl
2-(2-iodobenzyl)-3-oxobutyrate: 2.68 g; methyl 2-cyano-3-(2-
iodophenyl)propionate: 2.54 g] and ethynyltrimethylsilane
(9.67 mmol, 0.95 g), in NEt3 (30 mL), was added under ni-
Dimethyl 2-(2-bromo-4-nitrobenzyl)malonate: Yield:
1.14 g, starting from 3.24 g of 2-bromo-1-bromomethyl-4-ni-
trobenzene (30%); yellow solid; mp 119–1218C. IR (KBr):
n=1746 (s), 1522 (m), 1437 (m), 1352 (s), 1236 (m), 1158
1
(m), 1080 (w), 889 (m), 746 (m) cmÀ1. H NMR (300 MHz,
trogen PdCl2ACHTNUTRGNEUNG(PPh3)2 (0.16 mmol, 113 mg). The mixture was
CDCl3): d=8.43 (d, J=2.3 Hz, 1H), 8.10 (dd, J=8.5, 2.3 Hz,
1H), 7.46 (d, J=8.5 Hz, 1H), 3.88 (t, J=7.7 Hz, 1H), 3.74
(s, 6H), 3.44 (d, J=7.7 Hz, 2H); 13C NMR (75 MHz,
CDCl3): d=168.5, 144.6, 132.0, 128.1, 124.8, 122.3, 52.9, 50.6,
35.0; GC-MS (EI, 70 eV): m/z=347 (<0.5) [(M+2)+], 345
(<0.5) [M+], 266 (100), 206 (56), 160 (17), 102 (10), 89 (8);
anal. calcd. for C12H12BrNO6 (346.13): C 41.64, H 3.49, Br
23.08; found: C 41.60, H 3.48, Br 23.05.
stirred for 5 min, and then CuI (15.4 mg, 0.081 mmol) was
added. The resulting mixture was stirred at room tempera-
ture for 12 h. The resulting ammonium salt was removed by
filtration, the solvent was evaporated, and products were pu-
rified by column chromatography on silica gel, using the fol-
lowing mixtures as eluent: 95:5 hexane-AcOEt (for 1a’ and
1d’); 8:2 hexane-acetone (for 1c’ and 1b’); 9:1 hexane
AcOEt (for 1e’), 98:2 hexane-AcOEt (for 1f’ and 1g’).
Dimethyl
2-(2-trimethylsilanylethynylbenzyl)malonate
(1a’): Yield: 2.41 g, starting from 2.81 g of dimethyl 2-(2-io-
dobenzyl)malonate (94%); yellow oil. IR (film): n=2156
(m), 1739 (s), 1483 (w), 1436 (m), 1251 (s), 1152 (m), 871
Preparation of Methyl 2-Cyano-3-(2-iodophenyl)-
propionate
1
(s), 843 (s), 761 (m) cmÀ1. H NMR (300 MHz, CDCl3): d=
To a suspension of NaH (12 mmol, 0.29 g) in anhydrous
THF (20 mL) and HMPA (24 mmol, 4.2 mL) were sequen-
tially added, under nitrogen at room temperature, methyl
cyanoacetate (1.19 g, 12 mmol) dissolved in anhydrous THF
(20 mL, 30 min) and 2-iodobenzyl bromide (3.56 g,
12 mmol). The resulting mixture was stirred at room temper-
ature for 2 h. Saturated NH4Cl (50 mL) was added, and the
aqueous phase was extracted with CH2Cl2 (3ꢂ50 mL). The
collected organic layers were washed with brine and dried
over Na2SO4. After filtration and evaporation of the solvent,
the product was purified by column chromatography on
silica gel using, as eluent, 95:5 hexane-AcOEt; yield: 3.67 g,
starting from 1.19 g of methyl cyanoacetate (97%); colorless
solid; mp 80–818C. IR (KBr): n=2252 (w), 1736 (s), 1449
(m), 1432 (m), 1266 (s), 1242 (m), 1023 (m), 900 (w), 747
(m) cmÀ1. 1H NMR (300 MHz, CDCl3): d=7.86 (d, J=
7.8 Hz, 1H), 7.43–7.31 (m, 2H), 7.06–6.96 (m, 1H), 3.94 (dd,
J=9.9, 6.0 Hz, 1H), 3.84 (s, 3H), 3.48 (distorted dd, J=13.9,
6.0 Hz, 1H), 3.22 (distorted dd, J=13.9, 9.9 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=165.7, 139.9, 137.9, 131.0,
129.7, 128.9, 115.6, 100.0, 53.7, 40.5, 37.5; GC-MS (EI,
70 eV): m/z=315 (10) [M+], 217 (74), 188 (100), 156 (3),
145 (2), 129 (17), 102 (11), 90 (18), 77 (7); anal. calcd. for
C11H10INO2 (315.11): C 41.93, H 3.20, I 40.27, N 4.45; found:
C 41.80, H 3.21, I 40.22, N 4.44.
7.47–7.42 (m, 1H), 7.24–7.14 (m, 3H), 3.97 (t, J=7.7 Hz,
1H), 3.69 (s, 6H), 3.37 (d, J=7.7 Hz, 2H), 0.25 (s, 9H);
13C NMR (75 MHz, CDCl3): d=169.3, 140.0, 132.5, 129.9,
128.6, 126.8, 122.8, 102.8, 99.4, 52.4, 51.8, 33.9, À0.2; GC-MS
(EI, 70 eV): m/z=318 (17) [M+], 303 (50), 287 (5), 271 (9),
259 (27), 243 (14), 213 (9), 183 (16), 173 (70), 155 (98), 145
(27), 129 (27), 115 (36), 105 (27), 89 (95), 73 (32), 59 (100);
anal. calcd for C17H22O4Si (318.44): C 64.12, H 6.96, Si 8.82;
found: C 64.28, H 6.95, Si 8.83.
Dimethyl 2-(5-methoxy-2-trimethylsilanylethynylbenzyl)-
malonate (1b’): Yield: 1.91 g, starting from 3.05 g of dimeth-
yl 2-(2-iodo-5-methoxybenzyl)malonate (68%); yellow oil.
IR (film): n=2150 (m), 1739 (s), 1605 (m), 1492 (m), 1436
(m), 1250 (s), 1159 (m), 1040 (m), 872 (m), 861 (m) cmÀ1
;
1H NMR (300 MHz, CDCl3): d=7.37 (d, J=8.4 Hz, 1H),
6.75 (distorted d, J=2.6 Hz, 1H), 6.71 (distorted dd, J=8.4,
2.6 Hz, 1H), 3.97 (t, J=7.7 Hz, 1H), 3.77 (s, 2H), 3.70 (s,
6H), 3.33 (d, J=7.7 Hz, 2H), 0.24 (s, 9H); 13C NMR
(75 MHz, CDCl3): d=169.2, 159.7, 141.9, 133.9, 115.6, 115.0,
112.5, 103.0, 97.6, 55.3, 52.4, 51.8, 34.1, À0.1; GC-MS (EI,
70 eV): m/z=348 (100) [M+], 333 (22), 317 (9), 301 (14),
289 (15), 285 (10), 273 (11), 243 (20), 213 (13), 203 (40), 185
(41), 159 (16), 145 (10), 128 (9), 89 (43); anal. calcd. for
C18H24O5Si (348.47): C 62.04, H 6.94, Si 8.06; found: C
62.19, H 6.93, Si 8.07.
Preparation of Substrates
Dimethyl 2-(4,5-dimethoxy-2-trimethylsilanylethynylben-
zyl)malonate (1c’): Yield: 2.93 g, starting from 3.29 g of di-
methyl 2-(2-iodo-4,5-dimethoxybenzyl)malonate (96%);
yellow oil. IR (film): n=2147 (m), 1734 (s), 1603 (w), 1512
Starting dimethyl 2-(2-trimethylsilanylethynylbenzyl)malo-
nates 1a’–e’, methyl 2-{2-[2-(trimethylsilyl)ethynyl]benzyl}-3-
oxobutanoate 1f’ and methyl 2-cyano-3-(2-trimethylsilanyl-
(m), 1439 (m), 1347 (m), 1222 (m), 1151 (m), 869 (m) cmÀ1
;
ACHTUNGTRENNUNGethynylphenyl)propionate 1g’ were prepared by Sonogashira
1H NMR (300 MHz, CDCl3): d=6.93 (s, 1H), 6.72 (s, 1H),
3.93 (t, J=7.8 Hz, 1H), 3.86 (s, 6H), 3.70 (s, 6H), 3.31 (d,
J=7.8 Hz, 2H), 0.25 (s, 9H); 13C NMR (75 MHz, CDCl3):
d=169.3, 149.4, 147.5, 133.7, 114.8, 114.6, 113.1, 103.1, 97.7,
56.0, 52.4, 52.1, 33.7, À0.1. GC-MS (EI, 70 eV): m/z=378
(100) [M+], 363 (7), 347 (6), 319 (6), 303 (5), 273 (5), 247
(55), 233 (30), 215 (28), 189 (16), 89 (15); anal. calcd. for
C19H26O6Si (378.49): C 60.29, H 6.92, Si 7.42; found: C
60.11, H 6.93, Si 7.40.
coupling between the appropriate dimethyl 2-(2-haloben-
zyl)malonate, methyl 2-(2-iodobenzyl)-3-oxo-butyrate or
methyl 2-cyano-3-(2-iodophenyl)propionate (prepared as de-
scribed above) with ethynyltrimethylsilane, as described
below.
General Procedure for 2-(2-Trimethylsilanylethynyl)-
benzyl Ester Derivatives 1a’–1g’
To a stirred solution of the 2-halobenzyl ester derivative
(8.06 mmol) [dimethyl 2-(2-iodobenzyl)malonate: 2.81 g; di-
Dimethyl
2-(4,5-dimethyl-2-trimethylsilanylethynylben-
zyl)malonate (1d’): Yield: 2.35 g, starting from 3.03 g of di-
Adv. Synth. Catal. 2014, 356, 2547 – 2558
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2553

FULL PAPERS
Bartolo Gabriele et al.
methyl
yellow oil. IR (film): n=2153 (m), 1739 (s), 1436 (m), 1344
(w), 1250 (m), 1149 (m), 1031 (w), 862 (s), 760 (w) cmÀ1
2-(2-iodo-4,5-dimethylbenzyl)malonate
(84%);
General Procedure for the Synthesis of Indanylidene
Amide Derivatives 3-E
;
1st Step: general procedure for the deprotection of 2-(2-tri-
methylsilanylethynyl)benzyl ester derivatives 1a’–1g’ to give
crude 2-(2-ethynylbenzyl)malonates and analogs 1a–1g: To
a solution of the 2-(2-trimethylsilanylethynyl)benzyl ester
derivatives 1’ (1.5 mmol) [1a’: 478 mg; 1b’: 523 mg; 1c’:
568 mg; 1d’: 519 mg; 1e’: 545 mg; 1f’: 454 mg; 1g’: 428 mg] in
MeOH (12 mL) was added KF (305 mg, 5.3 mmol) at room
temperature. The resulting mixture was stirred for 15 h at
the same temperature, then water (30 mL) was added fol-
lowed by Et2O (30 mL). Phases were separated, and the or-
ganic phase was extracted with diethyl ether (30 mLꢂ2).
The collected organic layers were dried over anhydrous
Na2SO4. After filtration and evaporation of the solvent,
crude products 1a–1g were used as such for the tandem car-
bonylation–carbocyclization step.
1H NMR (300 MHz, CDCl3): d=7.21 (s, 1H), 6.95 (s, 1H),
3.94 (t, J=7.7 Hz, 1H), 3.69 (s, 6H), 3.29 (d, J=7.7 Hz,
2H), 0.24 (s, 9H); 13C NMR (75 MHz, CDCl3): d=169.4,
137.6, 137.4, 135.1, 133.5, 131.2, 120.0, 103.3, 98.1, 52.4, 52.0,
33.5, 19.7, 19.1, À0.1; GC-MS (EI, 70 eV): m/z=346 (75)
[M+], 331 (40), 315 (9), 301 (12), 287 (34), 271 (19), 255 (5),
241 (21), 215 (14), 201 (98), 183 (100), 173 (17), 157 (28),
128 (14), 89 (37); anal. calcd. for C19H26O4Si (346.49): C
65.86, H 7.56, Si 8.11; found: C 65.70, H 7.55, Si 8.12.
Dimethyl 2-(4-nitro-2-trimethylsilanylethynylbenzyl)malo-
nate (1e’): Yield: 2.28 g, starting from 2.79 g of dimethyl 2-
(2-bromo-4-nitrobenzyl)malonate (78%); yellow oil. IR
(film): n=2153 (m), 1739 (s), 1526 (m), 1437 (m), 1352 (m),
1251 (m), 1155 (m), 1027 (w), 939 (w), 850 (s) cmÀ1
;
1H NMR (300 MHz, CDCl3): d=8.29 (d, J=2.4 Hz, 1H),
8.07 (dd, J=8.4, 2.4 Hz, 1H), 7.42 (d, J=8.4 Hz, 1H), 3.96
(t, J=7.6 Hz, 1H), 3.72 (s, 6H), 3.44 (d, J=7.6 Hz, 2H),
0.28 (s, 9H); 13C NMR (75 MHz, CDCl3): d=168.7, 147.1,
146.9, 131.1, 127.4, 124.6, 123.1, 102.8, 100.2, 52.7, 51.2, 33.8,
À0.4; GC-MS (EI, 70 eV): m/z=363 (5) [M+], 348 (100),
316 (26), 304 (34), 286 (14), 263 (3), 218 (37), 200 (20), 167
(10), 128 (9), 105 (9), 89 (67); anal. calcd. for C17H21NO6Si
(363.44): C 56.18, H 5.82, Si 7.73; found: C 56.10, H 5.83, Si
7.72.
2nd Step: general procedure for the tandem oxidative car-
bamoylation–carbocyclization of 1 to give functionalized
indane derivatives 3-E: A 250-mL stainless steel autoclave
was charged in the presence of air with PdI2 (5.4 mg, 1.5ꢂ
10À2 mmol), KI (24.9 mg, 1.5ꢂ10À1 mmol), anhydrous
CH3CN (15 mL or 30 mL, see Table 2), crude substrates 1a–
g, obtained as described above (formally corresponding to
1.5 mmol), and the amine 2 (2a: 261 mg; 2b: 255 mg, 2c:
213 mg; 2d: 220 mg, 2e: 388; 2f: 304 mg; 3.0 mmol). The au-
toclave was sealed and, while the mixture was stirred, the
autoclave was pressurized with CO (32 atm) and air (up to
40 atm). After being stirred at 1008C for the required time
(see Table 2), the autoclave was cooled, degassed and
opened. The solvent was evaporated, and products 3-E were
purified by column chromatography on silica gel using the
following mixtures as eluent: 7:3 hexane-acetone (3aa-E,
3ca-E, 3da-E), 8:2 hexane-acetone (3ba-E), 95:5 hexane-
AcOEt (3fa-E, 3ga-E), hexane (3ad-E), 7:3 hexane-AcOEt
(3ea-E, 3ab-E, 3ac-E, 3ae-E, 3af-E). In some cases, small
amounts of the corresponding Z isomers were detected by
GLC-MS in the reaction crude, (see Table 2), even though
most of them (with the exception of 3ae-Z) could not be iso-
lated in the pure state.
Methyl 2-{2-[2-(trimethylsilyl)ethynyl]benzyl}-3-oxobuta-
noate (1f’): Yield: 1.90 g, starting from 2.68 g of methyl 2-(2-
iodobenzyl)-3-oxo-butyrate (78%); yellow oil, IR (film): n=
2156 (m), 1739 (s), 1436 (m), 1299 (w), 1251 (m), 1152 (m),
872 (m), 842 (m), 761 (m) cmÀ1. 1H NMR (300 MHz,
CDCl3): d=7.44 (m, 1H), 7.26–7.13 (m, 3H), 4.11–4.03 (m,
1H), 3.68 (s, 3H), 3.35 (distorted dd, J=13.5, 6.9 Hz, 1H),
3.26 (distorted dd, J=13.5, 7.9 Hz, 1H), 2.20 (s, 3H), 0.25 (s,
9H); 13C NMR (75 MHz, CDCl3): d=202.3, 169.5, 140.4,
132.7, 129.9, 128.8, 126.7, 122.6, 103.2, 99.2, 59.5, 52.3, 33.1,
29.6, À0.1; GC-MS (EI, 70 eV): m/z=302 (4) [M+], 287
(83), 271 (11), 259 (45), 243 (34), 227 (51), 213 (34), 198
(10), 185 (32), 173 (50), 155 (86), 145 (24), 127 (27), 115
(21), 89 (100), 73 (92); anal. calcd. for C17H22O3Si (302.44):
C 67.51, H 7.33, Si 9.29; found: C 67.40, H 7.35, Si 9.18.
Methyl 2-cyano-3-(2-trimethylsilanylethynylphenyl)propi-
onate (1g’): Yield: 1.63 g, starting from 2.54 g of methyl 2-
cyano-3-(2-iodophenyl)-propionate (71%); yellow oil. IR
(film): n=2250 (vw), 2156 (m), 1752 (s), 1483 (w), 1437 (m),
Dimethyl
(E)-1-(2-morpholin-4-yl-2-oxoethylidene)in-
dane-2,2-dicarboxylate (3aa-E): Yield: 350 mg, starting from
478 mg of dimethyl 2-(2-trimethylsilanylethynylbenzyl)malo-
nate 1a’ (65%; Table 2, entry 1); yellow oil. IR (film): n=
3018 (w), 1733 (s), 1622 (s), 1435 (m), 1242 (m), 1216 (m),
1251 (m), 874 (s), 760 (m) cmÀ1 1H NMR (300 MHz,
;
1114 (w), 1055 (w), 755 (s) cmÀ1 1H NMR (300 MHz,
;
CDCl3): d=7.53–7.45 (m, 1H), 7.36–7.22 (m, 3H), 4.07 (dd,
J=9.6, 6.0 Hz, 1H), 3.81 (s, 3H), 3.58 (distorted dd, J=13.3,
6.0 Hz, 1H), 3.18 (distorted dd, J=13.3, 9.6 Hz, 1H), 0.27 (s,
9H); 13C NMR (75 MHz, CDCl3): d=166.1, 137.6, 132.7,
130.1, 129.1, 127.8, 122.8, 116.0, 102.2, 100.4, 53.4, 37.7, 35.1,
À0.2; GC-MS (EI, 70 eV): m/z=285 (5) [M+], 270 (100),
240 (90), 238 (37), 213 (26), 183 (13), 172 (42), 155 (10), 145
(18), 143 (16), 129 (12), 115 (15), 89 (67); anal. calcd. for
C16H19NO2Si (285.41): C 67.33, H 6.71, N 4.91, Si 9.84;
found: C 67.40, H 6.72, N 4.90, Si 9.82.
CDCl3): d=7.62 (d, J=7.3 Hz, 1H), 7.38–7.17 (m, 3H), 6.38
(s, 1H), 3.83–3.68 (m, 8H), 3.71 (s, 6H), 3.64–3.57 (m, 2H);
2D-NOESY data: the NOESY spectrum evidenced a strong
interaction between the aromatic protons and the morpho-
line protons, in agreement with an E stereochemistry;
13C NMR (75 MHz, CDCl3): d=170.3, 166.5, 143.4, 142.8,
135.8, 130.1, 127.6, 124.9, 124.5, 120.3, 114.4, 67.0, 66.6, 63.7,
53.4, 46.5, 41.7, 39.3; GC-MS (EI, 70 eV): m/z=359 (26)
[M+], 328 (1), 300 (22), 273 (94), 214 (16), 213 (100), 186
(17), 181 (13), 171 (14), 155 (25), 141 (12), 127 (35), 115
(13), 86 (12); anal. calcd. for C19H21NO6 (359.37): C 63.50, H
5.89, N 3.90; found: C 63.41, H 5.90, N 3.91.
Dimethyl
(Z)-1-(2-morpholin-4-yl-2-oxo-ethylidene)in-
dane-2,2-dicarboxylate (3aa-Z): GLC yield ca. 3%, based on
starting 1a’ (purity ca. 70%, by GLC-MS; Table 2, entry 1);
2554
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 2547 – 2558

FULL PAPERS
Cascade Reactions: A Multicomponent Approach to Functionalized Indane Derivatives
brown solid; mp 165–1688C. IR (KBr): n=2862 (w), 1748
20.2; GC-MS (EI, 70 eV): m/z=387 (16) [M+], 355 (1), 328
(14), 301 (58), 241 (100), 214 (13), 209 (18), 183 (18), 155
(13), 153 (12), 128 (6), 115 (8); anal. calcd. for C21H25NO6
(387.43): C 65.10, H 6.50, N 3.62; found: C 65.01, H 6.48, N
3.61.
(s), 1646 (s), 1613 (w), 1433 (m), 1384 (m), 1272 (m), 1242
1
(w), 1112 (m), 1062 (w) cmÀ1; H NMR (300 MHz, CDCl3):
d=7.62–7.54 (d, 1H), 7.40–7.23 (m, 3H), 6.84 (s, 1H), 3.78–
3.62 (m, 8H), 3.76 (s, 6H), 3.61–3.54 (m, 2H); GC-MS (EI,
70 eV): m/z=359 (31) [M+], 328 (3), 300 (15), 273 (94), 214
(16), 213 (100), 186 (13), 181 (13), 171 (16), 169 (11), 155
(24), 141 (11), 127 (39), 115 (13), 86 (11).
Dimethyl (Z)-5,6-dimethyl-1-(2-morpholin-4-yl-2-oxoethy-
lidene)indane-2,2-dicarboxylate (3da-Z): GLC yield: ca. 6%,
starting from 1d’ (Table 2, entry 4) The product was not
1
Dimethyl (E)-5-methoxy-1-(2-morpholin-4-yl-2-oxo-ethyli-
dene)indane-2,2-dicarboxylate (3ba-E): Yield: 368 mg, start-
ing from 523 mg of dimethyl 2-(4-methoxy-2-trimethylsilany-
lethynylbenzyl)malonate 1b’ (63%; Table 2, entry 2); yellow
oil. IR (film): n=1733 (s), 1639 (s), 1493 (w), 1435 (s), 1255
pure enough to register IR, H and 13C NMR data; GC-MS
(EI, 70 eV): m/z=387 (23) [M+], 355 (1), 328 (18), 301 (68),
241 (100), 214 (16), 209 (16), 183 (17), 155 (14), 153 (15),
128 (7), 115 (7).
Dimethyl (E)-1-(2-morpholin-4-yl-2-oxoethylidene)-6-ni-
troindane-2,2-dicarboxylate (3ea-E): Yield: 352 mg, starting
from 545 mg of dimethyl 2-(4-nitro-2-trimethylsilanylethy-
nylbenzyl)malonate 1e’ (58%; Table 2, entry 5); pale yellow
solid; mp 177–1798C. IR (KBr): n=1734 (s), 1623 (s), 1524
(m), 1434 (m), 1346 (m), 1264 (s), 1110 (m), 1066 (m), 755
(m), 1090 (m) cmÀ1 1H NMR (300 MHz, CDCl3): d=7.59
;
(d, J=8.8 Hz, 1H), 6.82–6.73 (m, 3H), 6.23 (s, 1H), 3.85–
3.58 (m, 10H), 3.81 (s, 3H), 3.78 (s, 6H); 2D-NOESY data:
the NOESY spectrum evidenced a neat interaction between
the aromatic protons and the morpholine protons, in agree-
ment with an
E
stereochemistry; 13C NMR (75 MHz,
(s) cmÀ1 1H NMR (300 MHz, CDCl3): d=8.55 (d, J=
;
CDCl3): d=170.4, 166.8, 161.6, 145.8, 143.0, 128.8, 126.0,
117.4, 114.6, 109.0, 67.1, 66.8, 64.4, 55.4, 53.3, 46.6, 41.7,
39.4; GC-MS (EI, 70 eV): m/z=389 (28) [M+], 330 (12), 303
(100), 276 (7), 243 (80), 216 (20), 211 (11), 201 (13), 185
(23), 157 (10), 142 (11), 114 (12); anal. calcd. for C20H23NO7
(389.40): C 61.69, H 5.95, N 3.60; found: C, 61.54, H 5.93, N
3.61.
1.9 Hz, 1H), 8.18 (dd, J=8.4, 1.9 Hz, 1H), 7.44 (d, J=
8.4 Hz, 1H), 6.61 (s, 1H), 3.89–3.77 (m, 6H), 3.81 (s, 6H),
3.75–3.67 (m, 2H), 3.66–3.59 (m, 2H); 13C NMR (75 MHz,
CDCl3): d=169.5, 165.4, 150.0, 148.1, 140.7, 137.3, 125.6,
125.0, 123.7, 120.0, 67.1, 66.7, 64.0, 53.7, 46.6, 41.8, 39.2; GC-
MS (EI, 70 eV): m/z=404 (25) [M+], 345 (24), 318 (100),
258 (59), 231 (11), 207 (18), 200 (17), 154 (14), 126 (18), 86
(33); anal. calcd. for C19H20N2O8 (404.37): C 56.43, H 4.99, N
6.93; found: C 56.53, H 4.98, N 6.95.
Dimethyl (Z)-5-methoxy-1-(2-morpholin-4-yl-2-oxo-ethyli-
dene)indane-2,2-dicarboxylate (3ba-Z): GLC yield: ca. 2%,
starting from 1b’ (Table 2, entry 2). The product was not
Methyl
(E)-2-acetyl-1-(2-morpholin-4-yl-2-oxoethyli-
1
pure enough to register IR, H and 13C NMR data; GC-MS
dene)indane-2-carboxylate (3fa-E): Yield: 366 mg, starting
from 454 mg of methyl 3-oxo-2-(2-trimethylsilanylethynyl-
benzyl)butyrate 1f’ (71%; Table 2, entry 6); yellow oil. IR
(film): n=1714 (s), 1633 (s), 1434 (m), 1359 (w), 1238 (s),
(EI, 70 eV): m/z=389 (26) [M+], 330 (6), 303 (100), 276 (9),
243 (76), 216 (24), 211 (11), 201 (13), 185 (27), 157 (9), 114
(9).
1
Dimethyl (E)-5,6-dimethoxy-1-(2-morpholin-4-yl-2-oxo-
ethylidene)indane-2,2-dicarboxylate (3ca-E): Yield: 472 mg,
starting from 568 mg of dimethyl 2-(4,5-dimethoxy-2-trime-
thylsilanylethynylbenzyl)malonate 1c’ (75%; Table 2,
entry 3); yellow oil. IR (film): n=3016 (m), 1735 (s), 1639
(s), 1503 (w), 1434 (m), 1347 (w), 1244 (s), 1115 (m), 754 (s)
1114 (m), 760 (m) cmÀ1; H NMR (300 MHz, CDCl3): d=
7.68–7.62 (m, 1H), 7.38–7.20 (m, 3H), 6.25 (s, 1H), 3.86–
3.56 (m, 10H), 3.81 (s, 3H), 2.24 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=201.5, 170.7, 166.4, 143.3, 142.8, 136.2,
130.3, 127.7, 125.0, 124.8, 120.4, 70.6, 67.0, 66.7, 53.2, 46.6,
41.7, 38.1, 26.1; GC-MS (EI, 70 eV): m/z=343 (absent)
[M+], 301 (64), 284 (1), 269 (14), 241 (8), 214 (100), 186
(96), 171 (18), 155 (64), 141 (5), 127 (48), 114 (12), 88 (25);
anal. calcd. for C19H21NO5 (347.37): C 66.46, H 6.16, N 4.08;
found: C 66.29, H 6.17, N 4.09.
1
cmÀ1; H NMR (300 MHz, CDCl3): d=7.28 (s, 1H), 6.74 (s,
1H), 6.23 (s, 1H), 3.89 (s, 3H), 3.85 (s, 3H), 3.80–3.70 (m,
6H), 3.78 (s, 6H), 3.66–3.61 (m, 4H); 2D-NOESY data: the
NOESY spectrum evidenced a strong interaction between
the aromatic protons and the morpholine protons, in agree-
Methyl
(E)-2-cyano-1-(2-morpholin-4-yl-2-oxoethyli-
ment with an
E
stereochemistry; 13C NMR (75 MHz,
dene)indane-2-carboxylate (3ga-E): Yield: 343 mg, starting
from 428 mg of methyl 2-cyano-3-(2-trimethylsilanylethynyl-
phenyl)propionate 1g’ (70%; Table 2, entry 7); yellow oil. IR
(film): n=2244 (w), 1742 (s), 1646 (vs), 1447 (m), 1273 (m),
CDCl3): d=170.4, 166.7, 151.5, 148.9, 143.8, 137.1, 128.3,
117.2, 106.9, 106.6, 67.1, 66.8, 64.4, 55.9, 53.3, 46.6, 41.7,
39.3; GC-MS (EI, 70 eV): m/z=419 (33) [M+], 360 (13), 333
(67), 306 (11), 273 (100), 246 (25), 241 (22), 231 (12), 215
(17), 171 (13), 115 (9); anal. calcd. for C21H25NO8 (419.43):
C 60.14, H 6.01, N 3.34; found: C 60.28, H 6.03, N 3.33.
Dimethyl (E)-5,6-dimethyl-1-(2-morpholin-4-yl-2-oxoethy-
lidene)indane-2,2-dicarboxylate (3da-E): Yield: 366 mg,
starting from 519 mg of dimethyl 2-(4,5-dimethyl-2-trime-
thylsilanylethynylbenzyl)malonate 1d’ (63%; Table 2,
entry 4); yellow oil. IR (film): n=1737 (s), 1628 (s), 1435
(m), 1272 (m), 1198 (w), 1109 (m), 1059 (m), 976 (m), 885
1237 (m), 1214 (m), 1114 (m), 762 (m) cmÀ1 1H NMR
;
(300 MHz, CDCl3): d=7.73 (d, J=7.8 Hz, 1H), 7.43–7.24
(m, 3H), 6.51 (s, 1H), 3.90–3.68 (m, 4H), 3.84 (s, 3H), 3.68–
3.48 (m, 6H); 13C NMR (75 MHz, CDCl3): d=167.0, 164.8,
144.7, 143.0, 134.2, 131.3, 128.3, 125.6, 125.1, 118.8, 66.9,
66.7, 54.5, 51.6, 46.6, 41.9, 40.7; GC-MS (EI, 70 eV): m/z=
326 (26) [M+], 311 (1), 295 (9), 267 (41), 241 (20), 240 (100),
228 (3), 214 (14), 196 (27), 180 (37), 155 (59), 153 (55), 127
(34), 86 (72); anal. calcd. for C18H18N2O4 (326.35): C 66.25,
H 5.56, N 8.58; found: C 66.39, H 5.57, N 8.60.
1
(w), 806 (w) cmÀ1; H NMR (300 MHz, CDCl3): d=7.36 (s,
1H), 7.04 (s, 1H), 6.26 (s, 1H), 3.77 (s, 6H), 3.82–3.55 (m,
10H), 2.25 (s, 3H), 2.23 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=170.5, 166.8, 143.0, 141.3, 139.5, 136.0, 133.8,
125.8, 125.2, 118.7, 67.1, 66.7, 64.1, 53.3, 46.5, 41.7, 39.1, 30.9,
Dimethyl (E)-1-(2-oxo-2-piperidin-1-ylethylidene)indane-
2,2-dicarboxylate (3ab-E): Yield: 300 mg, starting from
478 mg of dimethyl 2-(2-trimethylsilanylethynylbenzyl)malo-
nate 1a’ (56%; Table 2, entry 8); yellow solid; mp 104–
Adv. Synth. Catal. 2014, 356, 2547 – 2558
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2555

FULL PAPERS
Bartolo Gabriele et al.
1058C. IR (KBr): n=1736 (s), 1618 (s), 1426 (s), 1280 (m),
155 (27), 141 (12), 128 (65), 127 (26), 115 (10), 86 (11); anal.
calcd. for C23H31NO5 (401.50): C 68.80, H 7.78, N 3.49;
found: C 68.68, H 7.76, N, 3.50.
1213 (m), 1152 (w), 1079 (m), 1024 (w), 953 (w), 897 (w),
850 (w), 785 (m), 763 (w) cmÀ1
;
1H NMR (500 MHz,
Dimethyl (Z)-1-(dibutylcarbamoylmethylene)indane-2,2-
dicarboxylate (3ae-Z): Yield: 42 mg, starting from 478 mg of
dimethyl 2-(2-trimethylsilanylethynylbenzyl)malonate 1a’
(7%; Table 2, entry 11); yellow oil. IR (film): n=1738 (s),
1633 (s), 1591 (m), 1531 (w), 1460 (m), 1433 (m), 1378 (w),
CDCl3): d=7.61 (d, J=7.8 Hz, 1H), 7.30–7.23 (m, 2H),
7.23–7.17 (m, 1H), 6.41 (s, 1H), 3.78 (s, 6H), 3.74–3.66 (m,
4H), 3.65–3.59 (m, 2H), 1.70–1.56 (m, 4H), 1.53–1.44 (m,
2H); 2D-NOESY data: the NOESY spectrum evidenced
neat interactions between the aromatic protons and the pi-
peridine protons, and no nOe between the aromatic protons
and the olefinic proton, in agreement with an E stereochem-
istry; 13C NMR (75 MHz, CDCl3): d=170.5, 166.2, 143.3,
142.1, 136.4, 129.8, 127.5, 125.0, 124.7, 121.6, 64.15, 53.1, 47.3
(br), 42.4 (br), 39.6, 26.5 (br), 25.7 (br), 24.8; GC-MS (EI,
70 eV): m/z=357 (absent) [M+], 298 (18), 273 (63), 238
(19), 213 (100), 186 (24), 171 (16), 155 (30), 141 (13), 127
(39), 115 (13), 84 (58); anal. calcd. for C20H23NO5 (357.40):
C 67.21, H 6.49, N 3.92; found: C 67.17, H 6.48, N 3.92.
1253 (s), 1098 (w), 784 (m) cmÀ1 1H NMR (300 MHz,
;
CDCl3): d=7.60–7.53 (m, 1H), 7.37–7.22 (m, 3H), 6.87 (s,
1H), 3.72 (s, 6H), 3.67 (s, 2H), 3.43–3.31 (m, 4H), 1.72–1.59
(m, 2H), 1.59–1.45 (m, 2H), 1.45–1.23 (m, 4H), 0.98 (t, J=
7.3 Hz, 3H), 0.86 (t, J=7.3 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=170.1, 166.0, 150.9, 143.2, 139.8, 130.4, 127.5,
125.1, 121.1, 113.7, 63.1, 52.6, 48.3 (br), 46.0 (br), 43.5, 31.8
(br), 30.2 (br), 20.3, 13.9; GC-MS (EI, 70 eV): m/z=401
(absent) [M+], 342 (24), 310 (43), 300 (3), 273 (96), 254 (7),
229 (5), 213 (100), 186 (22), 181 (14), 171 (15), 155 (25), 141
(11), 128 (52), 115 (10); anal. calcd. for C23H31NO5 (401.50):
C 68.80, H 7.78, N 3.49; found: C 68.68, H 7.76, N 3.50.
Dimethyl (E)-1-(diisopropylcarbamoylmethylene)indan-
2,2-dicarboxylate (3af-E): Yield: 280 mg, starting from
478 mg of dimethyl 2-(2-trimethylsilanylethynylbenzyl)malo-
nate 1a’ (50%; Table 2, entry 12); yellow solid; mp 105–
1078C. IR (KBr): n=1737 (s), 1623 (s), 1438 (m), 1371 (w),
1324 (m), 1255 (m), 1170 (w), 1098 (w), 1045 (m), 757 (m)
Dimethyl
(E)-1-(2-oxo-2-pyrrolidin-1-yl-ethylidene)in-
dane-2,2-dicarboxylate (3ac-E): Yield: 294 mg, starting from
478 mg of dimethyl 2-(2-trimethylsilanylethynylbenzyl)malo-
nate 1a’ (57%; Table 2, entry 9); yellow oil. IR (film): n=
1737 (s), 1616 (s), 1435 (m), 1248 (m), 1097 (w), 1056 (w),
1
754 (s) cmÀ1; H NMR (300 MHz, CDCl3): d=7.86 (d, J=
7.7, 1H), 7.31–7.15 (m, 3H), 6.42 (s, 1H), 3.77 (s, 6H), 3.70
(s, 2H), 3.65–3.57 (m, 2H), 3.54–3.46 (m, 2H), 1.97–1.84 (m,
4H); 13C NMR (75 MHz, CDCl3): d=170.4, 165.8, 143.6,
143.5, 136.3, 130.1, 127.5, 125.4, 124.6, 121.5, 64.3, 53.2, 47.1,
45.5, 39.5, 26.1, 24.5; GC-MS (EI, 70 eV): m/z=343 (24)
[M+], 312 (5), 284 (24), 273 (79), 252 (10), 229 (4), 213
(100), 186 (15), 181 (14), 171 (13), 155 (21), 141 (9), 127
(28), 70 (16); anal. calcd. for C19H21NO5 (343.37): C 66.46, H
6.16, N 4.08; found: C 66.59, H 6.15, N 4.09.
cmÀ1 1H NMR (300 MHz, CDCl3): d=7.70 (d, J=7.7 Hz,
;
1H), 7.34–7.13 (m, 3H), 6.40 (s br, 1H), 4.46 (heptuplet, J=
6.7 Hz, 1H), 3.82–3.57 (m, 3H), 3.77 (s, 6H), 1.55 (d, J=
6.7 Hz, 6H), 1.15 (d, J=6.7 Hz, 6H); 13C NMR (75 MHz,
CDCl3): d=170.5, 167.1, 143.0, 140.7, 136.5, 129.6, 127.2,
124.73, 124.68, 123.2, 63.8, 53.1, 50.0, 45.7, 39.5, 21.1, 20.5;
GC-MS (EI, 70 eV): m/z=373 (absent) [M+], 342 (5), 314
(6), 273 (95), 228 (7), 213 (100), 186 (27), 171 (16), 155 (26),
141 (12), 127 (32), 115 (14), 100 (76); anal. calcd. for
C23H31NO5 (401.50): C 68.80, H 7.78, N 3.49; found: C 68.94,
H 7.77, N 3.50.
Dimethyl (E)-1-(diethylcarbamoylmethylene)indane-2,2-
dicarboxylate (3ad-E): Yield: 363 mg, starting from 478 mg
of dimethyl 2-(2-trimethylsilanylethynylbenzyl)malonate 1a’
(70%; Table 2, entry 10); yellow oil. IR (film): n=1736 (s),
1634 (s), 1465 (m), 1432 (m), 1257 (m), 1098 (m), 786 (m)
cmÀ1 1H NMR (300 MHz, CDCl3): d=7.66 (d, J=7.7 Hz,
;
1H), 7.31–7.15 (m, 3H), 6.45 (s, 1H), 3.78 (s, 6H), 3.71 (s,
2H), 3.60–3.44 (m, 4H), 3.49 (q, J=7.1 Hz, 2H), 1.25 (t, J=
7.1 Hz, 3H), 1.11 (t, J=7.1 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=170.4, 167.1, 143.3, 142.1, 136.2, 129.8, 127.4,
124.9, 124.7, 121.5, 64.0, 53.2, 42.7, 39.4, 14.3, 12.9; GC-MS
(EI, 70 eV): m/z=345 (17) [M+], 286 (19), 273 (60), 226 (6),
213 (100), 186 (22), 171 (12), 155 (23), 141 (10), 127 (28),
115 (10), 100 (5), 72 (39); anal. calcd. for C19H23NO5
(345.39): C 66.07, H 6.71, N 4.06; found: C 66.25, H 6.73, N
4.06.
Sonogashira Coupling Between N,N-Diethylpropiol-
amide and Dimethyl 2-(2-Iodobenzyl)malonate to
Give Dimethyl (E)-1-(Diethylcarbamoylmethylene)-
indane-2,2-dicarboxylate (3ad-E) (Scheme 5)
1st Step: preparation of N,N-diethylpropiolamide: To
a cooled (À208C), stirred solution of propiolic acid (1.0 g,
15 mmol) in anhydrous CH2Cl2 were added, under nitrogen,
dicyclohexylcarbodiimide (3.1 g, 15 mmol) and diethylamine
(1.1 g, 15 mmol). The mixture was allowed to warm up to
room temperature and stirred for 15 h. The mixture was
then filtered through a short pad of silica gel, which was
washed with CH2Cl2. After concentration under vacuum, the
resulting oil was purified by column chromatography on
silica gel, using 8:2 hexane/Et2O as eluent, to give pure N,N-
diethylpropiolamide; yield: 0.83 g (44%); yellow oil. IR
(film): n=2978 (m), 2874 (w), 2101 (m), 1628 (s), 1432 (m),
Dimethyl (E)-1-(dibutylcarbamoylmethylene)indane-2,2-
dicarboxylate (3ae-E): Yield: 410 mg, starting from 478 mg
of dimethyl 2-(2-trimethylsilanylethynylbenzyl)malonate 1a’
(68%; Table 2, entry 11); colorless oil. IR (film): n=2957
(m), 1736 (s), 1629 (m), 1464 (w), 1432 (m), 1247 (s), 1097
1
(w), 1055 (w) cmÀ1; H NMR (300 MHz, CDCl3): d=7.70–
7.64 (m, 1H), 7.30–7.14 (m, 3H), 6.44 (s, 1H), 3.77 (s, 6H),
3.70 (s, 2H), 3.51–3.37 (m, 4H), 1.71–1.58 (m, 2H), 1.55–
1.20 (m, 6H), 0.98 (t, J=7.2, 3H), 0.86 (t, J=7.2, 3H);
13C NMR (75 MHz, CDCl3): d=170.4, 167.4, 143.2, 142.1,
136.2, 129.8, 127.4, 125.0, 124.6, 121.6, 64.0, 53.2, 48.2, 44.7,
39.5, 31.0, 29.7, 20.4, 19.9, 13.9, 13.8; GC-MS (EI, 70 eV): m/
z=401 (absent) [M+], 344 (12), 342 (29), 310 (41), 274 (18),
273 (100), 214 (21), 213 (97), 186 (26), 181 (14), 171 (16),
1276 (m), 1150 (w), 741 (w) cmÀ1 1H NMR (300 MHz,
;
CDCl3): d=3.61 (q, J=7.1 Hz, 2H, NCH2), 3.43 (q, J=
ꢀ
7.1 Hz, 2H, NCH2), 3.09 (s, 1H, CH), 1.23 (t, J=7.1 Hz,
3H, CH2CH3), 1.15 (t, J=7.1 Hz, 3H, CH2CH3); 13C NMR
(75 MHz, CDCl3): d=152.9, 77.7, 77.5, 43.6, 39.5, 14.4, 12.8;
GC-MS (EI, 70 eV): m/z=125 (8) [M+], 97 (88), 82 (90), 69
(51), 67 (100), 56 (58), 54 (64); anal. calcd. for C7H11NO
2556
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 2547 – 2558

FULL PAPERS
Cascade Reactions: A Multicomponent Approach to Functionalized Indane Derivatives
(125.17): C 67.17, H 8.86, N 11.19; found: C 67.03, H 8.87, N
11.17.
2009, 13, 1432–1474; s) A. Padwa, Chem. Soc. Rev.
2009, 38, 3072–3081; t) J. Poulin, C. M. Grise-Bard, L.
Barriault, Chem. Soc. Rev. 2009, 38, 3092–3101;
u) M. M. Hussain, P. J. Walsh, Acc. Chem. Res. 2008,
41, 883–893; v) D. Enders, C. Grondal, M. R. M.
Huettl, Angew. Chem. 2007, 119, 1590–1601; Angew.
Chem. Int. Ed. 2007, 46, 1570–1581; w) M. B. Boxer,
B. J. Albert, H. Yamamoto, Aldrichimica Acta 2009, 42,
3–15; x) K. C. Nicolaou, J. S. Chen, Chem. Soc. Rev.
2009, 38, 2993–3009; y) J. Barluenga, F. Rodriguez, F. J.
FaÇanꢃs, Chem. Asian J. 2009, 4, 1036–1048; z) M. J.
Climent, A. Corma, S. Iborra, ChemSusChem 2009, 2,
500–506; aa) J. Poulin, C. M. Grise-Bard, L. Barriault,
Chem. Soc. Rev. 2009, 38, 3092–3101.
2nd Step: Sonogashira coupling between N,N-diethylpro-
piolamide and dimethyl 2-(2-iodobenzyl)malonate leading
to 3ad-E: N,N-Diethylpropiolamide (125 mg; 1.0 mmol), was
added under nitrogen to a stirred solution of dimethyl 2-(2-
iodobenzyl)malonate (400 mg, 1.1 mmol), CuI (9.5 mg,
0.05 mmol), NaOAc (246 mg, 3.0 mmol) and PdACTHNUGTRNEG(UN PPh3)4
(116 mg, 0.1 mmol) in anhydrous DMF (10 mL). The reac-
tion mixture was stirred for 2 h at 608C. After cooling, the
mixture was diluted with AcOEt (50 mL) followed by water
(50 mL). Phases were separated, and the organic phase was
washed with water (50 mL) and then dried over Na2SO4.
After filtration and evaporation of the solvent, the product
was purified by column chromatography on silica gel, using
as eluent 6:4 hexane-AcOEt, to give pure dimethyl (E)-1-
(diethylcarbamoylmethylene)indane-2,2-dicarboxylate (3ad-
E); yield: 194 mg (56%).
[3] a) A. N. Aba, X. Companyo, M. Viciano, R. Rios, Curr.
Org. Chem. 2009, 13, 1432–1474; b) A. Padwa, Chem.
Soc. Rev. 2009, 38, 3072–3081; c) L. F. Tietze, T. Kinzel,
C. C. Brazel, Acc. Chem. Res. 2009, 42, 367–378; d) N.
Shindoh, Y. Takemoto, K. Takasu, Chem. Eur. J. 2009,
15, 12168–12179; e) S. F. Kirsch, Synthesis 2008, 3183–
3204; f) K. C. Nicolaou, T. Lister, R. M. Denton, C. F.
Gelin, Tetrahedron 2008, 64, 4736–4757; g) B. Crone,
S. F. Kirsch, Chem. Eur. J. 2008, 14, 3514–3522; h) H.
Miyabe, Y. Takemoto, Chem. Eur. J. 2007, 13, 7280–
7286; i) D. Enders, C. Grondal, H. R. M. Huttl, Angew.
Chem. 2007, 119, 1590–1601; Angew. Chem. Int. Ed.
2007, 46, 1570–1581; j) K. C. Nicolaou, D. J. Edmonds,
P. G. Bulger, Angew. Chem. 2006, 118, 7292–7344;
Angew. Chem. Int. Ed. 2006, 45, 7134–7186.
Acknowledgements
Thanks are due to the European Commission, FSE (Fondo
Sociale Europeo) and Calabria Region for a fellowship grant
to R.M.
References
[4] B. Gabriele, G. Salerno, L. Veltri, M. Costa, J. Organo-
met. Chem. 2001, 622, 84–88.
[1] a) L. F. Tietze, G. Brasche, K. M. Gericke, Domino Re-
actions in Organic Chemistry, Wiley-VCH, Weinheim,
2007; b) L. F. Tietze, Chem. Rev. 1996, 96, 115–136;
c) N. Shindoh, Y. Takemoto, K. Takasu, Chem. Eur. J.
2009, 15, 12168–12179; d) P. A. Wender, V. A. Verma,
T. J. Paxton, T. H. Pillow, Acc. Chem. Res. 2008, 41, 40–
49; e) P. A. Wender, B. L. Miller, Nature 2009, 460,
197–201.
[2] For recent reviews on cascade reactions, see: a) H.
Ohno, Asian J. Org. Chem. 2013, 2, 18–28; b) R. K.
Shiroodi, V. Gevorgyan, Chem. Soc. Rev. 2103, 42,
4991–5001; c) P. Xie, Y. Huang, Eur. J. Org. Chem.
2013, 6213–6226; d) H. Pellissier, Chem. Rev. 2013, 113,
[5] For reviews, see: a) B. Gabriele, G. Salerno, M. Costa,
Synlett 2004, 2468–2483; b) B. Gabriele, G. Salerno, M.
Costa, Top. Organomet. Chem. 2006, 18, 239–272; c) B.
Gabriele, R. Mancuso, G. Salerno, Eur. J. Org. Chem.
2012, 6825–6839; d) X.-F. Wu, H. Neumann, M. Beller,
Chem. Rev. 2013, 1–35.
[6] For recent examples, see: a) B. Gabriele, G. Salerno, P.
Plastina, M. Costa, A. Crispini, Adv. Synth. Catal. 2004,
346, 351–358; b) B. Gabriele, G. Salerno, P. Plastina,
Lett. Org. Chem. 2004, 1, 134–136; c) B. Gabriele, P.
Plastina, G. Salerno, M. Costa, Synlett 2005, 935–938;
d) B. Gabriele, G. Salerno, L. Veltri, R. Mancuso, Z. Li,
A. Crispini, A. Bellusci, J. Org. Chem. 2006, 71, 7895–
7898; e) B. Gabriele, P. Plastina, G. Salerno, R. Mancu-
so, Synthesis 2006, 4247–4251; f) B. Gabriele, P. Plasti-
na, G. Salerno, R. Mancuso, M. Costa, Org. Lett. 2007,
9, 3319–3322; g) P. Plastina, B. Gabriele, G. Salerno,
Synthesis 2007, 3083–3087.
[7] For recent reviews on multicomponent reactions, see:
a) Y. Liu, H. Wang, J. Wan, Asian J. Org. Chem. 2013,
2, 374–386; b) S. Brauch, S. S. van Berkel, B. Wester-
mann, Chem. Soc. Rev. 2013, 42, 4948–4962; c) Y.-M.
Ren, C. Cai, R.-C. Yang, RSC Adv. 2013, 3, 7182–7204;
d) P. Slobbe, E. Ruijter, R. V. A. Orru, Med. Chem.
Commun. 2012, 3, 1189–1218; e) S. S. van Berkel,
B. G. M. Bogels, M. A. Wijdeven, B. Westermann,
F. P. J. T. Rutjes, Eur. J. Org. Chem. 2012, 3543–3559;
f) V. A. Chebanov, S. M. Desenko, Chem. Heterocycl.
Compd. 2012, 48, 566–583; g) A. Domling, W. Wang, K.
Wang, Chem. Rev. 2012, 112, 3083–3135; h) C. M.
Marson, Chem. Soc. Rev. 2012, 41, 7712–7722; i) Y. Gu,
442–524; e) H. Clavier, H. Pellissier, Adv. Synth. Catal.
ˇ
ˇ
2012, 354, 3347–3403; f) Z. Galestokovꢃ, R. Sebesta,
Eur. J. Org. Chem. 2012, 6688–6695; g) Y. Liu, J.-P.
Wan, Chem. Asian J. 2012, 7, 1488–1501; h) H. Pellissi-
er, Adv. Synth. Catal. 2012, 354, 237–294; i) A. Gross-
mann, D. Enders, Angew. Chem. 2012, 124, 320–332;
Angew. Chem. Int. Ed. 2012, 51, 314–325; j) L.-Q. Lu,
J.-R. Chen, W.-J. Xiao, Acc. Chem. Res. 2012, 45, 1278–
1293; k) C. Bhanja, S. Jena, S. Nayak, S. Mohapatra,
Beilstein J. Org. Chem. 2012, 8, 1668–1694; l) M. Ruia,
P. Lopez-Alvarado, G. Giorgi, J. C. Menendez, Chem.
Soc. Rev. 2011, 40, 3445–3454; m) E. Ricca, B. Brucher,
J. H. Schrittwieser, Adv. Synth. Catal. 2011, 353, 2239–
2262; n) T. Vlaar, E. Ruijter, R. V. A. Orru, Adv.
Synth. Catal. 2011, 353, 809–841; o) C. Grondal, M.
Jeanty, D. Enders, Nat. Chem. 2010, 2, 167–178; p) Y. F.
Han, M. Xia, Curr. Org. Chem. 2010, 14, 379–413; q) J.
Zhou, Chem. Asian J. 2010, 5, 422–434; r) A.-N. Alba,
X. Companyo, M. Viciano, R. Rios, Curr. Org. Chem.
Adv. Synth. Catal. 2014, 356, 2547 – 2558
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2557

FULL PAPERS
Bartolo Gabriele et al.
Green Chem. 2012, 14, 2091–2128; j) M. S. Sing, S.
Chowdhury, RSC Adv. 2012, 2, 4547–4592; k) C. de
Graaff, E. Ruijter, R. V. A. Orru, Chem. Soc. Rev.
2012, 41, 3969–4009; l) M. J. Climent, A. Corma, S.
Iborra, RSC Adv. 2012, 2, 16–58; m) J. Yu, F. Shi, L.-Z.
Gong, Acc. Chem. Res. 2011, 44, 1156–1171; n) E.
Ruijter, R. Scheffelaar, R. V. A. Orru, Angew. Chem.
2011, 123, 6358–6371; Angew. Chem. Int. Ed. 2011, 50,
6234–6246; o) N. Isambert, M. d. N. Sanchez, J.-C. Pla-
quevent, Y. Genisson, J. Rodriguez, T. Constantieux,
Chem. Soc. Rev. 2011, 40, 1347–1357; p) N. R. Candeias,
F. Montalbano, P. M. S. D. Cal, P. M. P. Gois, Chem.
Rev. 2010, 110, 6169–6193; q) J.-P. Wan, Y. Liu, Synthe-
sis 2010, 3943–3953; r) E. Doemling, Y. Huang, Synthe-
sis 2010, 2859–2883; s) J. E. Biggs-Houck, A. Younai,
J. T. Shaw, Curr. Opin. Chem. Biol. 2010, 14, 371–382;
t) A. Basso, L. Banfi, R. Riva, Eur. J. Org. Chem. 2010,
1831–1841; u) Y.-F- Han, M. Xia, Curr. Org. Chem.
2010, 14, 379–413; v) V. Estevez, M. Villacampa, C.
Menendez, Chem. Soc. Rev. 2010, 39, 4402–4421;
w) A. V. Ivachtchenko, Y. A. Ivanenkov, V. M. Kysil,
M. Y. Krasavin, A. P. Ilyin, Russ. Chem. Rev. 2010, 9,
787–817; x) Multicomponent Reactions, (Eds.: J. Zhu,
H. Bienaymꢄ), Wiley-VCH, Weinheim, 2005.
Med. Chem. 2011, 19, 7318–7337; b) A. Stroba, W.
Froehner, R. W. Hartmann, M. Engel, F. Schaeffer, V.
Hindie, L. Lopez-Garcia, I. Adrian, R. M. Biondi, J.
Med. Chem. 2009, 52, 4683–4693; c) E. R. Wood, L.
Kuyper, K. G. Petrov, N. Hunter, P. A. Harris, K.
Lackey, Bioorg. Med. Chem. Lett. 2004, 14, 953–958;
d) D. L. Musso, F. R. Cochran, J. L. Kelley, E. W.
McLean, J. L. Selph, G. C. Rigdon, G. F. Orr, R. G.
Davis, B. R. Cooper, V. L. Styles, J. B. Thompson, W. R.
Hall, J. Med. Chem. 2003, 46, 399–408; e) D. L. Musso,
G. Orr, G. Faye, F. R. Cochran, J. L. Kelley, J. L. Selph,
G. C. Rigdon, B. R. Cooper, M. L. Jones, J. Med. Chem.
2003, 46, 409–416; f) N. V. S. Ramakrishna, A. K. Jain,
A. V. Ghate, R. D. Gupte, R. V. S. V. Vadlamudi,
Indian J. Chem. B 1999, 38, 407–412.
[10] For some recent references on palladium-catalyzed car-
bonylative cyclization, related to indane derivatives,
see: a) L. Nassar-Hardy, S. Fabre, A. M. Amer, E. Fou-
quet, F.-X. Felpin, Tetrahedron Lett. 2012, 53, 338–341;
b) K. H. Kim, S. H. Kim, S. Park, J. N. Kim, Tetrahe-
dron 2011, 67, 3328–3336; c) D. Marosvçlgyi-Haskꢅ, A.
Takꢃcs, Z. Riedl, L. Kollꢃr, Tetrahedron 2011, 67, 1036–
1040; d) Y. Harada, J. Nakanishi, H. Fujihara, M.
Tobisu, Y. Fukumoto, N. Chatani, J. Am. Chem. Soc.
2007, 129, 5766–5771.
[8] The substrate was used as crude material because it un-
derwent partial decomposition (to give a mixture of un-
identified products) when purification by column chro-
matography was attempted.
[9] Several 2-(1-indanylidene)acetamide derivatives have
shown important pharmacological activity; see, for ex-
ample: a) C. Nitsche, C. Steuer, C. D. Klein, Bioorg.
[11] H.-P. Bi, L.-N. Guo, X.-H. Duan, F.-R. Gou, S. Huang,
Org. Lett. 2007, 9, 397–400.
[12] J. Ruiz, A. Ardeo, R. Ignacio, N. Sotomayor, E. Lete,
Tetrahedron 2005, 61, 3311–3324.
[13] B. Gabriele, L. Veltri, V. Maltese, R. Spina, R. Mancu-
so, G. Salerno, Eur. J. Org. Chem. 2011, 5626–5635.
2558
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 2547 – 2558