Solvent-free iridium(III)-catalyzed [2+2+2] cycloaddition providing access to fused arenes: Isoindolines, dihydroisobenzofurans and indanes

Article abstract of DOI:10.1055/s-0033-1338483

A practical and convenient solvent-free iridium-catalyzed [2+2+2] cycloaddition of α,ω-diynes and alkynes to prepare fused arenes has been developed. The method has shown high efficiency as isoindolines, dihydroisobenzofurans and indanes have been synthes

Full text of DOI:10.1055/s-0033-1338483

PAPER
▌2003
paper
Solvent-Free Iridium(III)-Catalyzed [2+2+2] Cycloaddition Providing Access
to Fused Arenes: Isoindolines, Dihydroisobenzofurans and Indanes
Solvent-Free Iridium(III)-Catalyzed [2+2+2] Cycloaddition
Anne-Laure Auvinet,a,b Véronique Michelet,*a,b Virginie Ratovelomanana-Vidal*a,b
a
Chimie ParisTech, Laboratoire Charles Friedel (LCF), 11 rue P. et M. Curie, 75231 Paris cedex 05, France
Fax +33(1)44071062; E-mail: veronique-michelet@chimie-paristech.fr; E-mail: virginie-vidal@chimie-paristech.fr
b
CNRS, UMR 7223, 75231 Paris cedex 05, France
Received: 15.03.2013; Accepted after revision: 29.04.2013
In this paper, we describe our preliminary results on irid-
Abstract: A practical and convenient solvent-free iridium-cata-
ium-catalyzed [2+2+2]-cycloaddition reactions under sol-
lyzed [2+2+2] cycloaddition of α,ω-diynes and alkynes to prepare
vent-free conditions leading to functionalized N-protected
isoindolines, dihydroisobenzofurans and indanes.
fused arenes has been developed. The method has shown high effi-
ciency as isoindolines, dihydroisobenzofurans and indanes have
been synthesized in good to excellent yields.
We first compared the reaction under our general condi-
tions using isopropyl alcohol, as previously reported, with
the same reaction under solvent-free conditions. The re-
sults are depicted in Scheme 1. In both cases, the cycload-
dition run with diyne 1 and cyclopropylacetylene
provided compound 2 in 61% yield. Pleasingly, the cyclo-
addition carried out with diyne 3 and n-hex-1-yne afford-
ed the desired isoindoline 4 with yield improvement when
run under solvent-free conditions. We could therefore as-
sume that the solvent-free conditions provide a potential
route to access fused arenes efficiently in a greener fash-
ion.
Keywords: cycloadditions, iridium, atom economy, solvent-free
conditions, benzannulation
The development of solvent-free reactions has attracted
much interest due to environmental concerns.1 As one of
the most important and effective carbon–carbon bond-
forming processes, and in terms of atom economy,
benzannulation is widely used in both academia and in-
dustry due to the diverse functional group tolerance.2 In
addition, this transformation provides a practical and easy
access to the formation of complex structures in a single
step. Transition metals have proven their synthetic utility
in the construction of complex and heavily substituted
benzene-derived systems from relatively simple starting
materials. The most useful cobalt, nickel, rhodium and
ruthenium catalysts offer the possibility of catalyzing
[2+2+2] cycloadditions, leading to aromatic compounds;3
however, iridium catalysis has been less studied with re-
gard to [2+2+2] cycloaddition4 which prompted us to in-
vestigate the potential of an iridium(III) complex.
Recently, we reported that [{Ir(H)[rac-binap]}2(μ-I)3]I
complex5 is able to catalyze the [2+2+2] cycloaddition of
α,ω-diynes to provide isoindolines, useful building blocks
for pharmaceutical purposes.6 In line with the 12 princi-
ples of green chemistry,7 one key point of our study was
to use a simple, easy-to-handle and air-stable catalyst that
would operate under environmentally friendly conditions.
As benzannulation reactions are always performed in the
presence of organic solvent, the challenge was to explore
the method and expand the scope of the reaction using sol-
vent-free conditions. As far as the solvent-free [2+2+2]-
cycloaddition reaction is concerned, only one example of
tandem double A3-coupling and [2+2+2]-cycloaddition
reactions in the presence of rhodium and copper as cata-
lysts has been reported so far.8
We then turned our attention to investigation of the reac-
tivity of alternative alkynes as precursors of a series of
functionalized isoindoline derivatives. The scope of the
reaction is highlighted in Table 1. Pleasingly, the cycload-
dition was successful with several alkynes bearing an al-
cohol or a chloride substituent, and provided the
corresponding isoindolines 7–13 in good yields (Table 1,
entries 1–7). The reaction conditions are compatible with
both the tosyl- and Boc-protected diynes 1 and 3. The re-
action was also successful with the functionalized alkyne
1-methyl-4-(prop-2-yn-1-yl)piperazine (Table 1, entry 8).
Compound 14 was isolated in 49% yield and is of partic-
ular significant importance as it is a key intermediate in
the synthesis of a biologically active compound.9 We also
wanted to extend the scope of the reaction to include ter-
minally disubstituted diynes, thus targeting highly func-
[Ir] (4 mol%)
80 °C, 17 h
TsN
TsN
1
2
i-PrOH 61%
NO SOLVENT 61%
[Ir] (4 mol%)
80 °C, 17 h
n-Bu
BocN
BocN
n-Bu
3
4
i-PrOH 63%
NO SOLVENT 71%
SYNTHESIS 2013, 45, 2003–2008
Advanced online publication: 06.06.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Scheme 1 Comparative results of [2+2+2] cycloaddition under iso-
DOI: 10.1055/s-0033-1338483; Art ID: SS-2013-Z0212-OP
© Georg Thieme Verlag Stuttgart · New York
propyl alcohol and solvent-free conditions

2004
A.-L. Auvinet et al.
PAPER
Table 1 Scope of the Iridium-Catalyzed [2+2+2] Cycloaddition: Synthesis of Isoindolinesa
R2
[Ir] (4 mol%)
80 °C, 17–24 h
R2
R3
R1N
R1N
R3
R2
1 R1 = Ts, R2 = H
3 R1 = Boc, R2 = H
5 R1 = Ts, R2 = Me
6 R1 = Ts, R2 = Ph
R2
Entry
1
Starting material Alkyne
Product
Yieldb (%)
59
OH
3
OH
3
1
7
TsN
OH
3
OH
OH
OH
3
BocN
BocN
BocN
2
3
4
3
8
9
60
85
77
OH
2
2
3
OH
3
10
OH
OH
5
1
11
75
TsN
OH
OH
6
7
3
1
12
13
68
59
BocN
TsN
Cl
N
3
Cl
3
NMe
N
TsN
TsN
8
1
5
14
15
49
43
NMe
n-Bu
n-Bu
9c,d
OH
OH
OH
10c
5
6
16
17
62
60
TsN
TsN
Ph
Ph
OH
11c
a Reaction conditions: diyne (1 equiv), alkyne (3 equiv), [{Ir(H)[rac-binap]}2(μ-I)3]I (4 mol%), 80 °C, 17–24 h.
b Isolated yield.
c 110 °C.
d Using 10 equivalents of alkyne.
Synthesis 2013, 45, 2003–2008
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Solvent-Free Iridium(III)-Catalyzed [2+2+2] Cycloaddition
2005
tionalized aromatic systems (Table 1, entries 9–11). our attention to alcohols as alkyne partners. The cycload-
Promising results were observed using diyne 5 with n- dition was fruitful with both the carbon- and oxygen-teth-
hex-1-yne which provided the corresponding isoindoline ered diynes 18 and 19, and provided the corresponding
15 in 43% yield (Table 1, entry 9). To our delight, the indanes 22 and 24 and dihydroisobenzofurans 2310 and 25
yield of the reaction could be improved when using but-3- in good yields (Table 2, entries 3–6). It is noteworthy that
yn-2-ol as the alkyne partner, leading to compound 16 in variation of the length of the side chain was rewarding,
62% yield (Table 1, entry 10). Finally, the use of a more with compounds 23 and 25 being obtained in similar
hindered diyne 6 gave a similar result, as isoindoline 17 yields (Table 2, entries 4 and 6). Other functional groups,
was isolated in 60% yield (Table 1, entry 11).
such as cyclic alkynes, were tolerated. The reaction of cy-
clohex-1-enylacetylene led to the desired indane 264a and
dihydroisobenzofuran 27 in 55% and 68% yield, respec-
tively (Table 2, entries 7 and 8). Cyclopentylacetylene
was also employed and provided the desired compounds
28 and 29 in satisfying yields (Table 2, entries 9 and 10).
The reaction of diyne 19 with cyclohexylacetylene led to
the formation of dihydroisobenzofuran 30 in 53% (Table
2, entry 11).
We then examined the reactivity of diynes 18 and 19 with
additional alkynes, which allows the preparation of in-
danes and dihydroisobenzofurans (Table 2). To our de-
light, the cycloaddition reactions were successful at
110 °C. The hydrocarbon n-hex-1-yne underwent cyclo-
addition to furnish the desired indane 204a (Table 2, entry
1) and dihydroisobenzofuran 214a (Table 2, entry 2) in
good yields of 80% and 76%, respectively. We also turned
Table 2 Synthesis of Indanes and Dihydroisobenzofuransa
[Ir] (4 mol%)
R1
110 °C, 17–24 h
X
X
R1
18 X = C(CO2Me)2
19 X = O
Entry
1c
Starting material
Alkyne
Product
Yieldb (%)
80
n-Bu
n-Bu
MeO2C
MeO2C
18
20
21
22
n-Bu
n-Bu
2c
3
19
18
76
70
O
OH
MeO2C
MeO2C
3
3
OH
OH
3
3
OH
O
4
19
18
23
24
63
52
OH
MeO2C
MeO2C
5
OH
OH
OH
6
7
19
18
25
26
61
55
O
MeO2C
MeO2C
8
19
27
68
O
© Georg Thieme Verlag Stuttgart · New York
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A.-L. Auvinet et al.
PAPER
Table 2 Synthesis of Indanes and Dihydroisobenzofuransa (continued)
[Ir] (4 mol%)
R1
110 °C, 17–24 h
X
X
R1
18 X = C(CO2Me)2
19 X = O
Entry
Starting material
Alkyne
Product
Yieldb (%)
44
9c
18
19
19
28
MeO2C
MeO2C
10c
11c
29
30
64
53
O
O
a Reaction conditions: diyne (1 equiv), alkyne (3 equiv), [{Ir(H)[rac-binap]}2(μ-I)3]I (4 mol%), 110 °C, 17–24 h.
b Isolated yield.
c Using 10 equivalents of alkyne.
1 H), 7.00 (br, 2 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.69 (d, J = 8.0 Hz, 2
H).
13C NMR (75 MHz, CDCl3): δ = 21.5, 31.8, 34.3, 53.5, 53.6, 62.0,
122.5, 127.6, 128.0, 129.8, 133.6, 136.3, 141.8, 143.6.
We have demonstrated that iridium-catalyzed [2+2+2] cy-
cloaddition can be performed efficiently under solvent-
free conditions. The value of this transformation has been
highlighted via the functional group tolerance, the large
substrate scope and the application of the method to the HRMS (ESI): m/z [M + Na]+ calcd for C18H21O3NSNa: 354.1134;
found: 354.1137.
synthesis of a biorelevant intermediate target. The reac-
tion conditions are compatible with mono- and disubsti-
tert-Butyl 5-(3-Hydroxypropyl)isoindoline-2-carboxylate (8)
tuted carbon-, nitrogen- and oxygen-tethered diynes, as
well as with functionalized alkynes. Fused arenes are ac-
cessed in good to excellent yields in a practical, conve-
nient and environmentally friendly manner.
Yield: 43 mg (60%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.44 (s, 9 H), 1.76–1.86 (m, 2 H),
2.62–2.67 (m, 2 H), 3.60 (t, J = 6.5 Hz, 2 H), 4.55–4.65 (m, 4 H),
6.99–7.13 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 28.5, 31.9, 34.4, 51.8, 51.9, 62.1,
79.6, 122.4, 122.7, 127.6, 134.5, 134.9, 137.2, 137.6, 141.1, 154.6.
HRMS (ESI): m/z [M + Na]+ calcd for C16H23O3NNa: 300.1570;
found: 300.1572.
All manipulations were carried out under an argon atmosphere. 1H
NMR and 13C NMR were recorded on Bruker AV300 or AV400 in-
struments. All signals were expressed as ppm (δ) and internally ref-
erenced to residual protio solvent signals. Coupling constants (J)
are reported in Hz and refer to apparent peak multiplicities. High-
resolution mass spectra were performed at the University Pierre and
Marie Curie (Paris). [{Ir(H)[rac-binap]}2(μ-I)3]I was prepared ac-
cording to the previously published procedure.5a All alkynes were
commercially available, except 14, which was prepared according
to the literature.9b
tert-Butyl 5-(2-Hydroxyethyl)isoindoline-2-carboxylate (9)
Yield: 58 mg (85%); white solid. Spectral data were in agreement
with those reported in the literature.6a
tert-Butyl 5-(Hydroxymethyl)isoindoline-2-carboxylate (10)
Yield: 50 mg (77%); colorless oil. Spectral data were in agreement
with those reported in the literature.
Fused Arenes by Iridium-Catalyzed Cycloaddition; General
Procedure
1-(2-Tosylisoindolin-5-yl)ethanol (11)
Yield: 48 mg (75%); colorless oil.
To a screw-cap tube was added [{Ir(H)[rac-binap]}2(μ-I)3]I (4
mol%), the diyne (1 equiv) was added, followed by addition of the
alkyne (3 equiv or 10 equiv). The tube was purged with argon and
capped and the reaction mixture was stirred overnight (17–24 h) at
80 °C or 110 °C. The crude reaction mixture was purified by flash
chromatography over silica gel (cyclohexane–EtOAc).
1H NMR (300 MHz, CDCl3): δ = 1.37 (d, J = 6.5 Hz, 3 H), 2.33 (s,
3 H), 4.51 (s, 4 H), 4.80 (q, J = 6.5 Hz, 1 H), 7.05 (d, J = 8.0 Hz, 1
H), 7.13–7.17 (m, 2 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.68 (d, J = 8.0
Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 21.5, 25.4, 53.5, 53.6, 70.0, 119.6,
122.6, 125.1, 127.6, 129.8, 133.6, 135.2, 136.4, 143.7, 145.9.
HRMS (ESI): m/z [M + Na]+ calcd for C17H19O3NSNa: 340.0978;
3-(2-Tosylisoindolin-5-yl)propan-1-ol (7)
Yield: 40 mg (59%); colorless oil.
found: 340.0980.
1H NMR (300 MHz, CDCl3): δ = 1.71–1.80 (m, 2 H), 2.33 (s, 3 H),
2.50–2.62 (m, 2 H), 3.57 (t, J = 6.5 Hz, 2 H), 4.51 (s, 4 H), 6.93 (s,
Synthesis 2013, 45, 2003–2008
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Solvent-Free Iridium(III)-Catalyzed [2+2+2] Cycloaddition
2007
tert-Butyl 5-(1-Hydroxyethyl)isoindoline-2-carboxylate (12)
13C NMR (75 MHz, CDCl3): δ = 21.5, 25.1, 53.6, 53.9, 66.4, 125.6,
127.2, 127.6, 127.8, 127.9, 128.0, 128.4, 128.8, 129.8, 132.8, 133.6,
134.2, 136.1, 137.0, 137.4, 139.5, 143.6, 144.0.
HRMS (ESI): m/z [M + Na]+ calcd for C29H27O3NSNa: 492.1604;
found: 492.1604.
Yield: 46 mg (68%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.42 (d, J = 6.5 Hz, 3 H), 1.44 (s,
9 H), 4.56–4.58 (m, 4 H), 4.84 (q, J = 6.5 Hz, 1 H), 7.12 (d, J = 8.0
Hz, 1 H), 7.17–7.22 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 24.5, 28.5, 51.8, 51.9, 52.1, 52.7,
119.5, 119.7, 122.5, 122.7, 124.7, 136.2, 136.5, 137.3, 137.6, 145.4,
154.6.
HRMS (ESI): m/z [M + Na]+ calcd for C15H21O3NNa: 286.1414;
found: 286.1418.
Dimethyl 5-(Butyl)indane-2,2-dicarboxylate (20)
Yield: 56 mg (80%); colorless oil. Spectral data were in agreement
with those reported in the literature.4a
5-Butyl-1,3-dihydroisobenzofuran (21)
Yield: 71 mg (76%); colorless oil. Spectral data were in agreement
with those reported in the literature.4a
5-(3-Chloropropyl)-2-tosylisoindoline (13)
Yield: 42 mg (59%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.90–1.99 (m, 2 H), 2.32 (s, 3 H),
2.64–2.69 (m, 2 H), 3.41 (t, J = 6.5 Hz, 2 H), 4.51 (s, 4 H), 6.93 (s,
1 H), 6.97–7.03 (m, 2 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.69 (d, J = 8.0
Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 21.5, 32.5, 34.0, 44.0, 53.5, 53.6,
122.7, 127.6, 128.1, 129.8, 133.7, 134.0, 136.5, 140.6, 143.7.
HRMS (ESI): m/z [M + Na]+ calcd for C18H20O2NS35ClNa:
372.0796; found: 372.0799.
Dimethyl 5-(3-Hydroxypropyl)indane-2,2-dicarboxylate (22)
Yield: 49 mg (70%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.86–1.91 (m, 2 H), 2.64–2.69 (m,
2 H), 3.56 (s, 4 H), 3.66 (t, J = 6.5 Hz, 2 H), 3.74 (s, 6 H), 6.99–7.03
(m, 2 H), 7.10 (d, J = 7.5 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 31.9, 34.4, 40.3, 40.6, 53.0, 60.5,
62.4, 124.2, 124.3, 127.3, 137.5, 140.2, 140.8, 172.2.
HRMS (ESI): m/z [M + Na]+ calcd for C16H20O5Na: 315.1203;
found: 315.1203.
5-[(4-Methylpiperazin-1-yl)methyl]-2-tosylisoindoline (14)
3-(1,3-Dihydroisobenzofuran-5-yl)propan-1-ol (23)
Yield: 60 mg (63%); white solid. Spectral data were in agreement
with those reported in the literature.10
Yield: 38 mg (49%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 2.22 (s, 3 H), 2.31–2.47 (m, 11 H),
3.39 (s, 2 H), 4.52 (s, 4 H), 7.01–7.13 (m, 3 H), 7.25 (d, J = 8.0 Hz,
2 H), 7.72 (d, J = 8.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 20.5, 44.9, 52.0, 52.5, 52.6, 54.0,
61.6, 121.3, 122.2, 126.6, 127.7, 128.8, 132.7, 133.9, 135.2, 137.1,
142.6.
Dimethyl 5-(1-Hydroxyethyl)indane-2,2-dicarboxylate (24)
Yield: 35 mg (52%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.47 (d, J = 6.5 Hz, 3 H), 3.57–
3.60 (m, 4 H), 3.74 (s, 6 H), 4.86 (q, J = 6.5 Hz, 1 H), 7.16 (br, 2 H),
7.22 (s, 1 H).
HRMS (ESI): m/z [M + H]+ calcd for C21H28O2N3S: 386.1897;
found: 386.1906.
13C NMR (75 MHz, CDCl3): δ = 25.3, 40.4, 40.6, 53.0, 60.5, 70.5,
121.3, 124.3, 124.5, 139.3, 140.3, 145.0, 172.2.
HRMS (ESI): m/z [M + Na]+ calcd for C15H18O5Na: 301.1046;
found: 301.1049.
5-Butyl-4,7-dimethyl-2-tosylisoindoline (15)
Yield: 27 mg (43%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 0.84 (t, J = 6.5 Hz, 3 H), 1.18–
1.44 (m, 4 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 2.33 (s, 3 H), 2.42–2.47
(m, 2 H), 4.47–4.49 (m, 4 H), 6.75 (s, 1 H), 7.24 (d, J = 8.0 Hz, 2
H), 7.72 (d, J = 8.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.9, 14.9, 18.2, 21.5, 22.7, 32.6,
33.0, 53.4, 53.8, 127.5, 127.6, 129.4, 129.8, 132.2, 133.9, 135.4,
141.0, 143.5.
1-(1,3-Dihydroisobenzofuran-5-yl)ethanol (25)
Yield: 53 mg (61%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.50 (d, J = 6.5 Hz, 3 H), 4.93 (q,
J = 6.5 Hz, 1 H), 5.09 (s, 4 H), 7.19–7.28 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 25.5, 70.4, 73.4, 73.5, 118.0,
121.0, 124.8, 138.4, 139.6, 145.4.
HRMS (ESI): m/z [M – H]+ calcd for C10H11O2: 163.0754; found:
163.0750.
HRMS (ESI): m/z [M + Na]+ calcd for C21H27O2NSNa: 380.1655;
found: 380.1658.
1-(4,7-Dimethyl-2-tosylisoindolin-5-yl)ethanol (16)
Dimethyl 5-(Cyclohexenyl)indane-2,2-dicarboxylate (26)
Yield: 41 mg (55%); colorless oil. Spectral data were in agreement
with those reported in the literature.4a
Yield: 39 mg (62%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.34 (d, J = 6.5 Hz, 3 H), 2.05 (s,
3 H), 2.10 (s, 3 H), 2.34 (s, 3 H), 4.46–4.48 (m, 4 H), 5.05 (m, 1 H),
7.15 (s, 1 H), 7.25 (d, J = 8.0 Hz, 2 H), 7.71 (d, J = 8.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 14.6, 18.4, 21.5, 24.3, 53.4, 53.7,
66.5, 125.3, 126.0, 127.5, 129.8, 130.1, 133.7, 133.8, 135.5, 143.6,
143.7.
5-(Cyclohex-1-enyl)-1,3-dihydroisobenzofuran (27)
Yield: 72 mg (68%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.53–1.63 (m, 2 H), 1.67–1.75 (m,
2 H), 2.10–2.17 (m, 2 H), 2.30–2.35 (m, 2 H), 5.02 (s, 4 H), 6.00–
6.04 (m, 1 H), 7.09 (d, J = 8.0 Hz, 1 H), 7.17–7.22 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 22.1, 23.0, 25.8, 27.7, 73.4, 73.6,
117.5, 120.6, 124.3, 124.9, 136.5, 137.3, 139.2, 142.4.
HRMS (ESI): m/z [M + Na]+ calcd for C19H23O3NSNa: 368.1291;
found: 368.1293.
HRMS (EI): m/z [M + Na + O2]+ calcd for C14H16O3Na: 255.0991;
found: 255.0992.
1-(4,7-Diphenyl-2-tosylisoindolin-5-yl)ethanol (17)
Yield: 35 mg (60%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.26 (d, J = 6.5 Hz, 3 H), 2.33 (s,
3 H), 4.24–4.25 (m, 2 H), 4.62–4.63 (m, 2 H), 4.72 (q, J = 6.5 Hz, 1
H), 7.31–7.42 (m, 12 H), 7.51 (br, 1 H), 7.60 (d, J = 8.5 Hz, 2 H).
Dimethyl 5-Cyclopentylindane-2,2-dicarboxylate (28)
Yield: 32 mg (44%); colorless oil.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2003–2008

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A.-L. Auvinet et al.
PAPER
1H NMR (300 MHz, CDCl3): δ = 1.45–1.74 (m, 6 H), 1.92–2.00 (m,
2 H), 2.81–2.93 (m, 1 H), 3.49–3.50 (s, 4 H), 3.67 (s, 6 H), 6.96–
7.04 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 25.5, 34.8, 40.3, 40.6, 45.8, 52.9,
60.4, 122.8, 123.8, 126.0, 137.1, 139.8, 145.5, 172.2.
HRMS (ESI): m/z [M + Na]+ calcd for C18H22O4Na: 325.1410;
found: 325.1411.
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5-Cyclopentyl-1,3-dihydroisobenzofuran (29)
Yield: 64 mg (64%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.45–1.77 (m, 6 H), 1.96–2.04 (m,
2 H), 2.88–2.99 (m, 1 H), 5.02 (s, 4 H), 7.05 (m, 1 H), 7.07–7.08 (m,
2 H).
13C NMR (75 MHz, CDCl3): δ = 25.5, 34.8, 45.8, 73.4, 73.5, 119.4,
120.6, 126.3, 136.5, 139.3, 145.9.
HRMS (ESI): m/z [M – H2O + O2 + Na]+ calcd for C13H14O2Na:
225.0885; found: 225.0886.
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5-Cyclohexyl-1,3-dihydroisobenzofuran (30)
Yield: 57 mg (53%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.18–1.37 (m, 5 H), 1.67–1.80 (m,
5 H), 2.40–2.47 (m, 1 H), 5.01 (s, 4 H), 7.02–7.07 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 26.1, 26.9, 34.7, 44.5, 73.4, 73.5,
119.2, 120.7, 126.1, 136.6, 139.2, 147.6.
HRMS (EI): m/z [M – H]+ calcd for C14H17O: 201.1274; found:
201.1274.
Acknowledgment
This work was supported by the Ministère de l’Education et de la
Recherche and the Centre National de la Recherche Scientifique
(CNRS). A.-L.A. is grateful to the Fondation Pierre-Gilles de
Gennes pour la Recherche for a grant. Johnson Matthey Inc. is
acknowledged for a generous loan of IrCl3. We are grateful to Quentin
Llopis for his valuable help.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
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