Iridium(III)-catalyzed approach for the synthesis of fused arenes: Access to isoindolines, indanes, and dihydroisobenzofurans

Article abstract of DOI:10.1002/cctc.201300068

A facile and efficient method for the synthesis of isoindoline, indane, and dihydroisobenzofuran derivatives has been developed through the application of a halogen-bridged iridium(III) complex to the [2+2+2] cycloaddition of α,ω-diynes with alkynes. The

Full text of DOI:10.1002/cctc.201300068

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Triple-edged sword: Isoindoline,
indane, and dihydroisobenzofuran deriv-
atives are synthesized by using a triply
halogen-bridged iridium(III) complex in
the [2+2+2] cycloaddition of a,w-
diynes with alkynes. A broad range of
substitution groups such as alcohol,
alkyl, ether, and halogen can be used
and the chemistry extended to prepare
the corresponding borylated fused
arenes.
A.-L. Auvinet, M. Ez-Zoubir, S. Bompard,
M. R. Vitale, J. A. Brown, V. Michelet,*
V. Ratovelomanana-Vidal*
&& – &&
Iridium(III)-Catalyzed Approach for the
Synthesis of Fused Arenes: Access to
Isoindolines, Indanes, and
Dihydroisobenzofurans
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DOI: 10.1002/cctc.201300068
Iridium(III)-Catalyzed Approach for the Synthesis of Fused
Arenes: Access to Isoindolines, Indanes, and
Dihydroisobenzofurans
Anne-Laure Auvinet,[a, b] Mehdi Ez-Zoubir,[a, b] Savinien Bompard,[a, b] Maxime R. Vitale,[a, b]
Jack A. Brown,[c] Vꢁronique Michelet,*[a, b] and Virginie Ratovelomanana-Vidal*[a, b]
Dedicated to Professor Irina P. Beletskaya for her tremendous contribution to metal-catalyzed reactions
A facile and efficient method for the synthesis of isoindoline,
indane, and dihydroisobenzofuran derivatives has been devel-
oped through the application of a halogen-bridged iridium(III)
complex to the [2+2+2] cycloaddition of a,w-diynes with al-
kynes. The cycloaddition tolerates a broad range of substitu-
tion groups, such as alcohol, alkyl, ether, and halogen, and the
chemistry can be extended to prepare the corresponding bory-
lated fused arenes. The reaction shows that hindered starting
materials are also good partners, which provide the desired
fused arenes in good yields.
Introduction
Fused arenes are key motifs present in a number of biological-
ly active compounds, and the development of diverse synthet-
ic methods for their preparation and subsequent functionaliza-
tion is of considerable interest.[1] In this context, benzannula-
tion holds promise for converting simple and generally avail-
able raw materials into elaborate complex molecules, such as
pharmaceutical and natural products. In addition, ring synthe-
sis is the most straightforward and atom-economical route to
prepare polysubstituted benzene derivatives and, compared to
existing Friedel–Crafts functionalization methodologies, has
the advantage of not being limited to specific substitution
groups governed by the preexisting directing groups.[2] Transi-
tion-metal complexes are indispensable tools for organic syn-
thesis and have proven their synthetic utility in the preparation
of complex and heavily substituted benzene-derived systems.[3]
Iridium(III) complexes have been explored less,[4] although they
Scheme 1. CÀH and CÀC bond-forming processes.
[a] Dr. A.-L. Auvinet, Dr. M. Ez-Zoubir, S. Bompard, Dr. M. R. Vitale,
Dr. V. Michelet, Dr. V. Ratovelomanana-Vidal
ENSCP Chimie ParisTech Laboratoire Charles Friedel
11 rue P. et M. Curie
have a great potential in CÀH and CÀC bond-forming process-
es (Scheme 1). In our previous reports, we demonstrated the
versatility of halogen-bridged iridium(III) complexes.[5] Notably,
such catalytically active species proved to be highly efficient in
the asymmetric hydrogenation of a wide range of unsaturated
C=N bonds present in cyclic imines, quinolines, quinolinium
salts, and quinoxalines.[6] In addition, the catalyst system was
excellent for mediating the stereoselective dimerization of
enynes.[7] We showed recently that the iodo-bridged iridium(III)
catalyst system [{Ir(H)[rac-binap]}2(m-I)3]I could be involved in
the [2+2+2] cycloaddition of a,w-diynes and alkynes to pro-
vide the biologically relevant isoindoline scaffolds.[8] We devel-
oped a reliable and robust iridium(III)-catalyzed strategy that
enables the synthesis of various fused isoindolines with
75005 Paris (France)
Fax: (+33)144071062
E-mail: veronique-michelet@chimie-paristech.fr
virginie-vidal@chimie-paristech.fr
[b] Dr. A.-L. Auvinet, Dr. M. Ez-Zoubir, S. Bompard, Dr. M. R. Vitale,
Dr. V. Michelet, Dr. V. Ratovelomanana-Vidal
CNRS
UMR 7223
75005 Paris (France)
[c] J. A. Brown
GlaxoSmithKline
Medicines Research Centre
Gunnels Wood Road, Stevenage
SG1 2NY (UK)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201300068.
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a common and environmentally friendly solvent such as 2-
propanol. To extend our endeavors to the synthesis and study
of aromatic compounds, we used this catalyst system for the
preparation of the corresponding carbon- and oxygen-based
fused arenes.
Table 1. Substrate scope with terminal diynes and terminal alkynes.[a]
Herein, we report the detailed results of our studies of the
[2+2+2] cycloaddition of a,w-diynes and alkynes in the pres-
ence of our catalyst system, which yields isoindoline, indane,
and dihydroisobenzofuran derivatives.
Entry
1
X
Alkyne Product
Yield [%]
76
C(CO2Me)2
6
7
8
9
2
3
4
5
6
7
8
9
O
68
85
70
Results and Discussion
NBoc
C(CO2Me)2
NTs
In our preliminary studies, diyne 1 was reacted with 3 equiv. of
propargyl alcohol to give an isoindoline derivative 2 in the
presence of a catalytic amount of [{Ir(H)[rac-binap]}2(m-I)3]I.[8]
The catalytic activity varied according to the solvent. Reaction
optimization showed that 2-propanol was the most efficient
solvent to perform the reaction. The reaction was completed
within 17 h at 808C, which furnished the desired isoindoline 2
in satisfactory 78% yield (Scheme 2).
10 69
11 90
12 77
13 70
14 64
NBoc
C(CO2Me)2
NTs
NBoc
Scheme 2. [{Ir(H)[rac-binap]}2(m-I)3]I-catalyzed reaction of diyne 1 with
3 equiv. of propargyl alcohol toward isoindoline derivative 2.[8]
10
11
12
C(CO2Me)2
NTs
15 87[c]
16 62[c]
17 63[c]
We reported previously that diynes 1 and 3 reacted with ter-
minal alkynes to give the corresponding isoindoline derivatives
in good to excellent yields.[8] With these promising results in
hand, we decided to apply the methodology to diynes 4 and
5. The results are summarized in Table 1. Then, propargyl alco-
hol underwent cycloaddition with malonate-based diyne 4,
oxygen-based diyne 5, and nitrogen-based diyne 3, which af-
forded the desired fused arenes: indane 6 (entry 1), dihydro-
benzofuran 7 (entry 2), and isoindoline 8 (entry 3) in 76, 68,
and 85% yields, respectively. Another alkynyl alcohol, 3-butyn-
1-ol, was evaluated with different diynes; 1, 3, and 4. The cy-
cloaddition was successful in the formation of compound 9
(entry 4), compound 10 (entry 5), and alcohol 11 (entry 6) in
excellent yield (up to 90%). Various substitution groups were
shown to be tolerated on the alkyne partner. Methyl propargyl
ether provided the corresponding fused arenes 12 (entry 7), 13
(entry 8), and 14 (entry 9) in good yields (64–77%). We then
studied the cycloaddition with alkyl-substituted alkynes such
as n-hexyne, cyclopropylacetylene, and 1-chloro-pent-4-yne
(entries 10–18). Thus, we could access compounds 15–17 with
satisfactory yields (entries 10–12). The cyclopropyl-substituted
18 was obtained in 82% yield by using 8 mol% of the iridium
complex (entry 13). Cycloadducts 19–21 were observed in ac-
ceptable yields (entries 14–16). Finally, the reaction of diynes 4
and 1 with the halogen-substituted alkyne led to the desired
compounds 22 and 23 in 40 and 61% yields, respectively (en-
tries 17 and 18). The cycloaddition with aryl-substituted al-
NBoc
13
C(CO2Me)2
18 82[c,d]
14
15
16
17
O
19 30[c]
20 61[c]
21 66[c]
22 40[c]
NTs
NBoc
C(CO2Me)2
18
19
NBoc
NBoc
23 61[c]
24 47
20
NBoc
25 59
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kynes was also successful, which led to the corresponding iso-
indolines 24–26 in good yields (entries 19–21).
Table 1. (Continued)
Entry
21
X
Alkyne Product
Yield [%]
We next turned our attention to monosubstituted diynes.
The reaction provided the desired compounds, in most cases
favoring the ortho regioisomer. The results are summarized in
Table 2. We first looked at diyne malonates bearing sp3 (methyl
27) and sp2 (phenyl 28) centers. The reaction performed in the
presence of propargyl alcohol and diyne malonates 27 and 28
showed a slight improvement in the regioselectivity in the
case of the methyl-substituted diyne 27. The methyl group has
a significant effect on the regioselectivity of the cyclization,
probably because of the presence of an sp3 center, which is
more sterically demanding than that of the more planar sp2
center; this explains the ortho/meta ratio of 50:50 obtained
with aryl substituents. As the steric hindrance seemed to play
a role in the regioselectivity, we investigated the same reaction
with a different side-chain length within the alkyne partner.
We can clearly see that the regioselectivity that is in favor of
the ortho isomer increased with the length of the side chain. A
ratio of 58:42 was observed with propargyl alcohol (entry 1),
and a significant improvement was observed with 3-butyn-1-ol
(entry 3) and 4-pentyn-1-ol, which provided 34 with a ratio of
78:22 in favor of the ortho isomer (entry 4). The use of n-
hexyne gave a regiospecificity (entry 5) similar to that obtained
with 3-butyn-1-ol (entry 3). We also performed the reaction
with methyl propargyl ether; however, no significant improve-
ment was observed (entry 6). To expand the scope of the reac-
tion, oxygen- and nitrogen-tethered diynes were tested. The
cycloaddition of monosubstituted dipropargyl ether 29 was
studied in the presence of propargyl alcohol. The desired com-
pound 37 was obtained with satisfactory regioselectivity
(entry 7). The cycloaddition of N-Boc-protected diyne 30 with
propargyl alcohol furnished the desired compound in excellent
yield and with good regioselectivity (entry 8). The reaction was
also successful with cyclopropylacetylene, which delivers the
desired product with useful regioselectivity (entry 9). By com-
paring carbon-, oxygen-, and nitrogen-based diynes, one may
observe that a better regiocontrol is observed in the case of
the heteroatom-linked derivatives. Propargyl alcohol as the
alkyne partner seems to approach differently, depending on
the nature of the diyne tether (entries 1, 2, 7, and 8). This may
be due to a higher steric hindrance of the malonate moiety,
which could disturb the insertion of the alkyne partner and
thus give lower regioselectivities.
NBoc
26 52
[a] Reaction conditions: 1 equiv. of the diyne, 3 equiv. of the alkyne,
4 mol% of [{Ir(H)[rac-binap]}2(m-I)3]I in 1 mL of 2-propanol stirred at 80 or
110 8C for 17 h; [b] Isolated yield; [c] 10 equiv. of the alkyne; [d] 8 mol%
of [{Ir(H)[rac-binap]}2(m-I)3]I.
Table 2. Cycloaddition with unsymmetrical diynes and terminal alkynes.[a]
Entry Diyne Alkyne Product
Diyne Yield[b] [%]
(ortho/meta
ratio)[c]
1
2
27
28
31
32
60 (58:42)
62 (50:50)
3
4
5
6
27
27
27
27
33
34
35
36
70 (71:29)
33 (78:22)
78 (72:28)
64 (63:37)
The results from the experiments detailed above demon-
strate that the ortho regioisomer is favored, which can be ra-
tionalized in Scheme 3. As binap has a bite angle comparable
to that of DPPF,[9] we can assume that the initial oxidative cycli-
zation of the iridium complex with the diyne is followed by
the dissociation of one phosphorus moiety of binap because
of the steric hindrance of the substituent (methyl, phenyl)
from the diyne (Scheme 4); this hypothesis is in agreement
with Takeuchi’s work.[4a] Then, the alkyne could fill the vacancy
through coordination to iridium, which leads to intermediate
A. The insertion step toward iridium–cycloheptadiene B would
be followed by a reductive elimination, which would preferen-
tially afford the ortho isomer of the benzanulated product.
7
29
30
30
37
38
39
61 (71:29)
97 (72:28)
27 (67:33)
8
9[d]
[a] Reaction conditions: 1 equiv. of the diyne, 3 equiv. of the alkyne,
4 mol% of [{Ir(H)[rac-binap]}2(m-I)3]I in 1 mL of 2-propanol stirred at 80 or
110 8C for 17 h; [b] Isolated yield; [c] Determined from 1H NMR analysis of
the crude reaction mixture; [d] 10 equiv. of the alkyne.
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Owing to the synthetic utility of aromatic boronic esters, we
also envisaged the use of alkynylboronates in this study.[10] The
reaction was performed in toluene to prevent transesterifica-
tion of the boronate moiety (Scheme 5). The terminal alkynyl-
boronate 50 proved to be an excellent partner as the reaction
Scheme 3. Reaction mechanism accountable for the formation of the ortho
isomer of the benzanulated product.
Scheme 5. Cycloaddition with alkynylboronates toward aromatic boronic
esters.
proceeded smoothly to afford the desired structures in good
yields. The cycloaddition performed well with alkyl- and aryl-
substituted diynes such as nitrogen-, malonate-, and oxygen-
tethered diynes, which furnished the highly substituted boryl
isoindolines 51 and 53 in good yields as well as boryl indane
52 and boryl dihydroxyisobenzofuran 54, which were isolated
in 49 and 62% yields, respectively. Notably, disubstituted
diynes reacted similarly as observed previously in Scheme 4,
which makes our catalyst system highly versatile with regard
to the choice of the alkyne partner.
Scheme 4. Cycloaddition with disubstituted diynes and terminal alkynes.
To evaluate the limit of the catalyst system, we studied the
challenging and less well explored reactivity of alkyl- and aryl-
disubstituted diynes. The results presented in Scheme 4 indi-
cate that a range of different functional groups can be tolerat-
ed. The steric hindrance of the substituent on the diyne has
a significant effect on the reaction outcome. The reaction per-
formed with alkyl-substituted diyne malonate 40 was success-
ful and provided 44 in 51% yield. The NTs (Ts=tosyl) diyne 43
also proved to be a good partner, as the corresponding cyclo-
adduct 45 was isolated in 73% yield. The aryl-substituted
diyne 41 reacted sluggishly with propargyl alcohol to give 46
in 27% yield, whereas a slight improvement could be observed
with methyl propargyl ether, which led to 47 in 42% yield. As
expected, the reaction of the highly hindered silylated-substi-
tuted diyne 42 proved to be unsuccessful, probably because
of the prominent steric hindrance generated by trimethylsilyl
substituents.
Conclusions
In summary, we have developed a convenient and efficient
protocol for the preparation of fused arenes. Isoindolines, in-
danes, and dihydroisobenzofurans bearing a wide range of
substitution groups could be accessed through an iridium(III)-
catalyzed [2+2+2] cycloaddition of a,w-diynes with alkynes.
The reaction proceeds with symmetrical and unsymmetrical
diynes, which affords highly substituted benzene derivatives in
good to excellent yields (up to 97%). This methodology can
be applied to alkynylboronates, which is a convenient means
to generate the challenging, highly functionalized borylated
fused arenes that present great potential for further elabora-
tion. Notably, these processes are extremely robust and simple
to perform. The catalyst system is compatible with commercial
grade non-degassed solvents, whereas the alkynes herein do
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1.26Hm), 2.26 (s, 1.74Ho), 3.51–3.60 (m, 4Ho,m), 3.75 (s, 6Ho,m),
4.61 (d, J=5.5 Hz, 0.84Hm), 4.67 (d, J=5.4 Hz, 1.16Ho), 7.07–6.96
(m, 1.42Ho,m), 7.17 ppm (d, J=7.7 Hz, 0.58Ho); 13C NMR (75 MHz,
CDCl3): d=15.0, 18.9, 39.2, 39.6, 40.6 (2C), 53.0 (2C), 59.9 (2C),
63.4, 65.2, 120.3, 121.4, 126.9, 127.4, 132.2, 133.8, 137.3, 138.2,
139.3, 139.6, 140.0, 140.2, 172.2 ppm (2C); HRMS (ESI) m/z: calcd
for C15H18O5Na: 301.1046 [M+Na]+; found: 301.1048.
not necessitate purification before use. For these reasons, this
iridium(III)-catalyzed [2+2+2] cycloaddition is a practical and
attractive synthetic method.
Experimental Section
General
Dimethyl 5-(hydroxymethyl)-4-phenyl-1H-indene-2,2(3H)-dicarboxy-
late and dimethyl 6-(hydroxymethyl)-4-phenyl-1H-indene-2,2(3H)-
dicarboxylate (32o/32m): Starting from diyne 28 (56.9 mg,
0.20 mmol), the reaction afforded compounds 32o and 32m sepa-
rately as yellow oils [21 mg (32o) and 21.0 mg (32m), 50:50 mix-
ture of ortho/meta regioisomers 32o/32m, 62% global yield]. 32o:
1H NMR (300 MHz, CDCl3): d=3.34 (s, 2H), 3.67 (s, 2H), 3.72 (s, 6H),
4.46 (s, 2H), 7.22–7.31 (m, 2H), 7.37–7.48 ppm (m, 5H); 13C NMR
(75 MHz, CDCl3): d=40.1, 40.7, 52.9, 60.2, 63.0, 123.5, 127.4, 127.5,
128.6, 128.9, 137.2, 137.6, 138.4, 139.2, 139.4, 172.0 ppm; 32m:
1H NMR (300 MHz, CDCl3) d=3.66 (s, 4H), 3.74 (s, 6H), 4.71 (s, 2H),
7.23–7.24 (m, 2H), 7.34–7.41 (m, 2H), 7.45–7.46 ppm (m, 3H);
13C NMR (75 MHz, CDCl3): d=40.1, 40.6, 53.0, 60.4, 65.3, 121.9,
126.5, 127.2, 128.4, 128.9, 137.1, 138.5, 140.4, 140.5, 141.1,
172.0 ppm; HRMS (ESI): m/z: calcd for C20H20O5Na: 363.1203
[M+Na]+; found: 363.1205.
1H NMR and 13C NMR signals were internally referenced to residual
protio solvent signals. Coupling constants (J) referred to apparent
peak multiplicities. High-resolution mass spectra were performed
at the Universitꢁ Pierre et Marie Curie (Paris). Toluene was distilled
over calcium hydride, and 2-propanol (Normapur grade) was used
without further purification. [{Ir(H)[rac-binap]}2(m-I)3]I was prepared
according to the method described in the literature.[5]
Materials
Diynes 1, 3, 4, 27–30, 40–43, 49 and alkynylboronate 50 were pre-
pared according to methods described in the literature (see the
Supporting Information). Diyne 5 was purchased from Aldrich and
used without further purification.
Dimethyl 5-(2-hydroxyethyl)-4-methyl-1H-indene-2,2(3H)-dicarboxy-
late and dimethyl 6-(2-hydroxyethyl)-4-methyl-1H-indene-2,2(3H)-
dicarboxylate (33o/33m): Starting from diyne 27 (41.3 mg,
0.19 mmol), the reaction afforded compound 33 as a yellow oil
and as an inseparable 71:29 mixture of ortho/meta regioisomers
Cycloaddition of diynes with alkynes
General procedure: [{Ir(H)[rac-binap]}2(m-I)3]I (4 mol%) and 2-propa-
nol (2 mL/0.4 mmol of the diyne) were added to a sealed tube. The
mixture was stirred under argon for 5 min at RT. Then, the diyne
(1 equiv.) was added, followed by the addition of the alkyne (3 or
10 equiv.). The tube was sealed, and the reaction mixture was
stirred at 80–1108C for 17–48 h. Purification of the crude mixture
by using flash chromatography over silica gel provided the desired
compound.
1
33o/33m (38.0 mg, 70% yield). H NMR (300 MHz, CDCl3): d=2.22
(s, 2.13Ho), 2.23 (s, 0.87Hm), 2.79 (t, J=6.5 Hz, 0.58Hm), 2.87 (t, J=
6.8 Hz, 1.42Ho), 3.46–3.62 (m, 5Ho,m), 3.70–3.86 (m, 2Ho,m), 3.75
(s, 6Ho,m), 6.84 (s, 0.29Hm), 6.89 (s, 0.29Hm), 6.97 (d, J=7.8 Hz,
0.71Ho), 7.01 ppm (d, J=7.8 Hz, 0.71Ho); 13C NMR (75 MHz, CDCl3):
d=15.6, 19.0, 36.2, 38.9, 39.2, 40.0, 40.7, 45.8, 53.0 (2C), 59.8 (2C),
62.8, 63.7, 121.4, 122.1, 128.7, 129.0, 132.3, 133.8, 134.9, 137.0,
137.6, 137.9, 139.6, 140.0, 172.3 ppm (2C); HRMS (EI): m/z: calcd for
C16H20O5Na: 315.1203 [M+Na]+; found: 315.1201.
The analytical data obtained for cycloaddition products 2,[11a] 6,[4a]
7,[11b] 8,[11c] 9,[4a] 10,[8] 11,[8] 12,[4a] 13,[8] 14,[8] 15,[4a] 16,[11d] 17,[11e] 20,[8]
21,[8] 22,[4a] 23,[8] 24,[11e] 25,[8] 26,[8] 34,[4a] 35,[4a] 38,[8] 39,[8] 44,[4a] 45,[8]
51,[8] 53,[8] and 54[11f] were in agreement with those reported in the
literature.
Dimethyl 5-(methoxymethyl)-4-methyl-1H-indene-2,2(3H)-dicarbox-
ylate and dimethyl 6-(methoxymethyl)-4-methyl-1H-indene-2,2(3H)-
dicarboxylate (36o/36m): Starting from diyne 27 (41.3 mg,
0.19 mmol), the reaction afforded compound 36 as a yellow oil
and as an inseparable 61:39 mixture of ortho/meta regioisomers
Dimethyl 5-cyclopropyl-1H-indene-2,2(3H)-dicarboxylate (18): Start-
ing from diyne 4 (38.7 mg, 0.18 mmol), compound 18 was isolated
1
as a yellow oil (42.0 mg, 82% yield). H NMR (300 MHz, CDCl3): d=
1
36o/36m (34.8 mg, 64% yield). H NMR (300 MHz, CDCl3): d=2.24
0.54–0.60 (m, 2H), 0.81–0.87 (m, 2H), 1.78 (tt, J=8.5, 5.1 Hz, 1H),
3.47 (s, 4H), 3.66 (s, 6H), 6.80–6.83 (m, 2H), 6.99 ppm (d, J=8.0 Hz,
1H); 13C NMR (75 MHz, CDCl3): d=8.0, 14.2, 39.2, 39.5, 51.9, 59.5,
120.4, 122.9, 123.7, 135.9, 139.0, 141.9, 171.1 ppm; HRMS (EI): m/z:
calcd for C16H19O4: 275.1278 [M+H]+; found: 275.1278.
(s, 1.83Ho), 2.25 (s, 1.17Hm), 3.37 (s, 1.17Hm), 3.38 (s, 1.83Ho),
3.51–3.60 (m, 4Ho,m), 3.75 (s, 6Ho,m), 4.37 (s, 0.78Hm), 4.41 (s,
1.22Ho), 6.93–7.05 (m, 1.39Ho,m), 7.13 ppm (d, 0.61Ho); 13C NMR
(75 MHz, CDCl3): d=15.0, 18.9, 39.2, 39.7, 40.7 (2C), 52.9 (2C), 58.1
(2C), 59.9 (2C), 73.1, 74.7, 121.0, 121.1, 127.6, 128.3, 132.7, 133.7,
134.6, 137.3, 138.3, 139.4, 139.5, 139.9, 172.2 ppm (2C); HRMS (EI):
m/z: calcd for C16H20O5Na: 315.1203 [M+Na]+; found: 315.1204.
5-Cyclopropyl-1,3-dihydroisobenzofuran (19): Starting from diyne 5
(37.6 mg, 0.40 mmol), the reaction afforded compound 19 as
a yellow oil (19.0 mg, 30% yield). 1H NMR (300 MHz, CDCl3): d=
0.58–0.63 (m, 2H), 0.85–0.92 (m, 2H), 1.80–1.89 (m, 1H), 4.99 (s,
4H), 6.87–6.93 (m, 2H), 7.04 ppm (d, J=8.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d=8.8, 14.9, 72.9, 73.0, 117.6, 120.2, 124.6, 135.8,
138.9, 142.9 ppm; HRMS (EI): m/z: calcd for C11H11O: 159.0804
[MÀH]+; found: 159.0806.
(4-Phenyl-1,3-dihydroisobenzofuran-5-yl)methanol and (7-phenyl-
1,3-dihydroisobenzo-furan-5-yl)methanol (37o/37m): Starting from
diyne 29 (100.0 mg, 0.59 mmol), the reaction afforded compounds
37o and 37m separately as yellow oils [41.7 mg (37o) and 17.1 mg
(37m), 71:29 mixture of ortho/meta regioisomers 37o/37m, 61%
1
global yield]. 37o: H NMR (300 MHz, CDCl3): d=4.42 (s, 2H), 4.78
Dimethyl 5-(hydroxymethyl)-4-methyl-1H-indene-2,2(3H)-dicarboxy-
late and dimethyl 6-(hydroxymethyl)-4-methyl-1H-indene-2,2(3H)-
dicarboxylate (31o/31m): Starting from diyne 27 (41.3 mg,
0.19 mmol), the reaction afforded compound 31 as a yellow oil
and as an inseparable 58:42 mixture of ortho/meta regioisomers
(s, 2H), 5.09 (s, 2H), 7.15–7.18 (m, 2H), 7.30–7.41 ppm (m, 5H);
13C NMR (75 MHz, CDCl3): d=62.6, 73.3, 74.0, 120.2, 127.7, 127.9,
128.5, 128.6, 135.1, 137.6, 138.0, 138.6, 138.7 ppm; 37m: 1H NMR
(300 MHz, CDCl3): d=4.69 (s, 2H), 5.09–5.11 (m, 4H), 7.18 (s, 1H),
7.25 (s, 1H), 7.27–7.39 ppm (m, 5H); 13C NMR (75 MHz, CDCl3): d=
1
31o/31m (31 mg, 60% yield). H NMR (300 MHz, CDCl3): d=2.26 (s,
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CHEMCATCHEM
FULL PAPERS
www.chemcatchem.org
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65.2, 73.4, 73.7, 118.6, 126.4, 127.7, 127.9, 128.8, 136.3, 136.7, 140.0,
140.7, 141.2 ppm; HRMS (ESI): m/z: calcd for C15H13O2: 225.0910
[MÀH]+; found: 225.0910.
Dimethyl 5-(hydroxymethyl)-4,7-diphenyl-1H-indene-2,2(3H)-dicar-
boxylate (46): Starting from diyne 41 (69.3 mg, 0.19 mmol), the re-
action afforded compound 46 as a yellow oil (21.6 mg, 27% yield).
1H NMR (300 MHz, CDCl3): d=3.30 (s, 2H), 3.61 (s, 6H), 3.65 (s, 2H),
4.43 (s, 2H), 7.22–7.25 (m, 2H), 7.29–7.45 ppm (m, 9H); 13C NMR
(75 MHz, CDCl3): d=40.2, 40.5, 52.9, 60.2, 63.1, 127.3, 127.5, 128.0
(2C), 128.5, 128.6, 128.9, 136.6, 136.9, 137.6, 137.9, 138.3, 140.0,
140.3, 171.9 ppm; HRMS (EI): m/z: calcd for C26H24O5Na: 439.1516
[M+Na]+; found: 439.1516.
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Dimethyl 5-(methoxymethyl)-4,7-diphenyl-1H-indene-2,2(3H)-dicar-
boxylate (47): Starting from diyne 41 (69.3 mg, 0.19 mmol), the re-
action afforded compound 47 as a yellow oil (34.8 mg, 42% yield).
1H NMR (300 MHz, CDCl3): d=3.27 (s, 3H), 3.39 (s, 2H), 3.68 (s, 6H),
3.71 (s, 2H), 4.22 (s, 2H), 7.29–7.33 (m, 2H), 7.36–7.52 ppm (m, 9H);
13C NMR (75 MHz, CDCl3): d=40.3, 40.5, 52.9, 58.2, 60.2, 72.2, 127.1,
127.2, 128.3, 128.4 (2C), 128.5, 129.1, 135.3, 136.9, 137.0, 137.4,
138.5, 139.7, 140.4, 171.9 ppm; HRMS (EI): m/z: calcd for
C27H26O5Na: 453.1672 [M+Na]+; found: 453.1670.
Dimethyl 5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-4,7-diphenyl-1H-
indene-2,2(3H)-dicarboxylate (52): Starting from diyne 41
(100.0 mg, 0.028 mmol), the reaction afforded compound 52 as
a yellow oil (67.7 mg, 49% yield). 1H NMR (300 MHz, CDCl3): d=
0.87 (s, 6H), 3.48 (s, 6H), 3.67–3.70 (m, 8H), 7.29–7.52 (m, 10H),
7.59 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): d=21.9, 31.6, 40.5,
40.8, 53.0, 60.2, 73.3, 126.6, 127.0, 127.7, 128.4, 128.7, 129.0, 133.7,
136.7, 138.8, 139.1, 140.8, 142.1, 142.3, 172.1 ppm; HRMS (ESI): m/z:
calcd for C30H31O6BNa: 521.2106 [M+Na]+; found: 521.2108.
Acknowledgements
This work was supported by the Ministꢀre de l’Education Supꢁr-
ieure et de la Recherche (MESR) and the Centre National de la Re-
cherche Scientifique (CNRS). M.E.-Z. thanks GSK and CNRS, and
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.
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Keywords: alkynes
systems · iridium
· cycloaddition · diynes · fused-ring
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Received: January 26, 2013
Published online on && &&, 0000
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 7
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These are not the final page numbers!