Synthesis of 2-bromo-1-aryl-1H-indenes via a Ag(I) promoted domino 2π-electrocyclic ring-opening/4π-electrocyclization reaction of 1,2-diaryl substituted gem-dibromocyclopropanes

Article abstract of DOI:10.1016/j.tet.2013.07.086

2-Bromo-1-aryl substituted indenes can be synthesized from 1,2-diaryl substituted gem-dibromocyclopropanes via a domino reaction sequence. The cascade reaction involves silver(I) promoted ionization and 2π-disrotatory electrocyclic ring-opening, followed by a 4π-conrotatory electrocyclic ring closing reaction of the allylic carbocation intermediate. Reaction conditions utilize silver tetrafluoroborate (AgBF₄) in dichloroethane at 65 C. Selectivity effects for the electrocyclization were also studied. The 2-bromoindenes can be further functionalized using cross-coupling reactions, such as the Suzuki-Miyaura protocol. The alkene π-bond of the indenes can also be isomerized to give the thermodynamically more stable 2-bromo-3-aryl-1H-indene isomers using triethylamine in dichloromethane at room temperature.

Full text of DOI:10.1016/j.tet.2013.07.086

Tetrahedron 69 (2013) 8758e8768
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of 2-bromo-1-aryl-1H-indenes via a Ag(I) promoted
domino 2p-electrocyclic ring-opening/4p-electrocyclization
reaction of 1,2-diaryl substituted gem-dibromocyclopropanes
*
Gregory Rosocha, Robert A. Batey
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 May 2013
Received in revised form 23 July 2013
Accepted 25 July 2013
Available online 1 August 2013
2-Bromo-1-aryl substituted indenes can be synthesized from 1,2-diaryl substituted gem-di-
bromocyclopropanes via a domino reaction sequence. The cascade reaction involves silver(I) promoted
ionization and 2p-disrotatory electrocyclic ring-opening, followed by a 4p-conrotatory electrocyclic ring
closing reaction of the allylic carbocation intermediate. Reaction conditions utilize silver tetra-
fluoroborate (AgBF4) in dichloroethane at 65 ꢀC. Selectivity effects for the electrocyclization were also
studied. The 2-bromoindenes can be further functionalized using cross-coupling reactions, such as the
Keywords:
SuzukieMiyaura protocol. The alkene
p-bond of the indenes can also be isomerized to give the ther-
Electrocyclization
Electrocyclic ring-opening
Cationic cyclization
Indene
modynamically more stable 2-bromo-3-aryl-1H-indene isomers using triethylamine in dichloromethane
at room temperature.
Ó 2013 Published by Elsevier Ltd.
Cyclopropane
1. Introduction
temperature. Selectivity outcomes reflect the inductive and meso-
meric effects of the substituents for an electrophilic aromatic sub-
Indenes are important structural motifs that are found in a variety
of biologically active molecules,1 in ligands useful for catalysis, and as
precursors for many chemical products.2 There are numerous strat-
egies that can be used to synthesize indenes, and related indanes,
most commonly involvingeithercyclization orannulation to formthe
five-membered ring of the indene using cationic or transition metal
catalyzed reactions.3 Another method that has been utilized is the
ionization of 1,3-biphenyl allyl alcohols in acidic media4 originally
reported by Pittman5 and Olah.6 In this approach allylic cations are
generated, which then undergo cyclization in a process, which can be
viewed as an intramolecular FriedeleCrafts reaction,7 but which is
perhaps more accurately described as an electrocyclization reaction.
In the case of a 1,3-diaryl substituted allylic cation cyclization must
occur via initial isomerization of the ‘W’ shaped cation 1 into an ‘U’-
shaped shaped cation 2 followedbycyclization and proton lossto give
the indenes 3 (Scheme 1). For differentially substituted 1,3-biaryl
systems the issues that control from which ring electrocyclization
occurs, to give either 3a or 3b have recently been elaborated.8 The
allylic carbocations were generated from the corresponding alcohols
and boron trifluoride diethyl etherate in dichloromethane at room
stitution mechanism, while a computational study supports a 4
conrotatory electrocyclization pathway.
p-
R3
+
R3
R1
R1
3a
2a
R2
R2
R3
+
+
R1
R2
1
R3
R3
3b
R2
R2
2b
R1
R1
Scheme 1. Synthesis of substituted indenes via cationic cascade cyclization pathway.
In the previous study the presence of a substituent was found to
be essential for the electrocyclization of the allylic cations, since in
* Corresponding author. Tel.: þ1 416 978 5059; fax: þ1 416 978 6033; e-mail
address: rbatey@chem.utoronto.ca (R.A. Batey).
0040-4020/$ e see front matter Ó 2013 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tet.2013.07.086

G. Rosocha, R.A. Batey / Tetrahedron 69 (2013) 8758e8768
8759
its absence the ‘W’-cation is favored from which cyclization cannot
occur.8 As an extension of these studies we envisaged an analogous
approach to the synthesis of 2-bromo-1-aryl substituted indenes. In
principle, as for the previous study an approach based upon the
ionization of appropriately substituted allylic alcohols (i.e., 2-
bromo-1,3-biaryl substituent pattern) could be used. However,
(Table 1). The stilbenes were obtained with excellent trans-
selectivity (ꢁ98:2 dr) consistent with previous reports using the
McMurry coupling reaction.16
Table 1
Symmetrical stilbene synthesis using the McMurry coupling reaction
O
a more expeditious route was suggested by the known 2p-elec-
TiCl4 (1.2 eq)
Zn (2.4 eq)
R
trocyclic ring-opening reactions of gem-dihalocyclopropanes to
give products resulting from reaction of intermediate 2-bromo al-
lylic cations. The use of gem-dihalocyclopropanes in organic syn-
thesis has been documented by many researchers,9 including
thermal openings.10 West has reported the domino ring-opening of
gem-dichlorocyclopropanes followed by conrotatory Nazarov cy-
clization to give chlorocyclopentenones, as well as subsequent
FriedeleCrafts reaction to generate benzohydrindenones.11 The
thermal reactions (139 ꢀC, m-xylenes) of some monophenyl-
substituted dibromocyclopropanes have been reported to give
mixtures of indenes and dienes.12 In addition, gem-dicyanoethanes
in the presence of samarium have also been used to synthesize
indenes as reported by Zhang.13 Banwell and co-workers have
utilized ring-opening of gem-dihalocyclopropanes followed by
nucleophilic trapping of the allylic cations for natural product
synthesis.14
H
R
R
THF 0.6M
0-85 °C
9a-f
Entry
R
Timea (h)
E/Zb
Yield (%)
Stilbene
1
2
3
4
5
6
o-Me
p-Me
o-Cl
p-Cl
m-OMe
3,4-OMe
2
2.5
2
1.5
20
2
ꢁ98:2
ꢁ98:2
ꢁ98:2
ꢁ98:2
ꢁ98:2
ꢁ98:2
87
85
77
81
84
88
9a
9b
9c
9d
9e
9f
a
Reaction was stirred at 0 ꢀC during addition of TiCl4 and aldehyde for 30 min
prior to reflux.
b
E/Z ratio determined by 1H NMR integration of purified products.
Unsymmetrical stilbenes 10 were synthesized either using Heck
or WittigeHorner reactions. Heck reaction of styrene and aryl io-
dides 11 using palladium acetate and triethylamine in acetonitrile
afforded stilbenes 10aeg in generally high yields and isolated dr’s
favoring the trans-isomers (Table 2). Alternatively, a more conve-
nient WittigeHorner reaction using benzyl phosphonate ester and
aryl aldehydes could also be used affording the stilbenes in high
yields and isolated dr’s (Table 3).
Accordingly, we were interested in investigating a pathway
based upon a domino 2
p-electrocyclic ring-opening of cyclopro-
panes 4 followed by a 4
p
-electrocyclic ring-closure to give the
product indenes 8 (Scheme 2). Of particular interest were whether
similar substituent effects would be observed to those of our pre-
vious study. The overall synthetic approach would allow for rapid
formation of highly substituted indenes in a two-step protocol,
involving dibromocyclopropanation of readily accessible stilbenes,
followed by the subsequent domino cascade reaction.15 The re-
sultant CeBr functionality of the product indenes could then serve
as a valuable synthetic handle for late stage diversification through
reactions, such as transition metal catalyzed couplings. We now
report the results of this study and briefly demonstrate the syn-
thetic utility of the products.
Table 2
Unsymmetrical stilbene synthesis using the Heck reaction
I
R
(1.0 eq)
R
11a-f
Pd(OAc)2 (10 mol%)
10a-f
(3.0 eq)
NEt3 (6.0 eq) MeCN (8.0 M)
85 °C
Br
+
Br
Br
Entry
Aryl iodide
R
Time (h)
E/Za
95:5
85:15
95:5
ꢁ98:2
ꢁ98:2
ꢁ98:2
Yield (%)
Stilbene
– Br–
1
2
3
4
5
6
11a
11b
11c
11d
11e
11f
o-Me
p-Me
3,5-Me
m-NO2
p-NO2
m-OMe
24
20
24
22
46
72
63
24
53
99
87
97
10a
10b
10c
10d
10e
10f
4
5
R1
R2
R1
R2
Br
2π-disrotatory
4π-conrotatory
electrocyclization
+
electrocyclic
ring-opening
R1/R2
a
E/Z ratio determined by 1H NMR integration of purified products.
6
R1/R2
– H+
+
Br
Br
R1/R2
R1/R2
H
Table 3
R1/R2
R1/R2
7
8
Unsymmetrical stilbene synthesis using the WittigeHorner reaction
PO(OEt)2
O
Scheme 2. Synthesis of 2-bromoindenes 8 via cascade electrocyclic ring-opening/cy-
clization pathway.
R
(1.0 eq)
H
R
KOtBu (1.1 eq)
Toluene (0.10 M)
Reflux
10a-b, 10d, 10f
2. Results and discussion
The synthesis of symmetric and unsymmetric 1,2-diaryl gem-
dihalocyclopropanes was accomplished using a two-step protocol
involving olefination followed by cyclopropanation. The requisite
stilbenes were synthesized using three different methods. For
symmetrically substituted stilbenes 9aef McMurry reaction of aryl
aldehydes in refluxing THF with Zn metal and TiCl4 was employed
Entry
R
Time (h)
E/Za
Yield (%)
Stilbene
1
2
3
4
o-Me
p-Me
m-NO2
m-OMe
7
24
6
ꢁ98:2
ꢁ98:2
ꢁ98:2
ꢁ98:2
64
58
quant
69
10a
10b
10d
10f
6
a
E/Z ratio determined by 1H NMR integration of purified products.

8760
G. Rosocha, R.A. Batey / Tetrahedron 69 (2013) 8758e8768
Table 5
There are various reports in the literature of procedures that
can be applied for dihalocyclopropanation reactions.9,17 The use
of a modified procedure based on a method reported by West
was found to be the most efficient for the formation of the gem-
Optimization of conditions suitable for the 2
4a into 8a
pe4
p
electrocyclic cascade reaction of
Br
Br
dibromocyclopropanes
4
in moderate to excellent yields.11
West’s method utilizes benzyltriethylammonium bromide and
benzyltriethylammonium chloride in solvent with the corre-
sponding haloform and stilbene. Our modification involved
more concentrated conditions of the stilbene with bromoform
as the solvent (0.12 M) to give the gem-dibromocyclopropanes
4aem (Table 4). Reaction of the unsubstituted stilbene 12 pro-
vided the gem-dibromocyclopropane 4a in 77% yield (Table 4,
entry 1). A similar reaction using chloroform as solvent afforded
the corresponding gem-dichlorocyclopropane in 81% yield. In
general, reaction of alkyl-substituted stilbenes led to moderate
to good product yields, while symmetrical ortho- and para-
chloro substituted compounds were obtained in moderate
yields. Reaction of the more electron deficient m-NO2 and p-NO2
substituted stilbenes 10d and 10e, provided the cyclo-
propanated products in 75% and 95% yields, respectively (Table
4, entries 11 and 12). Reaction of the more electron-rich
methoxy substituted symmetrical stilbenes occurred in lower
yields, perhaps reflecting the instability of the products (Table 4,
entries 6 and 7).
Br
4a
8a
Entry
Solvent
Additive
Temp
(ꢀC)
Time
(h)
Isolated
yield (%)
1
2
3
4
5
6
7
Toluene (0.07 M)
THF (0.07 M)
THF (0.07 M)
Toluene (0.07 M)
DCE (0.07 M)
DCE (0.07 M)
DCE (0.07 M)
d
Reflux
rt
60
48
72
72
120
24
1
N.R.
17
77
55
<5
73
AgBF4 (4.0 equiv)
AgBF4 (4.0 equiv)
AgBF4 (4.0 equiv)
AgBF4 (2.0 equiv)
AgBF4 (2.0 equiv)
AgBF4 (2.0 equiv)
60
rt
60
60
2.5
95
The optimized conditions were then applied to the domino
indene formation reaction using the symmetrical gem-dibromo-
cyclopropanes and reaction times of 4e48 h (Table 6). Reaction of
the m-Me substrate 4b was accomplished with poor conversion
under these conditions. However, reaction for 48 h afforded the
product as an inseparable 1:1 mixture of the 5-methyl and 7-
methyl substituted indenes 8b-A and 8b-B, respectively, in 90%
yield (Table 6, entry 1 and Fig. 1). Reaction of the p-Me substrate 4c
occurred in good yields after 4 h (Table 6, entry 2). Interestingly,
reaction of the chloro-substituted precursors 4d and 4e required
the use of more silver tetrafluoroborate salt (4.0e5.0 equiv) to
achieve full conversion (Table 6, entries 3e4). Reaction of the more
electron-rich m-OMe substrate 4f led to inseparable product
mixtures.
Table 4
Cyclopropanation of stilbenes to gem-dihalocyclopropanes 4
Br
Br
CHBr3 (0.12 M)
NaOH (sat'd aq.)
R2
BnEt3N+Cl– (20 mol%)
rt, 2–24h
R1
R2
R1
9a-f, 10a-f
12
4a-m
Entry Stilbene R1
R2
Time (h) dra
(trans:cis) (%)
Yield Product
1
2
3
4
5
6
7
8
12
9a
9b
9c
9d
9e
9f
10a
10b
10c
10d
10e
10f
H
H
19
6
6
24
4
5
ꢁ98:2
ꢁ98:2
ꢁ98:2
ꢁ98:2
ꢁ98:2
90:10
d
77
91
78
60
66
73
ꢂ2b
61
42
55
75
95
73
4a
4b
4c
4d
4e
4f
4g
4h
4i
m-Me
p-Me
o-Cl
p-Cl
m-OMe
3,4-OMe 3,4-OMe 2e24
o-Me
p-Me
3,5-Me
m-NO2
p-NO2
m-OMe
m-Me
p-Me
o-Cl
p-Cl
m-OMe
Table 6
2pe4p Electrocyclic cascade reaction of symmetric gem-dibromocyclopropanes 4
into 2-bromoindenes 8
Br
Br
AgBF4 (2.0 eq)
DCE, 65 °C
H
H
H
H
H
H
3
24
7
18
4
19
ꢁ98:2
ꢁ98:2
ꢁ98:2
ꢁ98:2
ꢁ98:2
ꢁ98:2
Br
9
4
8
10
11
12
13
4j
4k
4l
R
R
R
R
4m
a
dr determined by 1H NMR integration of purified product.
Entry
R
Substrate
AgBF4 (equiv)
Time (h)
Yield (%)
Indene
b
Minor amounts obtained as determined by 1H NMR and MS analysis.
1
2
3
4
m-Me
p-Me
o-Cl
4b
4c
4d
4e
2
2
5
4
48
4
48
5
quant
86
93
8ba
8c
8d
8e
p-Cl
91
Optimization of reaction conditions suitable for the ring-
a
Product 8b was obtained as a 1:1 mixture of the 8b-A and 8b-B regioisomers
opening/closure cascade were evaluated using the 1,2-
diphenyl substrate 4a (Table 5). Whereas thermal conditions
failed to give product (Table 5, entry 1), the use of silver salts,
and in particular silver tetrafluoroborate (AgBF4) to initiate
carbocation formation and subsequent reaction to give 8a was
more successful (Table 5, entries 2e7). Reaction in THF afforded
a low 17% yield of 8a after 3 days at room temperature, while
similar reaction at 60 ꢀC afforded an improved 77% yield. The
use of toluene as solvent was less successful, whereas 1,2-
dichloroethane solvent gave the product in excellent yields
after 2.5 h using just 2.0 equiv of AgBF4 at 60 ꢀC (Table 5, entry
7). These conditions were optimal providing the indene 8a in
95% yield on a one hundred milligram scale and 85% on a four-
gram scale.
(See Fig. 1).
Me
Br
Br
Me
8b–B
8b–A
Me
Me
(1 : 1)
Fig. 1. The two m-Me substituted indene isomers 8b-A and 8b-B obtained in the
electrocyclic cascade reaction of 4b.

G. Rosocha, R.A. Batey / Tetrahedron 69 (2013) 8758e8768
8761
Table 7
In the case of cyclization of the unsymmetrical dibromocyclo-
2pe4p Electrocyclic cascade reaction of unsymmetrical gem-dibromocyclopropanes
propane substrates 4 a selectivity issue arises for which aryl ring
participates in the electrocyclization reaction (Scheme 3). Thus, 2p-
disrotatory electrocyclic opening of 4 can lead to the ‘U’-shaped
cations 6-A and 6-B, which under the reaction conditions could
Br
Br
R
8-B
Br
Br
8-A
equilibrate with each other. 4p-Conrotatory electrocyclization of 6-
R
AgBF4 (2.0 eq)
DCE, 65 °C
A can lead to 8-A, whereas electrocyclization of 6-B can lead to the
isomeric indene 8-B, which differs in the positioning of the R1 and
4
2 substituents on the indene ring or the 1-aryl ring.
R
R
Br
Br
R
13-B
Br
Br
13-A
R
Entry Substrate
R
Time (h) Ratio (8-A:8-B:13-A:13-B)a Yield (%)
R2
R1
4
1
2
3
4
5
4h
4i
4j
4k
4l
o-Me
p-Me
3,5-di-Me 16
m-NO2
p-NO2
6
75:25:0:0
55:45:0:0
25:75:0:0
90:0:10:0
90:0:10:0
74
97
92
75
93
2π-disrotatory
electrocyclic
ring-opening
2π-disrotatory
electrocyclic
ring-opening
21
Ag(I)
Ag(I)
22
12
Br
Br
a
+
Determined by 1H NMR analysis of the crude products.
+
R2
R1
6-A
6-B
R1
We next set out to develop derivatization methods based upon
R2
4π-conrotatory
4π-conrotatory
reactions of the CeBr bond of the indenes. 2-Bromo-1-phenyl-1H-
indene 8a was evaluated as a model substrate. Several Suzu-
kieMiyaura cross coupling protocols were attempted for 8a and
phenylboronic acid. A modification of the procedure reported by
O’Shea and Kurata18 using 0.01 mol % Pd(PPh3)4, 1.0 equiv of the
boronic acid, and 4.0 equiv of K2CO3 in a refluxing 4:1 DME/H2O
solvent mixture led to an 80% yield of the isomerized indene 14a
(Table 8, entry 1). Several different arylboronic acids were reacted
with 8a under the same conditions to give the cross-coupled
electrocyclization
electrocyclization
+
+
H
Br
Br
R2
R1
H
7-A
7-B
R1
R2
– H+
– H+
Br
Br
Table 8
R2
R1
8-A
8-B
SuzukieMiyaura cross coupling reactions of 8a
B(OH)2
R1
R2
R
R
(1.3 eq)
Scheme 3. Electrocyclization cascade mechanism leading to the formation of isomeric
indenes 8-A and 8-B.
Br
Pd(PPh3)4 (10 mol%)
K2CO3 (4.0 eq)
DMF/H2O (4:1)
reflux (0.75-5 h)
Reaction of the unsymmetrical gem-dibromocyclopropane
substrates 4hem led to the formation of the anticipated 2-bromo-
1-aryl-1H-indenes 8-A and 8-B, and for reaction of the more
electron-deficient substrates the corresponding 2-bromo-3-aryl-
1H-indenes 13-A and 13-B were also formed (Table 7). Reaction of
the o-Me substrate 4h gave a 3:1 ratio of indenes 8h-A and 8h-B
with a product yield of 74% (Table 7, entry 1). Reaction of the p-Me
substrate 4i yielded a 55:45 ratio of indene 8i-A and 8i-B in
a combined yield of 97% (Table 7, entry 2). Reaction of the 3,5-
dimethyl substrate 4j afforded a 1:3 mixture of indene products
8j-A and 8j-B in 92% yield (Table 7, entry 3). The selectivities ob-
tained for each of these reactions are consistent with previous re-
sults on electrocyclization selectivities.8 Reaction of both the m-
NO2 and p-NO2 substrates 4k and 4l resulted in exclusive electro-
cyclization occurring through the more electron-rich phenyl ring to
give mixtures of the indenes and isomerized indenes 8k-A/13k-A
and 8l-A/13l-A, respectively (Table 7, entries 4 and 5). The forma-
tion of isomerized products and the highly selective initial elec-
trocyclization through the phenyl ring are consistent with previous
studies.8 Reaction of 4m led to an inseparable mixture of isomers
(predominantly compound 8m-B) in 90% yield. While the selec-
tivities obtained in these examples are consistent with equilibra-
tion between cations 6-A and 6-B occurring prior to cyclization, the
alternative possibility of reaction selectivity reflecting the initial
ring-opening of 4 cannot be ruled-out.
8
14a-f
Entry
1
ArB(OH)2 (1.1e1.3 equiv)
Time (h)
4
Yield (%)
82
Indene
14a
2
5
72
14b
3
4
4
1
79
87
14c
14d
5
6
0.75
90
78
14e
14f
2

8762
G. Rosocha, R.A. Batey / Tetrahedron 69 (2013) 8758e8768
Cl
indene products 14 (Table 8, entries 2e7). In each of the examples
the cross-coupled products were obtained solely as the isomerized
species 14. The formation of the isomerized compounds 14 reflects
both the greater thermodynamic stability of these products, which
incorporate a tetra-substituted and more highly conjugated alkene,
as well as the ease with which base catalyzed isomerization occurs
under the reaction conditions. The yields were generally very high
using both electron-rich and electron-deficient arylboronic acids.
Cross-coupling of phenyl acetylene with 2-bromo-1-phenyl
indene 8a gave unsatisfactory results using several literature pro-
tocols,19 but reaction using phenyl acetylene (1.2 equiv), PdCl2
(10 mol %), and PPh3 (20 mol %) in refluxing water, with pyrrolidine
(for 4 h) afforded the isomerized cross-coupled indene 15a in 80%
yield under copper-free conditions (Scheme 4). Reaction of 8a and
propargyl alcohol was unsuccessful under similar conditions.
However, reaction using piperidine (2.0 equiv) in an acetone/water
mixture at 60 ꢀC for 4 h afforded 15b in 32% yield. Reaction at room
temperature for 45 h using piperidine afforded a mixture of 15b in
24% yield and the reduced product 1-phenylindene 16 in 25% yield.
Br
Br
Br
Cl
Cl
O2N
13k-A (70%)
Cl
13e (94%)
13d (quant)
Br
COOEt
Cl
NO2
13l-A (90%)
21 (78%)
Fig. 2. Products resulting from base-catalyzed isomerization using triethylamine.
While there are various mechanisms that are known for the
isomerization of indenes, the base promoted reaction conditions
and substituent effects for isomerization are consistent with
a deprotonation/protonation mechanism. Deprotonation of the
acidic hydrogen at the 1-position of the indene 3 to give the aro-
matic indenyl anion 22 is then followed by protonation to give the
more thermodynamically stable isomerized indene 23 (Scheme 6).
Ph
(1.2 eq)
Br
Ph
PdCl2 (10 mol%)
PPh3 (20 mol%)
pyrrolidine (2.0 eq)
water, 120 °C, 4 h
15a (80%)
8a
CH2OH
(1.2 eq)
+ H+
– H+
CH2OH
R3
R3
R3
PdCl2 (5 mol%)
PPh3 (10 mol%)
piperidine (2.0 eq)
water/acetone (0.10 M)
60 °C (4 h) or rt (45 h)
–
R1
R1
R1
R2
R2
23
R2
15b
16 (25% at rt)
3
22
(32% at 60 °C,
24% at rt)
Scheme 6. Mechanism of base catalyzed indene isomerization.
Scheme 4. Alkyne cross-coupling reaction of 8a.
3. Conclusions
In summary, 2-bromo-substituted indenes have been synthe-
sized via a domino electrocyclic cascade reaction of gem-dibro-
mocyclopropanes. The reaction is promoted by silver
The observation of isomerized indenes 13 as side products and
the formation of the cross-coupled products in isomerized form
(Tables 7 and 8 and Scheme 4) suggested that a general set of
conditions could be established for isomerization of the indenes.
Various base catalyzed conditions were evaluated using substrate
8a to form 13a. Reactions using potassium phosphate (1.4 equiv) in
DMA solvent for 72 h at room temperature afforded 13a in 68%
yield. Reaction of 8a with triethylamine (1.5 equiv) in dichloro-
methane at room temperature for 2 h afforded the isomerized
product 13a in 85% isolated yield (Scheme 5). Similar reaction of the
indenes 178 and 188 for 24 h afforded the corresponding isomerized
products 19 and 20 in 89% and 85% isolated, respectively. Applica-
tion of the same conditions to the isomerizations of 4d, 4e, 4k, and
4l led to the formation of the indenes 13d, 13e, 13k-A, and 13l-A in
good to excellent yields (Fig. 2). The ester substituted compound 21
was formed in a similar manner in 78% yield.
tetrafluoroborate facilitating initial 2
ring-opening to form an allylic carbocation. This species then un-
dergoes a 4 -conrotatory electrocyclization to form the indene
p-disrotatory electrocyclic
p
ring. Selectivity for the electrocyclization parallel those of our
previous study, which in general can be rationalized based upon
substituent effects for electrophilic aromatic substitution. The
product indenes are useful intermediates, and the CeBr function-
ality can be used as a synthetic handle for cross-coupling and
isomerization reactions.
4. Experimental section
4.1. General
The following general experimental applies for all experiments
described in this paper. Unless otherwise stated, all reactions were
performed under nitrogen. All reagents, unless otherwise stated
were used as received. Reaction solvents were distilled under an
inert atmosphere before use and transferred via syringe using
standard techniques unless otherwise stated. Dichloromethane was
distilled from CaH2 under nitrogen. All other solvents were ob-
tained as ACS grade (or better). All reagents, unless otherwise
stated, were used as received (Aldrich, Fischer Scientific Ltd., or
Lancaster). FT-IR spectra were obtained on a PerkineElmer Spec-
Et3N (1.5 eq)
R
R
CH2Cl2, rt, 2-24 h
8a (R = Br)
17 (R = Me)
13a (R = Br) 85%
19 (R = Me) 89%
20 (R = COOEt) 85%
18 (R = COOEt)
Scheme 5. Base promoted isomerization of indenes.
trum 1000, with samples loaded as films on NaCl plates. 1H and 13
C

G. Rosocha, R.A. Batey / Tetrahedron 69 (2013) 8758e8768
8763
NMR spectra were obtained on Varian Mercury 300 or Unity 400
spectrometers as solutions in deuterated solvents (CDCl3 were
obtained from Cambridge Isotope Labs) and referenced to their
corresponding solvent peaks (i.e., CHCl3 7.26 ppm for proton res-
onances, and CHCl3, 77.23 ppm for carbon resonances). Chemical
Shifts are expressed in parts per million values. Peak multiplicities
are designated by the following abbreviations: s, singlet; d, dou-
blet; t, triplet; q, quartet; dd, doublet of doublets; dt, doublet of
triplets; m, multiplet; J, coupling constant in Hertz. Low and high-
resolution electron ionization (EI) mass spectra were measured
using a GCT Premier time-of-flight mass spectrometer (Waters
Corporation, Milford, MA). Calculated exact masses and molecular
formula determinations were generated using the data processing
software Mass Lynx version 4.1 (Waters). Waters software does not
consider the mass of the electron at any point in the calibration of
the instrument, measurement of high-resolution masses or calcu-
lation of exact masses; therefore, all measured and calculated
HRMS masses are given as neutral species (M) and not ions (Mþ).
Melting points were obtained on a Fisher-Johns melting point ap-
paratus and are uncorrected. Flash column chromatography on
layer was dried over Na2SO4 gravity filtered, and evaporated in
vacuo. Purification using flash column chromatography (ethyl ac-
etate/hexanes) afforded the product stilbene 10.
4.5. General dibromocyclopropanation procedure for syn-
thesis of 4
To a stirred solution of stilbene 9/10b (2.40 mmol) in bromoform
(20.0 mL, 0.12 M) was added triethylbenzylammonium chloride
(109 mg, 0.480 mmol). An equal volume of a saturated aqueous
solution of concentrated sodium hydroxide was added dropwise.
The reaction was stirred at room temperature until full reaction
conversion was achieved (as monitored by 1H NMR analysis). The
reaction mixture was quenched with water (150.0 mL) and stirred
at room temperature for 15 min. The reaction mixture was washed
with water (5ꢃ100 mL) and dichloromethane (3ꢃ75 mL). The or-
ganic phase was evaporated under high vacuum to remove bro-
moform. Purification using flash column chromatography
(hexanes) afforded cyclopropane 4.
ꢀ
silica gel (60 A, 230e400 mesh, low acidity, obtained from Silicycle
Inc.) Analytical thin-layer chromatography (TLC) was performed on
pre-coated aluminum-backed silica gel plates (Alugram SIL/G/
UV254 purchased from Silicycle Inc.), visualized with a UV lamp
(254 nm), potassium permanganate, phosphomolybdic acid, and
vanillin. Spectral data are provided for all new compounds and for
compounds that lack full characterization in the literature.
4.6. General procedure for indene synthesis 8
To a stirred solution of gem-dibromocyclopropane 4 (7.50 mmol)
in 1,2-dichloroethane (120.0 mL) at 65 ꢀC was added silver tetra-
fluoroborate (2.91 g, 15.0 mmol). The reaction was heated for
4e48 h and then quenched with water (100 mL) and ethyl acetate
(100 mL). The reaction mixture was washed with water (3ꢃ75 mL),
brine (3ꢃ75 mL). The organic layer was dried over sodium sulfate,
filtered, and evacuated. Purification using flash column chroma-
tography (ethyl acetate/hexanes) was necessary in some cases.
4.2. McMurry reaction general procedure for stilbene 9
synthesis
To a stirred suspension of Zn powder (4.70 g, 71.9 mmol) in THF
(50.0 mL, 0.60 M) in a flame dried sealed tube at 0 ꢀC was added
TiCl4 (3.93 mL, 35.9 mmol) dropwise. The mixture was stirred at
4.7. General procedure for SuzukieMiyaura cross coupling for
synthesis of 14
0
ꢀC for 30 min and then aldehyde (29.9 mmol) was added. The
mixture was then refluxed for 24 h and then slowly quenched with
water (25 mL) at 0 ꢀC. The mixture was then extracted with CH2Cl2
(3ꢃ75 mL), and the combined organic extracts dried over sodium
sulfate, filtered, and evaporated in vacuo. Purification using flash
column chromatography (ethyl acetate/hexanes) afforded the
product stilbene 9.
A
solution of 2-bromo-1-phenyl indene 8a (150.0 mg,
0.555 mmol), arylboronic acid (0.833 mmol), and potassium car-
bonate (574 mg, 4.16 mmol) in dimethoxyethane (14.0 mL) was
stirred at room temperature for 10 min. Water (5.5 mL) was then
added, followed by palladium tetrakistriphenylphosphine (6.4 mg,
10 mol %), and the mixture was refluxed until the reaction was
complete as monitored by TLC analysis (0.75e5 h). The reaction
mixture was cooled to room temperature and quenched with water
(30 mL), ethyl acetate (100 mL) and washed with 1 M HCl
(3ꢃ25 mL), water (3ꢃ75 mL), and brine (3ꢃ50 mL). The organic
phase was dried with sodium sulfate, filtered, and evaporated in
vacuo. Purification using flash column chromatography (ethyl ac-
etate/hexanes) afforded the product indene 14.
4.3. Heck reaction general procedure for stilbene 10 synthesis
To a flame dried round bottom flask was added styrene (4.43 mL,
38.8 mmol), aryl iodide 11 (12.9 mmol), freshly distilled triethyl-
amine (10.7 mL, 77.5 mmol), Pd(OAc)2 (289 mg, 1.29 mmol), and
acetonitrile (2.0 mL). The mixture was heated at reflux under a ni-
trogen atmosphere until reaction was complete as monitored by
TLC analysis. The mixture was quenched with water (20 mL) and
HCl (25.0 mL, 1 M), extracted with CH2Cl2 (3ꢃ25 mL), dried over
sodium sulfate, and evaporated in vacuo. Purification using flash
column chromatography (ethyl acetate/hexanes) afforded the
product stilbene 10.
4.8. General procedure for alkyne trapping method for syn-
thesis of 15
A
solution of 2-bromo-1-phenyl indene 8a (100.0 mg,
0.369 mmol), propargyl alcohol (25.7
L, 0.443 mmol), triphenyl-
phosphine (9.7 mg, 0.036 mmol), palladium chloride (3.5 mg,
0.020 mmol), and piperidine (73 L, 0.738 mmol) in acetone
4.4. WittigeHorner general procedure for stilbene 10
synthesis
m
m
To
a
flame dried round flask was added aryl aldehyde
(3.8 mL) was stirred at room temperature for 10 min. Water
(3.0 mL) was added dropwise, and the reaction mixture heated at
60 ꢀC until reaction was complete as monitored by TLC analysis. The
reaction mixture quenched with water (3.0 mL), allowed to cool to
room temperature, and extracted with diethyl ether (3ꢃ25 mL).
The organic phase was dried with sodium sulfate, filtered, and
evaporated in vacuo. Purification using flash column chromatog-
raphy (ethyl acetate/hexanes) afforded the product indene 15.
(8.32 mmol) and toluene (83 mL), followed by dieth-
ylbenzylphosphonate (1.73 mL, 8.32 mmol). The reaction was stir-
red at room temperature for 20 min, and KOtBu (980 mg,
8.73 mmol) was added. The reaction was heated to reflux for 7 h
monitoring for the disappearance of the aryl aldehyde. The reaction
was quenched with water (50.0 mL) and ethyl acetate (75.0 mL) and
washed with water (3ꢃ75 mL) and brine (3ꢃ50 mL). The organic

8764
G. Rosocha, R.A. Batey / Tetrahedron 69 (2013) 8758e8768
4.9. General procedure for base promoted isomerization
(EIþ): m/z¼342 (4), 340 (7), 261 (8), 228 (31), 225 (100), 199 (3), 189
(53), 178 (3), 149 (3), 113 (3), 94 (8). HRMS (EIþ): m/z calcd for
C15H10Cl2Br [MꢄBr] 338.9343, found¼338.9349.
To a solution of 2-bromo-1-aryl indene (0.555 mmol) in
dichloromethane (5.50 mL) at room temperature was added trie-
thylamine (0.101 mL, 0.723 mmol) dropwise and the reaction stir-
red for 2e24 h until reaction was complete as monitored by 1H
NMR analysis. Water (25.0 mL) was added and the reaction mixture
stirred for 10 min, extracted with dichloromethane (3ꢃ25 mL),
dried over Na2SO4, and evaporated in vacuo to give the indene
products. Purification using flash column chromatography (ethyl
acetate/hexanes) was necessary in some cases.
4.10.6. 3,30-(3,3-Dibromocyclopropane-1,2-diyl)bis(methox-
ybenzene) 4f. Isolated by flash column chromatography (10e20%
EtOAc in hexanes) as a tan oil in 73% yield as a 90:10 mixture of cis
and trans isomers. IR (Thin Film): 3001, 2939, 2833, 1927, 1720,
1612, 1489, 1458, 1433, 1319, 1259, 1196, 1158, 1087, 1045, 995, 960,
870, 784, 733 cmꢄ1
.
1H NMR (300 MHz, CDCl3)
d
7.30 (2H, t,
J¼8.0 Hz), 7.26 (2H, t, J¼8.0 Hz), 7.11 (2H, m), 7.04 (2H, m), 3.84 (6H,
s), 3.82 (2H, s). 13C NMR (75 MHz, CDCl3)
d 159.8, 137.6, 129.7, 129.1,
4.10. Characterization data
121.4, 114.9, 55.4, 40.4, 36.6. LRMS (EIþ): m/z¼252 (8), 240 (100),
225 (18), 224 (12), 209 (48),197 (16),182 (20),177 (11),165 (93),153
(41), 102 (4), 77 (5). HRMS (EIþ): m/z calcd for C17H16O2Br [MꢄBr]
331.0334, found¼331.0331.
4.10.1. (3,3-Dibromocyclopropane-1,2-diyl)dibenzene 4a.12 Isolated
by flash column chromatography (5e10% EtOAc in hexanes) as
a light yellow opaque waxy solid in 77% yield. Mp¼52e54 ꢀC. IR
(Thin Film): 3064, 3028, 2904, 1602, 1496, 1446, 1086, 1041, 837,
4.10.7. 1-(2,2-Dibromo-3-phenylcyclopropyl)-2-methylbenzene
4h. Isolated by flash column chromatography (0e5% EtOAc in
hexanes) as a white crystalline solid in 61% yield. Mp¼62e63 ꢀC. IR
(Thin Film): 3062, 3028, 2944, 2920, 1584, 1602, 1496, 1458, 1447,
753, 693 cmꢄ1. 1H NMR (300 MHz, CDCl3)
d 7.38 (10H, m), 3.27 (2H,
s). 13C NMR (75 MHz, CDCl3)
d 136.2, 129.2, 128.7, 128.1, 40.3. LRMS
(EIþ): m/z¼274 (8), 271 (26), 195 (47), 191 (100), 189 (27), 165 (21),
115 (14), 94 (11), 63 (9).
1110, 1083, 1057, 1029, 914, 841, 790, 740, 713 cmꢄ1 1H NMR
.
(400 MHz, CDCl3) d 7.42e7.32 (5H, m), 7.30e7.25 (2H, m), 7.20e7.12
4.10.2. 3,30-(3,3-Dibromocyclopropane-1,2-diyl)bis(methylbenzene)
4b. Isolated by flash column chromatography (5% EtOAc in hex-
anes) as a tan oil in 91% yield IR (Thin Film): 3031, 2995, 3917, 1519,
1447, 1413, 1377, 1220, 1178, 1124, 1065, 1018, 907, 856, 817,
(2H, m), 3.27 (1H, d, J¼7.0 Hz), 3.12 (1H, d, J¼7.0 Hz), 2.52 (s, 3H). 13C
NMR (75 MHz, CDCl3) d 139.4, 136.4, 135.7, 130.3, 129.2, 128.8, 128.3,
128.1, 128.1, 126.3, 40.2, 40.0, 37.1, 20.6. LRMS (EIþ): m/z¼288 (9),
285 (58), 209 (74), 206 (100), 191 (45), 189 (21), 165 (14), 128 (22),
102 (9), 91 (16), 77 (11), 63 (9). HRMS (EIþ): m/z calcd for C16H14Br
[MꢄBr] 285.0279, found¼285.0282.
708 cmꢄ1. 1H NMR (400 MHz, CDCl3)
d
7.27 (2H, dd, J¼7.5, 7.5 Hz),
7.20e7.14 (6H, m), 3.25 (2H, s), 2.38 (6H, m). 13C NMR (75 MHz,
CDCl3) d 138.3, 136.1, 129.9, 128.8, 128.5, 126.1, 40.2, 37.2, 21.7. LRMS
(EIþ): m/z¼302 (2), 299 (14), 220 (48), 219 (100), 205 (34), 203 (18),
189 (8), 165 (3), 128 (5), 86 (7), 77 (3). HRMS (EIþ) m/z calcd for
C17H16Br [MꢄBr] 299.0435, found 299.0443.
4.10.8. 1-(2,2-Dibromo-3-phenylcyclopropyl)-4-methylbenzene
4i.20 Isolated by flash column chromatography (0e5% EtOAc in
hexanes) as a light yellow oil in 42% yield. 1H NMR (400 MHz,
CDCl3)
d
7.44e7.35 (5H, m), 7.27 (2H, d, J¼8.0 Hz), 7.21 (2H, d,
4.10.3. 4,40-(3,3-Dibromocyclopropane-1,2-diyl)bis(methylbenzene)
4c. Isolated by flash column chromatography (5% EtOAc in hex-
anes) as a white crystalline solid in 78% yield. Mp¼137e139 ꢀC. IR
(Thin Film): 3041, 3005, 2917, 1517, 1450, 1377, 1119, 102, 1021, 905,
J¼8.0 Hz), 3.21 (2H, s), 2.29 (3H, s). 13C NMR (75 MHz, CDCl3)
d
137.8, 136.2, 133.1, 129.3, 129.1, 128.9, 128.6, 128.0, 40.2, 40.0, 37.3,
21.4.
863, 807, 696 cmꢄ1
.
1H NMR (300 MHz, CDCl3)
d
7.26 (4H, d,
4.10.9. 1-(2,2-Dibromo-3-phenylcyclopropyl)-3,5-dimethylbenzene
4j. Isolated by flash column chromatography (10e20% EtOAc in
hexanes) as a clear oil in 55% yield. IR (Thin Film): 3086, 3060, 3028,
2916, 2946, 2862, 1603, 1497, 1447, 1376, 1334, 1156, 1107, 1083,
J¼8.0 Hz), 7.20 (4H, d, J¼8.0 Hz), 3.19 (2H, s), 2.37 (6H, s). 13C NMR
(75 MHz, CDCl3)
d 137.8, 133.2, 129.3, 129.0, 40.0, 37.7, 21.4. LRMS
(EIþ): m/z¼302 (2), 299 (14), 298 (6), 220 (48), 219 (100), 205 (34),
202 (18), 189 (8), 165 (3), 128 (5), 89 (4), 77 (3). HRMS (EIþ) m/z
calcd for C17H16Br [MꢄBr] 299.0435, found 299.0449.
1056, 1030, 1001, 953, 908, 830, 850, 771, 742 cmꢄ1 1H NMR
.
(400 MHz, CDCl3)
d
7.37 (5H, m), 6.99 (3H, s), 3.23 (1H, d, J¼9.0 Hz),
3.19 (1H, d, J¼9.0 Hz), 2.35 (6H, s). 13C NMR (75 MHz, CDCl3)
d 138.2,
4.10.4. 2,20-(3,3-Dibromocyclopropane-1,2-diyl)bis(chlorobenzene)
4d. Isolated by flash column chromatography (10e20% EtOAc in
hexanes) as a white crystalline solid in 60% yield. Mp¼124e125 ꢀC.
IR (Thin Film): 3072, 2995, 3015, 1592, 1568, 1475, 1434, 1279, 1264,
1212, 1132, 1065, 1057, 1034, 954, 874, 838, 752, 727, 706 cmꢄ1. 1H
136.3, 135.9, 129.7, 129.1, 128.6, 128.0, 126.9, 40.2, 40.2, 37.1, 21.5.
LRMS (EIþ): m/z¼302 (8), 299 (61), 243 (4), 220 (100), 219 (92), 205
(53), 195 (58), 189 (19), 178 (17), 165 (12), 128 (8), 115 (18), 84 (23),
63 (8). HRMS (EIþ): m/z calcd for C17H16Br [MꢄBr] 299.0435,
found¼299.0431.
NMR (300 MHz, CDCl3)
d
7.52 (2H, dd, J¼7.5, 1.5 Hz), 7.32 (2H, ddd,
J¼7.5, 7.5, 2.0 Hz), 7.27 (2H, ddd, J¼7.5, 7.5, 1.5 Hz), 7.22 (2H, dd,
4.10.10. 1-(2,2-Dibromo-3-phenylcyclopropyl)-3-nitrobenzene
4k. Isolated by flash column chromatography (0e10% EtOAc in
hexanes) as a light yellow oil in 75% yield. IR (Thin Film): 3063,
3030, 1724, 1603, 1581, 1496, 1449, 1349, 1219, 1145, 1095, 963, 904,
J¼7.5, 1.5 Hz), 3.32 (2H, s). 13C NMR (75 MHz, CDCl3)
d 136.8, 134.9,
129.8, 129.7, 129.5, 127.1, 39.5, 35.2. LRMS (EIþ): m/z¼344 (2), 340
(39), 338 (12), 262 (61), 260 (100), 259 (26), 227 (24), 225 (93), 189
(46), 178 (4), 125 (4), 94 (19). HRMS (EIþ): m/z calcd for C15H10Cl2Br
[MꢄBr] 338.9343, found¼338.9340.
826, 803, 748 cmꢄ1 1H NMR (300 MHz, CDCl3)
. d 8.23 (1H, d,
J¼1.5 Hz), 8.22 (1H, m), 7.60 (1H, ddd, J¼8.0, 1.0, 1.0 Hz), 7.62e7.58
(1H, m), 7.46e7.36 (5H, m), 3.28 (2H, s). 13C NMR (75 MHz, CDCl3)
4.10.5. 4,40-(3,3-Dibromocyclopropane-1,2-diyl)bis(chlorobenzene)
4e. Isolated by flash column chromatography (0e5% EtOAc in
hexanes) as a white crystalline solid in 66% yield. Mp¼185 ꢀC. IR
(Thin Film): 3046, 3005, 2927, 2834, 1648, 1594, 1573, 1493, 1403,
1367, 1308, 1287, 1238, 1178, 1091, 1060, 1016, 907, 858, 814, 755,
d 148.5, 138.3, 135.4, 135.2, 129.7, 129.0, 128.8, 128.4, 124.0, 123.1,
40.8, 39.5, 35.3. LRMS (EIþ): m/z¼316 (8), 236 (35), 191 (51), 189
(100), 165 (35), 152 (20), 126 (4), 115 (32), 89 (25). HRMS (EIþ): m/z
calcd for C15H11NO2Br [MꢄBr] 315.9973, found¼315.9973.
729, 701, 652 cmꢄ1
.
1H NMR (400 MHz, CDCl3)
d
7.37 (4H, ddd,
4.10.11. 1-(2,2-Dibromo-3-phenylcyclopropyl)-4-nitrobenzene
4l. Isolated by flash column chromatography (20% EtOAc in hex-
anes) as a light yellow oil in 95% yield. IR (Thin Film): 3085, 3078,
J¼8.5, 2.0, 2.0 Hz), 7.29 (4H, ddd, J¼8.5, 2.0, 2.0 Hz), 3.16 (2H, s). 13C
NMR (75 MHz, CDCl3)
d 134.3, 134.1, 130.4, 128.9, 39.8, 35.7. LRMS

G. Rosocha, R.A. Batey / Tetrahedron 69 (2013) 8758e8768
8765
3065, 3060, 3061, 1596, 1512, 1447, 1412, 1401, 1110, 1073, 970, 872,
853, 832, 763, 748 cmꢄ1. 1H NMR (400 MHz, CDCl3)
8.24 (2H, dd,
J¼8.0, 1.5 Hz), 7.59 (2H, dd, J¼8.0, 1.5 Hz), 7.40 (5H, m), 3.35 (2H, s).
57.9. LRMS (EIþ): m/z¼339 (11), 263 (4), 261 (54), 259 (100), 223 (4)
189 (18), 187 (4). HRMS (EIþ): m/z calcd for C15H9Cl2Br [M]
337.9265, found¼337.9274.
d
13C NMR (75 MHz, CDCl3)
d 147.7, 143.4, 135.2, 130.1, 129.0, 128.9,
128.4, 123.9, 41.0, 39.8, 35.1. LRMS (EIþ): m/z¼319 (4), 316 (13), 272
(4), 237 (48), 191 (100), 189 (58), 178 (11), 165 (12), 149 (8), 131 (8),
115 (6), 69 (43). HRMS (EIþ): m/z calcd for C15H11NO2Br [MꢄBr]
315.9973, found¼315.9975.
4.10.17. 2-Bromo-6-chloro-1-(4-chlorophenyl)-1H-indene
8e. Isolated as a white solid in 91% yield. Mp¼69e71 ꢀC. IR (Thin
Film): 3066, 3010, 2896, 2958, 1583, 1449, 1454, 1408, 1330, 1261,
1192, 1176, 1092, 1064, 1015, 913, 835, 807, 785, 744, 682, 618 cmꢄ1
.
1H NMR (400 MHz, CDCl3)
d 7.29 (2H, m), 7.23 (2H, m), 7.09 (1H, m),
4.10.12. 1-(2,2-Dibromo-3-phenylcyclopropyl)-3-methoxybenzene
4m. Isolated by flash column chromatography (0e10% EtOAc in
hexanes) as a light yellow oil in 73% yield. IR (Thin Film): 3058, 2939,
2337, 1945, 1491, 1451, 1431, 1318, 1273, 1244, 1157, 1072, 1047, 961,
6.99 (2H, m), 6.98 (1H, s), 4.56 (1H, s). 13C NMR (75 MHz, CDCl3)
d
148.7, 141.4, 135.3, 133.8, 132.6, 132.0, 131.3, 129.9, 129.4, 127.9,
124.5, 121.4, 60.5. LRMS (EIþ): m/z¼341 (6), 339 (11), 337 (8), 263
(4), 261 (48), 259 (100), 223 (4) 189.5 (13), 129 (3). HRMS (EIþ): m/z
calcd for C15H9Cl2Br [M] 337.9265, found¼337.9274.
866, 836, 777, 749, 717 cmꢄ1. 1H NMR (300 MHz, CDCl3)
d
7.42e7.34
(5H, m), 7.33e7.28 (1H, dd, J¼8.5, 8.0 Hz), 6.96 (1H, d, J¼8.0 Hz), 6.89
(2H, m), 3.82 (3H, s), 3.21 (2H, s). 13C NMR (75 MHz, CDCl3)
159.9,
d
4.10.18. 2-Bromo-1-(o-tolyl)-1H-indene 8h-A and 2-bromo-4-
methyl-1-phenyl-1H-indene 8h-B. Isolated as a mixture of 8h-A
and 8h-B in a 3:1 ratio as a pale tan oil in 74% yield. IR (Thin Film):
3072, 3031, 2932, 2849, 1597, 1555, 1496, 1450, 1382, 1331, 1258,
137.7, 136.2, 129.7, 129.1, 128.7, 128.1, 121.4, 114.9, 113.5, 55.5, 40.4,
40.3, 36.8. LRMS (EIþ): m/z¼301 (4), 221 (25), 210 (100),194 (29),179
(63), 178 (84), 165 (95), 152 (51), 115 (17), 89 (6). HRMS (EIþ): m/z
calcd for C16H14OBr [MꢄBr] 301.0228, found¼301.0233.
1191, 1160, 1073, 1026, 998, 949, 910, 876, 861, 765, 747, 706 cmꢄ1
.
1H NMR (400 MHz, CDCl3)
J¼8.0 Hz), 4.88 (0.25H, d, J¼2.0 Hz), 4.48 (0.75H, s), 2.64 (0.75H, s),
2.42 (2.25H, s). 13C NMR (75 MHz, CDCl3)
147.7, 141.9, 137.8, 133.4,
d 7.42e6.94 (8.75H, m), 6.50 (0.25H, d,
4.10.13. 2-Bromo-1-phenyl-1H-indene 8a. Isolated by flash column
chromatography (20% EtOAc in hexanes) as a white solid in 95%
yield. Mp¼74e76 ꢀC. IR (Thin Film): 3062, 2981, 1951, 1599, 1548,
1491, 1451, 1419, 1335, 1263, 1187, 1152, 1093, 1072, 1029, 908, 876,
d
133.1, 132.5, 132.0, 131.6, 131.5, 131.4, 130.9, 130.8, 129.8, 129.0,
128.6, 128.5, 127.6, 127.5, 127.2, 126.9, 126.8, 125.8, 125.6, 123.8,
121.5, 120.6, 61.5, 56.7, 20.5, 18.7. LRMS (EIþ): m/z¼286 (7), 205
(100), 203 (10), 202 (11), 190 (6), 189 (5), 178 (4), 102 (2), 77 (1)
HRMS (EIþ): m/z calcd for C16H13Br [M] 284.0201, found¼284.0209.
851, 693, 647 cmꢄ1. 1H NMR (400 MHz, CDCl3)
d 7.34e7.22 (5H, m),
7.15e7.06 (4H, m), 7.00 (1H, d, J¼1.5 Hz), 4.58 (1H, s). 13C NMR
(75 MHz, CDCl3) d 147.8, 143.2, 137.8, 133.3, 131.8, 129.2, 128.8, 127.8,
127.5, 125.9, 124.2, 120.7, 61.4. LRMS (EIþ): m/z¼273 (3), 272 (6), 191
(100), 189 (29), 165 (15), 163 (4), 95 (1), 63 (1). HRMS (EIþ): m/z
calcd for C15H11Br [M] 270.0044, found¼270.0037.
4.10.19. 2-Bromo-1-(p-tolyl)-1H-indene 8i-A and 2-bromo-6-
methyl-1-phenyl-1H-indene 8i-B. Isolated as a mixture of 8i-A and
8i-B in a 55:45 ratio as a tan oil in 97% yield. IR (Thin Film): 3025,
2920,1602,1551,1512,1494,1473,1334,1256,1189,1109,1072,1023,
4.10.14. 2-Bromo-5-methyl-1-(m-tolyl)-1H-indene 8b-A and 2-
bromo-7-methyl-1-(m-tolyl)-1H-indene 8b-B. Isolated by flash col-
umn chromatography (hexanes) to provide the indene isomers 8b-
A and 8b-B in a 1:1 ratio as a clear oil in quantitative yield. IR (Thin
Film): 3041, 3015, 2963, 2906, 2855, 1605, 1558, 1491, 1466, 1455,
1419, 1385, 1258, 1168, 1096, 1034,1016, 913, 887, 845, 771, 745, 732,
935.7, 863.8, 808.5, 772.4, 746.7 cmꢄ1 1H NMR (400 MHz, CDCl3)
.
d
7.34e6.94 (9H, m), 4.53 (1H, s), 2.32 (1.35H, s), 2.27 (1.65H, s). 13
C
NMR (75 MHz, CDCl3)
d 147.7, 147.6, 142.8, 140.1, 137.7, 137.1, 135.3,
134.2,132.7,132.7,131.6,130.0,129.5,128.7,128.4,128.2,127.8,127.3,
127.0,125.4,124.6,123.7,120.2,119.9, 60.8, 60.7, 21.4, 21.1. LRMS (EIþ)
m/z¼286 (5), 205 (100), 189 (27), 178 (19), 165 (6), 128 (19), 77 (15).
HRMS (EIþ) m/z calcd C16H13Br [M] 284.0201, found 284.0198.
701 cmꢄ1
(0.5H, s), 4.43 (0.5H, s), 2.36 (1.5H, s), 2.30 (1.5H, s), 2.28 (1.5H, s),
1.97 (1.5H, s). 13C NMR (75 MHz, CDCl3)
145.5, 144.9, 143.5, 143.1,
. d 7.21e6.80 (8H, m), 4.45
1H NMR (400 MHz, CDCl3)
d
138.5, 138.4, 137.7, 137.0, 136.5, 133.8, 133.0, 132.5, 132.3, 131.7, 129.1,
129.1, 128.8, 128.6, 128.4, 128.3, 127.7, 127.3, 126.4, 125.9, 125.6,
123.7, 121.2, 118.1, 60.9, 60.9, 21.6, 21.6, 18.8 (missing 1 aliphatic
signal). LRMS (EIþ): m/z¼298 (5), 220 (4), 219 (100), 202 (3). HRMS
(EIþ): m/z calcd for C17H15Br [M] 298.0357, found 298.0364.
4.10.20. 2-Bromo-1-(3,5-dimethylphenyl)-1H-indene 8j-A and 2-
bromo-5,7-dimethyl-1-phenyl-1H-indene 8j-B. Isolated as a mix-
ture of 8j-A and 8j-B in a 25:75 ratio as a light yellow solid in 92%
yield. Mp¼73e76 ꢀC. IR (Thin Film): 3026, 2916, 1610, 1563, 1492,
1454, 1379, 1230, 1173, 1073, 1029, 883, 861, 748, 726, 648,
628 cmꢄ1. 1H NMR (400 MHz, CDCl3)
d 7.32e7.00 (5.75H, m), 6.91
4.10.15. 2-Bromo-6-methyl-1-(p-tolyl)-1H-indene 8c. Isolated as
a tan oil in 86% yield. IR (Thin Film): 3015, 2912, 2855, 1594, 1548,
1509, 1470, 1450, 1382, 1258, 1189, 1132, 1111, 1021, 863, 812,
(0.25H, s), 6.87 (0.75H, d, J¼2.0 Hz), 6.75 (0.75H, s), 6.68 (0.5H, s),
4.48 (0.25H, s), 4.46 (0.75H, s), 2.35 (2.25H, s), 2.27 (1.5H, s), 1.92
(2.25H, s). 13C NMR (75 MHz, CDCl3)
d 147.6, 143.4, 142.4, 138.2,
755 cmꢄ1. 1H NMR (400 MHz, CDCl3)
d
7.18 (1H, d, J¼7.5 Hz), 7.12
137.3,137.0,136.8,133.2,132.7,132.2,132.1,131.5,129.2,128.9,128.6,
128.4, 127.9, 127.2, 127.0, 126.0, 125.4, 123.8, 120.2, 118.7, 61.0, 60.4,
21.3, 21.2, 18.4. LRMS (EIþ): m/z¼298 (10), 220 (4), 219 (100), 204
(3), 203 (9), 189 (3), 115 (4), 101 (3). HRMS (EIþ): m/z calcd for
C17H15Br [M] 298.0357, found¼298.0349.
(2H, d, J¼7.5 Hz), 7.06 (1H, d, J¼7.5 Hz), 6.99e6.96 (3H, m), 6.94 (1H,
s), 4.49 (1H, s), 2.33 (3H, s), 2.23 (3H, s). 13C NMR (75 MHz, CDCl3)
d
148.0, 140.3, 137.2, 135.5, 134.8, 132.8, 130.4, 129.7, 128.5, 127.9,
124.8, 120.1, 60.8, 21.6, 21.4. LRMS (EIþ): m/z¼298 (5), 220 (4), 219
(100), 204 (3), 203 (4),189 (3),128 (2), 86 (4), 84 (7). HRMS (EIþ): m/
z calcd for C17H15Br [M] 298.0357, found¼298.0358.
4.10.21. 2-Bromo-1-(3-nitrophenyl)-1H-indene 8k-A and 2-bromo-
3-(3-nitrophenyl)-1H-indene 13k-A. Isolated by flash column chro-
matography (10e20% EtOAc in hexanes) as indenes 8k-A and 13k-A
in a 9:1 ratio as a white solid in 75% yield. Mp¼142e143 ꢀC. IR (Thin
Film): 3070, 2902, 1604, 1531, 1473, 1457, 1355, 1256, 1195, 1095,
1080,1025, 934, 908, 887, 821,184, 757, 733 cmꢄ1.1H NMR (400 MHz,
4.10.16. 2-Bromo-4-chloro-1-(2-chlorophenyl)-1H-indene
8d. Isolated as a white solid in 93% yield. Mp¼69 ꢀC. IR (Thin Film):
3066, 3010, 2896, 1581, 1550, 1441, 1474, 1453, 1427, 1257, 1184,
1168, 1134, 1052, 1035, 917, 862, 837, 771, 756, 652, 640 cmꢄ1 1H
.
NMR (400 MHz, CDCl3)
7.12 (2H, ddd, J¼8.0, 1.0, 1.0 Hz), 7.06 (m, 1H), 6.67 (1H, dd, J¼8.0,
1.0 Hz), 5.41 (1H, s). 13C NMR (75 MHz, CDCl3)
148.8, 141.3, 135.2,
134.8, 131.7, 131.4, 130.0, 129.1, 128.4, 127.8, 127.7, 127.1, 125.8, 122.2,
d
7.50 (1H, dd, J¼8.0, 1.0 Hz), 7.23 (3H, m),
CDCl3)
d
8.15 (1H, ddd, J¼8.0, 2.0,1.0 Hz), 7.97 (1H, dd, J¼2.0, 2.0 Hz),
7.37 (1H, dd, J¼8.0, 8.0 Hz), 7.38 (2H, m), 7.28 (1H, ddd, J¼7.5, 7.5,
d
1.0 Hz), 7.19e6.95 (3H, m), 4.66 (1H, s). 13C NMR (75 MHz, CDCl3)
d
146.2, 142.8, 139.9, 134.5, 133.9, 129.7, 129.6, 127.8, 125.9, 123.7,

8766
G. Rosocha, R.A. Batey / Tetrahedron 69 (2013) 8758e8768
123.5,122.6,120.8, 60.2 (1 aromatic C missing). LRMS (EIþ): m/z¼315
(8), 285 (5), 236 (100), 189 (96), 163 (11), 94.5 (6). HRMS (EIþ): m/z
calcd for C15H10NO2Br [M] 314.9895, found 314.9892.
crystals in 87% yield. Mp¼118e120 ꢀC. IR (Thin Film): 3046, 3015,
2917, 1604, 1576, 1511, 1491, 1465, 1442, 1390, 1238, 1191, 1176, 1158,
1073, 1026, 1116, 938, 820, 770, 724, 703 cmꢄ1. 1H NMR (400 MHz,
CDCl3)
d
7.56 (1H, d, J¼6.0 Hz), 7.38 (3H, m), 7.26e7.15 (6H, m), 7.05
4.10.22. 2-Bromo-1-(4-nitrophenyl)-1H-indene 8l-A and 2-bromo-3-
(4-nitrophenyl)-1H-indene 13l-A. Obtained as a mixture of indenes
8l-A and 13l-A in a 9:1 ratio (crude NMR). Compounds 8l-A and
13l-A were isolated by flash column chromatography in a combined
93% yield (0e10% EtOAc in hexanes). Compound 8l-A was obtained
as yellow oil. IR (Thin Film): 3062, 2941, 2868, 1731, 1697, 1533,
1455, 1356, 1257, 1182, 1148, 1095, 1078, 1027, 1010, 933, 882, 848,
(2H, d), 3.9 (2H, s), 3.9 (1H, s), 2.23 (3H, s). 13C NMR (75 MHz, CDCl3)
d
147.0, 142.3, 141.1, 139.2, 136.7, 136.3, 133.6, 129.3, 128.9, 128.7,
128.1, 127.3, 126.4, 124.8, 123.5, 120.2, 41.1, 21.1. LRMS (EIþ): m/
z¼282 (100), 267 (13), 265 (8), 252 (28), 239 (3), 205 (3), 189 (4),
165 (4), 126 (3). HRMS (EIþ): m/z calcd for C22H18 [M] 282.1409,
found¼282.1403.
816, 807, 749, 729, 679 cmꢄ1. 1H NMR (400 MHz, CDCl3)
d
8.19e8.16
4.10.27. 2-(3-Methoxyphenyl)-3-phenyl-1H-indene 14e. Isolated by
flash column chromatography (10% EtOAc in hexanes) as a light
yellow oil in 90% yield. IR (Thin Film): 3067, 3015, 2958, 2829, 1607,
1486, 1462, 1429, 1393, 1323, 1292, 1264, 1217, 1173, 1034, 910, 866,
(2H, m), 7.35 (1H, d, J¼7.5 Hz), 7.31e7.23 (3H, m), 7.15 (1H, ddd,
J¼7.5, 7.5, 1.0 Hz), 7.11e7.08 (2H, m), 4.67 (1H, s). 13C NMR (75 MHz,
CDCl3)
d 147.6, 146.4, 145.6, 143.0, 134.2, 129.7, 129.4, 128.0, 126.2,
124.3,124.0,121.0, 60.6. LRMS (EIþ): m/z¼317 (6), 315 (6), 236 (100),
190 (21), 189 (51), 187 (3), 94 (4). HRMS (EIþ): m/z calcd for
C15H10BrNO2 [M] 314.9895, found¼314.9896. Compound 13l-A was
obtained as a light yellow oil. IR (Thin film): 3070, 2947, 2857, 1714,
1597, 1513, 1457, 1339, 1311, 1104, 1012, 942, 849, 771, 721, 690,
773, 727, 701, 600 cmꢄ1. 1H NMR (400 MHz, CDCl3)
d 7.55e7.52 (1H,
m), 7.46e7.42 (2H, m), 7.39e7.34 (3H, m), 7.28e7.19 (3H, m), 7.14
(1H, t, J¼8.0 Hz), 6.92 (1H, ddd, J¼8.0, 1.5, 1.0 Hz), 6.80 (1H, dd,
J¼2.5, 1.5 Hz), 6.72 (1H, ddd, J¼8.0, 2.5, 1.0), 3.92 (2H,s), 3.55 (3H, s).
13C NMR (75 MHz, CDCl3)
d 159.4, 147.1, 142.5, 141.1, 140.5, 138.0,
620 cmꢄ1. 1H NMR (400 MHz, CDCl3)
d
8.37 (2H, dd, J¼7.0, 2.0 Hz),
136.4, 129.6, 129.4, 129.0, 127.7, 126.8, 125.4, 123.8, 120.9, 120.6,
113.5, 113.4, 55.1, 41.3. LRMS (EIþ): m/z¼299 (9), 298 (100), 283 (7),
267 (5), 252 (5), 239 (4), 191 (4), 165 (3), 126 (3), 86 (4). HRMS (EIþ):
m/z calcd for C22H18O [M] 298.1358, found¼298.1353.
7.72 (2H, dd, J¼7.0, 2.0 Hz), 7.23e7.20 (4H, m), 3.82 (2H, s). 13C NMR
(75 MHz, CDCl3) d 143.1,142.0,140.8,140.4,135.1,130.0, 129.6, 126.9,
126.9, 125.7,123.8, 119.4, 45.9. LRMS (EIþ): m/z¼317 (5), 315 (5), 236
(100), 206 (18), 189 (41), 177 (1), 94 (4). HRMS (EIþ): m/z calcd for
C15H10NO2Br [M] 314.9895, found¼314.9892.
4.10.28. 2-(4-Nitrophenyl)-3-phenyl-1H-indene 14f. Isolated by flash
column chromatography (10% EtOAc in hexanes) as an orange crys-
talline solid in 78% yield. Mp¼149e151 ꢀC. IR (Thin Film): 3062,
2360, 2341, 1589, 1509, 1459, 1443, 1391, 1296, 1243, 1191, 1108, 909,
848, 775, 752, 725, 701, 667, 617 cmꢄ1. 1H NMR (400 MHz, CDCl3)
4.10.23. 2,3-Diphenyl-1H-indene 14a. Isolated by flash column
chromatography (20% EtOAc in hexanes) as a tan oil in 82% yield. IR
(Thin Film): 3056, 3024, 2882, 1948, 1808, 1600, 1490, 1458, 1442,
1389, 1357, 1242, 1210, 1173, 1156, 1074, 1026, 941, 917, 841,
d
8.05 (2H, m), 7.59e7.55 (1H, m), 7.48e7.42 (3H, m), 7.39 (2H, m),
810 cmꢄ1. 1H NMR (400 MHz, CDCl3)
d
7.54 (1H, d, J¼6.60 Hz), 7.38
7.36e7.30 (4H, m), 7.28e7.24 (1H, m), 3.96 (2H, s). 13C NMR (75 MHz,
(5H, m), 7.30e7.16 (9H, m), 3.93 (1H, s). 13C NMR (75 MHz, CDCl3)
CDCl3)
d 146.2, 144.1, 143.2, 142.5, 138.3, 135.1, 129.3, 129.2, 129.0,
d
146.9, 142.3, 141.0, 139.9, 136.5, 136.0, 129.3, 128.8, 128.2, 128.1,
128.6, 128.1, 126.8, 126.2, 123.7, 123.5, 121.2, 40.9. LRMS (EIþ): m/
z¼225 (4), 208 (7), 193 (63), 165 (54), 139 (19), 105 (28), 92 (100), 91
(71), 77 (54), 63 (57), 51 (56). HRMS (EIþ): m/z calcd for C21H15NO2
[M] 313.1103, found¼313.1095.
127.3, 126.9, 125.0, 123.5, 120.3, 104.7, 41.1. LRMS (EIþ): m/z¼268
(100), 267 (27), 265 (18), 263 (5), 252 (4), 191 (12), 189 (10), 165 (8),
134 (3), 131 (4), 126 (8), 119 (5), 113 (4). HRMS (EIþ): m/z calcd for
C21H16 [M] 268.1252, found¼268.1251.
4.10.29. 3-Phenyl-2-(phenylethynyl)-1H-indene 15a. Isolated by flash
column chromatography (hexanes) as a light yellow oil in 80% yield.
IR (Thin Film): 3047, 3019, 2930, 2347, 2190, 1967, 1599, 1487, 1459,
1443, 1387, 1361, 1333, 1177, 1154, 1126, 1065, 1020, 942, 903, 754,
4.10.24. 3-Phenyl-2-(o-tolyl)-1H-indene 14b. Isolated by flash col-
umn chromatography (20% EtOAc in hexanes) as yellow needle
crystals in 72% yield. Mp¼118e120 ꢀC. IR (Thin Film) 3062, 3024,
2916, 2943, 2873, 2334, 1951, 1908, 1884, 1803, 1706, 1604, 1575,
690 cmꢄ1. 1H NMR (400 MHz, CDCl3)
d
7.79 (2H, dt, J¼7.0, 1.5 Hz),
7.56e7.47 (4H, m), 7.46e7.38 (3H, m), 7.34e7.26 (5H, m), 3.76 (2H, s).
13C NMR (75 MHz, CDCl3)
148.6, 144.0, 143.2, 134.7, 131.6, 129.0,
1486, 1454, 1386, 1354, 1171, 1120, 1077, 1026, 905, 755, 728 cmꢄ1
.
1H NMR (400 MHz, CDCl3)
3.80 (2H, s), 1.97 (3H, s). 13C NMR (75 MHz, CDCl3)
d
7.54e7.47 (2H, m), 7.28e7.06 (11H, m),
145.4, 143.1,
d
d
128.5, 128.5, 128.3, 128.2, 126.8, 126.2, 124.0, 123.7, 122.8, 121.2, 95.8,
87.5, 42.6. LRMS (EIþ): m/z¼293 (8), 292 (100), 291 (46), 289 (26),
276 (4), 215 (14), 144 (3), 131 (1). HRMS (EIþ): m/z calcd for C23H16
[M] 292.1252, found¼292.1251.
143.1, 140.3, 137.2, 136.0, 135.4, 130.1, 129.8, 128.8, 128.2, 127.1, 127.0,
126.4, 125.4, 124.8,123.7,120.3, 43.5, 20.2. LRMS (EIþ): m/z¼297 (2),
296 (8), 282 (100), 282 (29), 265 (5), 252 (3), 239 (2). HRMS (EIþ):
m/z calcd for C22H18 [M] 282.1409, found¼282.1408.
4.10.30. 3-(3-Phenyl-1H-inden-2-yl)prop-2-yn-1-ol 15b. Isolated by
flash column chromatography (10% EtOAc in hexanes) as a light
yellow oil in 32% yield. IR (Thin Film): 3053, 2914, 2837, 1592, 1488,
1435, 1387, 1323, 1173, 1064, 1036, 920, 881, 851, 782, 699, 658,
4.10.25. 3-Phenyl-2-(m-tolyl)-1H-indene 14c. Isolated by flash col-
umn chromatography (0e5% EtOAc in hexanes) as yellow crystals
in 79% yield. Mp¼118e120 ꢀC. IR (Thin Film): 3029, 2927, 2878,
1948, 1873, 1806, 1604, 1494, 1389, 1327, 1292, 1260, 1212, 1174,
1152, 1075, 1015, 878, 773, 720, 701, 601, cmꢄ1. 1H NMR (300 MHz,
614 cmꢄ1. 1H NMR (400 MHz, CDCl3)
d
7.69e7.66 (2H, m), 7.51e7.46
(4H, m), 7.42e7.38 (1H, m), 7.33e7.26 (2H, m), 4.44 (2H, s), 3.66 (2H,
s), 1.62 (1H, br s). 13C NMR (75 MHz, CDCl3)
148.9, 143.9, 143.0,
CDCl3)
7.15e6.88 (3H, m), 3.91 (2H, s), 2.24 (3H, s). 13C NMR (75 MHz,
CDCl3) 146.7, 142.5, 140.5, 139.9, 138.8, 138.1, 130.9, 130.5, 130.4,
d
7.55e7.52 (1H, m), 7.44e7.32 (6H, m), 7.28e7.19 (3H, m),
d
134.5, 128.9, 128.6, 128.3, 126.9, 126.4, 124.1, 121.3, 93.5, 83.2, 52.1,
42.7 (1 carbon missing). LRMS (EIþ): m/z¼252 (100), 251 (7), 237
(4), 215, (39), 202 (53), 189 (8), 187 (4), 187 (4), 139 (2), 128 (2), 94
(4), 86 (33), 84 (53). HRMS (EIþ): m/z calcd for C18H14O [M]
246.1045, found¼246.1042.
d
130.1, 129.9, 129.8, 128.9, 127.5, 126.5, 124.5, 123.9, 120.1, 41.5, 21.5.
LRMS (EIþ): m/z¼283 (5), 282 (100), 267 (12), 265 (7), 239 (3), 252
(3), 265 (8), 189 (3), 133 (1). HRMS (EIþ): m/z calcd for C22H18 [M]
282.1409, found¼282.1412.
4.10.31. 2-Bromo-3-phenyl-1H-indene 13a. Isolated as a light yel-
low oil in 85% yield. IR (Thin Film): 3067, 3013, 2884, 1948, 1881,
1798, 1696, 1604, 1569, 1486, 1451, 1386, 1338, 1292, 1166, 1075,
4.10.26. 3-Phenyl-2-(p-tolyl)-1H-indene 14d. Isolated by flash col-
umn chromatography (20% EtOAc in hexanes) as yellow needle

G. Rosocha, R.A. Batey / Tetrahedron 69 (2013) 8758e8768
8767
1023, 940, 854, 789, 744, 720, 639, 615 cmꢄ1. 1H NMR (400 MHz,
CDCl3)
7.56 (2H, dt, J¼7.0, 1.5 Hz), 7.47 (2H, tt, J¼8.0, 1.0 Hz), 7.40
(2H, m), 7.28e7.18 (3H, m), 3.74 (2H, s). 13C NMR (75 MHz, CDCl3)
7.42e7.26 (5H, m), 7.12e7.09 (1H, m), 4.18e4.05 (2H, m), 3.94 (1H,
d, J¼24.0 Hz), 3.85 (1H, d, J¼24.0 Hz) 1.05 (3H, t, J¼7.0 Hz). 13C NMR
d
(75 MHz, CDCl3) d 164.7,150.1,144.2,143.3,134.3,133.2,132.8,130.0,
d
144.4, 142.7, 142.4, 133.8, 129.2, 128.7, 128.3, 126.9, 125.4, 123.6,
129.4, 129.1, 127.7, 126.8, 126.3, 124.1, 122.5, 60.1, 39.1, 13.8. LRMS
(EIþ): m/z¼298 (1), 263 (59), 249 (100), 235 (43), 225 (51), 189 (46),
176 (50), 163 (6), 88 (1). HRMS (EIþ): m/z calcd for C18H15O2Cl [M]
298.0761, found¼298.0768.
122.0, 120.1, 45.8. LRMS (EIþ): m/z¼265 (4), 264 (21), 235 (1), 219
(2), 218 (2), 205 (1), 192 (11), 191 (45), 189 (10), 165 (2), 163 (1).
HRMS (EIþ): m/z calcd for C18H16O2 [M] 246.1150, found¼246.1147.
4.10.32. 2-Methyl-3-phenyl-1H-indene 19.21 Isolated by flash col-
Acknowledgements
umn chromatography (20% EtOAc in hexanes) as a clear oil in 89%
yield. 1H NMR (400 MHz, CDCl3)
d
7.48e7.31 (6H, m), 7.26e7.20 (2H,
m), 7.18e7.12 (1H, m), 3.46 (2H, s), 2.14 (3H, s). 13C NMR (75 MHz,
CDCl3) 146.6, 142.6, 140.8, 138.8, 135.7, 129.4, 128.6, 127.2, 126.4,
The Natural Science and Engineering Research Council (NSERC)
of Canada funded this work. We thank Dr. Alex B. Young and Dr. M.
W. Forbes for mass spectrometric analysis and Dr. Tim Burrow for
NMR assistance.
d
124.2, 123.6, 119.5, 43.3, 15.1.
4.10.33. Ethyl 3-phenyl-1H-indene-2-carboxylate 20. Isolated as
a light yellow oil in 85% yield. IR (Thin Film): 3051, 2970, 2889,1698,
1615, 1572, 1459, 1440, 1389, 1373, 1298, 1263, 1239, 1190, 1112,
References and notes
1. (a) Elliot, J. D.; Lago, M. A.; Cousins, R. D.; Gao, A.; Leber, J. D.; Erhard, K. F.; Nambi,
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1091, 1150, 1021, 945, 862, 833, 776, 755, 698 cmꢄ1 1H NMR
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(400 MHz, CDCl3)
d
7.59 (1H, dt, J¼8.5, 1.0 Hz), 7.45e7.38 (5H, m),
ꢁ
7.36 (1H, td, J¼7.5, 2.0 Hz), 7.30e7.25 (2H, m), 4.25 (2H, q, J¼7.0 Hz),
Dallemagne, P.; Leger, J.-M.; Sopkova, J.; Bovy, P. R.; Jarry, C.; Rault, S. Bioorg. Med.
3.58 (2H, s), 1.25 (3H, t, J¼7.0). 13C NMR (300 MHz, CDCl3)
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153.3,145.2, 143.7, 134.7, 131.3, 129.1,128.2, 128.1,127.9,126.9,124.3,
123.0, 60.3, 39.6, 14.2. LRMS (EIþ): m/z¼265 (4), 264 (21), 235 (1),
219 (4), 191 (100), 189 (22), 165 (5), 163 (1). HRMS (EIþ): m/z calcd
for C18H16O2 [M] 264.1150, found¼264.1147.
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4.10.34. 2-Bromo-7-chloro-3-(2-chlorophenyl)-1H-indene
13d. Isolated as a light yellow oil in quantitative yield. IR (Nujol thin
film): 3053, 2907, 2851, 1594, 1487, 1445, 1387, 1289, 1258, 1168, 1090,
1017, 944, 908, 802, 735, 690, 620, 528 cmꢄ1 1H NMR (400 MHz,
.
3. For selected recent examples, see: (a) Basavaiah, D.; Reddy, B. S.; Lingam, H.
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CDCl3)
d
7.51e7.40 (4H, m), 7.36e7.30 (1H, m), 7.22e7.16 (2H, m), 3.73
145.7, 141.7, 139.7, 133.7, 132.8,
(2H, s). 13C NMR (75 MHz, CDCl3)
d
131.5, 130.1, 130.0, 129.6, 128.6, 127.1, 125.6, 125.0, 118.8, 45.1. LRMS
(EIþ): m/z¼341 (8), 339 (31), 337 (14), 261 (91), 260 (11), 259 (100),
223 (11), 189 (51), 187 (16), 111 (3), 93 (3). HRMS (EIþ): m/z calcd for
C15H9Cl2Br [M] 337.9265, found¼337.9273.
4.10.35. 2-Bromo-5-chloro-3-(4-chlorophenyl)-1H-indene
13e. Isolated as a clear oil in 94% yield. IR (Nujol): 2907 (Nujol thin
film), 2722, 2678, 2358, 1451, 1370, 1294, 1258, 1163, 1093, 1073,
1014, 956, 869, 833, 799, 729, 670, 555 cmꢄ1. 1H NMR (400 MHz,
CDCl3)
d 7.56e7.50 (1H, m), 7.42e7.29 (3H, m), 7.21e7.16 (2H, m),
6.92e6.86 (1H, m), 3.92e3.74 (2H, m). 13C NMR (75 MHz, CDCl3)
d
145.6, 141.1, 140.4, 134.5, 133.2, 131.6, 130.7, 130.4, 125.4, 124.6,
124.1, 120.1, 45.4. LRMS (EIþ): m/z¼341 (2), 339 (9), 261 (42), 259
(100), 189 (15), 187 (4), 129 (2). HRMS (EIþ): m/z calcd for
C15H9Cl2Br [M] 337.9265, found¼337.9260.
4.10.36. 2-Bromo-3-(3-nitrophenyl)-1H-indene 13k-A. Isolated as
a light yellow oil in 70% yield. IR (Thin Film): 3070, 2902,1604,1531,
1473, 1457, 1355, 1256, 1195, 1095, 1080, 1025, 934, 908, 887, 821,
184, 757, 733 cmꢄ1. 1H NMR (400 MHz, CDCl3)
d 8.42 (1H, s), 8.30
(1H, d, J¼8.0 Hz), 7.89 (1H, d, J¼8.0 Hz), 7.68 (1H, dd, J¼8.0, 1.0 Hz),
7.48 (1H, d, J¼8.0 Hz), 7.30e7.20 (3H, m), 3.83 (2H, s). 13C NMR
(75 MHz, CDCl3)
d 148.6, 146.2, 142.8, 139.9, 134.5, 133.9, 129.6,
127.8, 125.9, 124.0, 123.7, 123.5, 122.6, 120.8, 60.2. LRMS (EIþ): m/
z¼315 (8), 237 (12), 236 (100), 190 (34), 189 (66), 163 (7), 131 (12)
94.5 (6), 69 (38). HRMS (EIþ): m/z calcd for C15H10NO2Br [M]
314.9895, found¼314.9882.
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4.10.37. Ethyl 3-(2-chlorophenyl)-1H-indene-2-carboxylate 21. Iso
lated as a light yellow oil in 78% yield. IR (Thin Film): 3062, 2986,
2895, 2366, 1736, 1704, 1610, 1577, 1464, 1392, 1368, 1343, 1249,
1193, 1109, 1093, 1058, 1018, 951, 919, 865, 76, 749, 717 cmꢄ1 1H
.
NMR (400 MHz, CDCl3)
d 7.58e7.56 (1H, m), 7.51e7.48 (1H, m),

8768
G. Rosocha, R.A. Batey / Tetrahedron 69 (2013) 8758e8768
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