Synthesis of 2-indol-3-ylbenzofulvenes through a tandem reaction catalyzed by cationic gold(I) complexes

Article abstract of DOI:10.1055/s-0031-1290950

A new access to benzofulvenes bearing an indol-3-yl substituent at C-2 has been developed. Treatment of 3-propargylindoles possessing an additional hydroxy group at the other propargylic position with a cationic gold(I) complex triggers a tandem 1,2-indol

Full text of DOI:10.1055/s-0031-1290950

1874▌
SPECIAL TOPIC
special topic
Synthesis of 2-Indol-3-ylbenzofulvenes through a Tandem Reaction Catalyzed
by Cationic Gold(I) Complexes
Benzofulvenes by a Tandem Reaction
Estela Álvarez,a Delia Miguel,a,1 Patricia García-García,a Manuel A. Fernández-Rodríguez,a Félix Rodríguez,b
Roberto Sanz*a
a
Área de Química Orgánica, Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Pza. Misael Bañuelos s/n, 09001 Burgos,
Spain
Fax +(34)947258831; E-mail: rsd@ubu.es
b
Instituto Universitario de Química Organometálica ‘Enrique Moles’, Universidad de Oviedo, C/ Julián Clavería, 8, 33006 Oviedo, Spain
Received: 08.03.2012; Accepted: 30.03.2012
Dedicated to our good friend Professor Francisco J. Fañanás on the occasion of his 60th birthday
ent approaches to methyleneindenes are known, mainly
Abstract: A new access to benzofulvenes bearing an indol-3-yl
from indane or indanone derivatives, although more re-
substituent at C-2 has been developed. Treatment of 3-propargylin-
cently some useful routes have been developed based on
doles possessing an additional hydroxy group at the other pro-
pargylic position with a cationic gold(I) complex triggers a tandem
the direct cyclization of monocyclic precursors.13
1,2-indole migration/aura-iso-Nazarov cyclization/elimination se-
quence that takes place under mild conditions.
We have recently studied the behavior of 3-propargylin-
doles, easily available by direct nucleophilic substitution
of propargylic alkynols with indoles,14 in the presence of
Key words: benzofulvenes, catalysis, gold, indoles, tandem reac-
tions
cationic gold complexes, and we have described that the
indole nucleus is able to undergo a 1,2-migration process
triggering different tandem reactions depending on the
substitution pattern of the starting alkyne.15 When an (het-
ero)aromatic substituent is present at the propargylic po-
sition of the starting 3-propargylindole, a metalla-iso-
Nazarov reaction follows the initial 1,2-migration of the
indole.16 This tandem sequence affords interesting 2-(in-
dol-3-yl)indene derivatives with a wide variety of differ-
ent substituents at C-1 (Scheme 1).15b
The terms domino, cascade, and tandem reactions are gen-
erally used to designate a chemical transformation of an
organic molecule through two or more consecutive elabo-
rations with a single workup step.2 Several authors have
distinguished between domino or cascade reactions in
which the starting material undergoes a transformation via
two (domino) or more (cascade) reactions one after anoth-
er in an inseparable fashion,3 and tandem reactions that
are considered to be two-step reactions that proceed in a
consecutive fashion where each of the steps can be per-
formed separately.4 Thus, in the case of cascade catalysis,5
intermediates are not generally isolable and multiple
transformations take place via a single catalytic mecha-
nism. Regardless of the notation of this type of reactions,
these are of great interest because they offer a convenient
and economical manner to access to complex organic
molecules in general from simple starting materials in a
one-pot process with all the catalysts being present from
the beginning.
Ar
Ar
R2
R3
R2
[Au]+ (5 mol%)
R3
CH2Cl2, r.t.
ref. 15
N
N
R1
R1
R3 = H, aryl, alkyl, SR, CO2Et,...
Scheme 1 Gold(I)-catalyzed tandem 1,2-indole migration/iso-
Nazarov reactions of 3-propargylindoles
Whereas most of the catalyzed cascade or tandem reac-
tions have been triggered by palladium catalysts,6 in the
last years several examples of these processes (often de-
noted as tandem) have been reported in the context of gold
catalysis.7 Moreover, many of these tandem reactions are
initiated by acyloxy migrations.8
On the other hand, it is well known that propargylic esters
are able to undergo 1,2- or 1,3-acyloxy migration under
gold catalysis, giving rise to diverse products depending
on the subsequent evolution of the initially formed Au-
carbenoid or Au-allene complex intermediate.17 There-
fore, at this point and following our interest in the synthe-
sis of indene derivatives,18 we decided to evaluate the
reactivity of an internal alkyne containing an indole at one
of the propargylic positions and an acetate group at the
other propargylic position. In a starting material like the
present one, a 1,2-indole- or a 1,2-acetate-migration could
be the initial step of a tandem process.
On the other hand, benzofulvenes are interesting com-
pounds that have found versatile applications in material
science,9 as precursors of indenyl ligands10 and other in-
dene derivatives,11 and in medicinal chemistry.12 Differ-
SYNTHESIS 2012, 44, 1874–1884
Advanced online publication: 04.05.2012
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DOI: 10.1055/s-0031-1290950; Art ID: SS-2012-C0244-ST
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Benzofulvenes by a Tandem Reaction
1875
With this aim, compound 1a was treated with a catalytic be enhanced by using a gold complex bearing the IPr (en-
amount of the gold complex Ph3PAuNTf2, developed by try 6) as ligand. Finally, the employment of the less basic
Gagosz and co-workers,19 in dichloromethane at room phosphite ligand afforded the highest ratio of 5a/4a, ca.
temperature. Under these conditions product 3a, arising 3.5:1 (entry 7). Once the triphenylphosphite was selected
from the previously reported tandem 1,2-indole migra- as the best ligand to favor the desired tandem process, the
tion/aura-iso-Nazarov cyclization reaction, was obtained influence of the solvent was studied. However, none of
in 31% yield as a mixture of diastereoisomers. Moreover, the tested solvents (entries 8–11) afforded a better result
a new product 5a, possessing an interesting benzofulvene than that obtained with CH2Cl2 (entry 7). Then, different
core, was also isolated in 57% yield as a ca. 2:1 mixture silver salts, used for the generation of the cationic gold
of geometrical isomers (Scheme 2). The structure of both catalyst, were tested (entries 12–15) and similar selectivi-
compounds, 3a and 5a, indicates that the migration of the ties were observed with all of them showing that the
indole has selectively occurred without competitive ace- gold(I) counterion has a negligible effect. Finally, with the
tate migration. In addition, starting from alkynol 2a in- optimized catalytic system, (PhO)3PAuCl/AgNTf2 in
stead of acetate 1a, alcohol 4a was obtained as a mixture CH2Cl2, a further improvement on the selectivity was ob-
of diastereoisomers (36% yield), whereas methylenein- served by lowering the temperature. Thus, carrying out
dene 5a was isolated in 41% yield and as a single geomet- the reaction at –78 °C afforded a 7:1 ratio in favor of the
rical isomer (Scheme 2).20
desired 1-methyleneindene 5a, which was isolated as a
single geometrical isomer in 75% yield (entry 16).
In order to examine the scope of this tandem process, at
first, various alkynols 2 were prepared using our devel-
oped methodology for accessing 3-propargylindoles
(Scheme 3).14 Thus, terminal alkynes 8 obtained from N-
methylindole (6) by PTSA-catalyzed direct substitution of
terminal alkynols 7, were reacted with n-BuLi and then
with different carbonyl derivatives affording alkynols 2a–
c,e–h in good yields (Scheme 3). On the other hand, other
propargylic alcohols like 2d,i–l could be prepared in only
OR
n-Pr
OR
N
Me
n-Pr
3a: R = COMe
4a: R = H
Ph3PAuNTf2 (5 mol%)
+
N
CH2Cl2, r.t.
Me
1a: R = COMe
2a: R = H
Ar
n-Pr
HO
(i)
(ii)
+
Ar
ref. 14
N
N
N
Me
5a
Me
Me
6
7
8
OH
R3
Scheme 2 Reaction of propargylic acetate 1a and alkynol 2a under
gold(I) catalysis
Ar
R2
R2
R3
2
Ar
Yield (%)
Although benzofulvene 5a could be thought to be pro-
duced from a simple elimination reaction under the reac-
tion conditions from the corresponding acetate 3a or
alcohol 4a, this possibility was ruled out by checking that
isolated 4a did not afford 5a by its treatment with the cat-
alyst under the reaction conditions or even at reflux. Due
to the interest in the development of novel routes for the
generation of functionalized 1-methyleneindenes,13 we
decided to further investigate this tandem reaction with
the aim of improving its selectivity towards the benzoful-
vene derivative 5a.
N
a
b
c
e
f
Ph
Ph
Ph
Ph
Ph
88
76
78
68
60
64
66
n-Pr
H
4-ClC6H4
Me
4-ClC6H4 4-ClC6H4
4 H
4 4-ClC6H4
OH
H
H
H
Me
Me
2a–c, e–h
g
h
4-MeOC6H
4-MeOC6H
H
H
6
+
Ar
Ar
R1
HO
HO
R1
(i)
R2
R1
R2
2 Ar
Yield (%)
N
For the screening experiments we selected alkynol 2a as a
model substrate (Table 1). After the initial experiment at
room temperature with Ph3PAuNTf2 (Table 1, entry 1),
the effect of an acid or base additive was checked and no
change on the selectivity was observed (entries 2 and 3).
d Ph
4-ClC6H4
Ph
k 2-thienyl
Ph
72
73
44
68
66
c-Pr Me
c-Pr Me
Me
Me
i-Pr
Me
2d, i–l
R2
i
j
9
H
H
Me
l
Switching the Ph3P ligand to the more basic XPhos (entry Scheme 3 Synthesis of alkynols 2 from N-methylindole (6). Reagents
and conditions: (i) PTSA (5 mol%), MeCN, r.t.; (ii) (a) n-BuLi (1.1
4) or Et3P (entry 5) gave rise to a minor amount of the de-
sired benzofulvene. Gratifyingly, the ratio of 5a/4a could
equiv), THF, –78 °C to r.t.; (b) R2COR3 (1.1 equiv), –78 °C to r.t.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1874–1884

1876
E. Álvarez et al.
SPECIAL TOPIC
one step from diols 9 by regioselective nucleophilic sub- ray analysis (entry 3).21 Even in the case of alkynol 2d
stitution of the more activated hydroxy group with indole possessing a methyl group at the propargylic position ad-
6, under the same Brønsted acid catalyzed conditions jacent to the hydroxy (R2), the corresponding benzoful-
(Scheme 3). As expected, all these alkynols 2 were ob- vene 5d was obtained in high yield and with complete
tained as a ca. 1:1 mixture of diastereoisomers.
stereoselectivity (entry 4). However, with tertiary al-
kynols 2e and 2f the formation of the corresponding 1-
tert-hydroxyalkylindenes 4e and 4f was preferred and
when starting with alkynol 2f benzofulvene 5f was only
obtained in a poor 8% yield (entries 5 and 6). Primary and
secondary alkynols 2g,h bearing an electron-rich 4-meth-
oxyphenyl group instead of phenyl at the propargylic
position also reacted to give the corresponding benzoful-
venes 5g,h although in moderate yields and selectivities
(entries 7 and 8). For substrate 2i, bearing an electron-
withdrawing group (chlorine) on the benzene ring and a
With alkynols 2 in hand, the effect of the substitution pat-
tern at the hydroxylic carbon was evaluated (Table 2, en-
tries 1–6). Surprisingly, it was found that the
methyleneindene derivative was also the major product
when using the primary propargylic alcohol 2b and ben-
zofulvene 5b was isolated in 77% yield (entry 2). A simi-
lar behavior was observed in the case of a secondary
benzylic alkynol such as 2c that afforded benzofulvene 5c
in excellent yield and as a single geometrical isomer,
whose structure was confirmed by using single-crystal X-
Table 1 Effect of the Catalyst and Reaction Conditions on the Reactivity of 2aa
OH
catalyst (5 mol%)
solvent, temp
n-Pr
OH
n-Pr
+
n-Pr
N
N
N
Me
2a
Me
Me
4a
5a
Ratio 4a/5ab
Entry
Catalyst
Solvent
Temp
1
2
Ph3PAuNTf2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
THF
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
–78 °C
1:2
Ph3PAuNTf2/PTSA
Ph3PAuNTf2/Cs2CO3 (3 equiv)
1:2
3
1:2
c
4
2:1
XPhosAuNTf2
5
Et3PAuCl/AgNTf2
1.5:1
1:3e
1:3.5
1:2
IPrAuCld/AgNTf2
6
7
(PhO)3PAuCl/AgNTf2
(PhO)3PAuCl/AgNTf2
(PhO)3PAuCl/AgNTf2
(PhO)3PAuCl/AgNTf2
(PhO)3PAuCl/AgNTf2
(PhO)3PAuCl/AgOTf
(PhO)3PAuCl/AgBF4
(PhO)3PAuCl/AgOTs
(PhO)3PAuCl/AgSbF6
(PhO)3PAuCl/AgNTf2
8
1:3e
1:2e
1:3
1:3
1:3
1:3
1:3
1:7
9
10
11
12
13
14
15
16
DME
MeNO2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
a All reactions were carried out with 0.1 mmol of 2a in 0.2 mL of the corresponding solvent. Conversion was complete and the reactions exclu-
sively afforded compounds 4a and 5a.
b Determined by 1H NMR analysis of the crude reaction mixture.
c XPhos = 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl.
d IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene.
e Benzofulvene 5a was obtained as a mixture of geometrical isomers.
Synthesis 2012, 44, 1874–1884
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Benzofulvenes by a Tandem Reaction
1877
methyl group as R2 substituent, the reaction proceeded vated alkyne affording an alkylidenecyclopropane inter-
smoothly to afford the E-isomer of benzofulvene 5i in mediate 10. Subsequent rearrangement and 1,2-migration
high yield (entry 9). However, changing the aliphatic sub- of the indole nucleus through a torquoselective 4π-elec-
stituent at the propargylic position adjacent to the indole trocyclic ring opening gives rise to a gold carbenoid/
(R1) from cyclopropyl to other alkyl groups including carbocation species 11. Then, a gold variant of the iso-
methyl or isopropyl (substrates 2j–l) led to a decrease in Nazarov cyclization takes place on the gold-stabilized
the selectivity and, the corresponding benzofulvenes 5j–l carbocation leading to intermediate 12. At this point, usu-
could only be isolated in moderate yields (entries 10–12). al protodemetalation would render the expected alcohols
The presence of a thiophene group at the propargylic po- 4 regenerating the catalytic gold species. To account for
sition in 2k allowed the preparation of a 5-indolyl-4-meth- the generation of benzofulvenes 5, we tentatively propose
ylenecyclopenta[b]thiophene derivative 5k. This product that some type of interaction between gold and oxygen at-
resulted to be acid-sensitive and could only be isolated in oms could induce a competitive elimination process that
low yield (entry 11).
finally leads to the loss of water, in a concerted or a step-
wise manner, with the subsequent recovery of the cationic
gold complex and release of the final methyleneindene de-
rivative 5 (Scheme 4). From the obtained experimental re-
sults, the preferred pathway seems to be dependent on the
nature of the ligand in the gold complex, the temperature
A possible mechanism for this tandem process is depicted
in Scheme 4. According to our previous theoretical and
experimental studies,15 initial coordination of the gold
complex to the triple bond of the starting alkynol 2 would
trigger an intramolecular attack of the indole on the acti-
Table 2 Synthesis of Benzofulvenes 5 by Gold-Catalyzed Tandem 1,2-Indole Migration/Iso-Nazarov Cyclization/Elimination from Alkynols 2
OH
Ar
Ar
R1
R3
R1
R2
(PhO)3PAuCl/AgNTf2 (5 mol%)
CH2Cl2, –78 °C
R2
N
R3
Me
N
2
Me
5
R1
R2
R3
Ratio 5/4a
Yield (%)b
Entry
Alkynol
Ar
Product
1
2
2a
2b
2c
2d
2e
2f
Ph
c-Pr
c-Pr
c-Pr
c-Pr
c-Pr
c-Pr
c-Pr
c-Pr
c-Pr
Me
n-Pr
H
7:1
9:1
5a
5b
5c
5d
5e
5f
75
77
80
84
32c
8d
Ph
H
H
3
Ph
4-ClC6H4
H
>10:1
6:1
4
Ph
Me
H
5
Ph
Me
Me
1:1.5
1:7
6
Ph
4-ClC6H4
4-ClC6H4
7
2g
2h
2i
4-MeOC6H4
4-MeOC6H4
4-ClC6H4
Ph
H
H
H
H
H
H
H
2:1
5g
5h
5i
45
51
78
8
4-ClC6H4
3.1
9
Me
H
7:1
35e
30g
50i
10
11
12
2j
3:1
5j
f
2k
2l
2-thienyl
Ph
Me
H
5k
–
5lh
i-Pr
Me
1.5:1
a Determined by 1H NMR analysis of the crude reaction mixture.
b Isolated yield after column chromatography.
c Compound 4e was also isolated in 52% yield.
d Compound 4f was also isolated in 70% yield.
e Compound 4j was also isolated in 18% yield.
f Not determined.
g Partial decomposition of the product under purification on silica gel chromatography.
h Obtained as a ca. 5:1 mixture of E/Z isomers.
i Compound 4l was also isolated in 31% yield.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1874–1884

1878
E. Álvarez et al.
SPECIAL TOPIC
ments were recorded on an Agilent 6890N/5973 Network GC
System, equipped with a HP-5MS column.
Ar
Ar
[AuL]
OH
R3
1,2-indole
migration
R1
R1
[AuL]+
OH
Alkynols 2a–c,e–h; 1-Cyclopropyl-1-(1-methyl-1H-indol-3-yl)-
1-phenylhept-2-yn-4-ol (2a); Typical Procedure
2
R2
BuLi (1.31 mL of 1.6 M solution in hexane, 2.1 mmol) was added
to a solution of the corresponding 3-propargylindole 8 (Ar = Ph; 571
mg, 2 mmol) in anhyd THF (2 mL) at –78 °C. The mixture was
stirred from –78 °C to r.t. for 1 h and then recooled to –78 °C. Bu-
tyraldehyde (159 mg, 2.2 mmol) was slowly added and the resulting
mixture was stirred at r.t. for 2 h. Sat. aq NH4Cl (10 mL) was added,
the separated aqueous phase was extracted with Et2O (2 × 20 mL),
and the combined organic layers were dried (Na2SO4). The solvent
was removed under reduced pressure and the crude residue was pu-
rified by flash column chromatography on silica gel using hexane–
EtOAc (4:1) as eluent to afford 2a as a ~1:1 mixture of diastereoiso-
mers; yield: 628 mg (88%); pale yellow foam; Rf = 0.15 (hexane–
EtOAc, 4:1).
1H NMR (300 MHz, CDCl3): δ = 0.47–0.74 (m, 4 H, CH2CH2CH),
0.89–0.96 (m, 3 H, CH2CH2CH3), 1.39–1.74 (m, 6 H, CH2CH2CH
+ CH2CH2CH3 + OH), 3.81 (s, 3 H, NCH3), 4.41 (t, J = 6.6 Hz, 1 H,
CHOH), 6.86–6.93 (m, 1 H, ArH), 7.11–7.30 (m, 7 H, ArH), 7.47–
7.53 (m, 2 H, ArH). The signals of both isomers appear completely
overlapped.
N
R2
R3
Me
10
N
4
Me
11
[AuL]+
aura-iso-
Nazarov
protodemetalation
Ar
H
5
+
H2O
R1
[AuL]
elimination
OH
R3
R2
N
Me
12
Scheme 4 Proposed mechanism for the formation of benzofulvenes 5
13C NMR (75.4 MHz, CDCl3): δ = 2.5 (CH2), 2.6 (CH2), 3.8 (CH2),
3.9 (CH2), 13.9 (CH3, both isomers), 18.6 (CH2, both isomers), 21.3
(CH), 21.4 (CH), 32.9 (CH3, both isomers), 40.3 (CH2, both iso-
mers), 45.5 (C, both isomers), 62.6 (CH, both isomers), 85.5 (C,
both isomers), 85.76 (C), 85.78 (C), 109.3 (CH, both isomers),
118.80 (CH), 118.81 (CH), 119.7 (C), 119.8 (C), 121.2 (CH, both
isomers), 121.6 (CH, both isomers), 126.2 (C, both isomers), 126.5
(CH, both isomers), 127.10 (CH), 127.12 (CH), 127.2 (2 × CH, both
isomers), 128.1 (2 × CH, both isomers), 137.8 (C, both isomers),
145.68 (C), 145.71 (C).
of the reaction, the nature of the alkyl group (R1) at the
propargylic position, and mainly on the steric hindrance
of the hydroxy group. With primary or secondary alco-
hols, the coordination of the hydroxy group with the me-
tallic center could be favored compared with more
encumbered tertiary alcohols leading to a higher selectiv-
ity for the elimination pathway. These facts also support
that the generation of benzofulvenes 5 is not due to an
elimination of water from alcohols 4 that would be more
favored with highly substituted alcohols.
MS (EI, 70 eV): m/z (%) = 357 (64, M+), 329 (100), 157 (68), 144
(95).
HRMS-EI: m/z [M]+ calcd for C25H27NO: 357.2093; found:
In summary, we have developed a gold-catalyzed intra-
molecular transformation of 3-propargylindoles to give
new and interesting benzofulvene derivatives with an in-
dol-3-yl substituent at the C-2 position in moderate to
good yields under mild conditions. This process involves
a tandem 1,2-indole migration/aura-iso-Nazarov cycliza-
tion/elimination sequence.
357.2086.
2b
Yield: 479 mg (76%); white solid; Rf = 0.19 (hexane–Et2O, 1:1); mp
54–56 °C.
1H NMR (300 MHz, CDCl3): δ = 0.55–0.76 (m, 4 H, CH2CH2CH),
1.55 (br s, 1 H, OH), 1.56–1.67 (m, 1 H, CH2CH2CH), 3.81 (s, 3 H,
NCH3), 4.29 (s, 2 H, CH2OH), 6.87–6.94 (m, 1 H, ArH), 7.12–7.31
(m, 7 H, ArH), 7.50–7.56 (m, 2 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 2.5 (CH2), 3.8 (CH2), 21.3 (CH),
32.8 (CH3), 45.5 (C), 51.3 (CH2), 82.6 (C), 86.4 (C), 109.3 (CH),
118.8 (CH), 119.5 (C), 121.1 (CH), 121.6 (CH), 126.0 (C), 126.6
(CH), 127.20 (CH), 127.22 (2 × CH), 128.1 (2 × CH), 137.8 (C),
145.4 (C).
MS (EI, 70 eV): m/z (%) = 315 (38, M+), 287 (49), 274 (33), 157
(54), 144 (100), 131 (32).
All reactions involving air-sensitive compounds were carried out
under a N2 atmosphere, in oven-dried glassware, with magnetic stir-
ring. Temperatures are reported as bath temperatures. Solvents used
in extraction and purification were distilled prior to use. TLC was
performed on alumina-backed plates coated with silica gel 60 with
F254 indicator and the chromatograms were visualized by UV light
(254 nm and/or 366 nm) and/or by staining with a Ce/Mo reagent
and subsequent heating. Rf values refer to silica gel. NMR spectra
were measured on Varian Mercury-Plus 300 MHz and Varian Ino-
HRMS-EI: m/z [M]+ calcd for C22H21NO: 315.1623; found:
315.1628.
1
va-400 MHz spectrometers. H NMR: standard abbreviations are
used for indicating the multiplicities; the chemical shifts are report-
ed in ppm using residual solvent peak as reference. 13C NMR spec-
tra were recorded at 75.4 MHz or 100.6 MHz using broadband
proton decoupling and chemical shifts are reported in ppm using re-
sidual solvent peaks as reference (CDCl3: δ = 77.16 ppm) and the
multiplicities were determined by DEPT experiments. High-resolu-
tion mass spectra (HRMS) were recorded on a Micromass Autospec
spectrometer using EI at 70eV. Melting points were measured on a
Gallenkamp apparatus using open capillary tubes and are uncorrect-
ed. GC-MS and low-resolution mass spectra (LRMS) measure-
2c
Isolated as a ~1:1 mixture of diastereoisomers; yield: 663 mg
(78%); white foam; Rf = 0.15 (hexane–EtOAc, 4:1).
1H NMR (300 MHz, CDCl3): δ = 0.56–0.78 (m, 4 H, CH2CH2CH),
1.62–1.71 (m, 1 H, CH2CH2CH), 2.46 (br s, 1 H, OH), 3.80 (s, 3 H,
NCH3), 5.43 (s, 1 H, CHOH), 6.90–6.97 (m, 1 H, ArH), 7.17–7.36
(m, 9 H, ArH), 7.41 (d, J = 8.3 Hz, 2 H, ArH), 7.53–7.58 (m, 2 H,
ArH). The signals of both isomers appear completely overlapped.
13C NMR (75.4 MHz, CDCl3): δ = 2.59 (CH2), 2.62 (CH2), 3.9
(CH2, both isomers), 21.5 (CH, both isomers), 32.9 (CH3, both iso-
Synthesis 2012, 44, 1874–1884
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Benzofulvenes by a Tandem Reaction
1879
mers), 45.7 (C, both isomers), 64.1 (CH, both isomers), 83.9 (C),
84.0 (C), 88.26 (C), 88.29 (C), 109.3 (CH, both isomers), 118.9
(CH, both isomers), 119.35 (C), 119.39 (C), 121.2 (CH, both iso-
mers), 121.7 (CH, both isomers), 126.1 (C, both isomers), 126.7
(CH, both isomers), 127.2 (3 × CH, both isomers), 128.1 (2 × CH,
both isomers), 128.2 (2 × CH, both isomers), 128.6 (2 × CH, both
isomers), 133.91 (C), 133.94 (C), 137.8 (C, both isomers), 139.6 (C,
both isomers), 145.20 (C), 145.23 (C).
MS (EI, 70 eV): m/z (%) = 425 (42, M+), 397 (52), 284 (59), 157
(65).
HRMS-EI: m/z [M]+ calcd for C28H24ClNO: 425.1546; found:
425.1546.
1H NMR (300 MHz, CDCl3): δ = 0.54–0.92 (m, 4 H, CH2CH2CH),
1.57–1.69 (m, 1 H, CH2CH2CH), 3.77 (s, 3 H, NCH3 or OCH3), 3.79
(s, 3 H, NCH3 or OCH3), 4.57 (br s, 1 H, OH), 5.43 (d, J = 4.9 Hz,
1 H, CHOH), 6.73–6.83 (m, 2 H, ArH), 6.88–6.95 (m, 1 H, ArH),
7.05–7.10 (m, 1 H, ArH), 7.13–7.49 (m, 9 H, ArH). The signals of
both isomers appear completely overlapped.
13C NMR (75.4 MHz, CDCl3): δ = 2.6 (CH2, both isomers), 3.8
(CH2, both isomers), 21.6 (CH, both isomers), 32.9 (CH3, both iso-
mers), 45.0 (C, both isomers), 55.3 (CH3, both isomers), 64.1 (CH,
both isomers), 83.65 (C), 83.67 (C), 88.6 (C), 88.7 (C), 109.4 (CH,
both isomers), 113.4 (2 × CH, both isomers), 118.9 (CH, both iso-
mers), 119.6 (C, both isomers), 121.3 (CH, both isomers), 121.7
(CH, both isomers), 126.1 (C, both isomers), 127.1 (CH, both iso-
mers), 128.16 (2 × CH), 128.20 (2 × CH), 128.3 (2 × CH, both iso-
mers), 128.65 (2 × CH), 128.66 (2 × CH), 133.9 (C), 134.0 (C),
137.3 (C), 137.4 (C), 137.8 (C, both isomers), 139.6 (C, both iso-
mers), 158.2 (C, both isomers).
2e
Yield: 466 mg (68%); white solid; Rf = 0.20 (hexane–EtOAc, 3:1);
mp 55–57 °C.
1H NMR (300 MHz, CDCl3): δ = 0.54–0.86 (m, 4 H, CH2CH2CH),
1.57 (s, 6 H, CH3CCH3), 1.60–1.70 (m, 1 H, CH2CH2CH), 2.19 (br
s, 1 H, OH), 3.81 (s, 3 H, NCH3), 6.93–7.01 (m, 1 H, ArH), 7.18–
7.37 (m, 7 H, ArH), 7.56–7.62 (m, 2 H, ArH).
MS (EI, 70 eV): m/z (%) = 455 (39, M+), 427 (70), 314 (100), 157
(53).
HRMS-EI: m/z [M]+ calcd for C29H26ClNO2: 455.1652; found:
13C NMR (75.4 MHz, CDCl3): δ = 2.5 (CH2), 3.8 (CH2), 21.3 (CH),
31.67 (CH3), 31.71 (CH3), 32.8 (CH3), 45.3 (C), 65.4 (C), 82.8 (C),
89.4 (C), 109.2 (CH), 118.7 (CH), 119.8 (C), 121.2 (CH), 121.5
(CH), 126.3 (C), 126.5 (CH), 127.0 (CH), 127.1 (2 × CH), 128.0 (2
× CH), 137.8 (C), 145.9 (C).
MS (EI, 70 eV): m/z (%) = 343 (54, M+), 315 (100), 302 (41), 157
(41), 144 (61).
455.1651.
1-Cyclopropyl-1-(1-methyl-1H-indol-3-yl)-1-phenylhept-2-yn-
4-yl Acetate (1a)
To a solution of alkynol 2a (179 mg, 0.5 mmol) in CH2Cl2 (1 mL)
were added successively Et3N (202 mg, 2 mmol), 4-dimethylamino-
pyridine (12 mg, 0.1 mmol) and Ac2O (102 mg, 1 mmol). The reac-
tion mixture was stirred overnight, cooled to 0 °C and quenched
with sat. aq NH4Cl (10 mL). The resulting mixture was extracted
with Et2O (2 × 10 mL) and the combined organic layers were
washed with brine (10 mL), and dried (Na2SO4). The solvent was
removed under reduced pressure and the crude residue was purified
by flash column chromatography on silica gel using hexane–Et2O
(3.5:1) as eluent to afford 1a as a ~1:1 mixture of diastereoisomers;
yield: 156 mg (78%); yellow oil; Rf = 0.22 (hexane–Et2O, 3.5:1).
HRMS-EI: m/z [M]+ calcd for C24H25NO: 343.1936; found:
343.1939.
2f
Yield: 644 mg (60%); white solid; Rf = 0.22 (hexane–Et2O, 3:1); mp
80–82 °C.
1H NMR (300 MHz, CDCl3): δ = 0.51–0.71 (m, 4 H, CH2CH2CH),
1.58–1.69 (m, 1 H, CH2CH2CH), 2.73 (br s, 1 H, OH), 3.81 (s, 3 H,
NCH3), 6.85–6.92 (m, 1 H, ArH), 7.15–7.33 (m, 11 H, ArH), 7.37–
7.51 (m, 6 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 2.7 (CH2), 4.1 (CH2), 21.6 (CH),
33.0 (CH3), 45.9 (C), 73.9 (C), 86.4 (C), 89.9 (C), 109.4 (CH), 119.0
(CH), 119.3 (C), 121.2 (CH), 121.8 (CH), 126.2 (C), 126.8 (CH),
127.18 (2 × CH), 127.23 (CH), 127.6 (4 × CH), 128.2 (2 × CH),
128.45 (2 × CH), 128.46 (2 × CH), 133.7 (2 × C), 137.9 (C), 143.6
(2 × C), 145.2 (C).
1H NMR (300 MHz, CDCl3): δ = 0.49–0.74 (m, 4 H, CH2CH2CH),
0.88–0.92 (m, 3 H, CH2CH2CH3), 1.39–1.46 (m, 2 H, CH2CH2CH3),
1.55–1.76 (m, 3 H, CH2CH2CH + CH2CH2CH3), 2.04 (s, 3 H,
OCOCH3), 3.80 (s, 3 H, NCH3), 5.38–5.44 (m, 1 H, CHOAc), 6.87–
6.92 (m, 1 H, ArH), 7.12–7.29 (m, 7 H, ArH), 7.49–7.53 (m, 2 H,
ArH). The signals of both isomers are overlapped.
13C NMR (75.4 MHz, CDCl3): δ = 2.50 (CH2), 2.53 (CH2), 3.78
(CH2), 3.83 (CH2), 13.7 (CH3, both isomers), 18.5 (CH2, both iso-
mers), 21.1 (CH, both isomers), 21.3 (CH3, both isomers), 32.8
(CH3, both isomers), 37.0 (CH2, both isomers), 45.5 (C, both iso-
mers), 64.38 (CH), 64.43 (CH), 82.1 (C), 82.2 (C), 86.0 (C), 86.1
(C), 109.2 (CH, both isomers), 118.7 (CH, both isomers), 119.4 (C),
119.5 (C), 121.2 (CH), 121.3 (CH), 121.5 (CH, both isomers), 126.1
(C, both isomers), 126.5 (CH, both isomers), 127.07 (CH), 127.09
(CH), 127.1 (2 × CH), 127.2 (2 × CH), 128.0 (2 × CH, both iso-
mers), 137.7 (C, both isomers), 145.58 (C), 145.60 (C), 170.1 (C),
170.2 (C).
2g
Yield: 442 mg (64%); white solid; Rf = 0.19 (hexane–Et2O, 1:2); mp
62–64 °C.
1H NMR (300 MHz, CDCl3): δ = 0.52–0.74 (m, 4 H, CH2CH2CH),
1.56–1.64 (m, 2 H, CH2CH2CH + OH), 3.78 (s, 3 H, NCH3 or
OCH3), 3.80 (s, 3 H, NCH3 or OCH3), 4.28 (s, 2 H, CH2OH), 6.81
(d, J = 8.9 Hz, 2 H, ArH), 6.88–6.95 (m, 1 H, ArH), 7.13–7.31 (m,
4 H, ArH), 7.43 (d, J = 8.9 Hz, 2 H, ArH).
MS (EI, 70 eV): m/z (%) = 399 (58, M+), 371 (53), 157 (55), 144
13C NMR (75.4 MHz, CDCl3): δ = 2.6 (CH2), 3.7 (CH2), 21.4 (CH),
32.9 (CH3), 44.9 (C), 51.6 (CH2), 55.3 (CH3), 82.4 (C), 87.0 (C),
109.3 (CH), 113.4 (2 × CH), 118.9 (CH), 119.8 (C), 121.3 (CH),
121.6 (CH), 126.1 (C), 127.2 (CH), 128.4 (2 × CH), 137.6 (C),
137.8 (C), 158.2 (C).
MS (EI, 70 eV): m/z (%) = 345 (67, M+), 317 (100), 304 (88), 157
(46), 144 (43).
(100).
HRMS-EI: m/z [M]+ calcd for C27H29NO2: 399.2198; found:
399.2196.
Alkynols 2d,i–l; 5-Cyclopropyl-5-(1-methyl-1H-indol-3-yl)-5-
phenylpent-3-yn-2-ol (2d); Typical Procedure
To a mixture of the corresponding alkynol 9 (Ar = Ph, R1 = c-C3H5,
R2 = Me; 477 mg, 2.2 mmol) and N-methylindole (6; 262 mg, 2
mmol) in MeCN (2 mL) was added PTSA (19 mg, 0.1 mmol). The
reaction mixture was stirred at r.t. until the indole was consumed, as
determined by GC-MS and/or TLC. The solvent was removed, aq 1
M NaOH (10 mL) was added and the mixture extracted with Et2O
(2 × 10 mL). The combined organic layers were dried (Na2SO4) and
the solvent was removed under reduced pressure. The residue was
HRMS-EI: m/z [M]+ calcd for C23H23NO2: 345.1729; found:
345.1726.
2h
Isolated as a ~1:1 mixture of diastereoisomers; yield: 601 mg
(66%); brown solid; Rf = 0.19 (hexane–Et2O, 2:1); mp 55–57 °C.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1874–1884

1880
E. Álvarez et al.
SPECIAL TOPIC
purified by silica gel column chromatography using hexane–Et2O
(1.5:1) as eluent to afford 2d as a ~1:1 mixture of diastereoisomers;
yield: 474 mg (72%); white foam; Rf = 0.13 (hexane–Et2O, 1.5:1).
1H NMR (300 MHz, CDCl3): δ = 0.51–0.79 (m, 4 H, CH2CH2CH),
1.47 (d, J = 6.6 Hz, 3 H, CHCH3), 1.56–1.67 (m, 1 H, CH2CH2CH),
1.84 (br s, 1 H, OH), 3.81 (s, 3 H, NCH3), 4.55 (q, J = 6.6 Hz, 1 H,
CHOH), 6.89–6.96 (m, 1 H, ArH), 7.14–7.33 (m, 7 H, ArH), 7.51–
7.57 (m, 2 H, ArH). The signals of both isomers appear completely
overlapped.
13C NMR (75.4 MHz, CDCl3): δ = 2.50 (CH2), 2.54 (CH2), 3.80
(CH2), 3.82 (CH2), 21.30 (CH), 21.32 (CH), 24.8 (CH3, both iso-
mers), 32.9 (CH3, both isomers), 45.4 (C, both isomers), 58.7 (CH,
both isomers), 84.8 (C, both isomers), 86.6 (C, both isomers), 109.3
(CH, both isomers), 118.8 (CH), 118.9 (CH), 119.7 (C, both iso-
mers), 121.2 (CH, both isomers), 121.6 (CH, both isomers), 126.2
(C, both isomers), 126.6 (CH, both isomers), 127.11 (CH), 127.13
(CH), 127.2 (2 × CH, both isomers), 128.1 (2 × CH, both isomers),
137.8 (C, both isomers), 145.6 (C), 145.7 (C).
ArH), 7.15 (dd, J = 5.1, 1.3 Hz, 1 H, HetArH), 7.17–7.23 (m, 1 H,
ArH), 7.27–7.31 (m, 1 H, ArH), 7.53–7.57 (m, 1 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 31.8 (CH3), 32.7 (CH3), 36.7 (C),
51.2 (CH2), 80.3 (C), 90.6 (C), 109.5 (CH), 119.0 (CH), 119.7 (C),
120.9 (CH), 121.7 (CH), 124.1 (CH), 124.2 (CH), 125.6 (C), 126.2
(CH), 126.3 (CH), 137.7 (C), 151.7 (C).
MS (EI, 70 eV): m/z (%) = 295 (57, M+), 280 (100), 264 (71).
HRMS-EI: m/z [M]+ calcd for C18H17NOS: 295.1031; found:
295.1034.
2l
Isolated as a ~1:1 mixture of diastereoisomers; yield: 437 mg
(66%); white foam; Rf = 0.14 (hexane–Et2O, 1.5:1).
1H NMR (300 MHz, CDCl3): δ = 0.91 (d, J = 6.5 Hz, 3 H,
CHOHCHCH3), 1.26 (d, J = 6.5 Hz, 3 H, CH3CHCH3), 1.59 (d, J =
6.5 Hz, 3 H, CH3CHCH3), 2.02 (br s, 1 H, OH), 2.84 (sept, J = 6.5
Hz, 1 H, CH3CHCH3), 3.76 (s, 3 H, NCH3), 4.73 (q, J = 6.5 Hz, 1
H, CHOH), 6.98–7.03 (m, 1 H, ArH), 7.12–7.20 (m, 3 H, ArH),
7.24–7.29 (m, 3 H, ArH), 7.61–7.64 (m, 2 H, ArH), 7.66–7.71 (m,
1 H, ArH). The signals of both isomers appear completely over-
lapped.
MS (EI, 70 eV): m/z (%) = 329 (68, M+), 301 (100), 288 (48), 157
(67), 144 (92).
HRMS-EI: m/z [M]+ calcd for C23H23NO: 329.1780; found:
13C NMR (75.4 MHz, CDCl3): δ = 19.0 (CH3, both isomers), 20.2
(CH3, both isomers), 24.9 (CH3, both isomers), 32.9 (CH3, both iso-
mers), 35.95 (CH), 35.97 (CH), 50.0 (C, both isomers), 58.9 (CH,
both isomers), 86.2 (C, both isomers), 88.1 (C, both isomers), 109.2
(CH, both isomers), 118.6 (C, both isomers), 118.8 (CH, both iso-
mers), 121.46 (CH, both isomers), 121.48 (CH, both isomers),
126.2 (CH, both isomers), 126.6 (C, both isomers), 126.7 (CH, both
isomers), 127.3 (2 × CH, both isomers), 127.9 (2 × CH, both iso-
mers), 137.5 (C, both isomers), 144.4 (C, both isomers).
329.1778.
2i
Isolated as a ~1:1 mixture of diastereoisomers; yield: 530 mg
(73%); white solid; Rf = 0.18 (hexane–Et2O, 1:1); mp 59–61 °C.
1H NMR (300 MHz, CDCl3): δ = 0.51–0.76 (m, 4 H, CH2CH2CH),
1.45 (d, J = 6.6 Hz, 3 H, CHCH3), 1.51–1.62 (m, 1 H, CH2CH2CH),
1.83 (br s, 1 H, OH), 3.81 (s, 3 H, NCH3), 4.54 (q, J = 6.6 Hz, 1 H,
CHOH), 6.90–6.98 (m, 1 H, ArH), 7.15–7.32 (m, 6 H, ArH), 7.42–
7.49 (m, 2 H, ArH). The signals of both isomers appear completely
overlapped.
MS (EI, 70 eV): m/z (%) = 331 (9, M+), 289 (75), 288 (100), 245
(55), 244 (39).
13C NMR (75.4 MHz, CDCl3): δ = 2.45 (CH2), 2.49 (CH2), 3.84
(CH2), 3.86 (CH2), 21.25 (CH), 21.27 (CH), 24.7 (CH3, both iso-
mers), 32.9 (CH3, both isomers), 45.1 (C, both isomers), 58.6 (CH,
both isomers), 84.3 (C, both isomers), 86.9 (C, both isomers), 109.4
(CH, both isomers), 118.97 (CH), 118.99 (CH), 119.2 (C, both iso-
mers), 121.0 (CH, both isomers), 121.8 (CH, both isomers), 126.0
(C, both isomers), 127.12 (CH), 127.13 (CH), 128.2 (2 × CH, both
isomers), 128.7 (2 × CH, both isomers), 132.3 (C, both isomers),
137.8 (C, both isomers), 144.32 (C), 144.34 (C).
MS (EI, 70 eV): m/z (%) = 363 (52, M+), 335 (77), 322 (39), 157
(70), 144 (100).
HRMS-EI: m/z [M]+ calcd for C23H22ClNO: 363.1390; found:
363.1388.
HRMS-EI: m/z [M]+ calcd for C23H25NO: 331.1936; found:
331.1931.
1-(3-Cyclopropyl-2-(1-methyl-1H-indol-3-yl)-1H-inden-1-
yl)butyl Acetate (3a)
PPh3AuNTf2 (18.5 mg, 5 mol%) was added to a solution of acetate
1a (200 mg, 0.5 mmol) in anhyd CH2Cl2 (1 mL) and the mixture was
stirred at r.t. until complete consumption of starting material (as ev-
ident by TLC or GC-MS analysis). The mixture was filtered through
a pad of silica gel, the solvent was removed, and the crude residue
was purified by flash column chromatography on silica gel using
hexane–EtOAc (20:1) as eluent to afford 3a as a ~1:1 mixture of di-
astereoisomers; yield: 62 mg (31%); orange oil; Rf = 0.25 (hexane–
Et2O, 2:1).
1H NMR (300 MHz, CDCl3): δ = 0.44–1.19 (m, 22 H both isomers,
CH2CH2CH + CH2CH2CH3), 1.44 (s, 3 H, COCH3), 1.87–2.02 (m,
2 H both isomers, CH2CH2CH), 2.22 (s, 3 H, COCH3), 3.88 (s, 3 H,
NCH3), 3.89 (s, 3 H, NCH3), 4.33–4.36 (m, 1 H, CHCHOAc), 4.45–
4.49 (m, 1 H, CHCHOAc), 5.10–5.17 (m, 1 H, CHOAc), 5.30–5.37
(m, 1 H, CHOAc), 7.10–7.40 (m, 12 H both isomers, ArH), 7.45–
7.59 (m, 4 H both isomers, ArH), 7.63–7.67 (m, 1 H, ArH), 7.85–
7.90 (m, 1 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 5.6 (CH2), 5.9 (CH2), 6.8 (CH2),
6.9 (CH2), 9.2 (CH), 9.8 (CH), 13.7 (CH3, both isomers), 19.0
(CH2), 19.4 (CH2), 20.9 (CH3), 21.6 (CH3), 29.6 (CH2), 30.5 (CH2),
33.1 (CH3), 33.2 (CH3), 54.1 (CH), 54.6 (CH), 75.8 (CH), 76.5
(CH), 109.3 (CH, both isomers), 110.6 (C), 112.0 (C), 119.5 (CH),
119.6 (CH), 119.78 (CH), 119.79 (CH), 120.8 (CH), 121.5 (CH),
121.6 (CH), 121.8 (CH), 123.2 (CH), 124.0 (CH), 124.4 (CH, both
isomers), 126.95 (CH), 127.00 (CH), 127.6 (C), 128.4 (C), 128.7
(CH), 129.0 (CH), 136.9 (C), 137.0 (C), 137.1 (C), 137.9 (C, both
isomers), 139.4 (C), 143.3 (C), 143.5 (C), 146.5 (C), 147.4 (C),
171.2 (C), 171.3 (C).
2j
Yield: 254 mg (44%); brown foam; Rf = 0.19 (hexane–Et2O, 1:1).
1H NMR (300 MHz, CDCl3): δ = 2.02 (br s, 1 H, OH), 2.07 (s, 3 H,
CCH3), 3.78 (s, 3 H, NCH3), 4.33 (s, 2 H, CH2OH), 6.97–7.07 (m,
2 H, ArH), 7.18–7.43 (m, 6 H, ArH), 7.56–7.62 (m, 2 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 31.1 (CH3), 32.8 (CH3), 39.4 (C),
51.5 (CH2), 80.9 (C), 91.1 (C), 109.4 (CH), 118.9 (CH), 119.9 (C),
121.1 (CH), 121.7 (CH), 125.9 (C), 126.4 (CH), 126.5 (CH), 126.6
(2 × CH), 128.2 (2 × CH), 137.8 (C), 145.9 (C).
MS (EI, 70 eV): m/z (%) = 289 (61, M+), 274 (100), 258 (58), 83
(22).
HRMS-EI: m/z [M]+ calcd for C20H19NO: 289.1467; found:
289.1478.
2k
Yield: 401 mg (68%); brown foam; Rf = 0.23 (hexane–Et2O, 1:1.5).
1H NMR (300 MHz, CDCl3): δ = 1.65 (br s, 1 H, OH), 2.13 (s, 3 H,
CCH3), 3.75 (s, 3 H, NCH3), 4.34 (s, 2 H, CH2OH), 6.90 (dd, J =
5.1, 3.5 Hz, 1 H, HetArH), 7.01 (s, 1 H, NCH=), 7.02–7.06 (m, 2 H,
Synthesis 2012, 44, 1874–1884
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Benzofulvenes by a Tandem Reaction
1881
MS (EI, 70 eV): m/z (%) = 399 (54, M+), 339 (37), 296 (46), 284
(100).
HRMS-EI: m/z [M]+ calcd for C27H29NO2: 339.2198; found:
339.2197.
5b
Yield: 114 mg (77%); yellow solid; Rf = 0.28 (hexane–Et2O, 1.5:1);
mp 128 °C (dec.).
1H NMR (300 MHz, CDCl3): δ = 0.73–0.94 (m, 4 H, CH2CH2CH),
1.93–2.04 (m, 1 H, CH2CH2CH), 3.89 (s, 3 H, NCH3), 5.61 (s, 1 H,
HHC=C), 6.02 (s, 1 H, HHC=C), 7.09 (s, 1 H, NCH=), 7.10–7.17
(m, 1 H, ArH), 7.18–7.32 (m, 4 H, ArH), 7.37–7.41 (m, 1 H, ArH),
7.62–7.69 (m, 2 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 6.1 (2 × CH2), 10.8 (CH), 33.0
(CH3), 109.0 (C), 109.3 (CH), 111.3 (CH2), 119.4 (2 × CH), 119.5
(CH), 121.2 (CH), 121.8 (CH), 124.9 (CH), 128.1 (CH), 128.5 (C),
128.9 (CH), 130.9 (C), 136.8 (C), 136.9 (C), 142.7 (C), 143.1 (C),
147.9 (C).
Gold-Catalyzed Reaction of Alkynols 2; 3-[(11E)-1-Butylidene-
3-cyclopropyl-1H-inden-2-yl]-1-methyl-1H-indole (5a) and 1-
[3-Cyclopropyl-2-(1-methyl-1H-indol-3-yl)-1H-inden-1-yl]bu-
tan-1-ol (4a); Typical Procedure
(PhO)3PAuCl (13.6 mg, 5 mol%) and AgNTf2 (9.7 mg, 5 mol%)
were successively added to a solution of alkynol 2a (179 mg, 0.5
mmol) in anhyd CH2Cl2 (1 mL) at –78 °C. The mixture was stirred
at a low temperature until complete consumption of starting materi-
al (as evident by TLC or GC-MS analysis). The mixture was filtered
through a pad of silica gel, the solvent was removed, and the crude
residue was purified by flash column chromatography on silica gel
using hexane–EtOAc (20:1) as eluent to afford 5a and then hexane–
EtOAc (4:1) as eluent to afford 4a (Table 2).
MS (EI, 70 eV): m/z (%) = 297 (100, M+), 296 (64), 282 (28), 268
(23).
HRMS-EI: m/z [M]+ calcd for C22H19N: 297.1517; found: 297.1517.
5c
5a
Yield: 163 mg (80%); orange solid; Rf = 0.26 (hexane–Et2O, 15:1);
Yield: 127 mg (75%); yellow oil; Rf = 0.23 (hexane–EtOAc, 20:1).
mp 124–126 °C.
1H NMR (300 MHz, CDCl3): δ = 0.67–0.82 (m, 4 H, CH2CH2CH),
1.06 (t, J = 7.4 Hz, 3 H, CH3CH2), 1.54–1.73 (m, 2 H, CH3CH2),
1.88–2.02 (m, 1 H, CH2CH2CH), 2.83 (q, J = 7.5 Hz, 2 H,
=CHCH2), 3.92 (s, 3 H, NCH3), 6.31 (t, J = 7.5 Hz, 1 H, HC=C),
7.08 (s, 1 H, NCH=), 7.15–7.23 (m, 1 H, ArH), 7.24–7.52 (m, 5 H,
ArH), 7.64–7.71 (m, 1 H, ArH), 7.83–7.90 (m, 1 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 5.9 (2 × CH2), 9.9 (CH), 14.3
(CH3), 23.0 (CH2), 31.8 (CH2), 33.0 (CH3), 109.2 (CH), 109.4 (C),
119.3 (CH), 119.4 (CH), 121.2 (CH), 121.7 (CH), 123.4 (CH),
124.5 (CH), 127.1 (CH), 129.0 (C), 129.1 (CH), 132.7 (C), 135.8
(C), 136.0 (CH), 136.8 (C), 139.0 (C), 140.4 (C), 144.5 (C).
1H NMR (300 MHz, CDCl3): δ = 0.65–0.95 (m, 4 H, CH2CH2CH),
1.91–1.99 (m, 1 H, CH2CH2CH), 3.91 (s, 3 H, NCH3), 6.98–7.08
(m, 2 H, ArH), 7.11–7.23 (m, 2 H, ArH), 7.24–7.52 (m, 9 H, ArH),
7.66–7.72 (m, 1 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 6.1 (2 × CH2), 10.4 (CH), 33.1
(CH3), 109.0 (C), 109.4 (CH), 119.5 (CH), 119.6 (CH), 121.1 (CH),
121.9 (CH), 122.9 (CH), 124.7 (CH), 128.1 (CH), 128.6 (2 × CH),
128.9 (C), 129.3 (CH), 130.1 (CH), 130.9 (2 × CH), 132.7 (C),
133.6 (C), 134.9 (C), 136.1 (C), 136.9 (C), 141.7 (C), 142.1 (C),
144.6 (C).
MS (EI, 70 eV): m/z (%) = 407 (100, M+), 406 (27), 296 (37), 282
(29).
HRMS-EI: m/z [M]+ calcd for C28H22ClN: 407.1441; found:
407.1443.
MS (EI, 70 eV): m/z (%) = 339 (100, M+), 310 (34), 296 (52), 281
(27), 268 (30).
HRMS-EI: m/z [M]+ calcd for C25H25N: 339.1987; found: 339.1982.
4a
5d
Isolated in the reaction of 2a with PPh3AuNTf2 at r.t. in 36% yield
(64 mg) and as a ~1.5:1 mixture of diastereoisomers; brown oil; Rf =
0.10 (hexane–EtOAc, 6:1).
Yield: 131 mg (84%); yellow solid; Rf = 0.32 (hexane–Et2O, 10:1);
mp 58–60 °C.
1H NMR (300 MHz, CDCl3): δ = 0.63–0.79 (m, 4 H, CH2CH2CH),
1.91 (quint, J = 7.1 Hz, 1 H, CH2CH2CH), 2.33 (d, J = 7.6 Hz, 3 H,
=CHCH3), 3.89 (s, 3 H, NCH3), 6.33 (q, J = 7.6 Hz, 1 H, =CHCH3),
7.05 (s, 1 H, NCH=), 7.11–7.18 (m, 1 H, ArH), 7.21–7.47 (m, 5 H,
ArH), 7.59–7.63 (m, 1 H, ArH), 7.82–7.86 (m, 1 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 5.9 (2 × CH2), 9.9 (CH), 15.7
(CH3), 33.0 (CH3), 109.2 (CH), 109.4 (C), 119.3 (CH), 119.4 (CH),
121.1 (CH), 121.7 (CH), 123.5 (CH), 124.5 (CH), 127.1 (CH),
128.9 (C), 129.1 (CH), 129.8 (CH), 132.5 (C), 136.0 (C), 136.8 (C),
139.0 (C), 141.5 (C), 144.5 (C).
1H NMR (300 MHz, CDCl3): δ = 0.44–0.97 (m, 7 H major + 7 H
minor, CH2CH2CH + CH2CH2CH3), 1.17–1.58 (m, 4 H major + 4 H
minor, CH2CH2CH3), 1.83–1.96 (m, 1 H major + 1 H minor,
CH2CH2CH), 3.85 (s, 3 H major, NCH3), 3.86 (s, 3 H minor, NCH3),
3.96–3.99 (m, 1 H major, CHOH), 4.00–4.05 (m, 1 H minor,
CHOH), 4.22 (br s, 1 H minor, CHCHOH), 4.31 (d, J = 4.1 Hz, 1 H
major, CHCHOH), 7.13–7.51 (m, 7 H major + 8 H minor, ArH),
7.75 (d, J = 8.0 Hz, 1 H major, ArH), 7.67 (d, J = 7.4 Hz, 1 H minor,
ArH), 7.80 (d, J = 8.0 Hz, 1 H major, ArH). The signal correspond-
ing to the OH is not observed.
13C NMR (75.4 MHz, CDCl3): δ = 5.68 (CH2, minor), 5.71 (CH2,
major), 7.0 (CH2, minor), 7.1 (CH2, major), 9.2 (CH, both isomers),
13.9 (CH3, major), 14.2 (CH3, minor), 19.2 (CH2, major), 19.9
(CH2, minor), 33.0 (CH2, major), 33.1 (CH3, major), 33.2 (CH3, mi-
nor), 36.6 (CH2, minor), 57.4 (CH, minor), 57.9 (CH, major), 73.1
(CH, minor), 73.6 (CH, major), 109.5 (CH, major), 109.6 (CH, mi-
nor), 111.1 (C, both isomers), 119.71 (CH, major), 119.74 (CH, ma-
jor), 119.85 (CH, minor), 119.94 (CH, major), 120.8 (CH, major),
120.9 (CH, minor), 121.9 (CH, major), 122.0 (CH, minor), 123.8
(CH, minor), 124.1 (CH, major), 124.2 (CH, minor), 124.4 (CH,
major), 126.8 (CH, major), 127.1 (CH, minor), 127.5 (C, minor),
127.6 (C, major), 128.9 (CH, major), 129.1 (CH, minor), 137.0 (C,
major), 137.1 (C, minor), 137.6 (C, major), 138.0 (C, major), 138.1
(C, minor), 138.9 (C, minor), 142.7 (C, minor), 144.2 (C, major),
147.1 (C, major), 147.2 (C, minor).
MS (EI, 70 eV): m/z (%) = 311 (100, M+), 296 (61), 281 (34), 268
(21).
HRMS-EI: m/z [M]+ calcd for C23H21N: 311.1674; found: 311.1678.
5e
Yield: 52 mg (32%); yellow solid; Rf = 0.29 (hexane–Et2O, 15:1);
mp 165–167 °C.
1H NMR (300 MHz, CDCl3): δ = 0.49–0.71 (m, 4 H, CH2CH2CH),
1.69 (s, 3 H, CH3CCH3), 1.68–1.77 (m, 1 H, CH2CH2CH), 2.42 (s,
3 H, CH3CCH3), 3.86 (s, 3 H, NCH3), 6.94 (s, 1 H, NCH=), 7.04–
7.10 (m, 1 H, ArH), 7.17–7.26 (m, 3 H, ArH), 7.32–7.36 (m, 1 H,
ArH), 7.39–7.44 (m, 1 H, ArH), 7.78–7.81 (m, 1 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 5.5 (CH2), 6.2 (CH2), 9.5 (CH),
24.9 (CH3), 26.1 (CH3), 32.9 (CH3), 109.1 (CH), 113.5 (C), 119.3
(CH), 119.4 (CH), 120.7 (CH), 121.7 (CH), 123.9 (CH), 124.5
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1874–1884

1882
E. Álvarez et al.
SPECIAL TOPIC
(CH), 125.8 (CH), 127.8 (CH), 129.3 (C), 131.8 (C), 136.5 (C),
137.0 (C), 137.5 (C), 141.5 (C), 142.8 (C), 142.9 (C).
HRMS-EI: m/z [M]+ calcd for C23H21NO: 327.1623; found:
327.1614.
MS (EI, 70 eV): m/z (%) = 325 (100, M+), 310 (79), 295 (27), 282
(33).
5h
Yield: 111 mg (51%); orange solid; Rf = 0.25 (hexane–Et2O, 10:1);
mp 160–162 °C.
HRMS-EI: m/z [M]+ calcd for C24H23N: 325.1830; found: 325.1825.
1H NMR (300 MHz, CDCl3): δ = 0.62–0.91 (m, 4 H, CH2CH2CH),
1.85–1.97 (m, 1 H, CH2CH2CH), 3.68 (s, 3 H, OCH3), 3.89 (s, 3 H,
NCH3), 6.75–6.81 (m, 1 H, ArH), 6.99 (s, 1 H, NCH=), 7.06–7.44
(m, 10 H, ArH), 7.62–7.67 (m, 1 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 6.0 (2 × CH2), 10.6 (CH), 33.1
(CH3), 55.6 (CH3), 109.1 (C), 109.3 (CH), 110.3 (CH), 112.6 (CH),
119.5 (CH), 119.7 (CH), 121.1 (CH), 121.8 (CH), 128.7 (2 × CH),
128.9 (C), 129.2 (CH), 129.7 (CH), 130.7 (2 × CH), 131.0 (C),
133.7 (C), 136.1 (C), 136.6 (C), 136.9 (C), 137.6 (C), 141.8 (C),
142.1 (C), 157.7 (C).
MS (EI, 70 eV): m/z (%) = 437 (100, M+), 422 (15), 326 (18), 312
(15).
HRMS-EI: m/z [M]+ calcd for C29H24ClNO: 437.1546; found:
437.1543.
4e
Yield: 89 mg (52%); white solid; Rf = 0.14 (hexane–Et2O, 1:2); mp
72–74 °C.
1H NMR (300 MHz, CDCl3): δ = 0.34–0.44 (m, 2 H, CH2CH2CH),
0.57–0.64 (m, 1 H, CH2CHHCH), 0.79 (s, 3 H, CH3CCH3), 0.82–
0.94 (m, 1 H, CH2CHHCH), 1.32 (s, 3 H, CH3CCH3), 1.82–1.92 (m,
1 H, CH2CH2CH), 2.04 (br s, 1 H, OH), 3.86 (s, 3 H, NCH3), 4.08
(br s, 1 H, CHCOH), 7.14 (s, 1 H, NCH=), 7.15–7.19 (m, 2 H, ArH),
7.25–7.37 (m, 3 H, ArH), 7.45–7.50 (m, 1 H, ArH), 7.59–7.64 (m,
2 H, ArH), 7.72–7.78 (m, 1 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 5.2 (CH2), 6.5 (CH2), 9.4 (CH),
25.9 (CH3), 28.3 (CH3), 33.1 (CH3), 63.2 (CH), 74.4 (C), 109.5
(CH), 112.1 (C), 119.8 (CH), 119.9 (CH), 121.3 (CH), 122.2 (CH),
124.1 (CH), 124.9 (CH), 126.9 (CH), 127.5 (C), 129.0 (CH), 137.0
(C), 138.0 (C), 140.1 (C), 144.2 (C), 146.6 (C).
5i
MS (EI, 70 eV): m/z (%) = 343 (17, M+), 285 (100), 270 (23), 256
(15).
HRMS-EI: m/z [M]+ calcd for C24H25NO: 343.1936; found:
343.1930.
Yield: 135 mg (78%); yellow solid; Rf = 0.29 (hexane–Et2O, 10:1);
mp 61–63 °C.
1H NMR (300 MHz, CDCl3): δ = 0.61–0.79 (m, 4 H, CH2CH2CH),
1.81–1.92 (m, 1 H, CH2CH2CH), 2.30 (d, J = 7.6 Hz, 3 H,
=CHCH3), 3.89 (s, 3 H, NCH3), 6.37 (q, J = 7.6 Hz, 1 H, =CHCH3),
7.04 (s, 1 H, NCH=), 7.13–7.18 (m, 1 H, ArH), 7.25–7.42 (m, 4 H,
ArH), 7.56–7.61 (m, 1 H, ArH), 7.77–7.80 (m, 1 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 6.0 (2 × CH2), 9.7 (CH), 15.7
(CH3), 33.1 (CH3), 109.0 (C), 109.3 (CH), 119.5 (CH), 120.0 (CH),
121.0 (CH), 121.8 (CH), 123.7 (CH), 126.8 (CH), 128.8 (C), 129.1
(CH), 130.2 (C), 131.3 (CH), 133.0 (C), 136.8 (C), 137.4 (C), 138.4
(C), 140.8 (C), 142.9 (C).
4f
Yield: 187 mg (70%); pale orange solid; Rf = 0.24 (hexane–Et2O,
3:1); mp 87–189 °C.
1H NMR (300 MHz, CDCl3): δ = 0.28–0.39 (m, 2 H, CH2CH2CH),
0.51–0.58 (m,
CH2CHHCH), 1.56–1.65 (m, 1 H, CH2CH2CH), 3.21 (br s, 1 H,
OH), 3.75 (s, 3 H, NCH3), 4.73 (br s, 1 H, CHCOH), 6.04 (d, J = 7.6
Hz, 1 H, ArH), 6.63 (br s, 1 H, ArH), 6.79 (d, J = 8.5 Hz, 2 H, ArH),
6.89–6.95 (m, 1 H, ArH), 7.04–7.31 (m, 11 H, ArH), 7.42 (d, J = 7.6
Hz, 1 H, ArH).
1 H, CH2CHHCH), 0.70–0.79 (m, 1 H,
MS (EI, 70 eV): m/z (%) = 345 (100, M+), 330 (50), 295 (29).
HRMS-EI: m/z [M]+ calcd for C23H20ClN: 345.1284; found:
13C NMR (75.4 MHz, CDCl3): δ = 4.9 (CH2), 6.0 (CH2), 9.2 (CH),
33.0 (CH3), 63.4 (CH), 80.4 (C), 109.4 (CH), 111.0 (C), 119.9 (CH),
120.1 (CH), 120.7 (CH), 122.3 (CH), 124.6 (CH), 124.8 (CH),
127.5 (CH), 127.7 (2 × CH), 127.8 (2 × CH), 128.0 (2 × CH), 128.6
(CH), 128.9 (2 × CH), 133.0 (C), 133.2 (C), 136.8 (C), 136.9 (C),
142.1 (C), 142.6 (C), 142.7 (C), 143.8 (C), 146.5 (C). The signal of
one quaternary aromatic carbon is not observed, probably over-
lapped by other signal.
345.1293.
5j
Yield: 47 mg (35%); yellow solid; Rf = 0.25 (hexane–Et2O, 15:1);
mp 215–217 °C.
1H NMR (300 MHz, CDCl3): δ = 2.21 (s, 3 H, CCH3), 3.88 (s, 3 H,
NCH3), 5.66 (s, 1 H, HHC=C), 6.07 (s, 1 H, HHC=C), 7.05 (s, 1 H,
NCH=), 7.12–7.18 (m, 1 H, ArH), 7.23–7.42 (m, 5 H, ArH), 7.55–
7.59 (m, 1 H, ArH), 7.62–7.69 (m, 1 H, ArH).
MS (EI, 70 eV): m/z (%) = 285 (100), 270 (16), 139 (43). [M]+ was
13C NMR (75.4 MHz, CDCl3): δ = 12.2 (CH3), 33.1 (CH3), 108.9
(C), 109.4 (CH), 111.7 (CH2), 118.4 (CH), 119.4 (CH), 119.5 (CH),
121.1 (CH), 121.9 (CH), 125.1 (CH), 128.2 (CH), 128.3 (C), 128.8
(CH), 130.6 (C), 136.4 (C), 137.1 (C), 138.5 (C), 144.7 (C), 148.0
(C).
MS (EI, 70 eV): m/z (%) = 271 (100, M+), 270 (75), 256 (36), 127
(19).
not observed.
HRMS-EI: m/z [M]+ calcd for C34H27Cl2NO: 535.1470; found:
535.1467.
5g
Yield: 74 mg (45%); orange solid; Rf = 0.20 (hexane–Et2O, 10:1);
mp 200–202 °C.
1H NMR (300 MHz, CDCl3): δ = 0.74–0.83 (m, 2 H, CH2CH2CH),
0.94–0.99 (m, 2 H, CH2CH2CH), 1.93–2.03 (m, 1 H, CH2CH2CH),
3.88 (s, 3 H, NCH3 or OCH3), 3.89 (s, 3 H, NCH3), 5.58 (s, 1 H,
HHC=C), 5.98 (s, 1 H, HHC=C), 6.81–6.87 (m, 1 H, ArH), 7.09 (s,
1 H, NCH=), 7.11–7.22 (m, 2 H, ArH), 7.24–7.32 (m, 2 H, ArH),
7.37–7.41 (m, 1 H, ArH), 7.65–7.70 (m, 1 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 6.0 (2 × CH2), 11.1 (CH), 33.0
(CH3), 55.8 (CH3), 106.6 (CH), 109.1 (C), 109.3 (CH), 110.7 (CH2),
112.8 (CH), 119.3 (CH), 119.8 (CH), 121.2 (CH), 121.7 (CH),
128.5 (C), 128.8 (CH), 129.4 (C), 136.1 (C), 136.9 (C), 138.9 (C),
142.9 (C), 147.9 (C), 158.2 (C).
HRMS-EI: m/z [M]+ calcd for C20H17N: 271.1361; found: 271.1352.
4j
Yield: 26 mg (18%); white solid; Rf = 0.25 (hexane–Et2O, 1:2); mp
83–85 °C.
1H NMR (300 MHz, CDCl3): δ = 2.23 (d, J = 1.9 Hz, 3 H, CH3), 3.74
(dd, J = 10.8, 5.8 Hz, 1 H, CHHOH), 3.85 (s, 3 H NCH3), 4.00 (dd,
J = 10.8, 4.7 Hz, 1 H, CHHOH), 4.20 (br s, 1 H minor, CHCHOH),
7.13 (s, 1 H, NCH=), 7.14–7.20 (m, 1 H, ArH), 7.21–7.39 (m, 5 H,
ArH), 7.56–7.59 (m, 1 H, ArH), 7.66–7.70 (m, 1 H, ArH). The sig-
nal corresponding to the OH was not observed.
MS (EI, 70 eV): m/z (%) = 327 (100, M+), 326 (35), 312 (28).
13C NMR (75.4 MHz, CDCl3): δ = 12.3 (CH3), 33.1 (CH3), 54.5
(CH), 64.1 (CH2), 109.7 (CH), 110.8 (C), 119.0 (CH), 120.0 (CH),
Synthesis 2012, 44, 1874–1884
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Benzofulvenes by a Tandem Reaction
1883
120.6 (CH), 122.2 (CH), 123.0 (CH), 124.6 (CH), 127.3 (CH),
127.4 (C), 128.4 (CH), 134.8 (C), 136.2 (C), 137.2 (C), 144.2 (C),
147.4 (C).
MS (EI, 70 eV): m/z (%) = 289 (65, M+), 258 (100), 205 (18).
HRMS-EI: m/z [M]+ calcd for C20H19NO: 289.1467; found:
289.1462.
Acknowledgment
We acknowledge MICINN (CTQ2010-15358 and CTQ2009-
09949) and Junta de Castilla y León (BU021A09 and GR-172) for
financial support. We are also grateful to MEC (FPU predoctoral
fellowships to E.A. and D.M., ‘Ramón y Cajal’ contract to
M.A.F.R. and ‘Juan de la Cierva’ contract to P.G.G.
5k
Yield: 42 mg (30%); orange solid; Rf = 0.21 (hexane–Et2O, 15:1);
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.omnorinIftangonmSorniuifIatoprtngiSutpor
mp 70 °C (dec.).
1H NMR (300 MHz, CDCl3): δ = 2.17 (s, 3 H, CCH3), 3.86 (s, 3 H,
NCH3), 5.66 (s, 1 H, HHC=C), 5.92 (s, 1 H, HHC=C), 6.99 (s, 1 H,
NCH=), 7.11–7.16 (m, 2 H, ArH), 7.19–7.22 (m, 1 H, ArH), 7.23–
7.30 (m, 1 H, ArH), 7.35–7.39 (m, 1 H, ArH), 7.56–7.60 (m, 1 H,
ArH).
13C NMR (75.4 MHz, CDCl3): δ = 13.8 (CH3), 33.0 (CH3), 109.0
(C), 109.4 (CH), 115.2 (CH2), 119.5 (CH), 119.7 (CH), 121.0 (CH),
121.9 (CH), 124.2 (CH), 128.3 (C), 128.7 (CH), 129.1 (C), 134.0
(C), 137.0 (C), 140.2 (C), 144.9 (C), 149.0 (C).
References
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MS (EI, 70 eV): m/z (%) = 277 (100, M+), 276 (51), 262 (30), 261
(31).
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Peabody, S.; Manoharan, M.; Clark, R. J.; Alabugin, I. V.
Org. Lett. 2004, 6, 2457.
HRMS-EI: m/z [M]+ calcd for C18H15NS: 277.0925; found:
277.0927.
5l
Isolated as a ~5:1 mixture E/Z; yield: 78 mg (50%); yellow solid;
Rf = 0.30 (hexane–Et2O, 15:1); mp 146–148 °C. NMR data of the
major isomer are provided.
1H NMR (300 MHz, CDCl3): δ = 1.33 (d, J = 7.1 Hz, 3 H,
CH3CHCH3), 1.39 (d, J = 7.1 Hz, 3 H, CH3CHCH3), 2.31 (d, J = 7.6
Hz, 3 H, CH=CH3), 3.15 (sept, J = 7.1 Hz, 1 H, CH3CHCH3), 3.88
(s, 3 H, NCH3), 6.22 (q, J = 7.6 Hz, 1 H, CH=CH3), 6.97 (s, 1 H,
NCH=), 7.11–7.17 (m, 1 H, ArH), 7.22–7.36 (m, 3 H, ArH), 7.37–
7.43 (m, 1 H, ArH), 7.49–7.55 (m, 1 H minor, ArH), 7.58–7.65 (m,
1 H, ArH), 7.87 (d, J = 7.5 Hz, 1 H, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 15.6 (CH3), 21.5 (CH3), 21.8
(CH3), 27.8 (CH), 33.0 (CH3), 109.3 (CH), 109.5 (C), 119.4 (CH),
120.7 (CH), 120.8 (CH), 121.8 (CH), 123.8 (CH), 124.4 (CH),
126.8 (CH), 128.8 (CH), 129.4 (C), 130.2 (CH), 130.8 (C), 136.7
(C), 136.9 (C), 142.0 (C), 143.2 (C), 145.2 (C).
MS (EI, 70 eV): m/z (%) = 313 (100, M+), 298 (68), 270 (42), 202
(35).
HRMS-EI: m/z [M]+ calcd for C23H23N: 313.1830; found: 313.1821.
4l
Isolated as a ~6:1 mixture of diastereoisomers, yield: 51 mg (31%);
white solid; Rf = 0.24 (hexane–Et2O, 1:3); mp 66–68 °C. NMR data
of the major isomer are provided.
1H NMR (300 MHz, CDCl3): δ = 1.06 (d, J = 6.4 Hz, 3 H,
CHOHCHCH3), 1.26 (d, J = 7.1 Hz, 3 H, CH3CHCH3), 1.44 (br s,
1 H, OH), 1.53 (d, J = 7.1 Hz, 3 H, CH3CHCH3), 3.30 (sept, J = 7.1
Hz, 1 H, CH3CHCH3), 3.86 (s, 3 H, NCH3), 4.19 (d, J = 3.3 Hz, 1
H, CHCHOH), 4.23–4.30 (m, 1 H, CHOH), 7.07 (s, 1 H, NCH=),
7.15–7.25 (m, 2 H, ArH), 7.28–7.41 (m, 3 H, ArH), 7.51–7.55 (m,
1 H, ArH), 7.61–7.68 (m, 2 H minor, ArH).
13C NMR (75.4 MHz, CDCl3): δ = 19.4 (CH3), 21.2 (CH3), 21.7
(CH3), 27.6 (CH), 33.1 (CH3), 58.7 (CH), 69.6 (CH), 109.7 (CH),
111.4 (C), 120.0 (CH), 120.3 (CH), 121.5 (CH), 122.3 (CH), 123.8
(CH), 124.2 (CH), 126.7 (CH), 127.7 (C), 128.1 (CH), 134.7 (C),
137.2 (C), 144.3 (C), 144.9 (C), 146.7 (C).
(12) See, for instance: Clegg, N. J.; Paruthiyil, S.; Leitman, D. C.;
Scanlan, T. S. J. J. Med. Chem. 2005, 48, 5989.
(13) For selected recent benzofulvene syntheses from
monocyclic precursors, see: (a) Lee, C.-Y.; Wu, M.-J. Eur.
J. Org. Chem. 2007, 3463. (b) Bucher, G.; Mahajan, A. A.;
Schmittel, M. J. Org. Chem. 2008, 73, 8815. (c) Cordier, P.;
Aubert, C.; Malacria, M.; Lacôte, E.; Gandon, V. Angew.
Chem. Int. Ed. 2009, 48, 8757. (d) Jeffrey, J. L.; Sarpong, R.
Tetrahedron Lett. 2009, 50, 1969. (e) Ye, S.; Gao, K.; Zhou,
MS (EI, 70 eV): m/z (%) = 331 (96, M+), 287 (60), 272 (91), 244
(100).
HRMS-EI: m/z [M]+ calcd for C23H25NO: 331.1936; found:
331.1935.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1874–1884

1884
E. Álvarez et al.
SPECIAL TOPIC
H.; Yang, X.; Wu, J. Chem. Commun. 2009, 5406. (f) Bryan,
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(16) The selectivity of this tandem reaction (1,2-migration
followed by aura-iso-Nazarov cyclization) could be
switched by the proper choice of catalyst and reaction
conditions allowing the isolation of 2-(inden-3-yl)indenes
derived from an aura-Nazarov cyclization. See: Álvarez, E.;
(19) Mézailles, N.; Ricard, L.; Gagosz, F. Org. Lett. 2005, 7,
4133.
(20) The stereochemistry of the double bond was assigned by
NOESY experiments. See Supporting Information.
(21) CCDC 869753 (5c) contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge
Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Synthesis 2012, 44, 1874–1884
© Georg Thieme Verlag Stuttgart · New York