Gold(I)-catalyzed cycloisomerizations and alkoxycyclizations of ortho-(alkynyl)styrenes

Article abstract of DOI:10.1002/chem.201405789

Indenes and related polycyclic structures have been efficiently synthesized by gold(I)-catalyzed cycloisomerizations of appropriate ortho-(alkynyl)styrenes. Disubstitution at the terminal position of the olefin was demonstrated to be essential to obtain products originating from a formal 5-endo-dig cyclization. Interestingly, a complete switch in the selectivity of the cyclization of o-(alkynyl)-a-methylstyrenes from 6-endo to 5-endo was observed by adding an alcohol to the reaction media. This allowed the synthesis of interesting indenes bearing an all-carbon quaternary center at C1. Moreover, dihydrobenzo[a]fluorenes can be obtained from substrates bearing a secondary alkyl group at the β-position of the styrene moiety by a tandem cycloisomerization/1,2-hydride migration process. In addition, diverse polycyclic compounds were obtained by an intramolecular gold-catalyzed alkoxycyclization of o-(alkynyl)styrenes bearing a nucleophile in their structure. Finally, the use of a chiral gold complex allowed access to elusive chiral 1H-indenes in good enantioselectivities.

Full text of DOI:10.1002/chem.201405789

DOI: 10.1002/chem.201405789
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&
Asymmetric Catalysis
Gold(I)-Catalyzed Cycloisomerizations and Alkoxycyclizations of
ortho-(Alkynyl)styrenes
Ana M. Sanjuꢀn,[a] Muhammad A. Rashid,[a, c] Patricia Garcꢁa-Garcꢁa,[a] Alberto Martꢁnez-
Cuezva,[a, d] Manuel A. Fernꢀndez-Rodrꢁguez,[a] Fꢂlix Rodrꢁguez,[b] and Roberto Sanz*[a]
Abstract: Indenes and related polycyclic structures have
been efficiently synthesized by gold(I)-catalyzed cycloisome-
rizations of appropriate ortho-(alkynyl)styrenes. Disubstitu-
tion at the terminal position of the olefin was demonstrated
to be essential to obtain products originating from a formal
5-endo-dig cyclization. Interestingly, a complete switch in the
selectivity of the cyclization of o-(alkynyl)-a-methylstyrenes
from 6-endo to 5-endo was observed by adding an alcohol
to the reaction media. This allowed the synthesis of interest-
ing indenes bearing an all-carbon quaternary center at C1.
Moreover, dihydrobenzo[a]fluorenes can be obtained from
substrates bearing a secondary alkyl group at the b-position
of the styrene moiety by a tandem cycloisomerization/1,2-
hydride migration process. In addition, diverse polycyclic
compounds were obtained by an intramolecular gold-cata-
lyzed alkoxycyclization of o-(alkynyl)styrenes bearing a nucle-
ophile in their structure. Finally, the use of a chiral gold com-
plex allowed access to elusive chiral 1H-indenes in good
enantioselectivities.
array of catalytically useful transformations.[1,2] In this context,
the use of olefins as internal nucleophiles has been extensively
studied and, therefore, a wide number of synthetically and
mechanistically attractive metal-catalyzed cycloisomerizations
of enynes have been described.[3] The outcome of these rear-
rangements is determined by diverse factors, including the re-
action conditions, the catalyst, and the nature and position of
the different substituents of the enyne.[4]
Introduction
Transition-metal-catalyzed cyclization of polyunsaturated sub-
strates has nowadays become one of the most valuable tools
for the straightforward synthesis of cyclic compounds under
mild conditions.[1] These processes frequently provide a signifi-
cant increase in structural complexity furnishing functionalized
molecules not easily accessible by conventional methodologies
from rather simple precursors. Among all these strategies, the
p-activation of alkynes by carbophilic Lewis acids, mainly gold-
or platinum-derived complexes, towards attack by different nu-
cleophiles has prompted the development of an impressive
In particular, 1,3-dien-5-ynes, including ortho-(alkynyl)styr-
enes, although less studied than parent 1,5-enynes,[5] have ex-
hibited interesting transformations. Simple conjugated dien-
ynes afford benzene derivatives through varied cycloaromatiza-
tion mechanisms[6] regardless of the dienyne and the catalyst
employed.[7] In contrast, the substitution pattern of the olefin
plays a critical role in the cycloisomerization of ortho-(alkynyl)-
styrenes (Scheme 1). Thus, the skeletal rearrangement of o-(al-
kynyl)styrenes a-substituted and mono- or non-b-substituted
to produce naphthalenes through a 6-endo cyclization process
has been described using complexes derived from several
metals such as W,[8] Rh,[9] Ru,[9] Pd,[9–11] Pt,[9,11] Ag,[12] or Au[9,13] as
catalysts (Scheme 1a). Related cycloaromatizations of o-(alky-
nyl)biaryls also occurred allowing the efficient preparation of
substituted phenanthrenes and other polycyclic heteroar-
enes.[14] Notably, a total 6-endo selectivity is usually achieved in
these reported cyclizations and only in particular examples the
5-exo adducts are formed,[13a,c] whereas no products derived
from a 5-endo cyclization are even detected. Moreover, Liu and
co-workers have studied the ruthenium-catalyzed isomeriza-
tion of o-(ethynyl)styrenes to give different products by a cas-
cade reaction proceeding by formation of a vinylidene species
(Scheme 1b).[15]
[a] A. M. Sanjuꢀn, Dr. M. A. Rashid, Dr. P. Garcꢁa-Garcꢁa,
Dr. A. Martꢁnez-Cuezva, Dr. M. A. Fernꢀndez-Rodrꢁguez, Prof. Dr. R. Sanz
ꢂrea de Quꢁmica Orgꢀnica, Departamento de Quꢁmica
Facultad de Ciencias, Universidad de Burgos
Pza. Misael BaÇuelos s/n, 09001 Burgos (Spain)
E-mail: rsd@ubu.es
Homepage: http://www2.ubu.es/ginves/cien_biotec/sintorg/uk/index.htm
[b] Dr. F. Rodrꢁguez
Instituto Universitario de Quꢁmica Organometꢀlica “Enrique Moles”
Universidad de Oviedo
C/Juliꢀn Claverꢁa 8, 33006 Oviedo (Spain)
[c] Dr. M. A. Rashid
Current address:
Department of Chemistry
University of Agriculture, Faisalabad 38040 (Pakistan)
[d] Dr. A. Martꢁnez-Cuezva
Current address:
Departmento de Quꢁmica Orgꢀnica, Facultad de Quꢁmica
Regional Campus of International Excellence “Campus Mare Nostrum”
Universidad de Murcia, Murcia (Spain)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201405789.
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Table 1. Gold(I)-catalyzed cycloisomerization of model o-(alkynyl)styrenes
1–3.[a]
Entry
Enyne
R1
R2
R3
Product
Yield [%][b]
[c]
1
2
3
4
5
6
1a
1b
2a
2b
2c
3a
H
H
Me
Me
Me
H
H
Me
H
Me
Ph
Me
H
H
H
H
H
Me
–
–
–
–
83
84
88
88
[d]
4a
4b
4c
5a
[a] Reactions conducted using 0.5 mmol of o-(alkynyl)styrene derivative
1–3 in CH2Cl2 (1 mL) at RT. [b] Yield of isolated product based on starting
materials 1–3. [c] Starting material was recovered. [d] Unidentifiable mix-
ture of products based on 1H NMR spectroscopic analysis of the crude.
Scheme 1. Transition-metal-catalyzed cycloisomerizations of o-(alkynyl)styr-
enes.
entry 1). By using the b-monosubstituted (R2 =Me) o-(phenyle-
thynyl)styrene 1b, a mixture of unidentifiable compounds was
formed (Table 1, entry 2). Next, we tried the reaction with the
In this scenario we considered that o-(alkynyl)styrenes could
evolve through a different reaction pathway to give 1H-in-
denes derivatives (Scheme 1c). Thus, our experience in the
field of gold catalysis[16] led us to suggest that o-(alkynyl)styr-
enes possessing an internal acetylene and a disubstituted
alkene (R3, R4 ¼H) should evolve through a 5-endo-dig cycloiso-
merization to give intermediate A. An elimination reaction
from this cationic intermediate or treatment with an appropri-
ate nucleophile (i.e. an alcohol) should deliver the desired 1H-
indenes derivatives. Therefore, in a recent publication we have
reported the gold(I)-catalyzed cyclization and alkoxycyclization
of o-(alkynyl)styrenes disubstituted at the terminal position of
the olefin. This work proved our hypothesis and it allowed us
to develop an efficient method to get functionalized 1H-in-
denes (Scheme 1c).[17] In addition, we have also described an
efficient synthesis of dihydrobenzo[a]fluorenes from substrates
bearing a secondary alkyl group at the b-position of the sty-
rene moiety.[18] Herein, we wish to report a detailed study on
the evolution of o-(alkynyl)styrenes under gold catalysis.
a-substituted
(R1 =Me)
o-(phenylethynyl)styrenes
2a–
c (Table 1, entries 3–5). Considering previous reports (see
Scheme 1a) and also the stability of the two possible formal in-
termediates A and B formed after activation of the alkyne and
further attack of the olefin, we expected in these cases the for-
mation of the corresponding 6-endo-cyclization products. In
fact, we isolated the naphthalene derivatives 4a–c in very high
yield. Finally, a key experiment was performed with the b,b-
dibsubstituted (R2 =R3 =Me) o-(phenylethynyl)styrene 3a
(Table 1, entry 6). As previously commented, we thought that
in this case the reaction should proceed through intermediate
B to give the 5-endo product. Pleasantly, our plan came true
and accordingly we observed how the reaction cleanly evolved
to afford the indenyl derivative 5a in a very high yield
(88%).[19] Remarkably, the reaction took place with complete
regioselection as we did not observe the formation of products
coming from 6-endo or 5-exo additions of the alkene to the
carbon–carbon triple bond. A catalyst screening showed that
several cationic gold(I) complexes, either preformed (such as
[AuNTf2(Ph3P)]) or generated in situ with silver salts, were able
to promote the indene formation within 30 min, whereas no
reaction was observed with metal complexes such as AgSbF6,
PtCl2, [PtCl2(cod)] (cod=1,5-cyclooctadiene), CuI, AuCl3, AuCl or
[AuCl(Ph3P)].[20]
Results and Discussion
Preliminary results
To test our hypothesis regarding the influence of the substitu-
tion pattern at the olefin moiety on the outcome of the cycloi-
somerization, representative o-(phenylethynyl)styrenes 1–3
were prepared. Starting from the simplest o-(alkynyl)-styrene
1a (R1 =R2 =R3 =H) we did not observe reaction in the pres-
ence of the cationic gold(I) complex generated in situ from
5 mol% of [AuCl(Ph3P)] and 5 mol% of AgSbF6 (Table 1,
Synthesis of 1H-indenes by cycloisomerization of 2’,2’-disub-
stituted o-(alkynyl)styrenes 3
The previous study allowed us to identify the structural re-
quirements of the initial o-(alkynyl)styrenes to give 1H-indene
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derivatives.[21] At this point, the importance of developing new
methods to synthesize this skeleton should be remarked. Thus,
1H-indenes are found in pharmaceuticals,[22] functional materi-
als,[23] or as ligands in metal catalysis.[24] Therefore, the present
novel transformation seemed of interest and then, a deeper
study on its scope and limitations was performed. First, reac-
tions of 2’,2’-dimethyl o-(alkynyl)styrenes 3 with diverse substi-
tution at the central phenyl ring as well as in the alkyne termi-
nus were conducted under the optimized conditions; the re-
sults are given in Table 2. These data show that the formation
Table 2. Gold(I)-catalyzed cycloisomerization of 2’,2’-dimethyl o-(alkynyl)-
styrenes 3.[a]
Scheme 2. Gold(I)-catalyzed cycloisomerization of o-(alkynyl)styrenes 6 bear-
ing different substituents at the olefin. 3-Th=3-Thienyl.
Entry
3
R1
R2
R3
5
Yield [%][b]
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3 f
3g
3h
3i
H
H
H
H
F
Br
Ph
Ph
Ph
Ph
3-Th[c]
c-C6H9
nBu
nBu
c-C3H5
5a
5b
5c
5d
5e
5 f
5g
5h
5i
88
80
88
70
94
40[e]
73
64
76
87
83
over, substrates 6g–i bearing two different acyclic aliphatic
groups at the b-position of the styrene moiety also produced
the indene derivatives 7g–i. In those cases in which the forma-
tion of two Z/E isomers was possible (7 f,g), we observed mix-
tures of these two isomers, the Z/E ratio of which was inde-
pendent of the substrate stereochemistry. As expected, forma-
tion of internal alkenes was preferred. Thus, in the reaction to
get indenes 7g–i we only observed the formation of less than
10% of the alternative isomeric indenes containing a terminal
alkene.
ꢀOCH2Oꢀ
H
H
H
H
H
OMe
H
[d]
H
OMe
H
H
H
[f]
9
10
11
[g]
3j
3k
H
H
c-C6H11
SPh
5j
5k
[a] Reactions conducted using 0.5 mmol of o-(alkynyl)styrene derivative 3
in CH2Cl2 (1 mL) at RT. [b] Yield of isolated product based on starting ma-
terial 3. [c] 3-Thienyl. [d] Cyclohexenyl. [e] Using [AuNTf2(Ph3P)] as catalyst;
partial decomposition of the product and/or substrate accounts for the
low yield obtained. [f] Cyclopropyl. [g] Cyclohexyl.
It should be noted that all the reactions depicted in Table 2
and Scheme 2 exclusively afforded in high yields the corre-
sponding indene derivatives as a result of a 5-endo cycloisome-
rization and not even traces of regioisomeric 6-endo or 5-exo
adducts were detected.
of the corresponding indene derivatives is compatible with the
presence of both electron-withdrawing (Table 2, entries 2–3)
and -donating groups (entries 4 and 8) at the aromatic ring.
Moreover, different substituents at the alkyne (R3), including ar-
omatic (entries 1–4), heteroaromatic (entry 5), cycloalkenyl
(entry 6), linear- and cyclo-alkyl (entries 7–10), and heteroatom-
ic moieties (entry 11), are well tolerated. However, substrates
bearing R3 groups such as H, I, or TMS gave only decomposi-
tion products under these conditions.
Interestingly, a new reaction pathway was observed for o-(al-
kynyl)styrene 6j containing an isopropyl and a methyl at the
terminal position of the alkene (Scheme 3). Thus, its reaction
Next, we decided to explore the regio- and stereoselectivity
of the cycloisomerization with regard to the substitution at the
terminal carbon atom of the alkene. So, o-(alkynyl)styrenes 6
possessing different aliphatic and aromatic groups at this posi-
tion were prepared and their reactions under the optimized
conditions were conducted. As a result, several indenes 7 with
both (hetero)aromatic and aliphatic groups at C2 were accessi-
ble from dienynes 6 with total regioselection and in good
yields (Scheme 2). For instance, reactions of o-(alkynyl)styrenes
6a–b possessing an aliphatic ring as R1–R2 substituent at the
terminal position of the olefin, as well as 6c–f with mixed ali-
phatic-aromatic substitution at the same carbon atom, effi-
ciently furnished the corresponding carbocycles 7a–f. More-
Scheme 3. Gold(I)-catalyzed cycloisomerization of o-(alkynyl)styrene 6j.
[a]<10% of 7j were also formed under these reaction conditions.
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under the developed optimized conditions gave less than 10%
of the expected indene derivative 7j. Instead, we observed the
formation of a mixture of the tetracyclic compounds 8j (70%)
and 9j (10%). Interestingly, these regioisomeric dihydroben-
zo[a]fluorenes are the result of a formal gold-catalyzed [3+3]
cycloaddition.[25] After screening several reaction parameters,[18]
we determined that 8j was selectively obtained as a approxi-
mately 7:1 mixture of diastereoisomers[26] in a 75% yield when
conducting the reaction at 08C. In addition, 9j was exclusively
isolated in 79% yield by performing the reaction in 1,2-di-
chloroethane (DCE) at 808C. Remarkably, our initially desired
indene derivative 7j could be selectively isolated (78% yield)
when the reaction was performed with the catalyst generated
in situ from [AuCl(Ph3P)] and silver tosylate (Scheme 3). In addi-
tion, indene derivative 7j could be transformed into the dihy-
drobenzo[a]fluorene 9j by its treatment with our initial catalyt-
ic system ([AuCl(Ph3P)]/AgSbF6) but at 808C in 1,2-dichloro-
ethane (DCE). On the contrary, when this experiment was per-
formed at room temperature we did not observe the forma-
tion of the regioisomer 8j, which indicated that this fluorene
derivative is not directly derived from indene 7j. Moreover,
compound 9j could also be obtained from 7j by its treatment
with catalytic amounts of AgSbF6 (5 mol%) or triflic acid
(10 mol%) in DCE at 808C. In a similar way, isolated dihydro-
benzo[a]fluorene 8j could be transformed into its regioisomer
9j under the initial reaction conditions that imply the use of
[AuCl(Ph3P)]/AgSbF6 (5 mol%), but raising the temperature to
808C. Also, the same transformation could be observed under
acidic catalytic conditions (10 mol% of p-toluenesulfonic acid
(PTSA)) at 808C (Scheme 3). All these experiments seem to in-
dicate that formation of compound 9j is the result of a simple
isomerization reaction of the initially formed compound 8j
under acid conditions. In a similar way, the transformation of
7j into 9j seems to be a protic acid catalyzed process.[27]
Table 3. Synthesis of dihydrobenzo[a]fluorenes 8 and 9.[a]
Entry
6
R1
R2
R3
R4 R5
d.r.[b]
Yield (8) Yield (9)
[%][c]
[%][c]
1
2
3
4
5
6
7
8
6j
6k
6l
Me Me Me
Me Me Me
Me Me Me
H
H
H
H
H
H
H
H
H
H
H
Cl
7:1
5:1
75
79
81[d]
79
81
OMe 6:1
H
86[d]
[e]
[f]
6m Me Me Et
6n Me ꢀ(CH2)5ꢀ
68[d]
–
H
H
H
H
H
H
H
>20:1 75[d]
84
–
[f]
6o Et
Me Me
5:1
71[d]
6p Ph Me Me
6q Ph ꢀ(CH2)5ꢀ
>20:1 70[d]
71
80
72
78
83
[g]
–
–
–
–
–
72
67
76
9
10
11
6r
6s
6t
H
H
H
Me Me
ꢀ(CH2)5ꢀ
Me Me Br
[a] Reactions conducted using 0.5 mmol of o-(alkynyl)styrene derivative 6
in CH2Cl2 (1 mL) at 08C to RT (Method A) or in DCE (1 mL) at 808C (Meth-
od B). [b] Diastereomeric ratio of the corresponding product 8 deter-
1
mined by H NMR spectroscopy of the crude reaction mixture. [c] Yield of
isolated product based on starting material 6. [d] Reaction conducted
throughout at RT. [e] Obtained as a approximately 6:3:2:1 mixture of dia-
stereomers. [f] Reaction not performed under Method B. [g] Reaction not
performed under Method A.
larly remarkable is the reaction of substrates 6r–t (entries 9–
11). These substrates are monosubstituted at the b-carbon
atom of the styrene moiety (R1 =H) and it should be noted
that this type of substituted enyne derivatives did not give
positive results in our initial experiments (see Table 1, entry 2).
Here, for the first time, we observed a clean evolution of these
compounds to efficiently afford the corresponding formal
[3+3] cycloadducts.
Synthesis of dihydrobenzo[a]fluorenes 8 and 9 from o-(alky-
nyl)styrenes 6j–w
Considering the novelty and interest of this transformation, as
well as the common occurrence of the benzo[a]fluorene core
in natural products possessing biological activity[28] we decided
to explore the extent of its scope. Thus, two methods A and B
were employed to selectively obtain dihydrobenzo[a]fluorenes
8 and 9 (Table 3). As previously observed for 6j (entry 1),
under the method A reaction conditions (08C or RT depending
on the substrate) 6,6a-dihydro-5H-benzo[a]fluorenes 8j–t
could be obtained in good yields from o-alkynylstyrenes 6j–
t.[29] High diastereoselectivities, ranging from 5:1 to >20:1,
were observed in all cases. On the other hand, by using the
method B reaction conditions a series of 6,11-dihydro-5H-ben-
zo[a]fluorenes 9 were synthesized with total selectivity and
very good yields (Table 3).
We have also studied the applicability of these reactions for
the construction of other polycyclic frameworks by changing
the substituent at the triple bond (Scheme 4). In this sense, o-
alkynylstyrene 6u bearing a thienyl group reacted efficiently to
afford the corresponding tetracyclic adducts 8u and 9u under
conditions A and B, respectively. Nevertheless, reactions of sub-
It should be noted that the process works nicely with either
electron-withdrawing (entry 2) or -donating (entry 3) aryl sub-
stituents at the triple bond of the starting material, as well as
with diverse substitution patterns at the alkene, provided that
one of these groups is a secondary alkyl (entries 4–8). Particu-
Scheme 4. Gold(I)-catalyzed cycloisomerization of o-(alkynyl)styrenes 6u.
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strates 6v–w, possessing indolyl and cyclohexenyl groups
linked to the triple bond and carried out under method A con-
ditions, gave mixtures of the desired polycyclic compounds 8
and the corresponding indene derivatives 7 (see the Support-
ing Information). In these cases, thermal conditions B led to
low yields probably due to partial decomposition and, surpris-
ingly, did not improve the proportion of [3+3] adduct over in-
denes 7.
ry, in the presence of less basic SbF6 anion the 1,2-hydride mi-
gration would predominantly take place to finally produce 8j.
Also, formation of fluorene derivative 9j from indene 7j can
be easily explained through a protic acid catalyzed reaction im-
plying the protonation of the alkene,[27] which would afford
a cationic gold-free intermediate analogous to IV, followed by
a Friedel–Crafts-type alkylation reaction. Finally, it should be
noted that the formation of indene derivatives 5 from (alky-
nyl)styrenes 3 could be understood through a mechanism ana-
logue to that shown for the formation of indene derivative 7j.
Mechanism of cycloisomerization of o-(alkynyl)styrenes
According to all these results we propose the mechanism
shown in Scheme 5 to explain the formation of indenes 5 and
7 and dihydrobenzo[a]fluorenes 8 and 9. The proposal is illus-
trated for the model substrate 6j.[30] Thus, we suppose that the
Synthesis of oxygen-functionalized 1H-indenes
Considering the above mechanism (Scheme 5), we thought
that intermediate II could be trapped by the addition of an ap-
propriate external nucleophile to the reaction media, and thus,
new products with enhanced complexity could be easily ob-
tained. Pleasantly, reactions of the model substrate 3a con-
ducted under the optimized conditions in the presence of five
equivalents of methanol or water exclusively afforded the
oxygen functionalized 1H-indenes 10aa and 10ab in excellent
yields (Scheme 6). Moreover, parallel reactions using MeOD or
D2O as the nucleophile gave the deuterated compounds
[D]10aa and [D]10ab that displayed 85 and 92%, respectively,
deuterium incorporation at C-3.
Scheme 5. Proposed mechanisms for the formation of adducts 7–9 illustrat-
ed for model substrate 6j.
reaction is initiated by coordination of the cationic gold com-
plex to the triple bond of the starting o-(alkynyl)styrene 6j to
give intermediate I. An intramolecular nucleophilic attack by
the olefin leads to the cationic intermediate II, which can be
represented as the contribution of resonance structures IIa
and IIb that delocalize the positive charge along different posi-
tions of the molecule. Elimination of a proton in this intermedi-
ate, (path a/a’; elimination pathway), furnishes the vinyl-gold
intermediate III, which after a protodemetalation reaction
gives indene 7j and releases the gold catalyst for a new cycle.
On the other hand, intermediate II could also undergo a hy-
dride migration, giving rise to cationic intermediate IV (path b;
migration pathway). The subsequent Friedel–Crafts-type alkyla-
tion reaction affords the dihydrobenzo[a]fluorene derivative V,
which after protodemetalation furnishes compound 8j, regen-
erating the catalytic species.[31] So, the different behavior ob-
served for o-(alkynyl)styrene 6j, which leads to 7j or 8j de-
pending on the counterion of the gold complex, could be un-
derstood considering that the carbocationic intermediate II
would evolve through the elimination pathway to afford 7j,
when the relatively basic tosylate anion is used. On the contra-
Scheme 6. Gold(I)-catalyzed alkoxycyclization of o-(alkynyl)styrene 3a.
The scope of the alkoxycyclization process[32] to produce
functionalized indenes[33] was then analyzed. First we found
that besides methanol and water (Table 4, entries 1–2), other
primary alcohols, including functionalized ones such as allylic
alcohol or 2-bromoethanol, could be successfully employed as
external nucleophiles in this transformation (entries 3–5). Even
the isopropoxy derivative 10af was obtained as the major
adduct in 81% yield by using 20 equivalents of isopropanol as
the nucleophile, though the competitive formation of 5a took
place in a small amount (entry 6). Then, using methanol and/or
water as nucleophile a variety of functionalized indenes 10
with selected substitution at R1, R2, and R3 were synthesized
(entries 7–19). As expected by the results obtained in the cy-
cloisomerization in the absence of nucleophile the reaction tol-
erates both electron-withdrawing (entries 7–10) and -donating
(entries 11–12) groups at the internal phenyl ring as well as
a broad range of substituents at the triple bond including (het-
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Table 4. Gold(I)-catalyzed synthesis of oxygen-functionalized 1H-indenes
10.[a]
Table 5. Gold(I)-catalyzed alkoxycyclization of o-(alkynyl)styrenes 6 bear-
ing different substituents at the terminal position of the olefin.[a]
R1
R2
R3
R4
11
d.r
Yield
[%][b]
Entry
3
R1
R2
R3
R4
10
Yield
[%][b]
Entry
6
d.r.
(E/Z)
1
2
3[c]
4[c]
5[e]
6
6a
6a
6c
–
–
1:0
ꢀ(CH2)4ꢀ
ꢀ(CH2)4ꢀ
Ph
Ph
Me Ph
Me 11 aa
11 ab
Me 11 ca
–
–
3:1
96
71
88
75
1
2
3
4
3a
3a
3a
3a
3a
3a
3b
3b
3c
3c
3d
3d
3e
3e
3g
3g
3i
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
F
F
Br
Br
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
H
Et
allyl
(CH2)2Br
iPr
Me
H
Me
H
Me
H
Me
H
Me
H
10aa
10ab
10ac
10ad
10ae
10af
10ba
10bb
10ca
10cb
10da
10 db
10ea
10eb
10ga
10gb
10ia
90
95
85
93
H
Ph
Ph
6d 6:1
6g 1.5:1 Me Et
6j 4:1 Me iPr
Me 3-Th[d] Me 11 da 3:1
Ph
Ph
Me 11 ga 1.5:1 55[f]
5
85
[g]
6[c]
7
81[d]
95
Me
–
–
–
[a] Reactions conducted using 0.5 mmol of o-(alkynyl)styrene derivative 6
and 5 equiv of MeOH or 20 equiv of H2O (entry 2) in CH2Cl2 (1 mL) at RT.
[b] Isolated yield. [c] Using [AuNTf2(Ph3P)] as the catalyst. [d] 3-Thienyl.
[e] Performed with 100 equiv of MeOH. [f] 29% of 7g was also formed.
[g] A mixture of adducts 7–9j was obtained.
8
9
76
87
78[e]
98
72
94
84
81
78[e]
77
80
84
10
11
12
13
14
15
16
17
18
19
ꢀOCH2Oꢀ Ph
ꢀOCH2Oꢀ Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
3-Th[f]
3-Th[f]
nBu
nBu
c-C3H5
(entry 6). On the other hand, regarding the stereoselectivity of
the methoxycyclization, the experiment conducted with
a single isomer of 6c gave methoxy-functionalized indene
11 ca as a 3:1 mixture of diastereoisomers (entry 3). In the
same way, the reaction of 6d, enriched in one geometrical
isomer (6:1), produced the product 11 da with a lower diaste-
reoselectivity (d.r.=3:1) (entry 4). These results clearly revealed
that the alkoxycyclization is not diastereospecific.
[g]
Me
Me
Me
[h]
3j
3k
c-C6H11
SPh
10ja
10ka
[a] Reactions conducted using 0.5 mmol of o-(alkynyl)styrene derivative 3
and 5 equiv of nucleophile in CH2Cl2 (1 mL) at RT. [b] Isolated yield. [c] Re-
action performed using 20 equiv of iPrOH. [d] 8% of 5a was also formed.
[e] Using [AuNTf2(Ph3P)] as catalyst. [f] 3-Thienyl. [g] Cyclopropyl. [h] Cy-
clohexyl.
While working on the generalization of this reaction we ob-
tained some unexpected results. Thus, as shown in Table 1,
entry 2, the reaction of enyne derivative 1b monosubstituted
at the b-position of the styrene led to a mixture of unidentified
products when the reaction was performed under the conven-
tional reaction conditions. Surprisingly, the same reaction per-
formed in the presence of methanol (5 equiv) led to the forma-
tion of methoxy-functionalized indene 12b in good yield
(Scheme 7). In the same sense, o-(phenylethynyl)-b-phenylstyr-
ene 1c reacted in the presence of methanol to afford 12c in
high yield.
ero)aromatic (entries 7–14), (cyclo)alkyl (entries 15–18), and
heteroatomic moieties (entry 19). All these reactions were com-
pletely selective and we did not observe the formation of addi-
tional products derived from other possible reaction pathways.
Thus, the corresponding indenes 10 were isolated in good to
excellent yields.
To further test the scope of the process we explored the re-
action with starting materials in which the substitution at the
alkene terminal carbon atom was different from two methyl
groups. Some conclusions could be extracted from the results
obtained and depicted in Table 5. The alkoxycyclization is com-
pletely selective with o-(alkynyl)styrenes 2’,2’-disubstituted by
either aliphatic or aromatic groups allowing the preparation of
several functionalized indenes 11 in good to excellent yields
(entries 1–4). Moreover, and not surprisingly, the addition of
the external nucleophile to the terminal carbon atom of the
olefin was affected by the steric hindrance at that position as
was revealed for substrates 6g and 6j. Thus, reaction of 6g, in
which a methyl group was replaced by an ethyl group, fur-
nished the desired indene 11 ga in a moderate 55% yield with
the concomitant formation of 7g as a mixture of isomers and
in a 29% yield (entry 5). In the case of substrate 6j, bearing
a methyl and an iso-propyl group at the olefin, the incorpora-
tion of methanol in the final adduct was totally suppressed
and, therefore, a mixture of compounds 7–9j was detected
Scheme 7. Gold(I)-catalyzed alkoxycyclization of o-(alkynyl)styrenes 1, mono-
substituted at the terminal position of the olefin.
Other surprising results were found with enyne derivatives 2
substituted at the a-position of the styrene. Under convention-
al reaction conditions (see Table 1), these reagents selectively
evolve to give naphthalene derivatives through a 6-endo cycli-
zation process. However, an interesting switch of selectivity
was observed when the reactions were performed with metha-
nol as cosolvent of the process (Scheme 8).[34] Under these con-
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Scheme 8. Gold(I)-catalyzed synthesis of oxygen-functionalized 1H-indenes
13 bearing a quaternary centre at C-1.
ditions 1H-indenes 13c–i were isolated in high yields (ca. 2–
1.5:1 mixture of diastereoisomers) as a result of a 5-endo-dig
cyclization process.[35] Notably, the alkoxycyclization occurred
regardless of the electronic nature of the aromatic groups at
both the b-carbon atom of the styrene moiety and the alkyne
terminus. In addition, the methodology also allowed the syn-
thesis of alkyl-substituted indenes at C-2 as demonstrated for
13i (Scheme 8). Interestingly, in this reaction an all-carbon qua-
ternary stereocenter is generated at C1.
Scheme 9. Synthesis of polycyclic compounds 15 by gold(I)-catalyzed intra-
molecular alkoxycyclization of o-(alkynyl)styrenes 14.
With the aim of accessing diverse polycyclic compounds we
also tried the alkoxycyclization in an intramolecular fashion. To
this end, we synthesized o-(alkynyl)styrenes 14a–h possessing
a hydroxy group in their structure. Pleasantly, reaction of sub-
strates 14a–c proceeded smoothly under the standard condi-
tions, generating indenes fused to five-, six-, and seven-mem-
bered oxygen-containing heterocycles in good to high yields
(Scheme 9). Even 15d, a tricyclic compound with a fused oxo-
cane ring, could be obtained in a moderate 41% yield. More-
over, o-(alkynyl)styrenes 14e–g, in which the nucleophile is ap-
pended to an additional cycle, also partook efficiently in the in-
tramolecular alkoxycyclization reaction, giving rise to the corre-
sponding tetracycles. All these reactions were highly selective,
and only in the case of 14g formation of minor amounts of
the product 16, coming from direct attack of the alcohol to
the triple bond was observed.[36] Finally, we tried the reaction
with the o-(alkynyl)styrene 14h, possessing an isopropyl group
at the terminal carbon atom of the olefin. It should be noted
that the reaction of substrates with this type of substitution
pattern did not react in an intermolecular fashion with an alco-
hol (MeOH) as demonstrated in our attempt shown in Table 5,
entry 6. However, the reaction of 14h afforded as the major
product the furan derivative 15h along with a very minor
amount of pyran derivative 17 (Scheme 9).
Scheme 10. Proposed mechanism for the alkoxycyclization of o-(alkynyl)styr-
enes.
tion of the cationic gold complex to the triple bond of starting
o-(alkynyl)styrenes 1–3, 6, or 14, followed by intramolecular
nucleophilic attack of the olefin leading to cationic gold car-
beonid intermediate II’.[37] However, in the presence of water
or an alcohol, instead of the proton elimination suggested in
Scheme 5, this intermediate II’ would be trapped by the nucle-
ophile generating vinyl gold intermediate III’. After a protode-
metalation reaction, compounds 10–13 or 15 are formed and
The mechanism of all these alkoxycyclization processes
would initially follow a mechanism similar to that commented
before for the simple cycloisomerization reaction (see
Scheme 5 and 10). Thus, the reaction would start by coordina-
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the catalytic species are regenerated (Scheme 10). As previous-
ly noted, a switch in the selectivity of the cyclization is ob-
served for o-(alkynyl)-a-methylstyrenes 2, and thus indenes are
obtained in the presence of methanol and naphthalenes in its
absence. These facts could be explained by supposing that in
the presence of methanol the corresponding intermediate II’
(R2 =H; R1, R3 ¼H) rapidly reacts with the nucleophile at the
less-hindered position to afford the indene derivatives 13.
However, in the absence of an appropriate nucleophile, a ring-
opening reaction of intermediate II’ gives the more stable ben-
zylic cation IV’, which finally produces the naphthalene deriva-
tive 4 by proton elimination and subsequent protodeauration
(Scheme 10). In addition, the generation of a minor amount of
pyran derivative 17 (Scheme 9) could be easily explained
through the formation of intermediate IV (see Scheme 5 and
Supporting Information).
Table 6. Enantioselective synthesis of 1-alkenyl-1H-indenes 5 and 7.[a]
Entry 3/6 R1
R2
R3
R4
R5
5,7 Yield ee
[%][b] [%][c]
1
3a
3b
3d
3e
3 f
3g
3i
H
H
H
F
Me Me Ph
Me Me Ph
5a 81
5b 84
5d 84
5e 81
82
77
86
68
24
20
11
14
2[d]
3[d]
4
ꢀOCH2Oꢀ Me Me Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me Me 3-Th[e]
Me Me c-C6H9
Me Me nBu
[f]
5
5 f
71
6[d]
7[d]
8[d]
9[d]
10
11
5g 80
[g]
Me Me c-C3H5
5i
5j
75
43[i]
[h]
3j
Me Me c-C6H11
Me Me SPh
ꢀ(CH2)4ꢀ Ph
ꢀ(CH2)5ꢀ Ph
3k
6a
6b
5k 77
7a 93
7b 96
5
81
80 (92)
Enantioselective synthesis of 1H-indenes
[a] Reactions conducted using 0.3 mmol of o-(alkynyl)styrene derivative 3
or 6 in CH2Cl2 (0.6 mL) at ꢀ308C for 3–4 days. [b] Isolated yield. [c] Deter-
mined by HPLC analysis, see Supporting Information; in brackets ee after
recrystallization. [d] Reaction conducted at ꢀ208C. [e] 3-Thienyl. [f] Cyclo-
hexenyl. [g] Cyclopropyl. [h] Cyclohexyl. [i] 62% conversion.
Once we had established the versatility of o-(alkynyl)styrenes
as precursors of indene derivatives we thought about the pos-
sibility of preparing these adducts in an enantioselective fash-
ion by using chiral gold catalysts. Remarkably, the synthesis of
optically active indenes remains a challenge with only two
recent strategies for the enantioselective synthesis of these
compounds from achiral substrates having been published.[38]
Both approaches are based on the use of boronic acid deriva-
tives as starting materials and their coupling in tandem reac-
tions catalyzed by chiral palladium complexes producing the
corresponding indenes in good yields and variable enantiose-
lectivities.[39]
In this context, it should be noted that although gold cataly-
sis has witnessed tremendous activity in recent years, its appli-
cation in asymmetric synthesis is an underdeveloped area.[40]
Particularly, gold-catalyzed enantioselective processes involving
alkyne activation are relatively scarce.[34,41] Therefore, we were
pleased to find that, after some optimization,[42] we were able
to obtain indene derivatives with good enantiomeric excess
using the combination [(AuCl)2{(S)-3,5-xylyl-MeOBIPHEP}]/
AgOTs as catalyst in dichloromethane at ꢀ308C (Table 6).
Under these optimized catalytic conditions we found high
yields and enantioselectivities for o-(alkynyl)styrenes 3a–e, 6a–
b in which R5 is an aromatic or heteroaromatic group (en-
tries 1–4, 10–11). Interestingly, the possibility of increasing the
enantiomeric excess of the final products by a simple recrystal-
lization has been demonstrated for indene 7b that we were
able to isolate with 92% ee (entry 11). However, starting mate-
rials 3 f–k containing alkenyl, aliphatic, or heteroatomic substi-
tution in the alkyne led to low enantiomeric excess (entries 5–
9).
Scheme 11. Enantioselective synthesis of [3+3] adducts 9.
indenes could be at least partially explained considering the
higher temperatures needed for the formation of the [3+3] ad-
ducts, as well as the lack of complete diastereoselectivity in
the formation of adducts 8.
We also performed the enantioselective alkoxycyclization of
o-(alkynyl)styrenes 3 and 6 (Table 7). The model substrate 3a
cyclizes in the presence of water and primary alcohols afford-
ing the corresponding functionalized indenes in high yields
and good enantioselectivities (entries 1–4) that can be further
improved by recrystallization, allowing the isolation of the final
product even as a single enantiomer when methanol is used
as the nucleophile. By using isopropanol as the nucleophile,
the isopropoxy derivative 10af was obtained with the highest
ee, although as in the racemic reaction the competitive forma-
tion of 5a took place in a small amount. Next, we carried out
the alkoxycyclization of several o-alkynylstyrenes in the pres-
ence of water or methanol. Again, we obtained the corre-
sponding indenes in good to excellent yields and high enan-
tioselectivities when the substituent of the triple bond was an
(hetero)aromatic ring, independently of the substitution in
Like indenes 5 and 7, [3+3]-tetracyclic compounds 9 exhibit
a stereogenic center in their structure and, therefore, we also
attempted their enantioselective synthesis. Thus, under the
best reaction conditions found,[43] selected dihydrobenzo[a]-
fluorenes 9 were prepared in good yields although with
modest enantiomeric excess (Scheme 11). The significant de-
crease in the enantioselectivity compared with the analogous
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[3+3] cycloaddition. Moreover, parallel reactions in the pres-
ence of oxygen-centered nucleophiles such as water and alco-
hols provide the corresponding functionalized indene deriva-
tives. These gold-catalyzed alkoxycyclizations are also observed
with o-(alkynyl)-a-methylstyrenes which allows the preparation
of indenes bearing an all-carbon quaternary centre at C-1. No-
tably, the later results implies a critical effect of the alcohol in
the outcome of the cycloisomerization by switching the selec-
tivity from a 6-endo to 5-endo cyclization. In addition, we have
also accomplished the selective synthesis of polycyclic com-
pounds by a related intramolecular gold-catalyzed alkoxycycli-
zation of appropriate substituted o-(alkynyl)styrenes. Finally,
we have developed the asymmetric synthesis of 1H-indenes
and dihydrobenzo[a]fluorenes using a chiral gold complex de-
rived from electron-rich ligand 3,5-xylyl-MeOBIPHEP. Notably,
the enantiomerically enriched functionalized indenes are ob-
tained in high yields and with ee values up to 92% that can be
improved to >98% after a simple recrystallization.
Table 7. Enantioselective synthesis of oxygen-functionalized 1H-indenes
10 and 11.[a]
Entry 3/6 R1
R2
R3
R4
R5
10/11 Yield ee
[%][b] [%][c]
1
2
3[d]
4[d]
5[d]
6
7
8
9
10
11
12
13
14
15
16
17
18
3a
3a
3a
3a
3a
3b
3b
3c
3c
H
H
H
H
H
H
H
H
H
H
H
H
H
H
F
F
Br
Br
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me 10aa 99
88 (>98)
H
Et
10ab 93
10ac 88
86
81
80
allyl 10ad 94
iPr 10af 72[e] 92 (98)
Me 10ba 93
10bb 88
Me 10ca 95
10cb 94
Me 10da 98
10 db 80
82 (>98)
86
H
80 (>98)
80 (>98)
84 (>98)
88 (>98)
75 (>98)
78 (>98)
30
28
4
80
84
H
3d ꢀOCH2Oꢀ Me
3d ꢀOCH2Oꢀ Me
H
3e
3e
3g
3g
3k
6a
6a
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
Me
Me
Me
3-Th[f] Me 10ea 90
3-Th[f]
nBu
nBu
SPh
H
10eb 91
Me 10ga 88
10gb 90
Experimental Section
H
Me 10ka 69
Me 11 aa 87
Typical procedure for the gold(I)-catalyzed synthesis of 1H-
indenes 2 and 8: Synthesis of 2-phenylsulfanyl-1-(prop-1-en-
2-yl)-1H-indene (5k)
ꢀ(CH2)4ꢀ Ph
ꢀ(CH2)4ꢀ Ph
H
11 ab 77
[a] Reactions conducted using 0.3 mmol of o-(alkynyl)styrene derivative 3
or 6, 30 equiv of nucleophile, AgOTs as silver salt with ROH and AgSbF6
with H2O, in CH2Cl2 (1.2 mL) at ꢀ308C for 2–4 days. [b] Isolated yield.
[c] Determined by HPLC analysis, see Supporting Information; in brackets
ee after recrystallization. [d] Reaction conducted at ꢀ208C. [e] 12% of 5a
was also formed. [f] 3-Thienyl.
AgSbF6 (5.0 mol%, 8.5 mg) was added to a solution of [AuCl(Ph3P)]
(5.0 mol%, 12.3 mg) in CH2Cl2 (1.0 mL) and the reaction mixture
was stirred 5–10 min. A solution of o-(alkynyl)styrene derivative
3k[45] (0.5 mmol, 132 mg) in CH2Cl2 (1.0 mL) was added and the re-
action mixture was stirred at RT until complete disappearance of
the styrene derivative was observed by TLC or GCMS analysis. The
mixture was filtered through silica gel, the solvent was removed
under reduced pressure and the crude mixture was purified by
flash chromatography on silica gel using hexane as the eluent to
afford indene 5k (109 mg, 83%) as a yellow oil; Rf =0.28 (hexane);
1H NMR (300 MHz, CDCl3, 258C): d=1.38 (brs, 3H), 4.23 (brs, 1H),
5.10–5.17 (m, 1H), 6.48–6.50 (m, 1H), 7.05–7.36 (m, 5H), 7.38–7.45
(m, 3H), 7.58–7.67 ppm (m, 2H); 13C NMR (75.4 MHz, CDCl3, 258C):
d=16.7 (CH3), 60.9 (CH), 116.2 (CH2), 119.6 (CH), 123.1 (CH), 124.5
(CH), 127.2 (CH), 128.2 (CH), 128.8 (C), 129.3 (2ꢄCH), 133.1 (C),
133.5 (2ꢄCH), 143.0 (C), 144.1 (C), 145.7 (C), 146.7 ppm (C); LRMS
(EI): m/z (%): 265 [M+1+] (16), 264 [M+] (78), 155 (100); HRMS (EI):
calcd for C18H16S: 264.0973; found: 264.0968.
other positions of the substrate (entries 6–13 and 17–18). As
expected by the results obtained in the cycloisomerization in
the absence of an external nucleophile, nonaromatic alkyne-
substituted o-(alkynyl)styrenes 3g–k led to lower enantioselec-
tivities (entries 14–16). Unfortunately, all the efforts made to
produce 1H-indenes 13 bearing an all-carbon quaternary ena-
tioenriched centre at C-1 failed, we observed no reaction at
low temperature and very low ee (<10%) and moderate yield
at room temperature.
It is noteworthy that most of the functionalized indenes that
have been synthesized could be isolated as a single enantio-
mer after recrystallization. Moreover, the absolute configura-
tion of product 10ca was determined to be R by using single-
crystal X-ray diffraction,[44] and the rest were assigned by analo-
gy.
General procedure for the gold(I)-catalyzed enantioselective
synthesis of 1H-indenes 5, 7, and 10–11
AgSbF6 (10.0 mol%, 5.1 mg) or AgOTs (10.0 mol%, 8.4 mg) was
added to a solution of L*(AuCl)2 (5.0 mol%, 17.4 mg) in dry CH2Cl2
and the reaction mixture was stirred for 5–10 min and cooled to
ꢀ30 or ꢀ208C (see Tables 6 and 7 for the suitable Ag salt and tem-
perature for each substrate). The nucleophile (30 equiv, 9 mmol),
when appropriate, was added, followed by a solution of the corre-
sponding o-(alkynyl)styrene derivative 3 or 6 (0.3 mmol) in dry
CH2Cl2. The resulting reaction mixture was stirred until complete
disappearance of starting material, as monitored by TLC or GCMS
analysis. The mixture was diluted with hexanes and filtered
through a pad of silica gel, the solvent was removed and the
crude mixture was purified by flash chromatography on silica gel
using mixtures of hexane and EtOAc as eluents. The corresponding
Conclusion
In summary, we have shown that ortho-(alkynyl)styrenes are
valuable precursors of indene-derived compounds by gold-cat-
alyzed formal 5-endo-dig cycloisomerizations and alkoxycycliza-
tions. Thus, reactions of o-(alkynyl)styrenes disubstituted at the
b-position of the styrene moiety selectively afford 1H-indene
derivatives in high yields whereas substrates bearing a secon-
dary alkyl group at the terminal carbon atom of the olefin effi-
ciently produce dihydrobenzo[a]fluorenes through a formal
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[10] a) N. Kadoya, M. Murai, M. Ishiguro, J. Uenishi, M. Uemura, Tetrahedron
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132, 17710–17712.
1H-indenes 5, 7, 10, or 11 were isolated in the yields and enantio-
selectivities reported in Tables 6 and 7.
[11] K. Saito, H. Sogou, T. Suga, H. Kusama, N. Iwasawa, J. Am. Chem. Soc.
2011, 133, 689–691.
Acknowledgements
[12] T. Godet, P. Belmont, Synlett 2008, 2513–2517.
[13] a) J. Aziz, G. Frison, P. Le Menez, J.-D. Brion, A. Hamze, M. Alami, Adv.
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We gratefully acknowledge the Ministerio de Economꢁa y Com-
petitividad (MINECO) and FEDER (CTQ2010-15358 and
CTQ2013-48937-C2-1-P) and Junta de Castilla
y
Leꢅn
(BU237U13) for financial support. A.M.S. thanks the Junta de
Castilla y Leꢅn (Consejerꢁa de Educaciꢅn) and the Fondo Social
Europeo for a PIRTU contract. M.A.R. and P.G.-G. thank MEC for
a ‘‘Young Foreign Researchers’’ (SB2009-0186) contract and
MINECO for “Juan de la Cierva” contract, respectively.
ˇ
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Keywords: asymmetric
catalysis
·
cyclization
·
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[42] See Table S2 in the Supporting Information for details.
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[44] CCDC-766525 (10ca) 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.
[34] We have previously observed that the presence of an alcohol also led
to a switch in the selectivity of the cyclization of 1,3-dien-5-ynes, see:
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[35] Starting from 2b, the corresponding methoxy-functionalized indene
13b was isolated in 34% yield (ca. 6:1 mixture of diastereoisomers)
along with naphthalene derivative 4b as the major product (55% iso-
lated yield).
Received: October 23, 2014
Published online on && &&, 0000
Chem. Eur. J. 2014, 20, 1 – 12
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&
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FULL PAPER
Going for gold! A full account for the
gold(I)-catalyzed reactions of ortho-(al-
kynyl)styrenes is reported. Selective 5-
endo cyclizations are achieved by con-
trol of substrate olefin substitution pat-
terns, which give rise to a wide variety
of interesting 1H-indenes (see scheme).
These compounds can be prepared in
an enantioselective way by using
a chiral gold complex.
&
Asymmetric Catalysis
A. M. Sanjuꢀn, M. A. Rashid,
P. Garcꢁa-Garcꢁa, A. Martꢁnez-Cuezva,
M. A. Fernꢀndez-Rodrꢁguez, F. Rodrꢁguez,
R. Sanz*
&& – &&
Gold(I)-Catalyzed Cycloisomerizations
and Alkoxycyclizations of ortho-
(Alkynyl)styrenes
&
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Chem. Eur. J. 2014, 20, 1 – 12
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12
ꢃ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!