AuI-catalyzed tandem [3,3] rearrangement-intramolecular hydroarylation: Mild and efficient formation of substituted indenes

Article abstract of DOI:10.1002/anie.200600571

(Chemical Equation Presented) Dignified auration: The rearrangement of phenylpropargyl acetates to substituted indenes is catalyzed by [Au ¹(NHC)] complexes (see scheme, NHC = N-heterocyclic carbene) under extremely mild reaction conditions. This chemoselective transformation involves 1,3-migration of the acetate group and is proposed to proceed through an allene intermediate. TMS = trimethylsilyl, TBS = tert-butyldimethylsilyl.

Full text of DOI:10.1002/anie.200600571

Angewandte
Chemie
Synthetic Methods
DOI: 10.1002/anie.200600571
AuI-Catalyzed Tandem [3,3] Rearrangement–
Intramolecular Hydroarylation: Mild and
Efficient Formation of Substituted Indenes**
Nicolas Marion, Silvia Díez-Gonzµlez,
Pierre de FrØmont, April R. Noble, and Steven P. Nolan*
Recent reports have highlighted the use of gold(i) and gold(iii)
complexes as efficient homogeneous catalysts in several
organic transformations.[1] Notably, gold catalysts, in both
oxidation states, enable the cycloisomerization of enynes.[2]
Based on these earlier studies, we reasoned that the electron-
rich phenyl ring could replace an alkene moiety and lead to
[*] N. Marion, Dr. S. Díez-Gonzµlez, P. de FrØmont, A. R. Noble,
Prof. Dr. S. P. Nolan
Department of Chemistry
University of New Orleans
2000 Lakeshore Drive, New Orleans, LA 70148 (USA)
Fax: (+1)504-280-6860
E-mail: snolan@uno.edu
[**] The National Science Foundation is gratefully acknowledged for
financial support of this work. S.D.G. thanks the Education,
Research, and Universities Department of the Basque Government
(Spain) for a postdoctoral fellowship. We also thank the Department
of Chemistry of the University of Ottawa, and more specifically Prof.
Deryn Fogg, for hosting our group while the University of New
Orleans was recovering from Hurricane Katrina. Degussa AG,
Umicore AG, and Strem are also gratefully acknowledged.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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valuable cyclized products. Surprisingly, the only related
examples of intramolecular hydroarylation employ a het-
eroatom-containing tether to provide indoles, benzofurans, or
coumarins.[3] Carbocycles, especially indenes, are compounds
of great interest as synthetic targets and building blocks for
pharmaceutical[4] and materials chemistry.[5] As the inter- or
intramolecular formation of indenes usually requires high
temperature and/or a prolonged reaction time,[6] a mild and
efficient assembly protocol would be highly desirable.
Keeping in mind that propargylic acetates, in the presence
of cationic gold complexes, undergo 1,2-migration of the
acetate group and subsequent formation of carbenoid spe-
cies,[7] we first examined the reactivity of 1a with an
equimolar amount of [(IPr)AuCl] (IPr= N,N’-bis(2,6-diiso-
propylphenyl)imidazol-2-ylidene) and AgBF4. After five
minutes at room temperature, the reaction with 1a cleanly
yielded indene 2a (Table 1, entry 1). Interestingly, although
Scheme 1. Structures of NHC ligands.
tion (Table 1, entry 5). It is noteworthy that AuCl alone or in
conjunction with AgBF4 did not lead to 2a (Table 1, entries 11
and 12). Furthermore, PtCl2, which has been reported
recently to catalyze a closely related reaction,[8b] did not
lead to 2a under our conditions (Table 1, entry 13).
Table 1: Catalyst optimization.[a]
The scope of the reaction was investigated with a variety
of reactants 1, and the results are presented in Table 2. The
formation of indenes 2 was found to be compatible with
electron-poor or electron-rich arenes 1b–d. Benzodioxole 1e
reacted regioselectively to give 2e in excellent yield. Ortho-
substituted arenes 1 f and 1g gave 2 f and 2g’ and led to the
formation of indenes of type 3 as minor products. Interest-
Entry Catalyst (2 mol%)
t
2a [%][b] 3a [%][b] 4a [%][b]
1
2
[(IPr)AuCl]/AgBF4
[(IPr)AuCl]
5 min
92
–
–
overnight
30 min
5 min
no reaction
3
AgBF4
–
–
–
–
5
3
23
–
87
–
–
–
–
11
–
8
Table 2: Gold(i)-catalyzed formation of indenes from propargylic ace-
tates.
4
5
[(IPr)AuCl]/AgPF6
[(IPr)AuCl]/AgSbF6
90
73
88
76
54
89
51
5 min
6
7
8
[(SIPr)AuCl]/AgBF4 5 min
[(IMes)AuCl]/AgBF4 5 min
[(ITM)AuCl]/AgBF4 5 min
9
[(IAd)AuCl]/AgBF4
15 min
10
11
12
13
[(PPh3)AuCl]/AgBF4 5 min
AuCl
AuCl/AgBF4
PtCl2
32
1
Major product
Minor product
30 min
5 min
overnight
unidentified mixture
unidentified mixture
–
–
53
[a] Reaction conditions: alkyne 1a (0.5 mmol), catalyst (2 mol%),
CH2Cl2 (20 mL). [b] NMR spectroscopic yields with respect to 1,2-
dichloroethane.
the formation of indenes from aryl propargyl acetates such as
1a has two precedents in the literature, both leading to
products of type 5,[8] the structure of 2a is unexpected (see
Scheme 3). Reaction of 1a with AgBF4 (Table 1, entry 3)
resulted in the formation of allene 4a, which showed only
minor decomposition and no formation of cyclized product
upon prolonged stirring.[9] [(IPr)AuCl] alone was found to be
inactive toward alkyne 1a (Table 1, entry 2).
To gauge the influence of the ligand in this transforma-
tion, we carried out reactions with various [(NHC)AuCl]
complexes[10] (NHC = N-heterocyclic carbene, Scheme 1) and
silver tetrafluoroborate. Sterically demanding NHCs led to
sluggish reactions (Table 1, entry 9) while less encumbered
NHCs,[11] as well as PPh3, led to poor selectivity (Table 1,
entries 8 and 10).[12] Further optimization revealed that
tetrafluoroborate or hexafluorophosphate were both suitable
counterions (Table 1, entries 1 and 4), whereas hexafluo-
roantimonate produced a significant amount of oligomeriza-
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ingly, the naphthalene 1g produced the phenalene 2g’
regioselectively.[13] To further explore the generality of this
transformation, we carried out the reaction using 1h, which
cleanly produced indenes 2h and 3h.[14] Strikingly, no trace of
bicyclo[3.1.0] compounds was observed,[2a,h] thus highlighting
the chemoselectivity of the reaction. Furthermore, the latter
reaction shows that tertiary acetates are also suitable
substrates in this transformation. Finally, varying the sub-
stituent at the acetylenic position with a phenyl group in place
of the butyl group resulted in oligomerization of the starting
material. On the other hand, with a proton at the acetylenic
position, the formation of 5i was observed, resulting primarily
from a 1,2-migration of the propargylic acetate group in 1i
(Scheme 2). In this latter case, the reactivity of the aryl
1,3-migration) of the acetate group[17] to produce allene III,
which would be further activated by the [Au+] fragment for
hydroarylation,[18,19] thus leading to products of type 2.[20] To
gain insight into the mechanism, we synthesized allenes 4a,c,d
by treating 1a,c,d with AgSbF6 and subjected the allenes to
cyclization conditions. We observed the formation of the
corresponding indenes 2a,c,d after 15 minutes (Table 3).
Table 3: Gold(i)-catalyzed formation of indenes from aryl allenes.
4
2
3
Scheme 2. An example of gold(i)-catalyzed formation of an indene
from a terminal alkyne.
propargyl acetate is similar to that observed in transforma-
tions reported by the research groups of Uemura and Sarpong
with ruthenium and platinum catalysts, respectively.[8] There-
fore, it appears that the behavior of the [(IPr)Au]+ catalyst
and, subsequently, the outcome of the reaction are highly
dependent on the substitution pattern at the acetylenic
position. The apparent 1,3-migration of the acetate moiety
in products of type 2 and the observation of allene 4d led us to
propose the mechanism depicted in Scheme 3. p Complex-
ation of the in situ generated cationic gold complex to the
Unexpectedly, the reaction times were slightly longer than
with the propargylic acetates. This could be a consequence of
a higher “alkynophilicity” than “allenophilicity” of the
[(IPr)Au]+ fragment, a difference which is not observed
starting from 1 as a result of the mandatory proximity of the
gold center to the newly formed allene moiety.[21] Finally, the
minor formation of 3a,c,d, products of the direct hydro-
arylation of the alkyne, emphasizes the reversibility of the
gold(i)-catalyzed [3,3] rearrangement and the advantage of
using alkynes in this reaction for a higher selectivity.
In summary, we have described a novel type of metal-
mediated formation of indenes from aryl propargyl acetates.
This chemoselective transformation proceeds under
extremely mild reaction conditions. Studies aimed at explor-
ing mechanistic aspects of this transformation and developing
further uses of [(IPr)AuCl][22] are ongoing.
ꢀ
C C bond and subsequent direct nucleophilic attack by the
electron-rich phenyl ring would lead to products of type
3.[15,16] On the other hand, electrophilic activation of the
alkyne could trigger two successive 1,2-migrations (or a single
Experimental Section
General Procedure: AgBF4 (2mg, 0.02mmol) was added in the
absence of light to a solution of [(IPr)AuCl] (12.4 mg, 0.02 mmol) in
anhydrous CH2Cl2 (35 mL) in a round-bottom flask equipped with a
septum. The solution instantly became cloudy.
A solution of
propargylic acetate 1 (1 mmol) in anhydrous CH2Cl2 (5 mL) was
then injected through the septum. When TLC analysis showed total
consumption of the starting material, the solvent was removed under
vacuum. The resulting mixture was dissolved in pentane, filtered
through celite, and evaporated. The crude oil was purified by flash
chromatography on silica gel.
2a: The above general procedure employing 1a (230 mg) yielded
2a after flash chromatography on silica gel (pentane/methyl tert-butyl
1
ether, 95:5). Yield: 212 mg, 92%; H NMR (300 MHz, CDCl3): d =
7.35 (d, J = 7.2 Hz, 1H, ArH), 7.24–7.14 (m, 2H, ArH), 7.21–7.18 (m,
=
1H, ArH), 6.70 (d, J = 5.7 Hz, 1H, CArCH CH), 6.56 (d, J = 5.7 Hz,
=
Scheme 3. Proposed mechanism.
1H, CArCH CH), 2.22 (dt, J = 12.6, 4.5 Hz, 1H, CCH2CH2), 1.99 (s,
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3H, OAc), 1.93 (dt, J = 12.6, 4.5 Hz, 1H, CCH2CH2), 1.32–1.19 (m,
[11] For a study on the steric and electronic properties of NHCs, see:
R. Dorta, E. D. Stevens, N. M. Scott, C. Costabile, L. Cavallo,
C. D. Hoff, S. P. Nolan, J. Am. Chem. Soc. 2005, 127, 2485 – 2495.
[12] For details, see the Supporting Information.
[13] Characteristic signals for the expected indene could be observed
in the 1H NMR spectrum of the crude reaction mixture and
accounted for < 5% of the signal intensity, but this product could
not be cleanly isolated.
4H, CH2CH2CH3), 0.83 ppm (t, J = 7.5 Hz, 3H, CH2CH3); 13C NMR
=
(75 MHz, CDCl3): d = 170.0 (C O), 145.8 (CAr), 142.4 (CAr), 137.9
=
=
(CArH), 132.4 (CArCH CH), 128.7 (CArH), 126.2 (CArCH CH), 122.2
(CArH), 121.7 (CArH), 91.0 (COAc), 35.7 (CCH2CH2), 26.4
(CH2CH2CH3), 23.1 (CH2CH3), 21.9 (CH3, OAc), 14.0 ppm
(CH2CH3). Elemental analysis (%) calcd for C15H18O2 (Mr 230.30):
C 78.23, H 7.88; found: C 78.15, H 7.94.
[14] Compounds 2h and 3h were easily separated by flash chroma-
tography.
Received: February 12, 2006
[15] For selected examples of intramolecular electrophilic activation
of an alkyne toward aromatic substitution, see: a) B. M. Trost,
F. D. Toste, J. Am. Chem. Soc. 1996, 118, 6305 – 6306; b) C. Jia, D.
Piao, J. Oyamada, W. Lu, T. Kitamura, Y. Fujiwara, Science 2000,
287, 1992– 1995; c) H. Inoue, N. Chatani, S. Murai, J. Org. Chem.
2002, 67, 1414 – 1417; d) A. Fürstner, V. Mamane, J. Org. Chem.
2002, 67, 6264 – 6267; e) C. Nevado, A. M. Echavarren Chem.
Eur. J. 2005, 11, 3155 – 3164.
Published online: April 26, 2006
Keywords: alkynes · allenes · gold · hydroarylation · indenes
.
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À
[20] Cyclization occuring through C H activation and arene auration
cannot at this time be ruled out (see scheme below); for
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[21] An alternate explanation would imply that the reaction might
not go through a discrete allene intermediate; hence, a concerted
mechanism would be worth consideration.
[22] For an example of diazoacetate transfer catalyzed by
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