Gold-catalyzed oxidative cyclization of 4-allenyl-1-ynes with 8-methylquinoline oxide

Article abstract of DOI:10.1021/ol4020199

Gold-catalyzed oxidative cyclizations of 4-allenyl-1-ynes with 8-methylquinoline oxide are described; diverse products are produced depending on the allenyl substituents. This reaction comprises initial formation of α-oxo gold carbenes that are attacked b

Full text of DOI:10.1021/ol4020199

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Gold-Catalyzed Oxidative Cyclization of
4‑Allenyl-1-ynes with 8‑Methylquinoline
Oxide
Rahul Kisan Kawade and Rai-Shung Liu*
Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan, ROC
rsliu@mx.nthu.edu.tw
Received June 13, 2013
ABSTRACT
Gold-catalyzed oxidative cyclizations of 4-allenyl-1-ynes with 8-methylquinoline oxide are described; diverse products are produced depending on
the allenyl substituents. This reactioncomprises initial formationof R-oxogold carbenes thatare attacked by allene to form allyl cation intermediates.
The generation of R-oxo gold carbenes I via a regio-
selective oxidation of terminal alkynes with pyridine-based
N-oxides represents the current utility of gold catalysis;1ꢀ3
a general protocol is depicted in eq 1. Besides safe and
easy operation, R-oxo gold carbenes I might exhibit
chemoselectivity distinct from that of other metal carbenes
generated from diazo precursors.2d,4 One notable feature
of gold carbenes I is the cationic character as represented
by resonances I0,2,5 synthetic equivalents as R-oxo carbo-
cations are atypical in organic chemistry. For example, the
reactions of rhodium carbene intermediates II with allenes
were reported to undergo a typical cyclopropanation,
giving methylenecyclopropane derivatives.6
(1) Review: Xiao, J.; Li, X. Angew. Chem. 2011, 123, 7364. Angew.
Chem., Int. Ed. 2011, 50, 7226.
(2) For 8-methylquinoline oxides, see selected examples: (a) Li, B.; Li,
C.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 14070. (b) He, W.; Li, C.;
Zhang, L. J. Am. Chem. Soc. 2011, 133, 8482. (c) Luo, Y.; Ji, K.; Li, Y.;
Zhang, L. J. Am. Chem. Soc. 2012, 134, 17412. (d) Ghorpade, S.; Su,
M.-D.; Liu, R.-S. Angew. Chem. 2013, 125, 4323. Angew. Chem., Int. Ed.
2013, 52, 4229. (e) Bhunia, S.; Ghorpade, S.; Huple, D. B.; Liu, R.-S.
Angew. Chem. 2012, 124, 2993. Angew. Chem., Int. Ed. 2012, 51, 2939.
(f) Vasu, D.; Hung, H.-H.; Bhunia, S.; Gawade, S. A.; Das, A.; Liu, R.-S.
Angew. Chem. 2011, 123, 7043. Angew. Chem., Int. Ed. 2011, 50, 6911.
(g) Dateer, R. B.; Pati, K.; Liu, R.-S. Chem. Commun. 2012, 48, 7200.
(h) Fu, J.; Shang, H.; Wang, Z.; Chang, L.; Shao, W.; Yang, Z.; Tang, Y.
Angew. Chem. 2013, 125, 4292. Angew. Chem., Int. Ed. 2013, 52, 4198.
(i) Pawar, S. K.; Wang, C.-D.; Bhunia, S.; Jadhav, A. M.; Liu, R.-S.
Angew. Chem., Int. Ed. 2013, 52, 7559.
(3) For other pyridine N-oxides, see selected examples: (a) Ye, L.;
Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 3258. (b) Ye,
L.; He, W.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 8550. (c) Ye, L.; He,
W.; Zhang, L. Angew. Chem. 2011, 123, 3294. Angew. Chem., Int. Ed.
2011, 50, 3236. (d) Henrion, G.; Chavas, T. E. J.; Goff, X. L.; Gagosz, F.
Angew. Chem., Int. Ed. 2013, 52, 6277.
We envisage that this reaction pattern can be varied with
R-oxo gold carbene I as the intermediate. We report an
altered chemoselectivity in the reactions of gold carbenes I
with allenes to form allylic cations III that are subjected to
(4) (a) Pagar, V. V.; Jadhav, A. M.; Liu, R.-S. J. Am. Chem. Soc.
ꢀ
2011, 133, 20728. (b) Barluenga, J.; Lonzi, G.; Tomas, M.; Lopez, L. A.
Chem.;Eur. J. 2013, 19, 1573.
(5) (a) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2008, 47, 6754. (b)
Bhunia, S.; Liu, R.-S. J. Am. Chem. Soc. 2008, 130, 16488. (c) Benitez,
D.; Shapiro, N. D.; Tkatchouk, E.; Wang, Y.; Goddard, W. A., III;
Toste, F. D. Nat. Chem. 2009, 1, 482. (d) Seidel, G.; Mynott, R.;
(6) See selected examples: (a) Linday, V. N. G.; Fiset, D.; Gritsch,
P. J.; Azzi, S.; Charett, A. B. J. Am. Chem. Soc. 2013, 135, 1463. (b)
Huval, C. C.; Singleton, D. A. J. Org. Chem. 1994, 59, 2020. (c) Chen, J.;
Lu, L.; Ma, S. Tetrahedron 2008, 64, 8899. (d) Yao, T.; Hong, A.;
Sarpong, R. Synthesis 2006, 3605. (e) Taherirastgar, F.; Brandsma, L.
Synth. Commun. 1997, 27, 4035.
€
ꢀ
ꢀ~
Furstner, A. Angew. Chem., Int. Ed. 2009, 48, 2510. (e) Jimenez-Nunez,
E.; Clavarie, C. K.; Bour, C.; Cardenas, D. J.; Echavarren, A. M. Angew.
Chem., Int. Ed. 2008, 47, 7892. (f) Li, C. W.; Lin, G. Y.; Liu, R.-S.
Chem.;Eur. J. 2010, 16, 5803. (g) Miege, F.; Meyer, C.; Cossy, J.
Beilstein, J. Org. Chem. 2011, 7, 717.
r
10.1021/ol4020199
XXXX American Chemical Society

either deprotonation or nucleophilic addition, as depicted
in eq 3. This new reaction pattern truly reflects the cationic
character of the R-oxo gold carbene.2,5
IPrAuCl/AgNTf2 appeared to be inefficient in giving
desired 2a and 2a0, with their yields being <17%
(entry 6). In control experiemnts, AgNTf2 and HNTf2
alone were catalytically inactive (entries 7ꢀ8). In the pre-
sence of the HOTf additive (30 mol %), only one regio-
isomer 2a was obtained in 78% yield using P(t-Bu)2(o-
biphenyl)AuCl/AgNTf2 (entry 9); the other regioisomer
2a0 was presumably converted to species 2a with HOTf.
We also tested the reaction on pyridine oxide (O2) and
their subsituted derivatives O3ꢀO5 (entries 10ꢀ13);
2-phenylpyridine oxide gave compound 2a with the best
yield, ca. 46% (entry 13).
We tested the reactions on 4-allenyl-1-ynes 1bꢀ1g
to expand the substrate scope; the data are shown in
Scheme 1. In a typical reaction, substrates 1 were treated
with 8-methylquinoline oxide (O1, 2 equiv), P(t-Bu)2(o-
biphenyl)AuCl/AgNTf2 (8 mol %), and HOTf (30 mol %)
in DCM at 28 °C; these conditions assured the formation
of one isomeric product 2. This reaction was extensible
to 4-allenylalk-1-ynes 1bꢀ1e bearing a fluoro, chloro,
methyl, and methoxy substituent at the 4-phenyl carbon,
giving 2,4-dien-1-ones 2bꢀ2e with yields exceeding 79%.
The reactions were also compatible with substrates 1fꢀ1g
bearing an aliphatic group R = tert-butyl and isopropyl;
the corresponding 2,4-dien-1-ones 2f and 2g were obtained
in 78ꢀ81% yields. The molecular structure of 2,4-dien-1-
one 2c was determined by X-ray diffraction.8
We prepared 4-allenyl-1-yne 1a bearing a cyclopropyl
ring7 and a trisubstituted allene to stabilize postulate allylic
cation III (eq 3). We first tested 8-methylquinoline oxide
because it did not need the assistance of Brønsted acids.2
As shown in Table 1 (entry 1), the reaction of species 1a,
8-methylquinoline oxide (O1, 2 equiv), and Ph3AuCl/
AgSbF6 (8 mol %) in dichloromethane (DCM, 28 οC, 30 h)
gave oxidatively cyclized product 2a and its regioisomer
2a0, each in 30ꢀ32% yields, with complete conversion. The
yields of compounds 2a and 2a0 were slightly increased to
34ꢀ35% with Ph3AuCl/AgNTf2 (entry 2). To our plea-
sure, the use of P(t-Bu)2(o-biphenyl)AuCl/AgX (X =
SbF6 and NTf2) further enhanced the yields of each pro-
duct to exceed 40% (entries 3ꢀ4). P(t-Bu)2(o-biphenyl)-
AuCl/AgNTf2, at a 5 mol % loading, gave decreased
yields (31ꢀ32%) of each product (entry 5). Less acidic
Table 1. Oxidation Cyclizations with Various Catalysts
Scheme 1. Substrate Scope for Oxidative Cyclization
products
(yields)c
catalystb
(mol %)
additive time
oxide (mol %) (h) 1a 2a 2a0
entry
1
2
3
4
5
6
7
8
9
PPh3AuCI (8)/AgSbF6 (8) O1 ;
PPh3AuCI (8)/AgNTf2 (8) O1 ;
23
24
24
24
36
36
;
;
;
;
;
8
30 32
34 35
41 40
41 43
32 31
17 16
LAuCI (8)/AgSbF6 (8)
LAuCI (8)/AgNTf2 (8)
LAuCI (5)/AgNTf2 (5)
O1 ;
O1 ;
O1 ;
IPrAuCI (8)/AgNTf2 (8) O1 ;
AgNTf2 (8)
O1 ;
O1 ;
24 45
24 41
;
;
78
23
36
18
46
;
;
;
;
;
;
;
HNTf2 (8)
LAuCI (8)/AgNTf2 (8)
O1 HOTf (30) 24
O2 HOTf (30) 24
O3 HOTf (30) 24
O4 HOTf (30) 24
O5 HOTf (30) 24
;
;
;
;
;
10 LAuCI (8)/AgNTf2 (8)
11 LAuCI (8)/AgNTf2 (8)
12 LAuCI (8)/AgNTf2 (8)
13 LAuCI (8)/AgNTf2 (8)
b
c
a [1] = 0.025 M. L = P(t-Bu)2(o-biphenyl). Product yields are
reported after purification from a silica column.
a [1a] = 0.025 M. b L = P(t-Bu)2(o-biphenyl). c Product yields are
reported after purification from silica column.
We examined this oxidative cyclization on additional
substrates 3 bearing a varied trisubstituted allene; these
species afforded distinct 2,4-dien-1-one products 4, as
depicted in Scheme 2. Notably, the catalytic reactions were
performed without the HOTf additive because only one
regioisomer was produced. Entry 1 shows the applicability
of this catalysis to substrate 3a bearing a phenyl group
(Ar = Ph) to give desired 4a in 79% yield. The same
(7) Cyclopropyl alkynes were frequently used in gold-catalytic reac-
tions because their reactivities are greater than those of normal alkynes.
€
See: (a) Furstner, A.; Aıssa, C. J. Am. Chem. Soc. 2006, 128, 6306.
(b) Shi, M.; Liu, L.-P.; Tang, J. J. Am. Chem. Soc. 2006, 128, 7430. (c) Li,
C.-W.; Pati, K.; Lin, G.-Y.; Abu Sohel, S. M.; Hung, H.-H.; Liu, R.-S.
Angew. Chem. 2010, 122, 10087. Angew. Chem., Int. Ed. 2010, 49, 9891.
(d) Liao, H. H.; Liu, R.-S. Chem. Commun. 2011, 47, 1339. (e) Yang,
C.-Y.; Lin, M.-S.; Liao, H.-H.; Liu, R.-S. Chem.;Eur. J. 2010, 16, 2696.
(f) Gorin, D. J.; Watson, I. D. G.; Toste, F. D. J. Am. Chem. Soc. 2008,
130, 3736. (g) Ye, S.; Yu, Z.-X. Org. Lett. 2010, 12, 804.
(8) The crystallographic data for compound 2c was deposited at the
Cambridge Crystallographic Deposit Center (CCDC 943248).
B
Org. Lett., Vol. XX, No. XX, XXXX

reactions worked well with substrates 3bꢀ3d bearing a
chloro, trifluoromethyl, or tert-butyl group, giving desired
2,4-dien-1-ones 4bꢀ4d in satisfactory yields (72ꢀ81%,
entries 2ꢀ4). Substrates 3e and 3f bearing 2-furanyl and
2-thienyl were also compatible with this reaction (entries
5ꢀ6); resulting products 4e and 4f were obtained in
55ꢀ61% yields. In entry 7, we prepared 4-allenyl-1-yne
3g bearing a Me2C connecting unit; its gold catalysis in
DCM (24 h, 28 °C) led to its 68% recovery. This informa-
tion indicates that a cyclopropane ring can activate the
elctrophilic activation of alkyne because its σ-bond to
alkynyl has a large amount of s-characater.
Scheme 3. Proposed Reaction Mechanism
Scheme 2. Expanded Substrate Scope
D that might coexist with its syn-isomer in an equilibrium
state.9 Our previous calculation on a related system pre-
dicts the occurrence of both syn and anti isomers for allyl
cations D/D0.10 The interconversion between syn- and anti-
configured 1,2,3-trisubstituted allyl cations typically has a
barrier of <17 kcal/mol; this barrier is even smaller when
an electron-donating group is present.9
b
c
a [3a] = 0.025 M. L = P(t-Bu)2(o-biphenyl). Product yields are
reported after purification from a silica column.
Scheme 4. Gold-Catalyzed Reaction on 4-Allenyl-1-yne 5a
We postulate a mechanism to rationalize the formation
of 2,4-dien-1-ones 2a and 4a from 4-allenyl-1-ynes 1a and
3a (Scheme 3). An initial oxidation of compounds 1a and
3a is expected to form R-oxo gold carbenes A that induces
an attack of the tethered allene to give allylic cations B or
B0. For starting 1a, its corresponding cation B undergoes
a loss of a proton to give gold-containing diene C, further
producing observed product 2a0 upon hydrodeauration.
The 2a0f2a isomerization likely occurs under the reaction
conditions involving P(t-Bu)2(o-biphenyl)Au(H2O)þ as
the Brønsted acid. In the case of starting 3a, the corre-
sponding cation B0 forms gold-containing diene C0 with
a loss of a proton. Species C0 ultimately forms observed
2,4-dien-1-one 4a through hydrodeauration and a double
bond shift. We hypothesize a syn-configuration for allyl
cation B because it is less sterically hindered.
We prepared 4-allenyl-1-yne 5a bearing a tethered alco-
hol to implement a three-component oxidative cyclization;
its feasibility relies on an intramolecular alkoxylation on
a postulated anti-configured allyl cation D. The treatment
of species 5a with 8-methylquinoline oxide (2 equiv) and
P(t-Bu)2(o-biphenyl)AuCl/AgNTf2 (8 mol %) afforded
desired 3-en-1-one 6a in 78% yield (Scheme 4). This
observation suggeststhe roleofanti-configured allyl cation
We envisage that NTf2ꢀ or 8-methylquinoline oxide might
facilitate this syn/anti interconversion via a new intermediate
E because they are weak coordinating ligands.11 We per-
formed a control experiment involving the treatment of the
(10) We postulate that the resulting R-oxo carbene A preferably
undergoes a dis-rotation that has a smaller barrier than the con-rotation
(see ref 2d). Since there are two possible rotation modes (inward versus
outward) for starting 1a, the resulting allyl cation D is expected to exist
as a mixture of syn/anti forms, with its syn/anti ratio dependent upon the
relative rates of the two rotations.
(9) The barriers are expected to be small in our systems because a
cyclopropyl group and gold are present for allyl cations D/D0; see refs 5b,
5c, and: Bollinger, J. M.; Brinich, J. M.; Olah, G. A. J. Am. Chem. Soc.
1970, 92, 4025.
ꢀ
(11) Recent X-ray data revealed the coordinating ability of NTf2
see ref 3d.
;
Org. Lett., Vol. XX, No. XX, XXXX
C

4-allenyl-1-ynes 5fꢀ5j bearing various protected amines
(X = NTs, NMs, NBz, NBoc, and NCbz), giving desired
3-en-1-ones 6fꢀ6j in moderate to good yields (52ꢀ74%).
The cyclopropane rings of resulting products 2a and 6a
were readily cleaved by nucleophiles because their adjacent
carbonyl groups can be activated by acid catalysts. For
example, treatment of 2a and 6a with trimethylsilyl
iodide (TMSI, 1.2 equiv) in CCl4 (ꢀ10 °C, 2 h) afforded
5-iodoethyl derived products 8a and 9a in 82% and 68%
yields respectively (eqs 4ꢀ5).
Scheme 5. Three-Component Oxidative Cyclizations
In summary, we report gold-catalyzed oxidative cycliza-
tions of 4-allen-1-ynes14,15 1 and 3 to afford two distinct
2,4-dien-1-ones 2 and 4 efficiently. This process presum-
ably involves an attack of allene at R-oxo gold carbenes to
generate allyl cations, ending with a protodeauration. In
the case of 4-allenyl-1-ynes 5 bearing a tethered alcohol or
amine, their oxidative cyclizations afforded bicyclic 1,3-
dienones 6 via an intramolecular cyclization of postulated
allyl cation intermediates. These results manifested the
carbocation character of R-oxo-gold carbenes.
b
c
a [5a] = 0.033 M. L = P(t-Bu)2(o-biphenyl). Product yields are
reported after purification from a silica column.
same substrate with P(t-Bu)2(o-biphenyl)AuNTf2 (8 mol %)
alone in DCM (28 °C, 16 h), but only starting 5a was
recovered in 68% yield (Scheme 4). This observation indi-
cates that the alkyne group has a greater affinity than
allene to coordinate with gold, thus impeding an allene
alkoxylation. Accordingly the 5af6a transformation does
not involve intermediate 7, resulted from a prior allene
alkoxylation.12,13
Acknowledgment. We thank National Science Council,
Taiwan, for financial support of this work.
We assessed the substrate scope of this reaction on
4-allenyl-1-ynes 5bꢀ5j bearing a hydroxyl or an amine
group; the results are presented in Scheme 5. As shown in
entries 1ꢀ4, this three-component cyclization is applic-
able to trisubstituted allenes 5bꢀ5e bearing R = methyl,
n-butyl, cyclopropyl, and 2-phenylethyl; the correspond-
ing products 6bꢀ6e were obtained in satisfactory yields
(70ꢀ80%). Entries 5ꢀ9 depict the workability with
Supporting Information Available. Spectral data, NMR
spectra, X-ray crystallographic data and spectral data of
new compounds are provided in Supporting Information.
This materials is available free of charge via the Internet
at http://pubs.acs.org.
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systems,15 see selected review: Aubert, C.; Fensterbank, L.; Garcia, P.;
Malacria, M.; Simonneau, A. Chem. Rev. 2011, 111, 1954.
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L.; Malacria, M.; Marco-Constelles, J. J. Am. Chem. Soc. 2004, 126,
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2006, 575. (c) Yang, C. Y.; Lin, G.-Y.; Lio, H.-Y.; Datta, S.; Liu, R.-S.
J. Org. Chem. 2008, 73, 4907. (d) Cheong, P. H.-Y.; Morganelli, P.;
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(12) (a) Shapiro, N.; Toste, F. D. Synlett 2010, 675. (b) Rodolph, M.;
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(13) (a) Patil, N. T.; Lutete, L. M.; Nishina, N.; Yamamoto, Y.
Tetrahedron Lett. 2006, 47, 4749. (b) Lalonde, R. L.; Sherry, B. D.;
Kang, E. J.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 2452. (c) Kinder,
R. E.; Zhang, Z.; Widenhoefer, R. A. Org. Lett. 2008, 10, 3157. (d)
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The authors declare no competing financial interest.
D
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