Gold-catalyzed isomerization of unactivated allenes into 1,3-dienes under ambient conditions

Article abstract of DOI:10.1039/c2cc32131a

We have developed a gold-catalyzed isomerization of unactivated allenes into 1,3-dienes with nitrosobenzene as an additive. This reaction proceeded almost exclusively at room temperature for highly substituted allenes. The utility of this reaction is manifested by the development of one-pot [4+2]-cycloaddition of allenes and reactive alkenes.

Full text of DOI:10.1039/c2cc32131a

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COMMUNICATION
Gold-catalyzed isomerization of unactivated allenes into 1,3-dienes under
ambient conditionsw
Chun-Ming Ting, Yi-Ling Hsu and Rai-Shung Liu*
Received 23rd March 2012, Accepted 3rd May 2012
DOI: 10.1039/c2cc32131a
We have developed a gold-catalyzed isomerization of unactivated
allenes into 1,3-dienes with nitrosobenzene as an additive. This
reaction proceeded almost exclusively at room temperature for
highly substituted allenes. The utility of this reaction is manifested
by the development of one-pot [4+2]-cycloaddition of allenes and
reactive alkenes.
A subsequent B - C transformation relies on either a base to
implement a deprotonation–hydrodeauration sequence (path a),
or an additive to facilitate an intramolecular proton transfer
(path b). We report herein the success of this isomerization of
unfunctionalized allenes under a cooperative action of AuCl3
(5 mol%) and nitrosobenzene (10 mol%) at room temperature.
Table 1 shows our efforts to accomplish isomerization of
allene 1a into 1,3-diene 2a under ambient conditions. Cationic
gold catalysts such as LAuCl/AgX (L = PPh3, (o-biphenyl)-
(t-butyl)2P, 1,3-bis(diisopropylphenyl)-imidazol-2-ylidene, X =
SbF6 and NTf2) were inappropriate for the reactions.6 With
nitrosobenzene (10 mol%) as an additive, AuCl (5 mol%)
enabled the transformation of allene 1a into 1,3-diene 2a in 43%
yield together with unreacted 1a in 52% yield (entry 1). To our
delight, the AuCl3–nitrosobenzene mixture gave 1,3-diene 2a in
excellent yield (92%) at 100% conversion (entry 2). For this diene,
we did not obtain the nitrosobenzene cycloadduct in tractable
amounts; this secondary reaction proceeded very slowly under
reaction conditions.7 With the same additive, AuBr3 and
PtCl2/CO gave desired 2a in 78% and 18% yields respectively
(entries 3 and 4). Notably, a high loading of nitrosobenzene
(1.0 equiv.) inhibited the isomerization (entry 5) possibly due to
Alkynes, allenes and 1,3-dienes are important materials in
organic synthesis. The transformations of unactivated alkynes
into 1,3-dienes were reported by Hayashi et al.,1a Oshima et al.1b
and others1c–e using ruthenium or rhodium catalysts at elevated
temperatures. In contrast, the conversion of unactivated allenes
into dienes remains largely unexplored. Only allenes of special
types (Scheme 1) can be rearranged into 1,3-dienes via either a
skeletal rearrangement or a 1,2-alkene shift mediated by a base
or Brønsted acid.2–4 We sought to realize a gold-catalyzed
isomerization of unactivated allenes into 1,3-dienes (R = H,
alkyl) under ambient conditions. Scheme 1 shows a working
mechanism in which gold species initially forms a p-allene A
that can be visualized as an allylic cation B if a highly electro-
philic gold complex and an electron-rich allene are used.5
Table 1 Activity screening over catalysts and additives
Compounds
(Yields)b
Additive
Time
(h)
Entry Catalysta (mol%)
Solvent
1a
2a
1
2
3
AuCl
AuCl3
AuBr3
PhNO (10) DCM
PhNO (10) DCM
PhNO (10) DCM
10
2
8
52% 43%
—
—
92%
78%
4
5
6
7
8
9
10
11
12
PtCl2/CO PhNO (10) DCM
10
8
3
10
10
3
74% 18%
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
PhNO (10) DCM
DCM
DBU (10) DCM
Et3N (10) DCM
PhNO (10) CH3CN
PhNO (10) DCE
65%
—
92%
94%
—
—
—
—
—
91%
88%
c
—
Scheme 1 Catalytic isomerizations of alkynes and allenes.
3
—
PhNO (10) 1,4-Dioxane 10
PhNO (10) Toluene 10
85% 12%
93%
Department of Chemistry, National Tsing-Hua University, Hsinchu,
Taiwan, ROC. E-mail: rsliu@mx.nthu.edu.tw
w Electronic supplementary information (ESI) available: CCDC
871232. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c2cc32131a
–
a
b
[1a] = 0.10 M. Product yields are reported after separation from a
c
silica column. Complicated mixtures of products.
c
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Chem. Commun., 2012, 48, 6577–6579 6577

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Table 2 Gold-catalyzed room-temperature isomerization of allenes
Entry Allenesa Time (h) 1,3-Dienes (Yields)b
1
2
3
X = Cl (1b)
X = Br (1c)
X = Me (1d)
5.5
5.5
0.5
2b (85%)
2c (81%)
2d (95%)
Scheme 2 A proposed mechanism for the isomerization reaction.
its competition for gold coordination. In the absence of
nitrosobenzene, we observed no isomerization using AuCl3
alone (entry 6), which gave complicated mixtures of products.
Bases such as DBU (entry 7), triethylamine (entry 8),
2,6-lutidine, pyridine and imidazole, each at 10 mol%, were
ineffective in activating AuCl3 to implement the isomerization
under the same conditions. The yields of compound 3a depend
on the solvents: acetonitrile (91%), dichloroethane (88%),
1,4-dioxane (12%) and toluene (0%) (entries 9–12).
4
5
0.7
9.0
5.0
6
As organic bases are generally ineffective, we postulate that
nitrosobenzene accelerates this isomerization via an intra-
molecular proton transfer. Scheme 2 shows a proposed mechanism
involving a cooperative action of gold and nitrosobenzene.
A common reaction pattern of nitrosobenzene begins with an
electrophilic addition at its nitrogen, simultaneously increasing
its oxygen nucleophilicity.8 We suppose a similar action
between allylic cation D and nitrosobenzene, giving Au(I)-
containing oxyaniline E.9 The NH proton of species E is acidic
and undergoes a rearrangement to form intermediate F, thus
completing proton transfer.10
7
8
n = 1 (1h)
n = 2 (1i)
3.0
4.0
2h (92%)
2i (89%)
9
72
10
11
12
13
Ar = 2-thienyl (1k)
Ar = 3-thienyl (1l)
Ar = 3-furanyl (1m)
Ar = 3-benzothienyl (1n)
0.5
0.5
0.5
0.5
2k (90%)
2l (86%)
2m (73%)
2n (89%)
We prepared various tri- and tetrasubstituted allenes 1b–1q
to demonstrate the substrate scope. The reactions are performed
with AuCl3 (5 mol%) and nitrosobenzene (10 mol%) at 28 1C.
Because of the acidic gold species, resulting dienes 2f and 2p
were produced in thermodynamic equilibrium at the end of
the reactions. Entries 1–3 (Table 2) show the applicability to
1,1,-dimethyl-1-aryl-allenes 1b–1d (aryl = 4XC6H4, X = Cl,
Br, Me) giving desired 1,3-dienes 2b–2d in the E-form only
(81–95%). The same reaction with 1-methyl-1,2-diphenylallene
1e gave desired product 2e in the E-form only (88%). We also
tested the allene isomerizations of substrates 1f–1i bearing one
or two alkyl substituents; their resulting dienes 2f–2i were
obtained in 89–92% yields. In entry 5, we monitored the
reaction at 3 h (ca. 50% conversion), the crude products
contained an external olefin in a significant proportion (ca. 55%)
together with its internal olefins 2f (ca. 45%, E/Z = 1.7/1). We
waited for a protracted period (ca. 9 h) to obtain internal
olefin 2f (88%, E/Z = 1.3) as the exclusive species. This
information suggests that hydrogen elimination is easier for
methyl than n-butyl, but AuCl3(H2O) affects final product
distributions via olefin isomerization. This isomerization is
extensible to trisubstituted allenes 1k–1n bearing a heteroaryl
substituent (Ar = 2- and 3-thienyl, 3-furanyl, 3-benzothienyl);
the corresponding dienes 2k–2n were obtained in satisfactory
yields (73–90%, entries 10–13). For tetrasubstituted allenes
1o–1q, the catalytic isomerizations proceed smoothly, giving
expected dienes 2o/2o0, 2p–2q in 89–92% yields (entries 14–16).
In entry 14, we obtained species 2o predominantly at a 25%
conversion, indicating that initial deprotonation occurred
preferably at the Ph(CH3)CQposition.
14
15
4.5
3.0
4.5
16
a
[allene] = 0.1 M, AuCl3 (5 mol%), PhNO (10 mol %), 28 1C.
Product yields were reported after separation from a silica column.
b
The catalytic isomerization of disubstituted allenes appears to
be less feasible because their corresponding gold-allylic cations B
are less stable than those from highly substituted allenes 1. We
found that the selection of acetonitrile as solvent enabled a
complete isomerization of 1,1-disubstituted allenes 3a–c into
1,3-dienes 4a–c in 83–86% yields using the AuCl3–nitrosobenzene
mixture (40 1C, 24 h). This optimized condition failed to work
with 1,2-disubstituted allene 3d, which was recovered in 43%
yield. Accordingly, the generation of a tertiary carbon on gold-
allylic cation B is indispensable for this isomerization (Scheme 3).
We prepared deuterated allene d6-1a to study the reaction mecha-
nism. The corresponding product d6-2a has deuterium content of
ca. 11% and 21%, respectively, at its dienyl C(1) and C(2)-carbons;
this distribution partially supports our reaction mechanism that
c
6578 Chem. Commun., 2012, 48, 6577–6579
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Entries 5 and 6 show the applicability to the stereoselective
synthesis of tricyclic carbocycles 5e and 5f using allene 1i.
In summary, we have developed a gold-catalyzed isomeriza-
tion of unactivated allenes into 1,3-dienes with nitrosobenzene
as an additive. This reaction proceeded almost exclusively at
room temperature for highly substituted allenes. We postulate a
mechanism involving the intermediacy of gold allylic cation B
which is subjected to an intramolecular proton transfer
mediated by nitrosobenzene. The utility of this new catalysis
is manifested by the development of a gold-catalyzed [4+2]-
cycloaddition reaction between allene and electron-deficient
alkene. Further efforts to accomplish an isomerization of
1,2-disubstituted allenes at room temperature are in progress.
The authors thank the National Science Council, Ministry of
Education and National Tsing-Hua University for supporting
this work.
Scheme 3 Gold-catalyzed isomerization of disubstituted allenes.
Notes and references
Scheme 4 Deuterium-labeling experiment.
1 (a) R. Shintani, W. L. Duan, S. Park and T. Hayashi, Chem. Commun.,
2006, 3646; (b) H. Yasui, H. Yorimitsu and K. Oshima, Synlett, 2006,
1783; (c) M. Shiotsuki, Y. Ura, T. Ito, K. Wada, T. Kondo and T. J.
Mistudo, Organomet. Chem., 2004, 689, 3168; (d) G. Li, G. Zhang and
L. Zhang, J. Am. Chem. Soc., 2008, 130, 3740; (e) K. Hirai, H. Suzuki,
Y. Moro-oka and T. Ikawa, Tetrahedron Lett., 1980, 21, 3413.
2 For the transformation of functionalized allenes into dienes via
skeletal rearrangements, see: (a) X. Zhang, C. Fu and S. Ma,
Org. Lett., 2011, 13, 1920; (b) M. E. Krafft, K. M. Hallal,
D. V. Vidahani and J. W. Cran, Org. Biomol. Chem., 2011, 9, 535.
3 (a) S. Tsuboi, T. Masuda and A. Takeda, J. Org. Chem., 1982, 47, 4478;
(b) B. M. Trost and U. Kazmaier, J. Am. Chem. Soc., 1992, 114, 7933.
4 (a) E. Hayashi, R. P. Hsung, J. B. Feltenberger and A. G. Lohse,
Org. Lett., 2009, 11, 2125; (b) R. Sanz, D. Miguel, A. Martinez,
M. Gohain, P. Garcia-Garcia, M. A. Fernandez-Rodriguez,
E. Alvarez and F. Rodriguez, Eur. J. Org. Chem., 2010, 7027.
5 (a) R. W. Bates and V. Satcharoen, Chem. Soc. Rev., 2002, 31, 12;
(b) R. A. Widenhoefer, Chem.–Eur. J., 2008, 14, 5382; (c) G. Hamilton,
E. J. Kang, M. Mba and F. D. Toste, Science, 2007, 317, 496;
(d) Z. Zhang and R. A. Widenhoefer, Angew. Chem., Int. Ed., 2007,
46, 283; (e) J. H. Lee and F. D. Toste, Angew Chem., Int. Ed., 2007,
46, 912; (f) N. Nishina and Y. Yamamoto, Angew. Chem., Int. Ed.,
2006, 45, 3314.
C(2) has higher deuterium content than C(1). Herein, AuCl3
also catalyzes a proton exchange between water and the diene
protons of 2a to affect the deuterium distribution (Scheme 4).11
To demonstrate the utility of this isomerization, we have
developed gold-catalyzed isomerization–cycloaddition cascades
between allenes and reactive alkenes including maleic anhydride,
maleimides and 1,4-benzoquinolines (Table 3). These new reac-
tions allow one-pot synthesis of highly substituted polycyclic
carbocycles with high stereocontrol. In a typical operation, allene
1a (or 1i) was treated with the same catalyst mixture in dichloro-
methane over a suitable time (2 or 4 h) to complete an initial
allene isomerization; to the same solution was added an alkene to
achieve a subsequent endo-[4+2]-cycloaddition. Entries 1–4 show
the syntheses of bicyclic carbocycles 5a–5c and 5d0 with 83–91%
yields. In entry 4, we obtained a mixture of cycloadducts 5a and
5d0 in equal proportion, but species 5d is readily convertible to its
oxidized form 5d0 upon chromatographic separation. We
determined the stereochemistry of cycloadduct 5c via an X-ray
diffraction study;12 its ORTEP drawing is provided in ESI.w
6 These cationic gold complexes led to decomposition of starting allene
1a in DCM (28 1C, 2–5 h) even in the presence of nitrosobenzene
(10 mol%).
7 A 15-h period is required for the [4+2]-cycloaddition of nitrosobenzene
with diene 2a generated in situ, whereas the allene isomerization is com-
plete within 2 h. Spectral data of cycloadduct 6 are provided in ESIw.
Table 3 Isomerization/cycloaddition cascades between allenes and alkenes
8 See selected examples to support this route: (a) T. Tejero and P. Merino,
Angew. Chem., Int. Ed., 2004, 43, 2995; (b) N. Momiyama and
H. Yamamoto, J. Am. Chem. Soc., 2005, 127, 1080; (c) V. V. Pagar,
A. M. Jadhav and R.-S. Liu, J. Am. Chem. Soc., 2011, 133, 20728;
(d) A. Mukherjee, R. B. Dateer, R. Chaudhuri, S. Bhunia, S. N. Karad
and R.-S. Liu, J. Am. Chem. Soc., 2011, 133, 15372; (e) S. Murru,
A. A. Gallo and R. Srivastava, ACS Catal., 2011, 1, 29.
9 Some reactions gave a gold mirror in a small amount, we envisage
that the active gold species should be Au(I) rather than Au(III)
because allenes were known to cause Au(III) reduction. See
(a) G. Lemiere, V. Gandon, N. Agenet, J.-P. Goddard, A. de Kozak,
C. Aubert, L. Fensterbank and M. Malacria, Angew. Chem., Int. Ed.,
2006, 45, 7596; (b) A. S. K. Hashmi, M. C. Blanco, D. Fisher and
J. W. Bats, Eur. J. Org. Chem., 2006, 1387.
10 For a proton transfer in gold catalysis, see C. M. Krauter, A. S. K.
Hashmi and M. Pernpointner, ChemCatChem, 2010, 2, 1226.
11 In a separate experiment, the olefin protons of 1,3-diene 2a undergo
AuCl3-catalyzed proton exchange with external D2O (see ESIw).
12 X-ray crystallographic data of compound 5c. CCDC 871232.
a
b
[allene] = 0.1 M, 3 h for 1a and 4 h for 1i. Product yields are
reported after separation from a silica column.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 6577–6579 6579