Gold-catalyzed cyclization and subsequent arylidene group transfer of O-propioloyl oximes

Article abstract of DOI:10.1021/ol100581m

Gold-catalyzed cyclizations of O-propioloyl oximes via C-N bond formation followed by arylidene group transfer were successfully carried out to afford the corresponding 4-arylideneisoxazol-5(4H)-ones in good to excellent yields. As an example, (E)-benzaldehyde O-3-phenylpropioloyl oxime (1a) was reacted in acetonitrile at 25 °C in the presence of Au(PPh₃)NTf₂ (5 mol %) to give 4-benzylidene-3-phenylisoxazol-5(4H)-one (2a) in 90% yield. On the basis of crossover experiments, the arylidene "migration" was shown to proceed in an intermolecular manner.

Full text of DOI:10.1021/ol100581m

ORGANIC
LETTERS
2010
Vol. 12, No. 11
2453-2455
Gold-Catalyzed Cyclization and
Subsequent Arylidene Group Transfer of
O-Propioloyl Oximes
Itaru Nakamura,*,†,‡ Masashi Okamoto,‡ and Masahiro Terada‡
Research and Analytical Center for Giant Molecules, Graduate School of Science,
Tohoku UniVersity, Sendai 980-8578, Japan, and Department of Chemistry, Graduate
School of Science, Tohoku UniVersity, Sendai 980-8578, Japan
itaru-n@m.tains.tohoku.ac.jp
Received March 10, 2010
ABSTRACT
Gold-catalyzed cyclizations of O-propioloyl oximes via C-N bond formation followed by arylidene group transfer were successfully carried
out to afford the corresponding 4-arylideneisoxazol-5(4H)-ones in good to excellent yields. As an example, (E)-benzaldehyde O-3-phenylpropioloyl
oxime (1a) was reacted in acetonitrile at 25 °C in the presence of Au(PPh3)NTf2 (5 mol %) to give 4-benzylidene-3-phenylisoxazol-5(4H)-one (2a)
in 90% yield. On the basis of crossover experiments, the arylidene “migration” was shown to proceed in an intermolecular manner.
A powerful method of synthesizing nitrogen-containing
heterocyclic compounds involves a π-acidic transition-metal-
Scheme 1. Formation of Nitrogen-Containing Heterocycles via
catalyzed cyclization,1 which is generally initiated by an
intramolecular nucleophilic attack by a nitrogen atom onto
a carbon-carbon triple bond that possesses an enhanced
electrophilicity due to the π-coordinated metal catalyst. In
many of these reactions, the resulting vinyl metal species A
undergoes a subsequent 1,3-migration of a functional group
(E) from the nitrogen atom to the sp2-carbon that is bound
to the metal catalyst (Scheme 1). In the case of a hydrogen
atom (E ) H), the 1,3-migration is widely recognized as a
π-Acidic Transition Metal-Catalyzed Cyclization, Followed by
1,3-Migration Reaction: (a) 1,3-Hydrogen Migration, (b)
1,3-Alkyl Migration, and (c) 1,3-Alkylidene “Migration”
(Reported Herein)
† Research and Analytical Center for Giant Molecules.
‡ Department of Chemistry.
(1) For selected reviews on π-acidic transition-metal-catalyzed reaction,
see: (a) Kirsch, S. F. Synthesis 2008, 3183. (b) Jime´nez-Nu´n˜ez, E.;
Echavarren, A. M. Chem. ReV. 2008, 108, 3326. (c) Li, Z.; Brouwer, C.;
He, C. Chem. ReV. 2008, 108, 3239. (d) Skouta, R.; Li, C.-J. Tetrahedron
2008, 64, 4917. (e) Bongers, N.; Krause, N. Angew. Chem., Int. Ed. 2008,
47, 2178. (f) Hashmi, A. S. K. Chem. ReV. 2007, 107, 3180. (g) Yamamoto,
Y. J. Org. Chem. 2007, 72, 7817. (h) Fu¨rstner, A.; Davies, P. W. Angew.
Chem., Int. Ed. 2007, 46, 3410. (i) Gorin, D. J.; Toste, F. D. Nature 2007,
446, 395. (j) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chem., Int. Ed.
2006, 45, 7896. (k) Zhang, L.; Sun, J.; Kozmin, S. A. AdV. Synth. Catal.
2006, 348, 2271. (l) Ma, S.; Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006,
45, 200.
hydroamination reaction (type a) and has been extensively
investigated.2 On the other hand, carboamination reactions
(type b), which involve the 1,3-migration of carbon functional
10.1021/ol100581m  2010 American Chemical Society
Published on Web 04/30/2010

groups (E ) CR′3) such as acyl, allyl, methyl, methoxy-
methyl, ester, and carbamoyl groups, have been recently
reported by several groups, including ourselves.3,4 To the
best of our knowledge, however, a catalytic reaction involv-
ing a 1,3-migration of an alkylidene group (type c) has yet
to be reported.5,6 Herein, we report on the gold-catalyzed
cycloisomerizations of O-propioloyl aldoximes 1 via C-N
bond formation and the subsequent arylidene “migration”
to afford the corresponding 4-arylideneisoxazol-5(4H)-ones
2 in good to excellent yields under mild conditions (eq 1).
We disclosed that the present intriguing arylidene group
transfer proceeds via an intermolecular manner, and hence
is regarded as the formal 1,3-migration process.
Table 1. Optimization of Reaction Conditions
entry
catalyst (mol %)
AuCl3 (10)
solvent time/h yield/%a
1
toluene
toluene
21
12
6
76
2
AuBr3 (10)
69
3
Au(PPh3)Cl (10) + AgOTf (10) toluene
Au(PPh3)Cl (10) + AgNTf2 (10) toluene
Au(PPh3)Cl (10) + AgClO4 (10) toluene
Au(PPh3)Cl (10) + AgBF4 (10) toluene
Au(PPh3)NTf2 (10)
AgOTf (10)
Au(PPh3)NTf2 (5)
Au(PPh3)NTf2 (5)
Au(PPh3)NTf2 (5)
Au(PPh3)NTf2 (5)
84
4
1
82
5
24
24
1
24
0.5
1
1
1
50
6
24
7
toluene
toluene
MeCN
THF
CH2Cl2
EtOAc
86
8
13
9
94 (90)b
80
10
11
12
87
87
a The yields were determined using 1H NMR with CH2Br2 as an internal
standard. b Isolated yield in parentheses (Z/E ) 97:3).
First, as summarized in Table 1, the reaction conditions
were optimized using (E)-benzaldehyde O-3-phenylpropi-
oloyl oxime 1a as the substrate. Although the use of trivalent
gold salts such as AuCl3 and AuBr3 gave the desired product
2a in moderate yields (entries 1 and 2), the combination of
Au(PPh3)Cl and AgOTf was highly effective in promoting
the reaction. To investigate the effects of the counteranion,
various silver salts were examined (entries 3-6); optimal
results (reaction time and yield) were obtained for AgNTf2
(entry 4), which possesses a weakly coordinated counteran-
ion. Accordingly, preprepared Au(PPh3)NTf2 exhibited simi-
larly high catalytic activities (entry 7).7 In contrast, the use
of AgOTf by itself gave 2a in a low yield, whereas other
metal salts (PtCl2 and CuCl8) or a Brønsted acid (HCl) was
not effective in catalyzing the reaction. Among the solvents
tested, acetonitrile gave the best results (entries 7 and 9-12).
For the gold-catalyzed reaction of 1a, a trace amount of benzal-
alkyne or the oxime moieties (Table 2). For the alkyne terminus
group (R1), an electron-rich p-anisyl group accelerated the
Table 2. Au-Catalyzed Cycloisomerization of 1a
entry
1
R1
R2
2
time/h yield/%b(Z/E)
1
2
3
1b p-anisyl
Ph
1c p-F3CC6H4 Ph
2b
2c
2d
2e
2f
0.25
1
0.5
4.5
8
87 (97:3)
81 (92:8)
78 (96:4)
93 (>99:1)
90 (>99:1)
88 (>99:1)
69 (94:6)
50 (92:8)
87 (97:3)
94 (94:6)
decomp
1
1d n-Pr
1e Cy
1f t-Bu
1g Ph
1h Ph
1i Ph
1j p-tolyl
1k p-tolyl
1l Ph
Ph
Ph
Ph
p-anisyl
p-ClC6H4
p-F3CC6H4 2i
p-tolyl 2j
p-iPrC6H4 2k
Me
dehyde was detected in the crude products using H NMR.
Next, the optimal conditions (Table 1, entry 9) were
employed to investigate the effects of the substituents at the
4
5c
6
2g
2h 0.25
4.5
7
8
9
10
(2) For selected reviews, see: (a) Widenhoefer, R. H. Eur. J. Org, Chem.
0.25
0.5
0.5
2006, 4555. (b) Arcadi, A. Chem. ReV. 2008, 108, 3266
.
(3) The pioneering work of 1,3-carbon migration from a heteroatom to
carbon in π-acidic metal catalysis: (a) Fu¨rstner, A.; Szillat, H.; Stelzer, F.
J. Am. Chem. Soc. 2000, 122, 6785. (b) Fu¨rstner, A.; Stelzer, F.; Szillat, H.
11
-
0.25
a The reaction of 1 (0.2 mmol) was carried out in the presence of Au(PPh3)NTf2
J. Am. Chem. Soc. 2001, 123, 11863
.
(4) For an acyl group, see: (a) Shimada, T.; Nakamura, I.; Yamamoto,
Y. J. Am. Chem. Soc. 2004, 126, 10546. For an allyl group, see: (b) Fu¨rstner,
A.; Davies, P. W. J. Am. Chem. Soc. 2005, 127, 15024. (c) Istrate, F. M.;
Gagosz, F. Org. Lett. 2007, 9, 3181. (d) Cariou, K.; Ronan, B.; Mignani,
S.; Fensterbank, L.; Malacria, M. Angew. Chem., Int. Ed. 2007, 46, 1881.
For a methyl group, see: (e) Zeng, X.; Kinjo, R.; Donnadieu, B.; Bertrand,
G. Angew. Chem., Int. Ed. 2010, 49, 942. For ester and carbamoyl groups,
see: (f) Nakamura, I.; Sato, Y.; Konta, S.; Terada, M. Tetrahedron Lett.
2009, 50, 2075. For a sulfonyl group, see: (g) Nakamura, I.; Yamagishi,
U.; Song, D.; Konta, S.; Yamamoto, Y. Angew. Chem., Int. Ed. 2007, 46,
(5 mol %) in acetonitrile (1 mL) at 25 °C. b Isolated yield. c At 45 °C.
reaction affording 2b in a good yield (entry 1), whereas an
electron-deficient p-(trifluoromethyl)phenyl group resulted in
a lower yield (entry 2). Substrates that possess an alkyl R1 group
(1d, 1e, and 1f) were efficiently converted to the corresponding
3-alkylated isoxazolones (entries 3-5, respectively). In par-
ticular, the substrate possessing a bulky tert-butyl R2-group (1f,
entry 5) afforded the desired product 2f in an excellent yield,
albeit requiring a higher reaction temperature. Similarly, sub-
stituents on the oxime carbon (R2) exhibited significantly effects
2284
.
(5) Selected examples for 1,3-alkylidene migration from C to C by
π-acidic metal catalysts proceeds in an intramolecular manner. (a) Trost,
B. M.; Yanai, M.; Hoogsteen, K. J. Am. Chem. Soc. 1993, 115, 5294. (b)
Chatani, N.; Kataoka, K.; Murai, S.; Furukawa, N.; Seki, Y. J. Am. Chem.
Soc. 1998, 120, 9104. (c) Lin, M.-Y.; Das, A.; Liu, R.-S. J. Am. Chem.
Soc. 2006, 128, 9340
.
2454
Org. Lett., Vol. 12, No. 11, 2010

on the reaction; an electron-donating p-anisyl R2-group afforded
2g in a good yield (entry 6), whereas electron-withdrawing R2-
groups decreased the chemical yields due to the competitive
decomposition of the starting materials (entries 7 and 8). In
contrast, the reaction of the substrate 1l having an alkyl group
at the oxime moiety did not afford the desired product; 1l was
quickly decomposed under the reaction conditions (entry 11).
Furthermore, the present methodology was applied to ketoxime
1m to afford 2m in a good yield (eq 2).
Scheme 2. Proposed Mechanism
To gain insight into the mechanism, the reaction was carried
out using a 1:1 mixture of 1a and 1k under the optimal reaction
conditions. The resulting mixture of normal products 2a and
2k and crossover products 2n and 2o (ca. 1:1:1:1, as determined
by GC-MS) clearly suggested that the 1,3-arylidene “migra-
tion” proceeds in an intermolecular manner, in sharp contrast
to that of the 1,3-alkyl migration.4 In the presence of 3-phe-
nylisoxazolone 5a, the reaction of 1j afforded an approximately
1:1 mixture of 2j and 2p, whereas, in the presence of
benzaldehyde (1 equiv), the reaction of 1j afforded solely 2j;
in other words, isoxazolone 5 is generated as the reactive
intermediate in the arylidene-transfer process.
nitrogen atom of the oxime group onto the electrophilic
alkyne moiety of 1, which is coordinated to the π-acidic gold
catalyst. In the initial stage, 5-isoxazolone 5 and its enamine
tautomer 5′ are formed.9 As a note, trace amounts of water
may cause the hydrolysis of 4 to presumably form an
aldehyde along with the gold catalyst. The intermolecular
nucleophilic attack by 5′ onto the iminium moiety of another
molecule of 4 would lead to intermediate 6. ꢀ-Elimination
and subsequent protodemetalation would yield product 2,
while regenerating the gold catalyst and 5-isoxazolone 5. The
arylidene group transfer would occur via effective combina-
tion between the highly electrophilic iminium intermediate
4 and the highly nucleophilic isoxazolone species 5′, which
are generated in situ during the reaction. The high Z
selectivity is probably because the E isomer is destabilized
due to steric repulsion between R1 and R2.
In conclusion, we have developed a method to synthesize
4-arylideneisoxazolones from O-propioloyl oximes via cy-
clization, followed by intermolecular arylidene group transfer,
under mild conditions. Investigations to gain further insight
into the reaction mechanism are ongoing in our laboratories.
Acknowledgment. This work was financially supported
by a Grant-in-Aid for Scientific Research from the Japan
Society for Promotion in Science (JSPS).
Supporting Information Available: Experimental pro-
cedures and characterization of 1, 2, and 5b. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL100581M
(6) 1,3-Alkylidene migration from O to C by gold catalysts. Jin, T.;
Yamamoto, Y. Org. Lett. 2007, 9, 5259. During the migration from the
oxygen atom, the alkylidene group is inevitably tethered to the alkyne moiety.
(7) Me´zailles, N.; Ricard, L.; Gagosz, F. Org. Lett. 2005, 7, 4133.
(8) In contrast to the copper-catalyzed reactions of O-propargyl oximes,
the formation of ꢀ-lactam derivatives was not observed for the reactions of
O-propioloyl oximes. Nakamura, I.; Araki, T.; Terada, M. J. Am. Chem.
Soc. 2009, 131, 2804.
Based on our results, a mechanism for the gold-catalyzed
reaction of 1 is proposed (Scheme 2): first, cyclized vinyl
gold intermediate 4 is formed via nucleophilic attack by the
(9) Katritzky, A. R.; Karelson, M.; Harris, P. A. Heterocycles 1991,
32, 329.
Org. Lett., Vol. 12, No. 11, 2010
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