Phosphorus-containing lewis base catalyzed cascade reactions of isatin-derived oximes with allenic esters and further transformations

Article abstract of DOI:10.1002/ejoc.201200511

Phosphorus containing Lewis base catalyzed cascade reactions of isatin-derived oximes with allenic esters afford the corresponding functionalized nitrones. Further Lewis acid catalyzed highly regioselective intramolecular [3+2] cyclizations give the corre

Full text of DOI:10.1002/ejoc.201200511

Job/Unit: O20511
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Date: 18-06-12 11:45:12
Pages: 12
FULL PAPER
DOI: 10.1002/ejoc.201200511
Phosphorus-Containing Lewis Base Catalyzed Cascade Reactions of Isatin-
Derived Oximes with Allenic Esters and Further Transformations
Cheng-Kui Pei,[a] Yu Jiang,[a] and Min Shi*[a,b]
Keywords: Lewis bases / Domino reactions / Heterocycles / Allenes / Cyclization
Phosphorus containing Lewis base catalyzed cascade reac-
tions of isatin-derived oximes with allenic esters afford the
corresponding functionalized nitrones. Further Lewis acid
catalyzed highly regioselective intramolecular [3+2] cycliza-
tions give the corresponding bridged cycloadducts. More-
over, a combined “one-pot” reaction is also feasible for the
above two catalytic reactions.
Introduction
Oximes and their derivatives are valuable synthetic build- arrangement reactions to prepare amides,[3] and as precur-
ing blocks,[1] and they are well-known for their dehydration sors of 1,3-dipolar addition reactions.[4] Recently, allenoates
reactions to produce nitriles,[2] for their Beckmann re- have served as an attractive substrate class for Lewis base
Scheme 1. Reaction modes of oximes and allenoates.
catalyzed reactions, and they have attracted much synthetic
[a] Key Laboratory for Advanced Materials and Institute of Fine
interest because of their facile preparation and diverse reac-
tivity.[5] To our surprise, the reactions of oximes as sub-
strates with allenoates have been seldom mentioned. The
only example was reported by Kwon in 2011, providing βЈ-
umpolung addition products due to the nucleophilicity of
the oximes [Scheme 1, Equation (1)].[6] Herein, we wish to
report the discovery of the reaction of oximes derived from
Chemicals, East China University of Science and Technology,
130 Mei Long Road, Shanghai 200237, China
[b] State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China
Fax: +86-21-64166128
E-mail: Mshi@mail.sioc.ac.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200511.
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C.-K. Pei, Y. Jiang, M. Shi
FULL PAPER
isatins with allenic esters catalyzed by phosphorus-contain- Table 1. Optimization of the conditions for the reaction of (E)-1-
ing Lewis bases (“P” catalytic cycle)[7–9] to give function-
alized nitrones as the products, and we will also disclose
benzyl-3-(hydroxyimino)indolin-2-one (1a) and ethyl 2,3-butadi-
enoate (2a).[a]
that these nitrones as 1,3-dipoles can undergo highly re-
gioselective intramolecular [3+2] cycloaddition reac-
tions[10,11] in the presence of a Lewis acid (“LA” catalytic
cycle) to afford bridged-ring compounds, which are struc-
tural subunits in many natural products and biologically
active molecules[11] [Scheme 1, Equation (2)].
Entry
Solvent
Phosphane
T
[°C]
Time
[h]
Yield
[%][b]
Results and Discussion
1
2
3
4
5
6
7
8
THF
Et2O
DCM
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
12
12
12
12
12
12
12
12
12
12
12
12
12
62
53
46
48
63
65
We initially utilized (E)-1-benzyl-3-(hydroxyimino)-
indolin-2-one (1a; 0.1 mmol, 1.0 equiv.) and ethyl 2,3-buta-
dienoate (2a; 0.2 mmol, 2.0 equiv.) as substrates to investi-
gate their reaction behavior in THF at room temperature
in the presence of nitrogen-containing Lewis bases such as
1,4-diazabicyclo[2,2,2]octane (DABCO) (“N” catalytic cy-
cle, 20 mol-%). It was found that the reaction took place
smoothly to give the corresponding addition product 3aa in
87% yield [Scheme 1, Equation (2)]. Considering the dif-
ferent reaction profiles of phosphorus- and nitrogen-con-
DCE
CHCl3
toluene
CH3CN
DMF
DMSO
dioxane
toluene
toluene
[e]
–
[e]
–
[e]
9
–
10
11
12
PPh3
PBu3
NR
disorder
disorder
PMePh2
P(4-MeOC6H4)
taining Lewis bases, we changed the Lewis base from 13
toluene
45
3
DABCO to PPh3 and were pleased to find that nitrone
product 4aa had been afforded in 62% yield. These results
attracted our attention. Subsequently, we chose PPh3 as a
Lewis base and screened various solvents for this reaction.
We found that toluene was the best solvent for this reaction,
affording 4aa in 65% yield (Table 1, Entry 6). In acetonitrile
(CH3CN), N,N-dimethylformamide (DMF), and dimethyl
sulfoxide (DMSO), only addition product 3aa was pro-
14
15
16
17
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
P(4-FC6H4)3
r.t.
0
12
24
24
3
3
3
68
68
68
72
70
78
78
NR
P(4-FC6H4)3
P(4-FC6H4)3
P(4-FC6H4)3
P(4-FC6H4)3
P(4-FC6H4)3
P(4-FC6H4)3
–
–10
50
60
50
50
50
18
19[c]
20[d]
21
3
r.t.
[a] All reactions were carried out with 1a (0.10 mmol) and 2a
duced without the formation of 4aa (Table 1, Entries 7–9), (0.20 mmol) in solvent (2.0 mL) for 24 h. [b] Isolated yield.
and in dioxane, no reaction occurred (Table 1, Entry 10).
We next attempted to screen other phosphorus-containing
[c] Compound 2a was used as 3.0 equiv. [d] Compound 2a was used
as 4.0 equiv. [e] Only 3aa was formed.
Lewis base catalysts and found that tris(4-fluorophenyl)-
phosphane [P(4-FC6H4)3] was the best Lewis base for the products 4ba–da in good to high yields (up to 90%; Table 2,
reaction (Table 1, Entries 11–14). Lowering the reaction Entries 1–3). Changing the ester moiety of allenic esters 2
temperature to 0 or –10 °C did not improve the yield of 4aa from OEt to OBn provided a similar reaction outcome, af-
(Table 1, Entries 15 and 16). Raising the reaction tempera- fording desired product 4ab in 72% yield (Table 2, Entry 4).
ture to 50 °C furnished 4aa in 72% yield (Table 1, En- As for substrates 1e–m, regardless of whether an electron-
try 17), but further increase in the reaction temperature did donating or electron-withdrawing group was introduced at
not improve the reaction outcome (Table 1, Entry 18). In- the 5-, 6-, or 7-position of the benzene ring of the N-allyl-
creasing the amount of allenoate employed to 3.0 equiv. protected oximes, the reactions proceeded smoothly to give
produced 4aa in 78% yield (Table 1, Entry 19), and a fur- the corresponding products 4 in good yields (Table 2, En-
ther increase in the amount of allenoate employed did not tries 5–13). The use of oxime 1n (R1 = 5-Me, PG = Bn)
give a better reaction outcome (Table 1, Entry 20). We also as the substrate afforded desired product 4na in 88% yield
confirmed that no product was formed in the absence of (Table 2, Entry 14). However, as for oxime 1o having a
P(4-FC6H4)3 (Table 1, Entry 21). Thus, we established bromine atom at the 4-position of the benzene ring, only
the optimal conditions for this reaction: 20 mol-% addition product 3oa was formed rather than the nitrone
P(4-FC6H4)3 as the catalyst and toluene as a solvent with product, perhaps due to steric effects (Table 2, Entry 15).
3.0 equiv. allenoate at 50 °C.
The allenic ester α-methylallenoate was also used in the re-
Under the optimized reaction conditions, the reaction action. However, the corresponding βЈ-umpolung addition
generality was investigated by using various oximes 1 in the product was formed, which is similar to the finding of
reaction with several allenic esters 2, and the results of these Kwon[6] (Supporting Information, Scheme S1). The struc-
experiments are summarized in Table 2. With oximes 1b–d ture of 4da was unambiguously determined by X-ray dif-
bearing different N-protecting groups, the reactions pro- fraction. The ORTEP drawing is shown in the Supporting
ceeded smoothly to produce the corresponding nitrone Information.[12]
2
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Cascade Reactions of Isatin-Derived Oximes with Allenic Esters
Table 2. Substrate scope of the cascade reactions of oximes 1 and
allenic esters 2.[a]
Table 3. Optimization of the reaction conditions for the intramolec-
ular [3+2] cycloaddition of 4aa.[a]
Entry
1
R1
PG
R2
Product Yield
[%][b]
Entry
Lewis acid
Solvent
T [°C]
Yield [%][b]
1
2
3
4
5
6
7
8
1b
1c
1d
1a
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
H
H
H
Me
Et (2a)
Et (2a)
Et (2a)
Bn (2b)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
4ba
4ca
4da
4ab
4ea
4fa
4ga
4ha
4ia
89
70
90
72
89
83
85
87
80
87
77
90
80
88
1
2
3
4
5
6
7
8
9
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
BF3·Et2O
Sc(OTf)3
–
toluene
DCM
THF
toluene
toluene
toluene
toluene
toluene
toluene
r.t.
r.t.
r.t.
trace
trace
trace
50
65
60
CPh3
1-allyl
Bn
H
80
5-Me
5-Br
5-Cl
6-Me
6-Br
7-Cl
7-Br
7-F
1-allyl
1-allyl
1-allyl
1-allyl
1-allyl
1-allyl
1-allyl
1-allyl
1-allyl
Bn
100
100
100
100
100
disorder
51
9
–
10
11
12
13
14
15
4ja
[a] All reactions were carried out with 4da (0.10 mmol) catalyzed
by Lewis acid (20 mol-%) with the addition of 4 Å MS (100 mg) in
solvent (2.0 mL) for 36 h. [b] Isolated yield.
4ka
4la
4ma
4na
4oa
7-CF3
5-Me
4-Br
[c]
1-allyl
–
Table 4. Intramolecular [3+2] cycloaddition reaction of 4.[a]
[a] All reactions were carried out with 1 (0.10 mmol) and 2
(0.30 mmol) in toluene (2.0 mL) for 3 h. [b] Isolated yield. [c] Only
addition product 3oa was formed.
Next, we utilized nitrone product 4da as the substrate to
investigate its intramolecular [3+2] cycloaddition reaction
behavior in the presence of Yb(OTf)3 as the Lewis acid and
4 Å molecular sieves (100 mg for 0.1 mmol of 4da). The re-
sults are summarized in Table 3. We found that the cycliza-
tion gave a trace amount of 5da in conventional solvents,
such as toluene, DCM, and THF, at room temperature
(Table 3, Entries 1–3). An increase in the reaction tempera-
ture to 80 and 100 °C in toluene resulted in smooth cyclo-
addition to afford 5da in 50 and 65% yield, respectively, in
a highly regioselective manner (Table 3, Entries 4 and 5). A
further increase in the reaction temperature to 120 °C did
not improve the reaction outcome (Table 3, Entry 6). Other
Lewis acids such as BF3·OEt2 and Sc(OTf)3 were also tested
Entry
Substrate
R1
PG
Product
Yield [%][b]
1
2
3
4
5
4aa
4ca
4ga
4ha
4na
H
H
5-Cl
6-Me
5-Me
Bn
5aa
5ca
5ga
5ha
5na
65
60
68
65
70
CPh3
1-allyl
1-allyl
Bn
[a] All reactions were carried out at 100 °C by using 4 (0.10 mmol)
catalyzed by Yb(OTf)3 (20 mol-%) with the addition of 4 Å MS
(100 mg) in toluene (2.0 mL) for 3 h, unless otherwise specified.
[b] Isolated yield.
in the above reaction; a complex mixture of products was 1b and 1d with allenoate 2a by adding P(4-FC6H4)3
obtained in the former and a 51% yield of 5da was obtained (20 mol-%) in toluene and performing the reaction at 50 °C
in the latter (Table 3, Entries 7 and 8). We also found that for 3 h, followed by the addition of Yb(OTf)3 (20 mol-%)
the use of Yb(OTf)3 as a Lewis acid is essential for this and 4 Å molecular sieves without purification upon heating
transformation (Table 4, Entry 9). Therefore, Yb(OTf)3 was the reaction mixtures at 100 °C for 36 h. The corresponding
used as the catalyst in this cyclization reaction.
bridged-ring compounds 5ba and 5da could be obtained in
Under the optimized reaction conditions, we found that 57 and 61% yield, respectively (Scheme 2).
nitrone products 4 could undergo intramolecular [3+2] cy-
To clarify the reaction mechanism, several deuterium la-
cloaddition to afford bridged-ring compounds 5 in good beling experiments were conducted, and the results are
yields with high regioselectivities (Table 4, Entries 1–5), summarized in Scheme 3. The first experiment was carried
thus opening up a new route to synthesize bridged-ring out with 1d-d (80%D) and 2a under the standard reaction
compounds. Compound 5ca was characterized by spec- conditions to afford crude product 4da in 88% yield along
troscopy and the structure was confirmed by single-crystal with 26, 15, 9, and 11% Dcontent[14] incorporated at the
X-ray diffraction.[13] Next, under the optimized reaction D1, D2, D3, and D4 positions, respectively [Scheme 3, Equa-
conditions, we carried out the one-pot reaction of oximes tion (1)], after silica gel column chromatography. Consider-
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The mechanism for the reactions has not been unequivo-
cally established, but one rational explanation is shown in
Scheme 4 based on earlier reports[7] and our own deuterium
labeling investigations. Addition of phosphane to allenoate
2a delivers zwitterionic intermediate A. Deprotonation of
pronucleophile 1 by zwitterionic intermediate A forms in-
termediate B. The negatively charged oxygen ion of the
oxime can coordinate with the phosphate ion of the phos-
phonium enolate,[7e,7f,15] which precludes addition of the
negative oxygen ion to the enolate, and the following conju-
gate addition of the nitrogen atom of the oxime to the enol-
ate forms intermediate C. Subsequently, facile 1,2-proton
transfer affords intermediate D, and then elimination takes
place to give intermediate E. The existence of the positively
charged nitrogen ion of intermediate E makes deproton-
ation from the active methylene feasible by zwitterionic in-
termediate A to give intermediate F, which undergoes con-
jugate addition to give intermediate G, and then facile 1,2-
proton transfer affords intermediate H. Finally, elimination
takes place to give the corresponding product 4 and regen-
erates the phosphane catalyst. In the “LA” catalytic cycle,
the two esters of nitrone 4 can be activated by Yb(OTf)3 to
give intermediate I, which undergoes cyclization regioselec-
tively to give intermediate J. Intermediate J undergoes an-
other cyclization to furnish cycloaddition product 5 and re-
generates the Yb(OTf)3 catalyst, presumably through an
asynchronous concerted process. Therefore, the one-pot
synthetic sequence can be also summarized as a cascade
process including two phosphane-catalyzed cascade cata-
lytic cycles (“P” cycle) combined with a Lewis acid cata-
lyzed catalytic cycle (“LA” cycle) (Scheme 4). From what
has been discussed above, we can easily draw a conclusion
Scheme 2. One-pot reaction of oximes 1b and 1c with allenoate 2a.
ing that a trace amount of H2O would assist the 1,2-proton
transfer and affect the D content of 4da[15] that and 1d-d
could be also generated in situ from 1d and D2O, we carried
out the same reaction with 1d in toluene/D2O (1.0 equiv.)
and found that 4da was formed in 88% yield along with 38,
25, 15, and 17%D content incorporated at the D1, D2, D3,
and D4 positions, respectively [Scheme 3, Equation (2)]. In-
creasing the employed amount of D2O could improve the
D content incorporated at the D1, D2, D3, and D4 positions
[Scheme 3, Equation (2)]. Increasing the employed amount
of D2O to 15.0 equiv., we observed 100%D content incor-
porated at the D1, D2, D3, and D4 positions [Scheme 3,
Equation (2)]. These deuterium labeling experiments indi-
cate that proton transfer between the oxime or water and
the allenic ester can occur in the presence of a tertiary phos-
phane and several intermolecular proton transfers can take
place at the same time in the catalytic cycle.
Scheme 3. Deuterium labeling experiments.
4
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Cascade Reactions of Isatin-Derived Oximes with Allenic Esters
Scheme 4. A plausible reaction mechanism.
about the possible details on the formation of D1, D2, D3,
and D4 incorporated products. In the first “P” cycle, D2
incorporation could be obtained by proton transfer be-
tween the deuterium atom at the hydroxy group of the ox-
ime with intermediate A, and 1,2-proton transfer of inter-
mediate C gives D1 incorporation. Intermediates G and H
in the second “P” cycle could also undergo intermolecular
proton transfer with the deuterium atom at the hydroxy
group of the remaining oxime or D2O to provide D3 and
D4 incorporated products, suggesting that the correspond-
ing deuterated intermediate H could be regenerated through
deprotonation by the in situ generated counteranion to par-
ticipate in the catalytic cycle.[15]
sure, and the residue was purified by column chromatography on
silica gel (pentane/EtOAc, 2:1) to give 1a as a yellow solid (1.13 g,
90% yield).
(E)-1-Benzyl-3-(hydroxyimino)indolin-2-one (1a): A yellow solid
(1.13 g, 90% yield); m.p. 219–220 °C. 1H NMR (400 MHz, CDCl3,
TMS): δ = 4.94 (s, 2 H), 6.96 (d, J = 7.6 Hz, 1 H), 7.05 (t, J =
7.6 Hz, 1 H), 7.21–7.26 (m, 1 H), 7.29–7.35 (m, 5 H), 8.02 (d, J =
7.6 Hz, 1 H), 13.6 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3,
TMS): δ = 42.6, 109.6, 115.4, 122.8, 127.0, 127.2, 127.5, 128.7,
132.0, 136.3, 142.8, 143.5, 163.3 ppm. IR (CH Cl ): ν = 2982, 2933,
˜
2
2
1717, 1655, 1595, 1558, 1442, 1369, 1040, 964, 786, 730 cm–1. MS
(ESI): m/z
= 275.0 [M +
Na]+. HRMS (ESI): calcd. for
C15H12N2O2Na [M + Na]+ 275.0791; found 275.0797.
(E)-3-(Hydroxyimino)-1-methylindolin-2-one (1b): A yellow solid
(0.79 g, 90% yield); m.p. 209–210 °C. 1H NMR (400 MHz, [D6]-
DMSO, TMS): δ = 3.14 (s, 3 H), 7.01–7.07 (m, 2 H), 7.40 (t, J =
7.6 Hz, 1 H), 7.95 (d, J = 7.6 Hz, 1 H), 13.4 (s, 1 H) ppm. 13C
NMR (100 MHz, [D6]DMSO, TMS): δ = 25.8, 109.0, 115.2, 122.6,
Conclusions
In summary, we have found and developed an interesting
phosphorus-containing Lewis base catalyzed cascade reac-
tions of isatin-derived oximes with allenic esters to give the
corresponding functionalized nitrones in good to excellent
yields under mild conditions. The obtained nitrones could
further undergo intramolecular [3+2] cycloaddition to af-
ford bridged-ring compounds in good yields with high re-
gioselectivities, and these compounds are useful building
blocks in the organic synthesis of biologically useful com-
pounds.[11] Furthermore, a combined “one-pot” reaction is
126.8, 132.0, 143.7, 143.8, 163.1 ppm. IR (CH Cl ): ν = 3213, 2926,
˜
2
2
2851, 1716, 1609, 1558, 1457, 1374, 1329, 1071, 1015, 969, 801,
697, 541 cm–1. MS (ESI): m/z = 177.0 [M + H]+. HRMS (ESI):
calcd. for C9H9N2O2 [M + H]+ 177.0659; found 177.0657.
(E)-3-(Hydroxyimino)-1-tritylindolin-2-one (1c):
A yellow solid
(1.62 g, 80% yield); m.p. 263–265 °C. 1H NMR (400 MHz, [D6]-
DMSO, TMS): δ = 6.24 (d, J = 7.6 Hz, 1 H), 6.98 (t, J = 7.6 Hz,
1 H), 7.07 (t, J = 7.6 Hz, 1 H), 7.20 (t, J = 7.2 Hz, 3 H), 7.28 (t, J
= 7.2 Hz, 6 H), 7.47 (d, J = 7.2 Hz, 6 H), 8.04 (d, J = 7.6 Hz, 1
H), 13.4 (s, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO, TMS): δ
also feasible for the above two catalytic reactions. A plaus- = 73.9, 115.3, 116.9, 122.4, 126.5, 126.8, 127.8, 128.7, 130.3, 142.1,
143.0, 143.3, 164.0 ppm. IR (CH Cl ): ν = 3213, 2926, 2851, 1716,
˜
ible reaction mechanism has also been proposed on the ba-
sis of previous literature and our own deuterium labeling
investigations. Efforts are in progress to elucidate further
mechanistic details of these reactions and to understand
their scope and limitations.
2
2
1609, 1558, 1457, 1374, 1329, 1071, 1015, 969, 801, 697, 541 cm–1.
MS (ESI): m/z = 427.0 [M + Na]+. HRMS (ESI): calcd. for
C27H20N2O2Na [M + Na]+ 427.1417; found 427.1426.
(E)-1-Allyl-3-(hydroxyimino)indolin-2-one (1d):
A yellow solid
(0.90 g, 89% yield); m.p. 215–217 °C. 1H NMR (400 MHz, CDCl3,
TMS): δ = 4.34 (dt, J = 5.2, 1.5 Hz, 2 H), 5.23 (dd, J = 10.0,
1.5 Hz, 1 H), 5.25 (dd, J = 17.2, 1.5 Hz, 1 H), 5.79–5.87 (m, 1 H),
6.80 (d, J = 8.0 Hz, 1 H), 7.03 (dt, J = 8.0, 1.0 Hz, 1 H), 7.32 (dt,
J = 8.0, 1.0 Hz, 1 H), 8.07 (dd, J = 8.0, 1.0 Hz, 1 H), 11.48 (br. s,
1 H) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 42.2, 109.2,
115.6, 117.9, 123.2, 128.1, 130.9, 132.1, 143.2, 144.1, 164.0 ppm.
Experimental Section
General Procedure for 1: To a solution of N-Bn-protected isatin
(1.2 g, 0.50 mmol) in MeOH (10 mL) was added hydroxylamine hy-
drochloride (0.41 g, 0.60 mmol) and potassium carbonate (0.83 g,
0.60 mmol). The resulting mixture was stirred under reflux over-
night. The reaction mixture was concentrated under reduced pres-
IR (CH Cl ): ν = 3219, 2924, 1716, 1608, 1465, 1378, 1352, 1194,
˜
2
2
1043, 1017, 949, 751, 705 cm–1. MS (ESI): m/z = 224.9 [M +
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Na]+. HRMS (ESI): calcd. for C11H10N2O2Na [M
+
Na]+
1 H), 13.83 (s, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO, TMS):
225.0635; found 225.0641.
δ = 42.8, 114.6, 115.5, 118.1, 124.2, 125.9, 133.6, 133.9, 138.6,
142.2, 163.4 ppm. IR (CH Cl ): ν = 2915, 2851, 1717, 1600, 1442,
˜
2
2
(E)-1-Allyl-3-(hydroxyimino)-5-methylindolin-2-one (1e): A yellow
solid (0.97 g, 90% yield); m.p. 189–190 °C. 1H NMR (400 MHz,
CDCl3, TMS): δ = 2.29 (s, 3 H), 4.37 (d, J = 5.2 Hz, 2 H), 5.23 (d,
J = 10.0 Hz, 1 H), 5.24 (d, J = 17.2 Hz, 1 H), 5.79–5.88 (m, 1 H),
6.70 (d, J = 8.0 Hz, 1 H), 7.13 (d, J = 8.0 Hz, 1 H), 7.92 (s, 1 H),
11.2 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 20.9,
42.2, 109.0, 115.6, 117.8, 128.8, 131.1, 132.5, 132.8, 141.1, 144.4,
1329, 1175, 1035, 931, 795, 729, 519 cm–1. MS (ESI): m/z = 237.0
[M + H]+. HRMS (ESI): calcd. for C11H9N2O2ClNa [M + Na]+
259.0245; found 259.0242.
(E)-1-Allyl-7-bromo-3-(hydroxyimino)indolin-2-one (1i): A yellow
solid (1.16 g, 83% yield); m.p. 219–221 °C. 1H NMR (400 MHz,
[D6]DMSO, TMS): δ = 4.68 (d, J = 4.0 Hz, 2 H), 4.97 (d, J =
17.2 Hz, 1 H), 5.12 (d, J = 10.4 Hz, 1 H), 5.92–6.01 (m, 1 H), 7.00–
7.04 (m, 1 H), 7.55 (d, J = 8.4 Hz, 1 H), 8.10 (dd, J = 8.4, 1.2 Hz,
1 H), 13.83 (s, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO, TMS):
δ = 42.5, 102.1, 115.5, 118.4, 124.5, 126.4, 133.6, 137.2, 140.0,
164.0 ppm. IR (CH Cl ): ν = 3282, 2904, 1716, 1616, 1456, 1328,
˜
2
2
1195, 1076, 1041, 802, 729 cm–1. MS (ESI): m/z
= 217.1
[M + H]+. HRMS (ESI): calcd. for C12H12N2O2Na [M + Na]+
239.0791; found 239.0794.
142.1, 163.6 ppm. IR (CH Cl ): ν = 2920, 2856, 1723, 1595, 1558,
˜
2
2
(E)-1-Allyl-5-bromo-3-(hydroxyimino)indolin-2-one (1f): A yellow
solid (1.18 g, 85% yield); m.p. 237–238 °C. 1H NMR (400 MHz,
[D6]DMSO, TMS): δ = 4.31 (s, 2 H), 5.14 (d, J = 15.6 Hz, 1 H),
5.15 (d, J = 11.2 Hz, 1 H), 5.78–5.87 (m, 1 H), 6.94 (d, J = 8.4 Hz,
1 H), 7.55 (d, J = 8.4 Hz, 1 H), 8.05 (s, 1 H), 13.78 (s, 1 H) ppm.
13C NMR (100 MHz, [D6]DMSO, TMS): δ = 41.5, 111.6, 114.2,
116.9, 117.1, 129.0, 131.7, 134.3, 142.0, 142.6, 162.4 ppm. IR
1440, 1365, 1338, 1261, 1178, 1041, 931, 729, 507 cm–1. MS (ESI):
m/z = 281.0 [M + H]+. HRMS (ESI): calcd. for C11H10N2O2Br [M
+ H]+ 280.9920; found 280.9926.
(E)-1-Allyl-7-fluoro-3-(hydroxyimino)indolin-2-one (1l): A yellow
solid (0.88 g, 80% yield); m.p. 220–222 °C. 1H NMR (400 MHz,
[D6]DMSO, TMS): δ = 4.39 (d, J = 3.6 Hz, 2 H), 5.06 (d, J =
17.6 Hz, 1 H), 5.12 (d, J = 11.6 Hz, 1 H), 5.87–6.95 (m, 1 H), 7.06–
7.11 (m, 1 H), 7.29–7.32 (m, 1 H), 7.86 (d, J = 7.6 Hz, 1 H), 13.77
(s, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO, TMS): δ = 43.3
(CH Cl ): ν = 3143, 2857, 1725, 1603, 1559, 1430, 1369, 1329, 1263,
˜
2
2
1039, 1011, 816, 712, 689 cm–1. MS (ESI): m/z = 280.9 [M + H]+.
HRMS (ESI): calcd. for C11H10O2N2Br [M + H]+ 280.9920; found
280.9921.
(d, JC-F = 4.8 Hz), 116.1, 118.0 (d, JC-F = 3.0 Hz), 120.0 (d, JC-F
=
19.8 Hz), 123.3, 123.9 (d, JC-F = 6.0 Hz), 129.2 (d, JC-F = 8.4 Hz),
132.9, 142.8, 146.6 (d, JC-F = 242.0 Hz), 162.7 ppm. 19F NMR
(376 MHz, [D6]DMSO, CFCl3): δ = –130.065 to –130.027 (m,
(E)-1-Allyl-5-chloro-3-(hydroxyimino)indolin-2-one (1g): A yellow
solid (1.03 g, 87% yield); m.p. 188–190 °C. 1H NMR (400 MHz,
[D6]DMSO, TMS): δ = 4.33 (d, J = 4.4 Hz, 2 H), 5.15 (d, J =
16.8 Hz, 1 H), 5.16 (d, J = 10.4 Hz, 1 H), 5.78–5.88 (m, 1 H), 7.01
(d, J = 8.4 Hz, 1 H), 7.46 (dd, J = 8.4, 2.4 Hz, 1 H), 7.94 (d, J =
2.4 Hz, 1 H), 13.80 (s, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO,
TMS): δ = 41.6, 111.2, 116.5, 117.2, 126.3, 126.6, 131.5, 131.7,
1 F) ppm. IR (CH Cl ): ν = 3207, 2936, 2851, 1724, 1622, 1447,
˜
2
2
1340, 1197, 952, 937, 797, 726 cm–1. MS (ESI): m/z = 221.1 [M +
H]+. HRMS (ESI): calcd. for C11H9N2O2FNa [M + Na]+ 243.0540;
found 243.0540.
(E)-1-Allyl-3-(hydroxyimino)-7-(trifluoromethyl)indolin-2-one (1m):
A yellow solid (1.08 g, 80% yield); m.p. 245–247 °C. 1H NMR
(400 MHz, [D6]DMSO, TMS): δ = 4.43 (d, J = 4.0 Hz, 2 H), 4.90
(d, J = 17.2 Hz, 1 H), 5.04 (d, J = 10.4 Hz, 1 H), 5.78–5.87 (m, 1
H), 7.21 (t, J = 8.0 Hz, 1 H), 7.66 (d, J = 8.0 Hz, 1 H), 8.35 (d, J
= 8.0 Hz, 1 H), 14.02 (s, 1 H) ppm. 13C NMR (100 MHz,
141.7, 142.8, 162.5 ppm. IR (CH Cl ): ν = 3298, 2982, 2926, 1723,
˜
2
2
1606, 1467, 1436, 1324, 1191, 1069, 1042, 999, 924, 813 cm–1. MS
(ESI): m/z
= 237.0 [M +
H]+. HRMS (ESI): calcd. for
C11H9N2O2ClNa [M + Na]+ 259.0245; found 259.0240.
(E)-1-Allyl-3-(hydroxyimino)-6-methylindolin-2-one (1h): A yellow
solid (0.96 g, 89% yield); m.p. 227–229 °C. 1H NMR (400 MHz,
[D6]DMSO, TMS): δ = 2.33 (s, 3 H), 4.32 (d, J = 5.2 Hz, 2 H),
5.13 (d, J = 17.2 Hz, 1 H), 5.15 (d, J = 10.4 Hz, 1 H), 5.80–5.90
(m, 1 H), 6.84 (s, 1 H), 6.89 (d, J = 8.0 Hz, 1 H), 7.86 (d, J =
8.0 Hz, 1 H), 13.38 (s, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO,
TMS): δ = 22.0, 41.4, 110.2, 113.0, 116.9, 123.3, 126.8, 132.0, 142.6,
[D6]DMSO, TMS): δ = 43.7 (q, JC-F = 3.4 Hz), 111.3 (q, JC-F
=
31.9 Hz), 115.2, 118.0, 122.8, 123.3 (q, JC-F = 270.1 Hz), 129.0 (q,
JC-F = 5.9 Hz), 130.9, 132.3, 140.6, 141.1, 164.1 ppm. 19F NMR
(376 MHz[D ]DMSO, CFCl ): δ = –49.83 ppm. IR (CH Cl ): ν =
˜
6
3
2
2
3227, 3069, 2872, 1731, 1636, 1592, 1447, 1420, 1330, 1177, 1079,
811, 744, 701, 506 cm–1. MS (ESI): m/z = 271.0 [M + H]+. HRMS
(ESI): calcd. for C12H10N2O2F3 [M + H]+ 271.0689; found
271.0696.
143.2, 143.5, 163.3 ppm. IR (CH Cl ): ν = 2981, 2928, 1717, 1658,
˜
2
2
1614, 1558, 1485, 1455, 1368, 1335, 1262, 1182, 1040, 978, 810,
730, 699 cm–1. MS (ESI): m/z = 239.0 [M + Na]+. HRMS (ESI):
calcd. for C12H12N2O2Na [M + Na]+ 239.0791; found 239.0789.
(E)-1-Benzyl-3-(hydroxyimino)-5-methylindolin-2-one (1n): A yellow
solid (1.14 g, 86% yield); m.p. 209–211 °C. 1H NMR (400 MHz,
CDCl3, TMS): δ = 2.22 (s, 3 H), 4.94 (s, 2 H), 6.58 (d, J = 8.4 Hz,
1 H), 7.03 (d, J = 8.4 Hz, 1 H), 7.25–7.28 (m, 1 H), 7.30–7.31 (m,
4 H), 7.88 (s, 1 H), 11.06 (s, 1 H) ppm. 13C NMR (100 MHz,
CDCl3, TMS): δ = 20.8, 43.7, 109.1, 115.7, 127.3, 127.7, 128.8,
(E)-1-Allyl-5-bromo-3-(hydroxyimino)indolin-2-one (1i): A yellow
solid (1.19 g, 85% yield); m.p. 190–191 °C. 1H NMR (400 MHz,
[D6]DMSO, TMS): δ = 4.34 (d, J = 4.8 Hz, 2 H), 5.15 (d, J =
16.4 Hz, 1 H), 5.16 (d, J = 11.2 Hz, 1 H), 5.79–5.88 (m, 1 H), 7.22–
7.24 (m, 2 H), 7.88 (d, J = 7.6 Hz, 1 H), 13.65 (s, 1 H) ppm. 13C
NMR (100 MHz, [D6]DMSO, TMS): δ = 41.5, 112.7, 114.4, 117.1,
132.4, 132.8, 135.4, 141.0, 144.4, 164.4 ppm. IR (CH Cl ): ν =
˜
2
2
3223, 2884, 1716, 1616, 1594, 1481, 1455, 1339, 1275, 1260, 1190,
949, 809, 749, 699 cm–1. MS (ESI): m/z = 267 [M + H]+. HRMS
(ESI): calcd. for C16H14O2N2Na [M + Na]+ 289.0946; found
289.0952.
125.1, 125.4, 128.2, 131.7, 142.8, 144.2, 162.8 ppm. IR (CH Cl ): ν
˜
2
2
= 3144, 2856, 1725, 1603, 1558, 1430, 1369, 1328, 1263, 1040, 1011,
817, 712, 689 cm–1. MS (ESI): m/z = 281.0 [M + H]+. HRMS (ESI):
calcd. for C11H10N2O2Br [M + H]+ 280.9920; found 280.9928.
(E)-1-Allyl-4-bromo-3-(hydroxyimino)indolin-2-one (1o): A yellow
(E)-1-Allyl-7-chloro-3-(hydroxyimino)indolin-2-one (1j): (1.04 g,
solid (1.16 g, 83% yield); m.p. 211–213 °C. 1H NMR (400 MHz,
1
88% yield): a yellow solid; m.p. 226–228 °C. H NMR (400 MHz, [D6]DMSO, TMS): δ = 4.32 (s, 2 H), 5.13 (d, J = 10.4 Hz, 1 H),
[D6]DMSO, TMS): δ = 4.63 (d, J = 1.6 Hz, 2 H), 4.99 (d, J =
17.6 Hz, 1 H), 5.12 (d, J = 10.4 Hz, 1 H), 5.92–6.01 (m, 1 H), 7.08
5.14 (d, J = 16.8 Hz, 1 H), 5.78–5.87 (m, 1 H), 6.98–7.01 (m, 1 H),
7.25–7.27 (m, 2 H), 13.68 (s, 1 H) ppm. 13C NMR (100 MHz,
(t, J = 8.0 Hz, 1 H), 7.40 (d, J = 8.0 Hz, 1 H), 8.04 (d, J = 8.0 Hz, [D6]DMSO, TMS): δ = 41.2, 108.7, 115.0, 117.1, 117.7, 126.9,
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20511
/KAP1
Date: 18-06-12 11:45:12
Pages: 12
Cascade Reactions of Isatin-Derived Oximes with Allenic Esters
131.6, 131.7, 141.7, 143.8, 155.5 ppm. IR (CH Cl ): ν = 3011, 1675,
1605, 1444, 1350, 1247, 1216, 1170, 1101, 981, 948, 930, 791,
768 cm–1. MS (ESI): m/z = 281.0 [M + H]+. HRMS (ESI): calcd.
for C11H10N2O2Br [M + H]+ 280.9920; found 280.9926.
7.20–7.30 (m, 9 H), 7.44–7.46 (m, 6 H), 8.40–8.42 (m, 1 H) ppm.
13C NMR (100 MHz, CDCl3, TMS): δ = 14.1, 34.6, 60.3, 60.7,
67.6, 74.9, 115.1, 118.7, 122.7, 124.4, 125.08, 125.13, 127.0, 127.7,
129.1, 130.7, 134.4, 140.7, 141.5, 141.7, 142.2, 161.4, 165.3,
˜
2
2
165.7 ppm. IR (CH Cl ): ν = 2980, 2902, 2884, 1714, 1659, 1626,
˜
2
2
General Procedure for 4: A solution of 1a (25.2 mg, 0.10 mmol),
ethyl 2,3-butadienoate (2a; 36 µL, 0.30 mmol), and P(4-FC6H4)3
(6.2 mg, 20 mol-%) in toluene (2.0 mL) was stirred at 50 °C for 3 h.
The reaction was monitored by TLC. When 1a disappeared, the
solvent was removed under reduced pressure, and the residue was
purified by flash chromatography on silica gel (pentane/EtOAc,
4:1) to give 4aa as a deep red oil (37.1 mg, 78% yield).
1476, 1372, 1262, 1171, 1108, 1041, 992, 804, 700 cm–1. MS (ESI):
m/z = 651.2 [M + Na]+. HRMS (ESI): calcd. for C39H36O6N2Na
[M + Na]+ 651.2466; found 651.2460.
(2E,6E,NE)-N-(1-Allyl-2-oxoindolin-3-ylidene)-1,8-diethoxy-1,8-
dioxoocta-2,6-dien-4-amine Oxide (4da): A yellow solid (38.3 mg,
1
90% yield); m.p. 108–110 °C. H NMR (400 MHz, CDCl3, TMS):
δ = 1.23 (t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.73–2.79
(m, 1 H), 3.08–3.16 (m, 1 H), 4.13 (q, J = 7.2 Hz, 2 H), 4.19 (q, J
= 7.2 Hz, 2 H), 4.39–4.41 (m, 2 H), 5.25 (d, J = 16.8 Hz, 1 H), 5.26
(d, J = 11.2 Hz, 1 H), 5.81–5.91 (m, 1 H), 5.95 (d, J = 15.6 Hz, 1
H), 6.16 (d, J = 14.8 Hz, 1 H), 6.80–6.87 (m, 2 H), 7.03–7.12 (m,
3 H), 7.37 (t, J = 7.6 Hz, 1 H), 8.35 (d, J = 7.6 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3, TMS): δ = 14.09, 14.14, 34.7, 42.4, 60.3,
60.8, 68.3, 108.8, 117.8, 118.0, 123.2, 125.1, 125.3, 125.5, 130.9,
132.0, 134.3, 140.3, 141.4, 141.7, 159.9, 165.3, 165.7 ppm. IR
(2E,6E,NE)-N-(1-Benzyl-2-oxoindolin-3-ylidene)-1,8-diethoxy-
1,8-dioxoocta-2,6-dien-4-amine Oxide (4aa): A deep red oil
(37.1 mg, 78% yield). 1H NMR (400 MHz, CDCl3, TMS): δ = 1.23
(t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.75–2.81 (m, 1 H),
3.10–3.18 (m, 1 H), 4.14 (q, J = 7.2 Hz, 2 H), 4.20 (q, J = 7.2 Hz,
2 H), 4.94 (d, J = 15.6 Hz, 1 H), 5.00 (d, J = 15.6 Hz, 1 H), 5.96
(d, J = 15.6 Hz, 1 H), 6.18 (d, J = 14.8 Hz, 1 H), 6.74 (d, J =
7.6 Hz, 1 H), 6.83–6.90 (m, 1 H), 7.06–7.14 (m, 3 H), 7.28–7.36 (m,
6 H), 8.35 (d, J = 7.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3,
TMS): δ = 14.1, 34.8, 43.8, 60.4, 60.8, 68.4, 108.9, 117.8, 123.3,
125.2, 125.3, 125.5, 127.2, 127.9, 128.9, 132.0, 134.3, 135.2, 140.3,
(CH Cl ): ν = 2980, 2902, 2884, 1714, 1659, 1626, 1476, 1372, 1262,
˜
2
2
1171, 1108, 1041, 992, 804, 700 cm–1. MS (ESI): m/z = 427.2 [M +
H]+. C23H26N2O6 (426.46): calcd. C 64.78, H 6.15, N 6.57; found
C 64.05, H 6.28, N 6.41.
141.4, 141.8, 160.4, 165.3, 165.8 ppm. IR (CH Cl ): ν = 2973, 2924,
˜
2
2
1719, 1608, 1466, 1380, 1348, 1265, 1176, 1082, 1044, 878, 748,
697 cm–1. MS (ESI): m/z = 477.1 [M + H]+. HRMS (ESI): calcd.
for C27H28O6N2Na [M + Na]+ 499.1840; found 499.1844.
(2E,6E,NE)-N-(1-Allyl-7-chloro-2-oxoindolin-3-ylidene)-1,8-
diethoxy-1,8-dioxoocta-2,6-dien-4-amine Oxide (4ja): A deep red oil
(40.1 mg, 87% yield). 1H NMR (400 MHz, CDCl3, TMS): δ = 1.24
(t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.72–2.79 (m, 1 H),
3.06–3.16 (m, 1 H), 4.14 (q, J = 7.2 Hz, 2 H), 4.20 (q, J = 7.2 Hz,
2 H), 4.80–4.81 (m, 2 H), 5.15 (d, J = 16.4 Hz, 1 H), 5.20 (d, J =
10.8 Hz, 1 H), 5.92–6.02 (m, 2 H), 6.15 (d, J = 14.8 Hz, 1 H), 6.79–
6.85 (m, 1 H), 7.01–7.11 (m, 3 H), 7.31 (d, J = 7.6 Hz, 1 H), 8.38
(d, J = 7.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ
= 14.1, 34.7, 43.6, 60.4, 60.8, 68.9, 115.2, 116.8, 120.3, 123.5, 124.1,
125.3, 125.6, 132.4, 133.4, 134.1, 135.9, 141.1, 141.4, 160.4, 165.2,
(2E,6E,NE)-N-(1-Benzyl-2-oxoindolin-3-ylidene)-1,8-bis(benzyl-
oxy)-1,8-dioxoocta-2,6-dien-4-amine Oxide (4ab): A deep red oil
(43.2 mg, 72 % yield). 1H NMR (400 MHz, CDCl3, TMS): δ =
2.73–2.80 (m, 1 H), 3.10–3.17 (m, 1 H), 4.93 (s, 2 H), 5.12 (s, 2 H),
5.17 (s, 2 H), 6.01 (d, J = 15.6 Hz, 1 H), 6.22 (d, J = 14.4 Hz, 1
H), 6.72 (d, J = 8.0 Hz, 1 H), 6.87–6.95 (m, 1 H), 7.04–7.15 (m, 3
H), 7.25–7.36 (m, 15 H), 8.33 (d, J = 8.0 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3, TMS): δ = 34.8, 43.8, 66.2, 66.7, 68.3, 108.9,
117.7, 123.3, 125.0, 125.2, 127.2, 127.8, 128.07, 128.13, 128.3,
128.4, 128.49, 128.55, 128.9, 132.0, 134.3, 135.2, 135.5, 135.8,
165.6 ppm. IR (CH Cl ): ν = 2983, 2934, 1717, 1699, 1659, 1600,
˜
2
2
1557, 1472, 1445, 1369, 1337, 1275, 1165, 1094, 1039, 983, 787,
750, 731 cm–1. MS (ESI): m/z = 483.0 [M + Na]+. HRMS (ESI):
calcd. for C23H25ClN2O6Na [M + Na]+ 483.1293; found 483.1291.
140.3, 142.1, 142.3, 160.3, 165.1, 165.5 ppm. IR (CH Cl ): ν =
˜
2
2
3063, 3032, 2929, 1718, 1693, 1657, 1607, 1556, 1496, 1465, 1379,
1347, 1263, 1173, 1077, 972, 771, 735, 697 cm–1. MS (ESI): m/z =
601.1 [M + H]+. HRMS (ESI): calcd. for C37H32O6N2Na
[M + Na]+ 623.2153; found 623.2164.
(2E,6E,NE)-N-(1-Allyl-7-bromo-2-oxoindolin-3-ylidene)-1,8-
diethoxy-1,8-dioxoocta-2,6-dien-4-amine Oxide (4ka): A deep red
1
oil (40.6 mg, 77% yield). H NMR (400 MHz, CDCl3, TMS): δ =
(2E,6E,NE)-1,8-Diethoxy-N-(1-methyl-2-oxoindolin-3-ylidene)-
1,8-dioxoocta-2,6-dien-4-amine Oxide (4ba): A deep red oil
(35.6 mg, 89% yield). 1H NMR (400 MHz, CDCl3, TMS): δ = 1.23
(t, J = 7.2 Hz, 3 H), 1.27 (t, J = 7.2 Hz, 3 H), 2.71–2.78 (m, 1 H),
3.10–3.17 (m, 1 H), 3.28 (s, 3 H), 4.13 (q, J = 7.2 Hz, 2 H), 4.18
(q, J = 7.2 Hz, 2 H), 5.95 (d, J = 15.6 Hz, 1 H), 6.15 (d, J =
14.8 Hz, 1 H), 6.80–6.87 (m, 2 H), 7.02–7.13 (m, 3 H), 7.40 (t, J =
7.6 Hz, 1 H), 8.33 (d, J = 7.6 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3, TMS): δ = 14.1, 26.2, 34.5, 60.4, 60.8, 68.3, 107.9, 117.6,
123.2, 125.1, 125.2, 125.5, 132.1, 134.4, 141.1, 141.4, 141.8, 160.2,
1.24 (t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.72–2.78 (m,
1 H), 3.06–3.13 (m, 1 H), 4.14 (q, J = 7.2 Hz, 2 H), 4.19 (q, J =
7.2 Hz, 2 H), 4.85–4.86 (m, 2 H), 5.13 (d, J = 16.8 Hz, 1 H), 5.21
(d, J = 10.4 Hz, 1 H), 5.93 (d, J = 15.6 Hz, 1 H), 5.97–6.03 (m, 1
H), 6.15 (d, J = 14.4 Hz, 1 H), 6.78–6.85 (m, 1 H), 6.97 (t, J =
8.0 Hz, 1 H), 7.01–7.10 (m, 2 H), 7.49 (d, J = 8.0 Hz, 1 H), 8.44
(d, J = 8.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ
= 14.1, 34.7, 43.1, 60.3, 60.8, 68.9, 102.1, 116.7, 120.6, 123.9, 124.4,
125.3, 125.6, 132.4, 133.2, 137.3, 137.5, 141.1, 141.4, 160.6, 165.1,
165.6 ppm. IR (CH Cl ): ν = 2982, 2933, 1717, 1655, 1595, 1558,
˜
165.3, 165.8 ppm. IR (CH Cl ): ν = 2981, 1718, 1655, 1609, 1559,
˜
2
2
2
2
1442, 1369, 1040, 964, 786, 730 cm–1. MS (ESI): m/z = 507.0 [M +
H]+. HRMS (ESI): calcd. for C23H25N2O6BrNa [M + Na]+
527.0788; found 527.0780.
1471, 1374, 1330, 1022, 979, 852, 774, 730, 699, 543 cm–1. MS
(ESI): m/z = 423.0 [M + Na]+ . HRMS (ESI): calcd. for
C21H24N2O6Na [M + Na]+ 423.1527; found 423.1523.
(2E,6E,NE)-1,8-Diethoxy-1,8-dioxo-N-(2-oxo-1-tritylindolin-3-
(2E,6E,NE)-N-(1-Benzyl-5-methyl-2-oxoindolin-3-ylidene)-1,8-
diethoxy-1,8-dioxoocta-2,6-dien-4-amine Oxide (4na): A deep red oil
ylidene)octa-2,6-dien-4-amine Oxide (4ca): A yellow solid (45.5 mg,
1
70% yield); m.p. 108–110 °C. H NMR (400 MHz, CDCl3, TMS): (43.2 mg, 88% yield). 1H NMR (400 MHz, CDCl3, TMS): δ = 1.23
δ = 1.23 (t, J = 7.2 Hz, 3 H), 1.29 (t, J = 7.2 Hz, 3 H), 2.61–2.68
(m, 1 H), 3.02–3.10 (m, 1 H), 4.15 (q, J = 7.2 Hz, 2 H), 4.19 (q, J
(t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.31 (s, 3 H), 2.74–
2.81 (m, 1 H), 3.10–3.18 (m, 1 H), 4.12 (q, J = 7.2 Hz, 2 H), 4.19
= 7.2 Hz, 2 H), 5.91 (d, J = 15.6 Hz, 1 H), 6.06 (d, J = 14.4 Hz, 1 (q, J = 7.2 Hz, 2 H), 4.90 (d, J = 15.6 Hz, 1 H), 4.98 (d, J =
H), 6.21–6.24 (m, 1 H), 6.79–6.86 (m, 1 H), 6.97–6.76 (m, 4 H), 15.6 Hz, 1 H), 5.97 (d, J = 16.0 Hz, 1 H), 6.18 (d, J = 14.4 Hz, 1
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O20511
/KAP1
Date: 18-06-12 11:45:12
Pages: 12
C.-K. Pei, Y. Jiang, M. Shi
FULL PAPER
H), 6.62 (d, J = 8.0 Hz, 1 H), 6.83–6.91 (m, 1 H), 7.06–7.16 (m, 3 = 7.2 Hz, 2 H), 4.61–4.62 (m, 2 H), 5.10 (d, J = 17.2 Hz, 1 H), 5.17
H), 7.27–7.35 (m, 5 H), 8.20 (s, 1 H) ppm. 13C NMR (100 MHz, (d, J = 10.4 Hz, 1 H), 5.82–5.90 (m, 1 H), 5.94 (d, J = 16.0 Hz, 1
CDCl3, TMS): δ = 14.1, 20.9, 34.7, 43.7, 60.3, 60.7, 68.1, 108.6,
117.6, 125.2, 125.4, 125.7, 127.1, 127.7, 128.8, 132.4, 132.9, 134.4,
H), 6.16 (d, J = 14.8 Hz, 1 H), 6.78–6.85 (m, 1 H), 7.01–7.12 (m,
2 H), 7.19 (t, J = 8.0 Hz, 1 H), 7.68 (d, J = 8.0 Hz, 1 H), 8.70 (d,
J = 8.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ =
14.1, 34.7, 44.6 (q, JC-F = 4.6 Hz), 60.4, 60.9, 69.2, 112.5 (q, JC-F
= 33.0 Hz), 116.7, 120.1, 122.7, 123.1 (q, JC-F = 270.1 Hz), 125.4,
125.8, 128.1, 129.4 (q, JC-F = 6.1 Hz), 131.3, 132.6, 141.0, 141.3,
161.0, 165.2, 165.6 ppm. 19F NMR (400 MHz, CDCl3, TMS): δ =
135.3, 138.1, 141.4, 141.8, 160.3, 165.2, 165.6 ppm. IR (CH Cl ): ν
˜
2
2
= 2929, 1697, 1615, 1558, 1486, 1338, 1183, 1041, 978, 810, 698,
557 cm–1. MS (ESI): m/z = 491.0 [M + H]+. HRMS (ESI): calcd.
for C28H31N2O6 [M + H]+ 491.2177; found 491.2175.
(2E,6E,NE)-N-(1-Allyl-6-bromo-2-oxoindolin-3-ylidene)-1,8-
diethoxy-1,8-dioxoocta-2,6-dien-4-amine Oxide (4ia): A deep red oil
(42.2 mg, 80% yield). 1H NMR (400 MHz, CDCl3, TMS): δ = 1.24
(t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.72–2.79 (m, 1 H),
3.07–3.15 (m, 1 H), 4.13 (q, J = 7.2 Hz, 2 H), 4.19 (q, J = 7.2 Hz,
2 H), 4.38–4.81 (m, 2 H), 5.25 (d, J = 17.2 Hz, 1 H), 5.29 (d, J =
10.8 Hz, 1 H), 5.80–5.89 (m, 1 H), 5.94 (d, J = 15.6 Hz, 1 H), 6.15
(d, J = 14.8 Hz, 1 H), 6.78–6.85 (m, 1 H), 6.97–7.07 (m, 3 H), 7.24
(d, J = 8.4 Hz, 1 H), 8.20 (d, J = 8.4 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3, TMS): δ = 14.1, 34.6, 42.4, 60.4, 60.8, 68.6,
112.2, 116.5, 118.3, 125.3, 125.6, 125.9, 126.1, 130.4, 133.6, 141.1,
–55.432 ppm. IR (CH Cl ): ν = 2983, 2928, 2855, 1731, 1660, 1592,
˜
2
2
1557, 1451, 1429, 1327, 1176, 1124, 1080, 977, 804, 743, 704,
508 cm–1. MS (ESI): m/z = 495.1 [M + H]+. HRMS (ESI): calcd.
for C24H26N2O6F3 [M + H]+ 495.1738; found 495.1742.
(2E,6E,NE)-N-(1-Allyl-5-chloro-2-oxoindolin-3-ylidene)-1,8-di-
ethoxy-1,8-dioxoocta-2,6-dien-4-amine oxide (4ga): A deep red oil
(41.1 mg, 85% yield). 1H NMR (400 MHz, CDCl3, TMS): δ = 1.24
(t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.72–2.79 (m, 1 H),
3.08–3.15 (m, 1 H), 4.14 (q, J = 7.2 Hz, 2 H), 4.19 (q, J = 7.2 Hz,
2 H), 4.38–4.40 (m, 2 H), 5.23 (d, J = 16.8 Hz, 1 H), 5.27 (d, J =
9.6 Hz, 1 H), 5.80–5.87 (m, 1 H), 5.95 (d, J = 15.6 Hz, 1 H), 6.16
(d, J = 14.8 Hz, 1 H), 6.76–6.84 (m, 2 H), 7.02–7.06 (m, 2 H), 7.33
(dd, J = 8.0, 2.0 Hz, 1 H), 8.36 (d, J = 2.0 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3, TMS): δ = 14.1, 34.6, 42.5, 60.4, 60.8, 68.7,
109.7, 118.2, 118.7, 124.8, 125.4, 125.7, 128.6, 130.6, 131.4, 133.6,
141.2, 141.4, 159.7, 165.2, 165.6 ppm. IR (CH Cl ): ν = 2984, 2932,
˜
2
2
1716, 1558, 1478, 1462, 1244, 1039 cm–1. MS (ESI): m/z = 507.0
[M + H]+. HRMS (ESI): calcd. for C23H25N2O6BrNa [M + Na]+
527.0788; found 527.0779.
(2E,6E,NE)-N-(1-Allyl-5-methyl-2-oxoindolin-3-ylidene)-1,8-
diethoxy-1,8-dioxoocta-2,6-dien-4-amine oxide (4ea): A deep red oil
(41.2 mg, 89% yield). 1H NMR (400 MHz, CDCl3, TMS): δ = 1.24
(t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.34 (s, 3 H), 2.72–
2.79 (m, 1 H), 3.09–3.16 (m, 1 H), 4.13 (q, J = 7.2 Hz, 2 H), 4.19
(q, J = 7.2 Hz, 2 H), 4.36–38 (m, 2 H), 5.23 (d, J = 16.8 Hz, 1 H),
5.24 (d, J = 10.8 Hz, 1 H), 5.80–5.88 (m, 1 H), 5.95 (d, J = 15.6 Hz,
1 H), 6.15 (d, J = 14.4 Hz, 1 H), 6.73 (d, J = 8.0 Hz, 1 H), 6.79–
6.87 (m, 1 H), 7.03–7.08 (m, 2 H), 7.17 (d, J = 8.0 Hz, 1 H), 8.20
(s, 1 H) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 14.1, 21.0,
34.7, 42.4, 60.3, 60.8, 68.2, 108.5, 117.6, 117.8, 125.2, 125.4, 125.7,
131.0, 132.4, 132.9, 134.5, 138.2, 141.4, 141.8, 159.9, 165.3,
138.6, 141.1, 141.3, 159.5, 165.1, 165.6 ppm. IR (CH Cl ): ν =
˜
2
2
2982, 2932, 1717, 1655, 1608, 1558, 1465, 1443, 1369, 1326, 1275,
1184, 1040, 980, 812, 749, 682 cm–1. MS (ESI): m/z = 483.0 [M +
Na]+. HRMS (ESI): calcd. for C23H25ClN2O6Na [M + Na]+
483.1293; found 483.1286.
(2E,6E,NE)-N-(1-Allyl-6-methyl-2-oxoindolin-3-ylidene)-1,8-di-
ethoxy-1,8-dioxoocta-2,6-dien-4-amine oxide (4ea): A deep red oil
(38.3 mg, 87% yield). 1H NMR (400 MHz, CDCl3, TMS): δ = 1.23
(t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.39 (s, 3 H), 2.72–
2.79 (m, 1 H), 3.08–3.15 (m, 1 H), 4.13 (q, J = 7.2 Hz, 2 H), 4.19
(q, J = 7.2 Hz, 2 H), 4.37–4.38 (m, 2 H), 5.24 (d, J = 17.6 Hz, 1
H), 5.25 (d, J = 9.6 Hz, 1 H), 5.81–5.91 (m, 1 H), 5.94 (d, J =
15.6 Hz, 1 H), 6.15 (d, J = 14.8 Hz, 1 H), 6.65 (s, 1 H), 6.80–6.87
(m, 1 H), 6.91 (d, J = 8.0 Hz, 1 H), 7.00–7.10 (m, 2 H), 8.22 (d, J
= 8.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 14.1,
22.4, 34.6, 42.2, 60.3, 60.7, 67.9, 109.6, 115.2, 117.7, 123.8, 125.0,
125.1, 125.3, 130.9, 134.2, 140.6, 141.5, 141.9, 143.2, 160.2, 165.3,
165.7 ppm. IR (CH Cl ): ν = 2981, 2927, 2386, 1719, 1655, 1614,
˜
2
2
1560, 1486, 1038, 776, 734 cm–1. MS (ESI): m/z = 441.1 [M +-
H]+. HRMS (ESI): calcd. for C24H28N2O6Na [M + Na]+ 463.1840;
found 463.1849.
(2E,6E,NE)-N-(1-Allyl-7-fluoro-2-oxoindolin-3-ylidene)-1,8-di-
ethoxy-1,8-dioxoocta-2,6-dien-4-amine oxide (4la): A deep red oil
(42.0 mg, 90% yield). 1H NMR (400 MHz, CDCl3, TMS): δ = 1.24
(t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.72–2.79 (m, 1 H),
3.07–3.12 (m, 1 H), 4.13 (q, J = 7.2 Hz, 2 H), 4.20 (q, J = 7.2 Hz,
2 H), 4.53 (d, J = 5.6 Hz, 2 H), 5.21 (d, J = 9.2 Hz, 1 H), 5.25 (d,
J = 18.8 Hz, 1 H), 5.89–5.96 (m, 2 H), 6.16 (d, J = 14.4 Hz, 1 H),
6.78–6.86 (m, 1 H), 7.02–7.15 (m, 4 H), 8.19 (d, J = 7.6 Hz, 1
H) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 14.1, 34.7, 44.1
(d, JC-F = 4.9 Hz), 60.4, 60.8, 68.6, 117.5, 119.9 (d, JC-F = 19.7 Hz),
165.7 ppm. IR (CH Cl ): ν = 2983, 2930, 1717, 1616, 1558, 1457,
˜
2
2
1376, 1276, 1040, 980, 817, 749, 707 cm–1. MS (ESI): m/z = 441.1
[M + H]+. HRMS (ESI): calcd. for C24H29N2O6 [M + H]+
441.2020; found 441.2030.
(2E,6E,NE)-N-(1-Allyl-5-bromo-2-oxoindolin-3-ylidene)-1,8-di-
ethoxy-1,8-dioxoocta-2,6-dien-4-amine oxide (4fa): A deep red oil
(41.8 mg, 83% yield). 1H NMR (400 MHz, CDCl3, TMS): δ = 1.24
(t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.73–2.78 (m, 1 H),
3.07–3.13 (m, 1 H), 4.14 (q, J = 7.2 Hz, 2 H), 4.20 (q, J = 7.2 Hz,
2 H), 4.38–4.39 (m, 2 H), 5.25–5.28 (m, 2 H), 5.81–5.88 (m, 1 H),
5.95 (d, J = 15.6 Hz, 1 H), 6.15 (d, J = 14.8 Hz, 1 H), 6.72 (d, J =
8.4 Hz, 1 H), 6.78–6.83 (m, 1 H), 7.01–7.07 (m, 2 H), 7.48 (dd, J
= 8.4, 2.0 Hz, 1 H), 8.51 (d, J = 2.0 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3, TMS): δ = 14.1, 34.7, 42.5, 60.4, 60.9, 68.8,
110.2, 115.9, 118.2, 119.2, 125.4, 125.7, 127.6, 130.6, 131.4, 134.4,
120.3 (d, JC-F = 4.1 Hz), 121.0 (d, JC-F = 3.0 Hz), 123.9 (d, JC-F
=
6.0 Hz), 125.3, 125.6, 126.5 (d, J = 9.8 Hz), 131.6, 133.9, 141.1,
141.4, 146.7 (d, JC-F = 243.1 Hz), 159.6, 165.2, 165.6 ppm. 19F
NMR (CDCl3, 400 MHz, CFCl3): δ = –134.980 to –134.985 (m, 1
F) ppm. IR (CH Cl ): ν = 2982, 2934, 1719, 1655, 1628, 1560, 1491,
˜
2
2
1458, 1155, 1037, 981, 788, 727, 595 cm–1. MS (ESI): m/z = 467.0
[M + Na]+. HRMS (ESI): calcd. for C23H25FN2O6Na [M + Na]+
467.1589; found 467.1583.
139.1, 141.1, 141.4, 159.5, 165.2, 165.7 ppm. IR (CH Cl ): ν =
˜
2
2
2984, 2931, 1716, 1655, 1608, 1558, 1462, 1443, 1369, 1326, 1244,
1184, 1040, 980, 812, 749 cm–1. MS (ESI): m/z = 507.0 [M + H]+.
HRMS (ESI): calcd. for C23H25N2O6BrNa [M + Na]+ 527.0788;
found 527.0789.
(2E,6E,NE)-N-[1-allyl-2-oxo-7-(trifluoromethyl)indolin-3-ylidene]-
1,8-diethoxy-1,8-dioxoocta-2,6-dien-4-amine Oxide (4ma): A deep
1
red oil (39.6 mg, 80% yield). H NMR (400 MHz, CDCl3, TMS):
δ = 1.24 (t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.73–2.79
(m, 1 H), 3.07–3.14 (m, 1 H), 4.13 (q, J = 7.2 Hz, 2 H), 4.20 (q, J
(E)-Ethyl 3-{[(E)-(1-Benzyl-2-oxoindolin-3-ylidene)amino]oxy}but-2-
enoate [(3aa), the E-configuration was determined by its analogue
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20511
/KAP1
Date: 18-06-12 11:45:12
Pages: 12
Cascade Reactions of Isatin-Derived Oximes with Allenic Esters
3ca]: A yellow oil (30.9 mg, 85 % yield). 1H NMR (300 MHz,
CDCl3, TMS): δ = 1.29 (t, J = 7.5 Hz, 3 H), 2.57 (s, 3 H), 4.18 (q,
12.0, 8.0 Hz, 1 H), 3.32 (s, 1 H), 3.60 (q, J = 7.2 Hz, 2 H), 4.15 (q,
J = 7.2 Hz, 2 H), 4.66 (d, J = 16.0 Hz, 1 H), 5.16 (dd, J = 12.0,
J = 7.2 Hz, 2 H), 4.95 (s, 2 H), 6.19 (s, 1 H), 6.75 (d, J = 7.8 Hz, 7.2 Hz, 1 H), 5.27 (d, J = 16.0 Hz, 1 H), 5.58 (d, J = 4.8 Hz, 1 H),
1 H), 7.07 (t, J = 7.8 Hz, 1 H), 7.27–7.37 (m, 6 H), 8.00 (d, J =
7.8 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3, TMS): δ = 14.3,
16.1, 43.8, 59.8, 96.9, 109.9, 115.1, 123.4, 127.3, 127.9, 128.9, 129.0,
5.87 (d, J = 16.0 Hz, 1 H), 6.67 (d, J = 8.0 Hz, 1 H), 6.87 (dd, J =
16.0, 6.8 Hz, 1 H), 7.00 (t, J = 7.6 Hz, 1 H), 7.16 (d, J = 7.6 Hz, 1
H), 7.27–7.34 (m, 5 H), 7.47 (d, J = 7.6 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3, TMS): δ = 13.1, 14.2, 39.7, 44.2, 59.4, 60.3,
60.6, 60.7, 75.3, 82.4, 109.1, 121.4, 123.6, 125.8, 127.0, 127.8, 128.7,
129.2, 129.4, 134.9, 141.6, 147.6, 166.2, 168.6, 172.1 ppm. IR
134.0, 134.9, 144.7, 146.6, 162.9, 167.4, 169.2 ppm. IR (CH Cl ): ν
˜
2
2
= 2981, 2902, 2884, 1713, 1625, 1511, 1451, 1378, 1258, 1104, 990,
821, 769 cm–1. MS (ESI): m/z = 365.1 [M + H]+. HRMS (ESI):
calcd. for C21H20N2O4Na [M + Na]+ 387.1315; found 387.1327.
(CH Cl ): ν = 2980, 2902, 1707, 1653, 1612, 1493, 1471, 1374, 1351,
˜
2
2
1260, 1185, 1094, 1040, 973, 868, 795, 690 cm–1. MS (ESI): m/z =
477.2 [M + H]+. HRMS (ESI): calcd. for C27H29O6N2 [M + H]+
477.2026; found 477.2024.
(E)-Ethyl 3-{[(E)-(1-Allyl-4-bromo-2-oxoindolin-3-ylidene)amino]-
oxy}but-2-enoate [(3oa), the E-configuration was determined by its
analogue 3ca]: A yellow oil (33.1 mg, 80 % yield). 1H NMR
(300 MHz, CDCl3, TMS): δ = 1.31 (t, J = 7.2 Hz, 3 H), 2.54 (s, 3
H), 4.20 (q, J = 7.2 Hz, 2 H), 4.36 (d, J = 5.2 Hz, 2 H), 5.257 (d,
J = 16.4 Hz, 1 H), 5.264 (d, J = 11.2 Hz, 1 H), 5.77–5.86 (m, 1 H),
6.14 (s, 1 H), 6.80 (d, J = 7.6 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H),
7.29 (t, J = 7.6 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3, TMS):
δ = 14.4, 16.1, 42.2, 59.7, 96.1, 108.3, 117.1, 118.4, 128.0, 130.3,
(1R,2R,3R,4S,6S)-Ethyl 6-[(E)-3-Ethoxy-3-oxoprop-1-en-1-yl]-2Ј-
oxo-1Ј-trityl-7-oxa-1-azaspiro[bicyclo[2.2.1]heptane-2,3Ј-indoline]-
3-carboxylate (5ca): A white solid (37.7 mg, 65% yield); m.p. 160–
162 °C. 1H NMR (400 MHz, CDCl3, TMS): δ = 0.28 (t, J = 7.2 Hz,
3 H), 1.27 (t, J = 7.2 Hz, 3 H), 1.90–1.95 (m, 1 H), 2.18–2.23 (m,
1 H), 3.21 (s, 1 H), 3.46–3.59 (m, 2 H), 4.15–4.26 (m, 2 H), 4.77–
4.82 (m, 1 H), 5.51 (d, J = 5.2 Hz, 1 H), 5.93 (dd, J = 15.6, 1.2 Hz,
1 H), 6.25–6.27 (m, 1 H), 6.85–6.91 (m, 3 H), 7.20–7.28 (m, 10 H),
7.37–7.40 (m, 1 H), 7.45–7.47 (m, 6 H) ppm. 13C NMR (100 MHz,
CDCl3, TMS): δ = 13.0, 14.2, 39.7, 59.8, 59.9, 60.4, 60.5, 74.8, 76.2,
82.5, 115.5, 121.5, 123.0, 125.0, 127.0, 127.7, 127.9, 129.2, 129.4,
133.0, 144.7, 145.3, 155.7, 167.6, 170.0 ppm. IR (CH Cl ): ν =
˜
2
2
2928, 2902, 1718, 1643, 1595, 1449, 1332, 1270, 1248, 1170, 1126,
967, 697 cm–1. MS (ESI): m/z = 393.0 [M + H]+. HRMS (ESI):
calcd. for C17H17O4N2BrNa [M + Na]+ 415.0264; found 415.0254.
(E)-Ethyl 3-[(E)-2-Oxo-1-tritylindolin-3-ylideneaminooxy]but-2-eno-
ate (3ca): A yellow solid; m.p. 180–182 °C. 1H NMR (300 MHz,
CDCl3, TMS): δ = 1.25 (t, J = 7.2 Hz, 3 H), 2.53 (s, 3 H), 4.14 (q,
J = 7.2 Hz, 2 H), 6.13 (s, 1 H), 6.33 (d, J = 8.0 Hz, 1 H), 6.98 (t,
J = 8.0 Hz, 1 H), 7.06 (t, J = 8.0 Hz, 1 H), 7.20–7.29 (m, 9 H),
7.44–7.46 (m, 6 H), 8.01 (d, J = 8.0 Hz, 1 H) ppm. 13C NMR
(75 MHz, CDCl3, TMS): δ = 14.3, 16.0, 59.7, 75.1, 96.7, 116.0,
116.5, 122.8, 127.1, 127.8, 128.3, 129.3, 132.4, 141.4, 145.7, 146.3,
141.6, 142.2, 147.8, 166.2, 168.8, 172.5 ppm. IR (CH Cl ): ν =
˜
2
2
2980, 2902, 2884, 1714, 1659, 1626, 1476, 1372, 1262, 1171, 1108,
1041, 992, 804, 700 cm–1. MS (ESI): m/z = 629.2 [M + H]+. HRMS
(ESI): calcd. for C39H36O6N2Na [M + Na]+ 651.2466; found
651.2475.
(1R,2R,3R,4S,6S)-Ethyl 1Ј-Allyl-6-[(E)-3-ethoxy-3-oxoprop-1-en-1-
yl]-2Ј-oxo-7-oxa-1-azaspiro[bicyclo[2.2.1]heptane-2,3Ј-indoline]-3-
163.6, 167.5, 169.3 ppm. IR (EtOH): ν = 2919, 2850, 2362, 1734,
˜
1
carboxylate (5da): A yellow liquid (30.7 mg, 72% yield). H NMR
1702, 1645, 1597, 1449, 1241, 1130, 1051, 958, 843, 784, 745 cm–1.
MS (ESI): m/z = 539.2 [M + Na]+. HRMS (ESI): calcd. for
C33H28O4N2Na [M + Na]+ 539.1947; found 539.1944.
(400 MHz, CDCl3, TMS): δ = 0.62 (t, J = 7.2 Hz, 3 H), 1.23 (t, J
= 7.2 Hz, 3 H), 1.96–2.02 (m, 1 H), 2.31 (dd, J = 12.0, 8.4 Hz, 1
H), 3.25 (s, 1 H), 3.59–3.68 (m, 2 H), 4.14 (q, J = 7.2 Hz, 2 H),
4.19–4.25 (m, 1 H), 4.51–4.57 (m, 1 H), 5.10 (dd, J = 12.0, 7.6 Hz,
1 H), 5.23 (d, J = 9.6 Hz, 1 H), 5.26 (d, J = 16.4 Hz, 1 H), 5.56 (d,
J = 5.2 Hz, 1 H), 5.81–5.88 (m, 1 H), 5.94 (d, J = 15.6 Hz, 1 H),
6.79 (d, J = 7.6 Hz, 1 H), 6.85 (dd, J = 15.6, 6.8 Hz, 1 H), 7.03 (t,
J = 7.6 Hz, 1 H), 7.24–7.28 (m, 1 H), 7.47 (d, J = 7.6 Hz, 1 H) ppm.
13C NMR (100 MHz, CDCl3, TMS): δ = 13.3, 14.2, 39.6, 42.7,
59.3, 60.3, 60.6, 60.7, 75.3, 82.4, 108.8, 117.5, 121.4, 123.5, 125.8,
129.2, 129.4, 130.4, 141.8, 147.7, 166.2, 168.6, 171.7 ppm. IR
General Procedure for 3ac: Following the general procedure, the
E/Z ratio (10:1) was determined by 1H NMR spectroscopic analysis
of the mixed product purified by column chromatography; a yellow
oil (26.4 mg, 60% yield). 1H NMR (400 MHz, CDCl3, TMS, for
E-3ac): δ = 2.05 (d, J = 7.2 Hz, 3 H), 4.93 (s, 2 H), 5.23 (s, 2 H),
5.33 (s, 2 H), 6.69 (d, J = 7.2 Hz, 1 H), 6.94 (t, J = 7.2 Hz, 1 H),
7.18–7.42 (m, 12 H), 7.84 (d, J = 7.2 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3, TMS, for E-3ac): δ = 15.0, 43.6, 66.5, 70.2,
109.3, 115.8, 123.0, 127.3, 127.9, 128.0, 128.4, 128.8, 132.3, 135.3,
(CH Cl ): ν = 2981, 2958, 1739, 1708, 1657, 1612, 1488, 1468, 1370,
˜
2
2
1303, 1264, 1182, 1096, 926, 867, 754, 698 cm–1. MS (ESI): m/z =
449.2 [M + Na]+. HRMS (ESI): calcd. for C23H26O6N2Na [M +
Na]+ 449.1689; found 449.1681.
135.9, 143.5, 146.2, 163.5, 166.2 ppm. IR (CH Cl , for E-3ac): ν =
˜
2
2
2955, 1713, 1651, 1604, 1464, 1454, 1346, 1242, 1138, 1092, 1028,
967, 843, 728, 694 cm–1. MS (ESI, for E-3ac): m/z = 463.0 [M +
Na]+. HRMS (ESI): calcd. for C27H24O4N2Na [M + Na]+
463.1628; found 463.1618.
(1R,2R,3R,4S,6S)-Ethyl 1Ј-Allyl-5Ј-chloro-6-[(E)-3-ethoxy-3-oxo-
prop-1-en-1-yl]-2Ј-oxo-7-oxa-1-azaspiro[bicyclo[2.2.1]heptane-2,3Ј-
indoline]-3-carboxylate (5ga): A yellow solid (31.3 mg, 68% yield);
General Procedure for 5: Under an argon atmosphere, a solution of
4aa (47.6 mg, 0.10 mol), Yb(OTf)3 (20 mol-%), and 4 Å molecular
sieves (100 mg) were added into a Schlenk tube, and then toluene
(2.0 mL) was added. The mixture was stirred at 100 °C for 36 h,
and the reaction was monitored by TLC. When 4aa disappeared,
the solvent was removed under reduced pressure, and the residue
was purified by flash chromatography on silica gel (pentane/EtOAc,
5:1) to give 4aa as yellow solid (30.9 mg, 65% yield).
1
m.p. 127–129 °C. H NMR (400 MHz, CDCl3, TMS): δ = 0.72 (t,
J = 7.2 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.98–2.03 (m, 1 H),
2.31 (dd, J = 11.6, 8.4 Hz, 1 H), 3.25 (s, 1 H), 3.70–3.77 (m, 2 H),
4.14 (q, J = 7.2 Hz, 2 H), 4.18–4.23 (m, 1 H), 4.51–4.56 (m, 1 H),
5.06 (dd, J = 11.6, 7.6 Hz, 1 H), 5.24 (d, J = 16.8 Hz, 1 H), 5.25
(d, J = 10.8 Hz, 1 H), 5.57 (d, J = 5.2 Hz, 1 H), 5.79–5.86 (m, 1
H), 5.95 (d, J = 15.6 Hz, 1 H), 6.73 (d, J = 8.4 Hz, 1 H), 6.84 (dd,
J = 15.6, 6.8 Hz, 1 H), 7.24–7.26 (m, 1 H), 7.48 (d, J = 1.2 Hz, 1
H) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 13.4, 14.2, 39.6,
42.8, 59.3, 60.3, 60.6, 61.0, 75.2, 82.5, 109.8, 117.7, 121.5, 126.2,
129.0, 129.3, 130.0, 130.7, 140.3, 147.2, 166.1, 168.2, 171.2 ppm.
(1R,2R,3R,4S,6S)-Ethyl 1Ј-Benzyl-6-[(E)-3-ethoxy-3-oxoprop-1-en-
1-yl]-2Ј-oxo-7-oxa-1-azaspiro[bicyclo[2.2.1]heptane-2,3Ј-indoline]-
3-carboxylate (5aa): A yellow solid (30.9 mg, 65% yield); m.p. 160–
161 °C. 1H NMR (400 MHz, CDCl3, TMS): δ = 0.45 (t, J = 7.2 Hz,
3 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.99–2.04 (m, 1 H), 2.34 (dd, J =
IR (CH Cl ): ν = 2981, 2902, 1710, 1658, 1611, 1484, 1433, 1368,
˜
2
2
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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Job/Unit: O20511
/KAP1
Date: 18-06-12 11:45:12
Pages: 12
C.-K. Pei, Y. Jiang, M. Shi
1471, 1374, 1351, 1260, 1185, 1094, 1038, 981, 868, 795, 694 cm–1.
FULL PAPER
1351, 1261, 1180, 1096, 1037, 983, 852, 812, 720 cm–1. MS (ESI):
m/z = 483.1 [M + Na]+. HRMS (ESI): calcd. for C23H25O6ClN2Na MS (ESI): m/z = 423.2 [M + Na]+. HRMS (ESI): calcd. for
[M + Na]+ 483.1299; found 483.1286.
C21H24O6N2Na [M + Na]+ 423.1532; found 423.1556.
(1R,2R,3R,4S,6S)-Ethyl 1Ј-Allyl-6-[(E)-3-ethoxy-3-oxoprop-1-en-1-
yl]-6Ј-methyl-2Ј-oxo-7-oxa-1-azaspiro[bicyclo[2.2.1]heptane-2,3Ј-
indoline]-3-carboxylate (5ha): A white solid (28.6 mg, 65% yield);
Supporting Information (see footnote on the first page of this arti-
cle): Spectroscopic data and NMR spectra; X-ray crystal data of
1a, 3ca, 4da, and 5ca; detailed experimental procedures.
1
m.p. 132–134 °C. H NMR (400 MHz, CDCl3, TMS): δ = 0.65 (t,
J = 7.2 Hz, 3 H), 1.23 (t, J = 7.2 Hz, 3 H), 1.95–2.00 (m, 1 H),
2.29 (dd, J = 11.6, 8.4 Hz, 1 H), 2.32 (s, 3 H), 3.22 (s, 1 H), 3.63–
3.70 (m, 2 H), 4.14 (q, J = 7.2 Hz, 2 H), 4.18–4.23 (m, 1 H), 4.49–
4.54 (m, 1 H), 5.09 (dd, J = 11.6, 6.8 Hz, 1 H), 5.23 (d, J = 10.4 Hz,
1 H), 5.24 (d, J = 17.6 Hz, 1 H), 5.54 (d, J = 5.2 Hz, 1 H), 5.80–
5.89 (m, 1 H), 5.94 (d, J = 15.6 Hz, 1 H), 6.61 (s, 1 H), 6.83–6.88
(m, 2 H), 7.33 (d, J = 7.6 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3, TMS): δ = 13.3, 14.1, 21.6, 39.6, 42.6, 59.3, 60.2, 60.4, 60.7,
75.2, 82.4, 109.6, 117.2, 121.2, 124.0, 125.5, 126.2, 130.4, 139.7,
Acknowledgments
We thank the Shanghai Municipal Committee of Science and Tech-
nology (11JC1402600), National Basic Research Program of China
(973)-2010CB833302, the Fundamental Research Funds for the
Central Universities, and the National Natural Science Foundation
of China (21072206, 20872162, 20672127, 20732008, 21121062 and
20702013) for financial support.
141.8, 147.8, 166.3, 168.7, 171.9 ppm. IR (CH Cl ): ν = 2981, 2902,
˜
2
2
1708, 1657, 1620, 1503, 1449, 1378, 1345, 1266, 1183, 1117, 1038,
982, 867, 811, 701 cm–1. MS (ESI): m/z = 463.2 [M + Na]+. HRMS
(ESI): calcd. for C24H28O6N2Na [M + Na]+ 463.1645; found
463.1641.
[1] a) A. Y. Sukhorukov, S. L. Ioffe, Chem. Rev. 2011, 111, 5004–
5041; b) D. A. Alonso, C. Nájera, Chem. Soc. Rev. 2010, 39,
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Chem. Soc. 1960, 82, 4671–4675.
[3] Selected papers on the Beckmann rearrangement of oximes to
prepare amides: a) R. S. Ramón, J. Bosson, S. Díez-González,
N. Marion, S. P. Nolan, J. Org. Chem. 2010, 75, 1197–1202; b)
N. C. Ganguly, P. Mondal, Synthesis 2010, 3705–3709; c) C.
Ramalingan, Y.-T. Park, J. Org. Chem. 2007, 72, 4536–4538; d)
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Chem. Soc. 1951, 73, 2369–2370; f) R. L. Augustine, J. Am.
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Owston, A. J. Parker, J. M. J. Williams, Org. Lett. 2007, 9,
3599–3601.
[4] Selected papers on oximes as precursors of 1,3-dipolar: a) K.
Gutsmiedl, D. Fazio, T. Carell, Chem. Eur. J. 2010, 16, 6877–
6883; b) D. R. Kelly, S. C. Baker, D. S. King, D. S. Silva, G.
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B. C. Sanders, F. Friscourt, P. A. Ledin, N. E. Mbua, S. Aru-
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Chem. Soc. 2011, 133, 949–957; d) M. P. Bourbeau, J. T. Rider,
Org. Lett. 2006, 8, 3679–3680; e) S. Yamago, M. Nakamura,
X. Q. Wang, M. Yanagawa, S. Tokumitsu, E. Nakamura, J.
Org. Chem. 1998, 63, 1694–1703; f) É. Frank, G. Schneider, Z.
Kádár, J. Wölfling, Eur. J. Org. Chem. 2009, 3544–3553; g) S.
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h) S. Liu, Y. Yu, L. S. Liebeskind, Org. Lett. 2007, 9, 1947–
1950; i) Z. Zhang, Y. Yu, L. S. Liebeskind, Org. Lett. 2008, 10,
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2009, 121, 580–585; Angew. Chem. Int. Ed. 2009, 48, 572–577;
k) P. C. Too, Y.-F. Wang, S. Chiba, Org. Lett. 2010, 12, 5688–
5691; l) Y. Tan, J. F. Hartwig, J. Am. Chem. Soc. 2010, 132,
3676–3677.
(1R,2R,3R,4S,6S)-Ethyl 1Ј-Benzyl-6-[(E)-3-ethoxy-3-oxoprop-1-en-
1-yl]-5Ј-methyl-2Ј-oxo-7-oxa-1-azaspiro[bicyclo[2.2.1]heptane-2,3Ј-
indoline]-3-carboxylate (5na): A yellow solid (34.3 mg, 70% yield);
1
m.p. 150–151 °C. H NMR (400 MHz, CDCl3, TMS): δ = 0.47 (t,
J = 7.2 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.20–2.04 (m, 1 H),
2.45 (s, 3 H), 2.33 (dd, J = 12.0, 8.4 Hz, 1 H), 3.31 (s, 1 H), 3.58–
3.66 (m, 2 H), 4.15 (q, J = 7.2 Hz, 2 H), 4.65 (d, J = 16.0 Hz, 1
H), 5.16 (dd, J = 12.0, 7.6 Hz, 1 H), 5.58 (d, J = 5.2 Hz, 1 H), 5.96
(d, J = 16.0 Hz, 1 H), 6.55 (d, J = 7.6 Hz, 1 H), 6.88 (dd, J = 16.0,
7.2 Hz, 1 H), 6.95 (d, J = 7.6 Hz, 1 H), 7.26–7.33 (m, 6 H) ppm.
13C NMR (100 MHz, CDCl3, TMS): δ = 13.1, 14.2, 21.0, 39.6,
44.2, 59.4, 60.3, 60.6, 60.7, 75.4, 82.4, 108.8, 121.4, 126.4, 127.0,
127.7, 128.7, 129.1, 129.6, 133.2, 135.0, 139.2, 147.7, 166.2, 168.6,
172.0 ppm. IR (CH Cl ): ν = 2980, 2955, 1739, 1708, 1657, 1619,
˜
2
2
1496, 1454, 1370, 1350, 1302, 1269, 1190, 809, 698 cm–1. MS (ESI):
m/z = 513.2 [M + Na]+. HRMS (ESI): calcd. for C28H30O6N2Na
[M + Na]+ 513.2002; found 513.2000.
One-Pot Procedure for 5ba: A solution of 1b (88.0 mg, 0.50 mmol),
ethyl 2,3-butadienoate (2a; 0.18 mL, 1.50 mmol), and P(4-FC6H4)3
(30.1 mg, 20 mol-%) in toluene (10.0 mL) was stirred at 50 °C for
3 h. Without purification, Yb(OTf)3 (20 mol-%) and 4 Å molecular
sieves (300 mg) were added to the reaction mixture, and after heat-
ing the reaction temperate to 100 °C, the reaction mixture was
stirred for another 36 h. Then the reaction mixture was cooled to
room temperature and the solvent was quickly removed under re-
duced pressure. The residue was purified by flash chromatography
on silica gel (pentane/EtOAc, 4:1) to give 5ba as a yellow oil
(114.0 mg, 57% yield).
(1R,2R,3R,4S,6S)-Ethyl 6-[(E)-3-Ethoxy-3-oxoprop-1-en-1-yl]-1Ј-
methyl-2Ј-oxo-7-oxa-1-azaspiro[bicyclo[2.2.1]heptane-2,3Ј-indol-
ine]-3-carboxylate (5ba): A yellow oil (114.0 mg, 57% yield). 1H
NMR (400 MHz, CDCl3, TMS): δ = 0.62 (t, J = 7.2 Hz, 3 H), 1.23
(t, J = 7.2 Hz, 3 H), 1.96–2.01 (m, 1 H), 2.31 (dd, J = 12.0, 8.4 Hz,
1 H), 3.21 (s, 1 H), 3.27 (s, 3 H), 3.62 (dq, J = 7.2, 2.4 Hz, 2 H),
4.14 (q, J = 7.2 Hz, 2 H), 5.10 (dd, J = 12.0, 7.6 Hz, 1 H), 5.55 (d,
J = 5.2 Hz, 1 H), 5.94 (d, J = 16.0 Hz, 1 H), 6.85 (dd, J = 16.0,
7.2 Hz, 2 H), 7.05 (t, J = 7.6 Hz, 1 H), 7.30 (t, J = 7.6 Hz, 1 H),
7.46 (d, J = 7.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3, TMS):
δ = 13.3, 14.2, 26.8, 39.6, 59.3, 60.3, 60.4, 60.6, 75.4, 82.3, 107.9,
121.3, 123.6, 125.7, 129.1, 129.6, 142.6, 147.6, 166.2, 168.6,
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171.8 ppm. IR (CH Cl ): ν = 2980, 2904, 1708, 1658, 1612, 1493,
˜
2
2
10
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20511
/KAP1
Date: 18-06-12 11:45:12
Pages: 12
Cascade Reactions of Isatin-Derived Oximes with Allenic Esters
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[10]
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[12]
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Received: April 19, 2012
Published Online: ᭿
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11

Job/Unit: O20511
/KAP1
Date: 18-06-12 11:45:12
Pages: 12
C.-K. Pei, Y. Jiang, M. Shi
FULL PAPER
Tandem Reactions
C.-K. Pei, Y. Jiang, M. Shi* ........... 1–12
Phosphorus-Containing Lewis Base Cata-
lyzed Cascade Reactions of Isatin-Derived
Oximes with Allenic Esters and Further
Transformations
Keywords: Lewis bases / Domino reac-
tions / Heterocycles / Allenes / Cyclization
Phosphorus containing Lewis base cata-
lyzed cascade reactions of isatin-derived
oximes with allenic esters afford the corre-
sponding functionalized nitrones. Further
Lewis acid catalyzed highly regioselective
intramolecular [3+2] cyclizations give the
corresponding bridged cycloadducts.
combined “one-pot” reaction is also
feasible for the above two catalytic reac-
tions.
A
12
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