Lanthanide amides [(Me3Si)2N]3Ln(μ-Cl) Li(THF)3-catalyzed phospho-aldol-brook rearrangement reaction of dialkyl phosphites with isatins

Article abstract of DOI:10.1002/hc.21036

The tetracoordinated lanthanide amides [(Me₃Si) ₂N]₃Ln(μ-Cl)Li(THF)₃ were found to serve as highly active catalysts for the phospho-Aldol-Brook rearrangement reaction of various dialkyl phosphites and isatins. The reactions produced dialkyl 2-oxoindolin-3-yl phosphates in good to excellent yields in the presence of 1 mol% [(Me₃Si)₂N]₃La(μ-Cl)Li(THF)₃ at room temperature within 5 min. A mechanism for this highly efficient process was proposed. Copyright

Full text of DOI:10.1002/hc.21036

Heteroatom Chemistry
Volume 00, Number 0, 2012
Lanthanide Amides
[(Me Si) N] Ln(μ-Cl)Li(THF) -Catalyzed
3 2 3
3
Phospho-Aldol-Brook Rearrangement Reaction
of Dialkyl Phosphites with Isatins
Lu Wang, Zhigang Yao, Fan Xu, and Qi Shen
Key Laboratory of Organic Synthesis, College of Chemistry, Chemical Engineering and Material
Science, Soochow University, Suzhou 215123, People’s Republic of China
Received 30 March 2012; revised 23 May 2012, 2 June 2012
sulting in a wide range of synthetic pathways, most
ABSTRACT: The tetracoordinated lanthanide
of them involving addition of a nucleophile to the
amides [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3 were found
3-carbonyl of isatins. However, with regard to
to serve as highly active catalysts for the phospho-
the type of nucleophile, comparatively few papers
Aldol-Brook rearrangement reaction of various
[3–6] have described about phosphorus nucleophilic
dialkyl phosphites and isatins. The reactions pro-
reagents such as dialkyl phosphites, although the
duced dialkyl 2-oxoindolin-3-yl phosphates in
corresponding products, α-hydroxy phosphonates,
good to excellent yields in the presence of 1 mol%
are known to possess a broad spectrum of biolog-
[(Me3Si)2N]3La(μ-Cl)Li(THF)3 at room temperature
ical activities [7].
within 5 min. A mechanism for this highly efficient
In another respect, the tetracoordinated lan-
ꢀ
C
process was proposed.
2012 Wiley Periodicals, Inc.
thanide amides [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3,
chloride-bridged “ate” complexes derived from
Ln[N(SiMe3)2]3, have been found to be useful
replacements for homoleptic Ln[N(SiMe3)2]3. Their
synthesis is easier than that of Ln[N(SiMe3)2]3, and
they have been used as efficient catalysts for aldol
condensations [8], methyl methacrylate polymer-
izations [9], aza-Henry reactions [10], and guany-
lations of amines [11]. Recently, we reported the
Heteroatom Chem 00:1–8, 2012; View this article online
at wileyonlinelibrary.com. DOI 10.1002/hc.21036
INTRODUCTION
The oxindole skeleton exists in many natural
and synthetic biologically active materials [1].
3-Hydroxy-substituted oxindoles occupy an impor-
tant position in oxindole derivatives because of their
known and promising biological activities [2]. Many
research groups have focused on developing meth-
ods for the synthesis of this type of compounds, re-
[(Me3Si)2N]3Ln(μ-Cl)Li(THF)3-catalyzed
Pudovik
reaction of aryl aldehydes with dialkyl phosphites
[12]. The target products, α-hydroxy phosphonates,
were obtained in excellent yields in the presence of
0.1 mol% of catalyst at room temperature within
5 min. Considering the valuable properties of
3-hydroxy oxindoles and α-hydroxy phosphonates,
we investigated the effectiveness of lanthanide
amides as catalysts for phosphorus-nucleophilic
attack to isatins, with a hope of developing novel cat-
alysts and relevant processes for the high-efficiency
synthesis of α1-oxindole-α-hydroxyphosphonate
as valuable small molecules. However, the
Correspondence to: Fan Xu; e-mail: xufan@suda.edu.cn/ Qi
Shen; e-mail: qshen@suda.edu.cn
Contract grant sponsor: National Natural Science Foundation
of China.
Contract grant numbers: 20872106, 20972107.
Contract grant sponsor: Priority Academic Program Develop-
ment of Jiangsu Higher Education Institutions.
c
ꢀ
2012 Wiley Periodicals, Inc.
1

2
Wang et al.
O
P
O
H
OEt
OEt
O
Catalyst
O
O
HOP(OEt)2
+
25 oC, 5 min
N
N
1a
2a
3a
O
OEt
HO
P
OEt
O
N
4a not observed
SCHEME 1 Catalyzed reaction of diethyl phosphite 2a with N-allylisatin 1a.
[(Me3Si)2N]3Ln(μ-Cl)Li(THF)3-catalyzed
reac-
a typical Lewis acid, cannot initiate the reaction
with a catalyst loading of 1 mol% (entry 2), in-
dicating that the Lewis acidity of the lanthanide
compounds was not decisive in catalyzing this
reaction. The tetracoordinated lanthanum amide
[(Me3Si)2N]3La(μ-Cl)Li(THF)3 catalyzed the reac-
tion with high efficiency. To our surprise, 1-allyl-2-
oxoindolin-3-yl diethyl phosphate 3a, rather than the
expected diethyl (1-allyl-3-hydroxy-2-oxoindolin-3-
yl)phosphonate 4a, was obtained in 93% yield within
5 min (entry 3). A control experiment using homolep-
tic lanthanum amide, La[N(SiMe3)2]3, as the cat-
alyst instead of [(Me3Si)2N]3La(μ-Cl)Li(THF)3 gave
the product in 82% yield (entry 4), revealing that the
existence of LiCl in the latter was a key factor in the
catalytic activity. However, none of the desired prod-
uct was observed when anhydrous LiCl was used as
an independent catalyst in the present reaction (en-
try 5). Because [(Me3Si)2N]3La(μ-Cl)Li(THF)3 can be
tion of dialkyl phosphites with isatins afforded
dialkyl 2-oxoindolin-3-yl phosphates rather than
the expected α1-oxindole-α-hydroxyphosphonates
as products, through nucleophilic addition of the
phosphite to isatin and subsequent the phospha-
Brook rearrangement [13]. Herein, we wish to
report this highly efficient process affording dialkyl
2-oxoindolin-3-yl phosphates.
RESULTS AND DISCUSSION
First, the addition reaction of diethyl phosphite 2a
with N-allylisatin 1a was carried out as a model
reaction at room temperature (Scheme 1), and
the effects of various catalysts were examined. As
shown in Table 1, the reaction cannot proceed
in the absence of catalyst. Lanthanum trichloride,
TABLE 1 Catalyzed Reaction of Diethyl Phosphite 2a with N-Allylisatin 1aa
Entry
Catalyst
Loading (mol%)
Solvent
Yield (%)
1
2
3
4
5
6
7
8
–
–
1
1
1
1
1
3
1
1
1
1
1
1
THF
THF
THF
THF
THF
THF
THF
THF
0
0
93
82
0
83
76
89
81
86
90
88
91
LaCl3
[(Me3Si)2N]3La(μ-Cl)Li(THF)3
La[N(SiMe3)2]3
LiCl
La[N(SiMe3)2]3+ LiCl
LiN(SiMe3)2
[(Me3Si)2N]3Sm(μ-Cl)Li(THF)3
[(Me3Si)2N]3Yb(μ-Cl)Li(THF)3
[(Me3Si)2N]3La(μ-Cl)Li(THF)3
[(Me3Si)2N]3La(μ-Cl)Li(THF)3
[(Me3Si)2N]3La(μ-Cl)Li(THF)3
[(Me3Si)2N]3La(μ-Cl)Li(THF)3
9
THF
10
11
12
13
CH2Cl2
Toluene
CH3CN
DME
aReactions were performed with 0.5 mmol of N-allylisatin and 0.6 mmol of HOP(OEt)2 in 2 mL of THF at 25◦C for 5 min.
Heteroatom Chemistry DOI 10.1002/hc

Lanthanide Amides [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3-Catalyzed Phospho-Aldol-Brook Rearrangement Reaction
3
not the signal of the O H group.13C NMR spectrum
produced three doublets between 60 and 75 ppm
with similar phosphorus–carbon spin–spin coupling
constants (ca. 6 Hz), indicating the existence of
three P(O) O C groups. All these results show that
the reaction product is a phosphate rather than a
α-hydroxy phosphonate.
Several tetracoordinated lanthanide amides
were tested (entries 3, 8, and 9) to assess the in-
fluence of the central metal ion on the catalytic ac-
tivity. It was found that the progressive decrease in
the ionic radius of Ln(III) from the light rare-earth
metal La to the heavy rare-earth metal Yb led to a
gradual decrease in the product yields. So, the amide
complex of La, the largest metal among those tested,
was chosen as the representative lanthanide source
for carrying out the studies. Further optimization
of the reaction conditions revealed that the reaction
medium has a slight effect on the yields, and THF
gave the best result among the solvents screened.
The reaction conditions selected for further studies
were 1 mol% [(Me3Si)2N]3La(μ-Cl)Li(THF)3 at 25◦C
for 5 min with THF as the solvent.
FIGURE 1 X-ray structure of compound 3b.
regarded as a solvated adduct of La[N(SiMe3)2]3 and
LiCl, the reaction using a mixture of La[N(SiMe3)2]3
and anhydrous LiCl in a 1:1 ratio in THF as a cat-
alyst was tried (entry 6), but failed to produce the
same effect as that obtained with [(Me3Si)2N]3La(μ-
Cl)Li(THF)3. These results indicated that the manner
in which La[N(SiMe3)2]3 and LiCl are combined in
crystalline [(Me3Si)2N]3La(μ-Cl)Li(THF)3 is decisive
with respect to its catalytic activity. The use of 3
mol% LiN((SiMe3)2 gave the product in a moderate
yield of 76% (entry 7), showing that the Brønsted
basicity of the trimethylsilylamino group also plays
an important role in the catalytic process.
With the optimum reaction conditions iden-
tified, an exploration of substrate scope was
performed using various isatins 1 and dialkyl
phosphites 2 (Scheme 2). As shown in Table 2, all
the reactions proceeded smoothly and quickly, af-
fording the corresponding products 3 in good to ex-
cellent yields at room temperature within 5 min. The
method was general for various isatins, including N-
alkyl-, N-allyl-, and N-benzyl-substituted isatins, al-
though N-acyl-substituted isatin 1d gave a slightly
decreased yield. An electronic effect was observed in
the reactions of diethyl phosphite with different N-
allylisatins: The yield clearly increased when isatins
bearing electron-donating groups on the benzene
ring were used, rather than those bearing electron-
withdrawing groups (at either the 4- or 5-position).
Diisopropyl and diphenyl phosphites afforded the
corresponding products in lower yields, indicating
an obvious steric effect.
To confirm the structure of product, an X-ray
diffraction analysis of diethyl 1-benzyl-2-oxoindolin-
3-yl phosphate 3b, which was obtained from the re-
action of diethyl phosphite 2a with N-benzylisatin
1b, was performed because it forms crystals at room
temperature. The structure of 3b is shown in Fig. 1.
1
1H and 13C NMR spectra were also studied. The H
In view of the high efficiency of the reaction,
we tried to deduce a plausible mechanism. Based
on the distinctive properties of lanthanide amides,
NMR signal at 5.60 (d, J = 12.0 Hz, 1H) did not
disappear after D2O was added, indicating that it is
O
O
1.0 mol%
OR3
OR3
H
O
µ
[(Me3Si)2N]3La( -Cl)Li(THF)3
P
R2
R2
HOP(OR3)2
O
O
+
25oC, 5 min, THF
N
N
R1
R1
3
1
2
SCHEME 2 [(Me3Si)2N]3La(μ-Cl)Li(THF)3-catalyzed reaction of dialkyl phosphites with isatins.
Heteroatom Chemistry DOI 10.1002/hc

4
Wang et al.
TABLE 2 [(Me3Si)2N]3La(μ-Cl)Li(THF)3-Catalyzed Reac-
a possible mechanism (Scheme 3) for the present
reaction may involve rapid deprotonation of the di-
alkyl phosphite, which may exist in its tautomeric
form as the phosphonate, releasing an amine and
forming the intermediate 5, which is most prob-
ably the catalytically active species. Intermediate
5 then reacts as a nucleophile toward the keto
carbonyl carbon atoms of the isatin to generate
the α-hydroxy phosphonate, which is further trans-
formed to dialkyl 2-oxoindolin-3-yl phosphate by the
phospha-Brook arrangement. The unusual activity
that [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3 displayed here
may be rationalized on the basis of cooperation be-
tween lanthanide and lithium. When Ln[N(SiMe3)2]3
is used as the catalyst, the lanthanide center in
species 5 may coordinate to the isatin, forming a
transition state A, in which the lanthanide acts as
a Brønsted base to deprotonate HOP(OR)2 as well
as a Lewis acid to activate the isatin. However, the
tion of Dialkyl Phosphites with Isatinsa
Entry
R1
R2
R3 Product Yield (%)
1
2
3
4
5
6
7
8
CH2 CH CH2
PhCH2
CH3CH2
CH3C O
CH2 CH CH2
CH2 CH CH2
CH2 CH CH2 5-F
CH2 CH CH2 5-Cl
CH2 CH CH2 5-Br
CH2 CH CH2 5-CH3
CH2 CH CH2 5-CH3O
CH2 CH CH2 4-Cl
CH2 CH CH2 4-Br
H
H
H
H
H
H
Et
Et
Et
Et
i Pr
Ph
Et
Et
Et
Et
Et
Et
Et
Et
Et
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
93
91
95
83
85
76
75
81
89
95
91
78
86
94
93
9
10
11
12
13
14
15
PhCH2
CH3CH2
5-CH3
5-CH3
aReactions were performed with 0.5 mmol of isatin and 0.6 mmol of
dialkyl phosphite in 1 mL of THF at 25◦C for 5 min.
O
HO P(OR)2
H
P(OR)2
Ln[N(SiMe3)2]3
O
P
O
H
OR
OR
O
HN(SiMe3)2
O
O
N
N
[Ln]
O
P(OR)2
R'
R'
5
[Ln]
O
[Ln]
O
P
O
P
(RO)2P
O
H
OR
OR
OR
OR
O
O
O
N
N
R'
R'
A
[Ln]
O
P
OR
OR
O
HO P(OR)2
O
N
R'
Cl
[Ln]
O
Li
O
OR
P
OR
O
N
R'
B
SCHEME 3 Proposed mechanism for the lanthanide amide–catalyzed phospho-Aldol-Brook rearrangement reaction.
Heteroatom Chemistry DOI 10.1002/hc

Lanthanide Amides [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3-Catalyzed Phospho-Aldol-Brook Rearrangement Reaction
5
formation of the transition state A may be sup-
pressed to a certain extent by the steric repulsive in-
teractions of the two substrates. When the sterically
more flexible [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3 [14] is
used, the isatin may coordinate to the lithium to
form the sterically less crowded transition state B,
in which the Li moiety in the catalyst functions as
a Lewis acid instead of the lanthanide. The stabil-
ity of the transition state B caused by the cooper-
ation between lanthanide and lithium may be an
important factor resulting in the high efficiency of
[(Me3Si)2N]3Ln(μ-Cl)Li(THF)3.
indanone confirmed our hypothesis. Therefore, the
presence of the amide carbonyl is necessary for
the efficient addition of dialkyl phosphite to the 3-
carbonyl of isatin, although the amide carbonyl itself
does not take part in the reaction.
In conclusion, we have demonstrated a highly
efficient method for the synthesis of dialkyl 2-
oxoindolin-3-yl phosphates via the phospho-Aldol-
Brook rearrangement reaction of various dialkyl
phosphites and isatins, catalyzed by the tetra-
coordinated lanthanide amides [(Me3Si)2N]3Ln(μ-
Cl)Li(THF)3. The target products were obtained
in good to excellent yields in the presence of 1
mol% [(Me3Si)2N]3La(μ-Cl)Li(THF)3 at room tem-
perature within 5 min. The high efficiency of
the catalytic process can be rationalized by co-
operation between lanthanide and lithium in the
catalyst.
To obtain more information on the mecha-
nism of the present lanthanide amide–catalyzed re-
action, in situ IR spectroscopy was employed to
study the coordination of catalyst with the substrate.
[(Me3Si)2N]3La(μ-Cl)Li(THF)3 (1 equiv) was added
to a THF solution of N-allylisatin 1a; the spectrum
is shown in Fig. 2 (L). As can be seen, the peak
at 1750 cm−1, assigned to the 3-carbonyl of isatin,
shifted to a lower wave number 1732 cm−1, suggest-
ing coordination of the keto carbonyl with the metal
Lewis acid. However, the peak at 1616 cm−1, which
is assigned to the 2-carbonyl of isatin, only exhib-
ited a minor change, indicating that the amide car-
bonyl does not participate in the usual coordination
of a ketone function. Based on these phenomena, the
[(Me3Si)2N]3La(μ-Cl)Li(THF)3-catalyzed reaction of
indanone with diethyl phosphite was tried, but failed
to give the expected product. The in situ IR spec-
trum (Fig. 2, R) shows that when [(Me3Si)2N]3La(μ-
Cl)Li(THF)3 (1 equiv) was added to indanone, the
peak at 1724 cm−1 immediately shifted to 1668 cm−1
and then rapidly disappeared. This may be the result
of rapid coordination of carbonyl with the metal ion,
EXPERIMENTAL
General Remarks
All manipulations were conducted under an at-
mosphere of dry Ar with flame-dried glass-
ware. Ln[N(SiMe3)2]3 [15] and [(Me3Si)2N]3Ln(μ-
Cl)Li(THF)3 [9,16] were synthesized according to the
literature method. 1H and 13C NMR spectra were ob-
tained on Varian INOVA-400 and System-300 spec-
trometers (Varian Associates, Inc., Palo Alto, CA,
USA) using tetramethylsilane as an internal refer-
ence. IR spectra were obtained on a Nicolet FT-IR
1000 spectrophotometer. HRMS data were obtained
on a Micromass GCT instrument (Micromass UK
Limited, Manchester, UK). In situ IR spectra were
recorded using a ReactIR iC 10 from Mettler-Toledo
AutoChem Inc. (Columbia, MD, USA).
1
followed by enol formation. The H NMR spectrum
of the mixture of [(Me3Si)2N]3La(μ-Cl)Li(THF)3 and
FIGURE 2 Three-dimensional plots of IR spectra for the reaction of [(Me3Si)2N]3La(μ-Cl)Li(THF)3 with N-allylisatin 1a (L)
and indanone (R).
Heteroatom Chemistry DOI 10.1002/hc

6
Wang et al.
1H), 7.60 (d, J = 7.6 Hz, 1H), 7.42 (t, J = 8.0 Hz,
1H), 7.27 (t, J = 7.6 Hz, 1H), 5.78 (d, J = 12.4 Hz,
1H), 4.30–4.24 (m, 2H), 4.22–4.16 (m, 2H), 2.68 (s,
3H), 1.40 (t, J = 7.2 Hz, 3H), 1.36 (t, J = 7.2 Hz, 3H).
General Procedure
A mixture of [(Me3Si)2N]3La(μ-Cl)Li(THF)3 (4.4 mg,
0.005 mmol) and dialkyl phosphite (0.6 mmol) in
THF (0.5 mL) was stirred for 10 min. A solution of
isatin (0.5 mmol) in THF (0.5 mL) was then added,
and the resulting mixture was allowed to stir at 25◦C
for 5 min. Water was added, and the mixture was
extracted with ethyl acetate. The combined organic
layer was dried over anhydrous Na2SO4, concen-
trated in vacuo, and purified by chromatography on
silica gel [eluent: acetone/petroleum ether (60-90◦C)
1:7] to afford the desired phosphate.
Diisopropyl 1-allyl-2-oxoindolin-3-yl phosphate
(3e). 1H NMR (400 MHz, CDCl3) δ: 7.52 (d, J =
7.2 Hz, 1H), 7.23 (t, J = 7.6 Hz, 1H), 6.99 (t, J =
7.6 Hz, 1H), 6.73 (d, J = 7.6 Hz, 1H), 5.78–5.69 (m,
1H), 5.55 (d, J = 12.0 Hz, 1H), 5.19–5.13 (m, 2H),
4.80–4.72 (m, 1H), 4.68–4.60 (m, 1H), 4.29–4.15 (m,
2H), 1.33 (d, J = 6.4 Hz, 3H), 1.30 (d, J = 6.4 Hz,
3H), 1.25 (d, J = 6.0 Hz, 6H); 13C NMR (75 MHz,
CDCl3) δ: 171.5 (d, J = 7.4 Hz), 143.2, 130.8, 130.3,
126.0, 124.2, 122.9, 117.8, 109.3, 73.4 (d, J = 6.5 Hz),
73.1 (d, J = 6.2 Hz), 72.1 (d, J = 5.8 Hz), 42.4, 23.7,
23.6, 23.5, 23.4; IR ν: 2982, 2935, 1737, 1615, 1489,
1269 (s, P O), 1003 (s, P O C), 753 cm−1; HRMS
calcd for C17H25NO5P ([M + H]+) 354.1485, found
354.1478.
Diethyl 1-allyl-2-oxoindolin-3-yl phosphate (3a).
1H NMR (300 MHz, CDCl3) δ: 7.48 (d, J = 7.5 Hz,
1H), 7.24 (t, J = 7.5 Hz, 1H), 7.00 (t, J = 7.5 Hz,
1H), 6.74 (d, J = 7.8 Hz, 1H), 5.80-5.68 (m, 1H), 5.55
(d, J = 12.0 Hz, 1H), 5.20–5.13 (m, 2H), 4.28–4.16
(m, 4H), 4.13–4.06 (m, 2H), 1.31 (t, J = 7.2 Hz, 3H),
1.26 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
δ: 171.5 (d, J = 6.7 Hz), 143.3, 130.7, 130.5, 125.9,
124.0, 123.0, 117.9, 109.4, 72.2 (d, J = 5.6 Hz), 64.5
(d, J = 5.9 Hz), 64.2 (d, J = 5.8 Hz), 42.4, 16.0,
15.9; IR ν: 2993, 2907, 1745, 1614, 1266 (s, P O),
1022 (s, P O C), 966, 743 cm−1; HRMS calcd for
C15H21NO5P ([M + H]+) 326.1152, found 326.1161.
Diphenyl 1-allyl-2-oxoindolin-3-yl phosphate (3f).
1H NMR (300 MHz, CDCl3) δ: 7.36–7.17 (m, 12H),
6.97 (t, J = 7.5 Hz, 1H), 6.80 (d, J = 7.5 Hz, 1H),
5.85–5.74 (m, 2H), 5.27–5.21 (m, 2H), 4.38–4.23 (m,
2H).
Diethyl 1-allyl-5-fluoro-2-oxoindolin-3-yl phos-
phate (3g). 1H NMR (400 MHz, CDCl3) δ: 7.27 (d,
J = 7.2 Hz, 1H), 6.95 (t, J = 8.4 Hz, 1H), 6.70–6.67
(m, 1H), 5.78–5.69 (m, 1H), 5.53 (d, J = 12.4 Hz, 1H),
5.20–5.16 (m, 2H), 4.27–4.17 (m, 4H), 4.15–4.10 (m,
2H), 1.32 (t, J = 7.2 Hz, 3H), 1.28 (t, J = 7.2 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ: 171.3 (d, J = 6.8
Hz), 159.2 (d, J = 240.9 Hz), 139.2, 130.6, 125.6 (d,
J = 7.4 Hz), 118.2, 116.9 (d, J = 23.3 Hz), 114.1
(d, J = 25.1 Hz), 110.2 (d, J = 7.7 Hz), 72.0 (d, J
= 5.1 Hz), 64.8 (d, J = 6.0 Hz), 64.5 (d, J = 5.7
Hz), 42.6, 16.1, 16.0 cm−1; IR ν: 2986, 2931, 1736,
1491, 1268 (s, P O), 1028 (s, P O C), 818; HRMS
calcd for C15H20FNO5P ([M + H]+) 344.1058, found
344.1056.
Diethyl 1-benzyl-2-oxoindolin-3-yl phosphate
(3b). 1H NMR (400 MHz, CDCl3) δ: 7.48 (d, J = 7.6
Hz, 1H), 7.22–7.11 (m, 6H), 6.96 (t, J = 7.6 Hz, 1H),
6.62 (d, J = 7.6 Hz, 1H), 5.60 (d, J = 12.0 Hz, 1H),
4.83–4.71 (m, 2H), 4.28–4.18 (m, 2H), 4.14–4.07 (m,
2H), 1.31(t, J = 7.2 Hz, 3H), 1.25 (t, J = 7.2 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ: 171.9 (d, J = 6.8
Hz), 143.2, 135.1, 130.5, 128.8, 127.8, 127.3, 126.0,
124.1, 123.1, 109.5, 72.2 (d, J = 5.5 Hz), 64.6 (d,
J = 5.9 Hz), 64.3 (d, J = 5.7 Hz), 43.9, 16.0, 15.9.
Diethyl 1-ethyl-2-oxoindolin-3-yl phosphate (3c).
1H NMR (300 MHz, CDCl3) δ: 7.58 (d, J = 7.2 Hz,
1H), 7.36 (t, J = 7.8 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H),
6.85 (d, J = 8.1 Hz, 1H), 5.59 (d, J = 12.0 Hz, 1H),
4.35–4.26 (m, 2H), 4.24–4.15 (m, 2H), 3.74 (q, J =
7.2 Hz, 2H), 1.41 (t, J = 7.2 Hz, 3H), 1.35 (t, J = 7.2
Hz, 3H), 1.28 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ: 171.6 (d, J = 6.8 Hz), 143.3, 130.7, 126.2,
124.4, 123.0, 108.7, 72.4 (d, J = 5.5 Hz), 64.7 (d, J =
5.9 Hz), 64.4 (d, J = 5.6 Hz), 35.0, 16.2, 16.1, 12.5;
IR ν: 2983, 2936, 1732, 1615, 1490, 1372, 1274 (s,
P O), 1032 (s, P O C), 754 cm−1; HRMS calcd for
C14H21NO5P ([M + H]+) 314.1152, found 314.1153.
Diethyl 1-allyl-5-chloro-2-oxoindolin-3-yl phos-
phate (3h). 1H NMR (400 MHz, CDCl3) δ: 7.47 (s,
1H), 7.20 (d, J = 8.4 Hz, 1H), 6.68 (d, J = 8.4 Hz,
1H), 5.76–5.67 (m, 1H), 5.51 (d, J = 12.8 Hz, 1H),
5.19–5.15 (m, 2H), 4.25–4.17 (m, 4H), 4.16–4.09 (m,
2H), 1.31 (t, J = 7.2 Hz, 3H), 1.28 (t, J = 7.2 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ: 171.1 (d, J = 6.9 Hz),
141.9, 130.4, 128.5, 126.4, 125.7, 125.6, 118.3, 110.5,
71.8 (d, J = 5.6 Hz), 64.8 (d, J = 6.2 Hz), 64.5 (d,
J = 5.9 Hz), 42.6, 16.1, 16.0; IR ν: 2984, 2918, 1745,
1614, 1277 (s, P O), 1022 (s, P O C), 977, 808 cm−1;
Diethyl 1-acetyl-2-oxoindolin-3-yl phosphate (3d).
1H NMR (400 MHz, CDCl3) δ: 8.23 (d, J = 8.4 Hz,
Heteroatom Chemistry DOI 10.1002/hc

Lanthanide Amides [(Me3Si)2N]3Ln(μ-Cl)Li(THF)3-Catalyzed Phospho-Aldol-Brook Rearrangement Reaction
7
HRMS calcd for C15H20ClNO5P ([M + H]+) 360.0762,
P O C), 818 cm−1; HRMS calcd for C15H20ClNO5P
([M + H]+) 360.0762, found 360.0771.
found 360.0756.
Diethyl 1-allyl-4-bromo-2-oxoindolin-3-yl phos-
phate (3m). 1H NMR (400 MHz, CDCl3) δ: 7.20 (t,
J = 8.0 Hz, 1H), 6.95 (d, J = 8.0 Hz, 1H), 6.66 (d,
J = 8.0 Hz, 1H), 5.77–5.69 (m, 1H), 5.66 (d, J =
14.8 Hz, 1H), 5.21–5.14 (m, 2H), 4.23–4.22 (m, 2H),
4.18–4.11 (m, 4H), 1.27 (t, J = 6.8 Hz, 3H), 1.26 (t,
J = 6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ: 171.0,
145.2, 132.5, 131.9, 130.5, 123.6, 121.5, 118.1, 107.9,
71.9 (d, J = 5.0 Hz), 64.3, 64.2, 42.6, 16.0, 15.9; IR ν:
2982, 2935, 1737, 1615, 1489, 1269 (s, P O), 1003 (s,
P O C), 753 cm−1; HRMS calcd for C15H20BrNO5P
([M + H]+) 404.0257, found 404.0258.
Diethyl 1-allyl-5-bromo-2-oxoindolin-3-yl phos-
phate (3i). 1H NMR (400 MHz, CDCl3) δ: 7.62 (s,
1 H), 7.37 (d, J = 8.0 Hz, 1H), 6.63 (d, J = 8.4 Hz,
1H), 5.77–5.68 (m, 1H), 5.53 (d, J = 12.4 Hz, 1H),
5.19–5.16 (m, 2H), 4.26–4.18 (m, 4H), 4.15–4.10 (m,
2H), 1.33 (t, J = 6.8 Hz, 3H), 1.29 (t, J = 6.8 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ: 171.1 (d, J = 6.8
Hz), 142.4, 133.4, 130.5, 129.2, 126.1, 118.4, 115.8,
111.0, 71.8 (d, J = 5.5 Hz), 64.8 (d, J = 5.9 Hz),
64.6 (d, J = 5.8 Hz), 42.6, 16.1, 16.0; IR ν: 2984,
2918, 1745, 1614, 1266 (s, P O), 1034 (s, P O C),
977, 808 cm−1; HRMS calcd for C15H20BrNO5P ([M
+ H]+) 404.0257, found 404.0252.
Diethyl 1-benzyl-5-methyl-2-oxoindolin-3-yl phos-
phate (3n). 1H NMR (400 MHz, CDCl3) δ: 7.40 (s,
1H), 7.30–7.23 (m, 5H), 7.02 (d, J = 8.0 Hz, 1H),
6.59 (d, J = 8.0 Hz, 1H), 5.67 (d, J = 12.0 Hz, 1H),
4.89–4.78 (m, 2H), 4.39–4.28 (m, 2H), 4.25–4.18 (m,
2H), 2.29 (s, 3H), 1.41 (t, J = 7.2 Hz, 3H), 1.35 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 171.8 (d,
J = 6.9 Hz), 140.7, 135.2, 132.7, 130.7, 128.7, 127.6,
127.2, 126.6, 124.1, 109.2, 72.3 (d, J = 5.5 Hz), 64.5
(d, J = 6.1 Hz), 64.2 (d, J = 5.8 Hz), 43.8, 20.8, 16.0
(d, J = 2.9 Hz), 15.9 (d, J = 2.8 Hz); IR ν: 2984, 2918,
1731, 1604, 1496, 1273 (s, P O), 1030 (s, P O C),
813 cm−1; HRMS calcd for C20H25NO5P ([M + H]+)
390.1465, found 390.1456.
Diethyl 1-allyl-5-methyl-2-oxoindolin-3-yl phos-
phate (3j). 1H NMR (400 MHz, CDCl3) δ: 7.32 (s,
1H), 7.04 (d, J = 8.0 Hz, 1H), 6.63 (d, J = 8.0 Hz,
1H), 5.78–5.69 (m, 1H), 5.52 (d, J = 12.0 Hz, 1H),
5.19–5.13 (m, 2H), 4.28–4.18 (m, 4H), 4.15–4.08 (m,
2H), 2.25 (s, 3H), 1.32 (t, J = 6.8 Hz, 3H), 1.27 (t,
J = 6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ: 171.6
(d, J = 7.0 Hz), 140.9, 132.8, 130.9, 130.8, 126.8,
124.1, 117.9, 109.2, 72.4 (d, J = 5.5 Hz), 64.6 (d, J =
5.9 Hz), 64.3 (d, J = 5.7 Hz), 42.5, 21.0, 16.1, 16.0;
IR ν: 2993, 2918, 1736, 1623, 1501, 1277 (s, P O),
1022 (s, P O C), 977, 808 cm−1; HRMS calcd for
C16H23NO5P ([M + H]+) 340.1309, found 340.1302.
Diethyl 1-ethyl-5-methyl-2-oxoindolin-3-yl phos-
phate (3o). 1H NMR (400 MHz, CDCl3) δ: 7.40 (s,
1H), δ: 7.15 (d, J = 7.6 Hz, 1H), 6.75 (d, J = 7.6 Hz,
1H), 5.55 (d, J = 11.6 Hz, 1H), 4.37–4.25 (m, 2H),
4.24–4.17 (m, 2H), 3.72 (q, J = 7.2 Hz, 2H), 2.34 (s,
3H), 1.41 (t, J = 7.2 Hz, 3H), 1.36 (t, J = 7.2 Hz,
3H), 1.26 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ: 171.3 (d, J = 7.0 Hz), 140.7, 132.5, 130.7,
126.8, 124.2, 108.3, 72.3 (d, J = 5.7 Hz), 64.5 (d, J =
6.0 Hz), 64.2 (d, J = 5.8 Hz), 34.8, 20.8, 16.0, 15.9,
12.3; IR ν: 2983, 2935, 1731, 1603, 1496, 1276 (s,
P O), 1030 (s, P O C), 812 cm−1; HRMS calcd for
C15H23NO5P ([M + H]+) 328.1308, found 328.1301.
Diethyl 1-allyl-5-methoxy-2-oxoindolin-3-yl phos-
phate (3k). 1H NMR (400 MHz, CDCl3) δ: 7.11 (s,
1H), 6.76 (d, J = 8.8 Hz, 1H), 6.65 (d, J = 8.8 Hz,
1H), 5.78–5.68 (m, 1H), 5.52 (d, J = 12.0 Hz, 1H),
5.19–5.13 (m, 2H), 4.27–4.19 (m, 4H), 4.15–4.08 (m,
2H), 3.70 (s, 3H), 1.32 (t, J = 7.2 Hz, 3H), 1.27 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 171.2 (d,
J = 6.8 Hz), 156.2, 136.6, 130.9, 125.2, 117.9, 115.2,
112.8, 110.0, 72.4 (d, J = 5.7 Hz), 64.6 (d, J = 6.2
Hz), 64.3 (d, J = 5.9 Hz), 55.8, 42.5, 16.1, 16.0; IR
ν: 2985, 2933, 1731, 1603, 1494, 1274 (s, P O), 1034
(s, P O C), 816 cm−1; HRMS calcd for C16H23NO6P
([M + H]+) 356.1258, found 356.1250.
REFERENCES
Diethyl 1-allyl-4-chloro-2-oxoindolin-3-yl phos-
phate (3l). 1H NMR (400 MHz, CDCl3) δ: 7.15–7.10
(m, 2H), 6.71–6.68 (m, 1H), 5.78–5.68 (m, 1H), 5.56
(d, J = 15.2 Hz, 1H), 5.21–5.15 (m, 2H), 4.23–4.21
(m, 2H), 4.20–4.13 (m, 4H), 1.27 (t, J = 6.8 Hz, 3H),
1.25 (t, J = 6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ:
171.0, 145.2, 132.5, 131.9, 130.5, 123.6, 121.6, 118.1,
107.9, 72.0 (d, J = 5.3 Hz), 64.4, 64.3, 42.6, 16.1, 16.0;
IR ν: 2986, 2931, 1736, 1491, 1268 (s, P O), 1028 (s,
[1] (a) Howard, H. R.; Lowe, J. A., III; Seeger, T. F.;
Seymour, P. A.; Zorn, S. H.; Maloney, P. R.; Ewing,
F. E.; Newman, M. E.; Schmidt, A. W.; Furman, J.
S.; Robinson, G. L.; Jackson, E.; Johnson, C.; Mor-
rone, J. J Med Chem 1996, 39, 143; (b) Hibino, S.;
Choshi, T. Nat Prod Rep 2002, 19, 148; (c) Somei, M.;
Yamada, F. Nat Prod Rep 2003, 20, 216; (d)
Pajouhesh, H.; Parson, R.; Popp, F. D. J Pharm Sci
1983, 72, 318.
Heteroatom Chemistry DOI 10.1002/hc

8
Wang et al.
[2] (a) Tokunaga, T.; Hume, W. E.; Nagamine, J.; Kawa-
mura, T.; Taiji, M.; Nagata, R. Bioorg Med Chem Lett
2005, 15, 1789; (b) Yong, S. R.; Ung, A. T.; Pyne, S.
G.; Skelton, B. W.; White, A. H. Tetrahedron 2007, 63,
5579; (c) Kohno, J.; Koguchi, Y.; Nishio, M.; Nakao,
K.; Kuroda, M.; Shimizu, R.; Ohnuki, T.; Komatsub-
ara, S. J Org Chem 2000, 65, 990; (d) Tang, Y. Q.;
Sattler, I.; Thiericke, R.; Grabley, S.; Feng, X. Z. Eur J
Org Chem 2001, 261; (e) Gan, C. Y.; Kam, T. S. Tetra-
hedron Lett 2009, 50, 1059; (f) Tokunaga, T.; Hume,
W. E.; Umezome, T.; Okazaki, K.; Ueki, Y.; Kuma-
gai, K.; Hourai, S.; Nagamine, J.; Seki, H.; Taiji, M.;
Noguchi, H.; Nagata, R. J Med Chem 2001, 44, 4641;
(g) Suzuki, H.; Morita, H.; Shiro, M.; Kobayashi, J.
Tetrahedron 2004, 60, 2489.
eroatom Chem 2003, 14, 266; (e) Ganzhorn, A. J.;
Hoflack, J.; Pelton, P. D.; Strasser, F.; Chanal, M.;
Piettre, S. R. Bioorg Med Chem 1998, 6, 1865; (f)
Frechette, R. F.; Ackerman, C.; Beers, S.; Look, R.;
Moore, J. Bioorg Med Chem Lett 1997, 7, 2169; (g)
Patel, D. V.; Rielly-Gauvin, K.; Ryono, D. E.; Free,
C. A.; Rogers, W. L.; Smith, S. A.; DeForrest, J. M.;
Oehl, R. S.; Petrillo, E. W. J Med Chem 1995, 38,
4557.
[8] Zhang, L.; Wang, S.; Sheng, E.; Zhou, S. Green Chem
2005, 7, 683.
[9] (a) Zhou, S.; Wang, S.; Yang, G.; Liu, X.; Sheng, E.;
Zhang, K.; Cheng, L.; Huang, Z. Polyhedron 2003, 22,
1019; (b) Xie, M.; Liu, X.; Wang, S.; Liu, L.; Wu, Y.;
Yang, G.; Zhou, S.; Sheng, E.; Huang, Z. Chin J Chem
2004, 22, 678.
[10] Zhang, L.; Wu, H.; Su, S.; Wang, S. Chin J Chem 2009,
27, 2061.
[11] Li, Q.; Wang, S.; Zhou, S.; Yang, G.; Zhu, X.; Liu, Y.
J Org Chem 2007, 72, 6763.
[3] Mustafa, A.; Sidky, M. M.; Soliman, F. M. Tetrahe-
dron 1966, 22, 393.
[4] Gurevich, P. A.; Akhmetova, G. Z.; Gubaidullin, A. T.;
Moskva, V. V.; Litvinov, I. A. Russ J Gen Chem 1998,
68, 1501.
[5] Shankar, J.; Karnakar, K.; Srinivas, B.; Nageswar, Y.
V. D. Tetrahedron Lett 2010, 51, 3938.
[6] Peng, L.; Wang, L. L.; Bai, J. F.; Jia, L. N.; Yang, Q,
C.; Huang, Q. C.; Xu, X. Y.; Wang, L. X. Tetrahedron
Lett 2011, 52, 1157.
[12] Wu, Q. M.; Zhou, J.; Yao, Z. G.; Xu, F.; Shen, Q. J Org
Chem 2010, 75, 7498.
[13] (a) Hayashi, M.; Nakamura, S. Angew Chem, Int Ed
2011, 50, 2249; (b) Spilling, C. D. J Am Chem Soc
2003, 125, 11453.
[7] (a) Hilderbrand, R. L. The Role of Phosphonates
in Living Systems; CRC Press: Boca Raton, FL,
1983; (b) Engel, R. Handbook of Organophospho-
rus Chemistry; Marcel Dekker: New York, 1992; (c)
Szyman´ska, A.; Szymczak, M.; Boryski, J.; Stawin´ski,
J.; Kraszewski, A.; Collu, G.; Sanna, G.; Giliberti, G.;
Loddo, R.; Colla, P. L. Bioorg Med Chem 2006, 14,
1924; (d) Shi, D.; Sheng, Z.; Liu, X.; Wu, H. Het-
[14] Zhang, K.; Zhang, W.; Wang, S.; Sheng, E.; Yang, G.;
Xie, M.; Zhou, S.; Feng, Y.; Mao, L.; Huang, Z. Dalton
Trans 2004, 1029.
[15] Bradley, D. C.; Ghotra, J. S.; Hart, F. A. J Chem Soc,
Dalton Trans 1973, 1021.
[16] Sheng, E.; Wang, S.; Yang, G.; Zhou, S.; Cheng,
L.; Zhang, K.; Huang, Z. Organometallics 2003, 22,
684.
Heteroatom Chemistry DOI 10.1002/hc