Palladium-catalyzed asymmetric allylic amination of racemic butadiene monoxide with isatin derivatives

Article abstract of DOI:10.1039/c5ob00663e

Isatins and their derivatives are important functional moities and building blocks in pharmaceutical and synthetic chemistry. Numerous enantioselective transformations at the C-3 carbonyl group have been well developed. However, the asymmetric substitution reaction with isatins and their derivatives as nucleophiles based on the free N-H groups has been less studied due to the relatively weaker nucleophilicity resulting from the two electron-withdrawing carbonyl groups. In this paper, a palladium-catalyzed asymmetric allylic amination of racemic butadiene monoxide with isatin derivatives using a chiral phosphoramidite olefin hybrid ligand has been successfully developed under mild conditions. A variety of chiral amino alcohols were afforded in 55-87% yields with 10/1->20/1 regioselectivity ratios and 80-97% ees.

Full text of DOI:10.1039/c5ob00663e

Organic &
Biomolecular Chemistry
View Article Online
View Journal
PAPER
Palladium-catalyzed asymmetric allylic amination
of racemic butadiene monoxide with isatin
derivatives†
Cite this: DOI: 10.1039/c5ob00663e
Gen Li, Xiangqing Feng* and Haifeng Du*
Isatins and their derivatives are important functional moities and building blocks in pharmaceutical and
synthetic chemistry. Numerous enantioselective transformations at the C-3 carbonyl group have been
well developed. However, the asymmetric substitution reaction with isatins and their derivatives as
nucleophiles based on the free N–H groups has been less studied due to the relatively weaker nucleo-
philicity resulting from the two electron-withdrawing carbonyl groups. In this paper, a palladium-cata-
lyzed asymmetric allylic amination of racemic butadiene monoxide with isatin derivatives using a chiral
phosphoramidite olefin hybrid ligand has been successfully developed under mild conditions. A variety
of chiral amino alcohols were afforded in 55–87% yields with 10/1->20/1 regioselectivity ratios and
80–97% ees.
Received 3rd April 2015,
Accepted 16th April 2015
DOI: 10.1039/c5ob00663e
www.rsc.org/obc
tutions with diverse nucleophiles.4 Aliphatic amines,5 phthala-
mides,6 oxazolidinones,7 and succinimides8 were the most
Introduction
Isatins and their derivatives are important functional moieties often used amine nucleophiles. Recently, Mangion and co-
widely present in natural products and biologically active workers reported a Pd-catalyzed dynamic asymmetric allylic
compounds, which have attracted intensive attention in both amination of vinyl epoxide with hydrazines and hydroxyl-
synthetic and pharmaceutical chemistry.1 Meanwhile, they are amines as nucleophiles.9 In 2011, Trost and co-workers
also important building blocks, which can be transformed to reported an interesting asymmetric amination of divinyl car-
numerous useful optically active compounds. Undoubtedly, bonates with isatins for the synthesis of chiral diene
the most fascinating transformation occurred enantioselec- ligands.10a Recently, Shi and co-workers developed an efficient
tively at the highly reactive C-3 carbonyl group.2 The asym- enantioselective allylic amination of Morita–Baylis–Hillman
metric substitution reaction with isatins and their derivatives carbonates and aromatic aldehydes with isatins in the pres-
as nucleophiles based on the free N–H groups also seems to ence of cinchona alkaloids.10b These reports represent the few
be an efficient approach for the synthesis of optically active asymmetric transformations with isatins as nucleophiles.
compounds. However, due to the relatively weak nucleophili-
The field of chiral olefin ligands has witnessed an extremely
city that resulted from the two electron-withdrawing carbonyl rapid growth in recent years.11,12 As a novel class of ligands,
groups, such an enantioselective reaction has seldom been phosphine–alkene hybrid ligands have also been developed
reported. The majority of transformations based on the N–H and successfully applied in a wide range of asymmetric reac-
groups are the introduction of protecting groups on the nitro- tions. Notably, these ligands exhibited obvious advantages
gen atom.
over other ligand types in some cases.13 As part of our general
Palladium-catalyzed asymmetric allylic amination has been interest in exploring novel chiral olefin ligands, we have deve-
one of the most useful methods for the synthesis of optically loped a variety of chiral P/terminal-olefin ligands, which were
active amines.3 Racemic vinyl epoxides were an important highly effective for Pd-catalyzed asymmetric allylic alkyl-
class of substrates for the Pd-catalyzed asymmetric substi- ations.14 Herein, we report our efforts on the Pd-catalyzed
asymmetric amination of butadiene monoxide with isatins
and their derivatives as nucleophiles using a chiral phosphor–
amidite olefin hybrid ligand.
Beijing National Laboratory of Molecular Sciences, CAS Key Laboratory of Molecular
Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences,
Beijing 100190, China. E-mail: haifengdu@iccas.ac.cn; Fax: +86-10-62554449;
Tel: +86-10-62652117
†Electronic supplementary information (ESI) available: Procedure for the syn-
Results and discussion
thesis of isatin derivatives, characterization of the products along with the NMR
The Pd-catalyzed asymmetric allylic amination of isatin deriva-
tive 1a and racemic butadiene monoxide 2 (2.0 equiv.) at room
spectra. CCDC 1037747. For ESI and crystallographic data in CIF or other elec-
tronic format see DOI: 10.1039/c5ob00663e
This journal is © The Royal Society of Chemistry 2015
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
Table 2 Asymmetric allylic aminations of butadiene monoxide with
isatin derivativesa
Entry
Product (4)
Yieldb (%)
eec (%)
b/ld
Scheme 1 Asymmetric allylic amination of isatin derivatives.
Table 1 Optimization of reaction conditionsa
1
2
4a: R = H
4b: R = Cl
84
61
92
91
12/1
11/1
Entry
Solvent
Pd complex
Conv.b(%)
eec(%)
b/ld
1
2
3
4
THF
[PdCl(η3-C3H5)]2
[PdCl(η3-C3H5)]2
[PdCl(η3-C3H5)]2
[PdCl(η3-C3H5)]2
[PdCl(η3-C3H5)]2
[PdCl(η3-C3H5)]2
[PdCl(η3-C3H5)]2
Pd2(dba)3·CHCl3
80
84
15
86
45
Trace
60
87
84
69
82
82
—
92
92
12/1
4/1
6/1
3/1
5/1
—
11/1
12/1
3
4
5
4c: R = OMe
4d: R = Me
4e: R = Cl
81
87
55
90
91
92
14/1
13/1
10/1
Dioxane
Toluene
EtOAc
Et2O
CH3CN
THF
5
6
7e
8e
THF
95
a Reactions with 1a (0.2 mmol), 2 (0.4 mmol), Pd (0.012 mmol), ligand
3a (0.012 mmol) and solvent (1.0 mL) at room temperate for 14 h
unless otherwise noted. b Determined by crude 1H NMR. c Determined
by chiral HPLC. d Determined by crude 1H NMR. e The reaction was
performed at 0 °C for 14 h.
6
7
4f: R = Cl
4g: R = Me
59
62
91
91
10/1
12/1
temperature was initially examined using 6 mol% of chiral
phosphoramidite olefin ligand 3a and 3 mol% of [PdCl-
(η3-C3H5)]2. We were pleased to find that this reaction went
smoothly to furnish the branched substituted chiral amino
alcohol 2a as a major product in 80% conversion with 87% ee
and 12/1 regioselectivity ratio (Scheme 1). When ligand 3b was
used, no desired product was observed, which indicates the
importance of the terminal olefin moiety in ligand 3a for the
observed high activity and selectivity.
8
9
4h: R = H
4i: R = Me
67
75
94
97
>20/1
>20/1
10
11
12
4j: R = H
4k: R = Me
4l: R = Cl
68
65
69
93
89
90
>20/1
>20/1
>20/1
The reaction conditions were next optimized to further
improve the reactivity and enantioselectivity. Solvents were
found to have a large influence on this reaction, and THF proved
to be the optimal solvent to give better conversion, ees, and
regioselectivity ratios (Table 1, entries 1–6). Lowering the temp-
erature to 0 °C gave 92% ee with 60% conversion (Table 1,
entry 7). When Pd2(dba)3·CHCl3 was used as the catalyst pre-
cursor, the desired product 4a was obtained in 95% conversion
with 93% ee and a 12/1 regioselectivity ratio (Table 1, entry 8).
Various isatin derivatives 1a–i were subsequently subjected
to the Pd-catalyzed asymmetric amination of racemic buta-
diene monoxide 2 under the optimal reaction conditions. It
was found that all these reactions proceeded well to give
chiral amino alcohols 4a–i in 55–87% yields with 90–97% ees
and 10/1->20/1 b/l ratios (Table 2, entries 1–9). In comparison
13
4m
65
80
>20/1
14
15
4n: R = Me
4o: R = Cl
71
76
87
93
>20/1
>20/1
a Reactions with 1a (0.4 mmol),
2 (0.8 mmol), Pd2(dba)3·CHCl3
(0.012 mmol), 3a (0.024 mmol) in THF (2.0 mL). b Isolated yield for the
branched product. c Determined by chiral HPLC. d Determined by
crude 1H NMR.
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Organic & Biomolecular Chemistry
Paper
2-(4-Chloro-1-(1-hydroxybut-3-en-2-yl)-2-oxoindolin-3-ylidene)-
malononitrile (4b). Yellow solid; mp. 164–166 °C; [α]2D0 = −32.0
(c 0.2, CH2Cl2) (91% ee); IR (film) 3531, 2222, 1725, 1601 cm−1
;
1H NMR (400 MHz, CDCl3): δ 7.44 (dd, J = 8.0, 8.0 Hz, 1H),
7.10 (d, J = 8.0 Hz, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.01 (ddd, J =
17.6, 11.0, 4.8 Hz, 1H), 5.40 (d, J = 11.0 Hz, 1H), 5.31 (d, J =
17.6 Hz, 1H), 4.87–4.85 (m, 1H), 4.06–4.04 (m, 1H),
4.03–4.01 (m, 1H), 2.26 (brs, 1H); 13C NMR (100 MHz,
CDCl3): δ 163.6, 147.6, 146.6, 137.6, 135.5, 130.5, 126.0,
120.2, 117.3, 113.3, 112.4, 109.9, 86.0, 61.6, 58.4; HRMS
(ESI): Calcd for C15H10N3O2ClNa (M + Na): 322.0354; found:
322.0356.
Fig. 1 X-ray structure of compound 4f.
2-(1-(1-Hydroxybut-3-en-2-yl)-5-methoxy-2-oxoindolin-3-ylidene)-
malononitrile (4c). Purple solid; mp. 157–159 °C; [α]2D0 = −48.0
1
(c 0.2, CH2Cl2) (90% ee); IR (film) 3504, 2237, 1714 cm−1; H
NMR (400 MHz, CDCl3): δ 7.67 (s, 1H), 7.08 (d, J = 8.8 Hz, 1H),
6.86 (d, J = 8.8 Hz, 1H), 5.97 (ddd, J = 17.6, 10.8, 4.8 Hz, 1H),
5.37 (d, J = 10.8 Hz, 1H), 5.30 (d, J = 17.6 Hz, 1H), 4.76 (m, 1H),
4.20–4.18 (m, 1H), 4.07–4.00 (m, 1H), 3.82 (s, 3H), 2.31–2.27
(m, 1H); 13C NMR (100 MHz, CDCl3): δ 165.2, 156.5, 149.8,
140.4, 130.9, 124.6, 119.9, 119.2, 112.7, 112.6, 111.1, 110.9,
82.9, 62.0, 58.2, 56.2; HRMS (ESI): Calcd for C16H13N3O3Na
(M + Na): 318.0849; found: 318.0846.
with the substrates 1a–g containing two cyano groups, the sub-
strates 1h–i bearing only one cyano group gave better ees and
regioselectivity ratios (Table 2, entries 1–7 vs. 8–9). Isatins 1j–o
were also suitable substrates for this reaction to afford the
desired chiral amino alcohols 4j–o as the predominant pro-
ducts in 65–76% yields with 80–93% ees (Table 2, entries
10–15). The absolute configuration of product 4 was tentatively
assigned as R by analogy with compound (R)-4f, which was
determined by its X-ray structure (Fig. 1).
2-(1-(1-Hydroxybut-3-en-2-yl)-5-methyl-2-oxoindolin-3-ylidene)-
malononitrile (4d). Brown solid; mp. 165–167 °C; [α]2D0 = −31.0
1
(c 0.2, CH2Cl2) (91% ee); IR (film) 3565, 2230, 1713 cm−1; H
NMR (400 MHz, CDCl3): δ 7.92 (s, 1H), 7.33 (d, J = 8.4 Hz, 1H),
6.85 (d, J = 8.4 Hz, 1H), 5.99 (ddd, J = 17.6, 10.8, 5.6 Hz, 1H),
5.37 (d, J = 10.8 Hz, 1H), 5.30 (d, J = 17.6 Hz, 1H), 4.81–4.79
(m, 1H), 4.20–4.16 (m, 1H), 4.05–4.01 (m, 1H), 2.49 (brs, 1H),
2.35 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 163.5, 149.6, 144.2,
138.5, 134.0, 130.8, 127.3, 119.8, 118.8, 112.6, 111.7, 111.0,
Experimental section
General experimental procedure for the Pd-catalyzed
asymmetric allylic amination of racemic butadiene monoxide
with isatins (Table 2, entry 1)
To a Schlenk tube was added Pd2(dba)3·CHCl3 (0.0062 g, 82.3, 61.8, 58.0, 21.1; HRMS (ESI): Calcd for C16H13O2N3Na
0.012 mmol), ligand 3a (0.013 g, 0.024 mmol) and dry THF (M + Na): 302.0900; found: 302.0896.
(0.5 mL) under an argon atmosphere. The resulting mixture
2-(5-Chloro-1-(1-hydroxybut-3-en-2-yl)-2-oxoindolin-3-ylidene)-
was stirred for 15 min at room temperature followed by malononitrile (4e). Purple solid; mp. 169–172 °C; [α]2D0 = −45.0
the addition of 2-(2-oxoindolin-3-ylidene)malononitrile 1a (c 0.2, CH2Cl2) (92% ee); IR (film) 3406, 1731, 1614 cm−1; H
1
(0.078 g, 0.4 mmol) then racemic butadiene monoxide 2 NMR (400 MHz, CDCl3): δ 8.11 (s, 1H), 7.48 (d, J = 8.2 Hz, 1H),
(0.056 g, 0.8 mmol) in THF (0.5 mL) was added to the reaction 6.94 (d, J = 8.2 Hz, 1H), 5.99 (ddd, J = 16.0, 12.0, 4.0 Hz, 1H),
mixture slowly. The reaction mixture was stirred at 0 °C for 5.40 (d, J = 12.0 Hz, 1H), 5.31 (d, J = 16.0 Hz, 1H), 4.86–4.84
14 h, and the solvent was removed under reduced pressure. (m, 1H), 4.06–4.05 (m, 1H), 4.03–4.01 (m, 1H), 2.14 (brs, 1H);
The crude residue was purified by flash chromatography on 13C NMR (100 MHz, CDCl3): δ 163.0, 148.3, 144.7, 137.2, 130.5,
silica gel using PE/EtOAc (2/1) as the eluent to give the desired 129.8, 126.6, 120.2, 119.7, 113.1, 112.1, 110.6, 84.4, 61.7, 58.1;
4a as a red solid (0.089 g, 84% yield, 92% ee).
2-(1-(1-Hydroxybut-3-en-2-yl)-2-oxoindolin-3-ylidene)malono- found: 322.0350.
nitrile (4a). Red solid; mp. 148–150 °C; [α]2D0 = −36.0 (c 0.2,
2-(6-Chloro-1-(1-hydroxybut-3-en-2-yl)-2-oxoindolin-3-ylidene)-
CHCl3) (92% ee); IR (film) 3420, 2230, 1723, 1611, 1595 cm−1 malononitrile (4f). Red solid; mp. 152–154 °C; [α]D20 = −52.0
1H NMR (400 MHz, CDCl3): δ 8.15 (d, J = 8.0 Hz, 1H), 7.54 (dd, (c 0.2, CH2Cl2) (91% ee); IR (film) 3555, 2228, 1715, 1607,
J = 8.0, 8.0 Hz, 1H), 7.15 (dd, J = 8.0, 8.0 Hz, 1H), 6.96 (d, J = 1594 cm−1 1H NMR (400 MHz, CDCl3): δ 8.07 (d, 1H, J =
HRMS (ESI): Calcd for C15H10N3O2ClNa (M + Na): 322.0354;
;
;
8.0 Hz, 1H), 6.02 (ddd, J = 17.6, 12.0, 8.0 Hz, 1H), 5.39 (d, J = 8.2 Hz, 1H), 7.12 (d, J = 8.2 Hz, 1H), 7.0 (s, 1H), 6.0 (ddd, J =
12.0 Hz, 1H), 5.31 (d, J = 17.6 Hz, 1H), 4.81 (m, 1H), 4.28–4.17 17.6, 10.4, 5.6 Hz, 1H), 5.42 (d, J = 10.4 Hz, 1H), 5.33 (d, J =
(m, 1H), 4.07–4.04 (m, 1H), 2.21–2.17 (brs, 1H); 13C NMR 17.6 Hz, 1H), 4.84–4.82 (m, 1H), 4.21–4.20 (m, 1H), 4.05–4.02
(100 MHz, CDCl3): δ 163.4, 149.5, 146.2, 137.8, 130.7, 127.1, (m, 1H), 2.14–2.12 (m, 1H); 13C NMR (100 MHz, CDCl3):
124.1, 119.9, 118.7, 112.5, 111.9, 110.9, 82.8, 61.7, 58.0; HRMS δ 163.2, 147.8, 144.1, 130.2, 127.6, 124.1, 120.2, 116.9, 112.56,
(ESI): Calcd for C15H11O2N3Na (M + Na): 288.0744; found: 112.2, 110.6, 82.8, 61.6, 57.9; HRMS (ESI): Calcd for
288.0740.
C15H10O2N3ClNa (M + Na): 322.0354; found: 322.0354.
This journal is © The Royal Society of Chemistry 2015
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
2-(1-(1-Hydroxybut-3-en-2-yl)-6-methyl-2-oxoindolin-3-ylidene)-
4-Chloro-1-(1-hydroxybut-3-en-2-yl)indoline-2,3-dione
(4l).
malononitrile (4g). Purple solid; mp. 154–157 °C; [α]2D0 = −38.0 Red solid; mp. 118–120 °C; [α]D20 = +55.0 (c 0.2, CH2Cl2) (90%
(c 0.2, CH2Cl2) (91% ee); IR (film) 3524, 2226, 1716, 1616, ee); IR (film) 3462, 1739, 1600 cm−1
;
1H NMR (400 MHz,
1
1592 cm−1; H NMR (400 MHz, CDCl3): δ 8.02 (d, J = 8.0 Hz, CDCl3): δ 7.45 (dd, J = 8.0, 8.0 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H),
1H), 6.94 (d, J = 8.2 Hz, 1H), 6.75 (s, 1H), 6.03 (ddd, J = 16.8, 6.93 (d, J = 8.0 Hz, 1H), 6.01 (ddd, J = 17.6, 10.8, 6.4 Hz, 1H),
10.8, 6.0 Hz, 1H), 5.40 (d, J = 10.0 Hz, 1H), 5.31 (d, J = 16.8 Hz, 5.37 (d, J = 10.4 Hz, 1H), 5.32 (d, J = 16.8 Hz, 1H), 4.83–4.79
1H), 4.80–4.75 (m, 1H), 4.26–4.19 (m, 1H), 4.07–4.01 (m, 1H), (m, 1H), 4.22–4.20 (m, 1H), 4.06–4.02 (m, 1H), 2.92–2.90 (m,
2.44 (s, 3H), 2.27–2.22 (m, 1H); 13C NMR (100 MHz, CDCl3): 1H); 13C NMR (100 MHz, CDCl3): δ 180.0, 158.1, 152.0, 138.5,
δ 164.5, 150.4, 149.1, 146.7, 130.9, 127.4, 125.0, 119.8, 116.4, 134.2, 130.9, 125.8, 119.8, 115.2, 110.5, 61.8, 58.4. HRMS
112.8, 112.3, 111.1, 81.2, 61.9, 58.2, 23.4; HRMS (ESI): Calcd (ESI): Calcd for C12H10NO3Na (M + Na): 274.0241; found:
for C16H13N3O2ClNa (M + Na): 302.0900; found: 302.0903.
274.0242.
(Z)-2-(1-(1-Hydroxybut-3-en-2-yl)-2-oxoindolin-3-ylidene)-
1-(1-Hydroxybut-3-en-2-yl)-5-methoxyindoline-2,3-dione (4m).
acetonitrile (4h). Yellow solid; mp. 122–125 °C; [α]2D0 = −26.0 Red solid; mp. 122–125 °C; [α]D20 = +54.0 (c 0.2, CH2Cl2) (80%
(c 0.2, CH2Cl2) (94% ee); IR (film) 3446, 2216, 1716, 1606 cm−1
;
ee); IR (film) 3458, 1732, 1624, 1596 cm−1; H NMR (400 MHz,
1
1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 7.6 Hz, 1H), 7.41 (dd, CDCl3): δ 7.13 (s, 1H), 7.10 (d, J = 8.2 Hz, 1H), 6.91 (d, J =
J = 8.0, 7.2 Hz, 1H), 7.13 (dd, J = 8.0, 7.2 Hz, 1H), 6.91 (d, J = 8.2 Hz, 1H), 6.01 (ddd, J = 17.6, 10.8, 6.4 Hz, 1H), 5.40 (d, J =
8.0 Hz, 1H), 6.31 (s, 1H), 6.0 (ddd, J = 17.2, 10.8, 5.6 Hz, 1H), 10.8 Hz, 1H), 5.35 (d, J = 17.6 Hz, 1H), 4.77–4.76 (m, 1H),
5.33 (d, J = 10.8 Hz, 1H), 5.26 (d, J = 17.2 Hz, 1H), 4.82–4.78 4.18–4.16 (m, 1H), 4.06–4.02 (m, 1H), 3.79 (s, 1H), 3.06–3.04
(m, 1H), 4.20–4.13 (m, 1H), 4.07–4.01 (m, 1H), 2.88–2.84 (m, (m, 1H); 13C NMR (100 MHz, CDCl3): δ 183.4, 159.1, 156.6,
1H); 13C NMR (100 MHz, CDCl3): δ 166.3, 144.7, 143.4, 133.8, 144.6, 131.2, 124.7, 119.4, 118.6, 113.4, 109.7, 62.0, 58.1, 56.1;
131.3, 125.3, 123.6, 119.7, 119.2, 116.2, 111.0, 98.1, 62.2, 58.0; HRMS (ESI): Calcd for C13H13O4NNa (M + Na): 270.0737;
HRMS (ESI): Calcd for C14H12O2N2Na (M + Na): 263.0791; found: 270.0738.
found: 263.0794.
(Z)-2-(1-(1-Hydroxybut-3-en-2-yl)-5-methyl-2-oxoindolin-3-ylidene)- Yellow solid; mp. 166–169 °C; [α]2D0 = +45.0 (c 0.2, CH2Cl2)
acetonitrile (4i). Red solid; mp. 116–119 °C; [α]2D0 = −14.0 (87% ee); IR (film) 3406, 1731, 1721, 1614 cm−1 1H NMR
(c 0.2, CH2Cl2) (97% ee); IR (film) 3446, 2216, 1716, 1615 cm−1
(400 MHz, CDCl3): δ 7.50 (d, J = 7.6 Hz, 1H), 6.91 (d, J = 7.6 Hz,
1-(1-Hydroxybut-3-en-2-yl)-6-methylindoline-2,3-dione (4n).
;
;
1H NMR (400 MHz, CDCl3): δ 7.90 (s, 1H), 7.20 (d, J = 8.0 Hz, 1H), 6.79 (s, 1H), 6.0 (ddd, J = 18.8, 12.0, 6.4 Hz, 1H), 5.35
1H), 6.79 (d, J = 8.0 Hz, 1H), 6.31 (s, 1H), 6.0 (ddd, J = 16.8, (d, J = 12.0 Hz, 1H), 5.32 (d, J = 18.8 Hz, 1H), 4.77–4.76
10.4, 6.0 Hz, 1H), 5.33 (d, J = 10.4 Hz, 1H), 5.25 (d, J = 17.6 Hz, (m, 1H), 4.20–4.05 (m, 1H), 4.04–4.02 (m, 1H), 3.02 (brs, 1H);
1H), 4.75–4.74 (m, 1H), 4.18–4.13 (m, 1H), 4.07–4.02 (m, 1H), 13C NMR (100 MHz, CDCl3): δ 182.4, 159.6, 151.3, 150.8,
2.77–2.76 (m, 1H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3): 131.2, 125.74, 124.7, 119.4, 116.0, 112.8, 62.0, 58.2, 23.3;
δ 166.3, 143.7, 142.6, 134.3, 133.4, 131.5, 125.8, 119.8, 119.1, HRMS (ESI): Calcd for C13H13O3NNa (M + Na): 254.0788;
116.3, 110.7, 97.7, 62.4, 58.2, 21.1; HRMS (ESI): Calcd for found: 254.0790.
C15H14O2N2Na (M + Na): 277.0948; found: 277.0951.
6-Chloro-1-(1-hydroxybut-3-en-2-yl)indoline-2,3-dione
(4o).
1-(1-Hydroxybut-3-en-2-yl)indoline-2,3-dione
(4j). Yellow Yellow solid; mp. 127–129 °C; [α]2D0 = +65.0 (c 0.2, CH2Cl2)
solid; mp. 147–149 °C; [α]2D0 = +30.0 (c 0.2, CH2Cl2) (93% ee); (93% ee); IR (film) 3461, 1743, 1608 cm−1; H NMR (400 MHz,
1
IR (film) 3447, 2216, 1716, 1617 cm−1 1H NMR (400 MHz, CDCl3): δ 7.54 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 8.0 Hz, 1H), 7.02
;
CDCl3): δ 7.63 (d, J = 8.0 Hz, 1H), 7.57 (dd, J = 7.6, 7.6 Hz, 1H), (s, 1H), 6.01 (ddd, J = 17.2, 10.6, 5.6 Hz, 1H), 5.40 (d, J = 10.6
7.0 (dd, J = 7.6, 7.6 Hz, 1H), 7.0 (d, J = 8.0 Hz, 1H), 6.04 (ddd, Hz, 1H), 5.35 (d, J = 17.2 Hz, 1H), 4.83–4.78 (m, 1H), 4.20–4.05
J = 16.4, 10.6, 6.0 Hz, 1H), 5.38 (d, J = 10.6 Hz, 1H), 5.34 (d, J = (m, 1H), 4.04–4.02 (m, 1H), 2.85 (brs, 1H); 13C NMR (100 MHz,
17.2 Hz, 1H), 4.81–4.77 (m, 1H), 4.20–4.20 (m, 1H), 4.09–4.05 CDCl3): δ 181.7, 159.0, 151.8, 144.8, 130.7, 126.7, 124.3, 120.0,
(m, 1H), 2.76 (brs, 1H); 13C NMR (100 MHz, CDCl3): δ 183.1, 116.4, 113.1, 61.7, 58.2; HRMS (ESI): Calcd for C12H10O3NClNa
158.9, 150.9, 138.4, 131.1, 125.7, 124.1, 119.6, 118.1, 112.2, (M + Na): 274.0241; found: 274.0242.
62.1, 60.6, 58.2; HRMS (ESI): Calcd for C12H11O3NNa (M + Na):
240.0631; found: 240.0634.
1-(1-Hydroxybut-3-en-2-yl)-4-methylindoline-2,3-dione (4k).
Conclusions
Red solid; mp. 130–132 °C; [α]2D0 = +48.0 (c 0.2, CH2Cl2) (89%
1
ee); IR (film) 3443, 1732, 1641, 1601 cm−1; H NMR (400 MHz, A palladium-catalyzed asymmetric allylic amination of racemic
CDCl3): δ 7.40 (dd, J = 8.0, 8.0 Hz, 1H), 6.89 (d, J = 8.0 Hz, 1H), butadiene monoxide with isatins and their derivatives as
6.80 (d, J = 8.0 Hz, 1H), 6.02 (ddd, J = 16.4, 10.4, 5.6 Hz, 1H), nucleophiles under mild reaction conditions was successfully
5.35 (d, J = 10.4 Hz, 1H), 5.30 (d, J = 16.4 Hz, 1H), 4.78–4.74 realized using a chiral P/terminal-olefin ligand. A variety of
(m, 1H), 4.22–4.17 (m, 1H), 4.06–4.02 (m, 1H), 3.05 (brs, 1H), optically active chiral amino alcohols can be obtained in
2.56 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 183.5, 158.9, 150.9, 55–87% yields with 80–97% ees and 10/1->20/1 regioselectivity
141.7, 137.5, 131.3, 126.4, 119.3, 116.3, 109.3, 62.0, 58.3, 18.4; ratios. Further expansion of the application of the chiral
HRMS (ESI): Calcd for C13H13O3NNa (M + Na): 254.0788; P/olefin ligands in other asymmetric reactions is currently
found: 254.0787.
underway in our laboratory.
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Organic & Biomolecular Chemistry
Paper
9 I. Ian Mangion, N. Strotman, M. Drahl, J. Imbriglio and
E. Guidry, Org. Lett., 2009, 11, 3258–3260.
Acknowledgements
The authors are thankful for the financial support from the 10 (a) B. M. Trost, A. C. Burns and T. Tautz, Org. Lett., 2011,
National Natural Science Foundation of China (21222207) and
the 973 program (2011CB808600).
13, 4566–4569; (b) M.-X. Zhao, M.-X. Chen, W.-H. Tang,
D.-K. Wei, T.-L. Dai and M. Shi, Eur. J. Org. Chem., 2012,
3598–3606.
11 (a) T. Hayashi, K. Ueyama, N. Tokunaga and K. Yoshida,
J. Am. Chem. Soc., 2003, 125, 11508–11509; (b) C. Fischer,
C. Defieber, T. Suzuki and E. M. Carreira, J. Am. Chem. Soc.,
2004, 126, 1628–1629.
Notes and references
1 (a) A. F. Tarek, Int. J. Res. Pharm. Sci., 2010, 12, 113–126;
(b) K. Mazaahir, Med. Chem. Res., 2013, 22, 2717–2723; 12 For reviews on chiral olefin ligands, see: (a) F. Glorius,
(c) B. V. Silva, J. Braz. Chem. Soc., 2013, 24, 707–720.
2 (a) G. S. Singh and Z. Y. Desta, Chem. Rev., 2012, 112, 6104–
6155; (b) M. A. Borad, M. N. Bhoi, N. P. Prajapati and
H. D. Patel, Synth. Commun., 2014, 44, 1043–1057.
3 (a) B. M. Trost, Chem. Rev., 1996, 96, 395–422;
(b) B. M. Trost and M. L. Crawley, Chem. Rev., 2003, 103,
2921–2944; (c) B. M. Trost, M. R. Machacek and A. Aponick,
Acc. Chem. Res., 2006, 39, 747–760; (d) Z. Lu and S. Ma,
Angew. Chem., Int. Ed., 2008, 47, 258–297; (e) H. Miyabe,
A. Matsumura, K. Yoshida, M. Yamauchi and Y. Takemoto,
Synlett, 2004, 2123–2126.
Angew. Chem., Int. Ed., 2004, 43, 3364–3366;
(b) J. B. Johnson and T. Rovis, Angew. Chem., Int. Ed., 2008,
47, 840–871; (c) C. Defieber, H. Grützmacher and
E. M. Carreira, Angew. Chem., Int. Ed., 2008, 47, 4482–4502;
(d) R. Shintani and T. Hayashi, Aldrichimica Acta, 2009, 42,
31–35; (e) C.-G. Feng, M.-H. Xu and G.-Q. Lin, Synlett, 2011,
1345–1348; (f) P. Tian, H.-Q. Dong and G.-Q. Lin, ACS
Catal., 2012, 2, 95–119; (g) X. Feng and H. Du, Asian J. Org.
Chem., 2012, 1, 204–213; (h) Y. Li and M.-H. Xu, Chem.
Commun., 2014, 50, 3771–3782; (i) X. Feng and H. Du,
Chin. J. Org. Chem., 2015, 35, 259–272.
4 (a) J. He, J. Ling and P. Chiu, Chem. Rev., 2014, 114, 8037– 13 For examples on chiral P/olefin ligands, see: (a) P. Maire,
8128; (b) J. Shim and Y. Yamamoto, J. Org. Chem., 1998, 63,
3067–3071.
5 (a) B. M. Trost, D. R. Fandrick, T. Brodmann and
D. T. Stiles, Angew. Chem., Int. Ed., 2007, 46, 6123–6125;
(b) J. Llaveria, Y. Díaz, M. I. Matheu and S. Castillón,
Eur. J. Org. Chem., 2011, 1514–1519.
6 (a) B. M. Trost and R. C. Bunt, Angew. Chem., Int. Ed. Engl.,
1996, 35, 99–102; (b) B. M. Trost and R. C. Lemoine, Tetra-
hedron, 1996, 37, 9161–9164; (c) B. M. Trost, R. C. Bunt and
T. L. Calkins, J. Am. Chem. Soc., 2000, 122, 5968–5976;
(d) B. M. Trost, D. B. Horne and M. J. Woltering, Angew.
Chem., Int. Ed., 2003, 42, 5987–5990; (e) B. M. Trost,
D. B. Horne and M. J. Woltering, Chem. – Eur. J., 2006, 12,
6607–6620; (f) J. Llaveria and S. Castillo, Org. Lett., 2009,
S. Deblon, F. Breher, J. Geier, C. Böhler, H. Rüegger,
H. Schönberg and H. Grützmacher, Chem. – Eur. J., 2004,
10, 4198–4205; (b) R. Shintani, W.-L. Duan, T. Nagano,
A. Okada and T. Hayashi, Angew. Chem., Int. Ed., 2005, 44,
4611–4614; (c) W.-L. Duan, H. Iwamura, R. Shintani and
T. Hayashi, J. Am. Chem. Soc., 2007, 129, 2130–2138;
(d) R. T. Stemmler and C. Bolm, Synlett, 2007, 1365–1370;
(e) T. Minuth and M. M. K. Boysen, Org. Lett., 2009, 11,
4212–4215; (f) C. Defieber, M. A. Ariger, P. Moriel and
E. M. Carreira, Angew. Chem., Int. Ed., 2007, 46, 3139–3143;
(g) M. Roggen and E. M. Carreira, J. Am. Chem. Soc., 2010,
132, 11917–11919; (h) J. Y. Hamilton, D. Sarlah and
E. M. Carreira, J. Am. Chem. Soc., 2014, 136, 3006–
3009.
11, 205–208; (g) B. M. Trost, B. M. Boyle, W. Torres and 14 For chiral P/olefin ligands developed by our group:
M. K. Ameriks, Chem. – Eur. J., 2011, 17, 7890–7903.
7 Y. Natori, T. Imahori, K. Murakami, Y. Yoshimura,
S. Nakagawa, A. Kato, I. Adachi and H. Takahata, Bioorg.
Med. Chem. Lett., 2011, 21, 738–741.
8 (a) R. Alibes, P. Bayon, P. March, M. Figueredo, J. Font and
D. G. Galvez, Org. Lett., 2005, 7, 5107–5109; (b) G. David,
M. Galvez and J. Font, J. Org. Chem., 2009, 74, 6199–6211.
(a) Z. Liu and H. Du, Org. Lett., 2010, 12, 3054–3057;
(b) Z. Cao, Y. Liu, Z. Liu, X. Feng, M. Zhuang and H. Du,
Org. Lett., 2011, 13, 2164–2165; (c) Z. Cao, Z. Liu, Y. Liu and
H. Du, J. Org. Chem., 2011, 76, 6401–6404; (d) Z. Liu, Z. Cao
and H. Du, Org. Biomol. Chem., 2011, 9, 5369–5372;
(e) Y. Liu, Z. Cao and H. Du, J. Org. Chem., 2012, 77, 4479–
4482; (f) Y. Liu and H. Du, Org. Lett., 2013, 15, 740–744.
This journal is © The Royal Society of Chemistry 2015
Org. Biomol. Chem.