From allylic alcohols to chiral tertiary homoallylic alcohol: palladium-catalyzed asymmetric allylation of isatins

Article abstract of DOI:10.1016/j.tetasy.2009.04.012

A palladium-catalyzed asymmetric allylation of isatins with allylic alcohols as an allyl donor was developed by using chiral spiro phosphoramidite ligands. A variety of chiral tertiary homoallylic alcohols 3-allyl-3-hydroxy-2-oxindoles were prepared direc

Full text of DOI:10.1016/j.tetasy.2009.04.012

Tetrahedron: Asymmetry 20 (2009) 1254–1261
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
From allylic alcohols to chiral tertiary homoallylic alcohol:
palladium-catalyzed asymmetric allylation of isatins
*
Xiang-Chen Qiao, Shou-Fei Zhu, Qi-Lin Zhou
State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A palladium-catalyzed asymmetric allylation of isatins with allylic alcohols as an allyl donor was devel-
oped by using chiral spiro phosphoramidite ligands. A variety of chiral tertiary homoallylic alcohols 3-
allyl-3-hydroxy-2-oxindoles were prepared directly from allylic alcohols in one step with excellent yields
and moderate enantioselectivities. This represents the first catalytic asymmetric allylation of ketones
with allylic alcohol as the allylating agent.
Received 23 March 2009
Accepted 23 April 2009
Available online 3 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
presence of triethylborane, which is the first example of the asym-
metric allylation of ketones with allylic alcohols.9
Transition metal-catalyzed allylation of carbonyl compounds,
providing versatile and useful homoallylic alcohols, plays an
important role in modern organic synthesis. Over the past decades,
many efficient chiral catalysts have been developed for asymmet-
ric allylation of aldehydes with high regioselectivity as well as
enantioselectivity.1 In contrast, the asymmetric allylation of ke-
tones still remains a challenge, due to low reactivity of ketone to-
wards nucleophilic addition of allylating reagents. Only a few
transition metal-catalyzed allylations of ketones with allyl metal
reagents such as stannanes,2 boranes,3 and silanes4 as nucleophilic
allyl sources have afforded high enantioselectivities. However, the
allyl metals are air and moisture sensitive and require a multi-step
preparation, limiting their wide application in organic synthesis.
Thus, the search for more stable and easily available allylating
agents will advance the usefulness of this important transforma-
tion. Recently, Sigman et al.5 achieved the chromium-catalyzed
asymmetric allylation of aryl ketones with an allylic bromide as al-
lyl donor. This pioneering work has triggered the process of finding
better allyl donors instead of allyl metals. In view of the availability
and stability, the allylic alcohol is an ideal allylating agent. The di-
rect use of allylic alcohols can avoid the transformation of allylic
alcohols to their derivatives bearing a wasteful leaving group,
and enhances the synthetic application of the allylation reaction
of ketones. However in most cases, the hydroxy group of the allylic
alcohol is too unreactive to undergo heterolytic C–O bond cleavage.
By using activating reagents such as indium salts,6 diethyl zinc,7
and stannous chloride,8 the palladium-, nickel-, and iridium-cata-
lyzed allylations of ketones with allylic alcohols have been real-
ized. Herein we report the enantioselective palladium-catalyzed
allylation of isatin and its derivatives with allylic alcohols in the
2. Results and discussion
Chiral 3-allyl-3-hydroxy-2-oxindoles 3 are versatile intermedi-
ates for the preparation of many natural products and bioactive
compounds or potential pharmaceuticals (Fig. 1).10 Asymmetric
allylation of 2,3-indolinediones 1 (isatins) provides an efficient
route to generate useful 3-allyl-3-hydroxy-2-oxindole products.
By utilizing a chiral titanium complex as a Lewis acid catalyst,
Takayama et al.11 reported the asymmetric addition of allylstann-
ane to isatins with low enantioselectivity (42% ee). The highly
enantioselective allylation procedures for the preparation of 3-al-
lyl-3-hydroxy-2-oxindole compounds still remains a challenge.12
As a continuous effort on the palladium-catalyzed asymmetric
allylation of carbonyl compounds,13 we studied the palladium-cat-
alyzed asymmetric allylation of isatins with allylic alcohols
(Scheme 1). By using chiral spiro phosphoramidite ligands, a vari-
ety of 3-allyl-3-hydroxy-2-oxindoles were obtained in excellent
yields with moderate enantioselectivities.
In our initial studies, the palladium-catalyzed asymmetric ally-
lation of 1-methylindoline-2,3-dione 1a was carried out with
allylic alcohol 2a in THF at 30 °C with triethylborane as the activat-
ing agent (Scheme 1). Firstly, various chiral spiro ligands developed
in our laboratory14 were evaluated in this reaction. The phosphine
ligand 4, which gave good enantioselectivities in palladium-cata-
lyzed allylation of aldehydes with allylic alcohols,13 was found to
be reactive for the allylation reaction, giving the desired product,
3-allyl-3-hydroxy-1-methylindolin-2-one 3aa in high yield (85%),
while the enantioselectivity (35% ee) was low (Table 1, entry 1).
The phosphinite ligand 5 and phosphite ligand 6 were very unreac-
tive in the allylation reaction, giving very low yields (<20%) after
long reaction times (entries 2 and 3). The reactivity and enantiose-
lectivity of phosphoramidite ligands were quite different according
* Corresponding author. Tel.: +86 22 2350 0011; fax: +86 22 2350 6177.
E-mail address: qlzhou@nankai.edu.cn (Q.-L. Zhou).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.04.012

X.-C. Qiao et al. / Tetrahedron: Asymmetry 20 (2009) 1254–1261
1255
Br
HO
NHMe
HO
MeO
R
O
N
O
N
N
H
Br
N
H
H
convolutamydine A, R = COMe
convolutamydine E, R = CH2OH
donaxaridine
CPC-1
O
HO
HO
HO
N
O
N
R
O
S
O
OSO3
N
H
HO
S
N
H
SMe
O
O
N
HO
N
H
H
HO
HO
3'-hydroxyglucoisatisin
HIV protease inhibitor
dioxibrassinine
Figure 1. Natural products and bioactive compounds derived from 3-allyl-3-hydroxy-2-oxindoles.
3 eq. Et3B
HO
O
5 mol % Pd(OAc)2
10 mol % Ligand
R3
R3
*
R2
O
R2
OH
O
THF, 30 oC
N
N
R1
R1
2
3
1
O
O
P
O
P
P O
O
4
5
6
1
2
3
7a
R = R = Me, R = H
7b R1 = Me, R2 = Ph, R3 = H
R3
1
2
3
7c
R = Et, R = Ph, R = H
7d R1 = R2 = Ph, R3 = H
R1
R2
O
7e R1 = H, R2 = Ph, R3 = H
P
N
7f R1 = Me, R2 = p-MeOC6H4,3R3 = H
O
1
2
7g
R = Me, R = p-ClC6H4, R = H
R3
7h R1 = Me, R2 = 2,6-diMeC6H3, R3 = H
7i
R1-N-R2 = indolin-1-yl, R3 = H
7j R1 = Me, R2 = Ph, R3 = Me
7
Scheme 1. Palladium-catalyzed asymmetric allylation of isatins with allylic alcohols.
to the amine moiety of the ligand. Ligand 7a with a dimethylamino
group was inert for the reaction (entry 4). Interestingly, ligand 7b
produced by a simple replacement of one methyl group of ligand
7a with a phenyl afforded the allylation product 3aa in an almost
quantitative yield with 71% ee (entry 5). Noting that the introduc-
tion of an aromatic amine into the ligand had a notable effect on
the reactivity and enantioselectivity of the catalyst, we then syn-
thesized various phosphoramidite ligands 7c–7i bearing aryl
groups on the nitrogen atom. The experiments with those ligands
in the allylation reaction showed that the combination of a methyl
and a phenyl group on the nitrogen atom of ligand is necessary.
Changing the methyl group of ligand 7b to ethyl 7c, phenyl 7d or
hydrogen 7e either lowered the enantioselectivity (entry 6) and
reactivity of the reaction (entry 7) or fully prohibited the reaction
(entry 8). Modification of ligand 7b by varying the electronic and
steric properties of the N-phenyl of the ligand did not improve
the enantioselectivity of the reaction (entries 9–12). The steric ef-
fect on the spirobiindane scaffold was also examined. When two

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X.-C. Qiao et al. / Tetrahedron: Asymmetry 20 (2009) 1254–1261
Table 1
Palladium-catalyzed asymmetric allylation of 1a with allylic alcohol: optimizing the reaction conditionsa
3 eq. Et3B
O
HO
5 mol % Pd(OAc)2
10 mol % Ligand
*
OH
O
O
N
THF, 30 oC
N
2a
1a
3aa
Entry
Ligand
Solvent
Time (h)
Yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19d
(R)-4
(R)-5
(R)-6
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Et2O
Dioxane
12
48
48
48
4
85
Trace
18
Trace
97
96
75
Trace
99
99
89
99
95
80
99
99
87
85
97
35
—
38
—
71
60
65
—
63
70
47
52
30
57
66
55
37
53
67 (96)e
(R)-7a
(S)-7b
(R)-7c
(S)-7d
(S)-7e
(S)-7f
(S)-7g
(S)-7h
(S)-7i
(R)-7j
(S)-7b
(S)-7b
(S)-7b
(S)-7b
(S)-7b
(S)-7b
2
24
48
3
3
16
3
6
1.5
1.5
1.5
1.5
4
Diglyme
Toluene
CH2Cl2
THF
20
a
Reaction conditions: Pd(OAc)2/ligand/1a/allylic alcohol/Et3B = 0.0125/0.025/0.25/0.50/0.75 mmol, 2.0 mL solvent at 30 °C.
Isolated yield.
Determined by SFC using a Chiralpak AD-H column.
1 mol % catalyst was used.
After once recrystallization from ethyl acetate.
b
c
d
e
methyl groups were introduced onto the 6,60-position of the spiro
backbone of the ligand, the enantioselectivity of the reaction was
decreased to 30% ee (entry 13).
reaction conditions, the corresponding products were generally
obtained in excellent yields with moderate enantioselectivities
(entries 12–16). The absolute configuration of 3fa was determined
to be (R) by comparing the specific rotation of its deprotected prod-
With ligand 7b the reaction conditions including the palladium
source, solvent, and reaction temperature were carefully optimized
to improve the enantioselectivity; however, no enhancement was
observed (entries 14–18). It is worth mentioning that catalyst Pd/
7b has very high reactivity, the catalyst loading can be reduced
to 1 mol %, without diminishing the yield or enantioselectivity.
Furthermore, the enantiomeric purity of the allylation product
3aa was easily enhanced to 96% ee after one recrystallization from
ethyl acetate (entry 19).
Under the optimal reaction conditions, various isatin deriva-
tives were studied in the allylation reaction with allylic alcohols.
The effect of the N-protecting group of isatin on the reactivity
and enantioselectivity was evaluated first. With no N-protecting
group the isatin facilitates the allylation at both nitrogen and car-
bonyl group to generate bis-allylation product 1,3-diallyl-3-
hydroxyindolin-2-one 3ba in 90% yield with 63% ee (Table 2, entry
2). Other alkyl and aryl N-protecting groups with different steric
and electronic properties all gave the allylation products in slightly
lower enantioselectivities (entries 3–5 vs entry 1). When p-toly-
sulfonyl (Ts) was used as the N-protecting group, the allylation
reaction became sluggish and the yield as well as the ee value de-
creased (entry 6). We then investigated the allylation of 1-methy-
lindoline-2,3-dione bearing various substituents at the 5- or
7-position and found that the electronic property of the substitu-
ents had a negligible influence on the reactivity of the reaction
although the enantioselectivities of reactions were lower than that
in the reaction with N-methylisatin 1a (entries 7–11). The allylic
alcohols with alkyl or aromatic substituents at 2-position were also
suitable allylating agents for this reaction. Under the standard
uct 8 with the literature data {½a D26
ꢀ
¼ ꢁ10 (c 1.3, MeOH) for (S)-8}11
(Scheme 2).
3. Conclusion
In conclusion, we have reported a palladium-catalyzed asym-
metric allylation of isatins with allylic alcohols as the allyl donor.
By using chiral spiro phosphoramidite ligands containing an ani-
line moiety, various homoallylic alcohols such as 3-allyl-3-hydro-
xy-2-oxindoles were obtained directly from the allylic alcohols in
one step with excellent yields and moderate enantioselectivities.
This represents the first catalytic asymmetric allylation of ketones
with allylic alcohol as the allylating agent.
4. Experimental
4.1. General methods
All reactions and manipulations were performed using standard
Schlenk techniques. THF, diethyl ether, DME, and toluene, were
distilled from sodium benzophenone ketyl. CH2Cl2 and Et3N were
distilled over CaH2 under nitrogen atmosphere. DMSO was distilled
over CaH2 under reduced pressure and stored under nitrogen.
Pd(OAc)2, Et3B, isatin, 1b, and methallyl alcohol were purchased
from Acros or Aldrich Co. Ltd and used as received. The isatin deriv-
atives 1a, 1c–1k were prepared according to the literature proce-
dures.15 Pd2(dba)4 and Pd2(dba)3CHCl3 were prepared according
to the literature procedure.16 Chiral spiro phosphorous ligands

X.-C. Qiao et al. / Tetrahedron: Asymmetry 20 (2009) 1254–1261
1257
Table 2
Palladium-catalyzed asymmetric allylation of isatins with allylic alcoholsa
3 eq. Et3B
HO
O
5 mol % Pd(OAc)2
R3
R3
7b
10 mol % (S)-
*
OH
R2
O
R2
O
THF, 30 oC
N
N
R1
R1
2
3
1
Entry
R1
R2
R3
Prod.
Time (h)
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Me
H
CH2C(Me)3
Bn
Ph
Ts
Me
Me
Me
Me
Me
Me
Me
Me
H 1a
H 1b
H 1c
H 1d
H 1e
H 1f
5-Cl 1g
5-OMe 1h
5-Me 1i
7-Cl 1j
7-Me 1k
H 1a
H 2a
H 2a
H 2a
H 2a
H 2a
H 2a
H 2a
H 2a
H 2a
H 2a
H 2a
Me 2b
Ph 2c
4-MeOC6H4
2d
3aa
3bab
3ca
3da
3ea
3fa
3ga
3ha
3ia
4
20
4
12
5
20
2
3
3
2
2
97
90
85
99
93
74
98
96
99
89
98
99
93
88
71
63
62
56
62
47
46
53
54
52
64
48
57
50
3ja
3ka
3ab
3ac
3ad
3
5
5
H 1a
H 1a
15
Me
Me
H 1a
H 1a
4-F3CC6H4
2e
Bn 2f
3ae
3af
3
4
99
98
60
48
16
a
The reaction conditions were the same as those listed out in Table 1, entry 5.
Compound 3ba is 1,3-diallyl-3-hydroxyindolin-2-one.
b
mixture was stirred for 0.5 h at 0 °C, and then warmed to room
temperature and stirred overnight. The mixture was filtered under
nitrogen. The filtrate was evaporated under reduced pressure. The
residue was resolved in THF (10 mL), and was cooled to ꢁ78 °C,
treated with lithium N-methyl-N-phenylamide prepared from N-
methylaniline (1.95 mmol) and butyllithium (2.15 M solution in
hexane, 0.9 mL, 1.95 mmol) in 5 mL THF at ꢁ78 °C. The resulting
solution was warmed to room temperature and was stirred for
3 days. The solvent was removed in vacuum and the residue was
passed through a silica gel plug with ethyl acetate/petroleum ether
(1:25) to afford pure product N-methyl-N-phenyl-[(S)-1,10-spiro-
biindane-7,70-diyl]-phosphoramidite (S)-7b: 80% yield, white solid.
OH
OH
SmI2, HMPA
O
O
THF, reflux, 78%
N
H
N
Ts
8
3fa
47% ee
44% ee
[α]D22 = +4.8 (c 0.8, MeOH)
Scheme 2. Determination of the absolute configuration of 3fa.
Mp 186–187 °C. ½a D25
ꢀ
¼ ꢁ25:5 (c 1.0, CH2Cl2). 1H NMR (300 MHz,
CDCl3) d 7.23–7.05 (m, 5H), 6.98–6.84 (m, 5H), 6.54–6.49 (m,
1H), 3.02–2.92 (m, 2H), 2.77–2.69 (m, 2H), 2.21–2.11 (m, 5H),
1.98–1.85 (m, 2H). 13C NMR (75 MHz, CDCl3) d 147.8, 147.2,
146.8, 146.0, 145.8, 142.4, 140.5, 129.2, 128.7, 128.5, 122.2,
121.7, 121.3, 121.0, 119.3, 119.1, 59.1, 38.7, 38.2, 32.0, 31.1, 30.7.
4,13 and 517 were prepared according to the previously reported
procedures. The chiral phosphite ligand 6 can be purchased from
Strem Co. Ltd. Melting points were measured on a RY-I apparatus
and are uncorrected. 1H, 13C and 31P NMR spectra were recorded
on Varian Mercury 400 MHz or Bruker 300 MHz spectrometers.
Chemical shifts (d values) were reported in ppm down field from
31P NMR (121 MHz, CDCl3)
d 118.7 (s). EI-HRMS Calcd for
C24H22NO2P: 387.1388. Found: 387.1383.
internal Me4Si (1H and 13C NMR) and external 85% H3PO4 31P
(
NMR), respectively. Optical rotations were determined using a Per-
kin Elmer 341 MC polarimeter. Mass spectra were recorded on a
VG-7070E or VG ZAB-HS spectrometer. HPLC analyses were per-
formed on a Hewlett Packard Model HP 1100 Series or Waters
2996 instruments and SFC (Supercritical Fluid Chromatography)
analyses were performed on a Berger Analytix SFC instrument.
4.2.1. N-Ethyl-N-phenyl-[(R)-1,10-spirobiindane-7,70-diyl]-
phosphoramidite (R)-7c
Ligand (R)-7c was synthesized from (R)-SPINOL and lithium N-
ethyl-N-phenylamide by the same procedure as that for (S)-7b. 79%
yield, white solid, mp 186–188 °C. ½a D25
ꢀ
¼ þ89:8 (c 1.0, CH2Cl2). 1
H
NMR (400 MHz, CDCl3) d 7.36–7.20 (m, 5H), 7.15–6.99 (m, 5H),
6.69 (d, J = 7.6 Hz, 1H), 3.15–3.05 (m, 2H), 2.90–2.76 (m, 3H),
2.69–2.60 (m, 1H), 2.33–2.23 (m, 2H), 2.09–1.96 (m, 2H), 0.89 (t,
J = 6.8 Hz, 3H). 13C NMR (75 MHz, CDCl3) d 148.2, 146.1, 145.5,
145.0, 144.6, 142.4, 140.5, 129.2, 128.7, 128.4, 122.9, 122.2,
122.0, 121.7, 121.4, 120.8, 59.0, 40.1, 38.6, 38.2, 31.1, 30.7, 15.1.
4.2. General procedure for the synthesis of spiro
phosphoramidite ligands
A solution of (S)-1,10-spirobiindane-7,70-diol (SPINOL, 500 mg,
1.98 mmol), and Et3N (475 mg, 4.4 mmol) in THF (20 mL) was
cooled to 0 °C and a freshly distilled PCl3 (283 mg, 2.06 mmol)
was added with stirring. When the addition was over, the reaction
31P NMR (121 MHz, CDCl3)
C25H24NO2P: 401.1545. Found: 401.1547.
d 121.1 (s). EI-HRMS Calcd for

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X.-C. Qiao et al. / Tetrahedron: Asymmetry 20 (2009) 1254–1261
4.2.2. N,N-Diphenyl-[(S)-1,10-spirobiindane-7,70-diyl]-
phosphoramidite (S)-7d
127.3, 125.1, 121.9, 121.7, 121.1, 120.9, 120.3, 109.9, 109.6, 59.0,
46.5, 38.6, 38.2, 31.1, 30.7, 29.1; 31P NMR (121 MHz, CDCl3) d
120.7 (s); EI-HRMS Calcd for C25H22NO2P: 399.1388. Found:
399.1388.
Ligand (S)-7d was synthesized from (S)-SPINOL and lithium
N,N-diphenylamide by the same procedure as that for (S)-7b. 83%
yield, white solid, mp 138–140 °C. ½a D25
¼ ꢁ171 (c 1.0, CH2Cl2).
ꢀ
1H NMR (400 MHz, CDCl3)
d 7.23–7.02 (m, 10H), 6.94 (d,
4.2.7. N-Methyl-N-phenyl-[(R)-1,10-spirobiindane-6,60-dimethy
l-7,70-diyl]-phosphoramidite (R)-7j
J = 8.0 Hz, 1H), 6.73–6.71 (m, 5H), 3.09–3.01 (m, 2H), 2.89–2.73
(m, 3H), 2.24–2.13 (m, 2H), 2.01–1.93 (m, 1H), 1.78–1.71 (m,
1H). 13C NMR (75 MHz, CDCl3) d 146.3, 146.2, 144.8, 144.4, 144.3,
143.5, 143.4, 140.8, 139.6, 128.2, 127.6, 127.3, 124.0, 123.9,
122.7, 120.6, 120.0, 116.7, 58.0, 37.2, 36.9, 29.8, 29.4. 31P NMR
(121 MHz, CDCl3) d 117.0 (s). EI-HRMS Calcd for C29H24NO2P:
449.1545. Found: 449.1544.
Ligand (R)-7j was synthesized from (R)-SPINOL and lithium N-
methyl-N-phenylamide by the same procedure as that for (S)-7b.
72% yield, white solid, mp 162–164 °C. ½a D25
¼ þ219 (c 1.0, CH2Cl2).
ꢀ
1H NMR (400 MHz, CDCl3) d 7.33–7.22 (m, 4H), 7.08 (d, J = 7.6 Hz,
1H), 7.01–6.92 (m, 4H), 3.07–2.99 (m, 2H), 2.84–2.77 (m, 2H),
2.33–2.17 (m, 8H), 2.09–1.93 (m, 5H). 13C NMR (75 MHz, CDCl3)
d 147.4, 147.0, 146.0, 144.9, 143.2, 142.6, 142.4, 140.4, 130.2,
129.2, 121.5, 121.3, 120.6, 118.1, 117.9, 59.0, 38.7, 38.5, 31.0,
30.5, 30.1, 16.7, 16.6, 16.4. 31P NMR (121 MHz, CDCl3) d 116.0 (s).
EI-HRMS Calcd for C26H26NO2P: 415.1701. Found: 415.1703.
4.2.3. N-Methyl-N-(4-methoxyphenyl)-[(S)-1,10-spirobiindane-
7,70-diyl]-phosphoramidite (S)-7f
Ligand (S)-7f was synthesized from (S)-SPINOL and lithium N-
methyl-N-(4-methoxyphenyl)amide by the same procedure as that
for (S)-7b. 68% yield, white solid, mp 132–134 °C. ½a D25
¼ ꢁ20:4 (c
ꢀ
4.2.8. N-Phenyl-[(S)-1,10-spirobiindane-7,70-diyl]-
phosphoramidite (S)-7e
1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.23–7.16 (m, 3H),
7.12–7.03 (m, 3H), 6.96 (d, J = 7.6 Hz, 1H), 6.90 (d, J = 8.8 Hz, 2H),
6.69 (d, J = 8.0 Hz, 1H), 3.80 (s, 3H), 3.15–3.05 (m, 2H), 2.89–2.83
(m, 2H), 2.33–2.24 (m, 5H), 2.09–1.97 (m, 2H). 13C NMR (75 MHz,
CDCl3) d 155.7, 147.9, 146.0, 145.9, 145.6, 142.4, 140.6, 140.3,
139.9, 128.7, 122.0, 121.9, 121.6, 121.3, 120.9, 114.6, 59.0, 55.6,
38.6, 38.2, 32.9, 31.1, 30.7. 31P NMR (121 MHz, CDCl3) d 118.7 (s).
EI-HRMS Calcd for C25H24NO3P: 417.1494. Found: 417.1483.
Ligand (S)-7e was prepared according to the literature proce-
dures. To a mixture of ligand (S)-7a (520 mg, 1.6 mmol), 1H-tetra-
zole (112 mg, 1.6 mmol) in an argon filled Schlenk tube, aniline
(370 mg 4.0 mmol) and toluene (5 mL) were added, the reaction
mixture was stirred for 12 h at 120 °C. The solvent was removed
in vacuum and the residue was passed through a silica gel plug
with ethyl acetate/petroleum ether (1:20) to afford pure product
in 40% yield as a white solid, mp 64–66 °C. ½a D17
¼ ꢁ103 (c 0.5,
ꢀ
4.2.4. N-Methyl-N-(4-chlorophenyl)-[(S)-1,10-spirobiindane-
7,70-diyl]-phosphoramidite (S)-7g
CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.34–7.01 (m, 10H), 6.69 (d,
J = 6.0 Hz, 1H), 4.87 (s, 1H), 3.20 (br, 2H), 2.98–2.92 (m, 2H), 2.36
(br, 2H), 2.12 (br, 2H). 13C NMR (100 MHz, CDCl3) d 146.7, 144.7,
142.2, 142.1, 141.4, 140.9, 140.7, 139.9, 128.4, 127.7, 126.4,
121.3, 120.7, 120.1, 116.1, 116.0, 57.8, 37.5, 36.9, 29.9, 29.5. 31P
Ligand (S)-7g was synthesized from (S)-SPINOL and lithium N-
methyl-N-(4-chlorophenyl)amide by the same procedure as that
for (S)-7b. 67% yield, white solid, mp 164–166 °C. ½a D25
¼ þ8:9 (c
ꢀ
1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.30–7.21 (m, 3H),
7.16–7.04 (m, 5H), 6.96 (d, J = 8.0 Hz, 1H), 6.58 (d, J = 7.6 Hz, 1H),
3.16–3.06 (m, 2H), 2.90–2.83 (m, 2H), 2.33–2.24 (m, 5H), 2.08–
1.97 (m, 2H). 13C NMR (75 MHz, CDCl3) d 147.5, 146.0, 145.8,
145.6, 142.4, 140.4, 129.1, 128.8, 128.5, 127.2, 121.8, 121.4,
121.1, 120.2, 120.0, 59.0, 38.6, 38.2, 32.0, 31.9, 31.1, 30.7. 31P
NMR (162 MHz, CDCl3)
d 117.5 (s). ESI-HRMS Calcd for
[C23H20NO2PNa, M+Na]+: 396.1124. Found: 396.1123.
4.3. General procedure for the palladium-catalyzed asymmetric
allylation of isatins and analytical data for homoallylic alcohols
NMR (121 MHz, CDCl3)
C24H21NO2PCl: 421.0998. Found: 421.0993.
d
117.9 (s). EI-HRMS Calcd for
A mixture of Pd(OAc)2 (2.8 mg, 12.5
lmol) in THF (2.0 mL) in an argon filled Schlenk tube was stir-
lmol), (S)-7b (9.7 mg,
25
4.2.5. N-Methyl-N-(2,6-dimethylphenyl)-[(S)-1,10-
red at 30 °C for 10 min. The 1-methylindoline-2,3-dione (41 mg,
0.25 mmol), allyl alcohol (30 mg, 0.5 mmol), and Et3B (0.75 mL,
1.0 M in hexane, 0.75 mmol) were added sequentially. The result-
ing mixture was stirred at 30 °C until no more changes were ob-
served (monitored by TLC). The reaction mixture was diluted
with ethyl acetate (20 mL) and quenched by adding 3 g of silica
gel. After concentrated under reduced pressure, the crude product
was purified by a flash chromatography with ethyl acetate/petro-
leum ether (1:1.5) to afford (+)-3-allyl-3-hydroxy-1-methylindo-
spirobiindane-7,70-diyl]-phosphoramidite (S)-7h
Ligand (S)-7h was synthesized from (S)-SPINOL and lithium N-
methyl-N-(2,6-dimethylphenyl)amide by the same procedure as
that for (S)-7b. 70% yield, white solid, mp 130–132 °C.
½
a 2D5
ꢀ
¼ ꢁ105 (c 1.0, CH2Cl2). 1H NMR (300 MHz, CDCl3) d 7.18–
7.13 (m, 3H), 7.07–7.00 (m, 5H), 6.93 (d, J = 7.8 Hz, 1H), 3.13–
3.02 (m, 2H), 2.88–2.76 (m, 2H), 2.57 (s, 3H), 2.42 (s, 3H), 2.30–
2.18 (m, 5H), 2.10–1.90 (m, 2H). 13C NMR (75 MHz, CDCl3) d
149.0, 147.0, 146.8, 145.7, 145.4, 143.3, 142.9, 142.1, 140.8,
138.6, 129.2, 128.7, 128.2, 127.1, 121.8, 121.3, 120.8, 59.0, 38.4,
34.2, 30.9, 30.6, 19.9, 18.7. 31P NMR (121 MHz, CDCl3) d 124.0 (s).
EI-HRMS Calcd for C26H26NO2P: 415.1701. Found: 415.1709.
lin-2-one as
a pale yellow solid. The analytical data for
homoallylic alcohols are listed below.
4.3.1. (+)-3-Allyl-3-hydroxy-1-methylindolin-2-one 3aa
Pale yellow solid, 97% yield, 71% ee. Mp: 109–110 °C.
½
a 2D9
ꢀ
¼ þ21:4 (c 1.05, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.38
4.2.6. (Indolin-1-yl)-[(S)-1,10-spirobiindane-7,70-diyl]-
phosphoramidite [(S)-7i]
Ligand (S)-7i was synthesized from (S)-SPINOL and lithium
indolinate by the same procedure as that for (S)-7b. 70% yield,
(d, J = 7.6 Hz, 1H), 7.32 (t, J = 8.0 Hz, 1H), 7.09 (t, J = 7.6 Hz, 1H),
6.82 (d, J = 7.6 Hz, 1H), 5.69–5.59 (m, 1H), 5.12–5.07 (m, 2H),
3.17 (s, 3H), 2.74 (dd, J = 13.6, 6.4 Hz, 1H), 2.60 (dd, J = 13.2,
8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 177.9, 143.2, 130.6,
129.8, 129.6, 124.1, 123.0, 120.2, 108.3, 75.9, 42.9, 26.1. EI-HRMS
Calcd for C12H13NO2: 203.0946. Found: 203.0949. SFC condition:
white solid, mp 160–162 °C. ½a D25
ꢀ
¼ ꢁ144 (c 1.0, CH2Cl2); 1H NMR
(400 MHz, CDCl3) d 7.26–7.22 (m, 1H), 7.11–6.96 (m, 7H), 6.82 (t,
J = 7.2 Hz, 1H), 6.60 (t, J = 4.8 Hz, 1H), 3.58–3.51 (m, 1H), 3.15–
3.05 (m, 2H), 2.90–2.80 (m, 3H), 2.73–2.65 (m, 1H), 2.32–2.23
(m, 3H), 2.07–1.97 (m, 2H); 13C NMR (75 MHz, CDCl3) d 148.2,
147.8, 147.5, 146.2, 145.9, 145.6, 142.5, 140.7, 131.4, 128.2,
Chiralpak AD-H column, CO2/2-propanol = 90:10, flow rate
=
2.0 mL/min, pressure = 100 bar, wavelength = 210 nm, tR = 8.9 min
(major), and tR = 9.9 min (minor).

X.-C. Qiao et al. / Tetrahedron: Asymmetry 20 (2009) 1254–1261
1259
4.3.2. (+)-1,3-Diallyl-3-hydroxyindolin-2-one 3ba
4.3.7. (+)-3-Allyl-5-chloro-3-hydroxy-1-methylindolin-2-one
3ga
Pale yellow solid, 90% yield, 63% ee. Mp: 112–114 °C.
½
a 2D9
ꢀ
¼ þ18:9 (c 0.98, CH2Cl2). 1H NMR (300 MHz, CDCl3) d 7.42
Pale yellow solid, 98% yield, 46% ee. Mp: 132–134 °C.
(d, J = 7.2 Hz, 1H), 7.31 (t, J = 8.1 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H),
6.82 (d, J = 7.5 Hz, 1H), 5.87–5.74 (m, 1H), 5.67–5.51 (m, 1H),
5.26–5.19 (m, 2H), 5.13–5.05 (m, 2H), 4.47–4.38 (m, 1H), 4.21–
4.12 (m, 1H), 3.77 (s, 1H), 2.84–2.77 (m, 1H), 2.72–2.65 (m, 1H).
13C NMR (75 MHz, CDCl3) d 177.7, 142.5, 131.1, 130.6, 129.8,
129.5, 124.1, 123.0, 120.3, 117.6, 109.3, 76.0, 43.0, 42.3. ESI-HRMS
Calcd for [C14H15NO2Na, M+Na]+: 252.0995. Found: 252.1002. SFC
condition: Chiralpak AD-H column, CO2/2-propanol = 90:10, flow
½
a 2D9
ꢀ
¼ þ2:7 (c 0.98, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.35 (d,
J = 2.0 Hz, 1H), 7.28 (dd, J = 8.4, 2.0 Hz, 1H), 6.74 (d, J = 8.0 Hz,
1H), 5.62–5.51 (m, 1H), 5.10–5.06 (m, 2H), 4.16 (s, 1H), 3.14 (s,
3H), 2.74 (dd, J = 13.2, 6.4 Hz, 1H), 2.60 (dd, J = 9.2, 8.4 Hz, 1H).
13C NMR (75 MHz, CDCl3) d 177.7, 141.7, 131.5, 130.0, 129.4,
128.5, 124.7, 120.7, 109.3, 76.0, 42.8, 26.3. EI-HRMS Calcd for
C12H12NO2Cl: 237.0557. Found: 237.0556. SFC condition: Chiralcel
OD-H column, CO2/2-propanol = 85:15, flow rate = 2.0 mL/min,
pressure = 100 bar, wavelength = 254 nm, tR = 3.8 min (major),
and tR = 5.0 min (minor).
rate = 2.0 mL/min,
pressure = 100 bar,
wavelength = 210 nm,
tR = 10.4 min (major), and tR = 11.6 min (minor).
4.3.3. (+)-3-Allyl-3-hydroxy-1-neopentylindolin-2-one 3ca
4.3.8. (+)-3-Allyl-3-hydroxy-5-methoxy-1-methylindolin-2-one
3ha
White solid, 85% yield, 62% ee. Mp: 98–100 °C. ½a D29
¼ þ37:3 (c
ꢀ
1.35, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.39 (d, J = 7.6 Hz, 1H),
7.29–7.26 (m, 1H), 7.06 (t, J = 7.2 Hz, 1H), 6.89 (d, J = 8.0 Hz, 1H),
5.64–5.54 (m, 1H), 5.12–5.05 (m, 2H), 3.74 (d, J = 4.4 Hz, 1H),
3.65 (d, J = 14.0 Hz, 1H), 3.24 (d, J = 14.0 Hz, 1H), 2.81–2.75 (m,
1H), 2.69–2.64 (m, 1H), 0.99 (s, 9H). 13C NMR (75 MHz, CDCl3) d
179.4, 144.4, 130.7, 129.9, 129.2, 124.0, 122.7, 120.3, 109.6, 75.7,
51.9, 43.3, 34.5, 28.5. ESI-HRMS Calcd for [C16H21NO2Na, M+Na]+:
282.1465. Found: 282.1466. HPLC condition: Chiralpak AD-H col-
umn, n-hexane/2-PrOH = 90:10, flow rate = 1.0 mL/min, wave-
length = 254 nm, tR = 6.2 min (major), tR = 7.0 min (minor).
Pale yellow solid, 96% yield, 53% ee. Mp: 142–144 °C.
½
a 2D9
ꢀ
¼ þ8:0 (c 1.33, CH2Cl2). 1H NMR (400 MHz, D6-DMSO) d 6.94
(d, J = 2.0 Hz, 1H), 6.87–6.82 (m, 1H), 6.06 (s, 1H), 5.44–5.34 (m,
1H), 4.94–4.89 (m, 2H), 3.71 (s, 3H), 3.48 (s, 1H), 3.03 (s, 3H),
2.64–2.59 (m, 1H), 2.47–2.42 (m, 1H). 13C NMR (75 MHz, D6-
DMSO) d 176.6, 155.4, 136.4, 132.1, 131.6, 118.9, 113.1, 111.1,
108.6, 75.4, 55.5, 42.0, 25.7. ESI-HRMS Calcd for [C13H15NO3Na,
M+Na]+: 256.0944. Found: 256.0943. SFC condition: Chiralcel
OD-H column, CO2/2-propanol = 85:15, flow rate = 2.0 mL/min,
pressure = 100 bar, wavelength = 254 nm, tR = 3.9 min (major),
and tR = 5.0 min (minor).
4.3.4. (+)-3-Allyl-1-benzyl-3-hydroxyindolin-2-one 3da
Pale yellow solid, 99% yield, 56% ee. Mp: 146–148 °C.
4.3.9. (+)-3-Allyl-3-hydroxy-1,5-dimethylindolin-2-one 3ia
½
a 2D9
ꢀ
¼ þ5:2 (c 1.55, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.42–
Pale yellow solid, 99% yield, 54% ee. Mp: 138–140 °C.
7.40 (d, J = 7.2 Hz, 1H), 7.34–7.22 (m, 5H), 7.21–7.17 (t, J = 7.6 Hz,
1H), 7.08–7.03 (t, J = 7.6 Hz, 1H), 6.70–6.67 (d, J = 8.0 Hz, 1H),
5.65–5.54 (m, 1H), 5.16–5.00 (m, 3H), 4.73–4.68 (d, J = 16.0 Hz,
1H), 3.99 (br, 1H), 2.87–2.82 (dd, J = 13.2, 6.4 Hz, 1H), 2.76–2.70
(dd, J = 13.2, 8.4 Hz, 1H). 13C NMR (75 MHz, CDCl3) d 178.1,
142.4, 135.5, 130.6, 129.8, 129.5, 128.8, 127.7, 127.3, 124.2,
123.1, 120.5, 109.5, 76.1, 43.8, 43.0. ESI-HRMS Calcd for
[C18H17NO2Na, M+Na]+: 302.1151. Found: 302.1147. SFC condi-
tion: Chiralcel OD-H column, CO2/2-propanol = 88:12, flow
½
a 2D9
ꢀ
¼ þ7:0 (c 1.33, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.20 (s,
1H), 7.08 (d, J = 8.0 Hz, 1H), 6.68 (d, J = 8.0 Hz, 1H), 5.61–5.50 (m,
1H), 5.08–5.00 (m, 2H), 4.35 (s, 1H), 3.11 (s, 3H), 2.77–2.72 (m,
1H), 2.65–2.59 (m, 1H), 2.32 (s, 3H). 13C NMR (75 MHz, CDCl3) d
178.1, 140.8, 132.6, 130.8, 130.0, 129.7, 124.9, 119.9, 108.1, 76.2,
42.8, 26.1, 21.1. ESI-HRMS Calcd for [C13H15NO2Na, M+Na]+:
240.0995. Found: 240.1001. SFC condition: Chiralcel OD-H column,
CO2/2-propanol = 85:15, flow rate = 2.0 mL/min, pressure = 100 -
bar, wavelength = 254 nm, tR = 3.2 min (major), and tR = 3.8 min
(minor).
rate = 2.0 mL/min,
pressure = 100 bar,
wavelength = 210 nm,
tR = 8.7 min (major), and tR = 9.6 min (minor).
4.3.10. (+)-3-Allyl-7-chloro-3-hydroxy-1-methylindolin-2-one
4.3.5. (+)-3-Allyl-3-hydroxy-1-phenylindolin-2-one 3ea
3ja
Pale yellow solid, 93% yield, 62% ee. Mp: 110 °C. ½a D29
ꢀ
¼ þ23:3 (c
Pale yellow solid, 89% yield, 52% ee. Mp: 104–106 °C.
1.25, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.52–7.35 (m, 6H), 7.23
(t, J = 7.6 Hz, 1H), 7.12 (t, J = 7.2 Hz, 1H), 6.78 (d, J = 7.6 Hz, 1H),
5.66–5.56 (m, 1H), 5.15–5.08 (m, 2H), 4.02 (s, 1H), 2.88–2.74 (m,
2H). 13C NMR (75 MHz, CDCl3) d 177.3, 143.3, 134.0, 130.5, 129.6,
129.5, 129.4, 128.2, 126.5, 124.4, 123.5, 120.5, 109.7, 76.2, 43.5.
ESI-HRMS Calcd for [C17H15NO2Na, M+Na]+: 288.0995. Found:
288.1001. SFC condition: Chiralcel OD-H column, CO2/2-propa-
nol = 85:15, flow rate = 2.0 mL/min, pressure = 100 bar, wave-
length = 210 nm, tR = 5.0 min (major), and tR = 6.8 min (minor).
½
a 2D9
ꢀ
¼ þ11:3 (c 1.40, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.26
(d, J = 7.2 Hz, 1H), 7.21 (d, J = 8.4 Hz, 1H), 6.98 (t, J = 8.0 Hz, 1H),
5.57–5.46 (m, 1H), 5.05–5.02 (m, 2H), 4.39 (d, J = 3.2 Hz, 1H),
3.50 (s, 3H), 2.74–2.69 (m, 1H), 2.64–2.58 (m, 1H). 13C NMR
(75 MHz, CDCl3) d 178.5, 139.0, 132.8, 131.8, 130.1, 123.9, 122.7,
120.5, 115.8, 75.6, 43.1, 29.5. EI-HRMS Calcd for C12H12NO2Cl:
237.0557. Found: 237.0558. SFC condition: Chiralcel OD-H column,
CO2/2-propanol = 85:15, flow rate = 2.0 mL/min, pressure = 100 -
bar, wavelength = 254 nm, tR = 3.4 min (major), and tR = 3.8 min
(minor).
4.3.6. (R)-3-Allyl-3-hydroxy-1-tosylindolin-2-one 3fa
Pale yellow solid, 74% yield, 47% ee. Mp: 90–92 °C. ½a D29
ꢀ
¼ þ5:2
4.3.11. (+)-3-Allyl-3-hydroxy-1,7-dimethylindolin-2-one 3ka
(c 1.33, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.92–7.86 (m, 3H),
7.36 (t, J = 7.6 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 7.19 (t, J = 7.2 Hz,
1H), 5.34–5.23 (m, 1H), 4.91–4.83 (m, 2H), 3.50 (s, 1H), 2.64–
2.51 (m, 2H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3) d 176.6,
146.1, 138.8, 135.0, 130.6, 130.1, 129.3, 128.9, 128.2, 125.5,
124.7, 121.4, 113.8, 76.2, 43.8, 22.0. ESI-HRMS Calcd for
[C18H17NO4SNa, M+Na]+: 366.0770. Found: 366.0776. HPLC condi-
tion: Chiralcel OD-H column, n-hexane/2-propanol = 90:10, flow
Pale yellow solid, 98% yield, 64% ee. Mp: 116–118 °C.
½
a 2D9
ꢀ
¼ þ15:8 (c 1.33, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.23 (d,
J = 7.2 Hz, 1H), 7.05 (d, J = 7.6 Hz, 1H), 6.97 (t, J = 7.6 Hz, 1H), 5.65–
5.55 (m, 1H), 5.11–5.06 (m, 2H), 3.44 (s, 4H), 2.73–2.68 (m, 1H),
2.63–2.57 (m, 1H), 2.54 (s, 3H). 13C NMR (75 MHz, CDCl3) d 177.5,
161.3, 139.9, 132.4, 129.6, 122.0, 121.0, 119.2, 74.1, 42.2, 28.5,
18.0. ESI-HRMS Calcd for [C13H15NO2Na, M+Na]+: 240.0995. Found:
240.1003. SFC condition: Chiralcel OD-H column, CO2/2-propa-
nol = 85:15, flow rate = 2.0 mL/min, pressure = 100 bar, wave-
length = 254 nm, tR = 4.0 min (major), and tR = 4.5 min (minor).
rate = 1.0 mL/min,
wavelength = 254 nm,
tR = 13.2 min
(R),
tR = 15.3 min (S).

1260
X.-C. Qiao et al. / Tetrahedron: Asymmetry 20 (2009) 1254–1261
4.3.12. (+)-3-Hydroxy-1-methyl-3-(2-methylallyl)indolin-2-one
3ab
129.4, 128.5, 126.3, 124.7, 123.3, 117.2, 108.7, 77.0, 43.8, 43.6,
26.4. ESI-HRMS Calcd for [C19H19NO2Na, M+Na]+: 316.1308. Found:
316.1314. SFC condition: Chiralcel OD-H column, CO2/2-propanol =
85:15, flow rate = 2.0 mL/min, pressure = 100 bar, wave-
length = 254 nm, tR = 7.0 min (major), and tR = 8.6 min (minor).
Pale yellow solid, 99% yield, 48% ee. Mp: 92–94 °C. ½a D29
¼ þ15:1
ꢀ
(c 1.18, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.39 (d, J = 7.2 Hz, 1H),
7.32 (t, J = 8.0 Hz, 1H), 7.09 (t, J = 7.6 Hz, 1H), 6.82 (d, J = 8.0 Hz,
1H), 4.75 (s, 1H), 4.61 (s, 1H), 3.16 (d, J = 1.6 Hz, 3H), 2.70 (s, 2H),
1.52 (s, 3H). 13C NMR (75 MHz, CDCl3) d 178.5, 143.6, 139.4,
130.1, 129.8, 124.7, 123.2, 116.0, 108.6, 76.8, 46.3, 26.3, 24.2. ESI-
HRMS Calcd for [C13H15NO2Na, M+Na]+: 240.0995. Found:
240.0996. SFC condition: Chiralcel OD-H column, CO2/2-propa-
nol = 85:15, flow rate = 2.0 mL/min, pressure = 100 bar, wave-
length = 254 nm, tR = 3.5 min (major), and tR = 4.1 min (minor).
4.4. Deprotection of 3fa with SmI2/HMPA)18
A 0.1 M solution of SmI2 in THF (4.2 mL, 0.42 mmol) and HMPA
(0.15 mL, 0.88 mmol) were added to 3fa (70 mg, 0.21 mmol) at
room temperature. After refluxing for 5 h, the reaction mixture
was quenched with 10% HCl, and then extracted with EtOAc. The
organic layer was concentrated under reduced pressure. The crude
product was purified by a flash chromatography with ethyl ace-
tate/petroleum ether (1:1) to afford (R)-3-allyl-3-hydroxyindolin-
2-one (8) as a pale yellow solid with 78% yield and 44% ee. Mp:
4.3.13. (+)-3-Hydroxy-1-methyl-3-(2-phenylallyl)indolin-2-one
3ac
Pale yellow solid, 93% yield, 57% ee. Mp: 137–139 °C.
½
a 2D9
ꢀ
¼ þ6:0 (c 1.55, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.22–
132–134 °C. ½a 2D2
ꢀ
¼ þ4:8 (c 0.8, MeOH). 1H NMR (400 MHz, CDCl3)
7.15 (m, 5H), 7.02–6.99 (m, 2H), 6.90 (t, J = 7.6 Hz, 1H), 6.65 (d,
J = 8.0 Hz, 1H), 5.05 (s, 1H), 4.97 (s, 1H), 4.14 (s, 1H), 3.32–3.21
(m, 2H), 2.87 (s, 3H). 13C NMR (100 MHz, CDCl3) d 178.2, 143.5,
141.1, 129.6, 129.4, 128.0, 127.5, 126.6, 124.9, 123.0, 122.9,
118.3, 108.3, 77.0, 44.6, 26.0. ESI-HRMS Calcd for [C18H17NO2Na,
M+Na]+: 302.1151. Found: 302.1149. SFC condition: Chiralcel
OD-H column, CO2/2-propanol = 85:15, flow rate = 2.0 mL/min,
pressure = 100 bar, wavelength = 254 nm, tR = 6.5 min (major),
and tR = 7.6 min (minor).
d 8.35 (s, 1H), 7.30 (d, J = 7.2 Hz, 1H), 7.18 (t, J = 7.2 Hz, 1H), 7.00 (t,
J = 7.6 Hz, 1H), 6.81 (d, J = 8.4 Hz, 2H), 5.65–5.54 (m, 1H), 5.06 (d,
J = 8.8 Hz, 1H), 5.02 (s, 1H), 3.38 (s, 1H), 2.71–2.64 (dd, J = 13.2,
6.4 Hz, 1H), 2.58–2.51 (dd, J = 13.2, 8.4 Hz, 1H). HPLC condition:
Chiralpak AD-H column, n-hexane/2-propanol = 90:10, flow
rate = 1.0 mL/min,
wavelength = 210 nm,
tR = 10.5 min
(S),
tR = 16.3 min (R).
Acknowledgments
4.3.14. (+)-3-Hydroxy-3-(2-(4-methoxyphenyl)allyl)-1-methylin
dolin-2-one 3ad
We thank the National Natural Science Foundation of China
(Grant Nos. 20532010, 20702025), the Major Basic Research Devel-
opment Program (Grant No. 2006CB806106), the ‘111’ Project
(B06005) of the Ministry of Education of China for financial
support.
Pale yellow solid, 88% yield, 50% ee. Mp: 126–128 °C.
½
a 2D9
ꢀ
¼ þ1:1 (c 1.70, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.21–
7.16 (m, 2H), 6.93–6.88 (m, 3H), 6.68–6.61 (m, 3H), 4.94 (dd,
J = 9.2, 1.2 Hz, 1H), 4.85 (d, J = 4.4 Hz, 1H), 3.73 (s, 3H), 3.34–3.29
(m, 1H), 3.18 (d, J = 13.2 Hz, 1H), 2.82 (s, 3H). 13C NMR (100 MHz,
CDCl3) d 178.2, 159.0, 143.4, 142.8, 133.6, 129.5, 127.8, 124.9,
123.0, 122.9, 117.0, 113.4, 108.2, 77.0, 55.5, 44.6, 26.0. ESI-HRMS
Calcd for [C19H19NO3Na, M+Na]+: 332.1257. Found: 332.1261. SFC
condition: Chiralcel OD-H column, CO2/2-propanol = 85:15, flow
References
1. For reviews see: (a) Yanagisawa, A. In Comprehensive Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
Heidelberg, 1999. Chapter 27; (b) Denmark, S. E.; Fu, J. Chem. Rev.
2003, 103, 2763–2793; (c) Yamamoto, H.; Wadamoto, M. Chem. Asian J.
2007, 2, 692–698; (d) Shibasaki, M.; Kanai, M. Chem. Rev. 2008, 108,
2853–2873.
rate = 2.0 mL/min, pressure = 100 bar, wavelength
= 254 nm,
tR = 8.1 min (major), and tR = 9.5 min (minor).
4.3.15. (+)-3-Hydroxy-1-methyl-3-(2-(4-
(trifluoromethyl)phenyl) allyl)indolin-2-one 3ae
2. For representative examples, see: (a) Casolari, S.; D0Addario, D.; Tagliavini,
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6. (a) Jang, T.-S.; Keum, G.; Kang, S. B.; Chung, B. Y.; Kim, Y. Synthesis 2003, 775–
779; (b) Hirashita, T.; Kambe, S.; Tsuji, H.; Omori, H.; Araki, S. J. Org. Chem.
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3718.
Pale yellow solid, 99% yield, 60% ee. Mp: 154–156 °C.
½
a 2D9
ꢀ
¼ þ3:0 (c 1.90, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.38 (d,
J = 7.6 Hz, 2H), 7.21–7.13 (m, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.88 (t,
J = 7.6 Hz, 1H), 6.64 (d, J = 7.6 Hz, 1H), 5.10 (s, 1H), 5.08 (s, 1H),
3.32 (d, J = 13.2, 1H), 3.25 (d, J = 13.2 Hz, 1H), 2.88 (s, 3H). 13C
NMR (100 MHz, CDCl3) d 178.1, 144.8, 143.2, 142.5, 129.8, 129.4,
129.2, 129.1, 127.0, 125.7, 124.9, 123.1, 120.0, 108.4, 77.0, 44.5,
26.0. ESI-HRMS Calcd for [C19H16F3NO2Na, M+Na]+: 370.1025.
Found: 370.1028. SFC condition: Chiralcel OD-H column, CO2/2-
propanol = 85:15, flow rate = 2.0 mL/min, pressure = 100 bar,
wavelength = 254 nm, tR = 4.2 min (major), and tR = 5.0 min
(minor).
8. (a) Masuyama, Y.; Tsunoda, T.; Kurusu, Y. Chem. Lett. 1989, 1647–1650; (b)
Takahara, J. P.; Masuyama, Y.; Kurusu, Y. Chem. Lett. 1991, 879–882; (c)
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4.3.16. (+)-3-(2-Benzylallyl)-3-hydroxy-1-methylindolin-2-one
3af
Pale yellow solid, 98% yield, 48% ee. Mp: 144–146 °C.
½
a 2D9
ꢀ
¼ þ9:7 (c 1.80, CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.43 (d,
J = 7.2 Hz, 1H), 7.38–7.34 (m, 1H), 7.24 (t, J = 7.2 Hz, 2H), 7.19–
7.12 (m, 2H), 6.98 (d, J = 6.8 Hz, 2H), 6.84 (d, J = 8.0 Hz, 1H), 4.78
(s, 1H), 4.67 (d, J = 1.2 Hz, 1H), 4.07 (s, 1H), 3.15 (s, 3H), 3.10 (d,
J = 15.2 Hz, 1H), 2.95 (d, J = 15.6 Hz, 1H), 2.70 (s, 2H). 13C NMR
(100 MHz, CDCl3) d 178.5, 143.7, 142.5, 139.3, 130.1, 130.0,

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