Diastereo- and enantioselective construction of oxindole-fused spirotetrahydrofuran scaffolds through palladium-catalyzed asymmetric [3+2] cycloaddition of vinyl cyclopropanes and isatins

Article abstract of DOI:10.1021/om400473p

A novel asymmetric formal [3+2] cycloaddition of vinyl cyclopropanes and isatins in the presence of Pd₂(dba)₃ and the chiral imidazoline-phosphine ligand (aS,R,R)-L3 has been developed, affording the corresponding highly functionalized oxindole-fused spirotetrahydrofuran frameworks in good yields along with good diastereo- and high enantioselectivities under mild conditions.

Full text of DOI:10.1021/om400473p

Article
pubs.acs.org/Organometallics
Diastereo- and Enantioselective Construction of Oxindole-Fused
Spirotetrahydrofuran Scaffolds through Palladium-Catalyzed
Asymmetric [3+2] Cycloaddition of Vinyl Cyclopropanes and Isatins
Liang-yong Mei,† Yin Wei,*,‡ Qin Xu,*,† and Min Shi*,†,‡
†Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry & Molecular Engineering, East China
University of Science and Technology, 130 Mei-Long Road, Shanghai 200237, China
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354
Fenglin Road, Shanghai 200032, China
S
* Supporting Information
ABSTRACT: A novel asymmetric formal [3+2] cycloaddition of
vinyl cyclopropanes and isatins in the presence of Pd2(dba)3 and the
chiral imidazoline-phosphine ligand (aS,R,R)-L3 has been developed,
affording the corresponding highly functionalized oxindole-fused
spirotetrahydrofuran frameworks in good yields along with good
diastereo- and high enantioselectivities under mild conditions.
INTRODUCTION
■
Finding simple and sustainable strategies for obtaining the rich
structural diversity and complexity of natural molecules has
always drawn tremendous interest from synthetic and medicinal
chemists, especially with respect to biologically active
compounds.1 As a privileged structure moiety in many natural
products and clinical pharmaceuticals,2 the spirooxindoles have
recently become one of the most prevailing and attractive
synthetic subjects, and many elegant approaches have been
developed for their syntheses.3 Among the different types of
spirooxindoles, the oxindole-fused spirotetrahydrofuran is a
particularly intriguing scaffold, which is characterized by a large
spectrum of considerable bioactivities, such as antibacterial,
anticancer, and growth inhibitory activities (Figure 1).4 The
preparation of 3,2′-tetrahydrofuryl spirooxindoles has been
addressed in previous studies, such as transition metal-catalyzed
reactions,5 organocatalyst-mediated processes,6 and other
Figure 1. Bioactive compounds containing oxindole-fused spirote-
trahydrofuran scaffolds.
methods.7 However, as for the diastereoselective and
enantioselective synthesis of spirotetrahydrofuran oxindoles,
very limited approaches have been reported. Typical work was
Recently, vinyl cyclopropanes bearing electron-withdrawing
groups have been demonstrated as a new family of “three-
carbon-atom” precursors for the construction of cyclic
compounds.8 It is well known that the ring-opening of vinyl
cyclopropanes easily leads to a 1,3-dipolar species in the
presence of Pd(0) catalysts, followed by trapping with olefins,8e
conducted by Schreiber and co-workers by use of the
annulation of isatins with enantioselective crotylsilanes to
afford bioactive spirotetrahydrofuran oxindoles in good yields.4e
Another representative approach to access enantiopure 3,2′-
tetrahydrofuryl spirooxindoles was the catalytic asymmetric
[3+2] allylsilane annulation reaction, which was presented by
Franz et al.5a Therefore, a straightforward and flexible method
for diastereo- and enantioselective construction of oxindole-
fused spirotetrahydrofuran frameworks is still highly desirable.
Received: May 25, 2013
© XXXX American Chemical Society
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isocyanates,9 aldehydes,10 azlactone,8g and β,γ-unsaturated α-
keto esters11 to directly afford different substituted five-
membered rings (Scheme 1). Early in 1985, Tsuji and co-
enantioselective construction of spirotetrahydrofuran oxindoles
(Scheme 1, reaction d).
RESULTS AND DISCUSSION
■
Scheme 1. Palladium-Catalyzed Cycloaddition of Vinyl
Initial examinations using dimethyl 2-vinylcyclopropane-1,1-
dicarboxylate (1a) and 1-benzylindoline-2,3-dione (2a) as the
model substrates in the presence of chiral imidazoline-
phosphine-type ligand (aR,S,S)-L1 (10 mol %) and Pd2(dba)3
(5 mol %) were aimed at seeking out the suitable solvent for
this reaction, and the results of these experiments are
summarized in Table SI-1 (see Table SI-1 in the Supporting
Information). The examination of solvent effects revealed that
tetrahydrofuran (THF) was the best solvent for this reaction.
Subsequently, other chiral ligands were next screened. Using
(aR,R,R)-L2 as the ligand afforded the product 3aa in 44% yield
along with poor diastereoselectivity and enantioselectivity
(Table 1, entry 2). Another two newly synthesized chiral
imidazoline-phosphine ligands, (aS,R,R)-L3 and (aS,R,R)-L4,
were also tested. Using ligand (aS,R,R)-L3 in the reaction
furnished the desired product 3aa in 93% yield along with 88%
ee as well as opposite absolute configuration, albeit in poor
diastereoselectivity (Table 1, entry 3), while employing ligand
(aS,R,R)-L4 provided the product 3aa in 81% yield with poor
dr and 84% ee value (Table 2, entry 4). For comparison, we
also examined the chiral phosphine-oxazoline ligands (aR,S)-L5
and (aS,S)-L6 in this reaction under identical conditions.14 The
use of chiral phosphine-oxazoline ligand (aR,S)-L5 gave 3aa in
98% yield with −61% ee (Table 1, entry 5), while the use of
ligand (aS,S)-L6 resulted in the formation of 3aa in poor
diastereoselectivity and enantioselectivity, though in excellent
yield, suggesting that axially chiral imidazoline-phosphine ligand
L3 was the best choice for this reaction (Table 1, entry 6).
These different results of chiral phosphine-oxazoline ligands
and chiral imidazoline-phosphine ligands may lie in an
additional chiral center in chiral imidazoline-phosphine ligands
or the electronic property of the Ts substitution on the
nitrogen atom in these chiral imidazoline-phosphine ligands. As
compared with the opposite ee values using (aR,S,S)-L1,
(aR,R,R)-L2, and (aR,S)-L5 with (aS,R,R)-L3, (aS,R,R)-L4, and
(aS,S)-L6, we found that the absolute configuration of product
3aa is determined by the axial chirality of the ligands. Then,
different substituents R2 in substrates 1 were screened using
THF as solvent and chiral imidazoline-phosphine (aS,R,R)-L3
(10 mol %) as ligand, aiming at improving the diastereose-
lectivity and enantioselectivity, and the results are shown in
Table 1. The examination of different substrates 1 revealed that
by using dibenzhydryl 2-vinylcyclopropane-1,1-dicarboxylate
(1g), the desired product 3ga could be obtained in 88% yield
along with 96% ee, albeit in poor diastereoselectivity, and using
other substrates 1 such as 1b, 1c, 1d, 1e, or 1f gave the
corresponding adducts in lower yields or ee values under
identical conditions (Table 1, entries 7−12). Moreover, the
examination of different additives showed that the addition of
LiCl could afford the desired product in the best
diastereoselectivity with good enantioselectivity (see Table SI-
2 in the Supporting Information). Adding LiCl to the reaction
system of dibenzhydryl 2-vinylcyclopropane-1,1-dicarboxylate
(1g) and 1-benzylindoline-2,3-dione (2a) in the presence of
chiral imidazoline-phosphine-type ligand L3 (10 mol %) and
Pd2(dba)3 (5 mol %) in THF did improve the diastereose-
lectivity, but with a lower yield of 3ga (35%) (Table 1, entry
13). On the basis of these experiments, we chose dibenzhydryl
2-vinylcyclopropane-1,1-dicarboxylate (1g) and 1-benzylindo-
a
Cyclopropanes with Different Dipolarophiles
a
EWG = electron-withdrawing groups.
workers started the pioneering work by reporting Pd(0)-
catalyzed [3+2] cycloaddition of vinylcyclopropane with α,β-
unsaturated esters or ketones (Scheme 1, reaction a).8e Later, in
an ongoing study, Tsuji et al. showed a facile way to obtain γ-
lactams by replacing aryl isocyanates with α,β-unsaturated
esters or ketones in the palladium-catalyzed addition reaction
(Scheme 1, reaction b).9 Afterward, in a related process,
Johnson and co-workers introduced a palladium-catalyzed
addition of vinylcyclopropane with aldehydes to afford 2,5-cis-
disubstituted tetrahydrofuran derivatives in high yields and
diastereoselectivities (Scheme 1, reaction c).10a However, the
asymmetric version of vinylcyclopropane with aldehydes could
not be directly achieved in the presence of Pd catalyst, although
its asymmetric [3+2] cycloaddition could be realized in the
presence of chiral Lewis acids.10b,c Previously, the novel chiral
imidazoline-phosphines L1 and L2 with a 1,1′-binaphthalene
framework have been developed in our group and applied in
the palladium-catalyzed asymmetric allylic alkylation,12 zinc(II)-
catalyzed Mannich-type difluorination of hydrazones with
difluoroenoxysilanes,13 and Pd(0)-catalyzed [3+2] cycloaddi-
tion of vinylcyclopropane with β,γ-unsaturated α-keto esters11
(Figure 2). On the basis of our previous work, we envisaged to
apply these new chiral imidazoline-phosphines in the Pd(0)-
catalyzed ring-opening of vinylcyclopropane and the subse-
quent cycloaddition with isatins for the diastereo- and
Figure 2. Different chiral imidazoline phosphine ligands.
B
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Table 1. Screening of Ligands, Substrates 1, Temperature, and Additives for Pd-Catalyzed Asymmetric [3+2] Cycloaddition
a
b
c
d
entry
R2
temp [°C]
ligand
additive
yield [%]
dr
ee [%]
1
Me, 1a
Me, 1a
Me, 1a
Me, 1a
Me, 1a
Me, 1a
Bn, 1b
tBu, 1c
iPr, 1d
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
0
L1
L2
L3
L4
L5
L6
L3
L3
L3
L3
L3
L3
L3
L3
L3
L3
L3
L3
L3
L3
3aa, 86
3aa, 44
3aa, 93
3aa, 81
3aa, 98
3aa, 92
3ba, 88
3ca, 85
3da, 67
3ea, 80
3fa, 85
3ga, 88
3ga, 35
3ga, 63
3ga, 40
3ga, 35
3ga, 52
3ga, 69
3ga, 55
1:1.5
1:2.3
−53/12
−13/9
88/48
84/35
−61/19
34/8
2
3
1.2:1
4
1.8:1
1.7:1
1.1:1
1.6:1
2.4:1
1.1:1
1.0:1
5
6
7
87/53
76/37
88/55
90/69
85/40
96/75
95/60
95/64
95/52
89/80
93/49
94/70
95/55
95/55
8
9
e
10
11
12
13
3,5-DOMeBn, 1e
t
CH2 Bu, 1f
1:1.5
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
1.1:1
4:1
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
f
14
2.2:1
5:1
g
15
16
17
18
7:1
40
60
rt
rt
4:1
1.4:1
86:14
86:14
h
19
I
20
3ga, 91
a
b
c
The reaction was conducted with 1 (0.1 mmol) and 2a (0.15 mmol) in THF (0.5 mL). Isolated yield. The diastereomeric ratios were determined
d
e
1
by H NMR spectroscopy. The ee values were determined by chiral HPLC on Daicel Chiralpak PC-2, AD-H, PC-4. 3,5-DOMeBn = 3,5-
dimethoxybenzyl. 0.3 equiv of LiCl was added. Replace Pd2dba3 with Pd2dba3·CHCl3. The reaction was conducted with 1 (0.1 mmol) and 2a
(0.15 mmol) in THF (0.25 mL). The reaction was conducted with Pd2dba3 (7.5 mol %) and ligand L (15 mol %) in THF (0.25 mL).
f
g
h
I
line-2,3-dione (2a) as the substrates, THF as the solvent, LiCl
as an additive, and L3 as the ligand to further optimize the
reaction conditions. Using 0.3 equiv of LiCl gave 3ga in 63%
yield but with lower diastereoselectivity (Table 1, entry 14).
Replacing Pd2dba3 with Pd2dba3·CHCl3 or changing the
reaction temperature did not significantly improve the reaction
outcomes (Table 1, entries 15−18). Increasing the concen-
tration of the reaction mixtures from 0.1 to 0.2 M in THF
produced the corresponding product 3ga in 55% yield along
with 86:14 dr and 95% ee value at room temperature (Table 1,
entry 19). The use of Pd2dba3 (0.75 mol %) and ligand L3 (15
mol %) together with this concentration of reaction mixtures
produced the corresponding product 3ga in 91% yield along
with 86:14 dr and 95% ee values, which are the optimized
conditions for this reaction (Table 1, entry 20).
Having established the optimal reaction conditions, the
substrate scope was next investigated, and the results are
summarized in Table 2. At first, using dibenzhydryl 2-
vinylcyclopropane-1,1-dicarboxylate (1g) as the model sub-
strate, we examined various isatins 2 bearing different N-
protecting groups and substituents on the aromatic ring (Table
2, entries 1−14). Using 2b, 2c, and 2d as the substrates, the
corresponding adducts 3gb, 3gc, and 3gd were obtained in high
yields with 85:15−90:10 diastereoselectivities and excellent ee
values, demonstrating that the N-protecting groups of methyl,
allyl, and methoxymethyl (MOM) were all tolerable in this
reaction (Table 2, entries 1−3). Next, the influence of various
substituents at the aromatic rings of isatin has been explored in
this reaction. As can be seen from Table 2, a wide range of
substituents R3 having different electronic properties at the C5′,
C6′, or C7′ position of isatins did not have significant impact
on this reaction, smoothly affording structurally varied
spirotetrahydrofuran oxindoles 3ge−3gn in 70−98% yields
with 85/15−94/6 diastereoselectivities and 92−96% ee values
(Table 2, entries 4−13). However, when R3 is at the C4′
position of isatin, no reaction occurred perhaps due to the steric
effect (Table 2, entry 14). Using other vinylcyclopropanes 1
such as 1b, 1e, 1d, or 1a, the reactions also proceeded smoothly
to give the corresponding products in 82−95% yields along
with good diastereoselectivities and 74−82% ee values under
the standard conditions (Table 2, entries 15−18). Using
vinylcyclopropane (E)-dimethyl 2-styrylcyclopropane-1,1-dicar-
boxylate 1h (R1 = Ph) as substrate provided the desired
spirotetrahydrofuran oxindole 3hb in 28% yield along with
86:14 dr and 11% ee, and replacing the phenyl group on
vinylcyclopropane with a meta-tolyl group (R1 = m-MeC6H4)
C
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Table 2. Substrate Scope for Pd/L3-Catalyzed Asymmetric Formal [3+2] Cycloaddition
a
b
c
d
ee [%]
entry
R1
R2
R3
PG
yield [%]
dr
90:10
1
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
CHPh2, 1g
Bn, 1b
H
Me, 2b
MOM, 2c
allyl, 2d
Me, 2e
Me, 2f
Me, 2g
Me, 2h
Me, 2i
Me, 2j
Me, 2k
Me, 2l
Me, 2m
Me, 2n
Me, 2o
Bn, 2a
Bn, 2a
Bn, 2a
Bn, 2a
Me, 2b
Me, 2b
3gb, 90
3gc, 91
3gd, 92
3ge, 70
3gf, 95
3gg, 98
3gh, 93
3gi, 94
3gj, 98
3gk, 83
3gl, 93
3gm, 85
3gn, 97
3go, 0
92/64
2
H
85:15
87:13
87:13
95/63
94/59
96/66
3
H
4
5′-Me
5′-Cl
5′-Br
5′-F
6′-Me
6′-Cl
6′-Br
7′-Cl
7′-Br
7′-F
4′-Cl
H
e
e
5
90:10 (>20:1)
88:12
92/68 (96/42)
93/84
6
7
91:9
92/68
8
88:12
94/63
9
87:13
93/63
10
11
12
13
14
15
16
17
18
19
20
85:15
95/60
86:14
94/62
86:14
94/58
94:6
94/59
f
n.d.
3ba, 95
3ea, 87
3da, 82
3aa, 86
3hb, 28
3ib, 0
89:11
81:19
82:18
77:23
86:14
82/60
82/64
82/50
74/72
11/8
g
3,5-DOMeBn, 1e
iPr, 1d
H
H
Me, 1a
H
Me, 1h
H
3-MeC6H4
Me, 1i
H
n. d.
a
b
c
The reaction was conducted with 1 (0.1 mmol) and 2 (0.15 mmol) in THF (0.25 mL). Isolated yield. The diastereomeric ratios were determined
d
e
by 1H NMR spectroscopy. The ee values were determined by chiral HPLC on Daicel Chiralpak AD-H, REGIS, PC-2, PC-4. After crystallization
from DCM/PE. Not detected. 3,5-DOMeBn = 3,5-dimethoxybenzyl.
f
g
did not give the corresponding product, presumably due to the
steric effect (Table 2, entries 19 and 20). Moreover, the
absolute configuration of 3gf has been assigned by its X-ray
diffraction as 2S,5S (Figure 3). On the basis of the same sign of
the optical rotation of products 3gb−3ib as that of 3gf, we
concluded that products 3gb−3ib also have the 2S, 5S absolute
configuration. The ORTEP drawing of 3gf is shown in Figure 3,
and its CIF data are summarized in the Supporting
Information.15
To further illustrate the generality of this Pd(0)/L3-catalyzed
asymmetric [3+2] cycloaddition, 2-vinylcyclopropane-1,1-di-
carbonitrile (1j) and 2-vinyloxirane (1k) were used as the
substrates to react with 1-benzylindoline-2,3-dione (2a) under
the standard conditions, respectively (Scheme 2). However, the
desired products 3ja and 3ka were obtained in 98% and 99%
yields along with 56:44 and 2:1 dr values, but with very low ee
values. These results indicated that the dibenzhydryloxycar-
bonyl ester moiety in vinylcyclopropane has significant
Scheme 2. Pd/L3-Catalyzed Asymmetric [3+2]
Cycloaddition of 2-Vinylcyclopropane-1,1-dicarbonitriles
(1j) and 2-Vinyloxirane (1k) with Isatin 2a
Figure 3. Crystal structure of product 3gf.
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influence on the enantioselectivity of this Pd(0)-catalyzed
asymmetric formal [3+2] cycloaddition, probably due to its
steric effect or the electronic property. Besides the large steric
repulsion between the dibenzhydryloxycarbonyl ester moiety
and the ligand improving the ee values, the possible π−π
stacking interaction between the dibenzhydryloxycarbonyl ester
moiety and the aromatic rings in the ligand or isatin substrate
can also provide an additional influence on the enantioselectiv-
ities. These effects can also explain the observed poor ee values
in Scheme 2.
To our delight, on enlarging the reaction scale to 1.0 mmol
by employing dibenzhydryl 2-vinylcyclopropane-1,1-dicarbox-
ylate (1g) and 1-benzylindoline-2,3-dione (2a) as the
substrates, similar results could be obtained under the standard
conditions, affording 3ga in 78% yield along with 86:14 dr and
95% ee (Scheme 3).
We have further explored the transformations of products 3
in order to illustrate their synthetic utility. As shown in Scheme
4, product 3ga could be smoothly reduced by a simple
treatment with Pd/C under 1 atm H2 atmosphere in ethyl
acetate at room temperature, affording dicarboxylic acid 4 in
82% yield with >20:1 dr value. Furthermore, 3ga could be easily
converted into compounds 5a and 5b in 56% yield with a 94:6
dr and 95% ee values as well as in 29% yield and >20:1
diastereoselectivity, respectively, through Brown hydroboration
with BH3 in THF and subsequent treatment with a 1.0 M
aqueous solution of sodium hydroxide and a 30% aqueous
hydrogen peroxide solution. Moreover, the corresponding
aldehyde 6 could be obtained from 3gj in 91% yield with
93/7 dr and 93%/63% ee through ozonization, followed by
workup with zinc powder and acetic acid. No significant change
could be observed in enantioselectivities during these trans-
formations, while the diastereoselectivities were improved
probably due to the fact that during the isolation by silica gel
column chromatography the minor diastereoisomers of
products 4, 5, and 6 were separated out. Product 5b could
be further transformed to compound 7 through condensation
with 4-bromobenzoic aicd using dicyclohexylcarbodiimide
(DCC, 2.0 equiv) in the presence of 4-dimethylaminopyridine
(DMAP, 2.0 equiv) in 96% yield with >20:1 dr value.
Scheme 3. Pd/L3-Catalyzed Asymmetric [3+2]
Cycloaddition of Dibenzhydryl 2-Vinylcyclopropane-1,1-
dicarboxylate (1g) (1.0 mmol) with Isatin 2a (1.5 mmol)
On the basis of our experimental results and previously
reported mechanistic studies,8e,g,11 we tentatively proposed a
Scheme 4. Transformation of Products to the Other Spirotetrahydrofuran Oxindoles
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Scheme 5. Proposed Mechanistic Model
further purification. All reactions were monitored by TLC with
Huanghai GF254 silica gel-coated plates. Flash column chromatography
was carried out using 300−400 mesh silica gel at increased pressure.
All reactions were performed under argon using standard Schlenk
techniques. The optical purities of products were determined by
HPLC analysis using a Shimadzu SPD-10A vp series with chiral
columns (Chiralpak AD-H, PC-2, PC-4 and IC-H columns 4.6 × 250
mm, Daicel Chemical Ind., Ltd.), and the absolute configuration of the
major enantiomer was assigned according to the sign of the specific
rotation.
plausible reaction mechanism to explain the stereochemistry of
this Pd/L3-catalyzed asymmetric [3+2] cycloaddition reaction
(Scheme 5). The initial nucleophilic attack of palladium at the
double bond of vinylcyclopropane 1 results in cyclopropyl ring-
opening to afford the active zwitterionic (π-allyl) palladium
intermediates 8 and 8′. Through π−σ−π equilibration,
intermediates 8 and 8′ can be interconverted with each other.
Due to the more significant steric repulsion between the
malonate moiety and phenyl group in imidazoline-phosphine
ligand L3, intermediate 8 is thermodynamically more favored,
which undergoes nucleophilic addition to isatin 2b, giving
another (π-allyl) palladium complex, 9. The nucleophilic attack
of the oxygen anion in isatin to the backside of the in situ
generated (π-allyl) palladium complex 9 gives the major
diastereomer 3gb.
In conclusion, we have developed a highly efficient
palladium(0)-catalyzed asymmetric formal [3+2] cycloaddition
of vinylcyclopropanes with isatins, affording functionalized
spirotetrahydrofuran oxindoles in high yields with good to
excellent diastereo- and enantioselectivities under mild reaction
conditions, and the further transformations of these adducts
have been also explored. The newly synthesized chiral ligand
(aS,R,R)-L3 plays a crucial role for achieving satisfied diastereo-
and enantioselectivities in this reaction. Further studies on
expanding the scope of this reaction toward a range of other
dipolarophiles as well as the applications of this protocol to
natural product synthesis are in progress.
Ligands L1−L6 were prepared according to the previously reported
procedures.12,14b
Vinyl cyclopropanes 1a,16 1b,16 1c,17 1f,18 and 1h19 were prepared
according to the previously reported procedures.
1. Typical Procedure of the Preparation of Chiral Imidazoline-
Phosphine-Type Ligands L3 and L4. Synthesis of the Precatalysts
SI-3. A solution of (S)-BINDPCA SI-1 (0.5 mmol) in DMF (5.0 mL)
with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride
(EDCI) (1.0 mmol) and 1-hydroxybenzotriazole (HOBt) (1.5
mmol) was stirred at 0 °C for 10 min; then a solution of SI-2 (0.75
mmol) in 2.0 mL of DMF was added into the solution by a syringe at 0
°C. The reaction mixture was stirred at room temperature for 12 h.
The reaction mixture was diluted by the addition of 10 mL of EtOAc,
then washed with H2O and brine, and dried over anhydrous Na2SO4.
The solvent was removed under vacuum, and the residue was purified
by silica gel column chromatography (PE/EA = 1.5:1) to give the
desired product SI-3 as a pale yellow solid.
(S)-1-(2-(Dibutylphosphoryl)naphthalen-1-yl)-N-((1R,2R)-2-(4-
methylphenylsulfonamido)-1,2-diphenylethyl)-2-naphthamide, SI-
3a: pale yellow solid, 91% yield (367 mg); mp 112−115 °C; 1H
NMR (CDCl3, TMS, 400 MHz) δ 0.66 (t, J = 7.2 Hz, 3H, CH3),
0.77−1.05 (m, 8H, CH2, CH3), 1.36−1.57 (m, 5H, CH2), 1.99−2.15
(m, 2H, CH2), 2.23 (s, 3H, CH3), 4.95 (dd, J = 4.0 Hz, 9.6 Hz, 1H,
CH), 5.07 (dd, J = 4.0 Hz, 8.4 Hz, 1H, CH), 6.41 (d, J = 7.6 Hz, 2H,
ArH), 6.76 (d, J = 8.4 Hz, 1H, ArH), 6.83−6.91 (m, 4H, ArH), 7.00−
7.08 (m, 6H, ArH), 7.14−7.24 (m, 4H, ArH), 7.30 (d, J = 10.0 Hz, 1H,
ArH), 7.38−7.63 (m, 4H, ArH), 7.93 (d, J = 8.0 Hz, 1H, ArH), 8.00
(d, J = 8.4 Hz, 1H, ArH), 8.08 (dd, J = 2.4 Hz, 8.0 Hz, 1H, ArH),
10.10 (d, J = 8.4 Hz, 1H, NH); 31P NMR (CDCl3, 161 MHz, 85%
H3PO4) δ 49.07; IR (CH2Cl2) ν 3202, 3058, 2924, 2911, 2902, 2885,
1659, 1567, 1438, 1326, 1148, 1119, 1092, 983, 818, 749, 723, 699,
540, 525, 515 cm−1; MS (MALDI) m/z (%) 807.3 (100) [M+ + 1];
HRMS (MALDI) calcd for C50H52N2O4PS+(M+ + 1) requires
EXPERIMENTAL SECTION
■
General Remarks. MP was obtained with a Yanagimoto micro
melting point apparatus and is uncorrected. Optical rotations were
determined in a solution of CHCl3 or CH2Cl2 at 20 °C by using a
Perkin-Elmer-241 MC polarimeter; [α]D values are given in units of
10−1 deg cm2 g−1. Infrared spectra were measured on a spectrometer.
1H NMR spectra were recorded for a solution in CDCl3 with
tetramethylsilane (TMS) as internal standard; 31P NMR spectra were
recorded for a solution in CDCl3 with 85% H3PO4 as the external
reference. J-values are in Hz. Mass spectra were recorded with a HP-
5989 instrument, and HRMS was measured by a Finnigan MA+ mass
spectrometer. Organic solvents used were dried by standard methods
when necessary. Commercially available reagents were used without
807.3380, found 807.3372; [α]20 = −77.5 (c 0.20, CHCl3).
D
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dx.doi.org/10.1021/om400473p | Organometallics XXXX, XXX, XXX−XXX

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(S)-1-(2-(Dicyclohexylphosphoryl)naphthalen-1-yl)-N-((1R,2R)-2-
(4-methylphenylsulfonamido)-1,2-diphenylethyl)-2-naphthamide,
1494, 1447, 1372, 1339, 1265, 1185, 1171, 1117, 1088, 1056, 1021,
1002, 964, 914, 851, 816, 776, 750, 735, 697, 668 cm−1; MS (MALDI)
m/z (%) 825.4 (100) [M+ + 1]; HRMS (MALDI) calcd for
1
SI-3b: white solid, 95% yield (408 mg); mp 140−142 °C; H NMR
C54H54N2O2PS+(M+ + 1) requires 825.3644, found 825.3650; [α]20
−39.7 (c 0.20, CHCl3).
=
(CDCl3, TMS, 300 MHz) δ 0.66−1.14 (m, 6H, CH2), 1.22−1.28 (m,
3H, CH2), 1.40−1.52 (m, 9H, CH2), 1.73−1.85 (m, 3H, CH2, CH),
2.14−2.18 (m, 1H, CH), 2.23 (s, 3H, CH3), 5.21 (dd, J = 9.6 Hz, 9.6
Hz, 2H, CH), 6.52−6.56 (m, 3H, ArH), 6.81−6.95 (m, 6H, ArH),
6.98−7.09 (m, 4H, ArH), 7.14−7.33 (m, 6H, ArH), 7.40−7.54 (m,
3H, ArH), 7.89−7.97 (m, 3H, ArH), 8.04 (d, J = 7.2 Hz, 1H, ArH),
10.29 (d, J = 9.6 Hz, 1H, NH); 31P NMR (CDCl3, 121 MHz, 85%
H3PO4) δ 52.26; IR (CH2Cl2) 3388, 3058, 2956, 2925, 2855, 1633,
1529, 1497, 1460, 1348, 1311, 1265, 1166, 1091, 938, 854, 737, 698,
518 cm−1; MS (MALDI) m/z (%) 859.5 (100) [M+ + 1]; HRMS
(MALDI) calcd for C54H56N2O4PS+(M+ + 1) requires 859.3698,
D
2. General Procedure for the Synthesis of Cyclopropanes 1. The
corresponding C−H acidic compound (1 equiv) and 1,4-dibromobut-
2-ene (1 equiv) are added to a round-bottom flask with a stir bar under
an atmosphere of nitrogen. Then tetrahydrofuran (0.2 M) and cesium
carbonate (2.5 equiv) are added into this reaction vessel. A condenser
is charged, and reaction mixture is then heated to 60 °C overnight.
After cooling to room temperature, the reaction mixture is filtered over
Celite and washed with diethyl ether. The organic phase is washed
with saturated aqueous NaHCO3, followd by water and brine. After
filtration over Na2SO4, the solvent is removed under reduced pressure.
The crude product is purified by means of silica gel chromotagraphy
using petroleum ether and diethyl ether as the eluent. The yields are
not optimized for the synthesis of vinylcyclopropanes.
found 859.3685; [α]20 = −65.4 (c 0.20, CHCl3).
D
Synthesis of the Precatalysts SI-4 (ref 20). To a dried Schlenk tube
were added triphenylphosphine oxide (1.5 mmol) and trifluorome-
thanesulfonic anhydride (1.5 mmol) in CH2Cl2 (5.0 mL) at 0 °C, and
the reaction mixture was stirred at 0 °C for 0.5 h. Then the solution of
precatalyst SI-3 (0.50 mmol) in CH2Cl2 (5.0 mL) was added slowly
via syringe. After the completion of the addition, the mixture was
stirred at 0 °C for 3 h. The reaction was quenched with saturated
NaHCO3(aq), and the aqueous layer was extracted with CH2Cl2. The
combined organic phase was dried over anhydrous Na2SO4, and the
solvent was removed under vacuum. The residue was purified by silica
gel column chromatography (PE/EA = 1:1) to give crude product SI-4
(mixed with triphenylphosphine oxide).
Diisopropyl 2-vinylcyclopropane-1,1-dicarboxylate, 1d: 10.0
1
mmol scale, a colorless oil, 82% yield (1.97 g); H NMR (CDCl3,
400 MHz, TMS) δ 1.21 (d, J = 6.4 Hz, 3H, CH3), 1.24 (d, J = 6.4 Hz,
3H, CH3), 1.26 (d, J = 4.8 Hz, 3H, CH3), 1.28 (d, J = 4.8 Hz, 3H,
CH3), 1.49 (dd, J = 4.8 Hz, 8.8 Hz, 1H, CH2), 1.64 (dd, J = 4.8 Hz, 7.6
Hz, 1H, CH2), 2.51−2.58 (m, 1H, CH), 5.02−5.14 (m, 3H, CH, 
CH2), 5.26−5.31 (m, 1H, CH2), 5.38−5.48 (m, 1H, CH); 13C
NMR (CDCl3, 100 MHz, TMS) δ 20.0, 21.56, 21.6, 21.7, 21.8, 30.6,
36.1, 68.8, 69.1, 118.1, 133.2, 167.0, 169.3; IR (CH2Cl2) ν 3035, 2981,
1717, 1639, 1468, 1358, 1338, 1313, 1271, 1203, 1145, 1098, 1017,
991, 958, 916, 902, 820, 802, 785, 750, 716, 666 cm−1; MS (ESI) m/z
(%) 241.1 (100) [M+ + H]; HRMS (ESI) calcd for C13H21O4+ (M+ +
H) requires 241.1440, found 241.1433.
Synthesis of the Chiral Imidazoline-Phosphine Ligands L3 and
L4. To a dried Schlenk tube filled with argon was added crude
precatalyst SI-4 with Et3N (10.0 equiv) in 15 mL of anhydrous
toluene. The mixture was stirred at 0 °C for 10 min, 10.0 equiv of
HSiCl3 was added at 0 °C, and the mixture was stirred at that
temperature for 0.5 h. Then the mixture was allowed to warm to room
temperature and stirred under reflux overnight. After cooling to room
temperature, the reaction was quenched with saturated NaHCO3(aq),
the precipitates settled out, and the aqueous layer was extracted with
EtOAc. The combined organic phase was washed with brine and dried
over anhydrous Na2SO4, and the solvent was removed under vacuum.
The residue was purified by silica gel column chromatography (PE/EA
= 5:1) to give the desired product as a white solid.
Bis(3,5-dimethoxybenzyl) 2-vinylcyclopropane-1,1-dicarboxylate,
1
1e: 10.0 mmol scale, a colorless oil, 76% yield (3.47 g).; H NMR
(CDCl3, 400 MHz, TMS) δ 1.62 (dd, J = 4.8 Hz, 8.8 Hz, 1H, CH2),
1.77 (dd, J = 4.8 Hz, 8.0 Hz, 1H, CH2), 2.61−2.68 (m, 1H, CH), 3.74
(s, 12H, CH3), 5.06−5.15 (m, 5H, CH2, CH2), 5.26−5.31 (m, 1H,
CH2), 5.42 (ddd, J = 8.4 Hz, 9.6 Hz, 17.2 Hz, 1H, CH), 6.38−
6.39 (m, 2H, ArH), 6.45−6.46 (m, 2H, ArH), 6.47−6.48 (m, 2H,
ArH); 13C NMR (CDCl3, 100 MHz, TMS) δ 20.8, 31.7, 35.9, 55.2,
67.0, 67.1, 100.0, 100.1, 105.5, 105.8, 118.8, 132.8, 137.7, 160.78,
160.8, 167.1, 169.2; IR (CH2Cl2) ν 3032, 2996, 2944, 2840, 1726,
1598, 1460, 1431, 1377, 1321, 1299, 1268, 1205, 1154, 1128, 1070,
991, 956, 919, 833, 686 cm−1; MS (ESI) m/z (%) 457.2 (100) [M+ +
(4R,5R)-2-((S)-1-(2-(dibutylphosphino)naphthalen-1-yl)-
naphthalen-2-yl)-4,5-diphenyl-1-tosyl-4,5-dihydro-1H-imidazole,
L3: white solid, 55% yield for two steps (193 mg); mp 117−120 °C;
1H NMR (CDCl3, TMS, 400 MHz) δ 0.53−0.61 (m, 6H, CH3), 0.79−
+
H]; HRMS (ESI) calcd for C25H29O8 (M+ + H) requires 457.1862,
0.92 (m, 4H, CH2), 1.09−1.19 (m, 3H, CH2), 1.23−1.28 (m, 3H,
CH2), 1.55−1.69 (m, 2H, CH2), 2.25 (s, 3H, CH3), 4.46 (d, J = 6.0
Hz, 1H, CH), 4.56 (d, J = 6.0 Hz, 1H, CH), 5.79 (d, J = 7.6 Hz, 2H,
ArH), 6.82−6.92 (m, 6H, ArH), 7.00 (dd, J = 7.6 Hz, 7.6 Hz, 1H,
ArH), 7.06−7.14 (m, 3H, ArH), 7.18−7.27 (m, 4H, ArH), 7.31 (dd, J
= 7.6 Hz, 7.6 Hz, 1H, ArH), 7.46−7.54 (m, 2H, ArH), 7.73−7.89 (m,
2H, ArH), 7.91 (d, J = 8.8 Hz, 1H, ArH), 8.00 (d, J = 8.8 Hz, 2H,
ArH), 8.13 (dd, J = 4.0 Hz, 8.8 Hz, 2H, ArH); 31P NMR (CDCl3, 161
MHz, 85% H3PO4) δ −35.25; IR (CH2Cl2) ν 3401, 3058, 3024, 2955,
2926, 2870, 1606, 1592, 1494, 1465, 1453, 1420, 1377, 1352, 1263,
1200, 1029, 1005, 904, 866, 819, 750, 698 cm−1; MS (MALDI) m/z
(%) 773.3 (100) [M++1]; HRMS (MALDI) calcd for C50H50N2O2PS+
(M+ + 1) requires 773.3325, found 773.3328; [α]20D = −43.2 (c 0.20,
CHCl3).
(4R,5R)-2-((S)-1-(2-(Dicyclohexylphosphino)naphthalen-1-yl)-
naphthalen-2-yl)-4,5-diphenyl-1-tosyl-4,5-dihydro-1H-imidazole,
L4: white solid, 48% yield for two steps (188 mg); mp 147−150 °C;
1H NMR (CDCl3, TMS, 300 MHz) δ 0.62−0.89 (m, 8H, CH2), 1.04−
1.15 (m, 4H, CH2), 1.30 (br, 3H, CH2), 1.40−1.72 (m, 6H, CH2,
CH), 1.97−2.01 (m, 1H, CH), 2.25 (s, 3H, CH3), 4.47 (d, J = 5.7 Hz,
1H, CH), 4.57 (d, J = 5.7 Hz, 1H, CH), 5.80 (d, J = 6.9 Hz, 2H, ArH),
6.83−6.90 (m, 6H, ArH), 7.01 (dd, J = 7.2 Hz, 7.2 Hz, 1H, ArH),
7.11−7.19 (m, 6H, ArH), 7.23−7.35 (m, 3H, ArH), 7.45−7.55 (m,
2H, ArH), 7.73 (d, J = 8.4 Hz, 1H, ArH), 7.84 (d, J = 8.4 Hz, 1H,
ArH), 7.97−8.17 (m, 4H, ArH); 31P NMR (CDCl3, 121 MHz, 85%
H3PO4) δ −6.80; IR (CH2Cl2) ν 3059, 2922, 2903, 2848, 1642, 1597,
found 457.1849.
Dibenzhydryl 2-vinylcyclopropane-1,1-dicarboxylate, 1g: 10.0
mmol scale, a white solid, 72% yield (3.51 g); mp 110−113 °C; H
1
NMR (CDCl3, 400 MHz, TMS) δ 1.60 (dd, J = 4.8 Hz, 9.2 Hz, 1H,
CH2), 1.76 (dd, J = 4.8 Hz, 7.6 Hz, 1H, CH2), 2.62−2.69 (m, 1H,
CH), 4.97−5.01 (m, 1H, CH), 5.24−5.28 (m, 2H, CH2), 6.88 (s,
1H, CH), 6.89 (s, 1H, CH), 7.17−7.25 (m, 10H, ArH), 7.25−7.32 (m,
10H, ArH); 13C NMR (CDCl3, 100 MHz, TMS) δ 21.3, 32.3, 36.0,
78.5, 78.7, 118.9, 127.05, 127.1, 127.4, 127.86, 127.89, 127.9, 128.3,
128.4, 128.42, 128.5, 132.8, 139.5, 139.58, 139.6, 166.5, 168.7; IR
(CH2Cl2) ν 3031, 2956, 1721, 1638, 1600, 1496, 1455, 1318, 1261,
1185, 1125, 1080, 1030, 954, 869, 801, 781, 759, 742, 696 cm−1; MS
(ESI) m/z (%) 506.2 (100) [M+ + NH4]; HRMS (ESI) calcd for
+
C33H32NO4 (M+ + NH4) requires 506.2331, found 506.2325.
To a stirred suspension of NaH (60% dispersion in mineral oil, 433
mg, 11 mmol) in dimethylformamide (DMF) (14 mL) under nitrogen
was added trimethylsulfoxonium iodide (TMSI) (2.441 g, 11 mmol) in
a single portion. Vigorous evolution of hydrogen lasted for ca. 5 min.
After a further 15 min a solution of (E)-dimethyl 2-(3-m-
tolylallylidene)malonate (9.825 g, 10 mmol) in DMF (6 mL) was
added in a single portion, and the mixture was stirred for 1 h. Under
ice-cold water, 1 N HCl(aq) was added into the product solution, and
the resulting acidic solution (pH < 7) was extracted with diethyl ether
(3 × 15 mL). The extract was washed with water (3 × 10 mL), dried
over anhydrous Na2SO4, and evaporated under reduced pressure. The
G
dx.doi.org/10.1021/om400473p | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
crude material was purified by column chromatography using EtOAc/
petroleum ether (1:30) as eluent to give compound 1i.
755, 698 cm−1; MS (ESI) m/z (%) 650.3 (100) [M+ + Na]; HRMS
(ESI) calcd for C42H36NO6+ (M+ + H) requires 650.2543, found
650.2533.
(2S,5S)-Dibenzhydryl 1′-(methoxymethyl)-2′-oxo-5-vinyl-4,5-di-
hydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gc: white
solid, 91% yield (40 mg), 85:15 dr, 95%/63% ee; mp 137−140 °C.
The ee was determined by chiral HPLC (Daicel Chiralpak REGIS,
(E)-Dimethyl 2-(3-methylstyryl)cyclopropane-1,1-dicarboxylate,
1i: 10.0 mmol scale, a yellow oil, 55% yield (1.51 g); 1H NMR
(CDCl3, 400 MHz, TMS) δ 1.69 (dd, J = 5.2 Hz, 8.8 Hz, 1H, CH2),
1.85 (dd, J = 5.2 Hz, 7.6 Hz, 1H, CH2), 2.33 (s, 3H, CH3), 2.71−2.78
(m, 1H, CH), 3.74 (s, 3H, CH3), 3.77 (s, 3H, CH3), 5.79 (m, J = 8.8
Hz, 15.6 Hz, 1H, CH), 6.61 (d, J = 15.6 Hz, 1H, CH), 7.04 (d, J
= 7.2 Hz, 1H, ArH), 7.09−7.12 (m, 2H, ArH), 7.16−7.21 (m, 1H,
ArH); 13C NMR (CDCl3, 100 MHz, TMS) δ 21.29, 21.3, 31.7, 36.0,
52.66, 52.7, 123.3, 124.2, 126.8, 128.39, 128.4, 133.9, 136.6, 138.1,
168.0, 169.9; IR (CH2Cl2) ν 3032, 2952, 2907, 1723, 1603, 1489,
1435, 1317, 1280, 1256, 1208, 1126, 1065, 962, 899, 842, 783, 734,
693 cm−1; MS (ESI) m/z (%) 275.1 (100) [M+ + H]; HRMS (ESI)
hexane/iPrOH = 95:5, 0.5 mL/min, 230 nm); main product: tmajor
=
39.6 min, tminor = 35.5 min; [α]20D = +13.1 (c 1.60, CH2Cl2); 1H NMR
(CDCl3, 400 MHz, TMS) δ 2.69 (dd, J = 5.2 Hz, 13.2 Hz, 1H, CH2),
3.11 (s, 3H, CH3), 3.48 (dd, J = 9.6 Hz, 13.2 Hz, 1H, CH2), 4.44 (d, J
= 11.2 Hz, 1H, CH2), 4.67 (d, J = 11.2 Hz, 1H, CH2), 5.13−5.31 (m,
3H, CH, CH2), 6.29 (ddd, J = 8.0 Hz, 10.0 Hz, 17.2 Hz, 1H, 
CH), 6.58−6.63 (m, 1H, ArH), 6.76 (s, 1H, CH), 6.85 (d, J = 8.0 Hz,
1H, ArH), 6.88 (s, 1H, CH), 6.90−6.97 (m, 3H, ArH), 7.01−7.07 (m,
6H, ArH), 7.13−7.27 (m, 13H, ArH); 13C NMR (CDCl3, 100 MHz,
TMS) δ 39.4, 56.2, 66.0, 70.9, 79.1, 79.3, 79.4, 86.3, 109.8, 117.9,
123.3, 123.4, 125.3, 126.6, 126.7, 126.8, 127.55, 127.6, 127.8, 127.9,
128.0, 128.2, 128.3, 128.4, 130.4, 137.6, 138.6, 138.8, 138.9, 143.3,
167.6, 168.7, 174.7. IR (CH2Cl2) ν 3032, 2925, 2853, 1732, 1615,
1494, 1469, 1455, 1367, 1350, 1257, 1188, 1156, 1132, 1096, 1078,
1026, 955, 914, 757, 698 cm−1; MS (ESI) m/z (%) 702.2 (100) [M+ +
Na]; HRMS (ESI) calcd for C43H37NO7Na+ (M+ + Na) requires
702.2468, found 702.2435.
+
calcd for C16H19O4 (M+ + H) requires 275.1283, found 275.1268.
3. General Procedure for the Palladium-Catalyzed Asymmetric
formal [3+2] Cycloaddition of Vinylcyclopropane with Isatins in the
Presence of Pd2dba3 and Chiral Imidazoline-Phosphine Ligand L3.
A solution of enantiomerically pure ligand L3 (0.015 mmol, 15 mol %)
and palladium dibenzylideneacetone (Pd2dba3, 0.0075 mmol, 7.5 mol
%) in THF (0.10 mL) was stirred at room temperature under an argon
atmosphere for 30 min. To the solution was added a solution of
dimethyl dibenzhydryl 2-vinylcyclopropane-1,1-dicarboxylate (1g) (0.1
mmol, 1 equiv), 1-methylindoline-2,3-dione (2b) (0.15 mmol, 1.5
equiv) in THF (0.15 mL), and LiCl (0.25 mmol, 2.5 equiv), and the
reaction mixture was stirred at room temperature for 48 h. The
mixture was concentrated in vacuo to yield the crude product, which
was purified by flash chromatography on silica gel (eluent: PE/EtOAc
= 10:1−20:1) to furnish the desired spirotetrahydrofuran oxindole 3gb
as a white solid.
(2S,5S)-Dibenzhydryl 1′-allyl-2′-oxo-5-vinyl-4,5-dihydro-3H-
spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gd: white solid, 92%
yield (61 mg), 87:13 dr, 94%/59% ee; mp 122−125 °C. The ee was
determined by chiral HPLC (Daicel Chiralpak REGIS, hexane/iPrOH
= 95:5, 0.5 mL/min, 230 nm); main product: tmajor = 37.3 min, tminor
=
1
31.1 min. [α]20 = +13.6 (c 2.70, CH2Cl2); H NMR (CDCl3, 400
D
(2S,5S)-Dibenzhydryl 1′-benzyl-2′-oxo-5-vinyl-4,5-dihydro-3H-
spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3ga: white solid, 91%
yield (66 mg), 86:14 dr, 95%/55% ee; mp 142−145 °C. The ee was
determined by chiral HPLC (Daicel Chiralpak AD-H, hexane/iPrOH
= 70:30, 0.5 mL/min, 230 nm); main product: tmajor = 21.3 min, tminor
MHz, TMS) δ 2.66 (dd, J = 5.2 Hz, 13.2 Hz, 1H, CH2), 3.48 (dd, J =
9.2 Hz, 13.2 Hz, 1H, CH2), 3.55 (d, J = 5.2 Hz, 1H, CH2), 3.98 (dd, J
= 5.2 Hz, 16.0 Hz, 1H, CH2), 5.06−5.30 (m, 5H, CH, CH2), 5.55
(ddd, J = 5.6 Hz, 10.8 Hz, 15.6 Hz, 1H, CH), 6.27 (ddd, J = 8.0 Hz,
10.0 Hz, 17.6 Hz, 1H, CH), 6.55−6.64 (m, 2H, ArH), 6.79 (s, 1H,
CH), 6.87 (s, 1H, CH), 6.90−6.94 (m, 3H, ArH), 6.97 (d, J = 6.8 Hz,
2H, ArH), 7.02 (d, J = 6.8 Hz, 2H, ArH), 7.06−7.08 (m, 2H, ArH),
7.11−7.27 (m, 13H, ArH); 13C NMR (CDCl3, 100 MHz, TMS) δ
39.6, 41.7, 65.9, 79.1, 79.2, 85.9, 109.3, 117.7, 117.9, 122.8, 123.9,
125.3, 126.8, 126.9, 127.7, 127.8, 127.9, 128.0, 128.1, 128.3, 128.4,
128.43, 130.1, 131.0, 137.7, 138.7, 138.86, 138.9, 139.0, 144.2, 167.6,
168.9, 173.7; IR (CH2Cl2) ν 3062, 3032, 2925, 2846, 1725, 1614,
1495, 1614, 1495, 1467, 1655, 1366, 1243, 1186, 1155, 1080, 1029,
955, 802, 742, 697 cm−1; MS (ESI) m/z (%) 676.3 (100) [M+ + 1];
20
1
= 31.6 min. [α]D = +17.0 (c 1.00, CH2Cl2); H NMR (CDCl3, 400
MHz, TMS) δ 2.70 (dd, J = 5.2 Hz, 13.2 Hz, 1H, CH2), 3.52 (dd, J =
9.6 Hz, 13.2 Hz, 1H, CH2), 3.92 (d, J = 16.0 Hz, 1H, CH2), 4.60 (d, J
= 16.0 Hz, 1H, CH2), 5.18 (d, J = 10.4 Hz, 1H, CH2), 5.24−5.33
(m, 2H, CH, CH2), 6.30 (ddd, J = 4.8 Hz, 10.4 Hz, 18.0 Hz, 1H, 
CH), 6.46 (d, J = 7.6 Hz, 1H, ArH), 6.50 (dd, J = 7.6 Hz, 7.6 Hz, 1H,
ArH), 6.83 (s, 1H, CH), 6.88 (s, 1H, CH), 6.92−6.95 (m, 3H, ArH),
7.01−7.05 (m, 4H, ArH), 7.05−7.12 (m, 3H, ArH), 7.13−7.20 (m,
9H, ArH), 7.21−7.28 (m, 8H, ArH); 13C NMR (CDCl3, 100 MHz,
TMS) δ 39.6, 42.9, 66.0, 79.1, 79.27, 79.34, 86.1, 109.5, 117.9, 122.9,
123.9, 125.3, 126.8, 127.1, 127.4, 127.6, 127.7, 127.8, 127.85, 127.9,
128.0, 128.2, 128.3, 128.34, 128.4, 128.5, 128.6, 130.1, 135.2, 137.7,
138.7, 138.9, 139.0, 144.1, 167.7, 168.9, 174.1; IR (CH2Cl2) ν 3063,
3031, 2925, 1731, 1614, 1495, 1468, 1455, 1369, 1259, 1185, 1155,
1077, 1030, 1002, 954, 779, 741, 697 cm−1; MS (ESI) m/z (%) 748.3
(100) [M+ + Na]; HRMS (ESI) calcd for C48H39NO6Na+ (M+ + Na)
requires 748.2675, found 748.2665.
+
HRMS (ESI) calcd for C44H38NO6 (M+ + H) requires 676.2699,
found 676.2686.
(2S,5S)-Dibenzhydryl 1′,5′-dimethyl-2′-oxo-5-vinyl-4,5-dihydro-
3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3ge: white solid,
70% yield (46 mg), 87:13 dr, 96%/66% ee; mp 132−135 °C. The
ee was determined by chiral HPLC (Daicel Chiralpak AD-H, hexane/
iPrOH = 75:25, 0.4 mL/min, 230 nm); main product: tmajor = 44.1
1
min, tminor = 25.6 min; [α]20 = +10.3 (c 2.00, CH2Cl2); H NMR
D
(2S,5S)-Dibenzhydryl 1′-methyl-2′-oxo-5-vinyl-4,5-dihydro-3H-
spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gb: white solid, 90%
yield (58 mg), 90:10 dr, 92%/64% ee; mp 162−165 °C. The ee was
determined by chiral HPLC (Daicel Chiralpak AD-H, hexane/iPrOH
(CDCl3, 400 MHz, TMS) δ 1.92 (s, 3H, CH3), 2.61−2.67 (m, 4H,
CH2, CH3), 3.45 (dd, J = 8.8 Hz, 13.2 Hz, 1H, CH2), 5.16 (d, J = 10.4
Hz, 1H, CH2), 5.19−5.24 (m, 1H, CH), 5.27 (d, J = 17.2 Hz, 1H,
CH2), 6.25 (ddd, J = 8.0 Hz, 10.4 Hz, 17.2 Hz, 1H, CH), 6.53 (d,
J = 8.0 Hz, 1H, ArH), 6.74 (s, 1H, CH), 6.86 (s, 1H, ArH), 6.88 (s,
1H, CH), 6.92 (d, J = 11.2 Hz, 2H, ArH), 6.99 (d, J = 7.2 Hz, 2H,
ArH), 7.03−7.15 (m, 9H, ArH), 7.16−7.25 (m, 8H, ArH); 13C NMR
(CDCl3, 100 MHz, TMS) δ 20.8, 25.4, 39.7, 66.1, 78.9, 79.2, 79.3,
86.2, 108.4, 117.8, 124.1, 126.1, 126.9, 126.93, 127.1, 127.65, 127.7,
127.8, 128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 130.5, 132.6, 137.7,
138.8, 138.97, 139.00, 139.05, 142.7, 167.7, 168.9, 173.9; IR (CH2Cl2)
ν 3061, 3028, 2925, 1727, 1610, 1491, 1455, 1425, 1363, 1257, 1202,
1154, 1082, 1028, 990, 951, 871, 815, 778, 738, 698, 681, 659 cm−1;
MS (ESI) m/z (%) 664.3 (100) [M+ + 1]; HRMS (ESI) calcd for
= 90:10, 0.8 mL/min, 230 nm); main product: tmajor = 34.2 min, tminor
1
= 38.0 min. [α]20 = +12.8 (c 1.00, CH2Cl2); H NMR (CDCl3, 400
D
MHz, TMS) δ 2.60 (s, 3H, CH3), 2.65 (dd, J = 5.2 Hz, 13.2 Hz, 1H,
CH2), 3.47 (dd, J = 9.2 Hz, 13.2 Hz, 1H, CH2), 5.16 (d, J = 10.4 Hz,
1H, CH2), 5.19−5.24 (m, 1H, CH), 5.27 (d, J = 17.6 Hz, 1H, 
CH2), 6.26 (ddd, J = 8.4 Hz, 10.4 Hz, 17.6 Hz, 1H, CH), 6.57−6.63
(m, 2H, ArH), 6.80 (s, 1H, CH), 6.86 (s, 1H, CH), 6.89−6.94 (m, 5H,
ArH), 7.00 (dd, J = 1.6 Hz, 7.6 Hz, 2H, ArH), 7.05−7.11 (m, 4H,
ArH), 7.14−7.25 (m, 11H, ArH); 13C NMR (CDCl3, 100 MHz, TMS)
δ 25.3, 39.8, 65.8, 79.1, 79.2, 79.3, 85.8, 108.4, 117.8, 122.9, 123.9,
125.3, 126.7, 126.9, 127.7, 127.76, 127.8, 127.9, 128.0, 128.1, 128.3,
128.4, 130.2, 137.6, 138.71, 138.74, 138.9, 139.0, 144.9, 167.7, 169.0,
173.7; IR (CH2Cl2) ν 3062, 3031, 2925, 1720, 1615, 1496, 1471, 1455,
1375, 1354, 1261, 1246, 1186, 1154, 1098, 1080, 1029, 996, 940, 781,
+
C43H38NO6 (M+ + H) requires 664.2699, found 664.2682.
(2S,5S)-Dibenzhydryl 5′-chloro-1′-methyl-2′-oxo-5-vinyl-4,5-di-
hydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gf: white
solid, 95% yield (65 mg), 90:10 dr, 92%/68% ee (>20:1 dr, 96% ee
H
dx.doi.org/10.1021/om400473p | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
after recrystallization from DCM/PE); mp 138−141 °C. The ee was
determined by chiral HPLC (Daicel Chiralpak AD-H, hexane/iPrOH
CH2), 6.24 (ddd, J = 8.4 Hz, 10.0 Hz, 16.8 Hz, 1H, CH), 6.38−
6.41 (m, 2H, ArH), 6.77−6.82 (m, 2H, CH, ArH), 6.85 (s, 1H, CH),
6.89−6.94 (m, 4H, ArH), 7.01−7.03 (m, 2H, ArH), 7.06−7.12 (m,
4H, ArH), 7.14−7.25 (m, 10H, ArH); 13C NMR (CDCl3, 100 MHz,
TMS) δ 21.8, 25.3, 39.6, 65.8, 79.0, 79.1, 85.8, 109.2, 117.6, 120.9,
123.2, 124.9, 126.7, 126.9, 127.6, 127.67, 127.7, 127.8, 127.9, 128.0,
128.1, 128.3, 128.34, 137.7, 138.7, 138.8, 138.9, 140.5, 144.9, 167.6,
168.9, 174.0. IR (CH2Cl2) ν 3067, 3022, 2935, 1727, 1611, 1495,
1410, 1388, 1361, 1244, 1200, 1184, 1062, 1001, 998, 877, 813, 765,
712, 695, 659 cm−1; MS (ESI) m/z (%) 664.3 (100) [M+ + 1]; HRMS
= 70:30, 0.7 mL/min, 230 nm); main product: tmajor = 32.4 min, tminor
1
= 13.1 min; [α]20 = +15.1 (c 1.90, CH2Cl2); H NMR (CDCl3, 400
D
MHz, TMS) δ 2.63 (dd, J = 5.6 Hz, 13.2 Hz, 1H, CH2), 2.66 (s, 3H,
CH3), 3.44 (dd, J = 9.2 Hz, 13.2 Hz, 1H, CH2), 5.15−5.22 (m, 2H,
CH, CH2), 5.27 (d, J = 17.2 Hz, 1H, CH2), 6.21 (ddd, J = 8.0 Hz,
10.0 Hz, 17.2 Hz, 1H, CH), 6.50 (d, J = 8.4 Hz, 1H, ArH), 6.72 (s,
1H, CH), 6.88 (s, 1H, CH), 6.92−6.96 (m, 4H, ArH), 7.05−7.14 (m,
6H, ArH), 7.15−7.20 (m, 5H, ArH), 7.21−7.26 (m, 7H, ArH); 13C
NMR (CDCl3, 100 MHz, TMS) δ 20.6, 34.5, 61.3, 74.55, 74.6, 80.8,
104.6, 113.1, 120.85, 120.9, 121.8, 121.9, 122.1, 122.2, 122.7, 122.8,
123.1, 123.2, 123.3, 123.4, 123.5, 123.6, 125.3, 132.3, 133.5, 133.78,
133.8, 138.6, 162.4, 163.6, 168.7; IR (CH2Cl2) ν 3066, 3018, 2924,
2846, 1727, 1612, 1494, 1467, 1455, 1431, 1364, 1262, 1203, 1154,
1113, 1082, 1029, 1002, 951, 848, 814, 780, 755, 698, 666, 659 cm−1;
MS (ESI) m/z (%) 684.2 (100) [M+ + 1]; HRMS (ESI) calcd for
C42H35ClNO6+ (M+ + H) requires 684.2153, found 684.2134.
+
(ESI) calcd for C43H38NO6 (M+ + H) requires 664.2699, found
664.2676.
(2S,5S)-Dibenzhydryl 6′-chloro-1′-methyl-2′-oxo-5-vinyl-4,5-di-
hydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gj: white
solid, 98% yield (67 mg), 87/13 dr, 93%/63% ee; mp 150−152 °C.
The ee was determined by chiral HPLC (Daicel Chiralpak AD-H,
hexane/iPrOH = 70:30, 0.4 mL/min, 230 nm); main product: tmajor
=
16.5 min, tminor = 24.0 min; [α]20D = +14.5 (c 1.20, CH2Cl2); 1H NMR
(CDCl3, 300 MHz, TMS) δ 2.59 (s, 3H, CH3), 2.65 (dd, J = 5.1 Hz,
13.2 Hz, 1H, CH2), 3.46 (dd, J = 9.3 Hz, 13.2 Hz, 1H, CH2), 5.15−
5.30 (m, 3H, CH, CH2), 6.24 (ddd, J = 8.1 Hz, 9.9 Hz, 17.4 Hz, 1H,
CH), 6.46 (dd, J = 2.4 Hz, 8.4 Hz, 1H, ArH), 6.53−6.55 (m, 1H,
ArH), 6.70−6.77 (m, 1H, ArH), 6.79 (s, 1H, CH), 6.87 (s, 1H, CH),
6.91−6.94 (m, 4H, ArH), 6.99−7.08 (m, 4H, ArH), 7.11−7.32 (m,
13H, ArH); 13C NMR (CDCl3, 75 MHz, TMS) δ 25.4, 39.5, 65.8,
79.3, 85.3, 109.0, 117.9, 122.2, 122.4, 126.3, 126.6, 126.9, 127.6, 127.8,
127.9, 128.1, 128.3, 128.4, 136.0, 137.4, 138.5, 138.6, 138.68, 138.7,
146.1, 167.4, 168.8, 173.7; IR (CH2Cl2) ν 3052, 3014, 2911, 1721,
1655, 1466, 1445, 1363, 1312, 1255, 1151, 1012, 1001, 998, 921, 888,
770, 738, 693, 656 cm−1; MS (ESI) m/z (%) 706.2 (100) [M+ + Na];
(2S,5S)-Dibenzhydryl 5′-bromo-1′-methyl-2′-oxo-5-vinyl-4,5-di-
hydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gg: white
solid, 98% yield (70 mg), 88/12 dr, 93%/84% ee; mp 122−125 °C.
The ee was determined by chiral HPLC (Daicel Chiralpak AD-H,
hexane/iPrOH = 70:30, 0.7 mL/min, 230 nm); main product: tmajor
=
51.9 min, tminor = 14.0 min; [α]20D = +22.8 (c 1.00, CH2Cl2); 1H NMR
(CDCl3, 400 MHz, TMS) δ 2.60−2.66 (m, 4H, CH2, CH3), 3.43 (dd,
J = 9.6 Hz, 13.2 Hz, 1H, CH2), 5.15−5.29 (m, 3H, CH, CH2), 6.20
(ddd, J = 8.0 Hz, 10.0 Hz, 17.6 Hz, 1H, CH), 6.45 (d, J = 8.4 Hz,
1H, ArH), 6.71 (s, 1H, CH), 6.88 (s, 1H, CH), 6.93−6.97 (m, 4H,
ArH), 7.06−7.14 (m, 6H, ArH), 7.15−7.25 (m, 10H, ArH), 7.34−7.40
(m, 2H, ArH); 13C NMR (CDCl3, 100 MHz, TMS) δ 25.5, 39.4, 66.3,
79.49, 79.5, 79.6, 85.7, 110.0, 115.6, 118.1, 126.2, 126.7, 126.8, 126.9,
127.1, 127.6, 127.8, 128.1, 128.2, 128.3, 128.34, 128.5, 128.57, 128.6,
133.2, 137.3, 138.4, 138.7, 138.8, 144.1, 167.4, 168.5, 173.5. IR
(CH2Cl2) ν 3066, 3032, 2952, 2919, 1727, 1607, 1579, 1496, 1464,
1346, 1263, 1244, 1186, 1153, 1078, 1032, 1012, 977, 950, 909, 856,
780, 736, 695 cm−1; MS (ESI) m/z (%) 728.2 (100) [M+ + 1]; HRMS
+
HRMS (ESI) calcd for C42H34ClNNaO6 (M+ + H) requires
706.1972, found 706.1938.
(2S,5S)-Dibenzhydryl 6′-bromo-1′-methyl-2′-oxo-5-vinyl-4,5-di-
hydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gk: white
solid, 83% yield (60 mg), 85/15 dr, 95%/60% ee; mp 147−150 °C.
The ee was determined by chiral HPLC (Daicel Chiralpak AD-H,
+
(ESI) calcd for C42H35BrNO6 (M+ + H) requires 728.1648, found
hexane/iPrOH = 90:10, 0.7 mL/min, 230 nm); main product: tmajor
=
16.1 min, tminor = 26.3 min; [α]20D = +10.6 (c 1.00, CH2Cl2); 1H NMR
(CDCl3, 300 MHz, TMS) δ 2.59 (s, 3H, CH3), 2.65 (dd, J = 4.8 Hz,
13.5 Hz, 1H, CH2), 3.45 (dd, J = 9.0 Hz, 13.5 Hz, 1H, CH2), 5.16−
5.23 (m, 2H, CH, CH2), 5.27 (d, J = 17.4 Hz, 1H, CH2), 6.24
(ddd, J = 8.1 Hz, 9.3 Hz, 17.4 Hz, 1H, CH), 6.58−6.64 (m, 1H,
ArH), 6.67−6.70 (m, 2H, ArH), 6.78 (s, 1H, CH), 6.87 (s, 1H, CH),
6.90−6.94 (m, 4H, ArH), 6.99−7.08 (m, 4H, ArH), 7.12−7.22 (m,
9H, ArH), 7.25−7.34 (m, 3H, ArH); 13C NMR (CDCl3, 75 MHz,
TMS) δ 25.4, 39.6, 50.8, 65.9, 79.28, 79.3, 85.4, 111.8, 117.9, 122.8,
124.0, 125.5, 126.6, 126.7, 127.0, 127.6, 127.8, 127.9, 128.1, 128.2,
128.3, 128.4, 137.4, 138.55, 138.6, 138.7, 138.8, 146.1, 167.4, 168.8,
173.7. IR (CH2Cl2) ν 3062, 3031, 2925, 1729, 1606, 1495, 1455, 1432,
1371, 1255, 1201, 1185, 1154, 1101, 1063, 1026, 989, 953, 844, 811,
758, 741, 698 cm−1; MS (ESI) m/z (%) 728.2 (100) [M+ + 1]; HRMS
(ESI) calcd for C42H35BrNO6+ (M+ + H) requires 728.1648, found
728.1647.
728.1660.
(2S,5S)-Dibenzhydryl 5′-fluoro-1′-methyl-2′-oxo-5-vinyl-4,5-dihy-
dro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gh: colorless
oil, 93% yield (62 mg), 91/9 dr, 92%/68% ee; mp 163−166 °C. The
ee was determined by chiral HPLC (Daicel Chiralpak AD-H, hexane/
iPrOH = 90:10, 0.7 mL/min, 230 nm) main product: tmajor = 49.1 min,
tminor = 43.9 min; [α]20D = +16.0 (c 2.50, CH2Cl2); 1H NMR (CDCl3,
400 MHz, TMS) δ 2.61−2.67 (m, 4H, CH2, CH3), 3.48 (dd, J = 9.2
Hz, 13.2 Hz, 1H, CH2), 5.17 (d, J = 10.0 Hz, 1H, CH2), 5.19−5.24
(m, 1H, CH), 5.27 (d, J = 17.2 Hz, 1H, CH2), 6.22 (ddd, J = 8.0 Hz,
10.0 Hz, 17.2 Hz, 1H, CH), 6.48 (dd, J = 4.0 Hz, 8.4 Hz, 1H, ArH),
6.76 (s, 1H, CH), 6.82 (dd, J = 2.8 Hz, 8.4 Hz, 1H, ArH), 6.87 (s, 1H,
CH), 6.90−6.96 (m, 5H, ArH), 7.03−7.10 (m, 4H, ArH), 7.11−7.19
(m, 5H, ArH), 7.18−7.25 (m, 7H, ArH); 13C NMR (CDCl3, 75 MHz,
TMS) δ 25.4, 39.6, 66.0, 79.3, 79.4, 85.8, 108.9 (d, J = 7.8 Hz), 113.8
(d, J = 25.6 Hz), 116.4 (d, J = 22.8 Hz), 117.9, 125.5 (d, J = 8.2 Hz),
126.7, 126.8, 127.2, 127.6, 127.7, 127.9, 128.0, 128.2, 128.3, 128.38,
128.4, 137.3, 138.4, 138.68, 138.7, 138.8, 140.9, 158.9 (d, J = 240.0
Hz), 167.4, 168.7, 173.6; 19F NMR (CDCl3, 376 MHz, CFCl3) δ
−119.0; IR (CH2Cl2) ν 3062, 3032, 2925, 1724, 1622, 1497, 1469,
1454, 1365, 1273, 1260, 1204, 1152, 1133, 1096, 1079, 1028, 1002,
953, 885, 804, 758, 741, 699 cm−1; MS (ESI) m/z (%) 668.2 (100)
(2S,5S)-Dibenzhydryl 7′-chloro-1′-methyl-2′-oxo-5-vinyl-4,5-di-
hydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gl: white
solid, 93% yield (63 mg), 86/14 dr, 94%/62% ee; mp 149−152 °C.
The ee was determined by chiral HPLC (Daicel Chiralpak AD-H,
hexane/iPrOH = 75:25, 0.4 mL/min, 230 nm); main product: tmajor
=
40.7 min, tminor = 15.3 min; [α]20D = +24.5 (c 1.70, CH2Cl2); 1H NMR
(CDCl3, 400 MHz, TMS) δ 2.67 (dd, J = 5.2 Hz, 13.2 Hz, 1H, CH2),
3.04 (s, 3H, CH3), 3.46 (dd, J = 9.2 Hz, 13.2 Hz, 1H, CH2), 5.15−5.21
(m, 2H, CH, CH2), 5.27 (d, J = 18.0 Hz, 1H, CH2), 6.25 (ddd, J
= 8.4 Hz, 10.0 Hz, 18.0 Hz, 1H, CH), 6.41 (dd, J = 8.0 Hz, 8.0 Hz,
1H, ArH), 6.79−6.82 (m, 2H, ArH), 6.85 (s, 1H, CH), 6.88 (s, 1H,
ArH), 6.90 (s, 1H, CH), 6.96−7.00 (m, 4H, ArH), 7.09−7.13 (m, 3H,
ArH), 7.14−7.23 (m, 8H, ArH), 7.24−7.27 (m, 4H, ArH); 13C NMR
(CDCl3, 100 MHz, TMS) δ 28.9, 39.7, 66.1, 79.3, 79.4, 85.0, 115.5,
118.1, 123.5, 123.8, 126.6, 126.7, 126.9, 127.57, 127.6, 127.7, 127.85,
127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.47, 128.5, 132.4, 132.5,
137.4, 138.6, 138.67, 138.7, 138.8, 140.8, 167.5, 168.8, 174.1; IR
+
[M+ + 1]; HRMS (ESI) calcd for C42H35FNO6 (M+ + H) requires
668.2448, found 668.2460.
(2S,5S)-Dibenzhydryl 1′,6′-dimethyl-2′-oxo-5-vinyl-4,5-dihydro-
3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gi: white solid,
94% yield (62 mg), 88/12 dr, 94%/63% ee; mp 128−131 °C. The
ee was determined by chiral HPLC (Daicel Chiralpak AD-H, hexane/
iPrOH = 70:30, 0.4 mL/min, 230 nm); main product: tmajor = 18.7
min, tminor = 22.5 min; [α]20 = +14.4 (c 1.80, CH2Cl2); H NMR
1
D
(CDCl3, 400 MHz, TMS) δ 2.31 (s, 3H, CH3), 2.59−2.67 (m, 4H,
CH2, CH3), 3.44 (dd, J = 9.2 Hz, 13.2 Hz, 1H, CH2), 5.15 (d, J = 10.0
Hz, 1H, CH2), 5.19−5.23 (m, 1H, CH), 5.26 (d, J = 16.8 Hz, 1H,
I
dx.doi.org/10.1021/om400473p | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(CH2Cl2) ν 3059, 3032, 2949, 2919, 1725, 1609, 1496, 1464, 1366,
1340, 1248, 1201, 1154, 1125, 1081, 1066, 1032, 1002, 950, 910, 788,
759, 737, 698 cm−1; MS (ESI) m/z (%) 706.2 (100) [M+ + Na];
solid, 87% yield (60 mg), 81/19 dr, 82%/64% ee; mp 88−90 °C.
The ee was determined by chiral HPLC (Daicel Chiralpak AD-H,
hexane/iPrOH = 80:20, 0.7 mL/min, 230 nm); main product: tmajor
=
HRMS (ESI) calcd for C42H34ClNNaO6 (M+ + Na) requires
43.2 min, tminor = 60.4 min; [α]20D = +25.3 (c 1.80, CH2Cl2); 1H NMR
(CDCl3, 400 MHz, TMS) δ 2.73 (dd, J = 5.6 Hz, 13.2 Hz, 1H, CH2),
3.40 (dd, J = 9.2 Hz, 13.2 Hz, 1H, CH2), 3.65 (s, 6H, CH3), 3.69 (s,
6H, CH3), 4.51 (d, J = 16.0 Hz, 1H, CH2), 4.73 (d, J = 16.0 Hz, 1H,
CH2), 4.91 (d, J = 12.0 Hz, 1H, CH2), 5.02 (d, J = 12.0 Hz, 2H, CH2),
5.10 (d, J = 12.0 Hz, 1H, CH2), 5.20 (d, J = 10.4 Hz, 1H, CH2),
5.26−5.35 (m, 2H, CH, CH2), 6.24−6.26 (m, 2H, CH, ArH),
6.27−6.29 (m, 2H, ArH), 6.33−6.36 (m, 2H, ArH), 6.51 (d, J = 7.6
Hz, 1H, ArH), 6.82 (ddd, J = 0.8 Hz, 7.6 Hz, 7.6 Hz, 1H, ArH), 7.05−
7.14 (m, 2H, ArH), 7.22−7.30 (m, 6H, ArH); 13C NMR (CDCl3, 100
MHz, TMS) δ 38.8, 43.4, 55.1, 55.2, 66.3, 67.35, 67.4, 79.4, 86.0,
100.1, 100.3, 105.4, 105.9, 109.5, 117.8, 122.5, 124.1, 124.7, 127.0,
127.4, 128.6, 130.4, 135.3, 136.6, 136.9, 137.6, 144.2, 160.7, 168.2,
169.1, 174.5. IR (CH2Cl2) ν 3062, 3033, 2925, 2841, 1720, 1610,
1598, 1490, 1467, 1430, 1370, 1348, 1261, 1204, 1152, 1110, 1068,
1030, 992, 935, 835, 755, 734, 697 cm−1; MS (ESI) m/z (%) 694.3
+
706.1972, found 706.1958.
(2S,5S)-Dibenzhydryl 7′-bromo-1′-methyl-2′-oxo-5-vinyl-4,5-di-
hydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gm: white
solid, 85% yield (62 mg), 86/14 dr, 94%/58% ee; mp 130−133 °C.
The ee was determined by chiral HPLC (Daicel Chiralpak AD-H,
hexane/iPrOH = 90:10, 0.7 mL/min, 230 nm); main product: tmajor
=
49.4 min, tminor = 15.3 min. [α]20D = +29.2 (c 2.00, CH2Cl2); 1H NMR
(CDCl3, 400 MHz, TMS) δ 2.68 (dd, J = 5.2 Hz, 13.2 Hz, 1H, CH2),
3.06 (s, 3H, CH3), 3.45 (dd, J = 9.6 Hz, 13.2 Hz, 1H, CH2), 5.14−5.20
(m, 2H, CH, CH2), 5.27 (d, J = 17.2 Hz, 1H, CH2), 6.25 (ddd, J
= 8.0 Hz, 10.0 Hz, 17.2 Hz, 1H, CH), 6.32 (dd, J = 8.0 Hz, 8.0 Hz,
1H, ArH), 6.81−6.89 (m, 5H, CH, ArH), 7.08−7.12 (m, 2H, ArH),
7.13−7.23 (m, 8H, ArH), 7.24−7.30 (m, 5H, ArH); 13C NMR
(CDCl3, 100 MHz, TMS) δ 29.2, 39.8, 66.1, 79.27, 79.3, 84.7, 102.4,
118.0, 123.9, 124.3, 124.4, 126.7, 126.9, 127.0, 127.6, 127.7, 127.85,
127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 135.8, 137.4, 138.6,
138.7, 138.8, 142.2, 167.5, 168.8, 174.3; IR (CH2Cl2) ν 3059, 3032,
2934, 1724, 1607, 1579, 1496, 14575, 1364, 1248, 1200, 1185, 1154,
1062, 1029, 1011, 989, 950, 909, 781, 756, 734, 695, 663 cm−1; MS
(ESI) m/z (%) 728.2 (100) [M+ + 1]; HRMS (ESI) calcd for
+
(100) [M+ + 1]; HRMS (ESI) calcd for C40H40NO10 (M+ + H)
requires 694.2652, found 694.2638.
(2S,5S)-Dipropyl 1′-benzyl-2′-oxo-5-vinyl-4,5-dihydro-3H-spiro-
[furan-2,3′-indoline]-3,3-dicarboxylate, 3da: white solid, 82% yield
(39 mg), 82/18 dr, 82%/50% ee; mp 150−153 °C. The ee was
determined by chiral HPLC (Daicel Chiralpak AD-H, hexane/iPrOH
+
C42H35BrNO6 (M+ + H) requires 728.1648, found 728.1638.
= 70:30, 0.7 mL/min, 230 nm); main product: tmajor = 11.2 min, tminor
(2S,5S)-Dibenzhydryl 7′-fluoro-1′-methyl-2′-oxo-5-vinyl-4,5-dihy-
dro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3gn: white
solid, 97% yield (65 mg), 94/6 dr, 94%/59% ee; mp 140−143 °C.
The ee was determined by chiral HPLC (Daicel Chiralpak AD-H,
1
= 8.0 min; [α]20 = +11.3 (c 1.20, CH2Cl2); H NMR (CDCl3, 400
D
MHz, TMS) δ 1.01 (d, J = 6.4 Hz, 3H, CH3), 1.15 (d, J = 6.4 Hz, 3H,
CH3), 1.18 (d, J = 6.4 Hz, 3H, CH3), 1.22 (d, J = 6.4 Hz, 3H, CH3),
2.65 (dd, J = 5.6 Hz, 13.2 Hz, 1H, CH2), 3.31 (dd, J = 9.2 Hz, 13.2 Hz,
1H, CH2), 4.78 (d, J = 16.0 Hz, 1H, CH2), 4.95 (d, J = 16.0 Hz, 1H,
CH2), 4.99−5.09 (m, 2H, CH), 5.19−5.35 (m, 3H, CH, CH2), 6.30
(ddd, J = 8.0 Hz, 10.0 Hz, 17.6 Hz, 1H, CH), 6.64 (d, J = 8.0 Hz,
1H, ArH), 6.94 (dd, J = 8.0 Hz, 8.0 Hz, 1H, ArH), 7.16−7.21 (m, 2H,
ArH), 7.23−7.27 (m, 1H, ArH), 7.29−7.37 (m, 4H, ArH); 13C NMR
(CDCl3, 100 MHz, TMS) δ 21.2, 21.3, 21.49, 21.5, 39.1, 43.8, 66.3,
69.3, 70.1, 79.5, 85.9, 109.4, 117.5, 122.3, 124.7, 125.0, 127.2, 127.5,
128.7, 130.4, 135.4, 138.0, 144.3, 168.0, 169.1, 174.8; IR (CH2Cl2) ν
3066, 3012, 2985, 2918, 1744, 1718, 1616, 1493, 1468, 1456, 1434,
1375, 1368, 1290, 1266, 1240, 1216, 1189, 1165, 1146, 1106, 1078,
1057, 1028, 987, 944, 934, 906, 848, 801, 751, 733, 696, 679 cm−1; MS
(ESI) m/z (%) 478.2 (100) [M+ + 1]; HRMS (ESI) calcd for
hexane/iPrOH = 70:30, 0.4 mL/min, 230 nm); main product: tmajor
=
28.8 min, tminor = 15.9 min. [α]20D = +11.4 (c 2.30, CH2Cl2); 1H NMR
(CDCl3, 300 MHz, TMS) δ 2.66 (dd, J = 5.1 Hz, 13.2 Hz, 1H, CH2),
2.86 (d, J = 2.7 Hz, 3H, CH3), 3.46 (dd, J = 9.0 Hz, 13.2 Hz, 1H,
CH2), 5.14−5.30 (m, 3H, CH, CH2), 6.25 (ddd, J = 8.1 Hz, 10.2
Hz, 17.7 Hz, 1H, CH), 6.45−6.52 (m, 1H, ArH), 6.69−6.75 (m,
1H, ArH), 6.79 (s, 1H, CH), 6.88 (s, 1H, CH), 6.89−6.94 (m, 3H,
ArH), 6.97−7.02 (m, 4H, ArH), 7.08−7.13 (m, 4H, ArH), 7.14−7.20
(m, 6H, ArH), 7.22−7.27 (m, 4H, ArH); 13C NMR (CDCl3, 75 MHz,
TMS) δ 27.9 (d, J = 5.9 Hz), 39.6, 66.0, 79.2, 79.3, 79.4, 85.6 (d, J =
2.8 Hz), 117.9, 118.2 (d, J = 19.9 Hz), 121.1 (d, J = 3.4 Hz), 123.2 (d,
J = 5.8 Hz), 126.6, 126.7, 126.8, 127.5, 127.6, 127.8, 127.9, 128.0,
128.1, 128.3, 128.39, 128.4, 131.5 (d, J = 8.3 Hz), 137.4, 138.6, 138.7,
147.4 (d, J = 242.7 Hz), 167.4, 168.7, 173.5; 19F NMR (CDCl3, 282
MHz, CFCl3) δ −136.7; IR (CH2Cl2) ν 3073, 3032, 2905, 1723, 1632,
1601, 1482, 1455, 1370, 1343, 1242, 1204, 1153, 1087, 1002, 983, 951,
910, 879, 867, 781, 757, 735, 696 cm−1; MS (ESI) m/z (%) 690.2
(100) [M+ + Na]; HRMS (ESI) calcd for C42H34FNNaO6+ (M+ + Na)
requires 690.2268, found 690.2240.
+
C28H32NO6 (M+ + H) requires 478.2230, found 478.2238.
(2S,5S)-Dimethyl 1′-benzyl-2′-oxo-5-vinyl-4,5-dihydro-3H-spiro-
[furan-2,3′-indoline]-3,3-dicarboxylate, 3aa: white solid, 86% yield
(36 mg), 77/23 dr, 74%/72% ee; mp 116−119 °C. The ee was
determined by chiral HPLC (Daicel Chiralpak PC-2, hexane/iPrOH =
70:30, 0.5 mL/min, 230 nm); main product: tmajor = 24.9 min, tminor
=
1
15.6 min; [α]20 = +15.1 (c 1.50, CH2Cl2); H NMR (CDCl3, 400
(2S,5S)-Dibenzyl 1′-benzyl-2′-oxo-5-vinyl-4,5-dihydro-3H-spiro-
[furan-2,3′-indoline]-3,3-dicarboxylate, 3ba: white solid, 95% yield
(54 mg), 89/11 dr, 82%/60% ee; mp 107−110 °C. The ee was
determined by chiral HPLC (Daicel Chiralpak AD-H, hexane/iPrOH
= 70:30, 0.7 mL/min, 214 nm); main product: tmajor = 30.1 min, tminor
D
MHz, TMS) δ 2.69 (dd, J = 5.6 Hz, 13.2 Hz, 1H, CH2), 3.33 (dd, J =
9.2 Hz, 13.2 Hz, 1H, CH2), 3.62 (s, 3H, CH3), 3.70 (s, 3H, CH3), 4.75
(d, J = 16.0 Hz, 1H, CH2), 4.98 (d, J = 16.0 Hz, 1H, CH2), 5.17−5.29
(m, 2H, CH, CH2), 5.33 (d, J = 17.2 Hz, 1H, CH2), 6.29 (ddd, J
= 8.0 Hz, 10.4 Hz, 17.2 Hz, 1H, CH), 6.77 (d, J = 7.6 Hz, 1H, ArH),
6.95−7.00 (m, 1H, ArH), 7.18−7.28 (m, 1H, ArH), 7.30−7.35 (m,
4H, ArH), 7.38−7.40 (m, 2H, ArH); 13C NMR (CDCl3, 100 MHz,
TMS) δ 38.9, 43.9, 44.0, 52.8, 66.1, 79.4, 86.0, 111.0, 117.9, 123.8,
124.5, 125.4, 127.38, 127.4, 128.7, 129.0, 130.7, 135.4, 138.3, 144.3,
150.7, 169.0, 169.9, 174.7; IR (CH2Cl2) ν 3056, 3016, 2953, 2923,
2838, 1732, 1612, 1491, 1468, 1455, 1435, 1368, 1351, 1268, 1214,
1185, 1155, 1111, 1080, 1031, 996, 937, 880, 817, 781, 754, 736, 698
cm−1; MS (ESI) m/z (%) 422.2 (100) [M+ + 1]; HRMS (ESI) calcd
for C24H24NO6+ (M+ + H) requires 422.1604, found 422.1590.
(2S,5S)-Dimethyl 1′-methyl-2′-oxo-5-((E)-styryl)-4,5-dihydro-3H-
spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3hb. colorless oil, 28%
yield (12 mg), 86/14 dr, 11%/8% ee; mp 130−133 °C. The ee was
determined by chiral HPLC (Daicel Chiralpak AD-H, hexane/iPrOH
20
1
= 17.3 min; [α]D = +15.3 (c 1.50, CH2Cl2); H NMR (CDCl3, 300
MHz, TMS) δ 2.71 (dd, J = 5.1 Hz, 13.2 Hz, 1H, CH2), 3.38 (dd, J =
9.3 Hz, 13.2 Hz, 1H, CH2), 4.38 (d, J = 15.9 Hz, 1H, CH2), 4.74 (d, J
= 15.9 Hz, 1H, CH2), 4.98−5.03 (m, 2H, CH2), 5.13−5.21 (m, 2H,
CH2), 5.26−5.35 (m, 3H, CH, CH2), 6.26 (ddd, J = 7.8 Hz, 10.2
Hz, 17.7 Hz, 1H, CH), 6.51 (d, J = 7.8 Hz, 1H, ArH), 6.83 (dd, J =
7.8 Hz, 7.8 Hz, 1H, ArH), 7.02−7.17 (m, 6H, ArH), 7.21−7.28 (m,
11H, ArH); 13C NMR (CDCl3, 100 MHz, TMS) δ 38.9, 43.4, 66.3,
67.5, 67.7, 79.5, 86.0, 109.6, 117.8, 122.6, 124.3, 124.7, 127.1, 127.4,
128.1, 128.2, 128.3, 128.35, 128.4, 128.6, 130.3, 134.4, 134.7, 135.3,
137.6, 144.1, 168.2, 169.2, 174.5.; IR (CH2Cl2) ν 3058, 3033, 2922,
1719, 1613, 1491, 1468, 1455, 1368, 1263, 1186, 1155, 1109, 1077,
1029, 993, 935, 874, 799, 775, 733, 695 cm−1; MS (ESI) m/z (%)
574.2 (100) [M+ + 1]; HRMS (ESI) calcd for C36H32NO6+ (M+ + H)
requires 574.2230, found 574.2224.
= 70:30, 0.7 mL/min, 230 nm); main product: tmajor = 22.5 min, tminor
1
= 16.6 min; [α]20 = +7.8 (c 1.30, CH2Cl2); H NMR (CDCl3, 300
(2S,5S)-Bis(3,5-dimethoxybenzyl) 1′-benzyl-2′-oxo-5-vinyl-4,5-di-
D
hydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3ea: white
MHz, TMS) δ 2.75 (dd, J = 5.1 Hz, 13.2 Hz, 1H, CH2), 3.20 (s, 3H,
J
dx.doi.org/10.1021/om400473p | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
CH3), 3.35 (dd, J = 9.6 Hz, 13.2 Hz, 1H, CH2), 3.67 (s, 3H, CH3),
3.74 (s, 3H, CH3), 5.37−5.45 (m, 1H, CH), 6.60−6.65 (m, 2H, 
CH, ArH), 6.84 (d, J = 10.4 Hz, 1H, CH), 7.00−7.06 (m, 1H, ArH),
7.11−7.14 (m, 1H, ArH), 7.24−7.39 (m, 4H, ArH), 7.43−7.62 (m,
2H, ArH); 13C NMR (CDCl3, 75 MHz, TMS) δ 26.0, 39.0, 52.8, 66.3,
79.2, 86.0, 108.6, 122.6, 124.0, 124.5, 126.8, 127.8, 128.4, 128.8, 130.9,
133.3, 136.4, 145.1, 169.1, 170.0, 174.7; IR (CH2Cl2) ν 3066, 3021,
2956, 2850, 1734, 1612, 1495, 1471, 1436, 1371, 1353, 1261, 1199,
1093, 1027, 983, 865, 801, 780, 755, 696 cm−1; MS (ESI) m/z (%)
422.2 (100) [M++1]; HRMS (ESI) calcd for C24H24NO6+ (M+ + H)
requires 422.1604, found 422.1598.
mp 120−123 °C. The ee was determined by chiral HPLC (Daicel
Chiralpak AD-H, hexane/iPrOH = 80:20, 0.7 mL/min, 230 nm); main
product: tmajor = 15.0 min, tminor = 16.0 min; [α]20 = +1.6 (c 0.50,
D
CH2Cl2); 1H NMR (CDCl3, 300 MHz, TMS) δ 3.99 (dd, J = 6.9 Hz,
6.9 Hz, 1H, CH2), 4.74 (dd, J = 6.9 Hz, 6.9 Hz, 1H, CH2), 4.81−4.89
(m, 2H, CH2), 5.29−5.36 (m, 2H, CH, CH2), 5.49 (d, J = 17.4 Hz,
1H, CH), 6.00 (ddd, J = 7.5 Hz, 10.2 Hz, 17.4 Hz, 1H, CH), 6.65
(d, J = 7.5 Hz, 1H, ArH), 7.02−7.08 (m, 1H, ArH), 7.21−7.34 (m, 6H,
ArH), 7.40 (d, J = 7.5 Hz, 1H, ArH); 13C NMR (CDCl3, 75 MHz,
TMS) δ 43.3, 70.3, 78.2, 102.9, 109.6, 119.1, 123.2, 123.8, 124.8,
127.1, 127.6, 128.7, 131.5, 134.9, 135.0, 143.7, 173.2; IR (CH2Cl2) ν
3065, 3031, 2920, 2887, 2846, 1730, 1618, 1489, 1468, 1455, 1431,
1364, 1284, 1265, 1219, 1181, 1131, 1094, 1079, 1036, 1010, 981, 937,
846, 756, 735, 697 cm−1; MS (ESI) m/z (%) 308.1 (100) [M+ + 1];
HRMS (ESI) calcd for C19H18NO3+ (M+ + H) requires 308.1287,
found 308.1271.
(2S,5S)-Dineopentyl 1′-benzyl-2′-oxo-5-vinyl-4,5-dihydro-3H-
spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3fa: white solid, 85%
yield (45 mg), 60/40 dr, 40%/85% ee; mp 158−160 °C. The ee was
determined by chiral HPLC (Daicel Chiralpak AD-H, hexane/iPrOH
= 98:2, 0.7 mL/min, 230 nm); main product: tmajor = 13.6 min, tminor
=
1
32.1 min; [α]20 = +1.0 (c 1.70, CH2Cl2); H NMR (CDCl3, 400
4. General Procedure for the Synthesis of 4, 5, 6, and 7. A dried
flask was charged with (2S,5S)-dibenzhydryl 1′-benzyl-2′-oxo-5-vinyl-
4,5-dihydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate (3ga) (1.0
equiv) and Pd/C (20 mol %), and ethyl acetate (0.1 M) was added
slowly. The reaction mixture was stirred under 1 atm H2 atomsphere at
room temperature for 24 h. The mixture was concentrated in vacuo to
yield the crude product, which was purified by flash chromatography
on silica gel (eluent: PE/EtOAc = 1:1) to furnish the desired acid 4 as
a white solid.
D
MHz, TMS) δ 0.77 (s, 9H, CH3), 0.88 (s, 9H, CH3), 2.73 (dd, J = 5.2
Hz, 13.2 Hz, 1H, CH2), 3.37 (dd, J = 9.2 Hz, 13.2 Hz, 1H, CH2), 3.51
(d, J = 10.4 Hz, 1H, CH2), 3.65 (d, J = 10.4 Hz, 1H, CH2), 3.76 (d, J =
10.4 Hz, 1H, CH2), 4.01 (d, J = 10.4 Hz, 1H, CH2), 4.79−4.96 (m,
2H, CH2), 5.17−5.36 (m, 3H, CH, CH2), 6.33 (ddd, J = 8.0 Hz,
10.0 Hz, 17.2 Hz, 1H, CH), 6.62 (d, J = 8.0 Hz, 1H, ArH), 6.91−
6.96 (m, 1H, ArH), 7.07−7.18 (m, 2H, ArH), 7.24−7.43 (m, 5H,
ArH); 13C NMR (CDCl3, 100 MHz, TMS) δ 26.2, 26.3, 31.1, 31.2,
38.8, 43.7, 66.4, 74.9, 75.2, 79.2, 85.9, 110.0, 117.7, 122.5, 124.2, 124.7,
127.1, 127.4, 128.6, 130.4, 135.3, 137.8, 144.3, 168.4, 169.5, 174.9; IR
(CH2Cl2) ν 3052, 3026, 2958, 2872, 1723, 1614, 1491, 1468, 1436,
1367, 1258, 1203, 1186, 1158, 1111, 1079, 1031, 991, 969, 936, 798,
751, 737, 697 cm−1; MS (ESI) m/z (%) 534.3 (100) [M+ + 1]; HRMS
(ESI) calcd for C32H40NO6+ (M+ + H) requires 534.2856, found
534.2865.
(2S,5R)-1′-Benzyl-5-ethyl-2′-oxo-4,5-dihydro-3H-spiro[furan-2,3′-
indoline]-3,3-dicarboxylic acid, 4: white solid, 82% yield (32 mg),
>20/1 dr; mp 102−105 °C; [α]20D = +14.8 (c 1.7, CH2Cl2); 1H NMR
(CD3OD, 400 MHz, TMS) δ 0.97 (t, J = 7.2 Hz, 3H, CH3), 1.79−1.92
(m, 2H, CH2), 2.56 (dd, J = 6.0 Hz, 12.8 Hz, 1H, CH2), 3.10 (dd, J =
8.8 Hz, 12.8 Hz, 1H, CH2), 4.66−4.74 (m, 1H, CH), 4.77 (d, J = 16.4
Hz, 1H, CH2), 4.96 (d, J = 16.4 Hz, 1H, CH2), 6.68 (d, J = 7.6 Hz, 1H,
ArH), 6.98 (dd, J = 7.6 Hz, 7.6 Hz, 1H, ArH), 7.18−7.25 (m, 2H,
ArH), 7.28−7.35 (m, 3H, ArH), 7.37−7.40 (m, 2H, ArH); 13C NMR
(CD3OD, 100 MHz, TMS) δ 8.8, 9.6, 27.7, 28.8, 38.0, 43.0, 80.1,
109.2, 109.3, 122.2, 125.2, 125.3, 126.8, 126.84, 127.0, 128.3, 129.8,
135.7, 144.1, 176.1; IR (CH2Cl2) ν 3349, 3033, 2965, 2932, 1719,
1615, 1491, 1467, 1370, 1262, 1184, 1082, 1031, 798, 753, 697 cm−1;
MS (ESI) m/z (%) 396.1 (100) [M+ + 1]; HRMS (ESI) calcd for
(2S,5S)-Di-tert-butyl 1′-benzyl-2′-oxo-5-vinyl-4,5-dihydro-3H-
spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 3ca. white solid, 85%
yield (43 mg), 71/29 dr, 76%/37% ee; mp 145−148 °C. The ee was
determined by chiral HPLC (Daicel Chiralpak PC-4, hexane/iPrOH =
90:10, 0.5 mL/min, 230 nm); main product: tmajor = 11.8 min, tminor
=
1
19.6 min; [α]20 = +8.4 (c 2.50, CH2Cl2); H NMR (CDCl3, 300
D
MHz, TMS) δ 1.39 (s, 9H, CH3), 1.40 (s, 9H, CH3), 2.56 (dd, J = 6.0
Hz, 13.5 Hz, 1H, CH2), 3.33 (dd, J = 9.0 Hz, 13.5 Hz, 1H, CH2), 4.79
(d, J = 15.6 Hz, 1H, CH2), 4.97 (d, J = 15.6 Hz, 1H, CH2), 5.14−5.34
(m, 3H, CH, CH2), 6.29 (ddd, J = 7.8 Hz, 9.6 Hz, 17.7 Hz, 1H, 
CH), 6.64 (d, J = 7.8 Hz, 1H, ArH), 6.92−6.98 (m, 1H, ArH), 7.16−
7.38 (m, 7H, ArH); 13C NMR (CDCl3, 100 MHz, TMS) δ 27.7, 27.8,
39.8, 43.6, 67.4, 79.4, 82.0, 83.2, 86.0, 109.1, 117.3, 122.2, 125.7, 127.3,
127.4, 128.6, 130.2, 135.4, 138.2, 144.2, 167.6, 168.9, 174.8; IR
(CH2Cl2) ν 3055, 3012, 2979, 2932, 1720, 1615, 1491, 1468, 1456,
14393, 1367, 1298, 1253, 1167, 1142, 1077, 1029, 1000, 934, 842, 801,
752, 734, 698 cm−1; MS (ESI) m/z (%) 506.3 (100) [M+ + 1]; HRMS
+
C22H22NO6 (M+ + H) requires 396.1447, found 396.1436.
To a solution of (2S,5S)-dibenzhydryl 1′-benzyl-2′-oxo-5-vinyl-4,5-
dihydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate (3ga) (1.0
equiv) in THF (0.1 M) was added BH3 (1.0 M in THF, 3.0 equiv)
over 5 min at 0 °C, and the reaction was stirred at 0 °C for 1.5 h. To
the resulting solution was added 1.0 M NaOH aqueous (2.0 equiv)
slowly, followed by the addition of 30% aqueous H2O2 (2.0 equiv).
The mixture was stirred for 15 min, then diluted by the addition of
H2O, extracted with ethyl ether, and dried over anhydrous Na2SO4.
The solvent was removed under vacuum, and the residue was purified
by silica gel column chromatography (PE/EA = 5:1) to give the
desired products 5a and 5b, both as white solids.
+
(ESI) calcd for C30H36NO6 (M+ + H) requires 506.2543, found
506.2540.
1′-Benzyl-2′-oxo-5-vinyl-4,5-dihydro-3H-spiro[furan-2,3′-indo-
line]-3,3-dicarbonitrile, 3ja: white solid, 98% yield (35 mg), 56/44 dr,
1%/1% ee; mp 140−143 °C. The ee was determined by chiral HPLC
(Daicel Chiralpak IC-H, hexane/iPrOH = 70:30, 0.5 mL/min, 230
nm); main product: tmajor = 10.4 min, tminor = 9.9 min; [α]20D = +0.20
(c 2.20, CH2Cl2); 1H NMR (CDCl3, 300 MHz, TMS) δ 3.07 (dd, J =
5.7 Hz, 12.9 Hz, 1H, CH2), 3.65 (dd, J = 10.2 Hz, 12.9 Hz, 1H, CH2),
4.67 (d, J = 15.9 Hz, 1H, CH2), 5.09 (d, J = 15.9 Hz, 1H, CH2), 5.17−
5.52 (m, 3H, CH, CH2), 6.04−6.24 (m, 1H, CH), 6.75 (d, J = 8.1
Hz, 1H, ArH), 7.13−7.19 (m, 1H, ArH), 7.25−7.39 (m, 6H, ArH),
7.73−7.82 (m, 1H, ArH); 13C NMR (CDCl3, 100 MHz, TMS) δ 41.2,
42.8, 44.4, 82.3, 85.9, 110.2, 111.4, 112.6, 119.1, 120.4, 123.8, 126.1,
127.3, 128.9, 132.3, 134.2, 135.2, 143.4, 172.7; IR (CH2Cl2) ν 3066,
3023, 2920, 2842, 1720, 1613, 1488, 1469, 1439, 1367, 1351, 1254,
1182, 1125, 1093, 1079, 1012, 983, 937, 839, 802, 753, 732, 696 cm−1;
MS (ESI) m/z (%) 373.2 (100) [M+ + NH4]; HRMS (ESI) calcd for
(2S,5S)-Dibenzhydryl 1′-benzyl-5-(2-hydroxyethyl)-2′-oxo-4,5-di-
hydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 5a: white
solid, 56% yield (42 mg), 94/6 dr, 95%/55% ee; mp 101−104 °C.
The ee was determined by chiral HPLC (Daicel Chiralpak PC-4,
hexane/iPrOH = 85:15, 0.35 mL/min, 214 nm); main product: tmajor
=
1
130.0 min, tminor = 164.7 min; [α]20 = +19.5 (c 1.50, CH2Cl2); H
D
NMR (CDCl3, 300 MHz, TMS) δ 1.95−2.02 (m, 2H, CH2, OH),
2.24−2.33 (m, 1H, CH2), 2.63 (dd, J = 5.4 Hz, 13.2 Hz, 1H, CH2),
3.43 (dd, J = 9.0 Hz, 13.2 Hz, 1H, CH2), 3.76−3.78 (m, 2H, CH2),
3.95 (d, J = 15.9 Hz, 1H, CH2), 4.56 (d, J = 15.9 Hz, 1H, CH2), 5.00−
5.10 (m, 1H, CH), 6.48 (d, J = 7.8 Hz, 1H, ArH), 6.52−6.58 (m, 1H,
ArH), 6.81 (s, 1H, CH), 6.86 (s, 1H, CH), 6.89−6.96 (m, 3H, ArH),
7.00−7.06 (m, 4H, ArH), 7.08−7.27 (m, 20H, ArH); 13C NMR
(CDCl3, 75 MHz, TMS) δ 37.1, 39.2, 42.9, 60.7, 65.9, 79.1, 79.3, 86.1,
109.5, 122.8, 123.8, 125.2, 126.8, 127.1, 127.4, 127.6, 127.7, 127.8,
127.87, 127.9, 128.1, 128.2, 128.3, 128.38, 128.4, 128.6, 130.1, 135.2,
138.6, 138.8, 138.82, 138.9, 144.1, 167.6, 169.0, 174.0; IR (CH2Cl2) ν
3450, 3062, 3032, 2925, 1729, 1615, 1495, 1468, 1455, 1369, 1261,
1186, 1078, 1031, 949, 755, 698 cm−1; MS (ESI) m/z (%) 744.3 (100)
+
C22H21N4O2 (M+ + NH4) requires 373.1665, found 373.1655.
1′-Benzyl-4-vinylspiro[[1,3]dioxolane-2,3′-indolin]-2′-one, 3ka.
Major isomer: white solid, 99% yield (30 mg), 2/1 dr, 3%/5% ee;
K
dx.doi.org/10.1021/om400473p | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
+
[M+ + 1]; HRMS (ESI) calcd for C48H42NO7 (M+ + H) requires
744.2961, found 744.2971.
7.58 (d, J = 8.8 Hz, 2H, ArH), 7.92 (d, J = 8.8 Hz, 2H, ArH); 13C
NMR (CDCl3, 100 MHz, TMS) δ 17.3, 36.7, 43.0, 65.7, 72.7, 79.3,
79.4, 79.5, 86.3, 109.5, 123.0, 123.9, 125.4, 126.8, 126.9, 127.2, 127.5,
127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.35, 128.4, 128.5,
128.7, 129.4, 130.2, 131.3, 131.6, 135.2, 138.7, 138.8, 138.84, 138.9,
144.1, 165.0, 167.7, 168.5, 174.1; IR (CH2Cl2) ν 3016, 2978, 2913,
1718, 1614, 1482, 1466, 1457, 1364, 1255, 1219, 1181, 1131, 1092,
1079, 1026, 1010, 951, 917, 846, 805, 788, 756, 735, 697 cm−1; MS
(ESI) m/z (%) 926.2 (100) [M+ + 1]; HRMS (ESI) calcd for
(2S,5S)-Dibenzhydryl 1′-benzyl-5-(1-hydroxyethyl)-2′-oxo-4,5-di-
hydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 5b: white
solid, 29% yield (22 mg), >20/1 dr; mp 140−143 °C; [α]20
=
D
+13.8 (c 0.75, CH2Cl2); 1H NMR (CDCl3, 300 MHz, TMS) δ 1.18 (d,
J = 6.3 Hz, 3H, CH3), 2.94 (dd, J = 6.0 Hz, 13.2 Hz, 1H, CH2), 3.28
(dd, J = 9.0 Hz, 13.2 Hz, 1H, CH2), 3.66 (br, 1H, OH), 3.85 (d, J =
15.9 Hz, 1H, CH2), 4.16−4.20 (m, 1H, CH), 4.54 (d, J = 15.9 Hz, 1H,
CH2), 4.84−4.90 (m, 1H, CH), 6.48−6.57 (m, 2H, ArH), 6.85−6.89
(m, 4H, CH, ArH), 6.92−7.00 (m, 5H, CH, ArH), 7.09−7.28 (m,
20H, ArH); 13C NMR (CDCl3, 75 MHz, TMS) δ 19.2, 33.1, 42.8,
65.1, 67.0, 79.1, 79.8, 81.5, 85.6, 109.5, 123.0, 123.3, 125.4, 126.7,
126.9, 127.0, 127.4, 127.6, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3,
128.35, 128.4, 128.6, 130.1, 135.1, 138.4, 138.43, 138.6, 138.9, 144.2,
167.6, 170.5, 173.5; IR (CH2Cl2) ν 3502, 3059, 3032, 2963, 2923,
1720, 1614, 1495, 1468, 1455, 1369, 1260, 1185, 1157, 1079, 1029,
940, 909, 801, 781, 737, 697 cm−1; MS (ESI) m/z (%) 744.3 (100)
+
C55H45BrNO8 (M+ + H) requires 926.2329, found 926.2312.
ASSOCIATED CONTENT
■
S
* Supporting Information
Spectroscopic data and chiral HPLC traces of the compounds
shown in Tables 1 and 2 and Schemes 1−3, detailed
descriptions of experimental procedures, and the crystal
structure of 3gf (CCDC 917364). This material is available
free of charge via the Internet at http://pubs.acs.org.
+
[M+ + 1]; HRMS (ESI) calcd for C48H42NO7 (M+ + H) requires
744.2961, found 744.2978.
A solution of (2S,5S)-dibenzhydryl 6′-chloro-1′-methyl-2′-oxo-5-
vinyl-4,5-dihydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate
(3gj) (1.0 equiv) in a mixture of DCM/MeOH (10:1, 0.1 M) was
treated with O3 at −78 °C with stirring until a blue color was
maintained. The reaction was then degassed with Ar, treated with Zn
(2.0 equiv) and CH3COOH (2.0 equiv), and stirred at −78 °C for 3 h.
The mixture was warmed to room temperature and stirred for 18 h.
The solvent was removed under vacuum, and the residue was purified
by silica gel column chromatography (PE/EA = 4:1) to yield the
desired product 6 as a white solid.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: Mshi@mail.sioc.ac.cn. Fax: 86-21-64166128.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Shanghai Municipal Committee of Science and
Technology (11JC1402600), National Basic Research Program
of China ((973)-2010CB833302), the Fundamental Research
Funds for the Central Universities, and the National Natural
Science Foundation of China for financial support (20902019,
20872162, 20672127, 21121062, 21102166, 20732008,
20772030, and 20702059).
(2S,5S)-Dibenzhydryl 6′-chloro-5-formyl-1′-methyl-2′-oxo-4,5-di-
hydro-3H-spiro[furan-2,3′-indoline]-3,3-dicarboxylate, 6: white
solid, 91% yield (62 mg), 93/7 dr, 93%/63% ee; mp 95−98 °C.
The ee was determined by chiral HPLC (Daicel Chiralpak IC, hexane/
iPrOH = 90:10, 0.5 mL/min, 214 nm); main product: tmajor = 43.1
1
min, tminor = 77.9 min; [α]20 = +20.4 (c 3.00, CH2Cl2); H NMR
D
(CDCl3, 400 MHz, TMS) δ 2.62 (s, 3H, CH3), 2.93 (dd, J = 2.8 Hz,
13.6 Hz, 1H, CH2), 3.68 (dd, J = 10.8 Hz, 13.6 Hz, 1H, CH2), 4.83
(dd, J = 2.8 Hz, 10.8 Hz, 1H, CH), 6.40 (dd, J = 2.0 Hz, 8.0 Hz, 1H,
ArH), 6.61 (d, J = 2.0 Hz, 1H, ArH), 6.65 (s, 1H, ArH), 6.67 (s, 1H,
ArH), 6.82 (s, 1H, CH), 6.88 (s, 1H, CH), 6.90−6.94 (m, 6H, ArH),
7.01−7.05 (m, 2H, ArH), 7.13−7.19 (m, 4H, ArH), 7.20−7.26 (m,
7H, ArH), 7.30−7.35 (m, 1H, ArH), 9.86 (s, 1H, CHO); 13C NMR
(CDCl3, 100 MHz, TMS) δ 25.6, 36.6, 63.7, 79.3, 79.6, 81.3, 85.4,
109.3, 121.3, 122.7, 126.3, 126.5, 127.0, 127.7, 127.9, 128.0, 128.1,
128.3, 128.4, 128.43, 128.48, 128.5, 136.6, 138.2, 138.3, 138.5, 146.2,
166.5, 168.5, 173.7, 202.6; IR (CH2Cl2) ν 3077, 3033, 2927, 1720,
1614, 1491, 1428, 1455, 1371, 1264, 1187, 1077, 1029, 1001, 907, 848,
775, 733, 696 cm−1; MS (ESI) m/z (%) 708.2 (100) [M+ + Na];
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A dried flask was equipped with (2S,5S)-dibenzhydryl 1′-benzyl-5-
(1-hydroxyethyl)-2′-oxo-4,5-dihydro-3H-spiro[furan-2,3′-indoline]-
3,3-dicarboxylate (5b) (1.0 equiv), 4-bromobenzoic aicd (2.0 equiv),
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(2S,5S)-Dibenzhydryl 1′-benzyl-5-(1-((4-bromobenzoyl)oxy)-
ethyl)-2′-oxo-4,5-dihydro-3H-spiro[furan-2,3′-indoline]-3,3-dicar-
boxylate, 7: white solid, 96% yield (48 mg), >20/1 dr; mp 122−125
1
°C; [α]20 = +15.2 (c 0.50, CH2Cl2); H NMR (CDCl3, 400 MHz,
D
TMS) δ 1.40 (d, J = 6.4 Hz, 3H, CH3), 2.82 (dd, J = 6.0 Hz, 13.6 Hz,
1H, CH2), 3.39 (dd, J = 9.2 Hz, 13.6 Hz, 1H, CH2), 3.94 (d, J = 16.0
Hz, 1H, CH2), 4.55 (d, J = 16.0 Hz, 1H, CH2), 4.90−4.96 (m, 1H,
CH), 5.52−5.60 (m, 1H, CH), 6.47−6.54 (m, 2H, ArH), 6.82 (s, 2H,
CH), 6.88−6.91 (m, 3H, ArH), 6.98−7.02 (m, 4H, ArH), 7.06−7.10
(m, 3H, ArH), 7.14−7.20 (m, 9H, ArH), 7.22−7.27 (m, 8H, ArH),
L
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dx.doi.org/10.1021/om400473p | Organometallics XXXX, XXX, XXX−XXX