N-Heterocyclic Carbene-Catalyzed Formal [3 + 2] Annulation of α-Bromoenals with 3-Aminooxindoles: A Stereoselective Synthesis of Spirooxindole γ-Butyrolactams

Article abstract of DOI:10.1021/acs.joc.5b02188

A stereoselective synthetic approach to spirooxindole γ-butyrolactams is developed via N-heterocyclic carbene-catalyzed formal [3 + 2] annulation of α-bromoenals with 3-aminooxindoles. An enantioselective variant of this methodology is also investigated resulting in good substrate tolerance and high enantioselectivities.

Full text of DOI:10.1021/acs.joc.5b02188

Note
pubs.acs.org/joc
N‑Heterocyclic Carbene-Catalyzed Formal [3 + 2] Annulation of
α‑Bromoenals with 3‑Aminooxindoles: A Stereoselective Synthesis of
Spirooxindole γ‑Butyrolactams
Delu Jiang, Shuding Dong, Weifang Tang, Tao Lu,* and Ding Du*
State Key Laboratory of Natural Medicines, Department of Organic Chemistry, China Pharmaceutical University, Nanjing, 210009, P.
R. China
*
S Supporting Information
ABSTRACT: A stereoselective synthetic approach to spirooxindole γ-
butyrolactams is developed via N-heterocyclic carbene-catalyzed formal
[
3 + 2] annulation of α-bromoenals with 3-aminooxindoles. An
enantioselective variant of this methodology is also investigated
resulting in good substrate tolerance and high enantioselectivities.
pirooxindoles are attractive heterocyclic frameworks with1
functionalized 3,2′-spiropyrrolidine oxindoles with structural
S
broad and promising activities in various therapeutic fields.
diversity is still desirable.
As an important subtype of spirooxindoles, the 3,2′-
spiropyrrolidine oxindole unit is recognized as a privileged
structure that forms the core of numerous heterocyclic
compounds with a wide spectrum of significant bioactivities,
In recent years, N-heterocyclic carbene (NHC) catalysis has
been used as a powerful tool for a large number of untypical
6
chemical transformations. Among these transformations, α,β-
unsaturated acyl azoliums have emerged as fascinating 1,3-
biselectrophile synthons with unique and unprecedented
2
2c
3
such as antibacterial, antitubercular, antitumor, antifun-
2
c,4
2c
gal,
and antimalarial activities (Figure 1). Given its
chemistry that were pioneered by Zeitler in 2006 (Scheme
7
1
). Many research groups have made impressive contributions
Scheme 1. Applications of α,β-Unsaturated Acyl Azoliums to
the Synthesis of Various Heterocyclic Systems
to the applications of α,β-unsaturated acyl azoliums generated
8
from different precursors, such as ynals, enals (with external
8
b−d,9
10
11
oxidation),
α,β-unsaturated acyl fluorides, esters, α-
bromoenals, and in situ generated mixed anhydrides from
12
1
3
Figure 1. Representative biologically active compounds containing the
,2′-spiropyrrolidine oxindole skeleton.
carboxylic acids. The well-explored reactions involved NHC-
mediated formal [3 + 3] annulations of α,β-unsaturated acyl
azoliums with various 1,3-bisnucleophiles (such as stable enols
and enamines) to afford functionalized dihydropyranone-
3
8
a−d,9a,11c,12a−c,h
s
and dihydropyridinones (Scheme 1, eq
However, to the best of our knowledge, the
significant medicinal purposes, the 3,2′-spiropyrrolidine oxin-
dole motif has been synthesized by considerable synthetic
methods, particularly by the 1,3-dipolar cycloaddition of isatin-
9
b,c,11a,12c−e
a).
2
−5
derived azomethine ylides with alkenes.
However, the
Received: September 18, 2015
development of novel and efficient synthetic methods to access
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b02188
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
formal [3 + 2] annulations of α,β-unsaturated acyl azoliums
with 1,2-bisnucleophiles are rarely investigated, and only two
types of reactions were documented (Scheme 1, eq b). In 2014,
Table 1. Optimization of the Reaction Conditions
1
3
Ye first described the employment of α-amino ketones as the
,2-bisnucleophiles to react with the in situ generated α,β-
unsaturated acyl azoliums from α,β-unsaturated acids for the
1
14
synthesis of γ-butyrolactams. Very recently, Peng and Huang
reported a formal [3 + 2] annulation of α,β-unsaturated acyl
azoliums with aromatic aldehydes to assemble functionalized γ-
butyrolactones enabled by two consecutive NHC catalytic
systems.
In continuation of our studies on the exploration of NHC-
catalyzed annulations for the synthesis of diverse heterocyclic
b
d
entry
catalyst
base
solvent
yield (%)
dr
8
c,f,9i,15
systems,
we envision that 3-aminooxindoles 2 could
c
1
2
3
4
5
6
7
8
9
A
B−D
E
Cs CO3
2
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
0 (31)
−
−
serve as 1,2-bisnucleophiles to undergo formal [3 + 2]
annulation with α,β-unsaturated acyl azoliums (Scheme 2).
Cs CO3
2
0
Cs CO3
2
14
26
15
0
ND
ND
ND
−
ND
67:33
ND
ND
63:37
69:31
75:25
85:15
F
Cs CO3
2
Scheme 2. NHC-Catalyzed Formal [3 + 2] Annulation of α-
Bromoenals with 3-Aminooxindoles
F
Cs CO3
2
CH Cl2
2
F
Cs CO3
2
THF
F
Cs CO3
2
PhMe
trace
41
<10
13
76
73
74
84
F
Cs CO3
2
CH CN
3
F
DBU
CH CN
3
10
11
12
13
14
F
tBuOK
DIPEA
NEt3
CH CN
3
F
CH CN
3
F
CH CN
3
F
K CO3
2
CH CN
3
F
K CO3
2
DME
a
All reactions were performed in a 25 mL two-neck round-bottom
flask on a 0.2 mmol scale with 1.5 equiv of 1a, 1.0 equiv of 2a, 15 mol
of a carbene precursor, 1.5 equiv of a base, and 200 mg of 4 Å MS in
%
b
an anhydrous solvent (4 mL) at 45 °C for 10 h under N . Isolated
2
c
yields based on 2a. Compound 4 was isolated in 31% yield.
d
1
Diastereomeric ratio determined by H NMR of the crude product.
DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene; Mes = 2,4,6-(CH ) C H ;
3
3
6
2
DIPEA = N,N-diisopropylethylamine; DME = 1,2-dimethoxyethane;
ND = not determined.
with moderate diastereoselectivity in the presence of K CO in
2
3
CH CN (entry 13). Gratifyingly, both the reaction yield and
3
diastereoselectivity were improved by further changing the
solvent CH CN to DME, which was finally established as the
3
optimal reaction conditions (entry 14). As product 3a is a
16b
known compound, the structure and stereochemistry of 3a
was established by comparison to its known spectroscopic data.
With the optimized reaction conditions in hand, we turned
our attention to explore the reaction scope (Scheme 3).
Initially, the variation of the α-bromoenals was investigated. α-
Bromoenals with different substituents on the phenyl rings
were found suitable for the reaction; products 3b−h were
obtained in good yield and excellent diastereoselectivity. To our
delight, the reaction could also accommodate 2-furyl
substituted and 1-naphyl substituted α-bromoenals to give
products 3i and 3j in excellent diastereoselectivity. The lower
yield of 3j might be attributed to the steric effect of the more
hindered 1-naphthyl group. Unfortunately, we did not obtain
desired product 3k when using aliphatic-substituted α-
bromoenal. Substituted 3-aminooxindoles were also tested for
the generality of this protocol. 5-Me substituted 3-amino-
oxindole gave the desired product 3l in moderate yield and
good diastereoselectivity, while 5-F substituted 3-amino-
oxindole afforded product 3m in good yield but with poor
diastereoselectivity. However, when we changed the solvent to
The nucleophilic addition of 2 to α,β-unsaturated acyl azoliums
4
generated from α-bromoenals 1 followed by lactam formation
may afford functionalized spirooxindole γ-butyrolactams 3 that
contain the 3,2′-spiropyrrolidine oxindole core. Notably, the
desired products 3 can be also synthesized via NHC-catalyzed
3
3
a −d umpolung [3 + 2] annulations of enals with isatin-
16
derived ketimines. Herein, we wish to report our recent
results.
Our studies commenced with the model reaction of α-
bromoenal 1a (1.5 equiv) and 3-aminooxindole 2a (1.0 equiv)
in the presence of 15 mol % of a carbene precursor and 1.5
equiv of a base (Table 1). Initially, the efficiency of several
commonly used carbene precursors A−F was examined in 1,4-
dioxane using Cs CO as the base (entries 1−4). None of the
2
3
carbene precursors A−D were suitable for this reaction, and
compound 4 was obtained in 31% yield while employing A as
the precursor. Fortunately, precursor F was found to be
effective for this reaction although the desired product 3a was
isolated in a low yield (entry 4). After careful screening of the
solvents and bases, compound 3a was obtained in 74% yield
CH CN, the dr value was improved to 77:23.
3
B
DOI: 10.1021/acs.joc.5b02188
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Scheme 3. Reaction Scopea,b
3-aminooxindoles for the synthesis of functionalized spiroox-
indole γ-butyrolactams. This methodology offers an alternative
and rapid access to the 3,2′-spiropyrrolidine oxindole skeleton.
EXPERIMENTAL SECTION
■
General Methods and Materials. All reactions were carried out
under an atmosphere of nitrogen in dry glassware and were monitored
by analytical thin-layer chromatography (TLC), which was visualized
by ultraviolet light (254 nm). All solvents were obtained from
commercial sources and were purified according to standard
procedures. Purification of the products was accomplished by flash
chromatography using silica gel (200−300 mesh). Substrates 2 were
1
7
prepared according to a known method. All NMR spectra were
1
recorded on spectrometers, running at 300 or 500 MHz for H and 75
MHz for 13C respectively. Chemical shifts (δ) and coupling constants
(
J) are reported in ppm and Hz, respectively. The solvent signals were
used as references (residual CHCl in CDCl : δ = 7.26 ppm, δ =
3
3
H
c
7
7.0 ppm). The following abbreviations are used to indicate the
multiplicity in NMR spectra: s (singlet); d (doublet); t (triplet); q
quartet); m (multiplet). High resolution mass spectrometry (HRMS)
(
+
was recorded on TOF premier spectrometer for ES . The ee value was
determined via chiral HPLC analysis (Chiral pack IF, n-hexane/
enthanol/diethylamine = 90/10/0.1).
General Experimental Procedure for the Synthesis of
Products 3. An oven-dried 25 mL two-neck bound-bottom flask
was charged with α-bromoenal 1 (0.3 mmol), 3-aminooxindole 2 (0.2
mmol), carbene precursor F (8 mg, 0.03 mmol), K CO (41 mg. 0.3
2
3
mmol), and 200 mg of 4 Å MS under a N2 atmosphere. Then
anhydrous DME (4 mL) was added, and the resulting mixture was
stirred at 45 °C for 10 h under N . After completion of the reaction as
2
monitored by TLC, the mixture was cooled to room temperature. The
solvent was evaporated under reduced pressure, and the residue was
purified by chromatography on silica gel using hexane/EtOAc (5:1) as
eluent to afford the products 3.
(
2′S,3′R)- and (2′R,3′S)-tert-Butyl 1-Methyl-2,5′-dioxo-3′-
phenylspiro[indoline-3,2′-pyrrolidine]-1′-carboxylate (3a).
1
6b
Yield: 84% (66 mg). Known compound,
195 °C. H NMR (300 MHz, CDCl ): δ 7.39 (d, J = 7.2 Hz, 1H), 7.33
white solid, mp 193−
a
1
Reaction conditions: Same as in Table 1, and all yields are based on
3
b
2
. CH CN was used as the solvent.
(t, J = 7.5 Hz, 1H), 7.09−7.19 (m, 4H), 6.81 (d, J = 7.2 Hz, 2H), 6.59
3
(
3
d, J = 7.8 Hz, 1H), 3.56−3.74 (m, 2H), 2.74−2.79 (m, 1H), 2.71 (s,
H), 1.09 (s, 9H).
An enantioselective variant of this methodology was also
(
2′S,3′R)- and (2′R,3′S)-tert-Butyl 3′-(2-Chlorophenyl)-1-
investigated employing several commonly used chiral carbene
precursors (see Supporting Information). After optimizing the
reaction conditions, we found that chiral triazolium salt G was
the optimal precatalyst for this asymmetric formal [3 + 2]
annulation (Scheme 4). The results show that precatalyst G has
good substrate tolerance (including substituted phenyl and 2-
furyl substrates), affording the corresponding products with
high diastereo- and enantioselectivities.
methyl-2,5′-dioxospiro[indoline-3,2′-pyrrolidine]-1′-carboxy-
late (3b). Yield: 72% (61 mg). Unknown compound, white solid, mp
1
1
1
1
8
2
80−182 °C. H NMR (300 MHz, CDCl ): δ 7.55 (d, J = 7.8 Hz,
3
H), 7.41 (d, J = 7.2 Hz, 1H), 7.30 (d, J = 7.8 Hz, 1H), 7.19−7.24 (m,
H), 7.08−7.13 (m, 3H), 6.60 (d, J = 7.8 Hz, 1H), 4.49 (dd, J = 13.1,
.2 Hz, 1H), 3.41 (dd, J = 16.6, 13.3 Hz, 1H), 3.56−3.74 (m, 2H),
13
.74−2.79 (m, 1H), 2.79−2.87 (m, 4H), 1.09 (s, 9H). C NMR (75
MHz, CDCl ): δ 173.9, 172.9, 147.8, 143.2, 135.1, 131.1, 129.7, 129.5,
3
1
29.2, 129.1, 127.8, 126.6, 123.2, 122.9, 108.0, 83.7, 71.8, 42.8, 36.6,
27.3, 25.7. HRMS (ESI) calcd for C H ClN NaO (M+Na) :
+
In summary, we have demonstrated an NHC-catalyzed
stereoselective formal [3 + 2] annulation of α-bromoenals with
23 23 2 4
449.1239, found 449.1244.
2′S,3′R)- and (2′R,3′S)-tert-Butyl 1-Methyl-2,5′-dioxo-3′-(m-
tolyl)spiro[indoline-3,2′-pyrrolidine]-1′-carboxylate (3c). Yield:
(
a
Scheme 4. Enantioselective Studies of the Reaction
1
7
7% (63 mg). Unknown compound, white solid, mp 163−165 °C. H
NMR (500 MHz, CDCl ): δ 7.38 (d, J = 6.5 Hz, 1H), 7.32 (t, J = 7.5
3
Hz, 1H), 7.17 (t, J = 7.5 Hz, 1H), 6.97−7.02 (m, 2H), 6.58−6.63 (m,
3
9
1
8
H), 3.56−3.69 (m, 2H), 2.72−2.75 (m, 4H), 2.15 (s, 3H), 1.10 (s,
H). 13C NMR (75 MHz, CDCl ): δ 173.6, 173.6, 147.9, 143.7, 137.6,
3
32.2, 129.6, 128.8, 128.62, 128.57, 127.9, 124.8, 123.0, 121.8, 108.0,
3.6, 71.9, 49.0, 34.7, 27.3, 25.5, 21.2. HRMS (ESI) calcd for
+
C H N NaO (M+Na) : 429.1785, found 429.1786.
24
26
2
4
(
2′S,3′R)- and (2′R,3′S)-tert-Butyl 3′-(4-Fluorophenyl)-1-
methyl-2,5′-dioxospiro[indoline-3,2′-pyrrolidine]-1′-carboxy-
late (3d). Yield: 78% (64 mg), unknown compound, white solid, mp
1
2
(
3
02−204 °C. H NMR (300 MHz, CDCl ): δ7.31−7.39 (m, 2H), 7.18
3
t, J = 7.5 Hz, 1H), 6.76−6.85 (m, 4H), 6.61 (d, J = 7.5 Hz, H), 3.51−
13
.73(m, 2H), 2.72−2.79 (m, 4H), 1.09 (s, 9H). C NMR (75 MHz,
a
The ee value was determined by chiral HPLC analysis.
CDCl ): δ 173.5, 173.1, 162.5 (d, J = 247.3 Hz, 1C), 147.8, 143.6,
3
C
DOI: 10.1021/acs.joc.5b02188
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
1
=
29.8, 129.6 (d, J = 8.1 Hz, 1C), 128.3, 128.1, 123.2, 121.8, 115.0 (d, J
21.5 Hz, 1C), 108.2, 83.7, 71.7, 48.3, 34.9, 27.3, 25.6. HRMS (ESI)
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b02188.
■
*
S
+
calcd for C H FN NaO (M+Na) : 433.1534, found 433.1538.
23
23
2
4
(
2′S,3′R)- and (2′R,3′S)-tert-Butyl 3′-(4-Chlorophenyl)-1-
methyl-2,5′-dioxospiro[indoline-3,2′-pyrrolidine]-1′-carboxy-
16b
late (3e). Yield: 75% (64 mg). Known compound, white solid, mp
Optimization of the reaction conditions for asymmetric
1
1
7
2
4
94−196 °C. H NMR (300 MHz, CDCl ): δ 7.32−7.39 (m, 2H),
1
13
3
synthesis. H and C NMR spectra for the products.
.18 (t, J = 7.5 Hz, 1H), 7.10 (d, J = 8.4 Hz, 2H), 6.76 (d, J = 8.1 Hz,
H), 6.63 (d, J = 7.5 Hz, 1H), 3.50−3.72 (m, 2H), 2.72−2.77 (m,
H), 1.09 (s, 9H).
HPLC spectra for products 3a, 3d, 3h, and 3i (PDF)
AUTHOR INFORMATION
(
2′S,3′R)- and (2′R,3′S)-tert-Butyl 3′-(4-Bromophenyl)-1-
■
*
*
methyl-2,5′-dioxospiro[indoline-3,2′-pyrrolidine]-1′-carboxy-
Corresponding Authors
E-mail: lut163@163.com.
E-mail: ddmn9999@cpu.edu.cn.
16b
late (3f). Yield: 71% (67 mg). Known compound, white solid, mp
1
1
7
88−190 °C. H NMR (300 MHz, CDCl ): δ 7.34−7.41 (m, 2H),
3
.28 (s, 2H), 7.19 (t, J = 7.5 Hz, 1H), 6.71 (d, J = 8.4 Hz, 2H), 6.65 (d,
Notes
J = 7.8 Hz, 1H), 3.52−3.72 (m, 2H), 2.73−2.79 (m, 4H), 1.11 (s, 9H).
2′S,3′R)- and (2′R,3′S)-tert-Butyl 1-Methyl-2,5′-dioxo-3′-(p-
tolyl)spiro[indoline-3,2′-pyrrolidine]-1′-carboxylate (3g). Yield:
(
The authors declare no competing financial interest.
16b
1
7
1% (58 mg). Known compound, white solid, mp 187−189 °C. H
ACKNOWLEDGMENTS
■
NMR (300 MHz, CDCl ): δ 7.30−7.39 (m, 2H), 7.16 (t, J = 7.2 Hz,
3
This work is funded by the National Natural Science
Foundation of China (Nos. 21572270, 21002124, and
1172933), Jiangsu Provincial Natural Science Foundation of
China (No. BK20131305), and the Priority Academic Program
Development of Jiangsu Higher Education Institutions.
1
H), 6.92 (d, J = 7.8 Hz, 2H), 6.70 (d, J = 8.1 Hz, 2H), 6.60 (d, J = 7.8
Hz, 1H), 3.54−3.67 (m, 2H), 2.69−2.76 (m, 4H), 2.24 (s, 3H), 1.09
s, 9H).
2′S,3′R)- and (2′R,3′S)-tert-Butyl 3′-(4-Methoxyphenyl)-1-
methyl-2,5′-dioxospiro[indoline-3,2′-pyrrolidine]-1′-carboxy-
8
(
(
16b
late (3h). Yield: 75% (63 mg). Known compound, white solid, mp
1
1
7
3
97−199 °C. H NMR (300 MHz, CDCl ): δ 7.30−7.38 (m, 2H),
.16 (t, J = 7.2 Hz, 1H), 6.74 (d, J = 8.1 Hz, 2H), 6.59−6.66 (m, 3H),
.72 (s, 3H), 3.51−3.68 (m, 2H), 2.69−2.76 (m, 4H), 1.09 (s, 9H).
REFERENCES
3
■
(
1) For selected examples, see: (a) Galliford, C. V.; Scheidt, K. A.
Angew. Chem., Int. Ed. 2007, 46, 8748. (b) Santos, M. M. M.
Tetrahedron 2014, 70, 9735. (c) Cheng, D.; Ishihara, Y.; Tan, B.;
Barbas, C. F. ACS Catal. 2014, 4, 743. (d) Yu, B.; Yu, D.-Q.; Liu, H.-
M. Eur. J. Med. Chem. 2015, 97, 673. (e) Yu, B.; Yu, Z.; Qi, P.-P.; Yu,
D.-Q.; Liu, H.-M. Eur. J. Med. Chem. 2015, 95, 35.
(2) (a) Kathirvelan, D.; Haribabu, J.; Reddy, B. S. R.; Balachandran,
C.; Duraipandiyan, V. Bioorg. Med. Chem. Lett. 2015, 25, 389. (b) Wu,
G.; Ouyang, L.; Liu, J.; Zeng, S.; Huang, W.; Han, B.; Wu, F.; He, G.;
Xiang, M. Mol. Diversity 2013, 17, 271. (c) Haddad, S.; Boudriga, S.;
Akhaja, T. N.; Raval, J. P.; Porzio, F.; Soldera, A.; Askri, M.; Knorr, M.;
Rousselin, Y.; Kubicki, M. M.; Rajani, D. New J. Chem. 2015, 39, 520.
3) (a) Kumar, A.; Gupta, G.; Bishnoi, A. K.; Saxena, R.; Saini, K. S.;
Konwar, R.; Kumar, S.; Dwivedi, A. Bioorg. Med. Chem. 2015, 23, 839.
b) Arun, Y.; Saranraj, K.; Balachandran, C.; Perumal, P. T. Eur. J. Med.
Chem. 2014, 74, 50. (c) Girgis, A. S. Eur. J. Med. Chem. 2009, 44, 91.
4) Rajesh, S. M.; Perumal, S.; Menendez, J. C.; Yogeeswari, P.;
(
2′S,3′S)- and (2′R,3′R)-tert-Butyl 3′-(Furan-2-yl)-1-methyl-
2
,5′-dioxospiro[indoline-3,2′-pyrrolidine]-1′-carboxylate(3i).
16b
Yield: 71% (54 mg). Known compound, white solid, mp 182−184
1
°
(
(
C. H NMR (300 MHz, CDCl ): δ 7.32−7.39 (m, 2H), 7.13−7.17
m, 2H), 6.73 (d, J = 7.8 Hz, 1H), 6.19 (dd, J = 3.1, 1.8 Hz, 1H), 5.94
d, J = 3.1 Hz, 1H), 3.81 (dd, J = 13.3, 7.8 Hz, 1H), 3.51 (dd, J = 16.6,
3
1
9
3.5 Hz, 1H), 2.95 (s, 3H), 2.82 (dd, J = 16.7, 7.9 Hz, 1H), 1.09 (s,
H).
(
2′S,3′R)- and (2′R,3′S)-tert-Butyl 1-Methyl-3′-(naphthalen-
1
-yl)-2,5′-dioxospiro[indoline-3,2′-pyrrolidine]-1′-carboxylate
(
(
2
7
3j). Yield: 35% (31 mg). Unknown compound, white solid, mp 200−
1
02 °C. H NMR (300 MHz, CDCl ): δ 7.68−7.72 (m, 3H), 7.51−
3
(
.56 (m, 1H), 7.45 (t, J = 7.8 Hz, 1H), 7.23−9.29 (m, 2H), 7.11−7.18
m, 2H), 7.03−7.08 (m, 1H), 6.24−6.27 (m, 1H), 4.67 (dd, J = 12.9,
(
(
8.1 Hz, 1H), 3.71 (dd, J = 16.7, 13.2 Hz, 1H), 2.90 (dd, J = 16.8, 7.8
Sriram, D. MedChemComm 2011, 2, 626.
13
Hz, 1H), 2.55 (s, 3H), 1.06 (s, 9H). C NMR (75 MHz, CDCl ): δ
3
(5) (a) Shi, F.; Tao, Z.-L.; Luo, S.-W.; Tu, S.-J.; Gong, L.-Z. Chem. -
Eur. J. 2012, 18, 6885. (b) Tian, L.; Hu, X.-Q.; Li, Y.-H.; Xu, P.-F.
Chem. Commun. 2013, 49, 7213.
(6) For selected reviews, see: (a) Menon, R. S.; Biju, A. T.; Nair, V.
Chem. Soc. Rev. 2015, 44, 5040. (b) Flanigan, D. M.; Romanov-
Michailidis, F.; White, N. A.; Rovis, T. Chem. Rev. 2015, 115, 9307.
(c) Mahatthananchai, J.; Bode, J. W. Acc. Chem. Res. 2014, 47, 696.
(d) Albanese, D. C. M.; Gaggero, N. Eur. J. Org. Chem. 2014, 2014,
631. (e) Ryan, S. J.; Candish, L.; Lupton, D. W. Chem. Soc. Rev. 2013,
2, 4906. (f) De Sarkar, S.; Biswas, A.; Samanta, R. C.; Studer, A.
Chem. - Eur. J. 2013, 19, 4664. (g) Chen, X.-Y.; Ye, S. Org. Biomol.
Chem. 2013, 11, 7991. (h) Izquierdo, J.; Hutson, G. E.; Cohen, D. T.;
Scheidt, K. A. Angew. Chem., Int. Ed. 2012, 51, 11686.
1
1
4
73.8, 173.5, 147.9, 143.4, 133.3, 131.9, 129.6, 128.9, 128.7, 128.6,
28.5, 125.5, 125.3, 125.1, 124.9, 122.8, 122.2, 121.9, 108.1, 83.6, 72.5,
2.0, 36.7, 27.3, 25.4. HRMS (ESI) calcd for C H N NaO (M +
27
26
2
4
+
Na) : 465.1785, found 465.1791.
(
2′S,3′R)- and (2′R,3′S)- tert-Butyl 1,5-Dimethyl-2,5′-dioxo-
3
′-phenylspiro[indoline-3,2′-pyrrolidine]-1′-carboxylate (3l).
16b
Yield: 47% (38 mg). Known compound,
white solid, mp 171−
1
5
4
1
4
2
73 °C. H NMR (300 MHz, CDCl ): δ 7.21 (s, 1H), 7.10−7.18 (m,
3
H), 6.83 (d, J = 7.2 Hz, 2H), 6.47 (d, J = 7.8 Hz, 1H), 3.56−3.73 (m,
H), 2.68−2.77 (m, 4H), 2.40 (s, 3H), 1.10 (s, 9H).
(
2′S,3′R)- and (2′R,3′S)-tert-Butyl 5-Fluoro-1-methyl-2,5′-
dioxo-3′-phenylspiro[indoline-3,2′-pyrrolidine]-1′-carboxylate
(
7) Zeitler, K. Org. Lett. 2006, 8, 637.
(3m). Yield: 54% (44 mg). Unknown compound, white solid, mp
1
(8) (a) Kaeobamrung, J.; Mahatthananchai, J.; Zheng, P.; Bode, J. W.
J. Am. Chem. Soc. 2010, 132, 8810. (b) Zhu, Z.-Q.; Zheng, X.-L.; Jiang,
N.-F.; Wan, X.; Xiao, J.-C. Chem. Commun. 2011, 47, 8670. (c) Lu, Y.;
Tang, W.; Zhang, Y.; Du, D.; Lu, T. Adv. Synth. Catal. 2013, 355, 321.
(d) Mahatthananchai, J.; Kaeobamrung, J.; Bode, J. W. ACS Catal.
012, 2, 494. (e) Zhou, B.; Luo, Z.; Li, Y. Chem. - Eur. J. 2013, 19,
428. (f) Du, D.; Hu, Z.; Jin, J.; Lu, Y.; Tang, W.; Wang, B.; Lu, T.
1
7
1
79−181 °C. H NMR (300 MHz, CDCl ): δ 7.12−7.20 (m, 4H),
3
.01−7.07 (m, 1H), 6.84 (d, J = 7.2 Hz, 2H), 6.52 (dd, J = 8.4, 3.8 Hz,
13
H), 3.56−3.70 (m, 2H), 2.70−2.78 (m, 4H), 1.16 (s, 9H). C NMR
(
75 MHz, CDCl ): δ 173.3, 173.0, 159.4 (d, J = 242.7 Hz, 1C), 147.8,
3
1
=
8
39.6, 132.0, 130.2 (d, J = 7.8 Hz, 1C), 128.4, 128.1, 127.8, 115.8 (d, J
23.4 Hz, 1C), 110.1 (d, J = 25.3 Hz, 1C), 108.7 (d, J = 8.0 Hz, 1C),
3.9, 72.0, 49.1, 34.6, 27.4, 25.6. HRMS (ESI) calcd for: C H FN O
2
4
23
23
2
4
Org. Lett. 2012, 14, 1274. (g) Romanov-Michailidis, F.; Besnard, C.;
Alexakis, A. Org. Lett. 2012, 14, 4906.
+
(M+Na) : 433.1534, found 433.1537.
D
DOI: 10.1021/acs.joc.5b02188
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(
9) (a) De Sarkar, S.; Studer, A. Angew. Chem., Int. Ed. 2010, 49,
9266. (b) Kravina, A. G.; Mahatthananchai, J.; Bode, J. W. Angew.
Chem., Int. Ed. 2012, 51, 9433. (c) Wanner, B.; Mahatthananchai, J.;
Bode, J. W. Org. Lett. 2011, 13, 5378. (d) Rong, Z.-Q.; Jia, M.-Q.; You,
S.-L. Org. Lett. 2011, 13, 4080. (e) Biswas, A.; De Sarkar, S.; Tebben,
L.; Studer, A. Chem. Commun. 2012, 48, 5190. (f) Bera, S.; Samanta, R.
C.; Daniliuc, C. G.; Studer, A. Angew. Chem., Int. Ed. 2014, 53, 9622.
(
g) Mao, J.-H.; Wang, Z.-T.; Wang, Z.-Y.; Cheng, Y. J. Org. Chem.
2
015, 80, 6350. (h) Xie, D.; Yang, L.; Lin, Y.; Zhang, Z.; Chen, D.;
Zeng, X.; Zhong, G. Org. Lett. 2015, 17, 2318. (i) Hu, S.; Wang, B.;
Zhang, Y.; Tang, W.; Fang, M.; Lu, T.; Du, D. Org. Biomol. Chem.
2
(
(
015, 13, 4661.
10) (a) Candish, L.; Lupton, D. W. J. Am. Chem. Soc. 2013, 135, 58.
b) Ryan, S. J.; Candish, L.; Lupton, D. W. J. Am. Chem. Soc. 2011,
1
(
5
2
33, 4694.
11) (a) Cheng, J.; Huang, Z.; Chi, Y. R. Angew. Chem., Int. Ed. 2013,
2, 8592. (b) Candish, L.; Levens, A.; Lupton, D. W. J. Am. Chem. Soc.
014, 136, 14397. (c) Ryan, S. J.; Candish, L.; Lupton, D. W. J. Am.
Chem. Soc. 2009, 131, 14176.
12) (a) Sun, F.-G.; Sun, L.-H.; Ye, S. Adv. Synth. Catal. 2011, 353,
134. (b) Yao, C.; Wang, D.; Lu, J.; Li, T.; Jiao, W.; Yu, C. Chem. - Eur.
(
3
J. 2012, 18, 1914. (c) Yetra, S. R.; Bhunia, A.; Patra, A.; Mane, M. V.;
Vanka, K.; Biju, A. T. Adv. Synth. Catal. 2013, 355, 1089. (d) Zhang,
H.-M.; Jia, W.-Q.; Liang, Z.-Q.; Ye, S. Asian J. Org. Chem. 2014, 3, 462.
(
2
e) Gao, Z.-H.; Chen, X.-Y.; Zhang, H.-M.; Ye, S. Chem. Commun.
015, 51, 12040. (f) Ni, Q.; Song, X.; Raabe, G.; Enders, D. Chem. -
Asian J. 2014, 9, 1535. (g) Yetra, S. R.; Roy, T.; Bhunia, A.; Porwal, D.;
Biju, A. T. J. Org. Chem. 2014, 79, 4245. (h) Yetra, S. R.; Kaicharla, T.;
Kunte, S. S.; Gonnade, R. G.; Biju, A. T. Org. Lett. 2013, 15, 5202.
(
i) Zhang, H.-R.; Dong, Z.-W.; Yang, Y.-J.; Wang, P.-L.; Hui, X.-P. Org.
Lett. 2013, 15, 4750.
13) Chen, X.-Y.; Gao, Z.-H.; Song, C.-Y.; Zhang, C.-L.; Wang, Z.-X.;
Ye, S. Angew. Chem., Int. Ed. 2014, 53, 11611.
14) Zhao, Q.; Huang, W.; Han, B.; Wang, B.; Leng, H.-J.; Peng, C.
RSC Adv. 2015, 5, 26972.
15) (a) Zhang, Y.; Lu, Y.; Tang, W.; Lu, T.; Du, D. Org. Biomol.
(
(
(
Chem. 2014, 12, 3009. (b) Xu, J.; Hu, S.; Lu, Y.; Dong, Y.; Tang, W.;
Lu, T.; Du, D. Adv. Synth. Catal. 2015, 357, 923.
(
16) (a) Zhang, B.; Feng, P.; Sun, L.-H.; Cui, Y.; Ye, S.; Jiao, N.
Chem. - Eur. J. 2012, 18, 9198. (b) Lv, H.; Tiwari, B.; Mo, J.; Xing, C.;
Chi, Y. R. Org. Lett. 2012, 14, 5412.
(
17) Emura, T.; Esaki, T.; Tachibana, K.; Shimizu, M. J. Org. Chem.
2
006, 71, 8559.
E
DOI: 10.1021/acs.joc.5b02188
J. Org. Chem. XXXX, XXX, XXX−XXX