Effective and diastereoselective preparation of dispiro[cyclopent-3′-ene]bisoxindoles: Via novel [3 + 2] annulation of isoindigos and MBH carbonates

Article abstract of DOI:10.1039/c7ob03009f

A novel and diastereoselective [3 + 2] annulation of isoindigos and Morita-Baylis-Hillman carbonates has been developed for the highly efficient and one-step preparation of highly steric dispiro[cyclopent-3′-ene]bisoxindoles with two all-carbon quaternary

Full text of DOI:10.1039/c7ob03009f

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Effective and Diastereoselective Preparation of Dispiro[cyclopent-
3′-ene]bisoxindoles via Novel [3 + 2] Annulation of Isoindigos and
MBH Carbonates
Received 00th January 20xx,
Accepted 00th January 20xx
Hong-Xia Ren,a,b Lin Peng,a Xiang-Jia Song,a,b Li-Guo Liao,a,b Ying Zou,a,b Fang Tian a*
DOI: 10.1039/x0xx00000x
and Li-Xin Wanga*
www.rsc.org/
A novel and diastereoselective [3 + 2] annulation of isoindigos and Morita−Baylis−Hillman carbonates has been developed
for the highly efficient and one-step preparation of highly steric dispiro[cyclopent-3'-ene]bisoxindoles with two all-carbon
quaternary spirocenters and three adjacent cycles in excellent yields (up to >99%) and diastereoselectivities(up to >20:1)
under mild conditions within a few minutes. A series of dispiro[cyclopent-3′-ene]bisoxindoles were obtained and scale-up
experiment was conducted with excellent results demonstrating the potential applications of this protocol.
Introduction
6a
reductive dialkylation of isoindigo in high yields.
A
Diels−Alder reaction between readily available N-Ts isoindigo
and 1,3-butadiene to form the cyclohexene cycloadduct was
reported by Peter’s group.7 Dispiro(indoline-3,3'-pyrrolidine)
fragments were prepared by S. V. Kurbatov from cycloaddition
of isoindigo derivatives and in situ generated azomethineylide
from sarcosine and paraformaldehyde.8 We3 have also
successfully developed a sulfa-Michael/aldol cascade reaction
between 1,4-dithiane-2,5-diol and isoindigos to afford the
highly congested bispirooxindoletetrahydrothiophenes with
two vicinal quaternary spirocenters.
The spirooxindole scaffold, widely existed in huge numbers of
bioactive natural products, such as Coerulescine,1a Horsfiline,1b
Welwitindolinone A,1c Spirotryprostatin A1d and Alstonisine,1e is
an important structural motif with highly pronounced
pharmacological activities, which made spirooxindoles and
their derivatives unusual attractive synthetic targets.2
Bispirooxindoles, fusing two oxindole rings into one cyclic
molecule, may exhibit enhanced bioactivities compared with
mono-spirooxindoles.3 However, the catalytic approaches for
bispirooxindoles construction were inadequate, probably due
to the more constrained structure of bispirooxindole with at
least two quaternary spirocenters.4 Except for the syntheses of
bispirooxindoles from oxindole derivatives,5 the reported
methods directly from isoindigos are limited, which may
attribute to the less reactivity of isoindigos caused by
extremely steric congestion and big π bond conjugation.
Overman has reported a diastereoselective preparation of
meso-bispyrrolidinoindoline alkaloids by samarium-mediated
a Key Laboratory of Asymmetric Synthesis & Chirotechnology of Sichuan Province,
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu
610041, P.R. China. E-mail: wlxioc@cioc.ac.cn, 452553462@qq.com
b University of Chinese Academy of Sciences, Beijing 100039, P.R. China.
†Electronic Supplementary Informaꢀon (ESI) available: Experimental procedures,
spectral data of new products, and single crystal data of compound 3f. CCDC
1550592. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/x0xx00000x
Scheme 1 Related studies concerning with isoindigo
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On the other hand, Morita−Baylis−Hillman(MBH) reaction was still not accomplished after 120 h and the yields
carbonate is particularly useful synthon in organic syntheses, were observed to decrease slightly (Entries 14-16, Table 2),
for [2 + 1],9 [4 + 1],10 [3 + 2],11 [3 + 3],12 [4 + 3],13 [6 + 3]14
and the optimal reaction conditions were established as
：1.0
annulations, alkylations15 and domino reactions16, which are
generally catalyzed by organic phosphines or amines.
Especially, the in situ generated 1,3-dipole from MBH
carbonates in the presence of tertiary phosphine is usually
used for [3 + 2] annulations.11b
eq. 1a and 1.2 eq. 2a in toluene at room temperature under N2
atmosphere in the presence of 20 mol% Bu3P for 10 mins (0.17
hour).
Table 1 Screening of catalystsa
In recent years, we have successfully developed some
annulations of methyleneindolinone for the constructions of
mono- and bispirooxindoles, such as [2 + 2],17 [3 + 2]18 and
domino reactions19. We20 also reported a new isatin N,N'-cyclic
azomethine imine synthon and its unexpected abnormal [3 +
2] cycloaddition with maleimide catalyzed by 1, 4-diazabicyclo-
[2.2.2]-octane (DABCO) to construct mono-spirooxindoles.
Based on our series of work in spirooxindole syntheses3, 17-21
and related work in MBH carbonates22, herein, we wish to
Reaction
time (h)
Yieldb
(%)
Entry
Catalyst
Drc
report
a novel and highly effective diastereoselective
1
2
None
Ph3P
120
12
NR
90
-
4.2:1
2:1
3:1
>20:1
--
organocatalytic [3 + 2] annulation of isoindigos and MBH
carbonates to stepwise construct the dispiro[cyclopent-3'-
ene]bisoxindoles with two all-carbon quaternary spirocenters
and three adjacent cycles in excellent yields and
diastereoselectivities (up to >99% yield and >20:1 dr).
3
4d
MePh2P
DPPB
8
70
6
62
5
Bu3P
0.17
120
120
120
120
120
120
0.17
48
93
6
(S)-BINAP
(R)-BINAP
DBACO
Et3N
NR
NR
NR
Trace
13
7
--
Results and discussion
8
-
Our studies were conducted with N-Boc isoindigo 1a and MBH
carbonate 2a in CH2Cl2 in the presence of 20 mol% organic
phosphines or amines as catalysts (Table 1). No reaction was
observed without catalyst, while sorts of phosphines can
smoothly catalyze the reaction with good results (Entries 1-5,
Table 1). Compared with less nucleophilic phosphines, the
more nucleophilic Bu3P displayed higher catalytic activity with
excellent yield (up to 93%) and diastereoselectivity (up to
>20:1) (Entry 5, Table 1). For Chiral phosphines (S)-BINAP and
(R)-BINAP, the reaction did not occur without observable
result (Entry 6, 7, Table 1). Comparatively, when amine was
used as catalyst, less or no desired product was observed
(Entries 8-11, Table 1). So, Bu3P was chosen as the candidate
catalyst. When increasing the load of Bu3P to 30 mol%, no
better result was obtained (Entry 12, Table 1). Decreasing the
load to 10 mol% or 5 mol%, the yields were sharply reduced
with untouched diastereoselectivities (Entries 13-14, Table 1).
With the optical catalyst, other parameters were furtherly
screened (Table 2). Due to the excellent results afforded by
CH2Cl2, other halogenated hydrocarbon solvents were also
tested. However, no better result was obtained (Entries 1-6,
Table 2). When other aprotic solvents, such as THF, CH3CN,
DMF, DMAc and DMSO, were used, the yields decreased
9
-
10
11
12e
13f
14g
DMAP
DBU
9:1
-
NR
92
Bu3P
>20:1
>20:1
>20:1
Bu3P
78
Bu3P
120
45
a
Unless otherwise specified, the reaction was performed with 0.1
mmol 1a, 0.12 mmol 2a and 20 mol% catalyst in 1 mL CH2Cl2 at room
c
temperature under N2 atmosphere. b Isolated yields. Determined by
HPLC. d The reaction was conducted with 10 mol% DPPB (DPPB was the
e
abbreviation of 1, 4-Bis(diphenylphosphino)butane). 30 mol% Bu3P
used; f 10 mol% Bu3P used. g 5 mol% Bu3P used.
Under the optimized conditions, the generality of the
annulation was broadened, and the results were summarized
in Table 3. In general, the reaction could successfully occur
with different substituted isoindigos
providing corresponding products in excellent yields and
diastereoselectivities. Notably, MBH carbonates with no
1 and MBH carbonates 2,
2
matter ortho-, meta-, or para-substituted phenyl group (R3) as
the reactants, the reaction finished almost spontaneously with
excellent yields and diastereoselectivities (Entries 2-13, Table
3). When the aromatic ring of the MBH carbonates bearing an
electron-donating group such as methyl, excellent yields and
diastereoselectivities (Entries 9, 10, Table 3) were obtained.
When bearing a strong electron-withdrawing group of F or
slightly (Entries 7, 8, Table 2) or seriously (Entries 9-11, Table 2).
Protic solvent of EtOH gave only moderate yield (Entry 12,
Table 2). However, the best result was obtained in toluene (up
to >99% yield and >20:1 dr, Entry 13, Table 2). When changing
the substrate ratio of 1a and 2a to 1:1.1, 1:1 or even 1.2:1, the
2 | J. Name., 2012, 00, 1-3
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NO2, almost no decreasing yield or diastereoselectivity was Table 3 Generality of substrate scopea
observed (Entries 2, 3, 12, 13, Table 3). For hetereocyclic 2-
furyl MBH carbonate (Entry14, Table 3), excellent results were
still achieved. Alternatively, when changing the methyl ester to
butyl ester in MBH carbonates, equally excellent result was
obtained (Entry 15, Table 3). Furtherly, the reaction still
worked well for substrate isoindigos
1 with different
Yieldb
substitutions on N or aromatic ring (Entries 16–21, Table 3)
with both excellent yields and diastereoselectivities. For less
electron-withdrawing group or even electron-donnating
Entry
1
/R1/R2
2
/R3/R4
3
Drc
(%)
>99e
>99e
98
>99e
>99e
>99e
98
>99e
>99e
95
>99e
>99e
1
2
1a/Boc/H
1a/Boc/H
1a/Boc/H
1a/Boc/H
1a/Boc/H
1a/Boc/H
1a/Boc/H
1a/Boc/H
1a/Boc/H
1a/Boc/H
2a/Ph/Me
3a
3b
3c
3d
3e
3f
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
groups on Nitrogen atom in isoindigos 1, prolonged reaction
2b/2-FC6H4/Me
2c/4-FC6H4/Me
2d/2-ClC6H4/Me
2e/3-ClC6H4/Me
2f/4-ClC6H4/Me
2g/2-BrC6H4/Me
2h/3-BrC6H4/Me
2i/2-CH3C6H4/Me
2j/4-CH3C6H4/Me
time was required with slightly reduced yields, which may
attribute to the relative lower reactivity of the less electron-
deficiency double bond caused by the electron-withdrawing
deficient substitutions on Nitrogen atom (Entries 20, 21, Table
3). The configuration of the annulation products was
determined by X-ray crystal structural analysis of the
representative product 3f (see the Supporting Information for
details).
3
4
5
6
7
3g
3h
3i
8
9
10
11
12
3j
Table 2 Effect of solvent and substrate loadingsa
1a/Boc/H 2k/3-OBocC6H4/Me 3k
1a/Boc/H
1a/Boc/H
2l/3-NO2C6H4/Me
2m/4-NO2C6H4/Me
3l
3
m
13
97
>20:1
14
15
1a/Boc/H
1a/Boc/H
2n/2-Furyl/Me
2o /Ph/Bu
3n
3o
92
>99e
>20:1
>20:1
Reaction Yieldb
1b/Boc/5
,5'-2F
1c/Boc/7
,7'-2F
1d/Boc/5
,5'-2Cl
1e/Boc/6
,6'-2Cl
16
17
18
2a/Ph/Me
2a/Ph/Me
2a/Ph/Me
3p
3q
3r
95
92
92
>20:1
>20:1
>20:1
Entry
Solvent
Drc
time (h)
120
120
120
120
120
120
0.25
0.17
120
120
72
(%)
66
58
72
65
33
49
87
88
49
38
47
52
>99h
87
85
80
1d
2
CHCl3
ClCH2CH2Cl
Cl2CHCH3
Cl2CHCH2Cl
Cl2CHCHCl2
1-Chlorobutane
THF
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
3
>99e
89
>20:1
>20:1
>20:1
4
19
20d
21d
2a/Ph/Me
2a/Ph/Me
2a/Ph/Me
3s
3t
5
1f/Et/H
6
1g/Allyl/
H
3
w
85
7
8
CH3CN
a Unless otherwise specified, the reaction was performed with 0.1 mmol
0.12 mmol and 20 mol% Bu3P in 1 mL toluene at room temperature for 10
1,
9
DMF
2
mins under N2 atmosphere. b Isolated yields. Determined by HPLC. d After
120 hours, the reactants were still not consumed completely. e quantitative
yield.
c
10
11
12
13
14d,e
15d, f
16d, g
DMAc
DMSO
EtOH
24
Toluene
Toluene
Toluene
Toluene
0.17
120
120
120
a Unless otherwise specified, the reaction was performed with 0.1
mmol 1a, 0.12 mmol 2a and 20 mol% Bu3P in 1 mL solvent at room
temperature under N2 atmosphere. b Isolated yields. c Determined
≡
d
by HPLC. After 120 h, the reaction was still not accomplished
completely. e The ratio of 1a and 2a was 1:1.1. f The ratio of 1a and
2a was 1:1. g The ratio of 1a and 2a was 1.2:1. h quantitative yield.
Fig. 1 Representative X-ray crystallographic structure of
product 3f
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Based on previous reports on phosphine-catalyzed
Conclusions
annulations of MBH carbonates9-12, we proposed a plausible
mechanism (Scheme 2) for the present protocol. The reaction
was initiated by nucleophilic attack of Bu3P to form quaternary
In summary, we have developed
a
highly efficient
organocatalytic [3 + 2] annulation reaction of isoindigos and
MBH carbonates in the presence of Bu3P for the direct
salt
formed after the deprotonation of
the double bond in isoindigo 1a was attacked by the
nucleophilic site of to form intermediate with one
nucleophilic site and electron-deficient double bond. took
the intramolecular addition from less steric hindrance to
realize the construction of bispiro-adductive . The elimination
4, CO2 and tert-butoxide anion. The 1, 3-dipole
5 was
4
by tert-butoxide anion, and
construction
of
highly
steric
dispiro[cyclopent-3'-
ene]bisoxindole derivatives with two all-carbon quaternary
spirocenters and three adjacent cycles in excellent yields and
diastereoselectivities (up to >99% yield and >20:1 dr) under
mild conditions within a few minutes. A series of isoindigos
and MBH carbonates are compatible with this protocol. The
synthetic potential of this novel [3 + 2] annulation protocol
was demonstrated on a gram scale experiment. This strategy
will be useful in medicinal chemistry and diversity-oriented
synthesis and may also find potential applications in further
scale-up preparations.
5
6
6
7
of phosphine completed the catalytic cycle, yielding the
product and setting the catalyst free.
To demonstrate the synthetic potential of this new [3 + 2]
annulation protocol, scale-up experiment was conducted on
gram scale, almost equal result (98% yield and >20:1 dr) was
still achieved, which may lead to a further potential scale-up.
When product 3a was treated with CF3COOH in CH2Cl2 at room
temperature, two Boc groups were deprotected to form the N-
Experimental section
H dispiro[cyclopent-3'-ene]bisoxindoles 8 in 96% yield.
General information
Commercial grade solvent was dried and purified by standard
procedures as specified in Purification of Laboratory Chemicals,
4th Ed (Armarego, W. L. F.; Perrin, D. D. Butterworth
Heinemann: 1997). 1H NMR and 13C NMR spectra were recorded
1
on a Bruker Avance (300 MHz for H NMR, 75 MHz for 13C NMR)
instrument. Data for 1H NMR are reported as chemical shift
(ppm, tetramethylsilane as the internal standard), integration,
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m=
multiplet), coupling constant (Hz). Data for 13C NMR are
reported as chemical shift. High resolution mass spectra were
obtained with the Q-TOF-Premier mass spectrometer. Flash
column chromatography was carried out using silica gel eluting
with ethyl acetate and petroleum ether. Reactions were
monitored by TLC and visualized with ultraviolet light.
General procedure for [3 + 2] annulation
Scheme 2 Plausible reaction mechanism
The mixture of 0.1 mmol 1, 0.12 mmol 2 and 20 mol% Bu3P in 1
mL toluene was stirred at room temperature under N2
atmosphere, and the reaction was detected by TLC. After the
reaction was completed, the crude product was directly purified
by silica gel chromatography to give the desired [3 + 2] product
3
.
Anti-1'-tert-butoxycarbonyloxy-spiro[4.3']oxindole-spiro
[5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
methoxycarbonyl-3-benzene-1-ene (3a). >99% yield, dr >20:1,
white solid, mp 141.2 oC decomposition); 1H NMR (300 MHz,
(
DMSO-d6) δ 7.70 (d, J = 7.2 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.32–
7.27 (m, 5H), 7.09-7.14 (m, 4H), 6.86 (d, J = 2.5 Hz, 1H), 6.79 (dd,
J = 6.7, 2.8 Hz, 2H), 5.22 (d, J = 2.6 Hz, 1H), 3.67 (s, 3H), 1.55 (s,
Scheme 3 Scale-up preparation and the deprotection of [3 + 2]
product 3a
9H), 1.36 (s, 9H)
；
13C NMR (75 MHz, DMSO-d6) δ 171.5, 170.3,
4 | J. Name., 2012, 00, 1-3
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164.1, 147.9, 147.4, 141.7, 141.1, 139.5, 139.4, 135.2, 130.1, MHz, Chloroform-d) δ 172.7, 170.5, 163.8, 148.4, 148.1, 143.2,
129.9, 128.6, 127.7, 127.2, 125.8, 124.6, 124.5, 124.4, 124.1, 140.7, 139.9, 139.8, 134.1, 133.3, 132.6, 129.9, 129.6, 129.2,
122.5, 114.2, 114.1, 84.2, 83.9, 68.4, 66.3, 55.5, 51.9, 27.6, 27.4; 128.5, 127.1, 126.4, 126.0, 124.6, 123.9, 123.7, 122.3, 114.5,
HRMS-ESI (m/z): Calcd for C37H36N2O8, (M + H)+: 637.25444, 114.1, 84.5, 83.9, 68.9, 66.7, 52.1, 51.7, 28.0, 27.9, 27.8. HRMS-
found: 637.25458.
Syn-1 -tert-butoxycarbonyloxy-spiro[4.3
[5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
ESI (m/z): Calcd for C37H35ClN2O8, (M + H)+: 671.21547, found:
'
']oxindole-spiro
671.21503.
Anti-1'-tert-butoxycarbonyloxy-spiro[4.3'']oxindole-spiro
methoxycarbonyl-3-benzene-1-ene (3a’). 1H NMR (300 MHz, [5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
DMSO-d6) δ 7.49 (ddd, J = 9.2, 7.8, 1.1 Hz, 2H), 7.38 (t, J = 8.5 Hz, methoxycarbonyl-3-m-chlorobenzene-1-ene (3e). >99% yield, dr
2H), 7.31–7.24 (m, 1H), 7.15 (d, J = 1.3 Hz, 1H), 7.07 (dd, J = 3.6, 2.4 >20:1, white solid, mp 181.8 oC decomposition); 1H NMR (300
(
Hz, 4H), 6.83–6.72 (m, 3H), 6.66 (d, J = 7.6 Hz, 1H), 5.19 (d, J = 2.6 Hz, MHz, Chloroform-d) δ 7.74–7.69 (d, J = 7.9 Hz, 1H), 7.63 (dd, J =
1H), 3.66 (s, 3H), 1.39 (s, 9H), 1.36 (s, 9H); 13C NMR (75 MHz, DMSO- 8.1, 1.0 Hz, 1H), 7.48 (td, J = 7.9, 1.2 Hz, 2H), 7.29–7.21 (m, 3H),
d6) δ 170.9, 168.6, 164.1, 148.0, 147.9, 141.3, 139.4, 139.3, 138.8, 7.18 (dd, J = 7.6, 1.3 Hz, 1H), 7.15–6.98 (m, 3H), 6.85 (s, 1H),
134.9, 130.2, 129.5, 129.2, 127.4, 127.1, 125.5, 124.6, 124.4, 123.4, 6.78–6.70 (m, 2H), 5.28 (d, J = 2.6 Hz, 1H), 3.71 (s, 3H), 1.60 (s,
122.6, 114.6, 113.7, 83.7, 83.4, 67.9, 66.3, 55.1, 51.9, 27.6, 27.5. 9H), 1.43 (s, 9H); 13C NMR (75 MHz, Chloroform-d) δ 142.0,
HRMS-ESI (m/z): Calcd for C37H36N2O8, (M + H)+: 637.25444, 141.1, 140.2, 139.8, 137.2, 133.4, 129.9, 128.9, 128.9, 127.4,
found: 637.25456.
Anti-1 -tert-butoxycarbonyloxy-spiro[4.3
[5.3'']1 -tert-butoxycarbonyloxy-oxindole-cyclopent-2-
methoxycarbonyl-3-o-fluorobenzene-1-ene (3b). >99% yield, dr
>20:1, white solid, mp 171.2 oC decomposition); 1H NMR (300 [5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
MHz, Chloroform-d) δ 7.77 (dt, J = 7.7, 1.5 Hz, 1H), 7.67–7.64 (m, methoxycarbonyl-3-p-chlorobenzene-1-ene (3f). >99% yield, dr
1H), 7.54 (dd, J = 7.7, 1.4 Hz, 1H), 7.46 (dd, J = 8.1, 1.2 Hz, 1H), >20:1, white solid, mp 195.7 oC decomposition); 1H NMR (300
127.2, 126.8, 124.7, 124.4, 124.2, 123.9, 122.7, 114.7, 114.6,
84.6, 84.1, 68.8, 56.6, 51.8, 28.0, 27.8. HRMS-ESI (m/z): Calcd for
C37H35ClN2O8, (M + H)+ : 671.21547, found: 671.21509.
'
']oxindole-spiro
'
Anti-1'-tert-butoxycarbonyloxy-spiro[4.3']oxindole-spiro
(
(
7.29–7.24 (m, 3H), 7.16–7.10 (m, 3H), 6.75–6.9 (m, 1H), 6.81 MHz, Chloroform-d) δ 7.70 (dd, J = 7.5, 1.6 Hz, 1H), 7.66 (d, J =
(ddd, J = 9.6, 8.3, 1.3 Hz, 1H), 6.75 (d, J = 2.6 Hz, 1H), 5.71 (d, J = 8.2 Hz, 1H), 7.45 (td, J = 8.1, 1.2 Hz, 2H), 7.29–7.20 (m, 2H), 7.15
2.2 Hz, 1H), 3.72 (s, 3H), 1.64 (s, 9H), 1.46 (s, 9H); 13C NMR (75 (td, J = 7.6, 1.3 Hz, 1H), 7.12–7.03 (m, 3H), 6.85–6.77 (m, 2H),
MHz, Chloroform-d) δ 172.6, 170.6, 163.9, 148.3, 148.1, 142.0, 6.74 (d, J = 2.6 Hz, 1H), 5.29 (d, J = 2.6 Hz, 1H), 3.71 (s, 3H), 1.60
141.1, 140.2, 139.8, 135.3 (J = 282.67 Hz), 129.9, 128.9, 128.9, (s, 9H), 1.43 (s, 9H); 13C NMR (75 MHz, Chloroform-d) δ 172.6,
127.5, 127.2, 126.8, 124.7, 124.4, 124.2, 123.9, 122.7, 114.7, 170.7, 164.0, 148.3, 148.0, 142.2, 141.0, 140.2, 139.8, 133.7,
114.6, 84.6, 84.1, 68.9, 66.2, 56.6, 51.8, 28.0, 27.8. HRMS-ESI 133.1, 130.2, 130.0, 129.9, 127.9, 126.8, 124.7, 124.4, 124.2,
(m/z): Calcd for C37H35FN2O8, (M + H)+: 655.24502, found: 124.0, 122.8, 114.7, 114.6, 84.6, 84.1, 68.84, 66.2, 56.3, 51.8,
655.24536.
Anti-1 -tert-butoxycarbonyloxy-spiro[4.3
[5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
methoxycarbonyl-3-p-fluorobenzene-1-ene (3c). 98% yield, dr [5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
>20:1, white solid, mp 183.6 oC decomposition); 1H NMR (300 methoxycarbonyl-3-o-bromolbenzene-1-ene (3g). 98% yield, dr
MHz, Chloroform-d) δ 7.63 (dd, J = 7.4, 1.5 Hz, 1H), 7.60 (dt, J = >20:1, white solid, mp 190.5 oC decomposition); 1H NMR (300
28.0, 27.8. HRMS-ESI (m/z): Calcd for C37H35ClN2O8, (M + H)+:
'
']oxindolespiro
671.21547, found: 671.21545.
Anti-1'-tert-butoxycarbonyloxy-spiro[4.3']oxindole-spiro
(
(
8.2, 0.8 Hz, 1H), 7.47–7.46 (m, 1H), 7.42–7.42(m, 1H), 7.25–7.23 MHz, Chloroform-d) δ 7.84 (dd, J = 7.7, 1.3 Hz, 1H), 7.68–7.59
(m, 2H), 7.15 (dd, J = 7.6, 1.3 Hz, 1H), 7.08 (dd, J = 7.6, 1.1 Hz, (m, 1H), 7.52 (ddd, J = 7.9, 3.6, 1.5 Hz, 2H), 7.41 (dd, J = 8.3, 1.1
1H), 6.82–6.67 (m, 5H), 5.30 (d, J = 2.6 Hz, 1H), 3.69 (s, 3H), 1.59 Hz, 1H), 7.31 (dd, J = 8.0, 1.4 Hz, 1H), 7.29–7.14 (m, 3H), 7.08 (tt,
(s, 9H), 1.42 (s, 9H); 13C NMR (75 MHz, Chloroform-d) δ 172.6, J = 7.6, 1.3 Hz, 2H), 6.99 (d, J = 1.7 Hz, 1H), 6.76 (d, J = 2.6 Hz,
170.8, 164.1, 162.1 (J = 257.45 Hz ), 160.3, 148.3, 140.7, 140.2, 1H), 5.96 (d, J = 2.6 Hz, 1H), 3.62 (s, 3H), 1.61 (s, 9H), 1.43 (s, 9H);
139.8, 130.8, 130.8, 130.5, 130.4, 129.8, 129.8, 126.7, 124.6, 13C NMR (75 MHz, Chloroform-d) δ 172.9, 170.5, 163.8, 148.4,
124.3, 124.2, 124.0, 122.8, 114.7, 114.6, 114.5, 114.4, 84.6, 84.0, 148.1, 143.3, 140.7, 140.0, 135.1, 132.7, 132.7, 129.9, 129.7,
68.9, 66.1, 56.2, 51.8, 27.9, 27.8. HRMS-ESI (m/z): Calcd for 128.8, 127.3, 126.9, 126.7, 124.8, 124.6, 124.0, 123.7, 122.1,
C37H35FN2O8, (M + H)+: 655.24502, found: 655.24457.
114.6, 114.1, 84.6, 84.0, 69.2, 66.7, 54.6, 51.8, 28.0, 27.9, 27.8.
HRMS-ESI (m/z): Calcd for C37H35BrN2O8, (M + H)+: 715.16496,
found: 715.16559.
Anti-1'-tert-butoxycarbonyloxy-spiro[4.3']oxindole-spiro
[5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
methoxycarbonyl-3-o-chlorobenzene-1-ene (3d). >99 % yield, dr
Anti-1'-tert-butoxycarbonyloxy-spiro[4.3']oxindole-spiro
>20:1, white solid, mp 189.3 oC decomposition); 1H NMR (300 [5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
(
MHz, Chloroform-d) δ 7.80 (dd, J = 7.6, 1.4 Hz, 1H), 7.63 (d, J = methoxycarbonyl-3-m-bromolbenzene-1-ene (3h). >99% yield,
8.2 Hz, 1H), 7.52–7.48 (m, 2H), 7.41 (d, J = 8.2 Hz, 1H), 7.26–7.20 dr >20:1, white solid, mp 176.8 o decomposition); 1H NMR (300
C
(
(m, 3H), 7.09–7.06 (m, 5H), 6.76 (d, J = 2.6 Hz, 1H), 5.97 (d, J = MHz, Chloroform-d) δ 7.71 (dd, J = 7.5, 1.5 Hz, 1H), 7.63 (dd, J =
8.1, 1.0 Hz, 1H), 7.48 (td, J = 7.3, 1.2 Hz, 2H), 7.29–7.20 (m, 3H),
2.6 Hz, 1H), 3.63 (s, 3H), 1.61 (s, 9H), 1.43 (s, 9H)
；
13C NMR (75
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7.17 (dd, J = 7.6, 1.3 Hz, 1H), 7.08 (dd, J = 7.6, 1.1 Hz, 1H), 7.02– methoxycarbonyl-3-m-NO2-benzene-1-ene (3l). >99% yield, dr
6.91 (m, 2H), 6.80 (dt, J = 7.8, 1.4 Hz, 1H), 6.74 (d, J = 2.6 Hz, 1H), >20:1, white solid, mp 174.2 oC decomposition); 1H NMR (300
(
5.27 (d, J = 2.6 Hz, 1H), 3.71 (s, 3H), 1.60 (s, 9H), 1.44 (s, 9H); 13C MHz, Chloroform-d) δ 7.99 (d, J = 6.9 Hz, 1H), 7.80–7.73 (m, 1H),
NMR (75 MHz, Chloroform-d) δ 172.5, 170.6, 163.9, 148.3,148.1, 7.73–7.69 (m, 1H), 7.63 (d, J = 8.2 Hz, 1H), 7.47 (dd, J = 7.8, 1.3
142.0, 141.1, 140.2, 139.8, 137.4, 131.8, 130.3, 129.9, 129.2, Hz, 1H), 7.43 (dd, J = 8.0, 1.4 Hz, 1H), 7.26 (m, 5H), 7.07 (td, J =
127.6, 126.8, 124.7, 124.4, 124.1, 123.9, 122.6, 121.6, 114.7, 7.6, 1.2 Hz, 1H), 6.81 (d, J = 2.5 Hz, 1H), 5.42 (d, J = 2.6 Hz, 1H),
114.6, 84.6, 84.1, 68.9, 66.2, 56.5, 51.8, 28.0, 27.8. HRMS-ESI 3.72 (s, 3H), 1.60 (s, 9H), 1.40 (s, 9H); 13C NMR (75 MHz,
(m/z): Calcd for C37H35BrN2O8, (M + H)+: 715.16496, found: Chloroform-d) δ 172.2, 170.7, 163.6, 148.2, 147.8, 147.6, 141.7,
715.16534.
nti-1 -tert-butoxycarbonyloxy-spiro[4.3
[5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
141.3, 140.0, 139.8, 137.3, 135.2, 130.2, 130.1, 128.6, 126.6,
124.7, 124.6, 124.2, 124.0, 123.6, 122.3, 122.1, 114.7, 114.7,
84.7, 84.3, 68.7, 66.4, 56.1, 51.9, 27.9, 27.7. HRMS-ESI (m/z):
A
'
']oxindole-spiro
methoxycarbonyl-3-o-methylbenzene-1-ene (3i). >99% yield, dr Calcd for C37H35N3O10, (M + H)+: 704.22147, found: 704.22168.
>20:1, white solid, mp 192.3 oC decomposition); 1H NMR (300
Anti-1 -tert-butoxycarbonyloxy-spiro[4.3 ]oxindole-spiro
(
'
'
MHz, Chloroform-d) δ 7.78 (dd, J = 7.7, 1.4 Hz, 1H), 7.63 (d, J = [5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
8.1 Hz, 1H), 7.61–7.54 (m, 1H), 7.46 (d, J = 8.1 Hz, 1H), 7.35 (dd, J methoxycarbonyl-3-p-NO2-benzene-1-ene (3m) 97% yield, dr
= 7.7, 1.6 Hz, 1H), 7.26(m, 2H), 7.13–6.95 (m, 4H), 6.91–6.83 (m, >20:1, white solid, mp 206.9 oC decomposition); 1H NMR (300
(
1H), 6.73 (dd, J = 2.6, 1.0 Hz, 1H), 5.64 (d, J = 2.6 Hz, 1H), 3.62 (s, MHz, DMSO-d6) δ 8.03–7.87 (m, 2H), 7.72 (dd, J = 7.1, 1.3 Hz,
3H), 1.69 (s, 3H), 1.63 (s, 9H), 1.41 (s, 9H); 13C NMR (75 MHz, 1H), 7.61–7.50 (m, 1H), 7.41–7.15 (m, 5H), 7.14–6.99 (m, 3H),
Chloroform-d) δ 173.4, 170.3, 164.2, 148.4, 140.2, 139.8, 136.6, 6.88 (d, J = 2.5 Hz, 1H), 5.37 (d, J = 2.5 Hz, 1H), 3.69 (s, 3H), 1.54
133.5, 130.9, 129.9, 129.8, 129.7, 127.6, 127.0, 125.3, 125.1, (s, 9H), 1.35 (s, 9H); 13C NMR (75 MHz, DMSO-d6) δ 171.2, 170.1,
124.6, 124.4, 123.9, 123.3, 114.6, 114.5, 84.6, 83.9, 69.1, 66.3, 163.4, 147.7, 147.1, 146.6, 142.9, 141.8, 140.7, 139.5, 139.3,
53.4, 51.7, 28.0, 27.8, 19.7. HRMS-ESI (m/z): Calcd for C38H38N2O8, 130.0, 129.9, 129.8, 125.7, 124.4, 124.3, 124.2, 123.4, 122.5,
(M + H)+: 651.27009, found: 651.27051.
121.6, 114.2, 114.2, 84.0, 83.8, 79.1, 78.9, 78.7, 78.2, 68.2, 66.2,
55.0, 51.7, 27.5, 27.3. HRMS-ESI (m/z): Calcd for C37H35N3O10, (M
+ Na)+: 704.22147, found: 704.22119.
Anti-1'-tert-butoxycarbonyloxy-spiro[4.3']oxindole-spiro
[5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
methoxycarbonyl-3-p-methylbenzene-1-ene (3j). 95% yield, dr
Anti-1'-tert-butoxycarbonyloxy-spiro[4.3']oxindole-spiro
>20:1, white solid, mp 194.4 oC decomposition); 1H NMR (300 [5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
(
MHz, Chloroform-d) δ 7.72 (dd, J = 7.4, 1.5 Hz, 1H), 7.62 (d, J = methoxycarbonyl-3-fruyl-1-ene (3n). 92% yield, dr >20:1, red
8.3 Hz, 1H), 7.50 (dd, J = 7.6, 1.4 Hz, 1H), 7.44 (dd, J = 8.2, 1.2 Hz, solid, mp 146.8 oC decomposition); 1H NMR (300 MHz,
(
1H), 7.30–7.11 (m, 3H), 7.07 (td, J = 7.6, 1.1 Hz, 1H), 6.88 (d, J = Chloroform-d) δ 7.62 (ddd, J = 8.1, 3.3, 1.2 Hz, 2H), 7.52 (dd, J =
7.9 Hz, 2H), 6.74 (dd, J = 8.5, 2.3 Hz, 2H), 6.70 (d, J = 2.6 Hz, 1H), 8.4, 1.1 Hz, 1H), 7.49 (dd, J = 7.8, 1.4 Hz, 1H), 7.29–7.21 (m, 2H),
5.29 (d, J = 2.7 Hz, 1H), 3.70 (s, 3H), 2.20 (s, 3H), 1.60 (s, 9H), 7.18 (dd, J = 1.8, 0.8 Hz, 1H), 7.09 (dtd, J = 12.5, 7.6, 1.2 Hz, 2H),
1.41 (s, 9H); 13C NMR (75 MHz, Chloroform-d) δ 172.8, 170.8, 6.64 (d, J = 2.8 Hz, 1H), 6.16 (dd, J = 3.3, 1.8 Hz, 1H), 6.01–5.81
164.3, 148.4, 148.2, 142.9, 140.3, 139.8, 136.6, 131.9, 129.8, (m, 1H), 5.41 (d, J = 2.8 Hz, 1H), 3.73 (s, 3H), 1.58 (s, 9H), 1.48 (s,
129.6, 128.7, 128.4, 126.9, 124.6, 124.3, 124.2, 123.2, 114.6, 9H); 13C NMR (75 MHz, Chloroform-d) δ 172.3, 171.0, 163.6,
114.5, 84.5, 83.8, 69.0, 66.2, 56.7, 51.7, 28.0, 27.8, 21.0. HRMS- 149.5, 148.4,148.2, 141.7, 141.4, 140.2, 139.8, 139.4, 129.9,
ESI (m/z): Calcd for C38H38N2O8, (M + H)+: 651.27009, found: 129.8, 126.5, 124.6, 124.3, 124.2, 123.7, 122.9, 114.6, 114.5,
651.26990.
Anti-1 -tert-butoxycarbonyloxy-spiro[4.3']oxindole-spiro
110.3, 108.4, 84.5, 84.0, 67.6, 66.2, 51.8, 50.3, 27.9, 27.9. HRMS-
ESI (m/z): Calcd for C35H34N2O9, (M + H)+: 649.21565, found:
649.21594.
'
[5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
methoxycarbonyl-3-m-OBoc-benzene-1-ene (3k). >99% yield, dr
Anti-1'-tert-butoxycarbonyloxy-spiro[4.3']oxindole-spiro
>20:1, white solid, mp 174.8 oC decomposition); 1H NMR (300 [5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
(
MHz, Chloroform-d) δ 7.76–7.66 (m, 1H), 7.61 (d, J = 8.2 Hz, 1H), butyloxycarbonyl-3-benzene-1-ene (3o). >99% yield, dr >20:1,
7.46 (dd, J = 7.7, 4.4 Hz, 2H), 7.29–7.13 (m, 3H), 7.11–6.99 (m, white solid, mp 143.2 oC decomposition); 1H NMR (300 MHz,
(
2H), 6.97–6.87 (m, 1H), 6.74–6.60 (m, 3H), 5.32 (d, J = 2.6 Hz, Chloroform-d) δ 7.74 (dd, J = 7.4, 1.5 Hz, 1H), 7.68–7.57 (m, 1H),
1H), 3.67 (s, 3H), 1.58 (s, 9H), 1.48 (s, 9H), 1.41 (s, 9H); 13C NMR 7.52 (dd, J = 7.7, 1.3 Hz, 1H), 7.44 (dd, J = 8.1, 1.2 Hz, 1H), 7.30–
(75 MHz, Chloroform-d) δ 172.5, 170.5, 164.1, 151.3, 150.3, 7.14 (m, 3H), 7.13–7.01 (m, 4H), 6.94–6.79 (m, 2H), 6.71 (dd, J =
148.2, 148.0, 142.6, 140.5, 140.2, 139.7, 136.8, 129.8, 129.7, 2.7, 0.9 Hz, 1H), 5.32 (d, J = 2.6 Hz, 1H), 4.15 (dt, J = 11.1, 6.6 Hz,
128.4, 126.7, 126.1, 124.5, 124.2, 124.1, 123.9, 122.8, 121.8, 1H), 4.07–3.90 (m, 1H), 1.61 (s, 9H), 1.41 (m, 11H), 1.15–0.98 (m,
119.9, 114.7, 114.5, 84.5, 83.8, 83.0, 68.7, 66.3, 56.2, 51.7, 27.9, 2H), 0.77 (t, J = 7.3 Hz, 3H); 13C NMR (75 MHz, Chloroform-d) δ
27.7, 27.5. HRMS-ESI (m/z): Calcd for C42H44N2O11, (M + Na)+: 172.8, 170.7, 163.9, 148.4, 148.1, 143.3, 140.2, 140.0, 139.8,
775.28373, found: 775.28373.
Anti-1 -tert-butoxycarbonyloxy-spiro[4.3']oxindole-spiro
135.2, 129.8, 129.6, 128.9, 127.6, 127.0, 126.9, 124.6, 124.3,
124.2, 123.2, 114.6, 114.5, 84.5, 83.8, 69.0, 66.2, 64.4, 57.0,
'
[5.3'']1''-tert-butoxycarbonyloxy-oxindole-cyclopent-2-
6 | J. Name., 2012, 00, 1-3
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30.4, 28.0, 27.8, 18.9, 13.6. HRMS-ESI (m/z): Calcd for C40H42N2O8, 125.2, 124.8, 124.4, 122.4, 121.4, 115.5, 85.3, 84.6, 68.6, 65.7,
(M + Na)+: 701.28334, found: 701.28363.
Anti-1 -tert-butoxycarbonyloxy-5 -fluoro-spiro[4.3
oxindole-spiro[5.3'']1''-tert-butoxycarbonyloxy-5''-fluoro-
oxindole-cyclopent-2-methoxycarbonyl-3-benzene-1-ene (3p). oxindole-cyclopent-2-methoxycarbonyl-3-benzene-1-ene (3t).
57.2, 51.8, 27.9, 27.7. HRMS-ESI (m/z): Calcd for C37H34Cl2N2O8,
(M + Na)+: 727.15844, found : 727.15936.
'
'
']
Anti-1'-ethyl-spiro[4.3']oxindole-spiro[5.3'']1''-ethyl-
1
95% yield, dr >20:1, white solid, mp 198.3 o decomposition); 1H 89% yield, dr >20:1, white solid, mp 244.3-245.7 oC; H NMR (300
C (
NMR (300 MHz, Chloroform-d) δ 7.71 (dd, J = 9.0, 4.7 Hz, 1H), MHz, Chloroform-d) δ 7.79 (dd, J = 7.6, 1.3 Hz, 1H), 7.60 (dd, J =
7.59–7.41 (m, 2H), 7.32–7.22 (m, 1H), 7.18–7.05 (m, 3H), 6.97 7.6, 1.2 Hz, 1H), 7.17 (dtd, J = 9.2, 7.7, 1.3 Hz, 2H), 7.08–6.97 (m,
(tdd, J = 8.8, 4.0, 2.8 Hz, 2H), 6.90–6.80 (m, 2H), 6.69 (dd, J = 2.7, 4H), 6.93 (td, J = 7.6, 1.1 Hz, 1H), 6.81 (dt, J = 8.6, 2.1 Hz, 3H),
0.9 Hz, 1H), 5.28 (d, J = 2.7 Hz, 1H), 3.69 (s, 3H), 1.62 (s, 9H), 1.42 6.64 (d, J = 7.9 Hz, 1H), 6.39 (d, J = 7.8 Hz, 1H), 5.42 (d, J = 2.6 Hz,
(s, 9H); 13C NMR (75 MHz, Chloroform-d) δ 172.1, 170.1, 163.9, 1H), 3.85 (dq, J = 14.5, 7.3 Hz, 1H), 3.68 (s, 3H), 3.51 (dq, J = 14.2,
159.6(J= 242.6 Hz), 159.6(J = 214.9 Hz), 161.2, 161.2, 158.0, 7.2 Hz, 1H), 3.28 (dt, J = 14.4, 7.2 Hz, 1H), 3.04 (dq, J = 14.3, 7.1
148.4, 148.2, 143.1, 139.6, 134.5, 134.50, 128.8, 127.8, 127.4, Hz, 1H), 1.10 (t, J = 7.2 Hz, 3H), 0.42 (t, J = 7.1 Hz, 3H); 13C NMR
116.7, 116.6, 116.4, 116.3, 116.1, 116.0, 116.00, 115.9, 114.7, (75 MHz, Chloroform-d) δ 174.2,172.6, 164.6, 143.2, 143.1,
114.4, 112.0, 111.7, 85.2, 84.4, 68.8, 66.0, 57.2, 51.8, 27.8, 27.6. 142.9, 141.6, 135.7, 129.1, 129.0, 128.5, 128.2, 127.4, 127.2,
HRMS-ESI (m/z): Calcd for C37H34F2N2O8, (M + Na)+: 695.21754, 126.9, 126.7, 126.6, 125.3, 125.1, 122.6, 122.1, 121.2, 107.9,
found: 695.21814.
Anti-1 -tert-butoxycarbonyloxy-7
107.5, 107.0, 67.5, 64.4, 57.3, 57.0, 51.6, 34.8, 34.4, 33.5, 12.5,
'
'
-fluoro-spiro[4.3
'
]
11.4. HRMS-ESI (m/z): Calcd for C31H28N2O4, (M
515.19413, found: 515.19458.
+
Na)+:
oxindole-spiro[5.3'']1''-tert-butoxycarbonyloxy-7''-fluoro-
oxindole-cyclopent-2-methoxycarbonyl-3-benzene-1-ene (3q).
92% yield, dr >20:1, white solid, mp 165.4 o
Anti-1'-allyl-spiro[4.3']oxindole-spiro[5.3'']1''-allyl-oxindole-
decomposition); 1H cyclopent-2-methoxycarbonyl-3-benzene-1-ene (3w). 85%
1H NMR (300
C
(
NMR (300 MHz, Chloroform-d) δ 7.52 (dd, J = 7.8, 1.0 Hz, 1H), yield, dr >20:1, white solid, mp 177.1-178.0 oC
;
7.34–7.25 (m, 1H), 7.23–6.97 (m, 7H), 6.91–6.77 (m, 2H), 6.70 (d, MHz, Chloroform-d) δ 7.76 (dd, J = 7.6, 1.3 Hz, 1H), 7.57 (dd, J =
J = 2.6 Hz, 1H), 5.32 (d, J = 2.6 Hz, 1H), 3.69 (s, 3H), 1.52 (s, 9H), 7.7, 1.3 Hz, 1H), 7.22–6.97 (m, 6H), 6.93 (td, J = 7.7, 1.1 Hz, 1H),
1.31 (s, 9H); 13C NMR (75 MHz, Chloroform-d) δ 172.0, 170.3, 6.89–6.82 (m, 2H), 6.80 (d, J = 2.6 Hz, 1H), 6.61 (d, J = 7.8 Hz,
164.0, 149.8, 146.5, 142.9, 139.5, 134.5, 128.7, 127.8, 127.5, 1H), 6.35 (d, J = 7.7 Hz, 1H), 5.59 (ddt, J = 17.0, 10.3, 5.1 Hz, 1H),
127.2, 126.3, 126.1, 126.0, 125.7, 125.6, 121.5 (J
=
5.47 (d, J = 2.6 Hz, 1H), 5.12–4.92 (m, 2H), 4.82 (d, J = 17.1 Hz,
195.3Hz),121.5 (J = 198.8 Hz), 118.4, 118.1, 118.1, 117.8, 85.2, 1H), 4.73–4.60 (m, 1H), 4.50 (ddt, J = 16.6, 4.6, 2.0 Hz, 1H), 4.20–
84.3, 69.7, 66.7, 57.1, 51.8, 27.5, 27.4. HRMS-ESI (m/z): Calcd for 4.07 (m, 1H), 4.08–3.95 (m, 1H), 3.87 (ddt, J = 16.7, 4.3, 2.0 Hz,
C37H34F2N2O8, (M + Na)+: 695.21754, found: 673.23560.
Anti-1 -tert-butoxycarbonyloxy-5 -chloro-
spiro[4.3 ]oxindole-spiro[5.3'']1''-tert-butoxycarbonyloxy-5''
chloro-oxindole-cyclopent-2-methoxycarbonyl-3-benzene-1-
1H), 3.78–3.56 (m, 4H); 13C NMR (75 MHz, Chloroform-d) δ
174.3, 172.7, 164.5, 143.3, 143.2, 142.6, 141.9, 135.8, 130.6,
130.2, 129.2, 129.0, 128.7, 127.4, 127.2, 126.8, 126.2, 125.1,
125.0, 122.8, 122.4, 117.7, 116.3, 108.8, 108.4, 67.9, 57.0, 51.6,
'
'
'
-
ene (3r) 92% yield, dr >20:1, white solid, mp 180.1 oC 42.5, 41.1. HRMS-ESI (m/z): Calcd for C33H28N2O4, (M + Na)+:
1
decomposition); H NMR (300 MHz, Chloroform-d) δ 7.73 (d, J = 539.19413, found: 539.19458.
(
0.9 Hz, 1H), 7.71 (d, J = 5.7 Hz, 1H), 7.50 (d, J = 2.3 Hz, 1H), 7.49
(d, J = 4.3 Hz, 1H), 7.31–7.18 (m, 2H), 7.16–7.01 (m, 3H), 6.93–
6.76 (m, 2H), 6.68 (d, J = 2.6 Hz, 1H), 5.29 (d, J = 2.6 Hz, 1H), 3.68
(s, 3H), 1.65 (s, 9H), 1.44 (s, 9H); 13C NMR (75 MHz, Chloroform-
d) δ 171.9, 169.8, 163.9, 148.3, 148.1, 143.0, 139.7, 138.9, 138.5,
134.4, 130.2, 130.1, 130.0, 129.9, 128.7, 127.8, 127.4, 127.0,
125.7, 124.9, 124.4, 116.1, 116.0, 85.4, 84.6, 68.6, 65.8, 57.5,
51.8, 27.9, 27.7. HRMS-ESI (m/z): Calcd for C37H34Cl2N2O8, (M +
Na)+: 727.15844, found: 727.15857.
Conflicts of interest
There are no conflicts to declare.
Notes and references
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Effective and Diastereoselective Preparation of Dispiro[cyclopent-3
+ 2] Annulation of Isoindigos and MBH Carbonates
′-ene]bisoxindoles via Novel [3