Diversity-Oriented Synthesis of Oxacyclic Spirooxindole Derivatives through Ring-Closing Enyne Metathesis and Intramolecular Pauson–Khand (2+2+1) Cyclization of Oxindole Enynes

Article abstract of DOI:10.1002/adsc.201700511

An efficient approach for a reagent-based diversity-oriented synthesis (DOS) of novel fused spirooxindole scaffolds from oxindole enynes has been developed. The reaction involves a metal-catalyzed C-3 allylation/vinylation/homoallylation of N-substituted isatins which gives rise to the corresponding alcohols that can be converted into the required enynes. Further transformation to diverse complex molecular scaffolds proceeds via a subsequent ruthenium-catalyzed ring-closing enyne metathesis (RCEYM), or cobalt-catalyzed intramolecular Pauson–Khand (2+2+1) cyclization reaction (IPKR). This strategy provides a facile approach to various spirooxindole-vinyldihydropyrans/tetrahydrooxepines and spirocyclic fused cyclopentenones in good to excellent yields. (Figure presented.).

Full text of DOI:10.1002/adsc.201700511

Title: Diversity-Oriented Synthesis of oxacyclic spirooxindole
derivatives through ring-closing enyne metathesis and
intramolecular Pauson−Khand (2 + 2 + 1) cyclization of oxindole
enynes
Authors: Gowravaram Sabitha and Satheeshkumar Reddy Kandimalla
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700511
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10.1002/adsc.201700511
Advanced Synthesis & Catalysis
UPDATES
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Diversity-Oriented Synthesis of oxacyclic spirooxindole
derivatives through ring-closing enyne metathesis and
intramolecular Pauson−Khand (2 + 2 + 1) cyclization of
oxindole enynes
Satheeshkumar Reddy Kandimallaa,b and Gowravaram Sabitha*a,b
a
Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India.
Academy of Scientific and Innovative Research (AcSIR), New Delhi-110 025, India.
b
E-mail: gowravaramsr@yahoo.com, sabitha@iict.res.in; Fax: +91-40-27160512
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract: An efficient approach for a reagent-based cyclization reaction (IPKR). This strategy provided a facile
Diversity-Oriented Synthesis (DOS) of novel fused spiro- approach
oxindole scaffolds have been reported from oxindole enynes. dihydropyrans/tetrahydrooxepines and spirocyclic fused
The reaction involves metal-catalyzed C-3 cyclopentenones in good to excellent yields.
to
various
spirooxindole-vinyl
a
allylation/vinylation/homoallylation of N-substituted isatins
gives rise to corresponding alcohols that can be converted Keywords: Diversity-Oriented Synthesis, Ring-closing
into required enynes, further transformed to a diverse enyne metathesis, intramolecular Pauson−Khand (2 + 2 +
complex molecular scaffolds via subsequent Ruthenium 1) cyclization, Oxindole enynes, Oxacyclic spirooxindoles,
catalyzed ring-closing enyne metathesis (RCEYM), or Fused cyclopentenones
Cobalt catalyzed intramolecular Pauson−Khand (2 + 2 + 1)
spirocyclic oxindole derivatives, for example (Figure
1) XEN907,[6] compound A (luminescent),[7] CB2
Introduction
receptor antagonist,[8]
modulators,[9]
progesterone receptor
anti-HIV,[10]
anticancer,[11]
The discovery of new chemical entities for drug
discovery has received considerable attention during
the last few decades. In this context, Diversity-
Oriented Synthesis (DOS) has emerged as a powerful
tool to get the maximum structural variability from
simple starting materials.[1,2] Especially, oxygen- and
nitrogen-containing heterocycles have attracted the
attention of synthetic and medicinal chemists because
of the widespread occurrence of such structural motifs
in natural and unnatural products and their use as
building blocks.[3] Moreover, spirooxindoles have
become a privileged skeleton given their broad and
promising activities in various therapeutic areas.
antitubercular,[12] antimalarial,[13,14] and MDM2
inhibitors[15] were found in the literature. Therefore,
the construction of spirooxindole skeleton has
attracted great attention of synthetic chemists[16]
.
Spirooxindole frame-work has drawn tremendous
interest of researchers in the area of synthetic organic
chemistry and medicinal chemistry worldwide
because they occur in many natural products such as
Figure 1: Examples of some natural and bioactive
compounds containing spirocyclic oxindole scaffolds
spirotryprostatins,
horsfiline,
gelsemine,[4]
gelseverine,[4] (Figure 1)
rhynchophylline, and
Additionally, interesting and biologically active
elacomine, etc. and have been reported to have
various types of bioactivity.[5] Some of the bioactive
natural products containing
bicyclic fused
1
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10.1002/adsc.201700511
Advanced Synthesis & Catalysis
cyclopentenones are also common.[17-18] These are
Herein, we wish to report our results on the
demonstrated in Figure 2. Among these, synthesis
of
diverse
spirooxindole-vinyl
bicyclo[4.3.0]nonane,[17] and bicyclo[3.3.0]octane[18] dihydropyran/tetrahydrooxepines and spirooxindole-
frameworks are normally originate in bioactive 5,6-bicyclic/5,5-bicyclic cyclopentenone derivatives
natural products. For example, alisol-L,[17a] (Scheme 1) from oxindole enynes, which are
minwaninone,[17c] jiadifenin,[17c] hirsutanol A,[18a] constructed from isatins.
incarnal,[18a] chondrosterin A[18a] are some of the
representative natural products bearing 5,6-bicyclic,
We started our investigation with the preparation of
and 5,5-bicyclic cyclopentenone motifs in their the desired oxindole alcohols 3a-s from isatins
structures.
(Scheme 2). For this, first we synthesized N-alkylated
isatins 2a-n by treating various isatins (1) with K2CO3
and different alkyl halides. Then these were subjected
to a metal-mediated Nucleophilic addition to ketone
group at C3-position to get variety of transformations
such as C3-Allylation[22] 3a-n, C3-Vinylation[23] 3o-q,
C3-Homoallylation[24] 3r,s with good yields as
illustrated in Scheme 2.
Scheme 2: Diverse synthesis of oxindole alcohols starting
from isatins
Figure 2: Natural products having a bicyclic fused
cyclopentenone system.
These bicyclic fused cyclopentenone derivatives
serve as valuable building blocks in the synthesis of
various natural products,[19] such as (+)-
propindilactone
Penostatin
E,[19e]
Paecilomycine A.[19g]
G,[19c]
(+)-ryanodol,[19d]
A[19f]
(+)-
and
(+)-Sieboldine
The ring closing enyne metathesis (RCEYM),[20]
has attracted attention due to its synthetic potential in
the generation of ring structures with 1,3-diene
moieties, which can subsequently be further
functionalised. While, the Pauson-Khand reaction
(PKR)[21] is widely used as a powerful method for the
synthesis of cyclopentenone ring systems. The
intramolecular version of the reaction has gained
much
popularity
because
it
can
afford
cyclopentenone-fused ring systems, which are
difficult to construct. Due to their important roles,
we have utilized these two synthetic methods to
construct spirocyclic oxindole based compounds from
oxindole enynes.
Results and Discussion
Now, the desired enyne intermediates, 3-allyl-1-
substituted-3-prop-2-ynyloxy)-indolin-2-ones
(1,7-
enynes, 4a-n) could be accessed in 89-99% yields by
O-propargylation of the homoallylic alcohols 3a-n
with propargyl bromide in the presence of NaH and a
o
catalytic amount of TBAI in dry THF at 0 C-rt.
Under similar conditions, propargylation of 3o-q and
3r,s yielded 1-substituted-3-(prop-2-ynyloxy)-3-
vinylindolin-2-ones (1,6-enynes, 4o-q) and 1-benzyl-
3-(but-3-enyl)-3-(prop-2-ynyloxy)indolin-2-ones (1,8-
enynes, 4r,s) respectively as shown in Scheme 3.
These enynes 4a-s would in turn become suitable
substrates for selected transition metal catalyzed
transformations (ring-closing enyne metathesis
RCEYM, intramolecular Pauson−Khand reaction
Scheme 1: DOS strategy
2
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10.1002/adsc.201700511
Advanced Synthesis & Catalysis
Table 1: Optimization of RCEYM Reactiona
IPKR), aimed at obtaining a small collection of
structurally diverse molecules in a single step.
Scheme 3: Diverse synthesis of oxindole enynes
entry
substrate
Catalyst/conditions
yield(%)b
1
2
3
4
5
6
7
4a
4a
4a
4a
4a
4a
4b
G-1/THF, rt, 48 h
G-2/THF, rt, 72 h
G-1/Toluene, rt, 40 h
55
50
45
G-1/Toluene, 50 oC, 24 h 65
G-1/DCM, reflux, 12 h
G-2/DCM, reflux, 20 h
G-1/DCM, reflux, 12 h
90
76
92
aAll reactions performed under Ar atmosphere, Reaction
conditions: 4 (0.539 mmol, 1.0 eq), G-1 (5 mol %), DCM
b
(25 mL), reflux, 12 h. Yields refer to pure products after
column chromatography
Reagents and conditions: (a) Propargyl bromide, NaH,
TBAI (cat.), Dry THF, 0 oC-rt, 8-12 h.
The exo compound 5a was determined by using
detailed
NMR experiments.
The
observed
To evaluate the feasibility of RCEYM (ring
closing enyne metathesis) reaction,[20] 3-allyl-1-ethyl-
3-(prop-2-ynyloxy)indolin-2-one (4a) was chosen as a
model substrate and was initially treated with Grubbs-
I (containing PCy3 ligand) and Grubbs-II (containing
N-heterocyclic carbene (NHC) ligand) catalysts in
THF at room temperature for 48 h and 72 h, a vinyl
characteristic nOe cross-peaks between H1−H6, H5-H6,
H1’-H3 and H2−H4 indicates that the six membered
ring contains vinyl group as represented in Figure 3.
dihydropyran
derivative,
1-ethyl-5'-vinyl-3',6'-
dihydrospiro[indoline-3,2'-pyran]-2-one (5a) was
obtained in 55% and 50% yields respectively (Table 1,
entry 1 & 2). To improve the efficiency, different
solvents (toluene and DCM), temperatures and
timings were tried (entries 3−6). Among them, DCM
as the reaction medium at reflux temperature for 12 h
was the most efficient. The reaction with Grubbs-II
catalyst was less efficient than Grubbs-I in promoting
this reaction (entries 2 & 6). Since triple bond is more
electron donating than a double bond, the RCEYM
reaction occurs successfully with the less active first-
generation Grubbs catalyst and proceeds under mild
conditions. For consistency, we performed the
reaction of 4b with 5 mol% of Grubbs-I catalyst in
DCM (40 oC, 12 h), which yielded 5b in 92 % (Table
1, entry 7). In summary of the optimization study, we
observed only the exo product 5a formation over the
endo product 5’ with both Grubbs-I and Grubbs-II
catalysts[25] as shown in Table 1. The structure of 5a
was confirmed by NMR analysis and also finally
confirmed by NOE analysis.
Figure 3: Chemical and energy-minimized structures of
compound 5a.
With these optimized reaction conditions at hand,
we surveyed the substrate scope by varying the
structure of (1,7)-enynes (4a-n). As shown in Scheme
4, (1,7)-enynes bearing an alkyl substituent on the
i
nitrogen, including Et, Me, Pr, Bn 4a-d performed
well in RCEYM optimal conditions provided 5a-d in
excellent yields and we were delighted to find that the
reaction also accommodated several substituents,
including electron-donating and electron-withdawing
groups such as 5-Me, 5-OMe, 5-OCF3, 5-F, 5-Cl, 6-Cl,
7-Cl, 4-Br, 5-Br on the oxindole moiety, 4e-n giving
the corresonding spirooxindole-vinyl dihydropyrans
5e-n in 84%-90% yields.
3
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10.1002/adsc.201700511
Advanced Synthesis & Catalysis
Scheme 4: Scope of RCEYM Reaction of (1,7)-enynesa
time did not work to give the expected 1'-benzyl-4-
vinyl-5H-spiro[furan-2,3'-indolin]-2'-ones 5o-q
(Scheme 5). All the (1,6)-enynes 4o-q were intact and
recovered by column chromatography. One possible
reason for this lack of reactivity in the RCEYM step
is the steric hindrance of the oxindole in the starting
material.
Further investigations demonstrated with 1,8-
enynes (4r,s). Gratifyingly, RCEYM reaction of 4r,s
with Grubbs-I catalyst in refluxing DCM successfully
provided
1-benzyl-6'-vinyl-4',7'-dihydro-3'H-
spiro[indoline-3,2'-oxepin]-2-ones (5r,s) in 80% &
82% yields (Scheme 6).
Scheme 6: RCM of (1,8)-enynes (4r,s)
Next, we turned our attention towards IPKR.[21]
The Pauson-Khand reaction generates three new
carbon bonds as it forms a cyclopentenone in one
step. The intramolecular route is reliable for the
synthesis of [3.3.0] and [3.4.0] bicyclic systems.
Recently, Schreiber et al. used these kind of small
molecules in drug-discovery.[26] We carried out an
optimization of the reaction conditions, the results of
which are summarized in Table 2. Initially,
complexation of Co2(CO)8 to the alkyne was best
achieved in CH2Cl2 or THF,[27] occurring
quantitatively within 2 h at rt (entry 1-7, Table 2, The
alkyne-Co2(CO)8 complex formation was monitored
by TLC), while the cycloaddition could be effected
either in refluxing toluene within 2 h or in DCM at
room temperature for 12 h using N-methylmorpholine
N-oxide (NMO)[28] or Trimethylamine N-oxide
(TMANO)[28] as the promotor. The use of DCM
instead of toluene gave rise to a noticeable increase in
chemical yield and accompanied by the formation of a
isolated isomer 6a (dr up to >98 %) (entry 5-7, Table
2). The structure of 6a was established by NMR &
NOE analysis.
aReaction conditions: 4 (0.539 mmol, 1.0 eq), G-1 (5
mol %), DCM (25 mL), reflux, 12 h. Yields refer to pure
products after column chromatography.
b
To investigate the applicability of this method to
other ring systems, 4o-q were subjected to RCEYM
reaction. Unfortunately, RCEYM of 4o-q with both
Grubbs I & II in various solvents such as DCM,
toluene, THF at different temperatures (rt-reflux) and
Scheme-5: RCM of (1,6)-enynes 4o-q
4
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10.1002/adsc.201700511
Advanced Synthesis & Catalysis
Table 2: Optimization of intramolecular PKRa
a different R/R1 groups were subjected to a tertiary
amine
N-oxide
promoted
cyclization,
Intramolecular
which provided
Pauson−Khand
structurally diverse spirooxindole-5,6-bicyclic fused
cyclopentenones (6) at high yields as shown in
Scheme 7. (1,7)-Enyne with various N-substituted
i
substituents such as Et, Me, Pr, Bn delivered 6a-d as
entry
conditions for step-1/step-2
enone (%)b
56(6a)
drc
95:5
95:5
only isolated isomers (ratio >98:<2) in good yields. In
detail, the electronic nature of the oxindole enynes
had no obvious effect on the yields and isomeric ratio.
For example, in the case of
1
4a, Co2(CO)8 (1.1 eq), DCM, rt, 2 h/
NMO (6.0 eq), PhCH3, reflux, 2 h
2
3
4
5
6
7
4b, Co2(CO)8 (1.1 eq), DCM, rt, 2 h/
NMO (6.0 eq), PhCH3, reflux, 2 h
Scheme 7: Scope of intramolecular PKR of (1,7)-enynesa
45(6a)
4a, Co2(CO)8 (1.1 eq), THF, rt, 2 h/
NMO (6 eq), THF, rt, 20 h
72(6a)
65(6a)
86(6a)
74(6a)
85(6b)
5:1
5:1
4a, Co2(CO)8 (1.1 eq), THF, rt, 2 h/
Me3NO (6.0 eq), THF, rt, 24 h
4a, Co2(CO)8 (1.1 eq), DCM, rt, 2 h/
NMO (6.0 eq), DCM, rt, 12 h
>98:2
>98:2
>98:2
4a, Co2(CO)8 (1.1 eq), DCM, rt, 2 h/
Me3NO (6.0 eq), DCM, rt, 16 h
4b, Co2(CO)8 (1.1 eq), DCM, rt, 2 h/
NMO (6.0 eq), DCM, rt, 12 h
aReaction conditions: step-1) 4 (0.623 mmol, 1.0 eq),
Co2(CO)8 (0.685 mmol, 1.1 eq), DCM (15 mL), rt, 2 h;
step-2) NMO (3.73 mmol, 6.0 eq), rt, 12 h. bYields refer to
c
pure products after column chromatography. dr measured
by NMR Spectroscopy.
The compound 6a was determined by using detailed
NMR experiments, such as 2D-NOESY, TOCSY and
J-coupling analysis. The appearance of characteristic
nOe cross-peaks between H1’−H2, H1-H4 and H5-H6
indicates that the isolated compound is having fused
cyclopentenone ring as represented in Figure 4.
Figure 4: Chemical and energy-minimized structures of
compound 6a
aReaction conditions: step-1) 4 (0.623 mmol, 1.0 eq),
Co2(CO)8 (0.685 mmol, 1.1 eq), DCM (15 mL), rt, 2 h ;
step-2) NMO (3.73 mmol, 6.0 eq), rt, 12 h. bYields refer to
pure products after column chromatography. cdr measured
by NMR Spectroscopy.
As the optimized reaction conditions were
established, it was applied to a series of oxindole
(1,7)-enynes (4a-n). These (1,7)-enynes 4a-n bearing
5
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10.1002/adsc.201700511
Advanced Synthesis & Catalysis
R1 group at C5-position of oxindole moiety, both the
electron-donating groups such as methyl (Me),
methoxy (OMe) and electron-withdawing groups such
as fluorine (F), chlorine (Cl), bromine (Br),
trifluoromethoxy (OCF3) proved to suitable
substituents, which delivered the corresponding
compounds 6e-k. However, the other substrates
having R1 group at C4, C6, C7-position of the
oxindole moiety, 4l-n successfully participated in this
reaction and afforded 6l-n in good yields.
4r,s were transformed into the corresponding cobalt
complexes, which was submitted to different IPKR
reaction conditions as shown in Scheme 9.
Unfortunately decomposition occured during
cyclization in the presence of NMO and TMANO as
the promotor at room temperature using DCM as
solvent. Also, it was not successful in toluene and
DCE under reflux conditions.
Based on the experimental results, the generality
of these two methods (RCEYM and IPKR) were
studied on a number of oxindole enynes for the
synthesis of various oxacyclic spirooxindoles. As
outlined in Schemes 4 and 7, both the methods can be
used on (1,7)-enynes to obtain corresponding
Later, we were encouraged to prepare
spirooxindole 5,5-bicyclic fused cyclopentenones.
a
spirooxindole-vinyl
dihydropyrans
5a-n
and
spirooxindole-5,6-bicyclic fused cyclopentenone
derivatives 6a-n with good to excellent yields. At the
same time, in the case of (1,6)-enynes successfully
achieved 5,5-bicyclic fused cyclopentenones 6o-q
with good yields by using IPKR condition (Scheme 8).
But, failed to cyclize with Grubbs catalysts I and II to
produce 5o-q (Scheme 5). Here, oxindole (1,6)-
enynes may have steric hindrance and the starting
material was recovered. However, the (1,8)-enynes
easily cyclized with Grubbs catalyst to access
spirooxindole-vinyl tetrahydrooxepines 5r,s (Scheme
6). But, in the case of IPKR opposite results were
shown (Scheme 9). Finally, although the difficulty to
achieve ring sizes higher than five or six by using a
Pauson-Khand reaction is familiar.[29] Here, we tried
the reaction with various conditions as shown in
Scheme 9 were not successful. Now, we are
considering the scope of this IPKR for the formation
of higher ring size. We will report on this and other
aspects of this in due course.
Scheme 8: IPKR of (1,6)-enynes
bYields refer to pure products after column
chromatography. cdr measured by NMR Spectroscopy.
For which, (1,6)-enynes 4o-q were treated with
Co2(CO)8 (1.1 eq) in DCM at rt for 2 h, followed by
cyclization promoted with NMO (6.0 eq) at rt for 12 h
(IPKR conditions) to obtain the spirooxindole 5,5-
bicyclic cyclopentenones 6o-q as a isomeric ratio
>95:5 in 74-80% yields, which were shown in
Scheme 8.
Notably, to the best of our knowledge, this is the first
approach to synthesize diverse spirooxindole-vinyl
dihydropyran/tetrahydrooxepines and spirooxindole-
5,6-bicyclic/5,5-bicyclic cyclopentenone derivatives
from oxindole enynes proving the practical
application of the methodology.
However, (1,8)-enynes of isatin (4r,s) were failed
to give the respective PKR products 6r,s. Compounds
Conclusion
Scheme 9: IPKR of (1,8)-enynes
In summary, we have developed an efficient
strategy for Diversity-Oriented Synthesis (DOS) of
fused spiro-oxindole scaffolds from oxindole enynes
via ring-closing enyne metathesis (RCEYM) and
intramolecular Pauson−Khand (2 + 2 + 1) cyclization
reaction (IPKR). Here, we disclose the synthesis of
novel
dihydropyran/tetrahydrooxepines and spirooxindole-
5,6-bicyclic/5,5-bicyclic fused cyclopentenone
diverse
spirooxindole-vinyl
derivatives from (1,6)/(1,7)/(1,8)-enynes with good to
excellent yields. It provides the spirocycles that are of
6
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10.1002/adsc.201700511
Advanced Synthesis & Catalysis
119.9, 122.7, 125.0, 126.1, 130.1, 130.2, 142.9, 174.4;
HRMS calcd for C16H17NO2Na 278.1152 [M + Na]+, found
278.1150.
increasing interest to the pharmaceutical industry.
These kind of low molecular weight small libraries
used in drug-discovery, including those relying on
fragment-based drug discovery (FBDD), high-
throughput screening (HTS) and realtime biological
annotation.[26] We believe that the developed reaction
approach will find the applications on relevant
substrates to the synthesis of bioactive compounds.
General procedure for the RCEYM process:
Preparation of Spirocyclic Oxindoles 5a-n (Scheme 4).
A solution of the corresponding enyne 4 (0.54 mmol, 1.0
eq) in dry DCM (25.0 mL) was degassed with Argon for 15
min. Then 1st generation Grubbs’ catalyst (5 mol%) was
added under inert atmosphere and again degassed with
Argon for 5 min. Then the reaction mixture was heated at
40 ºC for 10-12 h. Upon completion, the reaction was
allowed to reach room temperature, solvents were removed
under reduced pressure and the residue purified by flash
chromatography using mixtures of n-hexanes:ethyl acetate
(95:5) as eluent.
EXPERIMENTAL SECTION
General Information. All the reactions were carried out in
anhydrous solvents under inert atmosphere. 1H NMR
spectra were measured on 300 MHz, 400 MHz and 500
MHz spectrometers. Chemical shifts were recorded as
follows: chemical shift in ppm from internal
tetramethylsilane on the δ scale, multiplicity (s = singlet; d
= doublet; t = triplet; q = quartet; m = multiplet; dd =
doublet of doublets; ddd = doublet of doublet of doublets;
br = broad), coupling constant (Hz), integration, and
assignment. 13C NMR spectra were measured on 100 MHz
and 125 MHz spectrometers. Chemical shifts were
recorded in ppm from the solvent resonance employed as
the internal standard (deuterochloroform at 77.0 ppm). 2D
(TOCSY and NOESY) NMR spectra were recorded on
Bruker Avance 400 MHz spectrometer in CDCl3 at 298 K.
High-resolution mass spectra (HRMS) were measured
(ESI) on orbitrap mass spectrometers. Characteristic peaks
in the infrared (IR) spectra were recorded in wave numbers,
cm−1. Melting points were determined on an Electro
thermal melting point apparatus and are uncorrected. Thin-
layer chromatography (TLC) was performed using 0.25
mm silica gel plates (60F-254). The products were purified
by short column chromatography on silica gel 60-120 or
100−200 mesh. Commercially available Co2(CO)8 and
NMO were used without further purification.
1-ethyl-5'-vinyl-3',6'-dihydrospiro[indoline-3,2'-pyran]-2-
one (5a): Rf = 0.7 (petroleum ether/ethyl acetate, 9:1); off
white solid (124 mg, 90%), mp 101−103 °C; IR (KBr)
3062, 2930, 1717, 1610, 1489, 1452, 1372, 1281, 1170,
1
1107, 1026, 751, 692 cm−1; H NMR (400 MHz, CDCl3) δ
1.28 (t, J = 7.2 Hz, 3H), 2.27 (dd, J1 = 17.9 Hz, J2 = 5.3 Hz,
1H), 2.86 (dd, J1 = 18.0 Hz, J2 = 2.7 Hz, 1H), 3.76 (qd, J1 =
7.2 Hz, J2 = 1.6 Hz, 2H), 4.54 (dd, J1 = 16.0 Hz, J2 = 2.0 Hz,
1H), 4.73 (d, J = 16.1 Hz, 1H), 5.00-5.10 (m, 2H), 5.97-
6.04 (m, 1H), 6.38 (dd, J1 = 17.8 Hz, J2 = 11.1 Hz, 1H),
6.88 (d, J = 7.8 Hz, 1H), 7.02 (td, J1 = 7.6 Hz, J2 = 0.9 Hz,
1H), 7.28 (dd, J1 = 7.5 Hz, J2 = 0.9 Hz, 1H), 7.33 (td, J1 =
7.7 Hz, J2 = 1.2 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ
12.5, 30.5, 34.6, 62.1, 74.2, 108.6, 111.7, 122.5, 122.6,
124.4, 129.2, 129.7, 134.3, 135.3, 142.6, 174.3; HRMS
calcd for C16H17NO2Na 278.1157 [M + Na]+, found
278.1168.
General Procedure for intramolecular Pauson−Khand
Reaction:
Preparation
of
Spirocyclic
fused
Cyclopentenones 6a-q (Scheme 7 & 8).
General procedure for the synthesis of (1,6)/(1,7)/(1,8)-
enynes (4a-s, Scheme 3).
To a solution of Co2(CO)8 (0.685 mmol, 1.1 eq) in
anhydrous CH2Cl2 (15 mL) at rt was added a solution of
the corresponding enyne 4 (0.623 mmol, 1.0 eq) in
anhydrous CH2Cl2 (5.0 mL). The mixture was stirred at rt
for 2 h, and then N-methylmorpholine N-oxide (NMO)
(3.73 mmol, 6.0 eq) was added onto the freshly prepared
cobalt complex solution. The resulting mixture was stirred
at rt for 12 h. The reaction was monitored by TLC. Upon
transformation of the complex, the mixture was filtered
through a Celite pad, and the solvent was evaporated. The
crude residue was purified by flash column
chromatography using a mixture of AcOEt/ hexane (20:80)
as the eluent.
3a (1.58 mmol, 1.0 eq) was dissolved in dry THF (15 mL)
at room temperature. NaH (60 %) (3.17 mmol, 2.0 eq) was
o
added to the reaction at 0 C and stirred for 20 min. Then
propargyl bromide (80% w/w in toluene, 3.17 mmol, 2.0
eq) was added dropwise and allowed to rt and stirred for
overnight. The reaction quenched with ice water and
extracted with EtOAC. The crude residue purified by
column chromatography (silica gel, 60-120) gave the
compound 4a in 99% yield.
3-allyl-1-ethyl-3-(prop-2-yn-1-yloxy)indolin-2-one (4a):
Rf = 0.7 (petroleum ether/ethyl acetate, 9:1); yellow color
liquid (399 mg, 99%); IR (neat) 3260, 3028, 2920, 2852,
2122, 1957, 1717, 1610, 1465, 1375, 1182, 1089, 992, 925,
749 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.24 (t, J = 7.2 Hz,
3H), 2.34 (t, J = 2.4 Hz, 1H), 2.65-2.72 (m, 1H), 2.76-2.83
(m, 1H), 3.64-3.73 (m, 1H), 3.76-3.85 (m, 2H), 3.92 (dd, J1
= 14.6 Hz, J2 = 2.4 Hz, 1H), 4.94-5.04 (m, 2H), 5.38-5.50
(m, 1H), 6.85 (d, J = 7.8 Hz, 1H), 7.10 (td, J1 = 7.6 Hz, J2 =
0.9 Hz, 1H), 7.32-7.38 (m, 2H); 13C NMR (125 MHz,
CDCl3) δ 12.6, 34.6, 41.9, 53.5, 74.5, 79.2, 81.8, 108.5,
1'-ethyl-4a,5-dihydro-1H-spiro[cyclopenta[c]pyran-3,3'-
indoline]-2',6(4H)-dione (6a): Rf
= 0.3 (petroleum
ether/ethyl acetate, 7:3); off white solid (152 mg, 86%), mp
142−144 °C; IR (KBr) 3065, 2932, 2821, 1709, 1622, 1491,
1
1469, 1334, 1190, 1065, 1010, 741, 691 cm−1; H NMR
(400 MHz, CDCl3) δ 1.29 (t, J = 7.2 Hz, 3H), 1.91-2.08 (m,
2H), 2.23 (dd, J1 = 13.7 Hz, J2 = 5.9 Hz, 1H), 2.68 (dd, J1 =
18.7 Hz, J2 = 6.6 Hz, 1H), 3.74 (q, J = 7.2 Hz, 2H), 3.91-
7
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10.1002/adsc.201700511
Advanced Synthesis & Catalysis
4.02 (m, 1H), 4.64 (d, J = 13.6 Hz, 1H), 5.40 (d, J = 13.6
Hz, 1H), 6.08 (s, 1H), 6.85 (d, J = 7.8 Hz, 1H), 7.09 (td, J1
= 7.6 Hz, J2 = 0.8 Hz, 1H), 7.24-7.38 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 12.5, 33.6, 34.3, 39.6, 41.7, 62.7, 75.3,
108.6, 123.1, 123.7, 127.7, 129.1, 130.1, 141.9, 174.7,
175.2, 207.5; HRMS calcd for C18H18NO3 284.1287 [M +
H]+, found 284.1289.
Lasterra, U.S. Pat. Appl. Publ. 2006, 56 pp. CODEN:
USXXCO US 2006019940 A1 20060126, CAN
144:150402; i) S. Seto, A. Tanioka, M. Ikeda, S. Izawa,
Bioorg. Med. Chem. 2005, 13, 5717–5732; j) S. Seto, A.
Tanioka, M. Ikeda, S. Izawa, Bioorg. Med. Chem. Lett.
2005, 15, 1479–1484; k) S. Seto, A. Tanioka, M. Ikeda,
S. Izawa, Bioorg. Med. Chem. Lett. 2005, 15, 1485–
1488; l) C. J. Ohnmacht, J. S. Albert, P. R. Bernstein,
W. L. Rumsey, B. B. Masek, B. T. Dembofsky, G. M.
Koether, D. W. Andisik, D. Aharony, Bioorg. Med.
Chem. 2004, 12, 2653–2669; m) P. Bernstein, PCT Int.
Appl. 2002, 33 pp. CODEN: PIXXD2 WO 2002026724
A1 20020404, CAN 136:294860; n) M. R. Stillings, S.
Freeman, P. L. Myers, M. J. Readhead, A. P. Welbourn,
M. J. Rance, D. C. Atkinson, J. Med. Chem. 1985, 28,
225–33; o) S. Tanaka, K. Hashimoto, Ger. Offen. 1971,
21 ppCODEN: GWXXBX DE 2044508 19710519,
CAN 75:36173; p) S. R. Kandimalla, G. Sabitha, RSC
Adv. 2016, 6, 67086–67095.
Supporting Information Available
Acknowledgements
KSR thank UGC, India for the award of fellowship. Both the
authors thank CSIR, New Delhi, India for financial support as
part of XII Five Year Plan Programme under title ORIGIN (CSC-
0108).
References
[4] a) F. L. Sonnenschein, Ber. 1876, 9, 1182-1186; b) C.
W. Moore, J. Chem. Soc. 1910, 97, 2223-2233; c) L.
Meyer, N. Boujedaini, C. Patte-Mensaha, A. G.
Mensah-Nyagana, Behavioural Brain Research 2013,
253, 90–94; d) X. Chen, S. Duan, C. Tao, H. Zhai, F. G.
Qiu, Nat. Commun. 2015, 6, 7204. (DOI:
10.1038/ncomms8204).
[1] For early reports on DOS, see: a) M. D. Burke, S. L.
Schreiber, Angew. Chem. Int. Ed. 2004, 43, 46−58; b) S.
L. Schreiber, Science 2000, 287, 1964−1969; c) H. S. G.
Beckmann, F. Nie, C. E. Hagerman, H. Johansson, Y.
S. Tan, D. Wilcke, D. R. Spring, Nature Chemistry
2013, 5, 861-867; d) E. Rodríguez, M. N. Grayson, A.
Asensio, P. Barrio, K. N. Houk, S. Fustero, ACS Catal.
2016, 6, 2506−2514; e) W. Tan, X.-T. Zhu, S. Zhang,
G.-J. Xing, R.-Y. Zhu, F. Shi, RSC Adv. 2013, 3,
10875-10886; f) S. Dandapani, J. T. Lowe, E. Comer,
L. A. Marcaurelle, J. Org. Chem. 2011, 76, 8042–8048;
g) E. Ascic, S. T. L. Quement, M. Ishoey, M. Daugaard,
T. E. Nielsen, ACS Comb. Sci. 2012, 14, 253−257.
[5] a) See for overview: J. J. Badillo, N. V. Hanhan, A. K.
Franz, Curr. Opin. Drug Discovery Dev. 2010, 13, 758-
76; b) G. S. Singh, Z. Y. Desta, Chem. Rev. 2012, 112,
6104−6155; C) T. L. Pavlovska, R. G. Redkin, V. V.
Lipson, D. V. Atamanuk, Mol Divers. DOI
10.1007/s11030-015-9629-8 (2015).
[6] S. Chowdhury, M. Chafeev, S. Liu, J. Sun, V. Raina, R.
Chui, W. Young, R. Kwan, J. Fu, J. A. Cadieux, Bioorg.
Med. Chem. Lett. 2011, 21 (12), 3676−3681.
[2] For recent reviews on DOS, see: a) C. Serba, N.
Winssinger, Eur. J. Org. Chem. 2013, 4195−4214; b) P.
MacLellan, A. Nelson, Chem. Commun. 2013, 49,
2383−2393; c) C. J. O’Connor, H. S. G. Beckmann, D.
R. Spring, Chem. Soc. Rev. 2012, 41, 4444− 4456; d) W.
R. J. D. Galloway, A. Isidro-Llobet, D. R. Spring, Nat.
Commun. 1:80 doi: 10.1038 / ncomms1081 (2010); e)
W. R. J. D. Galloway, D. R. Spring, Diversity Oriented
Synthesis 2013, 21-28; f) A. Rolfe, and L. A.
Marcaurelle (2015) Metathesis Strategies in Diversity-
Oriented Synthesis, in Handbook of Metathesis, Set
(Eds.: R. H. Grubbs, A. G. Wenzel, D. J. O'Leary and E.
Khosravi), Wiley-VCH Verlag GmbH & Co. KGaA,
[7] J. Schonhaber, T. J. J. Muller, Org. Biomol. Chem.
2011, 9, 6196-6199.
[8] X. Xie, C. Peng, G. He, H.-J. Leng, B. Wang, W.
Huang, B. Han, Chem. Commun. 2012, 48, 10487–
10489.
[9] A. Fensome, W. R. Adams, A. L. Adams, T. J. Berrodin,
J. Cohen, C. Huselton, A. Illenberger, J. C. Karen, M. A.
Hudak, A. G. Marella, E. G. Melenski, C. C. McComas,
C. A. Mugford, O. D. Slayeden, M. Yudt, J. Zhang, P.
Zhang, Y. Zhu, R. C. Winneker, J. E. Wrobel, J. Med.
Chem. 2008, 51, 1861-1873.
Weinheim,
Germany.
doi: 10.1002/9783527674107.ch25; g) Y. Liu, H. Wang,
J. Wan, Asian J. Org. Chem. 2013, 2, 374–386.
[10] G. Kumari, Nutan, M. Modi, S. K. Gupta, R. K. Singh,
Eur. J. Med. Chem. 2011, 46, 1181-1188.
[3] a) H.-J. Knolker, K. R. Reddy, Chem. Rev. 2002, 102,
4303–4427; b) N. L. Snyder, H. M. Haines, M. W.
Peczuh, Tetrahedron 2006, 62, 9301–9320; c) J. B.
Bremner, Progress in Heterocyclic Chemistry 2004, 16,
431–450; d) J. B. Bremner, Progress in Heterocyclic
Chemistry 2003, 15, 385–430; e) J. O. Hoberg,
Tetrahedron 1998, 54, 12631–12670; f) S. Kato, I.
Fujiwara, N. Yoshida, Medicinal Research Review 1999,
19, 25–73; g) A. D. Baxter, PCT Int. Appl. 2006, 18pp.
CODEN: PIXXD2 WO 2006095187 A1 20060914,
CAN 145:336084; h) A. D. Baxter, A. Walmsley, E.
[11] a) M. M.-C. Lo, C. S. Newmann, S. Nagayams, E. O.
Perlstein, S. L. Schreiber, J. Am. Chem. Soc. 2005, 127,
10130-10131; b) K. Ding, Y. Lu, Z. Nikolovska-
Coleska, S. Qui, Y. Ding, W. Gao, J. Stuckey, K.
Krajewski, P. P. Roller, Y. Tomita, D. A. Parrish, J. R.
Deschamps, S. Wang, J. Am. Chem. Soc. 2004, 126,
16077-16086; c) B. Yu, Y.-C. Zheng, X.-J. Shi, P.-P.
Qi, H.-M. Liu, Anticancer Agents Med Chem. 2016
16(10) 1315-24.
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700511
Advanced Synthesis & Catalysis
[12] V. V. Vintonyak, K. Warburg, H. Kruse, S. Grimme, [19] a) M. Calancea, S. Carret, J.-P. Depres, Eur. J. Org.
K. Hubel, D. Rauth, H. Waldmann, Angew. Chem., Int.
Ed. 2010, 49, 5902-5905.
Chem. 2009, 3134− 3137; b) G. Valot, J. Garcia, V.
Duplan, C. Serba, S. Barluenga, N. Winssinger, Angew.
Chem. Int. Ed. 2012, 51, 5391−5394; c) X. Verdaguer,
Science 2016, 353 (6302), 866-867; d) K. V. Chuang,
C. Xu, S. E. Reisman, Science 2016, 353 (6302), 912-
915; e) K. Fujioka, H. Yokoe, A. Inoue, K. Soga, M.
Tsubuki, K. Shishido, J. Org. Chem. 2014, 79 (16), pp
7512–7519; f) M. K. A. El-Gaber, S. Yasuda, E. Iida,
C. Mukai, Org. Lett. 2017, 19, 320−323; g) S.-J. Min,
S. J. Danishefsky, Angew. Chem. Int. Ed. 2007, 46,
2199 –2202.
[13] B. K. S. Yeung, B. Zou, M. Rottmann, S. B.
Lakshminarayana, S. H. Ang, S. Y. Leong, J. Tan, J.
Wong, S. Keller-Maerki, C. Fischli, A. Goh, E. K.
Schmitt, P. Krastel, E. Francotte, K. Kuhen, D. Plouffe,
K. Henson, T. Wagner, E. A. Winzeler, F. Petersen, R.
Brun, V. Dartois, T. T. Diagana, T. H. Keller, J. Med.
Chem. 2010, 53, 5155-5164.
[14] a) M. Rottmann, C. McNamara, B. K. S. Yeung, M. C.
S. Lee, B. Zhou, B. Russell, P. Seitz, D. M. Plouffe, N.
V. Dharia, J. Tan, S. B. Cohen, K. R. Spencer, G. E.
Gonzalez-Paez, S. B. Lakshminarayana, A. Goh, R.
Suwanarusk, T. Jegla, E. K. Schmitt, H.-P. Beck, R.
Brun, F. Nosten, L. Renia, V. Dartois, T. H. Keller, D.
A. Fidock, E. A. Winzeler, T. T. Diagana, Science 2010,
329, 1175-80; b) S. H. Ang, P. Crastel, S. Y. Leong, L.
J. Tan, W. L. J. Wong, B. K. S. Yeung, B. Zou,
(Novartis AG) Us Patent 2009/0275560 A1, 2009. J.-J.
Liu, Z. Zhang, (Hoffmann La Roche AG)
spiroindolinone derivatives: PCT Int. Appl. WO
2008/055812, 2008.
[20] a) T. J. Katz, T. M. Sivavec, J. Am. Chem.
Soc. 1985, 107 (3), pp 737–73; b) S. T. Diver, A. J.
Giessert, Chem. Rev. 2004, 104, 1317-1382; c) M.
Mori, Adv. Synth. Catal. 2007, 349, 121 – 135; d) H.
Villar, M. Fringsa, C. Bolm, Chem. Soc. Rev. 2007, 36,
55–66; e) Q. Yang, H. Alper, W.-J. Xiao, Org. Lett. Vol.
9, No. 5, 2007, 769-771; f) D. B. Ramachary, V.V.
Narayana, M. S. Prasad, K. Ramakumar, Org. Biomol.
Chem. 2009, 7, 3372–3378; g) L.-N. Zhang, W.-Z.
Zhang, X. Ren, X.-Y. Tan, X.-B. Lu, Tetrahedron
Letters 2012, 53, 3389–3392; h) A. K. Mailyan, I. M.
Krylov, C. Bruneau, P. H. Dixneuf, S. N. Osipov, Eur.
J. Org. Chem. 2013, 5353–5363; i) K. Jung, E. H.
Kang, J.-H. Sohn, T.-L. Choi, J. Am. Chem. Soc. 2016,
138, 11227−11233; j) A. Letort, D.-L. Long, J. Prunet,
J. Org. Chem. 2016, 81, 12318−12331.
[15] K. Ding, Y. Lu, Z. Nikolovska-Coleska, G. Wang, S.
Qiu, S. Shangary, W. Gao, D. Qin, J. Stukey, K.
Krajewski, P. P. Roller, S. Wang, J. Med. Chem. 2006,
49, 3432-3435.
[21] a) I. U. Khand, G. R. Knox, P. L. Pauson, W. E. Watts,
J. Chem. Soc. Chem. Commun. 1971, 36; b) N. E.
Schore, M. C. Croudace, J. Org. Chem. 1981, 46, 5436;
c) C. Exon, P. Magnus, J. Am. Chem. Soc. 1983, 105,
2477; d) P. Magnus, L. M. Principle, M. J. Slater, J.
Org. Chem. 1987, 52, 1483; e) O. Geis, H.-G. Schmalz,
Angew. Chem. Int. Ed. 1998, 37(7), 911-914; f) J. Adrio,
J. C. Carretero, J. Am. Chem. Soc. 1999, 121, 7411-
7412; g) Y. K. Chung, Coordination Chemistry Reviews
1999, 188, 297–341; h) J. Blanco-Urgoiti, L. Añorbe, L.
Pérez-Serrano, G. Domínguez, J. Pérez-Castells, Chem.
Soc. Rev. 2004, 33, 32-42; i) M. Turlington, Y. Du, S.
G. Ostrum, V. Santosh, K. Wren, T. Lin, M. Sabat, L.
Pu, J. Am. Chem. Soc. 2011, 133, 11780–11794; j) J. L.
G. Ruano, E. Torrente, A. Parra, J. Alemꢀn, A. M.
Martín-Castro, J. Org. Chem. 2012, 77, 6583−6599; k)
P. Wu, M. A. Petersen, A. E. Cohrt, R. Petersen, R.
Morgentin, H. Lemoine, C. Roche, A. Willaume, M. H.
Clausen. T. E. Nielsen, Org. Biomol. Chem. 2016, 14,
6947–6950.
[16] a) L. Hong, R. Wang, Adv. Synth. Catal. 2013, 355,
1023 – 1052; b) D. Cheng, Y. Ishihara, B. Tan, C. F.
Barbas, ACS Catal. 2014, 4, 743−762; c) D.-Y. Zhang,
L. Xu, H. Wu, L.-Z. Gong, Chem. Eur. J. 2015, 21,
10314 – 10317; d) J.-L. Wu, B.-X. Du, Y.-C. Zhang,
Y.-Y. He, J.-Y. Wang, P. Wu, F. Shi, Adv. Synth. Catal.
2016, 358, 2777 – 2790; e) Q.-N. Zhu, Y.-C. Zhang,
M.-M. Xu, X.-X. Sun, X. Yang, F. Shi, J. Org. Chem.
2016, 81, 7898−7907; f) Y.-M. Wang, H.-H. Zhang, C.
Li, T. Fan, F. Shi, Chem. Commun. 2016, 52, 1804—
1807.
[17] a) T. Hirukawa, H. Iwasaki, T. Kato, M. Takigawa, M.
Tomita, Yamahara, J. Bull. Chem. Soc. Jpn. 1994, 67,
1394−1398; b) M. Yoshikawa, N. Tomohiro, T.
Murakami, A. Ikebata, H. Matsuda, K. Michinori,
Chem. Pharm. Bull. 1999, 47, 524−528; c) S. P.
Simeonov, J. P. M. Nunes, K. Guerra, V. B. Kurteva, C.
A. M. Afonso, Chem. Rev. 2016, 116, 5744-5893.
[18] a) L. Huang, W.-J. Lan, R. Deng, G.-K. Feng, Q.-Y.
Xu, Z.-Y. Hu, X.-F. Zhu, H.-J. Li, Mar.
Drugs 2016, 14(9), 157; b) A. R. Viver, D. A. Nieto, R.
Gavino, A. PerezC, Phytochemistry 1995, 40, 167−
170; c) V. Hellwig, J. Dasenbrock, S. Schumann, W.
Steglich, K. Leonhardt, T. Anke, Eur. J. Org. Chem.
1998, 73−79; d) J. C. Wang, M. J. Krische, Angew.
Chem., Int. Ed. 2003, 42, 5855−5857; e) V.
Rukachaisirikul, C. Tansakul, S. Saithong, C.
Pakawatchai, M. Isaka, R. Suvannakad, J. Nat. Prod.
2005, 68, 1674−1676; f) H.-J. Li, Y.-L. Xie, Z.-L. Xie,
[22] a) V. Nair, S. Ros, C. N. Jayan, S. Viji, Synthesis 2003,
No. 16, pp 2542–2546; b) B. Alcaide, P. Almendros, R.
R. guez-Acebes, J. Org. Chem. 2006, 71, 2346-2351.
[23] S. Lu, S. B. Poh, W.-Y. Siau, Y. Zhao, Angew. Chem.
Int. Ed. 2013, 52, 1731 –1734.
[24] a) Y.-S. Hon, Y.-W. Liua, C.-H. Hsieh, Tetrahedron
60 (2004) 4837–4860; b) D. B. England, G. Merey, A.
Padwa, Org. Lett. 2007, 9 (19), pp 3805–3807.
Y. Chen, C.-K. Lam, W.-J. Lan, Mar. Drugs 2012, 10, [25] a) Y. Na, J.-H. Song, S.-Y. Han, Bull. Korean Chem.
627−638; g) H.-J. Li, W.-J. Lan, C.-K. Lam, F. Yang,
X.-F. Zhu, Chem. Biodiversity 2011, 8, 317−324.
Soc. 2011, Vol. 32, No. 8, 3164-3166; b) F. Nuꢁez-
9
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10.1002/adsc.201700511
Advanced Synthesis & Catalysis
Zarur, X. Solans-Monfort, L. Rodríguez-Santiago, M.
Sodupe, ACS Catal. 2013, 3, 206−218.
[26] a) S. D. Nelson, Jr., M. J. Wawer, S. L. Schreiber, Org.
Lett. 2016, 18, 6280–6283; b) DL. Ma, CH. Leung,
(2013) Future Frontiers in Diversity-Oriented Synthesis.
Organic Chem Curr Res 3: e128.
[27] a) R. S. Dickson, P. Fraser, Adv. Organomet. Chem.
1974, 12, 323; b) M. J. Went, Adv. Organomet. Chem.
1997, 41, 69– 125; c) S. Amiralaei, J. Gauld, J. R.
Green, Chem. Eur. J. 2011, 17, 4157 – 4165.
[28] a) S. Shambayati, W. E. Crewe, S. L. Schreiber,
Tetrahedron Lett. 1990, 31(37), 5289-5292; b) M. Iqbal,
N. Vyse, J. Dauvergne, P. Evans, Tetrahedron Lett.
2002, 43, 7859-7862; c) N. Jeong, Y. K. Chung, B. Y.
Lee, S. H. Lee, S. Yoo, Synlett 1991, 204-206; d) J. G.
Donkervoort, A. R. Gordon, C. Johnstone, W. J. Kerr,
U. Lange, Tetrahedron 1996, 52, 7391.
[29] a) N. E. Schore, In Comprehensive Organometallic
Chemistry II; E. W. Abel, F. G. A. Stone, G. Wilkinson,
Eds.; Pergamon: Oxford, U.K., 1995; Vol. 12, p 703; b)
M. E. Krafft, Z. Fu, L. V. R. Bonaga, Tetrahedron Lett.
2001, 42, 1427–1431; c) C. J. Lovely, H. Seshadri, B.
R. Wayland, A. W. Cordes, Org. Lett. 2001, 3, 2607-
2610.
10
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10.1002/adsc.201700511
Advanced Synthesis & Catalysis
UPDATES
Diversity-Oriented Synthesis of
oxacyclic spirooxindole derivatives
through
metathesis and intramolecular
Pauson−Khand (2 1)
ring-closing
enyne
+
2 +
cyclization of oxindole enynes
Adv. Synth. Catal. 2017, Volume,
Page – Page
Satheeshkumar Reddy Kandimallaa,b
and Gowravaram Sabitha*a,b
11
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