Direct alkenylation of indolin-2-ones by 6-aryl-4-methylthio-2H-pyran-2- one-3-carbonitriles: A novel approach

Article abstract of DOI:10.3762/bjoc.9.92

A direct one-pot base-induced alkenylation of indolin-2-ones has been developed by using 6-aryl-4-methylthio-2H-pyran-2-one-3- carbonitriles. Different bases such as MeONa, NaH and t-BuONa have been used to optimize the reaction conditions to obtain the desired product. NaH in THF was found to be the most suitable for the alkenylation of indolin-2-ones. Reaction in the presence of other bases led to the formation of 1-aryl-3-methoxy/methylthio-5H- dibenzo[d,f][1,3]diazepin-6(7H)-ones. Quantum chemical calculations have been performed to explain the nature of the weak noncovalent interactions operating in the supramolecular architectures of alkenylated indoline-2-ones and to explain the relative stability of one of the tautomers with respect to the others.

Full text of DOI:10.3762/bjoc.9.92

Direct alkenylation of indolin-2-ones by 6-aryl-4-
methylthio-2H-pyran-2-one-3-carbonitriles:
a novel approach
Sandeep Kumar1, Ramendra Pratap2, Abhinav Kumar1, Brijesh Kumar3,
Vishnu K. Tandon1 and Vishnu Ji Ram*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2013, 9, 809–817.
1Department of Chemistry, University of Lucknow, Lucknow-226007,
India, 2Department of Chemistry, North Campus, University of Delhi,
New Delhi-110007, India and 3Department of SAIF, Central Drug
Research Institute, Lucknow-226001, India
doi:10.3762/bjoc.9.92
Received: 27 November 2012
Accepted: 02 April 2013
Published: 25 April 2013
Email:
Vishnu Ji Ram* - vjiram@yahoo.com
Associate Editor: P. R. Hanson
* Corresponding author
© 2013 Kumar et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
alkenylation; dibenzo[d,f][1,3]diazepin-6(7H)-one; indolin-2-one;
ketene dithioacetal; 2H-pyran-2-one
Abstract
A direct one-pot base-induced alkenylation of indolin-2-ones has been developed by using 6-aryl-4-methylthio-2H-pyran-2-one-3-
carbonitriles. Different bases such as MeONa, NaH and t-BuONa have been used to optimize the reaction conditions to obtain the
desired product. NaH in THF was found to be the most suitable for the alkenylation of indolin-2-ones. Reaction in the presence of
other bases led to the formation of 1-aryl-3-methoxy/methylthio-5H-dibenzo[d,f][1,3]diazepin-6(7H)-ones. Quantum chemical
calculations have been performed to explain the nature of the weak noncovalent interactions operating in the supramolecular archi-
tectures of alkenylated indoline-2-ones and to explain the relative stability of one of the tautomers with respect to the others.
Introduction
6-Aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles have [9], and analgesic [9] activities. In addition, they also act as
emerged as versatile synthons for the construction of an array of inhibitors of lipoxygenase and butyrylcholinesterase enzymes
arenes and heteroarenes through base-induced ring transforma- [10].
tion by nitrogen, sulfur and carbon nucleophiles [1]. However,
suitably functionalized 2H-pyran-2-ones have not been investi- While alkylations and arylations of indole are well documented
gated for the alkenylation of indolin-2-ones. An extensive in the literature [11-19], acid-catalyzed alkenylation by α-oxo
literature survey on the pharmacological properties of ketene dithioacetals [20] have only recently been reported.
3-alkenylindolin-2-ones revealed that they possess potent anti- There are plenty of literature reports available on the construc-
tumor [2-5], antipyretic [6], antifungal [7,8], anti-inflammatory tion of 3-alkenylindolin-2-ones [21]. The widely used highly
809

Beilstein J. Org. Chem. 2013, 9, 809–817.
facile protocol for the alkenylation of indolin-2-ones is through ones (5, Figure 1) instead of the mechanistically possible prod-
aldol condensation [22] of isatin with compounds containing an ucts 2-phenyl-3,6-dioxa-4,5-dioxonaphtho[2,1-b]-7H-indole 6
active methylene group as well as by Wittig reaction [23,24]. or a carbazole derivative 7 or 3-alkenylindolin-2-ones 8
The growing importance of 3-alkenylindolin-2-ones has (Scheme 2 and Scheme 3).
resulted in the design of numerous new synthetic routes.
Recently, metal-catalyzed carbonylative annulation of alkynyl- Further, reactions of 3 and 4 in the presence of NaH as a base in
arylamines has been employed for the synthesis of this class of THF under reflux gave a product entirely different from 5, 6
compounds [25-31]. More recently, Kamijo, Yamamoto and and 7. The isolated product was finally characterized by single-
co-workers [32] have developed a palladium-catalyzed cycliza- crystal X-ray diffraction as (2Z,5E)-5-aryl-3-methylthio-5-(2-
tion of acetylenic aryl isocyanates in the presence of terminal oxoindolin-3-ylidene)pent-2-enenitrile 8. The reaction is initi-
alkynes. Halogenated arylpropionamides are commonly ated with Michael addition at C6 followed by ring opening with
employed for the preparation of 3-alkenylindolin-2-ones elimination of carbon dioxide to deliver product 8 without
involving tin hydride-AIBN initiated radical cyclization [33,34].
In 2005, Player and co-workers reported a tandem Heck/
Suzuki–Miyaura coupling process for the synthesis of (E)-3,3-
(diaryl)oxindoles [35-37]. Recently, alkenylation of indolin-2-
ones has been developed by palladium-catalyzed aromatic C–H
activation/Heck reaction starting from N-acryloylanilides [38].
The use of metal catalysis, especially of palladium, has played a
major role in the construction of 3-alkenylindolin-2-ones [38].
Despite significant progress in approaches for the construction
of 3-alkenylindolin-2-ones, use of complicated precursors,
expensive and sensitive metal catalysts, harsh reaction condi-
tions and incompatibility of reagents towards the functional
groups, restricted their frequent application. Thus, development
of new efficient routes by direct alkenylation, free from the
shortcomings of past procedures, is highly demanding and
remains a challenge to the state-of-art synthesis. The promising
pharmacological activities of 3-alkenylindolin-2-ones,
prompted us to develop an efficient and concise route for their
construction. Based on the topography and electronic features
of 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles 3, we
envisioned their use to alkenylate indolin-2-ones to deliver
Figure 1: ORTEP view with atom numbering scheme of compound 5
with displacement ellipsoids at the 30% probability level.
3-alkenylindolin-2-ones. An extensive literature survey revealed
that 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles 3 have
never been employed to alkenylate indolin-2-ones.
Results and Discussion
Synthesis
Herein, we report a short and efficient approach for the alkeny-
lation of indolin-2-ones by suitably functionalized 6-aryl-4-
methylthio-2H-pyran-2-one-3-carbonitriles 3. The precursor 3
was prepared from the reaction of methyl 2-cyano-3,3-
dimethylthioacrylate [39,40] (1) and aryl methyl ketone (2) in
the presence of powdered KOH in DMF at room temperature as
reported earlier [41,42] (Scheme 1).
The reaction between indolin-2-one (4) and 6-aryl-4-
methylthio-2H-pyran-2-one-3-carbonitriles 3 in the presence of
Scheme 1: Syntheses of 6-aryl-4-methylthio-2H-pyran-2-one-3-
carbonitriles 3.
t-BuOK/MeONa in tert-butanol/methanol under reflux resulted
in 1-aryl-3-methylthio-5H-dibenzo[d,f][1,3]diazepin-6(7H)-
810

Beilstein J. Org. Chem. 2013, 9, 809–817.
undergoing further cyclization to yield either 6 or 7, possibly As is evident from Scheme 3, there are three possible
due to the lower dielectric constant of THF (7.42) compared to tautomeric forms for 8, viz. 8x, 8y, 8z for the isolated com-
methanol (32.7) (Scheme 3).
pound. Single-crystal X-ray studies revealed that out of the
three tautomeric forms, the 8y is the most suitable structure
based on the bond lengths. Quantum chemical calculations have
been performed in order to gain information regarding the rela-
tive energy difference, which in turn reflects the relative
stability between the tautomeric forms 8x, 8y and 8z. The
energy calculations at the DFT level of theory for all of the
three tautomers indicate that 8y is 17.07 kJ·mol−1 more stable
than 8x, and it is more stable than 8z by 14.84 kJ·mol−1. A deep
structural study of 8y indicates the formation of intramolecular
C–H…O interaction which may be responsible for its extra
stability compared to 8x and 8z. However, for 8z the formation
of intramolecular C–H…O interactions is also possible, but the
existence of the relatively more stable trans-8z nullifies the
likelihood of this type of interaction. Hence, density functional
theory (DFT) calculations also indicate that the tautomer 8y is
relatively more stable than 8x and 8z (Figure 2).
Further, in order to generalize the reaction, attempts were made
for the alkenylation of indolin-2-one with 6-aryl-4-sec-amino-
2H-pyran-2-one-3-carbonitriles 9 [41,42], obtained by the
amination of 3 with sec-amine in boiling ethanol to yield a sec-
amino substituted alkenylated chain on position 3 of the
indolin-2-one (4). But to our utmost surprise the expected
alkenylated product 11 could not be isolated. However, in lieu
of this, the product isolated was characterized as 1-aryl-3-sec-
amino-5H-dibenzo[d,f][1,3]diazepin-6(7H)-one 10. The forma-
tion of 10 is possible only if the reaction is initiated with
Michael addition of indolin-2-one at C6 not at C4, due to the
presence of the secondary amino group, which reduces its elec-
trophilicity. Thus, preferential attack by carbanion generated
from 4 at C6 was inevitable for the formation of 10 (Scheme 4).
Scheme 2: A plausible mechanism for the formation of 1-aryl-3-
methylthio-5H-dibenzo[d,f][1,3]diazepin-6(7H)-ones.
Figure 2: ORTEP view with atom numbering scheme of compound
8yc with displacement ellipsoids at the 30% probability level.
811

Beilstein J. Org. Chem. 2013, 9, 809–817.
Scheme 3: Synthesis of 3-alkenylindolin-2-ones.
Scheme 4: Synthesis of 1-aryl-3-sec-amino-5H-dibenzo[d,f][1,3]diazepin-6(7H)-ones 10.
812

Beilstein J. Org. Chem. 2013, 9, 809–817.
X-ray crystallography
The molecular view (ORTEP) for the compounds 8yc with its
atom numbering scheme is presented in Figure 2. The com-
pound 8yc crystallizes in a monoclinic crystal system having
P21/c space group with four molecules in the unit cell. The
rings A and B are coplanar with respect to each other. However,
the dihedral angle between the rings A and C is 73.52°. The
bond lengths C2–C9, C9–C10, C9–C15, C10–C11 and
C11–C12 have dimensions 1.348(5), 1.513(5), 1.501(7),
1.510(5) and 1.331(5) Å, respectively. The angles
<C2–C9–C15, <C2–C11–C12 have magnitudes of 119.7(4)°,
123.2(3)° and 123.2(4)°, respectively.
The supramolecular aggregations in 8yc are stabilized by a pair
of weak C−H…π interactions (Figure 3) that led to the forma-
tion of a centrosymmetric dimer. The C–H…π interaction dis-
tance is 2.883 Å and the angle <C–H…π is 148.97°. Add-
itionally, the C5–H5…O1 intermolecular interactions lead to the
formation of a molecular chain having a H5…O1 interaction
length of 2.716 Å and a C5–H5…O1 interaction angle of
Figure 3: Centrosymmetric dimer of 8yc bound by a pair of weak
C−H…π intermolecular interactions (symm. op. 2 − x,1 − y, 2 − z).
127.60° (Figure 4). Along with the C–H…O interactions the the presence of weak noncovalent interactions between the two
molecule displays Ar–H…π interactions (Figure 5) having molecules of 8yc. The value of electron density (ρ), Laplacian
H22…C18 and H22…C19 interaction distances of 2.783 and of the electron density ( ρbcp), bond ellipticity (ε), electron
2.794 Å, respectively.
density (ρ), and total energy density (H) at the bond critical
point for all the three interactions are presented in Table 1. As
In order to analyze the various interactions that lead to the indicated in Table 1, the electron densities for all the three types
crystal structure, interaction energies and electrostatic poten- of interactions at the bond critical point (ρbcp) are less than
tials were calculated for dimer fragments (Figure 5). The +0.10 au, which indicates closed-shell hydrogen bonding inter-
analysis of the interaction energy in the crystal structures of 8yc actions. Additionally, the Laplacians of the electron density
by means of the dimer unit bound by C–H…π, C–H…O and
ρbcp in all the three cases are greater than zero, which indi-
Ar–H…π interactions at the DFT level of theory yields inter- cates the depletion of electron density in the region of contact
action energies of 22.33, 14.92 and 15.45 kJ·mol−1, respective- between the H…O and H…C atoms. The bond ellipticity (ε)
ly. To confirm further the presence of these weak interactions, measures the extent to which the density is preferentially accu-
bond critical points (bcp) were calculated for the different mulated in a given plane containing the bond path. The ε values
dimers by using the atoms in molecules theory [43]. The bond for all the three interactions indicate that these are not cylindri-
critical points observed between the interacting atoms confirm cally symmetrical in nature.
Figure 4: Supramolecular chain of 8yc bound by weak C−H…O intermolecular interactions (symm. op. x,1 + y, z).
813

Beilstein J. Org. Chem. 2013, 9, 809–817.
Figure 5: Supramolecular chain of 8yc bound by weak C−H…O and Ar-H…π intermolecular interactions (symm. op. 2 − x,−1/2 + y,3/2 − z).
Table 1: Selected topographical features for various interactions computed at the B3LYP/6-31G** level of theory.
Interaction type
ρbcp
ρbcp
ε
H (au)
C–H…π
C–O…H
Ar–H…π
+0.016942
+0.008118
+0.008257
+0.072948
+0.044151
+0.031372
+0.019047
+0.221799
+0.224819
+0.003173
+0.050545
+0.003505
Conclusion
respect to the other tautomers has been confirmed by single-
Owing to the numerous procedures known for the synthesis of crystal X-ray analysis and quantum chemical calculations.
3-alkenyl-2-oxindoles being based on expensive catalysts, non- X-ray diffraction displayed various C−H…π, C−H…O and
commercially available precursors, and multistep time- Ar-H…π intermolecular interactions. These interactions have
consuming synthetic protocols, the development of an efficient, been evaluated by quantum chemical calculations.
economical and short synthesis was inevitable and desirable. In
Experimental
this regard, we have now developed an efficient new protocol
for the direct alkenylation of 2-oxindole by 6-aryl-4-methylthio- General
2H-pyran-2-one-3-carbonitriles 3 to deliver 3-alkenyl-2-oxin- The reagents and the solvents used in this study were of analyt-
doles 8 in moderate yield. This procedure is quite efficient, ical grade and used without further purification. The melting
noncatalytic, economical and easy in workup. Moreover, it points were determined on an electrically heated Townson
opens a new avenue for the synthesis of 3-alkenyl-2-oxindoles. Mercer melting point apparatus and are uncorrected. Commer-
Furthermore, the synthesis of 8y and its relative stability with cial reagents were used without purification. 1H and 13C NMR
814

Beilstein J. Org. Chem. 2013, 9, 809–817.
spectra were measured on a Bruker WM-300 (300 MHz)/Jeol- mixture was neutralized with dilute HCl, and the precipitate
400 (400 MHz) spectrometer. CDCl3 and DMSO-d6 were used obtained was filtered, washed with water, and dried. The
as solvents. Chemical shifts are reported in parts per million (δ isolated product was purified by silica gel column chromatog-
value) from Me4Si (δ 0 ppm for 1H NMR) or based on the raphy using hexane/chloroform as eluent to afford products 10a
middle peak of the solvent (CDCl3) (δ 77.00 ppm for 13C and 10b (the analytical data and spectra are given in Supporting
NMR) as an internal standard. Signal patterns are indicated as s, Information File 1 and Supporting Information File 2).
singlet; bs, broad singlet; d, doublet; dd, double doublet; t,
triplet; m, multiplet; bh, broad hump. Coupling constants (J) are Structure determination
given in hertz. Infrared (IR) spectra were recorded on a Perkin- Intensity data for the yellow colored crystals of 8y and 5 were
Elmer AX-1 spectrophotometer in KBr disc and are reported in collected at 298(2) K on an OXFORD CrysAlis diffractometer
wave number (cm−1). ESIMS spectrometers were used for mass system equipped with a graphite-monochromated Mo Kα radia-
spectra analysis.
tion source, λ = 0.71073 Å. The final unit cell determination,
scaling of the data, and corrections for Lorentz and polarization
effects were performed with CrysAlis RED [44]. The structures
were solved by direct methods (SHELXS-97) [45] and refined
Synthesis of 1-phenyl-3-(methylthio)-5H-
dibenzo[d,f][1,3]diazepin-6(7H)-one (5)
A mixture of indoline-2-one (4, 1.1 mmol) and 2-pyranone (3, by a full-matrix least-squares procedure based on F2 [46]. All
1.0 mmol) and t-BuOK (2.1 mmol) in methanol/t-BuOH the calculations were carried out using WinGX system Ver-1.64
(10 mL) was heated under reflux for 6 h and was monitored by [47]. All nonhydrogen atoms were refined anisotropically;
TLC. After completion of the reaction, the excess of solvent hydrogen atoms were located at calculated positions and refined
was removed under reduced pressure and the reaction mixture using a riding model with isotropic thermal parameters fixed at
was poured onto crushed ice with vigorous stirring. The 1.2 times the Ueq value of the appropriate carrier atom.
aqueous reaction mixture was neutralized with dilute HCl and
the resulting precipitate was filtered, washed with water and Crystal data for compound 5
dried. The crude product was purified by silica gel column C42H38N4O3S3, formula mass 742.94, monoclinic space group
chromatography using chloroform/hexane as eluent to afford P121/C1, a = 19.5001(9), b = 8.4923(3), c = 22.8927(8) Å, β =
product 5 (analytical data and spectra are given in Supporting 92.088(3)°, V = 3788.5(3) Å3, Z = 4, dcalcd = 1.303 Mg·m−3,
Information File 1 and Supporting Information File 2).
linear absorption coefficient 0.241 mm−1, F(000) = 1560,
crystal size 0.29 × 0.20 × 0.18 mm, reflections collected 37984,
independent reflections 9203 [Rint = 0.0258], Final indices [I >
2σ(I)] R1 = 0.0797 wR2 = 0.1919, R indices (all data) R1 =
General procedure for the synthesis of alkenylindo-
line-2-ones 8y
A mixture of sodium hydride (2.1 mmol), indolin-2-one (4, 0.1048, wR2 = 0.2065, gof 1.107, largest difference peak and
1.1 mmol) and lactone 3 (1.0 mmol) in dry THF (10 mL) was hole 0.564 and −0.706 e·Å−3.
heated under reflux for 4–5 h. The excess of THF was removed
under reduced pressure, and the reaction mixture was poured Crystal data for compound 8yc
onto crushed ice with vigorous stirring. The aqueous reaction C27H22N2OS, formula mass 422.53, monoclinic space group
mixture was neutralized with dilute HCl. The precipitate P21/c, a = 10.1246(14), b = 9.0703(11), c = 22.641(4) Å, β =
obtained was filtered, washed with water, and dried. The 92.224(12)°, V = 2077.6(5) Å3, Z = 4, dcalcd = 1.351 Mg·m−3,
isolated crude product 8y was purified by silica gel column linear absorption coefficient 0.179 mm−1, F(000) = 888, crystal
chromatography using hexane/chloroform as eluent to afford size 0.30 × 0.25 × 0.18 mm, reflections collected 17655, inde-
products 8ya–8yj (the analytical data and spectra are given in pendent reflections 4949 [Rint = 0.0321], Final indices [I >
Supporting Information File 1 and Supporting Information 2σ(I)] R1 = 0.0994 wR2 = 0.2460, R indices (all data) R1 =
File 2).
0.1373, wR2 = 0.2727, gof 1.053, largest difference peak and
hole 0.455 and −0.644 e·Å−3.
General procedure for the synthesis of 1-aryl-3-
(sec-amino)-5H-dibenzo[d,f][1,3]diazepin-6(7H)-one
(10)
Computational details
Geometric characterization of all of the three tautomers of 8yc
A mixture of lactone (9, 1.0 mmol) sodium hydride (2.1 mmol), was performed at the level of density functional theory (DFT)
and indolin-2-one (4, 1.1 mmol) in dry THF (10 mL) was using the B3LYP functional [48,49]. For all the atoms 6-31G**
heated under reflux for 4–5 h. The excess of solvent was basis sets were used. All calculations were performed using the
removed under reduced pressure, and the reaction mixture was Gaussian 03 program [50]. The intermolecular interaction ener-
poured into ice-cold water under vigorous stirring. The aqueous gies were estimated at the MP2 level of theory. For the inter-
815

Beilstein J. Org. Chem. 2013, 9, 809–817.
References
action energy calculations, the C–H…π, Ar–H…π and Ar–H…O
distances were fixed for the dimer while all other degrees of
freedom were relaxed in the geometry optimization. The magni-
tude of the energy corresponding to this dimer was subtracted
from twice the energy of the monomer. The intermolecular
interaction strengths are significantly weaker than either ionic
or covalent bonding, therefore it was essential to perform basis
set superposition error (BSSE) corrections. The BSSE correc-
tions in the interaction energies were carried out using
Boys–Bernardi scheme [51]. In this paper all interaction ener-
gies are reported after BSSE correction.
1. Goel, A.; Ram, V. J. Tetrahedron 2009, 65, 7865–7913.
doi:10.1016/j.tet.2009.06.031
2. Andreani, A.; Burnelli, S.; Granaiola, M.; Leoni, A.; Locatelli, A.;
Morigi, R.; Rambaldi, M.; Varoli, L.; Calonghi, N.; Cappadone, C.;
Voltattorni, M.; Zini, M.; Stefanelli, C.; Masotti, L.; Shoemaker, R. H.
J. Med. Chem. 2008, 51, 7508–7513. doi:10.1021/jm800827q
3. Andreani, A.; Granaiola, M.; Leoni, A.; Locatelli, A.; Morigi, R.;
Rambaldi, M.; Garaliene, V. J. Med. Chem. 2002, 45, 2666–2669.
doi:10.1021/jm011123c
4. Hodges, R.; Shannon, J. S.; Jamieson, W. D.; Taylor, A. Can. J. Chem.
1968, 46, 2189–2194. doi:10.1139/v68-357
5. Sun, L.; Tran, N.; Tang, F.; App, H.; Hirth, P.; McMahon, G.; Tang, C.
J. Med. Chem. 1998, 41, 2588–2603. doi:10.1021/jm980123i
6. Hata, K.; Baba, K.; Kozawa, M. Chem. Pharm. Bull. 1978, 26,
2279–2280. doi:10.1248/cpb.26.2279
Supporting Information
7. Pedras, M. S. C.; Sorensen, J. L.; Okanga, F. I.; Zaharia, I. L.
Bioorg. Med. Chem. Lett. 1999, 9, 3015–3020.
The Supporting Information features the analytical data and
copies of 13C, 1H NMR, HRMS of all the compounds
including crystallographic data (cif files) for compounds 5
and 8yc. CCDC 897840 and 897838 contains the
supplementary crystallographic data for compound 5 and
8yc. These data can be obtained free of charge via
http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from
the Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK; fax (+44) 1223-336-033;
or email: deposit@ccdc.cam.ac.uk.
doi:10.1016/S0960-894X(99)00523-5
8. Pedras, M. S. C.; Chumala, P. B.; Suchy, M. Phytochemistry 2003, 64,
949–956. doi:10.1016/S0031-9422(03)00441-2
9. Zhou, L.; Yang, J.-S.; Wu, X.; Zou, J.-H.; Xu, X.-D.; Tu, G.-Z.
Heterocycles 2005, 65, 1409–1414. doi:10.3987/COM-04-10315
10.Fatima, I.; Ahmad, I.; Nawaz, S. A.; Malik, A.; Afza, N.; Luttfullah, G.;
Choudhary, M. I. Heterocycles 2006, 68, 1421–1428.
doi:10.3987/COM-06-10747
11.Zhang, G.; Huang, X.; Li, G.; Zhang, L. J. Am. Chem. Soc. 2008, 130,
1814–1815. doi:10.1021/ja077948e
12.Ishikawa, H.; Colby, D. A.; Boger, D. L. J. Am. Chem. Soc. 2008, 130,
420–421. doi:10.1021/ja078192m
Supporting Information File 1
Analytical data.
13.Phipps, R. J.; Grimster, N. P.; Gaunt, M. J. J. Am. Chem. Soc. 2008,
130, 8172–8174. doi:10.1021/ja801767s
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-9-92-S1.pdf]
14.Lebrasseur, N.; Larrosa, I. J. Am. Chem. Soc. 2008, 130, 2926–2927.
doi:10.1021/ja710731a
15.Lu, B.; Falck, J. R. Angew. Chem., Int. Ed. 2008, 120, 7508–7510.
doi:10.1002/anie.200802456
Supporting Information File 2
16.Stuart, D. R.; Villemure, E.; Fagnou, K. J. Am. Chem. Soc. 2007, 129,
12072–12073. doi:10.1021/ja0745862
HRMS, 1H and 13C NMR spectra.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-9-92-S2.pdf]
17.Yadav, A. K.; Peruncheralathan, S.; Illa, H.; Junjappa, H. J. Org. Chem.
2007, 72, 1388–1394. doi:10.1021/jo062302a
18.Kang, Q.; Zhao, Z.-A.; Yon, S.-L. J. Am. Chem. Soc. 2007, 129,
1484–1485. doi:10.1021/ja067417a
Supporting Information File 3
Crystallographic data of 5.
19.Haifeng, Y.; Yu, Z. Angew. Chem., Int. Ed. 2009, 48, 2929–2933.
doi:10.1002/anie.200900278
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-9-92-S3.cif]
20.Millemaggi, A.; Taylor, R. J. K. Eur. J. Org. Chem. 2010, 4527–4547.
doi:10.1002/ejoc.201000643
21.Redkin, R. G.; Shemchuk, L. A.; Chernykh, V. P.; Shishkin, O. V.;
Shishkina, S. V. Tetrahedron 2007, 63, 11444–11450.
doi:10.1016/j.tet.2007.08.050
Supporting Information File 4
Crystallographic data of 8yc.
22.Sassatelli, M.; Debiton, E.; Aboab, B.; Prudhomme, M.; Moreau, P.
Eur. J. Med. Chem. 2006, 41, 709–716.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-9-92-S4.cif]
doi:10.1016/j.ejmech.2006.03.021
23.Bouchikhi, F.; Rossignol, E.; Sancelme, M.; Aboab, B.; Anizon, F.;
Fabbro, D.; Prudhomme, M.; Moreau, P. Eur. J. Med. Chem. 2008, 43,
2316–2322. doi:10.1016/j.ejmech.2008.01.010
Acknowledgements
24.Hirao, K.; Morii, N.; Joh, T.; Takahashi, S. Tetrahedron Lett. 1995, 36,
6243–6246. doi:10.1016/0040-4039(95)01202-S
S. K. is thankful to the Department of Science and Technology
(DST), New Delhi, for the award of an INSPIRE fellowship
[IF10379]. The authors are thankful to the Division of SAIF,
CDRI, Lucknow, for providing spectroscopic data.
25.Park, J. H.; Kim, E.; Chung, Y. K. Org. Lett. 2008, 10, 4719–4721.
doi:10.1021/ol801978n
816

Beilstein J. Org. Chem. 2013, 9, 809–817.
26.Gabriele, B.; Salerno, G.; Veltri, L.; Costa, M.; Massera, C.
Eur. J. Org. Chem. 2001, 4607–4613.
License and Terms
doi:10.1002/1099-0690(200112)2001:24<4607::AID-EJOC4607>3.0.C
O;2-D
This is an Open Access article under the terms of the
Creative Commons Attribution License
27.Tang, S.; Yu, Q.-F.; Peng, P.; Li, J.-H.; Zhong, P.; Tang, R.-Y.
Org. Lett. 2007, 9, 3413–3416. doi:10.1021/ol701450n
28.Kobayashi, Y.; Kamisaki, H.; Yanada, K.; Yanada, R.; Takemoto, Y.
Tetrahedron Lett. 2005, 46, 7549–7552.
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
doi:10.1016/j.tetlet.2005.08.133
29.Hojo, D.; Noguchi, K.; Tanaka, K. Angew. Chem., Int. Ed. 2009, 48,
8129–8132. doi:10.1002/anie.200904024
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
30.Kobayashi, Y.; Kamisaki, H.; Yanada, R.; Takemoto, Y. Org. Lett.
2006, 8, 2711–2713. doi:10.1021/ol060733+
(http://www.beilstein-journals.org/bjoc)
31.Kobayashi, Y.; Kamisaki, H.; Takeda, H.; Yasui, Y.; Yanada, R.;
Takemoto, Y. Tetrahedron 2007, 63, 2978–2989.
doi:10.1016/j.tet.2007.01.060
The definitive version of this article is the electronic one
which can be found at:
32.Kamijo, S.; Sasaki, Y.; Kanazawa, C.; Schüßeler, T.; Yamamoto, Y.
Angew. Chem., Int. Ed. 2005, 44, 7718–7721.
doi:10.3762/bjoc.9.92
doi:10.1002/anie.200502252
33.Bowman, W. R.; Heaney, H.; Jordan, B. M. Tetrahedron Lett. 1988, 29,
6657–6660. doi:10.1016/S0040-4039(00)82423-5
34.Brunton, S. A.; Jones, K. J. Chem. Soc., Perkin Trans. 1 2000,
763–768. doi:10.1039/A907920C
35.Cheung, W. S.; Patch, R. J.; Player, M. R. J. Org. Chem. 2005, 70,
3741–3744. doi:10.1021/jo050016d
36.Arthuis, M.; Pontikis, R.; Floret, J.-C. Tetrahedron Lett. 2007, 48,
6397–6400. doi:10.1016/j.tetlet.2007.06.129
37.Yanada, R.; Obika, S.; Inokuma, T.; Yanada, K.; Yamashita, M.;
Ohata, S.; Takemoto, Y. J. Org. Chem. 2005, 70, 6972–6975.
doi:10.1021/jo0508604
38.Ueda, S.; Okada, T.; Nagasawa, H. Chem. Commun. 2010, 46,
2462–2464. doi:10.1039/b926560k
39.Gompper, R.; Kutter, E.; Töpfl, W. Justus Liebigs Ann. Chem. 1962,
659, 90–101. doi:10.1002/jlac.19626590110
40.Ram, V. J.; Verma, M. Indian J. Chem. 1990, 29B, 624.
41.Tominaga, Y.; Ushirogouchi, A.; Matsuda, Y.; Kobayashi, G.
Chem. Pharm. Bull. 1984, 32, 3384–3395. doi:10.1248/cpb.32.3384
42.Ram, V. J.; Verma, M.; Hussaini, F. A.; Shoeb, A.
J. Chem. Res., Synop. 1991, 98–99.
43.Bader, R. F. W. Atoms in Molecules: A Quantum Theory; Oxford
University Press: New York, 1990.
44.CrysAlis CCD, RED version 1.711.13, copyright 1995–2003, Oxford
Diffraction Poland Sp.
45.Sheldrick, G. M. SHELXS97, Program for Crystal Structure Solution,
University of Göttingen, Göttingen, 1997.
46.Sheldrick, G. M. SHELXL97, Program for Crystal Structure Refinement,
University of Göttingen, Göttingen, 1997.
47.Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837–838.
doi:10.1107/S0021889899006020
48.Becke, A. D. J. Phys. Rev. B: Condens. Matter Mater. Phys. 1993, 98,
5648–5652.
49.C. T., Lee; W. T., Yang; R. G., Parr.
Phys. Rev. B: Condens. Matter Mater. Phys. 1998, 37, 785–789.
doi:10.1103/PhysRevB.37.785
50.Gaussian 03, Revision D.01; Gaussian, Inc.: Wallingford, CT, USA,
2004.
51.Boys, S. F.; Bernardi, F. Mol. Phys. 1970, 19, 553–556.
doi:10.1080/00268977000101561
817