A facile synthesis of substituted indenones and piperidine-2,6-diones from the baylis-hillman acetates

Article abstract of DOI:10.1002/ejoc.201000739

Baylis-Hillman acetates were conveniently transformed into substituted indenone and piperidine-2,6-dione frameworks by treatment with (di)phenylacetonitrile followed by Friedel-Crafts cyclization or imide formation. Baylis-Hillman acetates were conveniently transformed into substituted indenone and piperidine-2,6-dione frameworks by treatment with (di)phenylacetonitrile followed by Friedel-Crafts cyclization or imide formation.

Full text of DOI:10.1002/ejoc.201000739

FULL PAPER
DOI: 10.1002/ejoc.201000739
A Facile Synthesis of Substituted Indenones and Piperidine-2,6-diones from the
Baylis–Hillman Acetates
Deevi Basavaiah*[a] and Dandamudi V. Lenin[a]
Keywords: Alkylation / Carbocycles / Cyclization / Baylis–Hillman reaction / Synthetic methods
Baylis–Hillman acetates were conveniently transformed into
substituted indenone and piperidine-2,6-dione frameworks
by treatment with (di)phenylacetonitrile followed by Friedel–
Crafts cyclization or imide formation.
with electrophiles under the influence of a catalyst or cata-
lytic system, and the reaction can usually be performed in
a one-pot, operationally simple procedure.[7] The B-H ad-
ducts have been successfully employed in various organic
transformation methodologies and have also been used as
synthons to obtain a number of natural products and biolo-
gically active molecules.[8]
Introduction
The ind-2-en-1-one framework represents an important
class of carbocyclic molecules, and many of these deriva-
tives are found in important natural products.[1] Some of
indenone derivatives are also known to be peroxisome pro-
liferator-activated receptor γ (PPAR γ, drug used against
type-2 diabetes) agonists,[2a,2b] estrogen receptor binding
agents,[2c,2d] cyclooxygenase-2 inhibitors,[2e] and potent re-
versible inhibitors of 3CP.[2f] Due to their significant medic-
inal importance, the development of facile strategies to ob-
tain such frameworks has become an attractive endeavor in
synthetic organic and medicinal chemistry. In fact, several
methodologies have been reported for their synthesis in re-
cent years.[3] The piperidine-2,6-dione framework is another
medicinally important skeleton present in several biolo-
gically active and natural products, such as: alonimid[4a,4b]
(sedative and hypnotic activity), thalidomide[4c] (drug to
prevent morning sickness of pregnant women), streptimid-
one[4d] (antibiotic), migrastatin[4e–4g] (antitumor agent), lac-
timidomycin[4h,4i] (antibiotic), and sesbanimide[4j,4k] (antitu-
mor). Therefore, the development of facile strategies for the
synthesis of these frameworks has become a challenging
task in synthetic organic chemistry.[4c,4d,4f,4k,5] In a continu-
ation of our interest in the synthesis of carbocyclic and het-
erocyclic molecules,[6] we herein report a facile, two-step
protocol for synthesis of 2-substituted ind-2-en-1-one and
3,5-disubstituted piperidine-2,6-dione derivatives from the
Baylis–Hillman (B-H) acetates.
Results and Discussion
A few years ago, we successfully used B-H adducts as
substrates in a number of Friedel–Crafts reactions to obtain
various trisubstituted alkenes[9a,9b] and carbocylic/heterocy-
clic molecules.[9c–9e] Very recently we reported a facile, two-
step protocol for the transformation of acetates (1) of the
B-H adducts (obtained from aryl aldehydes and tert-butyl
acrylate) into bis-(E)-benzylidene-tetralone-spiro-glutarimi-
des.[5b] This strategy proceeds through bis-alkylation of
benzyl cyanide with B-H acetates 1 followed by bis-cycliza-
tion involving a tandem intramolecular Friedel–Crafts reac-
tion and imide formation (Scheme 1). From this experience,
it occurred to us that it is possible to synthesize 2-arylmethyl-
idene-4-cyanotetralone derivatives 3 by monoalkylation of
benzyl cyanide with B-H acetates (1), followed by intramo-
lecular Friedel–Crafts cyclization of the resulting (E)-alkyl-
ated products 2 according to the retrosynthetic strategy
shown in Scheme 2. Similarly, the products 2 would be
transformed into 3-arylmethylidene-5-phenylpiperidine-2,6-
diones 4 by partial hydrolysis and cyclization (Scheme 2).
Accordingly, we performed the monoalkylaion of benzyl
cyanide with tert-butyl 3-acetoxy-2-methylene-3-phenylpro-
panoate (1a) in the presence of tBuOK. Thus, treatment of
benzyl cyanide (5 mmol) with 1a (5 mmol) in the presence
of tBuOK (5.5 mmol) in tetrahydrofuran (THF) at room
temperature for 10 hours provided the required mono-alkyl-
ated product, (E)-tert-butyl 2-benzylidene-4-cyano-4-phen-
ylbutanoate (2a), in 72% isolated yield (Table 1). We then
performed the intramolecular Friedel–Crafts reaction of 2a
with trifluoroacetic acid (TFA)/trifluoroacetic anhydride
In recent years, the B-H reaction has emerged as a
powerful synthetic tool with which to provide diverse
classes of multifunctional molecules, which are usually re-
ferred to as the Baylis–Hillman adducts. The products are
formed by coupling at the α-position of activated alkenes
[a] School of Chemistry, University of Hyderabad,
Hyderabad 500046, India
Fax: +91-40-23012460
E-mail: dbsc@uohyd.ernet.in
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000739.
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Eur. J. Org. Chem. 2010, 5650–5658

Substituted Indenones and Piperidine-2,6-diones
Scheme 1. Previously reported application of B-H adduct 1.[5b]
Scheme 2. Retrosynthetic strategy.
(TFAA). To our surprise, we did not obtain the expected Table 2. Synthesis of 2-(2-phenyl-2-cyano)ethylind-2-en-1-ones 5a
and 5b.[a]
tetralone derivative 3a (R = H), however, we were pleased
to see the formation of the unexpected indenone derivative
5a (R
= H) [2-(2-cyano-2-phenylethyl)ind-2-en-1-one].
Thus, treatment of 2a (0.5 mmol) with TFA (2.5 mmol)/
TFAA (1 mmol) in dichloroethane (DCE; 3 mL) at reflux
temperature for 5 hours provided 2-(2-phenyl-2-cyano)eth-
ylind-2-en-1-one[10] (5a) in 38% isolated yield (Table 2). Al-
though the yields were not that encouraging, this reaction
was interesting in the sense that tetralone derivative 3a,
which was expected to form easily, did not form, whereas,
the indenone derivative 5a, which was not expected to form
easily due to the trans orientation[11] of ester group and aryl
group (trans-cinnamic ester derivative), was obtained in rea-
sonably good yield.
Entry Substrate
R
Product[b]
R
Yield [%][c]
1
2
2a
2b
H
4-iPr
5a
5b
H
6-iPr
38
40
[a] Reactions were carried out on a 0.5 mmol scale of 2a and 2b.
[b] Obtained as yellow solids and well characterized. [c] Isolated
yields based on substrates 2a and 2b.
Although these reactions are quite interesting due to the
unexpected transformation of trans-cinnamic esters into
ind-2-en-1-one derivatives, the low yields of the products
were disappointing. From these results, it occurred to us
that it should be possible to transform trans-cinnamic acids/
esters into indenone derivatives using TFA/TFAA. Accord-
ingly, we directed our attention to the conversion of (2E)-
tert-butyl 3-phenyl-2-methylprop-2-enoate (6a) into 2-meth-
ylind-2-en-1-one (7a) by treatment with TFA/TFAA. The
required trans ester 6a was prepared by treatment of tert-
butyl 3-acetoxy-2-methylene-3-phenylpropanoate (1a) with
sodium borohydride following the procedure developed in
our laboratory.[8x] We then examined the Friedel–Crafts
cyclization of trans ester 6a into 2-methylind-2-en-1-one
(7a) using TFA/TFAA. The best results were obtained
Table 1. Synthesis of (E)-tert-butyl 2-arylmethylidene-4-cyano-4-
phenylbutanoates 2a and 2b.[a][11]
Entry
B-H acetate
R
Product[b]
Yield [%][c]
1
2
1a
1b
H
4-iPr
2a
2b
72
80
[a] Reactions were carried out on a 5 mmol scale of B-H acetates
1a and 1b. [b] Obtained as colorless viscous liquids and well charac-
terized. [c] Isolated yields based on B-H acetates 1a and 1b.
To understand the generality of this strategy, we trans- when (2E)-tert-butyl 3-phenyl-2-methylprop-2-enoate (6a;
formed tert-butyl 3-acetoxy-2-methylene-3-(4-isopropyl- 1.0 mmol) was heated to reflux for 5 h in DCE (3 mL) in
phenyl)propanoate (1b) into (E)-tert-butyl 2-(4-isopropyl- the presence of TFA (5 mmol) and TFAA (2 mmol), thus
benzylidene)-4-cyano-4-phenylbutanoate (2b) which, on providing the expected 2-methylind-2-en-1-one (7a) in 18%
treatment with TFA/TFAA, gave [2-(2-cyano-2-phenyl- isolated yield.[12] To understand the general nature of this
ethyl)-6-isopropylind-2-en-1-one] (5b) in 40% isolated yield reaction strategy, we extended this methodology to another
(Table 2).[12]
B-H acetate, tert-butyl 3-acetoxy-2-methylene-3-(4-isoprop-
Eur. J. Org. Chem. 2010, 5650–5658
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D. Basavaiah, D. V. Lenin
ylphenyl)propanoate (1b). Treatment of 1b with NaBH4 fol- Table 4. Synthesis of (E)-tert-butyl 2-arylmethylidene-4-cyano-4,4-
FULL PAPER
diphenylbutanoates 8a–g.[a],[11]
lowing the known methodology[8x] gave the trans-cinnamic
ester (6b). Subsequent treatment of 6b with TFA/TFAA
provided the desired 6-isopropyl-2-methylind-2-en-1-one
(7b) in 20% isolated yield (Table 3). Comparison of yields
obtained for 5a and 5b (38 and 40%) with those of 7a and
7b (18 and 20%) clearly indicates that trans-cinnamic esters
2a and 2b, containing sterically bulky phenylcyanomethyl
groups at the α-position, provided better yields of indenone
derivatives in comparison to those of 6a and 6b, which con-
tain a simple methyl group at the α-position.
Entry
B-H acetate
R
Product[b]
Yield [%][c]
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
H
8a
8b
81
83
78
79
75
80
77
4-iPr
3-Me
4-Et
4-Me
3-Br
2-Me
8c
8d[d]
8e
8f
8g
Table 3. Synthesis of 2-methylind-2-en-1-ones 7a and 7b.[a]
1g
[a] All reactions were carried out on a 2 mmol scale of B-H acetates
1a–g. [b] Obtained as colorless solids and well characterized. [c]
Isolated yields based on B-H acetates 1a–g. [d] The structure of
this molecule was further confirmed by single-crystal X-ray data
analysis.[13]
Entry
Substrate
R
Product[b]
R
Yield [%][c]
1
2
6a
6b
H
4-iPr
7a
7b
H
6-iPr
18
20
Table 5. Synthesis of 2-(2-cyano-2,2-diphenylethyl)ind-2-en-1-ones
10a–g.[a]
[a] Reactions were carried out on a 1 mmol scale of 6a and 6b. [b]
Obtained as yellow viscous liquids and well characterized. [c] Iso-
lated yields based on substrates 6a and 6b).
With a view to further understanding the influence of
steric factors in the formation of ind-2-en-1-one derivatives,
we selected (E)-tert-butyl 2-benzylidene-4-cyano-4,4-di-
phenylbutanoate (8a) as a substrate for intramolecular Frie-
del–Crafts cyclization. The required trans-cinnamic ester
(8a) was obtained by treatment of 1a (2 mmol) with di-
phenylacetonitrile (2 mmol) in anhydrous toluene (5 mL) in
the presence of NaH (5 mmol), in 81% isolated yield
(Table 4). The Friedel–Crafts cyclization of 8a was per-
formed with TFA/TFAA in DCE for 5 h at reflux tempera-
ture to provide 2-(2-cyano-2,2-diphenylethyl)ind-2-en-1-one
(10a) in 66% isolated yield (Table 5).[14] This result fasci-
nated us because trans-cinnamic ester 8a, containing the
sterically more hindered diphenylcyanomethyl group, pro-
vided superior yields of the indenone derivative (10a). To
Entry
Substrate
R
Product[b]
R
Yield [%][c]
1
2
3
4
5
6
7
8a
8b
8c
8d
8e
8f
H
10a[d]
10b
10c
10d
10e
10f
H
66
63
64
70
60
66
62
4-iPr
3-Me
4-Et
4-Me
3-Br
2-Me
6-iPr
5-Me
6-Et
6-Me
5-Br
4-Me
8g
10g
[a] All reactions were carried out on a 0.5 mmol scale of 8a–g. [b]
Obtained as yellow solids and well characterized. [c] Isolated yields
based on substrates 8a–g. [d] The structure of this molecule was
also confirmed by single-crystal X-ray data analysis.[13]
understand the generality of this methodology, we subjected [8.3.0.02,7]trideca-1(10),2(7),3,5,8,12-hexaene-11-one (10h)
a representative class of B-H acetates (1b–g) to this reaction in 64% isolated yield (Scheme 3).
strategy. The resulting alkylated trans-cinnamic esters (8b–
These results, to some extent, suggest that the reaction
g) were obtained in 75–83% isolated yields (Table 4) which, pathway may not proceed through isomerization of the
on intramolecular Friedel–Crafts reaction using TFA/ trans-cinnamic esters into the cis derivatives, and probably
TFAA, furnished the required indenone derivatives, 2-(2- involves the reorganization of the trans double bond so that
cyano-2,2-diphenylethyl)ind-2-en-1-ones (10a–g), in 60– the five-membered ring formation providing indenone de-
70% isolated yields (Table 5).[14] The structures of com- rivatives 5a, 5b, and 10a–h, becomes easier (which is other-
pounds 8d and 10a were further confirmed by single-crystal wise difficult to form) than the formation of the six-mem-
X-ray data analysis.[13]
bered ring (providing the tetralone derivatives 3 and 9). On
To understand the applicability of this strategy to the this basis, a plausible mechanism involving formation of a
naphthalene framework, we prepared (E)-tert-butyl 4-cy- ketene-type transition state through Michael addition of a
ano-2-(naphth-1-ylmethylidene)-4,4-diphenylbutanoate (8h) trifluoroacetoxide anion onto the trans-cinnamic ester de-
from tert-butyl 3-acetoxy-2-methylene-3-(naphth-1-yl)- rivative, is presented in Scheme 4.
propanoate (1h) in 76% yield by using the reaction with
We then turned our attention towards the synthesis of
diphenylacetonitrile in the prersence of NaH. Subsequent piperidine-2,6-dione frameworks (4) from the trans esters 2.
treatment of 8h with TFA/TFAA gave the expected inde- We selected (E)-tert-butyl 2-benzylidene-4-cyano-4-phenyl-
none derivative, 12-(2-cyano-2,2-diphenylethyl)tricyclo- butanoate (2a) as a substrate. The best results in this direc-
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Eur. J. Org. Chem. 2010, 5650–5658

Substituted Indenones and Piperidine-2,6-diones
Scheme 3. Synthesis of 10h.
Scheme 4. Plausible mechanism for the formation of substituted ind-2-en-1-one and piperidine-2,6-dione derivatives.
tion were obtained when 2a (0.5 mmol) was treated with was further confirmed by single-crystal X-ray data analy-
methanesulfonic acid (CH3SO3H; 1.5 mmol) and TFAA sis.[13] A plausible mechanism for the transformation of 8a–
(1 mmol) in DCE at reflux temperature for 4 h, thus provid- h into 11a–h is presented in Scheme 4.
ing the desired (E)-3-benzylidene-5-phenylpiperidine-2,6-di-
Table 7. Synthesis of (E)-3-arylmethylidene-5,5-diphenylpiperidine-
one (4a) in 70% isolated yield. Similarly, we transformed
(E)-tert-butyl 2-(3-methylbenzylidene)-4-cyano-4-phenyl-
2,6-diones 11a–h.[a]
butanoate (2c) into the piperidine-2,6-dione derivative (4b)
in 75% isolated yield (Table 6).
Table 6. Synthesis of (E)-3-arylmethylidene-5-phenylpiperidine-2,6-
diones 4a and 4b.[a]
Entry
Substrate
Ar
Product[b]
Yield [%][c]
1
2
3
4
5
6
7
8
8a
8b
8c
8d
8e
8f
Ph
11a[d]
11b
11c
11d
11e
11f
85
86
81
77
80
82
75
79
4-iPrC6H4
3-MeC6H4
4-EtC6H4
4-MeC6H4
3-BrC6H4
2-MeC6H4
1-naphthyl
Entry
Substrate
R
Product[b]
Yield [%][c]
1
2
2a
2c
H
3-Me
4a
4b
70
75
8g
8h
11g
11h
[a] Reactions were carried out on a 0.5 mmol scale of 2a and 2c.
[b] Obtained as colorless solids and well characterized. [c] Isolated
yields based on substrates 2a and 2c.
[a] All reactions were carried out on a 0.5 mmol scale of substrates
8a–h. [b] Obtained as colorless solids and well characterized. [c]
Isolated yields based on substrates 8a–h. [d] The structure of this
compound was also confirmed by single-crystal X-ray data analy-
sis.[13]
Encouraged by these results, we extended the same strat-
egy to the more hindered trans ester (E)-tert-butyl 2-benzyl-
idene-4-cyano-4,4-diphenylbutanoate (8a). In this case also,
treatment of 8a (0.5 mmol) with CH3SO3H (1.5 mmol) and
TFAA (1 mmol) in DCE at reflux temperature for 4 h fur-
nished (E)-3-benzylidene-5,5-diphenylpiperidine-2,6-dione
(11a) in 85% isolated yield. To understand the generality of
Conclusions
Baylis–Hillman acetates have been transformed into 2-
this methodology, we successfully transformed trans esters substituted ind-2-en-1-one derivatives in a two-step proto-
8b–h into the corresponding piperidine-2,6-dione deriva- col. This transformation proceeds through an unusual con-
tives 11b–h in 75–86% yields (Table 7). The structure of 11a version of trans-cinnamic esters into the ind-2-en-1-one
Eur. J. Org. Chem. 2010, 5650–5658
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5653

D. Basavaiah, D. V. Lenin
FULL PAPER
128.41, 128.99, 129.30, 134.99, 135.47, 138.13, 142.97, 166.38 ppm.
frameworks. The yields of the indenone derivatives depend
on the steric bulk of the substituent at the α-position of the
ester group of trans-cinnamic esters. We have also devel-
oped a simple two-step strategy to transform the B-H acet-
ates into substituted piperidine-2,6-dione derivatives.
LCMS: m/z = 348 [M + H]+.
2-(2-Cyano-2-phenylethyl)ind-2-en-1-one (5a): To a stirred solution
of (E)-tert-butyl 2-benzylidene-4-cyano-4-phenylbutanoate (2a;
0.5 mmol, 0.167 g) in DCE (3 mL), were added TFA (2.5 mmol,
0.285 g, 0.19 mL) and TFAA (1 mmol, 0.210 g, 0.14 mL) at r.t. The
reaction mixture was heated to reflux for 5 h and then allowed to
cool to r.t. The reaction mixture was poured into aqueous K2CO3
and extracted with diethyl ether (2ϫ10 mL). The combined or-
ganic layer was dried with anhydrous Na2SO4, the solvent was
evaporated and the residue, thus obtained, was purified by column
chromatography (ethyl acetate/hexanes, 5%) to provide 5a as a yel-
Experimental Section
General Remarks: Melting points were recorded with a Superfit
(India) capillary melting point apparatus. Infrared spectra were re-
corded with a JASCO FT/IR 5300 spectrophotometer; spectra were
calibrated against polystyrene absorption at 1601 cm–1. Solid sam-
low solid (38%, 0.049 g); m.p. 116–117 °C. IR (KBr): ν = 2237,
˜
1
1711, 1651, 1604 cm–1. H NMR (400 MHz, CDCl3): δ = 2.86 (d,
1
ples were recorded as KBr plates. H and 13C NMR spectra were
J = 7.6 Hz, 2 H), 4.13 (t, J = 7.6 Hz, 1 H), 7.01 (d, J = 7.2 Hz, 1 H),
7.16–7.22 (m, 1 H), 7.30–7.48 (m, 8 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 31.65, 36.70, 120.31, 122.31, 123.08, 127.35, 128.46,
128.89, 129.26, 130.38, 134.23, 134.39, 135.08, 143.99, 146.34,
197.49 ppm. LCMS m/z = 260 [M + H]+. C18H13NO (259.31):
calcd. C 83.37, H 5.05, N 5.40; found C 83.45, H 5.11, N 5.51.
recorded with a Bruker AVANCE-400 spectrometer. 1H NMR
(400 MHz) spectra were recorded in CDCl3 with TMS (δ = 0 ppm)
as internal standard. 13C NMR (100 MHz) spectra were measured
in CDCl3 with the central peak of the solvent triplet (δ =
77.10 ppm) as internal standard. Elemental analyses were recorded
with a Thermo-Finnigan Flash EA 1112 analyzer. Mass spectra
were recorded with a Shimadzu-LCMS-2010 A mass spectrometer.
The X-ray diffraction data were collected at 298 K with a Bruker
SMART APEX CCD area detector system equipped with a graph-
ite monochromator and a Mo-Kα fine-focus sealed tube (λ =
0.71073 Å).
2-(2-Cyano-2-phenylethyl)-6-isopropylind-2-en-1-one (5b): Yield
40%; m.p. 66–68 °C. IR (KBr): ν = 2241, 1705, 1606 cm–1. 1H
˜
NMR (400 MHz, CDCl3): δ = 1.22 (d, J = 6.4 Hz, 6 H), 2.75–2.95
(m, 3 H), 4.12 (t, J = 7.2 Hz, 1 H), 6.90 (d, J = 7.2 Hz, 1 H), 7.09–
7.48 (m, 8 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.71, 31.66,
34.13, 36.73, 120.34, 121.71, 122.17, 127.35, 128.40, 129.22, 130.80,
131.72, 133.85, 135.13, 141.51, 146.55, 150.32, 197.87 ppm. LCMS:
m/z = 302 [M + H]+. C21H19NO (301.39): calcd. C 83.69, H 6.35,
N 4.65; found C 83.65, H 6.39, N 4.77.
(E)-tert-Butyl 2-Benzylidene-4-cyano-4-phenylbutanoate (2a): To a
stirred solution of benzyl cyanide (5 mmol, 0.577 mL) and tBuOK
(5.5 mmol, 0.616 g) in anhydrous THF (10 mL), was added tert-
butyl 3-acetoxy-2-methylene-3-phenylpropanoate (1a; 5 mmol,
1.380 g) slowly at r.t. After stirring for 10 h at r.t., the reaction
mixture was diluted with diethyl ether (5 mL) and washed with
water (2ϫ5 mL). The aqueous layer was extracted with diethyl
ether (3ϫ10 mL) and the combined organic layer was dried with
anhydrous Na2SO4. The solvent was evaporated and the residue
thus obtained was purified by column chromatography (silica gel;
EtOAc/hexanes, 3%) to provide 2a as a colorless viscous liquid
2-Methylind-2-en-1-one (7a): To a stirred solution of (2E)-tert-butyl
2-methyl-3-phenylprop-2-enoate[15] (6a; 1.0 mmol, 0.218 g) in DCE
(3 mL), was added TFA (5 mmol, 0.570 g, 0.38 mL) and TFAA
(2 mmol, 0.420 g, 0.28 mL) at r.t. The reaction mixture was heated
to reflux for 5 h and then allowed to cool to r.t. The reaction mix-
ture was poured into aqueous K2CO3 and extracted with diethyl
ether (2ϫ10 mL). The combined organic layer was dried with an-
hydrous Na2SO4, the solvent was evaporated and the residue, thus
obtained, was purified by column chromatography (ethyl acetate/
hexanes, 2%) to provide 7a[3k,3l] as a yellow viscous liquid[16] (18%,
(72%, 1.20 g). IR (Neat): ν = 2245, 1714, 1631 cm–1. 1H NMR
˜
(400 MHz, CDCl3): δ = 1.57 (s, 9 H), 2.95 and 3.15 [d ABq, J =
13.6, 7.2 (8.8) Hz, 2 H], 4.35 (t, J = 8.4 Hz, 1 H), 7.18–7.42 (m, 10
H), 7.81 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 28.13,
33.70, 36.19, 81.51, 120.42, 127.33, 128.08, 128.50, 128.61, 128.98,
129.52, 135.02, 135.39, 142.75, 166.27 ppm. LCMS: m/z = 334 [M
+ H]+.
0.026 g). IR (Neat): ν = 1712, 1606 cm–1. 1H NMR (400 MHz,
˜
CDCl3): δ = 1.86 (s, 3 H), 6.92 (d, J = 7.2 Hz, 1 H), 7.08–7.19 (m,
2 H), 7.22–7.30 (m, 1 H), 7.36 (d, J = 6.8 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 10.07, 121.14, 122.62, 127.88, 130.79,
133.84, 136.24, 143.35, 144.95, 198.81 ppm. LCMS: m/z = 145 [M
+ H]+.
(E)-tert-Butyl 2-(4-Isopropylbenzylidene)-4-cyano-4-phenylbutano-
ate (2b): Yield 80%. IR (Neat): ν = 2241, 1712, 1631 cm–1. 1H
˜
6-Isopropyl-2-methylind-2-en-1-one (7b): Yield 20%. IR (Neat): ν =
˜
1712, 1616 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.21 (d, J =
7.2 Hz, 6 H), 1.85 (s, 3 H), 2.85 (sept, J = 7.2 Hz, 1 H), 6.83 (d, J
= 7.2 Hz, 1 H), 7.08–7.15 [m, 2 H, with a doublet at δ = 7.10 (J =
NMR (400 MHz, CDCl3): δ = 1.25 (d, J = 6.8 Hz, 6 H), 1.56 (s, 9
H), 2.84–3.03 (m, 2 H), 3.12–3.24 (m, 1 H), 4.26 (t, J = 8.0 Hz, 1
H), 7.04–7.42 (m, 9 H), 7.78 (s, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 23.90, 28.20, 33.79, 33.97, 36.28, 81.42, 120.58, 126.71,
127.43, 128.15, 128.97, 129.04, 132.49, 135.54, 142.82, 149.67,
166.53 ppm; In addition, peaks at δ = 21.41, 128.70, 128.85, 129.34,
132.10, 138.79 ppm with low intensity indicate that 2b was con-
taminated with 5% impurity. The material was used as such in the
next step.
7.2 Hz, 1 H) and a singlet at δ = 7.09 (1 H)], 7.28 (s, 1 H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 10.06, 23.76, 34.07, 120.97, 121.29,
131.23, 131.30, 135.76, 142.48, 143.50, 149.17, 199.20 ppm. LCMS:
m/z = 187 [M + H]+. C13H14O (186.25): calcd. C 83.83, H 7.58;
found C 83.75, H 7.65.
(E)-tert-Butyl 2-Benzylidene-4-cyano-4,4-diphenylbutanoate (8a): To
a stirred suspension of oil-free NaH (5 mmol, 0.120 g) in anhydrous
toluene (5 mL), were added successively diphenylacetonitrile
(2 mmol, 0.386 g) and tert-butyl 3-acetoxy-2-methylene-3-phenyl-
propanoate (1a; 2 mmol, 0.552 g) at r.t. The reaction mixture was
heated to reflux for 1 h under an N2 atmosphere and then allowed
(E)-tert-Butyl 4-Cyano-2-(3-methylbenzylidene)-4-phenylbutanoate
1
(2c): Yield 73%. IR (Neat): ν = 2241, 1695, 1631 cm–1. H NMR
˜
(400 MHz, CDCl3): δ = 1.57 (s, 9 H), 2.33 (s, 3 H), 2.95 and 3.15
[d ABq, J = 13.6, 7.6 (8.8) Hz, 2 H], 4.26 (t, J = 8.0 Hz, 1 H), 6.94
(s, 1 H), 7.00 (d, J = 7.6 Hz, 1 H), 7.12 (d, J = 7.6 Hz, 1 H), 7.20–
7.40 (m, 6 H), 7.77 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ to cool to 0 °C and the excess NaH was carefully quenched by slow
= 21.37, 28.16, 33.80, 36.21, 81.47, 120.51, 125.66, 127.41, 128.06,
addition of water. The reaction mixture was extracted with diethyl
5654
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5650–5658

Substituted Indenones and Piperidine-2,6-diones
ether (2ϫ10 mL) and the combined organic layer was dried with
anhydrous Na2SO4. The solvent was removed and the residue, thus
obtained, was subjected to column chromatography (ethyl acetate/
hexanes, 5%) to provide a solid, which was crystallized from ethyl
acetate/hexanes (3%) at 0 °C to afford 8a as a colorless crystalline
(E)-tert-Butyl 4-Cyano-2-(2-methylbenzylidene)-4,4-diphenylbutano-
ate (8g): Yield 77%; m.p. 108–110 °C. IR (KBr): ν = 2239, 1709,
˜
1599 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.48 (s, 9 H), 1.94 (s,
3 H), 3.80 (s, 2 H), 6.97–7.27 (m, 14 H), 7.67 (s, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 19.83, 28.01, 34.32, 51.20, 81.42,
121.44, 125.48, 127.15, 127.63, 127.74, 128.05, 128.45, 129.92,
solid (81%, 0.660 g); m.p. 78–80 °C. IR (KBr): ν = 2243, 1705,
˜
1631 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.44 (s, 9 H), 3.82 (s, 130.16, 134.63, 137.35, 139.82, 141.85, 166.87 ppm. LCMS: m/z =
2 H), 6.97–7.05 (m, 2 H), 7.15–7.32 (m, 13 H), 7.67 (s, 1 H) ppm. 422 [M – H]+.
13C NMR (100 MHz, CDCl3): δ = 28.02, 34.81, 51.21, 81.46,
(E)-tert-Butyl 4-Cyano-2-(naphth-1-ylmethylidene)-4,4-diphenylbut-
121.70, 127.39, 127.79, 127.88, 128.32, 128.52, 128.62, 129.73,
anoate (8h): Yield 76%; m.p. 116–118 °C. IR (KBr): ν = 2229, 1699,
˜
135.34, 139.99, 142.40, 166.94 ppm. LCMS: m/z = 410 [M + H]+.
1631 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.57 (s, 9 H), 3.82 (s,
2 H), 6.82–7.19 (m, 11 H), 7.22–7.49 (m, 3 H), 7.54 (d, J = 8.0 Hz,
1 H), 7.69 (d, J = 8.0 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H), 8.11 (s,
1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 28.15, 35.19, 51.08,
81.85, 121.53, 125.04, 125.42, 126.05, 127.01, 127.29, 128.12,
128.28, 128.49, 131.23, 131.48, 132.76, 133.39, 139.71, 141.03,
166.90 ppm. LCMS: m/z = 460 [M + H]+.
(E)-tert-Butyl 4-Cyano-2-(4-isopropylbenzylidene)-4,4-diphenylbut-
anoate (8b): Yield 83%; m.p. 90–92 °C. IR (KBr): ν = 2237, 1701,
˜
1
1622 cm–1. H NMR (400 MHz, CDCl3): δ = 1.21 (d, J = 6.8 Hz,
6 H), 1.44 (s, 9 H), 2.85 (sept, J = 6.8 Hz, 1 H), 3.83 (s, 2 H), 6.94
(d, J = 8.0 Hz, 2 H), 7.03 (d, J = 8.0 Hz, 2 H), 7.15–7.32 (m, 10
H), 7.64 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.89,
28.03, 33.88, 34.90, 51.27, 81.32, 121.74, 126.40, 127.42, 127.77,
128.48, 128.79, 132.75, 140.11, 142.55, 148.83, 167.12 ppm. LCMS:
m/z = 452 [M + H]+.
2-(2-Cyano-2,2-diphenylethyl)ind-2-en-1-one (10a): To a stirred solu-
tion of (E)-tert-butyl 2-benzylidene-4-cyano-4,4-diphenylbutanoate
(8a; 0.5 mmol, 0.205 g) in DCE (3 mL), were added TFA
(2.5 mmol, 0.285 g, 0.19 mL) and TFAA (1 mmol, 0.210 g,
0.14 mL) at r.t. The reaction mixture was heated at reflux for 5 h
and then allowed to cool to r.t. The reaction mixture was poured
into aqueous K2CO3 and extracted with diethyl ether (2ϫ10 mL).
The combined organic layer was dried with anhydrous Na2SO4, the
solvent was evaporated and the residue, thus obtained, was purified
by column chromatography (ethyl acetate/hexanes, 5%) to provide
(E)-tert-Butyl 4-Cyano-2-(3-methylbenzylidene)-4,4-diphenylbutano-
ate (8c): Yield 78%; m.p. 82–84 °C. IR (KBr): ν = 2245, 1703,
˜
1601 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.45 (s, 9 H), 2.22 (s,
3 H), 3.81 (s, 2 H), 6.68 (s, 1 H), 6.84 (d, J = 7.6 Hz, 1 H), 6.98 (d,
J = 7.6 Hz, 1 H), 7.05–7.12 (m, 1 H), 7.17–7.31 (m, 10 H), 7.64 (s,
1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.28, 27.98, 34.85,
51.15, 81.37, 121.68, 125.34, 127.33, 127.62, 128.09, 128.41, 128.63,
129.33, 129.44, 135.18, 137.74, 139.99, 142.59, 166.95 ppm. LCMS:
m/z = 422 [M – H]+.
10a as a yellow solid (66%, 0.110 g); m.p. 148–150 °C. IR (KBr): ν
˜
= 2235, 1709, 1599 cm–1. 1H NMR (400 MHz, CDCl3): δ = 3.82
(d, J = 0.8 Hz, 2 H), 6.95 (d, J = 7.2 Hz, 1 H), 7.10–7.18 (m, 1 H),
7.23–7.48 (m, 13 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 33.57,
51.44, 122.25, 122.40, 123.01, 127.08, 128.22, 128.70, 128.97,
129.84, 133.62, 134.00, 139.35, 144.24, 146.48, 196.85 ppm. LCMS:
m/z = 336 [M + H]+, 334 [M – H]+. C24H17NO (335.40): calcd. C
85.94, H 5.11, N 4.18; found C 85.79, H 5.06, N 4.05.
(E)-tert-Butyl 4-Cyano-2-(4-ethylbenzylidene)-4,4-diphenylbutano-
ate (8d): Yield 79%; m.p. 84–86 °C. IR (KBr): ν = 2224, 1699,
˜
1
1624cm–1. H NMR (400 MHz, CDCl3): δ = 1.18 (t, J = 7.6 Hz, 3
H), 1.43 (s, 9 H), 2.57 (q, J = 7.6 Hz, 2 H), 3.83 (s, 2 H), 6.95 (d,
J = 8.0 Hz, 2 H), 7.01 (d, J = 8.0 Hz, 2 H), 7.15–7.36 (m, 10 H),
7.66 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.47, 28.00,
28.62, 34.85, 51.25, 81.29, 121.76, 127.40, 127.77, 127.84, 128.49,
128.81, 132.60, 140.08, 142.57, 144.28, 167.10 ppm. LCMS: m/z =
438 [M + H]+.
Crystal Data for 10a:[13] C24H17NO (335.39), yellow block-shaped
crystals, crystal dimensions: 0.36ϫ0.24ϫ0.18 mm3; crystal
system: triclinic; lattice type: primitive; lattice parameters: a =
9.3189(11) Å, b = 10.0476(12) Å, c = 10.1708(12) Å, α = 95.696(2)°,
β = 107.552(2)°, γ = 92.075(2)°; V = 901.30(18) Å3; space group:
Crystal data for 8d:[13] C30H31NO2 (437.56), colorless crystal plates,
crystal dimensions: 0.38ϫ0.32ϫ0.22 mm3, crystal system: mono-
clinic; lattice type: primitive; lattice parameters: a = 10.7663(9) Å,
b = 19.0208 (16) Å, c = 14.8036 (9) Å, α = 90.00°, β = 122.66(4)°,
γ = 90.00°; V = 2252.1 (3) Å3; space group: p 2 (1)/c; Z = 4; Dcalcd.
= 1.139 g/cm3; F(000) = 936; λ (Mo-Kα) = 0.71073 Å; R (I Ն 2σ1)
= 0.0791, wR2 = 0.2130.
p1; Z = 2; Dcalcd. = 1.236 g/cm3; F(000) = 352; λ (Mo-Kα) =
¯
0.71073 Å; R (I Ն 2σ1) = 0.0716, wR2 = 0.1586.
2-(2-Cyano-2,2-diphenylethyl)-6-isopropylind-2-en-1-one
(10b):
Yield 63%; m.p. 146–148 °C. IR (KBr): ν = 2220, 1705, 1614 cm–1.
˜
1H NMR (400 MHz, CDCl3): δ = 1.19 (d, J = 6.8 Hz, 6 H), 2.85
(sept, J = 6.8 Hz, 1 H), 3.36 (d, J = 1.6 Hz, 2 H), 6.85 (d, J =
7.2 Hz, 1 H), 7.08–7.13 (m, 1 H), 7.23–7.39 (m, 8 H), 7.40–7.47 (m,
4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.67, 33.55, 34.06,
51.46, 121.62, 122.09, 122.39, 127.05, 128.15, 128.92, 130.25,
131.51, 133.05, 139.40, 141.77, 146.71, 150.09, 197.26 ppm. LCMS:
m/z = 378 [M + H]+. C27H23NO (377.48): calcd. C 85.91, H 6.14,
N 3.71; found C 85.87, H 6.09, N 3.78.
(E)-tert-Butyl 4-Cyano-2-(4-methylbenzylidene)-4,4-diphenylbutano-
ate (8e): Yield 75%; m.p. 112–114 °C. IR (KBr): ν = 2233, 1701,
˜
1639 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.41 (s, 9 H), 2.29 (s,
3 H), 3.82 (s, 2 H), 6.95 (d, J = 8.0 Hz, 2 H), 7.01 (d, J = 8.0 Hz,
2 H), 7.18–7.40 (m, 10 H), 7.64 (s, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 21.22, 27.98, 34.90, 51.27, 81.22, 121.75, 127.39,
127.74, 128.48, 128.76, 128.92, 129.02, 132.38, 137.96, 140.10,
142.47, 167.04 ppm. LCMS: m/z = 422 [M – H]+.
2-(2-Cyano-2,2-diphenylethyl)-5-methylind-2-en-1-one (10c): Yield
1
64%; m.p. 138–140 °C. IR (KBr): ν = 2220, 1701, 1620 cm–1. H
˜
(E)-tert-Butyl 2-(3-Bromobenzylidene)-4-cyano-4,4-diphenylbutano-
NMR (400 MHz, CDCl3): δ = 2.41 (s, 3 H), 3.36 (s, 2 H), 6.76 (d,
J = 7.2 Hz, 1 H), 6.90 (d, J = 8.0 Hz, 1 H), 7.10–7.16 (m, 1 H),
ate (8f): Yield 80%; m.p. 121–122 °C. IR (KBr): ν = 2235, 1701,
˜
1635 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.49 (s, 9 H), 3.77 (s, 7.20 (s, 1 H), 7.23–7.38 (m, 6 H), 7.39–7.48 (m, 4 H) ppm. 13C
2 H), 6.83–6.98 (m, 2 H), 7.00–7.09 (m, 1 H), 7.10–7.35 (m, 11 H), NMR (100 MHz, CDCl3): δ = 17.13, 33.45, 51.31, 120.07, 122.40,
7.56 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 28.07, 34.80, 126.36, 127.04, 128.12, 128.91, 131.85, 133.21, 133.37, 137.80,
51.08, 81.96, 121.52, 122.57, 126.74, 127.40, 127.95, 128.56, 129.77,
130.74, 131.02, 131.34, 137.45, 139.75, 140.66, 166.56 ppm. LCMS:
m/z = 488 [M + H]+, 490 [M + 2 + H]+.
139.40, 144.52, 145.26, 197.81 ppm. LCMS: m/z = 350 [M + H]+.
C25H19NO (349.43): calcd. C 85.93, H 5.48, N 4.01; found C 86.10,
H 5.51, N 4.07.
Eur. J. Org. Chem. 2010, 5650–5658
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5655

D. Basavaiah, D. V. Lenin
FULL PAPER
2-(2-Cyano-2,2-diphenylethyl)-6-ethylind-2-en-1-one (10d): Yield
7.96 (s, 1 H), 8.09 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
30.62, 47.68, 125.87, 127.87, 128.15, 128.73, 128.91, 129.45, 129.83,
1
70%; m.p. 122–124 °C. IR (KBr): ν = 2220, 1709, 1604 cm–1. H
˜
NMR (400 MHz, CDCl3): δ = 1.18 (t, J = 7.6 Hz, 3 H), 2.57 (q, J 134.40, 136.85, 140.97, 166.67, 172.64 ppm. LCMS: m/z = 278 [M
= 7.6 Hz, 2 H), 3.36 (s, 2 H), 6.84 (d, J = 7.2 Hz, 1 H), 7.08 (d, J
= 7.6 Hz, 1 H), 7.19 (s, 1 H), 7.23–7.38 (m, 7 H), 7.39–7.48 (m, 4
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.26, 28.68, 33.46,
51.42, 122.06, 122.36, 122.99, 127.01, 128.12, 128.88, 130.17,
132.73, 132.88, 139.33, 141.57, 145.31, 146.71, 197.17 ppm. LCMS:
m/z = 364 [M + H]+. C26H21NO (363.46): calcd. C 85.92, H 5.82,
N 3.85; found C 85.96, H 5.79, N 3.71.
+ H]+, 310 [M + H + MeOH]+. C18H15NO2 (277.32): calcd. C
77.96, H 5.45, N 5.05; found C 77.85, H 5.41, N 5.14.
(E)-3-(3-Methylbenzylidene)-5-phenylpiperidine-2,6-dione
(4b):
Yield 75%; m.p. 162–164 °C. IR (KBr): ν = 3200–2900 (multiple
˜
1
bands), 1720, 1697, 1626 cm–1. H NMR (400 MHz, CDCl3): δ =
2.35 (s, 3 H), 3.14–3.26 (m, 1 H), 3.28–3.42 (m, 1 H), 3.80–3.90 (m,
1 H), 7.08–7.42 (m, 9 H), 7.93 (s, 1 H), 8.10 (s, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 21.49, 30.66, 47.79, 125.65, 126.88,
127.92, 128.20, 128.65, 128.97, 130.34, 130.55, 134.41, 136.95,
138.53, 141.32, 166.66, 172.69 ppm. LCMS: m/z = 292 [M + H]+,
324 [M + H + MeOH]+. C19H17NO2 (291.35): calcd. C 78.33, H
5.88, N 4.81; found C 78.45, H 5.93, N 4.76.
2-(2-Cyano-2,2-diphenylethyl)-6-methylind-2-en-1-one (10e): Yield
1
60%; m.p. 141–142 °C. IR (KBr): ν = 2220, 1705, 1620 cm–1. H
˜
NMR (400 MHz, CDCl3): δ = 2.28 (s, 3 H), 3.36 (d, J = 1.2 Hz, 2
H), 6.83 (d, J = 7.2 Hz, 1 H), 7.03–7.09 (m, 1 H), 7.15 (s, 1 H),
7.27–7.38 (m, 7 H), 7.40–7.46 (m, 4 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 21.32, 33.51, 51.48, 122.00, 122.41, 124.15, 127.07,
128.15, 128.91, 130.16, 132.84, 133.79, 138.89, 139.38, 141.39,
146.71, 197.14 ppm. LCMS: m/z = 350 [M + H]+, 382 [M + H +
MeOH]+. C25H19NO (349.43): calcd. C 85.93, H 5.48, N 4.01;
found C 85.97, H 5.39, N 4.07.
(E)-3-Benzylidene-5,5-diphenylpiperidine-2,6-dione (11a): To
a
stirred solution of 8a (0.5 mmol, 0.205 g) in DCE (3 mL), were
added CH3SO3H (1.5 mmol, 0.144 g, 0.098 mL) and TFAA
(1 mmol, 0.210 g, 0.14 mL) at r.t. The reaction mixture was heated
to reflux for 4 h and then allowed to cool to r.t. and poured into
aqueous K2CO3 and extracted with EtOAc (2ϫ10 mL). The com-
bined organic layer was dried with anhydrous Na2SO4, the solvent
was evaporated and the residue, thus obtained, was purified by col-
umn chromatography (ethyl acetate/hexanes, 25%) to provide 11a
5-Bromo-2-(2-cyano-2,2-diphenylethyl)ind-2-en-1-one (10f): Yield
1
66%; m.p. 168–170 °C. IR (KBr): ν = 2220, 1714, 1601 cm–1. H
˜
NMR (400 MHz, CDCl3): δ = 3.39 (s, 2 H), 7.11 (s, 1 H), 7.18 (d,
J = 7.6 Hz, 1 H), 7.25–7.46 (m, 12 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 33.65, 51.41, 122.28, 124.14, 125.76, 127.08, 128.35,
128.40, 128.81, 129.06, 131.41, 135.09, 139.20, 145.12, 146.11,
195.46 ppm. LCMS (m/z): 414 [M + H]+, 416 (M + 2 + H)+.
C24H16BrNO (414.30): calcd. C 69.58, H 3.89, N 3.38; found C
69.48, H 3.82, N 3.45.
as a colorless solid (85%, 0.150 g); m.p. 218–221 °C. IR (KBr): ν
˜
= 3150–2900 (multiple bands), 1714, 1685, 1608 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 3.64 (s, 2 H), 6.95–7.08 (m, 4 H), 7.19–
7.52 (m, 11 H), 7.85 (s, 1 H), 8.32 (br. s, 1 H) ppm. 13C NMR
(100 MHz, 50% [D6]DMSO in CDCl3): δ = 34.34, 55.59, 125.84,
126.51, 126.69, 127.23, 127.66, 127.90, 133.02, 137.66, 139.16,
164.76, 172.80 ppm. LCMS: m/z = 354 [M + H]+. C24H19NO2
(353.42): calcd. C 81.56, H 5.42, N 3.96; found C 81.48, H 5.48, N
4.05.
2-(2-Cyano-2,2-diphenylethyl)-4-methylind-2-en-1-one (10g): Yield
1
62%; m.p. 116–119 °C. IR (KBr): ν = 2239, 1703, 1621 cm–1. H
˜
NMR (400 MHz, CDCl3): δ = 2.18 (s, 3 H), 3.37 (s, 2 H), 6.98–
7.04 (m, 1 H), 7.06 (d, J = 7.6 Hz, 1 H), 7.15 (d, J = 6.8 Hz, 1 H),
7.21–7.46 (m, 11 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 16.95,
33.53, 51.56, 120.70, 122.41, 127.12, 128.18, 128.57, 128.91, 129.75,
131.53, 132.82, 135.85, 139.39, 142.09, 144.90, 197.15 ppm. LCMS:
m/z = 350 [M + H]+. C25H19NO (349.43): calcd. C 85.93, H 5.48,
N 4.01; found C 85.96, H 5.41, N 4.10.
Crystal Data for 11a:[13] C24H19NO2 (353.40), colorless crystals,
block-shaped, crystal dimensions: 0.28ϫ0.20ϫ0.18 mm3; crystal
system: monoclinic; lattice type: primitive; lattice parameters: a =
7.2161(6) Å, b = 18.4306(16) Å, c = 13.8854(12) Å, α = 90.00°, β =
98.373(2)°, γ = 90.00°; V = 1827.0(3) Å3; space group: P2(1)/c; Z
= 4; Dcalcd. = 1.285 g/cm3; F(000) = 744; λ (Mo-Kα) = 0.71073 Å;
R (I Ն 2σ1) = 0.0404, wR2 = 0.0859.
12-(2-Cyano-2,2-diphenylethyl)tricyclo[8.3.0.02,7]trideca-1(10),2(7),-
3,5,8,12-hexaen-11-one (10h): Yield 64%; m.p. 184–186 °C. IR
(KBr): ν = 2220, 1712, 1620 cm–1. 1H NMR (400 MHz, CDCl ): δ
(E)-3-(4-Isopropylbenzylidene)-5,5-diphenylpiperidine-2,6-dione
˜
3
(11b): Yield 86%; m.p. 207–208 °C. IR (KBr): ν = 3150–2920 (mul-
˜
= 3.45 (s, 2 H), 7.27–7.41 (m, 6 H), 7.42–7.53 (m, 7 H), 7.65 (d, J
= 8.0 Hz, 1 H), 7.73–7.82 (m, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 33.55, 51.58, 119.25, 122.46, 123.21, 125.38, 126.65,
127.12, 127.17, 128.22, 128.25, 128.47, 128.80, 128.94, 132.08,
137.37, 139.33, 142.48, 143.48, 197.76 ppm. LCMS: m/z = 386 [M
+ H]+. C28H19NO (385.46): calcd. C 87.25, H 4.97, N 3.63; found
C 87.16, H 5.02, N 3.71.
1
tiple bands), 1710, 1685, 1624 cm–1. H NMR (400 MHz, CDCl3):
δ = 1.28 (d, J = 6.8 Hz, 6 H), 2.95 (sept, J = 6.8 Hz, 1 H), 3.66 (d,
J = 1.2 Hz, 2 H), 7.00–7.10 (m, 4 H), 7.22–7.37 (m, 10 H), 7.83 (s,
1 H), 8.18 (br. s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
23.78, 34.04, 36.54, 57.44, 125.38, 126.95, 127.66, 128.23, 128.45,
129.90, 132.02, 140.27, 141.29, 150.65, 166.40, 174.15 ppm. LCMS:
m/z = 396 [M + H]+. C27H25NO2 (395.50): calcd. C 82.00, H 6.37,
N 3.54; found C 82.15, H 6.30, N 3.61.
(E)-3-Benzylidene-5-phenylpiperidine-2,6-dione (4a): To a stirred
solution of (E)-tert-butyl 2-benzylidene-4-cyano-4-phenylbutanoate
(2a; 0.5 mmol, 0.167 g) in DCE (3 mL), were added CH3SO3H
(1.5 mmol, 0.144 g, 0.098 mL) and TFAA (1 mmol, 0.210 g,
0.14 mL) at r.t. The reaction mixture was heated to reflux for 4 h
and then allowed to cool to r.t. The reaction mixture was poured
into aqueous K2CO3 and extracted with EtOAc (2ϫ10 mL). The
combined organic layer was dried with anhydrous Na2SO4, the sol-
vent was evaporated and the residue, thus obtained, was purified
by column chromatography (ethyl acetate/hexanes, 25%) to provide
(E)-3-(3-Methylbenzylidene)-5,5-diphenylpiperidine-2,6-dione (11c):
Yield 81%; m.p. 207–208 °C. IR (KBr): ν = 3150–2925 (multiple
˜
1
bands), 1699, 1685, 1618 cm–1. H NMR (400 MHz, CDCl3): δ =
2.38 (s, 3 H), 3.63 (d, J = 1.6 Hz, 2 H), 6.98–7.18 (m, 4 H), 7.11–
7.38 (m, 10 H), 7.81 (s, 1 H), 8.27 (br. s, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 21.50, 36.39, 57.55, 126.09, 126.57, 127.72,
128.23, 128.48, 128.70, 130.27, 130.33, 134.52, 138.56, 140.15,
141.55, 166.29, 174.14 ppm. LCMS: m/z = 368 [M + H]+.
C25H21NO2 (367.45): calcd. C 81.72, H 5.76, N 3.81; found C
81.65, H 5.71, N 3.92.
4a as a colorless solid (70%, 0.098 g); m.p. 172–174 °C. IR (KBr):
1
ν = 3150–2900 (multiple bands), 1714, 1687, 1616 cm–1. H NMR
˜
(400 MHz, CDCl3): δ = 3.15–3.27 (m, 1 H), 3.30–3.42 (m, 1 H), (E)-3-(4-Ethylbenzylidene)-5,5-diphenylpiperidine-2,6-dione (11d):
3.80–3.92 (m, 1 H), 7.21 (d, J = 6.8 Hz, 2 H), 7.28–7.48 (m, 8 H), Yield 77%; m.p. 186–188 °C. IR (KBr): ν = 3140–2915 (multiple
˜
5656
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Eur. J. Org. Chem. 2010, 5650–5658

Substituted Indenones and Piperidine-2,6-diones
1
bands), 1716, 1682, 1620 cm–1. H NMR (400 MHz, CDCl3): δ =
strumental facilities. We thank the National Single-Crystal X-ray
1.27 (t, J = 7.2 Hz, 3 H), 2.68 (q, J = 7.2 Hz, 2 H), 3.65 (s, 2 H), facility, funded by DST. We thank Prof. S. Pal, School of Chemis-
6.98–7.07 (m, 4 H), 7.22–7.37 (m, 10 H), 7.83 (s, 1 H), 8.13 (br. s,
1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.17, 28.71, 36.50,
57.39, 125.41, 127.58, 128.17, 128.30, 128.38, 129.83, 131.88,
140.26, 141.20, 145.98, 166.50, 174.16 ppm. LCMS: m/z = 382 [M
+ H]+. C26H23NO2 (381.47): calcd. C 81.86, H 6.08, N 3.67; found
C 81.92, H 6.13, N 3.58.
try, University of Hyderabad for helpful discussions regarding the
X-ray crystal structures.
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(E)-3-(4-Methylbenzylidene)-5,5-diphenylpiperidine-2,6-dione (11e):
Yield 80%; m.p. 228–230 °C. IR (KBr): ν = 3150–2925 (multiple
˜
1
bands), 1712, 1682, 1625 cm–1. H NMR (400 MHz, CDCl3): δ =
2.40 (s, 3 H), 3.65 (s, 2 H), 6.98–7.07 (m, 4 H), 7.22–7.35 (m, 10
H), 7.82 (s, 1 H), 8.06 (br. s, 1 H) ppm. 13C NMR (100 MHz,
50% [D6]DMSO in CDCl3): δ = 19.81, 34.48, 55.51, 124.74, 124.98,
125.84, 126.55, 126.70, 127.99, 128.07, 130.12, 137.74, 139.25,
164.81, 172.80 ppm. LCMS: m/z = 368 [M + H]+. C25H21NO2
(367.45): calcd. C 81.72, H 5.76, N 3.81; found C 81.57, H 5.82, N
3.76.
(E)-3-(3-Bromobenzylidene)-5,5-diphenylpiperidine-2,6-dione (11f):
Yield 82%; m.p. 138–140 °C. IR (KBr): ν = 3150–2945 (multiple
˜
1
bands), 1715, 1690, 1614 cm–1. H NMR (400 MHz, CDCl3): δ =
3.58 (s, 2 H), 6.97–7.05 (m, 4 H), 7.20–7.32 (m, 8 H), 7.41 (s, 1 H),
7.51 (d, J = 7.6 Hz, 1 H), 7.73 (s, 1 H), 8.61 (br. s, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 36.14, 57.57, 122.92, 127.77, 127.81,
127.85, 128.15, 128.56, 130.35, 132.12, 132.34, 136.59, 139.43,
139.94, 165.85, 173.89 ppm. LCMS: m/z = 432 [M + H]+, 434 [M
+ 2 + H]+. C24H18BrNO2 (432.32): calcd. C 66.68, H 4.20, N 3.24;
found C 66.57, H 4.26, N 3.29.
(E)-3-(2-Methylbenzylidene)-5,5-diphenylpiperidine-2,6-dione (11g):
Yield 75%; m.p. 182–184 °C. IR (KBr): ν = 3150–2925 (multiple
˜
1
bands), 1716, 1682, 1622 cm–1. H NMR (400 MHz, CDCl3): δ =
2.14 (s, 3 H), 3.52 (d, J = 1.6 Hz, 2 H), 6.94–7.01 (m, 4 H), 7.13
(d, J = 7.6 Hz, 1 H), 7.18–7.38 (m, 9 H), 7.86 (s, 1 H), 8.18 (br. s,
1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 19.80, 36.30, 57.68,
125.86, 126.84, 127.69, 128.12, 128.47, 128.86, 129.40, 130.44,
133.59, 137.64, 140.06, 140.80, 166.27, 174.17 ppm. LCMS: m/z =
368 [M + H]+. C25H21NO2 (367.45): calcd. C 81.72, H 5.76, N 3.81;
found C 81.65, H 5.81, N 3.88.
(E)-3-(Naphth-1-ylmethylidene)-5,5-diphenylpiperidine-2,6-dione
(11h): Yield 79%; m.p. 158–160 °C. IR (KBr): ν = 3150–2920 (mul-
˜
1
tiple bands), 1722, 1685, 1624 cm–1. H NMR (400 MHz, CDCl3):
δ = 3.54 (s, 2 H), 6.92 (d, J = 7.6 Hz, 4 H), 7.08–7.61 (m, 10 H),
7.71 (d, J = 8.4 Hz, 1 H), 7.86–7.98 (m, 2 H), 8.13 (br. s, 1 H), 8.35
(s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 36.85, 57.59,
124.70, 125.13, 126.61, 126.83, 126.99, 127.66, 128.16, 128.34,
128.47, 128.67, 129.84, 131.44, 131.69, 133.57, 139.90, 140.03,
166.02, 174.22 ppm. LCMS: m/z = 404 [M + H]+. C28H21NO2
(403.48): calcd. C 83.35, H 5.25, N 3.47; found C 83.24, H 5.31, N
3.55.
Supporting Information (see also the footnote on the first page of
this article): 1H and 13C NMR spectra for all the indenones 5a,
5b, 7a, 7b, and 10a–h and piperidine-2,6-diones 4a, 4b, and 11a–h.
ORTEP diagrams of compound 8d (Figure S1), 10a (Figure S2),
and 11a (Figure S3).
Acknowledgments
We thank the Department of Science and Technology (DST) (New
Delhi) for funding this project. D. V. L. thanks the University
Grants Commission (UGC) (New Delhi) for his fellowship. We
thank UGC (New Delhi) for support and for providing some in-
Eur. J. Org. Chem. 2010, 5650–5658
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5657

D. Basavaiah, D. V. Lenin
FULL PAPER
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[9]
[10]
[11]
We also isolated approximately 20–30 mg of an unknown im-
pure product in the 0.5 mmol scale reaction. Although there
was no significant formation of the tetralone derivatives, the
presence of some minor amounts of such derivatives is not
ruled out because the yields of the indenone derivatives was
only 38–40%.
Chemical shifts of the β-vinyl protons cis to the carbonyl group
(ketone, ester, acid, and amide) were well differentiated from
those of corresponding β-vinyl protons trans to the carbonyl
1
group in the H NMR spectrum of trisubstituted alkenes. The
vinylic β-protons cis to the carbonyl group appear downfield
in comparison with those of vinylic β-protons trans to the car-
bonyl group.[5a,9a,9b,9d,9e] See also: L. M. Jackman, S. Sternhell,
Applications of nuclear magnetic resonance spectroscopy in or-
ganic chemistry, 2nd ed., Pergamon, Oxford, 1969, vol. 5; S. W.
Tobey, J. Org. Chem. 1969, 34, 1281–1298].
[12]
We also isolated approximately 30–40% of the trans-cinnamic
acid (in addition to the desired indenone derivative).
[13] Detailed X-ray crystallographic data is available from the Cam-
bridge Crystallographic Data Centre, 12 Union road, Cam-
bridge CB2 1EZ, UK, for compounds 8d (CCDC-775027), 10a
(CCDC-775028), and 11a (CCDC-776461).
[14] In this case also the formation of minor amounts of the tet-
ralone derivative cannot be ruled out because the yields of the
products were not quantitative.
[15] This compound was prepared by reduction of tert-butyl 3-ace-
toxy-2-methylene-3-phenylpropanoate with NaBH4 in tBuOH
following the known procedure developed by our research
group.[8x] Compound 7a is known in the literature and its spec-
1
troscopic data (IR, H NMR, and 13C NMR) are also report-
ed.[3k,3l] Our data is in agreement with those reported in the
literature.
[16] Literature report[3l] indicates that 7a is a low melting solid (44–
46 °C). Since yields of the compound were very low, we did not
attempt to obtain the compound as a solid.
Received: May 21, 2010
Published Online: August 24, 2010
5658
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Eur. J. Org. Chem. 2010, 5650–5658