Triphenylphosphine catalyzed, one-pot, multicomponent synthesis of spirooxindoles

Article abstract of DOI:10.2174/157017812800221771

Multicomponent reaction involving isatin (1), malononitrile (2), and dimedone (3), in the presence of triphenylphosphine as an efficient catalyst in the eco-friendly solvent ethanol, results in the formation of spirooxindole derivatives 4 i.e 2-Amino-5-oxo-7,7-dimethyl spiro[(4H)-5,6,7,8- tetrahydrochromene-4,3-(3H)-indol]-(10H)-2-onecarbonitrile. The reaction proceeds smoothly under mild conditions and the products are obtained in good to excellent yields. This method is applicable to a variety of isatin derivatives.

Full text of DOI:10.2174/157017812800221771

Letters in Organic Chemistry, 2012, 9, 101-105
101
Triphenylphosphine Catalyzed, One-Pot, Multicomponent Synthesis of
Spirooxindoles
Syed Riyaz*, A. Naidu and Pramod K. Dubey
Department of Chemistry, Jawaharlal Nehru Technological University Hyderabad College of Engineering, Kukatpally,
Hyderabad (A.P), 500 085, India
Received July 22, 2011: Revised September 14, 2011: Accepted October 19, 2011
Abstract: Multicomponent reaction involving isatin (1), malononitrile (2), and dimedone (3), in the presence of
triphenylphosphine as an efficient catalyst in the eco-friendly solvent ethanol, results in the formation of spirooxindole
derivatives
4 i.e 2-Amino-5-oxo-7,7-dimethyl spiro[(4H)-5,6,7,8-tetrahydrochromene-4,3-(3H)-indol]-(10H)-2-one-
carbonitrile. The reaction proceeds smoothly under mild conditions and the products are obtained in good to excellent
yields. This method is applicable to a variety of isatin derivatives.
Keywords: Cyclo addition, multicomponent reaction, spirooxindoles, triphenylphosphine.
INTRODUCTION
methodology for the preparation of spirooxindoles via
multicomponent reaction with triphenylphosphine [7, 8] as
an efficient catalyst and ethanol as an eco-friendly solvent.
Spirocyclic compounds represent a prominent class of
naturally occurring substances with highly pronounced
biological properties [1]. The spirooxindole system is the
core structure of many pharmaceutical agents and natural
alkaloids. Thus, the development of new and simple
synthetic methods for the preparation of spirooxindole
derivatives has become an interesting synthetic challenge.
Consequently, many synthetic methodologies have been
developed for constructing these spirooxindole derivatives,
most of which are based on cycloaddition or condensation
To realize the reaction shown in Scheme 1, isatin 1,
malononitrile 2, dimedone 3 and TPP (10mol%) were
refluxed for 20-30 min to afford the corresponding
spirooxindole product (Table 1). The reaction was examined
in different solvents including acetonitrile, methanol, ethyl
acetate and ethanol. The best results were obtained in ethanol
medium (Table 1).
R1
R2
R
R2 R1
O
CN
X
O
PPh3
EtOH
O
+
+
R
ꢀ
NH2
O
O
O
N
H
0.5-1hr
X
3 a,b
2 a,b
N
H
O
1
a) R1=H
a) X = CN
b) X = COOEt
b) R2=CH3
4a-p
Scheme 1.
reactions [2]. Particularly, domino multicomponent reactions
have emerged as an efficient and powerful tool for the
synthesis of complex molecules as a one-pot procedure [3].
Several reactions for the synthesis of spirooxindole through
multicomponent reactions have been developed, by using
In order to investigate the scope of these conditions,
several examples were studied and are summarized in Table
2. In all cases, the three component reaction proceeded
smoothly to give the corresponding spirooxindoles in good
yields. As shown in Table 2, it was found that this method
works with wide scope of substrates. A variety of various
halo substituted isatins and different 1,3-cyclohexanedione
were subjected to this reaction. Additionally, the reaction
with ethyl cyanoacetate or malononitrile also proceeded
without any side products formation. However, we observed
that the reaction time of ethyl cyanoacetate with isatins and
cyclic 1,3-dicarbonyl compounds was longer than those with
malononitrile, which is probably due to the lower reactivities
of the cyanoacetates, when compared with malononitrile.
indium(III) chloride [4] as
a
Lewis acid catalyst,
triethylamine [5] as lewis base and electrocatalysis [6].
However, the above mentioned reported methods suffer from
the usage of costly rare earth metals and toxic solvents such
as acetonitrile [4]. Herein, we developed a new and simple
*Address correspondence to this author at the Department of Chemistry,
Jawaharlal Nehru Technological University Hyderabad College of
Engineering, Kukatpally, Hyderabad (A.P), 500 085, India; Tel: +91-40-
23158661 Fax: 040-23158661; E-mail: riyazsd@gmail.com
1875-6255/12 $58.00+.00
© 2012 Bentham Science Publishers

102 Letters in Organic Chemistry, 2012, Vol. 9, No. 2
Riyaz et al.
R
R
OH
PPh3
O
O
CN
H
R
PPh3
O
COEt
PPh3
O
O
N
(1)
N
H
(2)
N
O
H
H
R
R
R
OH
CN
COEt
CN
OH
COEt
CN
-TPP
-H2O
O
O
N
H
O
O
O
N
H
N
COEt
H
(X)
O
R1
R2
R1
R2
OH
R
OH
C
O
CN
COEt
R
R
O
O
CN
COEt
N
R2
R1
COEt
O
O
O
O
O
O
N
H
(X)
N
H
R1
N
H
O
O
(Y)
(XI)
R2
R2
R1
O
C
R
O
O
NH
NH2
R
COEt
O
COEt
N
H
O
O
O
N
H
(4)
(YI)
Scheme 2.
Two possible mechanisms have been proposed to account
in the Scheme 3, TPP plays a typical base role by abstracting
a proton from active methylene group to afford the
intermediate X with the subsequent Michael addition to yield
the final product. In this study, all the derivatives were
characterized by melting point, IR, NMR and Mass spectral
data, as well as by elemental analyses.
for the formation of 4 from 1, 2 and 3. In the first mechanism
proposed (Scheme 2), the reaction includes
a fast
Knoevenagel condensation catalyzed by TPP in ethanol
between isatin and the active methylene group of the cyano
derivative to yield an ꢀ, ꢁ- unsaturated nitrile intermediate
(X). The formed knoevenagel intermediate is then attacked
by the enol form of cyclic 1,3-diketo compound (Michael
addition) followed by a keto-enol tautomerization to furnish
the enol intermediate (XI). Nucleophilic addition of the
hydroxyl group of intermediate (Y) to the cyano moiety
afforded imine intermediate (YI), which finally underwent
further reaction to give the desired product.
CONCLUSION
In conclusion, we have described a simple one-pot three
component reaction involving isatin, activated methylene
compound and cyclic 1,3-diketo compound to yield a series
of spirooxindoles derivatives using TPP as a novel and
inexpensive catalyst. Furthermore, this methodology
conveniently afforded the desired products in good yields
under mild conditions with operational simplicity.
In the second probable mechanism (Scheme 3), the lone
pair on the TPP abstracts the proton from the active
methylene group of the cyano derivative to afford carbanion
species, which further attacks the carbonyl group of the
isatin to result in a C-C bond intermediate. Loss of water
molecule gives the ꢀ, ꢁ- unsaturated nitrile intermediate (X).
The formation of the final product spirooxindole 4 from X is
similar to that as shown in the Scheme 2.
EXPERIMENTAL SECTION
Melting points were uncorrected and determined in open
capillary tubes in sulphuric acid bath. Thin-layer
chromatography (TLC) was performed on silica gel G, and
spotting was done using iodine or UV light. IR spectra were
recorded with Jasco FT-IR 5300, 1H NMR on Varian 400-
MHz instrument, and Mass spectra on an Agilent LC-MS
instrument giving only M+. values in Q+1 mode.
In substance, it can be said that the two mechanisms
(shown in Scheme 2 and Scheme 3) differ from one another
in that the Scheme 2 involves a C-P bond formation between
isatin and TPP to result in the intermediate X followed by
Michael addition with cyclic-1,3-diketo compound, whereas

Triphenylphosphine Catalyzed, One-Pot, Multicomponent Synthesis
Letters in Organic Chemistry, 2012, Vol. 9, No. 2
103
H
CN
CN
CN
Ph3P
Ph3P
H
+
COOEt
CN
O
CN
COOEt
OH
OH
CN
Ph3P
O
H
COOEt
- TPP
COOEt
O
- H2O
N
O
O
N
N
H
N
H
H
H
R1
R2
R1
R2
OH
R
OH
C
O
CN
COEt
R
R
O
O
CN
N
R2
R1
COEt
O
COEt
O
O
O
O
O
O
O
N
H
(X)
N
H
R1
N
H
(Y)
(XI)
R2
R2
R1
O
R
O
O
C
NH
COEt
NH2
R
O
COEt
O
N
H
O
O
N
H
(YI)
(4)
Scheme 3.
Table 1. Rate of Reaction in Different Solvent Mediums
Entry
Solvent
Time (hrs)
Yield(%)
1
2
3
4
Methanol
Ethylacetate
Acetonitrile
Ethanol
1.5
3.0
2.0
0.5
80-85
78-85
85-90
90-95
Table 2. TPP Catalyzed One-Pot Multi Component Synthesis of Spirooxindoles 4
Entry
(3)
Yield(%)
M.P (Lit) (oC)
(1)
R
(2)
X
Product
(4)
R1
R2
1
2
3
4
5
H
H
H
H
F
CN
COOEt
CN
H
H
4a
4b
4c
4d
4e
92
85
94
89
93
>300
(304-305)
H
H
265-267
(263-265)6
270-272
(268-270)4
CH3
CH3
H
CH3
CH3
H
COOEt
CN
260-262
(257-258) 6
275-277

104 Letters in Organic Chemistry, 2012, Vol. 9, No. 2
Riyaz et al.
(Table 2). Contd…..
Entry
(3)
Yield(%)
M.P (Lit) (oC)
(1)
R
(2)
X
Product
(4)
R1
R2
6
F
F
COOEt
CN
H
H
4f
4g
4h
4i
88
86
83
93
87
92
85
91
86
93
89
270-272
(273-74)6
268-270
7
CH3
CH3
H
CH3
CH3
H
(270-272)6
8
F
COOEt
CN
238-240
(240-42)6
274-276
9
Cl
Cl
Cl
Cl
I
10
11
12
13
14
15
16
COOEt
CN
H
H
4j
281-283
CH3
CH3
H
CH3
CH3
H
4k
4l
290-292
(289-291)6
275-278
COOEt
CN
4m
4n
4o
4p
277-279
280-282
>300
I
COOEt
CN
H
H
I
CH3
CH3
CH3
CH3
I
COOEt
281-283
General Procedure
mixture of appropriate isatin (1, 1.0mmol),
4i: IR (KBr): 3405, 3316 (unequal doublet, asymmetric
and symmetric stretching of -NH2), 2201 (-CN group, sharp),
1720 (-C=O of chromene moiety, sharp), 1645cm-1 (-C=O of
A
malononitrile or ethyl cyanoacetate (2, 1.0mmol),
appropriate 1,3-dicarbonyl (3, 1.0mmol) and catalytic
amount of TPP in EtOH (15ml) were refluxed for 20-30
mins at 780C and then cooled to R.T. The separated solid
was collected by filtration, washed with excess of EtOH
(5ml), and dried in oven to obtain crude 4. The latter, was
recrystallized from MeOH to get pure 4.
1
isatin amide group, broad), H- NMR (400MHz, DMSO-
d6/TMS): ꢀ 1.89 -2.81 (m, 6H –(CH2)3, 6.52-7.28 (m, 3H
aromatic), 7.19 (S, 2H, -NH2, D2O exchangeable), 10.55 (s,
1H, -NH, D2O exchangeable) m/z: (M++1): 342.
4j: IR (KBr): 3395, 3303 (unequal doublet, asymmetric
and symmetric stretching of -NH2), 2208 (-CN group, sharp),
1742 (-C=O of ester group), 1710 (-C=O of chromene
moiety, sharp), 1655cm-1 (-C=O of isatin amide group,
broad), 1H- NMR (400MHz, DMSO-d6/TMS): ꢀ 0.94 (t, 3H,
-COOCH2CH3), 1.86 -2.85 (m, 6H –(CH2)3), 3.62(m, 2H, , -
COOCH2CH3) 6.61-7.33 (m, 3H aromatic), 7.15 (S, 2H, -
NH2, D2O exchangeable), 10.52 (s, 1H, -NH, D2O
exchangeable). m/z: (M++1): 389.
Spectral Data of the Selected Compounds
4a: IR (KBr): 3390, 3310 (unequal doublet, asymmetric
and symmetric stretching of -NH2), 2208 (-CN group, sharp),
1720 (-C=O of chromene moiety, sharp), 1645cm-1 (-C=O of
1
isatin amide group, broad), H- NMR (400MHz, DMSO-
d6/TMS): ꢀ 1.96 -2.95 (m, 6H –(CH2)3), 6.72-7.15 (m, 4H
aromatic), 7.25 (S, 2H, -NH2, D2O exchangeable), 10.44 (s,
1H, -NH, D2O exchangeable) M, /Z (M++1): 308.
4k: IR (KBr): 3435, 3328 (unequal doublet, asymmetric
and symmetric stretching of -NH2), 2191 (-CN group, sharp),
1715 (-C=O of chromene moiety, sharp), 1640cm-1 (-C=O
1
4e: IR (KBr): 3395, 3306 (unequal doublet, asymmetric
and symmetric stretching of -NH2), 2205 (-CN group, sharp),
1720 (-C=O of chromene moiety, sharp), 1645cm-1 (-C=O of
of isatin amide group, broad), H- NMR (400MHz, DMSO-
d6/TMS): ꢀ 1.02 (s, 3H, -CH3) 1.08 (s, 3H, -CH3), 1.95-2.13
(m, 2H), 2.35-2.63 (m, 2H), 6.76-7.29 (m, 3H aromatic),
7.32 (S, 2H, -NH2, D2O exchangeable), . m/z: (M++1): 370.
1
isatin amide group, broad), H- NMR (400MHz, DMSO-
d6/TMS): ꢀ 1.91 -2.91 (m, 6H –(CH2), 6.62-7.18 (m, 3H
aromatic), 7.24 (S, 2H, -NH2, D2O exchangeable), 10.45 (s,
1H, -NH, D2O exchangeable) m/z: (M++1): 326.
4l: IR (KBr): 3408, 3327 (unequal doublet, asymmetric
and symmetric stretching of -NH2), 2203 (-CN group, sharp),
1720 (-C=O of chromene moiety, sharp), 1645cm-1 (-C=O of

Triphenylphosphine Catalyzed, One-Pot, Multicomponent Synthesis
Letters in Organic Chemistry, 2012, Vol. 9, No. 2
105
isatin amide group, broad), 1H-NMR (400MHz, DMSO-
d6/TMS): ꢂ 0.94 (t, 3H, -COOCH2CH3), 1.02 (s, 3H, -CH3)
1.08 (s, 3H, -CH3), 1.86 -2.85 (m, 6H –(CH2)3), 3.66(m, 2H,
-COOCH2CH3), 6.61-7.33 (m, 3H aromatic), 7.15 (S, 2H, -
NH2, D2O exchangeable), 10.52 (s, 1H, -NH, D2O
exchangeable). m/z: (M++1): 417.
C. T. SpirocyclicSystems, In The Total Synthesis of Natural
Products, Vol. 5; Simon, J., Ed.; John Wiley & Sons: New York,
1983, 264
[2]
(a) Fuchs, J. R.; Funk, R. L Indol-2-one Intermediates:ꢀ
Mechanistic Evidence and Synthetic Utility. Total Syntheses of
( )-Flustramines A and C. Org. Lett. 2005, 7, 677. (b) Yong, S. R.;
Ung, A. T.; Pyne, S. G.; Skelton, B. W.; White, A. H. Syntheses of
spiro[cyclopropane-1,3ꢃ-oxindole]-2-carboxylic
acid
and
cyclopropa[c]quinoline-7b-carboxylic acid and their derivatives
Tetrahedron 2007, 63, 1191. (c) Jiang, T.; Kuhen, K. L.; Wolff, K.;
Yin, H.; Bieza, K.; Caldwell, J.; Bursulaya, B.; Wu, T. Y.-H.; He,
Y. Design, synthesis and biological evaluations of novel oxindoles
as HIV-1 non-nucleoside reverse transcriptase inhibitors. Part I
Bioorg. Med. Chem.Lett. 2006, 16, 2105. (d) Yong, S. R.;
Williams, M. C.; Pyne, S. G.; Ung, A. T.; Skelton, B. W.; White,
A.H.;Turner, P. Synthesis of 2-azaspiro[4.4]nonan-1-ones via
phosphine-catalysed [3+2]-cycloadditions Tetrahedron 2005, 61,
8120. (e) Feldman, K. S.;Vidulova, D. B.; Karatjas, A. G.
4m: IR (KBr): 3401, 3310 (unequal doublet, asymmetric
and symmetric stretching of -NH2), 2210 (-CN group, sharp),
1719 (-C=O of chromene moiety, sharp), 1642cm-1 (-C=O of
1
isatin amide group, broad), H- NMR (400MHz, DMSO-
d6/TMS): ꢂ 1.85 -2.79 (m, 6H –(CH2)3, 6.49-7.18 (m, 3H
aromatic), 7.15 (S, 2H, -NH2, D2O exchangeable), 10.49 (s,
1H, -NH, D2O exchangeable) m/z: (M++1): 434.
4n: IR (KBr): 3397, 3307 (unequal doublet, asymmetric
and symmetric stretching of -NH2), 2215 (-CN group, sharp),
1745 (-C=O of ester group), 1715 (-C=O of chromene
moiety, sharp), 1649cm-1 (-C=O of isatin amide group,
broad), 1H- NMR (400MHz, DMSO-d6/TMS): ꢂ 0.96 (t, 3H,
-COOCH2CH3), 1.84 -2.84 (m, 6H –(CH2)3), 3.59(m, 2H, , -
COOCH2CH3) 6.51-7.29 (m, 3H aromatic), 7.19 (S, 2H, -
NH2, D2O exchangeable), 10.51 (s, 1H, -NH, D2O
exchangeable). m/z: (M++1): 481.
Extending Pummerer Reaction Chemistry. Development of
a
Strategy for the Regio- and Stereoselective Oxidative Cyclization
of 3-(ꢄ-Nucleophile)-Tethered Indoles J.Org. Chem. 2005, 70,
6429. (f) Osman, F. H.; Samahy, F. A. On the Reaction of Isatin
with Cyanomethylene(triphenyl)-phosphorane.
A Nucleophilic
Attack of Alkyl Phosphites on the Carbon–Carbon Double Bond of
(E)-OxindolylideneacetonitrileTetrahedron 2000, 56, 1863. (g)
Mao, Z.; Baldwin, S. W. New Spirocyclic Oxindole Synthesis
Based on a Hetero Claisen Rearrangement. Org. Lett. 2004, 6,
2425. (h) Feldman, K. S.; Karatjas, A. G. Extending Pummerer
Reaction Chemistry. Asymmetric Synthesis of Spirocyclic
Oxindoles via Chiral Indole-2-sulfoxides. Org. Lett. 2006, 8, 4137.
(i) Marti, C.; Carreira, E. M. Total Synthesis of (ꢀ)-
Spirotryprostatin B:ꢀ Synthesis and Related Studies. J. Am. Chem.
Soc. 2005, 127, 11505. (j) Robertson, D. W.; Krushinski, J. H.;
Pollock, G. D.; Wilson, H.; Kauffman, R. F.; Hayes, J. S.
Dihydropyridazinone cardiotonics: synthesis and inotropic activity
of 5'-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-spiro[cycloalkane-
1,3'-[3H]indol]-2'(1'H)-ones. J. Med.Chem. 1987, 30, 824. (k) Lo,
M.M.-C.; Neumann, C. S.; agayama, S.; Perlstein, E. O.; Schreiber,
S. L. A Library of Spirooxindoles Based on a Stereoselective
Three-Component Coupling Reaction. J. Am. Chem. Soc. 2004,
126, 16077.
4o: IR (KBr): 3415, 3325 (unequal doublet, asymmetric
and symmetric stretching of -NH2), 2195 (-CN group, sharp),
1710 (-C=O of chromene moiety, sharp), 1635cm-1 (-C=O of
1
isatin amide group, broad), H- NMR (400MHz, DMSO-
d6/TMS): ꢂ 1.04 (s, 3H, -CH3) 1.09 (s, 3H, -CH3), 1.99-2.17
(m, 2H), 2.35-2.73 (m, 2H), 6.76-7.39 (m, 3H aromatic),
7.40 (S, 2H, -NH2), . m/z: (M++1): 462.
4p: IR (KBr): 3409, 3321 (unequal doublet, asymmetric
and symmetric stretching of -NH2), 2201 (-CN group, sharp),
1710 (-C=O of chromene moiety, sharp), 1634cm-1 (-C=O of
isatin amide group, broad), 1H-NMR (400MHz, DMSO-
d6/TMS): ꢂ 0.99 (t, 3H, -COOCH2H3), 1.05 (s, 3H, -CH3)
1.11 (s, 3H, -CH3), 1.91 -2.95 (m, 6H –(CH2)3), 3.69(m, 2H,
-COOCH2H3), 6.71-7.39 (m, 3H aromatic), 7.19 (S, 2H, -
NH2, D2O exchangeable), 10.72 (s, 1H, -NH, D2O
exchangeable). m/z: (M++1): 509.
[3]
(a) Dömling, A.; Ugi, I. Multicomponent Reactions Isocyanides.
Angew. Chem. Int. Ed. 2000, 39, 3168. (b) Dömling, A. Chem. Rev.
2006, 106, 1. (c) Zhu, J. Recent Developments in the Isonitrile-
Based Multicomponent Synthesis of Heterocycles . Eur. J. Org.
Chem. 2003, 7, 1133.
Shanthi, G.; Subbulakshmi, G.; Perumal, P. T. A new InCl3-
catalyzed, facile and efficient method for the synthesis of
spirooxindoles under conventional and solvent-free microwave
conditions Tetrahedron 2007, 63, 2057.
Litvinov,M.Y.; Mortikov.V; and Shestopalov, A.M; Versatile
Three-Component Procedure for Combinatorial Synthesis of 2-
Aminospiro[(3ꢃH)-indol-3ꢃ,4-(4H)-pyrans]. J. Comb. Chem. 2008,
10, 741.
Elinson, M. N.; Ilovaisky, A. I.; Dorofeev, A. S.; Merkulova, V.
M.; Stepanov, N. O.; Miloserdov,F. M.; Ogibin, Y. N.; Nikishin, G.
I. Electrocatalytic multicomponent transformation of cyclic 1,3-
diketones, isatins, and malononitrile: facile and convenient way to
functionalized spirocyclic (5,6,7,8-tetrahydro-4H-chromene)-4,3ꢃ-
oxindole system Tetrahedron 2007, 63, 10543 .b) Dabiri.M,
baharamnejad. M, Baghbanzadeh. M; Ammonium salt catalyzed
multicomponent transformation: simple route to functionalized
spirochromenes and spiroacridines Tetrahedron 2009, 65, 9443.
Yadav, J.S; Subba Reddy, B.V; Basak, A.K ; Visali, B; Venkata
Narsaiah, A; Nagaiah, K; Phosphane-Catalyzed Knoevenagel
Condensation: A Facile Synthesis of ꢁ-cyanoacrylates and ꢁ-
Cyanoacrylonitriles, Eur. J.Org. Chem. 2004, 546.
[4]
[5]
[6]
ACKNOWLEDGEMENTS
The authors are thankful to the authorities of Jawaharlal
Nehru Technological University Hyderabad, for providing
laboratory facilities. They are also indebted to University
Grants Commission, Government of India, New Delhi, for
providing financial support.
REFERENCES
[7]
[8]
[1]
(a) James, D. M.; Kunze, H. B.; Faulkner, D. J. Two New
Brominated Tyrosine Derivatives from the Sponge Druinella
(=Psammaplysilla) purpurea J. Nat. Prod.1991, 54, 1137. (b)
Kobayashi, J.; Tsuda, M.; Agemi, K.;Shigemiri, H.; Ishibashi, M.;
Sasaki, T.; Mikami, Y. Purealidins B and C, new bromotyrosine
alkaloids from the okinawan marine sponge psammaplysilla purea
Tetrahedron 1991, 47, 6617. (c) Sannigrahi, M. Stereocontrolled
synthesis of spirocyclics Tetrahedron 1999, 55, 9007. (d)
Heathcock, C. H.; Graham,S. L.; Pirrung, M. C.; Plavac, F.; White,
Debache, A; Mouna. A.; Ali Belfaitah.; Rhouati, S; Carboni,B; A
one-pot Biginelli synthesis of 3,4-dihydropyrimidin-2-(1H)-
ones/thiones catalyzed by triphenylphosphine as Lewis base.
Tetrahedron Lett. 2008, 49, 6119.