Schwartz reagent mediated synthesis of thiazolones and imidazolones from thiazolidine-2,4-diones and imidazolidine-2,4-diones

Article abstract of DOI:10.1016/j.tetlet.2012.12.015

A novel reduction/elimination method of thiazolidine-2,4-dione and imidazolidine-2,4-dione derivatives using Schwartz reagent to synthesize numerous thiazolones and imidazolones in a single step is reported.

Full text of DOI:10.1016/j.tetlet.2012.12.015

Tetrahedron Letters 54 (2013) 925–928
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Schwartz reagent mediated synthesis of thiazolones and imidazolones
from thiazolidine-2,4-diones and imidazolidine-2,4-diones
Srinivasa Reddy Dandepally a, Radouane Elgoummadi b, Alfred L. Williams a,b,
⇑
a Biomanufacturing Research Institute and Technology Enterprise (BRITE), North Carolina Central University, Durham, NC 27707, USA
b Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC 27707, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 June 2012
Revised 1 December 2012
Accepted 5 December 2012
Available online 13 December 2012
A novel reduction/elimination method of thiazolidine-2,4-dione and imidazolidine-2,4-dione derivatives
using Schwartz reagent to synthesize numerous thiazolones and imidazolones in a single step is reported.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Schwartz reagent
Reduction/elimination
Thiazolones
Imidazolones
Imidazolone motifs are prevalent in many natural products1 and
have been used in the development of novel drug molecules.2 Thia-
zolone-based compounds are known to act as anticancer agents,3
generally, imidazolones and thiazolones are prepared from their
imidazolidine-2,4-dione and thiazolidine-2,4-dione precursors by
the metal hydride reduction of the lactam carbonyl group and the
subsequent dehydration of lactamol.4 Recently, during the course
of this study, a catalytic monoreduction of imidazolidine-2,4-
diones using tetra-n-butylammonium fluoride and polymethylhyd-
rosilaxane to obtain imidazolones has been reported.5 We have
previously prepared the N-alkylated imidazolone precursors in
two steps, by LiAlH4 or NaBH4 reduction of hydantoin derivatives
followed by an elimination using MsCl and excess of DIPEA.6
Schwartz reagent (Cp2Zr(H)Cl) mediated hydrozirconation of
alkenes and alkynes has been widely used in organic synthesis.7
Owing to its outstanding usefulness as a hydrozirconation reagent
and the ease of preparation, the scope and limitations of
Cp2Zr(H)Cl have been well investigated.8 The hydridic character
of Cp2Zr(H)Cl has also been demonstrated in its ability to reduce
a variety of carbonyl functionalities to Zr alkoxides at a rate
competitive with alkene and alkyne hydrozirconation.8g It reduces
nitrlies,8e,g isonitriles, epoxides, esters, ketones,9a thioketones,9b
aldehydes,9c lactones,9d lithium enolates,9e silyl esters,9f,g benzyl
esters, t-butyl esters,9h phosophine oxides and sulfides.9i Ganem
and co-workers have developed a method to prepare the imine
intermediates by a selective reduction of secondary amides and
lactams using Cp2Zr(H)Cl in THF followed by a nonaqueous work-
up.10 The chemoselective reduction of tertiary amides to aldehydes
via Cp2Zr(H)Cl was studied in detail by Georg and co-workers.11
Herein, we report our findings of Cp2Zr(H)Cl mediated synthesis
of thiazolones and imidazolones from their thiazolidine-2,4-dione
and imidazolidine-2,4-dione substrates.
During a model study towards the synthesis of
a-conhydrine,
we attempted to convert 3-(4-bromobut-3-ynyl)thiazolodine-
2-4-dione (1)12 into (Z)-3-(4-bromobut-3-enyl)thiazolodine-2-4-
dione (3) using dicyclohexylborane.13 This reaction resulted in an
inseparable (1:2) mixture of 3 and starting material 1. We next fo-
cused our attention on using Schwartz reagent. In the literature,
there are many reports on the hydrozirconation of alkyl or aromatic
disubstituted alkynes8 but, to the best of our knowledge, there are
none on alkynes substituted with a halogen group. When 1 was re-
acted with Cp2Zr(H)Cl (2 equiv), in anhydrous THF at ambient tem-
perature, we were surprised to see that a reduction/elimination
reaction occurred giving 3-(4-bromobut-3-ynyl)thiazol-2(3H)-one
(2) as the only product with some unreacted starting material 1
(Scheme 1). Attempts to consume 1 by using excess of Cp2Zr(H)Cl
(3–4 equiv) were not successful and resulted in a mixture of prod-
ucts 2 and 1 in a ratio of 8:1 (based on 1H NMR spectrum). Due to
the apparent diminished reactivity of the bromo alkyne, this obser-
vation demonstrates the ability of 1 to undergo a selective lactam
reduction/elimination reaction over the hydrozirconation.
Moreover, we were also interested in exploring the preference
of reduction/elimination reaction over the hydrozirconation on a
⇑
Corresponding author. Tel.: +1 919 530 6706; fax: +1 919 530 6600.
E-mail address: awilliams@nccu.edu (A.L. Williams).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.12.015

926
S. R. Dandepally et al. / Tetrahedron Letters 54 (2013) 925–928
O
Br
(10) using Cp2Zr(H)Cl under the standard reaction conditions.
Br
Cp2Zr(H)Cl
The careful monitoring of reaction showed a complete disappear-
ance of 10 by TLC after 10 min, but it reappeared after quenching
(Table 2, entry 11) indicating a strong coordination complex for-
mation without any hydride insertion. No expected product was
observed even after using excess reagent and extended reaction
times.
N
N
N
THF, rt, 1 h
H2O quench
71%
S
S
O
O
2
1
O
After the successful reduction/elimination of lactam functional-
ity of N-mono/dialkyl imidazolidine-2,4-diones, we were inter-
ested in examining a substrate with a N-alkoxycarbonyl lactam
moiety. Accordingly, tert-butyl 3-(2-iodobenzyl)-2,4-dioxoimidaz-
olidine-1-carboxylate (14) was treated with Cp2Zr(H)Cl. The ex-
pected reduction/elimination product was not formed, instead, it
gave the lactamol 15 (Table 3, entry 1). This observation has some
close resemblance to the very recent report by Piperno et al. in
which the lactamols were formed from N-alkoxycarbonyl lac-
tams.18 We then, investigated the reaction of Cp2Zr(H)Cl on
1,3-dibenzyldihydropyrimidine-2,4(1H,3H)-dione (16).19 Again,
only the lactamol product 17 was obtained (Table 3, entry 2). Final-
ly, 1-benzylpiperidin-2-one (18)20 and 1-(2-bromophenethyl)pyr-
rolidine-2,5-dione (19)21 were treated with Schwartz reagent.
They only formed the coordination complexes with the reagent
and reappeared after quenching (Table 3, entries 3 and 4).
Mechanistically, the Cp2Zr(H)Cl mediated reduction/elimina-
tion reaction is assumed to proceed by a simple hydride addition
to the lactam carbonyl group of thiazolidine-2,4-dione, imidazoli-
dine-2,4-dione and their N-alkylated derivatives thereby forming
a highly moisture sensitive Zr alkoxide complex II.22 In the pres-
ence of water, the lone pair electrons of nitrogen induces the elim-
ination of Cp2ZrCl(O)ꢀ forming an unstable iminium cation
derivative IV,23 which can instantaneously rearrange to the most
stable cyclic enamine product V (Fig. 1). During the course of our
studies, Oda et al. have recently shown the successful trapping of
the iminium ion in the acid mediated direct allylation of tertiary
amides.24 A mechanistic study of our Schwartz reagent mediated
reduction/elimination of N-alkyl thiazolidine-2,4-diones and N-al-
kyl imidazolidine-2,4-diones is under investigation and the results
will be reported in due course. Since the electron donating ability
of lactam nitrogen is compromised for N-alkoxycarbonyl imidaz-
olidine-2,4-diones, they only give alcohols upon quenching.
In conclusion, we have reported a novel reduction/elimination
method of thiazolidine-2,4-dione and imidazolidine-2,4-dione
derivatives using Schwartz reagent to synthesize numerous thia-
zolones and imidazolones in good to excellent yields in a single
step.25,26 This methodology avoids the traditional two step se-
quence to prepare the target compounds.
Br
S
O
3 (expected product)
Scheme 1.
suitable substrate. Accordingly, we treated 3-(but-3-ynyl)thiazol-
idine-2,4-dione (4) with varying amounts of Cp2Zr(H)Cl at differ-
ent temperatures and the results are summarized in Table 1. All
the reactions resulted in the inseparable mixtures of product 5
(both reduction/elimination and hydrozirconation), byproducts 6
(hydrozirconation) and 7 (reduction/elimination), and the recov-
ered 4 in varying amounts (Table 1, entries 1–5). Upon raising
the amount of Cp2Zr(H)Cl to 4 equiv and carrying the reaction
at room temperature gave 5 predominantly in 65% yield (Table
1, entry 5).
Encouraged by these results, we envisioned exploring the
potential of this reaction on a variety of thiazolidine-2,4-dione, imi-
dazolidine-2,4-dione and oxazolidine-2,4-dione derivatives using
commercially available Cp2Zr(H)Cl.14 Firstly, thiazolidine-2,4-dione
(8a) was treated with Cp2Zr(H)Cl to obtain the reduction/elimina-
tion product, thiazol-2(3H)-one (11a) in 76% yield without the
formation of any imine product (Table 2, entry 1). Similarly, imidaz-
olidine-2,4-dione (9a) was reacted with Cp2Zr(H)Cl to give 1H-imi-
dazol-2(3H)-one (12a) in good yield (Table 2, entry 4).
All the N-alkyl thiazolidine-2,4-diones, N-alkyl imidazolidine-
2,4-diones and N,N0-dialkyl imidazolidine-2,4-diones needed for
this study were prepared by following our previously reported
method.6 Interestingly, the N-alkyl thiazolidine-2,4-diones 8b15
and 8c,16 N-alkyl imidazolidine-2,4-diones 9b, 9c and 9d and
N,N0-dialkyl imidazolidine-2,4-diones 9e,17 9f and 9g on treatment
with Cp2Zr(H)Cl underwent the clean reduction/elimination reac-
tions to provide the corresponding thiazolone and imidazolone
derivatives in good to excellent yields (Table 2, entries 2–3 and
5–10).
After having success with N-alkyl thiazolidine-2,4-dione and
imidazolidine-2,4-dione substrates, we next attempted the reduc-
tion/elimination of 3-(4-bromobut-3-ynyl)oxazolidine-2,4-dione
Table 1
Schwartz reagent mediated hydrozirconation and reduction/elimination reactions
O
O
Cp2Zr(H)Cl
N
N
N
N
+
+
S
S
S
S
THF, 1 h
H2O quench
O
O
O
O
7
4
5
6
Entry
Reagent
(Equiv)
Conditions
Product 5a (%)
Byproducts
SM
6a (%)
7a (%)
4a (%)
1
2
3
4
5
2
2
2
3
4
ꢀ10 °C
0 °C
rt
rt
rt
<1
11
72
10
27
8
9
<1
7
11
2
2
<1
81
51
18
2
87
>97 (65b)
<1
a
The comparative yields are determined by 1H NMR analysis of crude mixtures.
Isolated yield.
b

S. R. Dandepally et al. / Tetrahedron Letters 54 (2013) 925–928
927
Table 2
Table 3
Schwartz reagent mediated reduction/elimination
Schwartz reagent mediated reduction reactions
Substratea
Product
OH
Yieldb (%)
O
Entry
Cp2Zr(H)Cl
R
R
O
I
I
N
N
THF, rt, 1 h
X
X
N
N
1
86
80
O
H2O (or) 2N HCl quench
O
N
N
O
O
Boc
O
Boc
8 : X = S
11 : X = S
14
15
9 : X = NH, NR
10 : X = O
12 : X = NH, NR
13 : X = O
OH
Bn
Bn
N
N
Entry
1
Substratea
Product
Yieldb (%)
2
N
O
N
O
O
NH
Bn
Bn
17
16
S
NH
S
76
69
11a
Br
O
8a
O
N
O
3
4
—
—
SMc
SMc
O
Br
Bn
18
N
N
2
O
S
S
S
O
O
11b
PMB
N
8b
Br
O
O
N
PMB
19
N
3
4
11c
78
71
O
a
b
c
S
Conditions: Schwartz reagent (2 equiv).
Isolated yields.
Starting material recovered.
O
8c
O
NH
O
HN
12a
NH
O
HN
9a
ZrCp2Cl
H
H
ZrCp2Cl
O
O
O
O
X
O
I
I
R
R
R
N
Cp2Zr(H)Cl
H2O
N
N
N
N
H
5
6
7
76
84
85
X
X
HN
HN
HN
O
O
O
O
O
O
X = S, NH, NR
III
12b
Br
9b
II
I
O
Br
Cl
ZrCp2Cl
N
N
H
H
O
X
HN
O
R
R
N
O
N
H
Cl
_Cp2Zr(OH)Cl
_H2O
9c
12c
X
O
O
O
V
IV
N
N
Figure 1. Plausible reaction mechanism.
Br
Br
HN
HN
O
N
O
12d
9d
Bn
O
Bn
Acknowledgments
N
N
12e
8
9
96
95
O
We gratefully acknowledge the Golden LEAF Foundation, Rocky
Mount, NC, for the financial support in setting-up the BRITE insti-
tute. We thank Dr. Li-An Yeh, Director, BRITE, for the encourage-
ment and support.
N
Bn
9e
O
Bn
O
Bn
N
Bn
N
N
12f
O
N
PMB
Me
9f
O
Supplementary data
PMB
Me
O
Bn
N
Supplementary data (1H & 13C NMR spectra of all new final
products) associated with this article can be found, in the online
version, at http://dx.doi.org/10.1016/j.tetlet.2012.12.015.
Bn
N
N
10
11
72
O
N
Bn
12g
O
Bn
9g
O
Br
References and notes
SMc
N
—
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Prod. Rep. 2009, 26, 382–445.
O
O
10
2. (a) Suijkerbuijk, B. M. J. M.; Niculescu-Duvaz, I.; Gaulon, C.; Dijkstra, H. P.;
Niculescu-Duvaz, D.; Menard, D.; Zambon, A.; Nourry, A.; Davies, L.; Manne, H.
A.; Friedlos, F.; Ogilvie, L. M.; Hedley, D.; Lopes, F.; Preece, N. P. U.; Moreno-
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Chem. 2010, 53, 2741–2756; (b) Hassanein, H. H.; Khalifa, M. M.; El-Samaloty,
O. N.; El-Rahim, M. A.; Taha, R. A.; Magda; Ismail, M. F. Arch. Pharm. Res. 2008,
31, 562–568; (c) Xue, N.; Yang, X.; Wu, R.; Chen, J.; He, Q.; Yang, B.; Lu, X.; Hu,
a
Conditions: 2 equiv of Schwartz reagent used.
b
Isolated yields, all the products were identified either with authentic com-
mercially available samples or the reported data, or new, fully characterized by 1H
NMR, 13C NMR and MS.
c
Starting material recovered.

928
S. R. Dandepally et al. / Tetrahedron Letters 54 (2013) 925–928
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anhydride and 2-bromophenethyl amine in 90% yield according to the
procedure reported in Verschueren, W. G.; Dierynck, I.; Amssoms, K. I. E.; Hu,
L.; Boonants, P. M. J. Z.; Pille, G. M. E.; Daeyaert, F. F. D.; Hertogs, K.; Surleraux,
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Supplementary data for the copies of 1H & 13C NMR spectra.
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25. General experimental procedure for Schwartz reagent mediated reduction/
elimination: To a suspension of Cp2Zr(H)Cl (0.63 mmol) in anhydrous THF
(2 mL) was added a substrate (0.31 mmol) in THF (1 mL) at room temperature
and stirred under nitrogen for 1 h. Water (2 mL) was added to the mixture and
kept stirring for 10 min. Then, it was extracted with EtOAc (20 mL), washed
with brine, dried (Na2SO4) and evaporated under reduced pressure. The crude
compound was purified by flash silica gel column chromatography to afford a
pure product. Note: The reactions involving 9a–9d are treated with 2 N HCl for
10 min to affect the complete cleavage of the complex materials, and then
neutralized with aqueous sat. NaHCO3 solution.
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26. Spectroscopic data of the selected final products:
3-(4-Bromobut-3-ynyl)thiazol-2(3H)-one (2): Light orange syrup. 1H NMR
(500 MHz, CDCl3) d (ppm) 2.61 (t, 2H, J = 6.5 Hz), 3.85 (t, 2H, J = 6.5 Hz), 6.12
(d, 1H, J = 5.5 Hz), 6.64 (d, 1H, J = 5.5 Hz). 13C NMR (125 MHz, CDCl3) d (ppm)
20.3, 41.2, 43.9, 76.3, 101.1, 124.7, 171.8. APCI/ESI-MS: m/z 232 [M+H]+. 3-(But-
3-enyl)thiazol-2(3H)-one (11b): Colorless syrup. 1H NMR (500 MHz, CDCl3) d
(ppm) 2.44 (q, 2H, J = 7.0 Hz), 3.77 (t, 2H, J = 7.0 Hz), 5.07–5.13 (m, 2H), 5.72–
5.81 (m, 1H), 6.09 (d, 1H, J = 5.5 Hz), 6.53 (d, 1H, J = 5.5 Hz). 13C NMR (125 MHz,
CDCl3) d (ppm) 33.4, 44.7, 100.9, 118.0, 124.5, 133.8, 171.9. APCI/ESI-MS: m/z
156 [M+H]+. 3-(2-Bromobenzyl)thiazol-2(3H)-one (11c): White solid, mp: 90–
92 °C. 1H NMR (500 MHz, CDCl3) d (ppm) 4.99 (s, 2H), 6.13 (d, 1H, J = 5.5 Hz),
6.58 (d, 1H, J = 5.5 Hz), 7.19 (dt, 1H, J = 1.5, 8.0 Hz), 7.23 (dd, 1H, J = 1.5, 8.0 Hz),
7.31 (dt, 1H, J = 1.0, 8.0 Hz), 7.58 (dd, 1H, J = 1.0, 8.0 Hz). 13C NMR (125 MHz,
CDCl3) d (ppm) 48.5, 101.5, 123.2, 124.2, 128.0, 129.7, 129.8, 133.0, 135.0,
172.0. APCI/ESI-MS: m/z 270 [M+H]+. 3-(4-Methoxybenzyl)thiazol-2(3H)-one
(11d): Off-white solid, mp: 84–86 °C. 1H NMR (500 MHz, CDCl3) d (ppm) 3.80
(s, 3H), 4.80 (s, 2H), 6.07 (d, 1H, J = 5.5 Hz), 6.46 (d, 1H, J = 5.5 Hz), 6.88 (d, 2H,
J = 8.5 Hz), 7.21 (d, 2H, J = 8.5 Hz). 13C NMR (125 MHz, CDCl3) d (ppm) 48.1,
55.3, 101.3, 114.3, 124.0, 128.0, 129.4, 159.5, 171.9. APCI/ESI-MS: m/z 222
[M+H]+. 1-(2-Iodobenzyl)-1H-imidazol-2(3H)-one (12b): White solid, mp: 105–
107 °C. 1H NMR (500 MHz, CDCl3) d (ppm) 4.85 (s, 2H), 6.17 (s, 1H), 6.34 (s, 1H),
6.99 (t, 1H, J = 7.5 Hz), 7.09 (d, 1H, J = 7.5 Hz), 7.32 (t, 1H, J = 8.0 Hz), 7.85 (d,
1H, J = 8.0 Hz), 10.97 (br s, 1H, NH). 13C NMR (125 MHz, CDCl3) d (ppm) 51.4,
98.0, 108.9, 111.3, 128.5, 128.7, 129.4, 138.9, 139.5. APCI/ESI-MS: m/z 301
[M+H]+. 1-(2-Bromo-5-chlorobenzyl)-1H-imidazol-2(3H)-one (12c): White solid,
mp: 158–160 °C. 1H NMR (500 MHz, CDCl3+CD3OD) d (ppm) 4.87 (s, 2H), 6.31
(d, 1H, J = 3.0 Hz), 6.39 (d, 1H, J = 3.0 Hz), 7.09 (d, 1H, J = 2.5 Hz), 7.18 (dd, 1H,
J = 2.5, 8.5 Hz), 7.54 (d, 1H, J = 8.5 Hz). 13C NMR (125 MHz, CDCl3+CD3OD) d
(ppm) 46.0, 1.08.4, 111.3, 120.1, 128.4, 128.9, 133.4, 133.6, 137.3, 153.7. APCI/
ESI-MS: m/z 287 [M+H]+. 1-(2-Bromophenethyl)-1H-imidazol-2(3H)-one (12d):
Colorless syrup. 1H NMR (500 MHz, CD3OD) d (ppm) 3.12 (t, 2H, J = 7.0 Hz),
3.88 (t, 2H, J = 7.0 Hz), 6.20 (d, 1H, J = 3.0 Hz), 6.30 (d, 1H, J = 3.0 Hz), 7.10–7.14
(m, 1H), 7.22–7.27 (m, 2H), 7.55 (d, 1H, J = 7.5 Hz). 13C NMR (75 MHz, CDCl3) d
(ppm) 36.0, 42.9, 107.8, 111.8, 124.5, 127.6, 128.4, 131.3, 132.9, 137.5, 154.5.
APCI/ESI-MS: m/z 267 [M+H]+. 1-Benzyl-3-(4-methoxybenzyl)-1H-imidazol-
2(3H)-one (12f): Light brown syrup. 1H NMR (500 MHz, CD3OD) d (ppm) 3.79
(s, 3H), 4.75 (s, 2H), 4.81 (s, 2H), 6.07 (s, 2H), 6.86 (d, 2H, J = 8.5 Hz), 7.22 (d, 2H,
J = 8.5 Hz), 7.24–7.29 (m 3H), 7.31–7.35 (m, 2H). 13C NMR (125 MHz, CDCl3) d
(ppm) 46.7, 47.2, 55.2, 110.1 (2), 114.1, 127.7, 127.8, 128.7, 129.0, 129.3, 137.0,
159.2. APCI/ESI-MS: m/z 295 [M+H]+. 1,3-Dibenzyl-4-methyl-1H-imidazol-
2(3H)-one (12g): Light orange syrup. 1H NMR (500 MHz, CD3OD) d (ppm)
1.86 (d, 3H, J = 1.5 Hz), 4.79 (s, 2H), 4.86 (s, 2H), 5.84 (d, 1H, J = 1.5 Hz), 7.22–
7.34 (m, 10H). 13C NMR (125 MHz, CDCl3) d (ppm) 10.4, 44.5, 46.9, 106.2, 119.0,
126.9, 127.3, 127.6, 127.8, 128.6 (3), 137.2, 137.6, 153.7. APCI/ESI-MS: m/z 279
[M+H]+. Tert-butyl 4-hydroxy-3-(2-iodobenzyl)-2-oxoimidazolidine-1-carboxylate
(15): White solid, mp: 150–152 °C. 1H NMR (500 MHz, CDCl3) d (ppm) 1.52 (s,
9H), 3.71 (dd, 1H, J = 1.5, 12.0 Hz), 3.84 (dd, 1H, J = 7.0, 12.0 Hz), 4.42 (d, 1H,
J = 16.0 Hz), 4.49 (d, 1H, J = 7.5 Hz, OH), 4.73 (d, 1H, J = 16.0 Hz), 5.01 (t, 1H,
J = 7.5 Hz), 6.96 (dt, 1H, J = 1.5, 8.0 Hz), 7.30 (dt, 1H, J = 1.0, 7.5 Hz), 7.35 (dd,
1H, J = 1.5, 8.0 Hz), 7.81 (dd, 1H, J = 1.5, 8.0 Hz). 13C NMR (125 MHz, CDCl3) d
(ppm) 28.1, 48.7, 50.4, 75.4, 83.0, 98.8, 128.5, 129.3, 129.8, 138.7, 139.6, 150.4,
8. For selected reviews of hydrozirconation (a) Wipf, P.; Kendall, C. Topics in
Organometallic Chemistry 08; Springer: Berlin, Germany, 2005; Lipshutz, B. H.;
Pfeiffer, S. S.; Noson, K.; Tomioka, T. Titanium and Zirconium in Organic
Synthesis; Wiley: Weinheim, Germany, 2002; (c) Wipf, P.; Nunes, R. L.
Tetrahedron 2004, 60, 1269–1279; (d) Wipf, P.; Jahn, H. Tetrahedron 1996, 52,
12853–12910; (e) Labinger, J. A. In In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Heathcock, C. H., Eds.; Pergamon Press: New York, 1991; Vol. 8,.
Chapter 3.9 (f) Negishi, E.; Takahashi, T. Aldrichim. Acta 1985, 18, 31–47; (g)
Schwartz, J.; Labinger, J. A. Angew. Chem., Int. Ed. Engl. 1976, 15, 333–340.
9. (a) Cesarotti, E.; Chiesa, A.; Maffi, S.; Ugo, R. Inorg. Chim. Acta 1982, 64, L207–
L208; (b) Laycock, D. E.; Alper, H. J. Org. Chem. 1981, 26, 289–293; (c) Majoral, J.
P.; Zablocka, M.; Igau, A.; Cenac, N. Chem. Ber. 1996, 129, 879–886; (d) Cenac,
N.; Zablocka, M.; Igau, A.; Majoral, J. P.; Skowronska, A. J. Org. Chem. 1999, 67,
796–798; (e) Godfrey, A. G.; Ganem, B. Tetrahedron Lett. 1992, 33, 7461–7464;
(f) Vincent, P.; Beaucourt, J.-P.; Pichat, L. Tetrahedron Lett. 1982, 23, 63–64; (g)
Vincent, P.; Beaucourt, J.-P.; Pichat, L.; Balzarini, J.; De Clercq, E. Nucleosides
Nucleotides 1985, 4, 447–462; (h) Schwartz, J.; Loots, M. J.; Kosugi, H. J. Am.
Chem. Soc. 1980, 102, 1333–1340; (i) Zablocka, M.; Delest, B.; Igau, A.;
Skowronska, A.; Majoral, J. M. Tetrahedron Lett. 1997, 38, 5997–6000.
10. (a) Schedler, D. J. A.; Li, J.; Ganem, B. J. Org. Chem. 1996, 61, 4115–4119; (b)
Schedler, D. J. A.; Godfrey, A. G.; Ganem, B. Tetrahedron Lett. 1993, 34, 5035–5038.
11. (a) Spletstoser, J. T.; White, J. M.; Tunoori, A. R.; Georg, G. I. J. Am. Chem. Soc.
2007, 129, 3408–3419; (b) Spletstoser, J. T.; White, J. M.; Georg, G. I.
Tetrahedron Lett. 2004, 45, 2787–2789; (c) White, J. M.; Tunoori, A. R.; Georg,
G. I. J. Am. Chem. Soc. 2000, 122, 11995–11996.
12. (4-Bromobut-3-ynyl)thiazolidine-2,4-dione (1) was prepared from 8a by the
Mitsunobu reaction of 3-butyn-4-ol and subsequent bromination by NBS and
AgNO3. Similarly, 3-(4-bromobut-3-ynyl)oxazolidine-2,4-dione (10) is
prepared from 10a
O
O
O
Br
3-butyn-4-ol,
DIAD, PPh3
NBS, AgNO3
NH
O
N
N
THF, 0 oC-rt, 12 h
X
X
X
acetone, rt, 1 h
O
O
4
: X = S, 78%
8a : X = S
1 : X = S, 80%
10b : X = O, 88%
10a : X = O
10 : X = O, 92%
.
13. (a) Molander, G. A.; Dehmel, F. J. Am. Chem. Soc. 2004, 126, 10313–10318; (b)
Hoshi, M.; Arase, A. Synth. Commun. 1997, 27, 567–572; (c) Brown, H. C.; Blue,
C. D.; Nelson, D. J.; Bhat, N. G. J. Org. Chem. 1989, 54, 6064–6067; (d) Zweifel, G.;
Arzoumanian, H. J. J. Am. Chem. Soc. 1967, 89, 5086–5088.
14. After several experiment trials, the optimal reaction conditions were identified,
that is 2 equiv Cp2Zr(H)Cl, THF as a solvent, and the reaction duration as 1 h at
ambient temperature. Although the suspension in reaction mixture got cleared
after 10–15 min indicating the complete disappearance of starting material by
TLC, the early quenching with water (or) 2 N HCl resulted in the reappearance
of the starting compound. This could be due to the strong complexation of
oxygen atoms of the substrate with the highly oxophilic Zr atom of the reagent.
15. (a) Barros, C. D.; Amato, A. A.; Oliveira, T. B.; Iannini, K. B. R.; Silva, A. L.; Silva, T.
G.; Leite, E. S.; Hernandes, M. Z.; Lima, M. C. A.; Galdino, S. L.; Neves, F. A. R.;
Pitta, I. R. Bioorg. Med. Chem. 2010, 18, 3805–3811; (b) Bozdag-Dundar, O.;
Ceylan-Unlusoy, M.; Verspohl, E. J.; Ertan, R. Arzneimittelforschung 2006, 56,
621–625.
153.4.
APCI/ESI-MS:
m/z
363
[(Mꢀt-Bu)+2H]+.
1,3-Dibenzyl-4-
hydroxytetrahydropyrimidin-2(1H)-one (17): Colorless syrup. 1H NMR
(500 MHz, CDCl3) d (ppm) 1.79–1.86 (m, 2H), 3.00–3.05 (m, 1H), 3.49–3.59
(m, 2H), 4.43 (d, 2H, J = 15.5 Hz), 4.73 (d, 1H, J = 15.0 Hz), 4.87 (s, 1H), 4.91 (d,
1H, J = 15.0 Hz), 7.22–7.33 (m, 10H). 13C NMR (125 MHz, CDCl3) d (ppm) 28.9,
40.0, 49.3, 51.5, 77.7, 127.2, 127.3, 127.7, 127.8, 128.5, 128.7, 138.0, 139.0,
155.2. APCI/ESI-MS: m/z 297 [M+H]+.
16. Borkar, M. R.; Sachan, N.; Kadam, S. S.; Kulkarni, V. M. Indian J. Heterocycl. Chem.
2009, 18, 295–300.