Rearrangement of 5-phenylthiazolidine-2,4-diones to chiral α-ketoamides via α-elimination

Article abstract of DOI:10.1016/j.tetlet.2010.09.046

An unexpected reaction took place when 5-phenylthiazolidine-2,4-diones were treated in basic media to produce phenyl-α-ketoamides in good yields. The 5-phenylthiazolidine-2,4-diones used as reactants were achieved through a rearrangement, which took place in the corresponding N-acyloxazolidinethiones.

Full text of DOI:10.1016/j.tetlet.2010.09.046

Tetrahedron Letters 51 (2010) 6041–6044
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Tetrahedron Letters
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Rearrangement of 5-phenylthiazolidine-2,4-diones to chiral a-ketoamides
via a-elimination
Laura Munive a, Sylvain Bernès b, Estibaliz Sansinenea a, Aurelio Ortiz a,
⇑
a Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72570, Mexico
b Facultad de Ciencias Químicas Universidad Autónoma de Nuevo León, Monterrey, NL 64570, Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 June 2010
Revised 10 September 2010
Accepted 13 September 2010
Available online 17 September 2010
An unexpected reaction took place when 5-phenylthiazolidine-2,4-diones were treated in basic media to
produce phenyl- -ketoamides in good yields. The 5-phenylthiazolidine-2,4-diones used as reactants were
achieved through a rearrangement, which took place in the corresponding N-acyloxazolidinethiones.
Ó 2010 Elsevier Ltd. All rights reserved.
a
a
-Ketoamides have received interest because of their variable
afforded the N-substituted 5-phenylthiazolidine-2,4-diones 2a–d
as diastereomeric mixtures in moderate yields (50–80%), as shown
in Scheme 2 and Table 1.
With the exception of 2a, which is solid, thiazolidinediones 2b–
d are dense liquids.
For the formation of 5-phenylthiazolidine-2,4-diones 2a–d, the
aqueous solution of NaHCO3 plays an important role. In the ab-
sence of NaHCO3 solution, the predominant products are the
respective diastereomeric mixtures of N-acyl oxazolidinethiones.
This is illustrated by the following example: when treating com-
pound 1a under the reaction conditions described above without
using NaHCO3, N-acyloxazolidinethione 4a was obtained as diaste-
reomeric mixture in 80% yield. However, purification of N-acylox-
biological activities1 and their applications in the elaboration of
important heterocycles.2 Different methods for their preparation
have recently been reviewed by Masson and Zhu.3 In particular, they
described a one-pot directed synthesis of alkyl- and aryl
ides by a ZnCl2-promoted formal oxidative coupling of aldehydes
and isocyanides. Chiral -ketoamides have been used for the
preparation of important reagents in asymmetric synthesis, such
as -cyano- -hydroxy-
-fluorophenylacetic acid (CFPA)4 and (R)-
phenylacetic acid.5
a-ketoam-
a
a
a
a
On the other hand, N-substituted-thiazolidine-2,4-dione,
5-methylthiazolidine-2,4-dione, and 1,3-thiazinane-2,4-dione were
achieved through rearrangement of oxazolidinethiones when
reacted with acyl halides and sodium hydride. During this rear-
rangement an unusual elimination reaction showed: one methyl
group of the oxazolidinethione moiety was converted into a
terminal alkene. These heterocycles are of synthetic utility for the
S
O
i
R2
R1
O
NH
R2
R1
N
S
preparation of chiral allyl ureas, 1,3-amino alcohols, and
a-methyl
b-aminoacids.6
O
We report herein, on the formation of chiral phenyl
a-ketoam-
ides 3a–d18–21 from an unexpected reaction that took place when
5-phenylthiazolidine-2,4-diones 2a–d14–17 were exposed to basic
media. 5-Phenylthiazolidine-2,4-diones 2a–d were prepared by
the above described rearrangement of oxazolidinethiones 1a–c
R3
2a R1 = H R2 = Ph R3 = H
2b R1 = Bn R2 = H R3 = H
2c R1 = iPr R2 = H R3 = H
2d R1 = H R2 = Ph R3 = OMe
1a R1 = H R2 = Ph
1b R1 = Bn R2 = H
1c R1 = iPr R2 = H
when reacted with
a-chlorophenylacetyl chloride and a-chloro-
p-methoxiphenylacetyl chloride7 in the presence of sodium
hydride, as shown in Scheme 1.
ii
Oxazolidinethiones8 1a–c were treated with NaH in CH2Cl2
R2
R1
NH O
followed by dropwise addition of racemic
chloride or -chloro-p-methoxiphenylacetyl chloride at 0 °C. After
stirring for 1 h at room temperature the reaction was quenched
with aq NH4Cl and washed with saturated aq NaHCO3 and brine.
Subsequent extraction with DCM (3 ꢀ 20 ml) and evaporation
a-chlorophenylacetyl
a
O
R3
3a-d
⇑
Corresponding author. Tel.: +52 222 2295500 7518; fax: +52 222 2295584.
E-mail address: jaortizm@siu.buap.mx (A. Ortiz).
Scheme 1. Reagents and conditions: (i) NaH, PhCHClCOCl or p-MeOPhCHClCOCl,
0 °C CH2Cl2, aq NaHCO3; (ii) base (1.5 equiv).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.09.046

6042
L. Munive et al. / Tetrahedron Letters 51 (2010) 6041–6044
O
S
R2
R1
i
N
S
O
NH
R2
PhR3
R1
1a-c
O
2a-d
a-PhCHClCOCl or p-MeOPhCHClCOCl,
Scheme 2. Reagents and conditions: (i) NaH,
0 °C, CH2Cl2, aq NaHCO3.
Table 1
Conversion of oxazolidinethiones to 5-phenylthiazolidine-2,4-diones
Entry
Product
R1
R2
R3
Yielda (%)
1
2
3
4
2a
2b
2c
2d
H
Ph
H
H
H
H
H
OMe
87
50
80
70
Bn
iPr
H
Ph
a
Purified yield corresponding to mixture of diastereomers.
Figure 1. Molecular structure of phenyl-a-ketoamide 3a. One of the two indepen-
dent molecules present in the asymmetric unit is shown, with displacement
ellipsoids at the 25% probability level.
O
S
S
O
Ph
i
ii
O
N
O
NH
Ph
N
S
Ph
O
Cl
R2
R2
R1
i
Ph
O
NH O
Ph
R1
N
S
4a
1a
2a
PhR3
O
PhR3
iii
OH
O
3a R1 = H R2 = Ph R3 = H
3b R1 = Bn R2 = H R3 = H
3c R1 = iPr R2 = H R3 = H
3d R1 = H R2 = Ph R3 = OMe
2a R1 = H R2 = Ph R3 = H
2b R1 = Bn R2 = H R3 = H
2c R1 = iPr R2 = H R3 = H
2d R1 = H R2 = Ph R3 = OMe
Ph
Cl
5a
Scheme 5. Reagents and conditions: (i) KOH (1.5 equiv), THF/H2O (3:1), 25 °C.
Scheme 3. Reagents and conditions: (i) NaH, PhCHClCOCl, 0 °C, CH2Cl2; (ii) column
chromatography; (iii) NaBH4, THF/H2O.
Table 3
Conversion of 5-phenylthiazolidine-2,4-diones to chiral phenyl-
a
-ketoamides
(c)b
Yielda%
Mp (°C)
½ ꢂ
a 2D5
Entry
Product
O
1
2
3
4
3a
3b
3c
3d
85
60
70
70
127.2
72.0
93.6
Liq
ꢁ114.5 (1.3)
ꢁ8.07 (1.0)
ꢁ7.40 (1.0)
ꢁ2.45 (1.0)
N
S
Base
NH O
Ph
Ph
O
O
Ph
Ph
2a
3a
a
Purified yield.
Determined in CHCl3 at 25 °C.
b
Scheme 4. Reaction explored in the presence of different bases.
Table 2
Conversion of 5-phenylthiazolidine-2,4-dione 2a to 3a
all cases, chiral phenyl-a-ketoamide 3a was the main product in
40–85% yield. The best yields (85%) were achieved using KOH in
THF/H2O, as shown in Scheme 4 and Table 2 (entry 2).
The structure of compound 3a was established by 1H and 13C
NMR spectroscopy, mass spectrometry, and X-ray diffraction anal-
ysis11 (Fig. 1).
An interesting feature figured by 3a in the solid-state is the fact
that this compound crystallizes with two independent molecules
in the asymmetric unit, which display dramatically different con-
formations. Although, both molecules have identical absolute con-
figuration, the allyl and phenyl groups bonded to the chiral C atom
Entry
Base (equiv)
Solvent
T (°C)
t (h)
Yield (%)
1
2
3
4
5
NaHMDS (1.5)
KOH (1.5)
DBU (1.5)
Et3N (1.5)
DBU (1.5)
THF
ꢁ78
25
0
25
Reflux
4
4
5
4
4
50
85
50
40
40
THF/H2O
CH2Cl2
CH2Cl2
CH2Cl2
azolidinethione 4a by column chromatography using silica gel
afforded its respective 5-phenylthiazolidine-2,4-dione 2a. Removal
of the chiral auxiliary in compound 4a was achieved with NaBH4 in
THF/H2O,9 affording 2-chloro-2-phenylethanol10 5a in 80% yield, as
shown in Scheme 3.
O
O
2
N
S
N3 1S
Ph
Ph
An unexpected reaction was observed during the attempt to
alkylate compound 2a with NaHMDS (1.5 equiv) and CH3I at
4
5
O
O
Ph
ꢁ78 °C in THF. The reaction mixture gave the chiral phenyl-
a-
2a
6a
ketoamide 3a in 50% yield as white solid. This reaction was carried
out in the presence of other bases, such as KOH, Et3N, and DBU. In
Scheme 6. Thiazolidine-2,4-diones with different substituents at C-5.

L. Munive et al. / Tetrahedron Letters 51 (2010) 6041–6044
6043
9. Prashad, M.; Har, D.; Kim, H.-Y.; Repic, O. Tetrahedron Lett. 1998, 39, 7067–
7070.
S
O
10. (a) Kotsuki, H.; Shimanouchi, T.; Ohshima, R.; Fujiwara, S. Tetrahedron 1998, 54,
2709–2722; (b) McCluskey, A.; Leitch, S. K.; Garner, J.; Caden, C. E.; Hill, T. A.;
Odell, L. R.; Stewart, S. G. Tetrahedron Lett. 2005, 46, 8229–8232; (c) France, S.;
Wack, H.; Taggi, A. E.; Hafez, A. M.; Wagerle, T. R.; Shah, M. H.; Dusich, C. L.;
Lectka, T. J. Am. Chem. Soc. 2004, 126, 4245–4255; (d) Sartillo-Piscil, F.;
Quintero, L.; Villegas, C.; Santacruz-Juarez, E.; Anaya de Parrodi, C. Tetrahedron
Lett. 2001, 43, 15–17.
α-elimination
N
O
C S
R
N
S
R
loss of
3a-d
recombination
reprotonation
O
O
Ph
Ph
2a-d
I
Scheme 7. A possible mechanism for the transformation of 2a–d to 3a–d.
11. Crystal data for 3a: C18H17NO2, M = 279.33, colorless prism, mp = 127.2 °C,
0.40 ꢀ 0.16 ꢀ 0.16 mm3, triclinic, space group P1, cell parameters a = 8.444(4),
b = 9.589(4), c = 9.801(5) Å,
a
= 90.86(5), b = 102.09(3),
c
= 104.25(5)°, Z =
Siemens P4
radiation (k = 0.71073 Å) in the
range 2h = 4–50°, of which 2651 are unique (Rint = 0.0485). 387 variables
refined: R1 = 0.052 [1755 data with I >2
(I)] and wR2 = 0.146 [all data].12 The
Z0 = 2, Dc = 1.236 g cmꢁ3
diffractometer at room temp, with the Mo K
. 5238 reflections collected on a
are free to rotate about C4–C5 and C4–C14
ior may have consequences for the reactivity of this class of chiral
-ketoamides in solution.
The rearrangement was explored also for compounds 2b–d un-
der the same reaction conditions (KOH, THF/H2O) to give phenyl-
-ketoamides 3b–d in moderated yields as white solids for 3b–c
and liquid for 3d, as shown in Scheme 5 and Table 3.
For a successful rearrangement, the presence of the phenyl
group at the C5 position of the heterocycle 2a is essential. If it is
replaced by a methyl group, the reaction does not proceed. For
example, when treating 5-methylthiazolidine-2,4-dione 6a under
the reaction conditions (KOH, THF/H2O), only starting material
was recovered as shown in Scheme 6.
A possible reaction mechanism could be the following: after
deprotonation opening of the cycle occurs via an
followed by recombination and cyclization, giving intermediate
(I). Finally a loss of fragment CS takes place, followed by reprotona-
tion to afford the a-ketoamide, as shown in Scheme 7.
In conclusion, we have found an unexpected reaction that takes
place when 5-phenylthiazolidine-2,4-diones are treated with base
r-bonds. Such a behav-
a
r
a
absolute configurations of C4 and C24 were deduced from the synthetic route:
S-C4, S-C24. Measured Friedel pairs were merged. CCDC-779340 contains
the supplementary crystallographic data for this paper. These data can
be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by
emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK. Fax:
+44 1223 336033.
a
12. Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112–122.
13. (a) Danehy, J. P.; Elia, V. J. J. Org. Chem. 1971, 36, 1394–1398; (b) Danehy, J. P.;
Elia, V. J. J. Org. Chem. 1972, 37, 369–373.
14. 3-[(S)-2-Methyl-1-phenylallyl)-5-phenylthiazolidine-2,4-dione (2a). White solid,
mp = 118 °C, 1H NMR (400 MHz, CDCl3): d: 7.44–7.31 (10H, m, Ph), 5.83 (1H, s,
CH–N), 5.23 (1H, s, CH@), 5.22 (1H, s, CH@), 4.78 (1H, s, CHS), 1.82 (3H, s, CH3);
13C NMR (100 MHz, CDCl3): d: 172.8 (C@O), 170.5 (C@O), 139.8 (C@), 135.8,
134.4, 130.9, 129.4, 129.2, 129.0, 128.9, 128.4, 128.3, 128.1 (Ph), 115.4 (CH2@),
a
-elimination,13
63.4, (C–N), 52.5 (C–S), 21.2 (CH3); IR
m
max: 2929.9, 1755.4, 1677.9, 1494.9,
1454.0, 1314.9, 1153.2, 697.2 cmꢁ1
323.0980; found, 323.0970.
; EI-HRMS: calculated for C19H17NO2S,
15. 3-[(S)-3-Methyl-1-phenybut-3-en-2-yl)-5-phenylthiazolidine-2,4-dione
(2b).
Dense liquid, 1H NMR (400 MHz, CDCl3) d: 7.31–7.03 (10H, m, Ph), 6.64 (1H,
d, J = 7.2 Hz, CH–N), 5.12 (1H, s, CH@), 5.10 (1H, s, CH@), 5.06 (1H, s, CH@), 4.92
(1H, s, CH@), 3.62 (1H, dd, J = 14.0, 12.0 Hz, CHaHb), 3.54 (1H, dd, J = 14.0,
12.0 Hz, CHbHa), 3.23 (1H, dd, J = 13.6, 4.8 Hz, CHaHb), 3.20 (1H, dd, J = 13.6,
4.8 Hz, CHbHa), 1.80 (6H, s, 2CH3); 13C NMR (100 MHz, CDCl3) d: 172.9, 172.7
(C@O), 170.8, 170.5 (C@O), 140.6, 140.5 (C@), 137.2, 137.1, 134.4, 133.9, 129.0,
128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 128.2, 128.0, 126.7 (Ph), 113.8, 113.7
(CH2@), 60.0, 59.3 (C–N), 52.5, 52.0 (C–S), 34.6, 34.1 (CH2) 21.0, 20.9 (CH3); IR
and the corresponding phenyl
a-ketoamides were obtained in
good yields. It was also found that NaHCO3 plays an important role
for the rearrangement of N-acyloxazolidinethiones to thiazolidine-
2,4-diones.
m
max: 2919.3, 1752.8, 1674.5, 1327.4, 1146.3, 746.6, 696.7 cmꢁ1; FAB-HRMS:
calculated for C20H20NO2S, 338.1215; found, 338.1206.
16. 3-[(S)-2,4-Dimethylpent-1-en-3-yl)-5-phenylthiazolidine-2,4-dione (2c). Dense
liquid, 1H NMR (300 MHz, CDCl3) d: 7.40–7.33 (10H, m, Ph), 5.40 (1H, s,
CH@), 5.35 (1H, s, CH@), 5.22 (1H, s, CH@), 5.20 (1H, s, CH@), 5.14 (1H, br s,
CHS), 5.04 (1H, br s, CHS), 4.28 (1H, d, J = 6.0 Hz, CH–N), 4.24 (1H, d, J = 6.3 Hz,
CH-N), 2.86 (1H, m, CH), 1.75 (3H, d, J = 6.9 Hz, CH3), 1.65 (3H, d, J = 6.0 Hz,
CH3), 1.24 (3H, d, J = 5.7 Hz, CH3), 1.22 (3H, d, J = 5.7 Hz, CH3), 0.94 (3H, d,
J = 6.6 Hz, CH3), 0.89 (3H, d, J = 6.6 Hz, CH3), 0.83 (3H, d, J = 6.6 Hz, CH3); 13C
NMR (75 MHz, CDCl3) d: 173.3, 173.2 (C@O), 171.0, 170.9 (C@O), 140.4, 140.3
(C@), 134.6, 134.4, 129.1, 129.0, 128.9, 128.8, 128.4, 128.3, 128.2, 128.0 (Ph),
117.3, 117.2 (CH2@), 67.4, 67.0 (C–N), 52.3, 52.1 (C–S), 25.4, 25.1 (CH3), 22.2,
Acknowledgments
The authors thank VIEP (project 107/I/NAT/10) and CONACyT
(project 80915). L.M. and R.S. acknowledge a grant from CONACyT.
The authors wish to thank Professor Herbert Höpfl (from Morelos
State University,UAEM) for critical reading of the manuscript.
22.1 (CH), 20.7, 20.5 (CH3), 19.6, 19.4 (CH3); IR mmax: 2968.8, 1751.4, 1675.0,
1454.3, 1378.0, 1315.9, 1185.7, 1113.7, 911.6, 774.8, 724.9, 694.6 cmꢁ1; EI-
HRMS: calculated for C16H19NO2S, 289.1137; found, 289.1130.
References and notes
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Nair, L. G.; Tong, X.; Cheng, K.-C.; Njoroge, F. G. Bioorg. Med. Chem. Lett. 2009, 19,
1105–1109; (c) Schmidt, E. W.; Raventos-Suarez, C.; Bifano, M.; Menendez, A.
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G.; Chen, K. X.; Shih, N.-Y.; Piwinski, J. J. Acc. Chem. Res. 2008, 41, 50–59.
2. (a) Newton, R.; Marsden, S. P. Synthesis 2005, 3263–3270; (b) George, J. H.;
Adlington, R. M. Synlett 2008, 2093–2096; (c) Tomaszewski, M. J.; Boisvert, L.;
Jin, S. Tetrahedron Lett. 2009, 50, 1435–1437; (d) Ayitou, A. J.-L.; Jesuraj, J. L.;
Barooah, N.; Ugrinov, A.; Sivaguru, J. J. Am. Chem. Soc. 2009, 131, 11314–11315.
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Grassol, J.-M.; Masson, G.; Zhu, J. Angew. Chem., Int. Ed. 2008, 47, 947–950.
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1991, 113, 6318–6320; (b) Takeuchi, Y.; Ithoh, N.; Satoh, T.; Koizumi, T.;
Yamaguchi, K. J. Org. Chem. 1993, 58, 1812–1820.
17. 3-[(S)-2-Methyl-1-phenylallyl)-5-p-methoxiphenyl-thiazolidie-2,4-dione
(2d).
Liquid, 1H NMR (400 MHz, CDCl3): d 7.43–7.31 (12H, m, Ph), 7.25 (2H, d,
J = 8.8 Hz, Ph), 7.22 (2H, d, J = 8.8 Hz, Ph), 6.88 (2H, d, J = 8.4 Hz, Ph), 5.85 (1H, s,
CH–N), 5.82 (1H, s, CH–N), 5.20 (1H, s, CHS), 5.17 (1H, s, CHS), 5.15 (1H, s,
CH@), 5.11 (1H, s, CH@), 4.78 (1H, s, CH@), 4.73 (1H, s, CH@), 3.80 (3H, s, OCH3),
3.78 (3H, s, OCH3), 1.82 (3H, s, CH3), 1.76 (3H, s, CH3); 13C NMR (100 MHz,
CDCl3): d 173.1, 173.0 (C@O), 170.7, 170.6 (C@O), 160.0 (Ph), 140.0, 139.6 (C@),
136.0, 135.8, 129.5, 129.4, 129.3, 128.4, 128.3, 128.2, 126.0 (Ph), 115.3, 115.1
(CH2@), 63.4, 63.1 (C–N), 55.3 (CH3O), 52.2, 52.0 (C–S), 21.2 (CH3); IR mmax
:
2930.6, 2362.6, 1753.9, 1681.9, 1511.7, 1325.1, 1256.2, 1176.1, 700.5 cmꢁ1
.
18. (S)-N-(2-Methyl-1-phenylallyl)-2-oxo-2-phenylacetamide (3a). White solid,1H
NMR (400 MHz, CDCl3) d: 8.35 (1H, dd, J = 8.6, 1.2 Hz, NH), 7.64–7.32 (10H,
m, Ph), 5.53 (1H, d, J = 8.8 Hz, CH–N), 5.07 (2H, s, CH2@), 1.72 (3H, s, CH3); 13
C
NMR (100 MHz, CDCl3) d: 187.4 (C@O), 160.5 (C@O), 143.1 (C@), 138.8, 134.5,
131.3, 128.9, 128.5, 128.4, 128.0, 127.4 (Ph), 112.2 (CH2@), 58.5 (C–N), 20.3
5. Kaoru, H.; Toratane, M. Bull. Chem. Soc. Jpn. 1984, 57, 3203–3209.
(CH3); IR mmax: 3286.6, 1683.2, 1660.5, 1632.1, 1579.4, 1543.3, 1218.5, 1173.3,
6. (a) Sabala, R.; Hernández, J.; Carranza, V.; Meza-León, R.; Bernés, S.; Sansinenea,
E.; Ortiz, A. Tetrahedron 2010, 66, 111–120; (b) Mendoza, G.; Hernández, H.;
Quintero, L.; Sosa-Rivadeneyra, M.; Bernès, S.; Sansinenea, E.; Ortiz, A.
Tetrahedron Lett. 2005, 46, 7867–7870; (c) Hernández, H.; Bernès, S.;
Quintero, L.; Sansinenea, E.; Ortiz, A. Tetrahedron Lett. 2006, 47, 1153–1156.
699.6, 667.3 cmꢁ1
279.1250.
; EI-HRMS: calculated for C18H17NO2, 279.1259; found,
19. (S)-N-(3-Methyl-1-phenylbut-3-en-2-yl)-2-oxo-2-phenyl acetamide (3b). White
solid, 1H NMR (400 MHz, CDCl3) d: 8.20 (1H, dd, J = 8.6, 1.6 Hz, NH), 7.60–7.10
(10H, m, Ph), 4.92 (1H, s, CH), 4.91 (1H, s, CH), 4.73 (1H, ddd, J = 8.6, 8.4, 6.0 Hz,
CH–N), 3.06 (1H, dd, J = 14.0, 6.0 Hz, CHaHb), 2.90 (1H, dd, J = 14.0, 8.4 Hz,
CHbHa), 1.84 (3H, s, CH3); 13C NMR (100 MHz, CDCl3) d: 187.7 (C@O), 161.0
(C@O), 143.3 (C@), 137.1, 134.3, 133.1, 131.1, 129.1, 128.4, 128.3, 126.6 (Ph),
7. The
a-chloro-p-methoxiphenylacetyl chloride was prepared following the
procedure described in: (a) Pirrung, M. C.; Tepper, R. J. J. Org. Chem. 1995, 60,
2461–2465; (b) Curini, M.; Epifano, F.; Genovese, S.; Marcotullio, M. C.; Rosati,
O. Org. Lett. 2005, 7, 1331–1333.
112.5 (CH2@), 55.4 (C–N), 39.4 (CH2), 19.8 (CH3); IR
mmax: 3268.4, 2922.6,
8. Ortiz, A.; Quintero, L.; Hernández, H.; Maldonado, S.; Mendoza, G.; Bernés, S.
Tetrahedron Lett. 2003, 44, 1129–1132.
1664.4, 1646.2, 1449.1, 1217.1, 898.6, 745.5, 697.4 cmꢁ1
calculated for C19H20NO2, 294.1494; found, 294.1563.
; FAB-HRMS:

6044
L. Munive et al. / Tetrahedron Letters 51 (2010) 6041–6044
20. (S)-N-(2,4-Dimethylpent-1-en-3-yl)-2-oxo-2-phenylacetamide (3c). White solid,
1H NMR (400 MHz, CDCl3) d: 8.35 (1H, dd, J = 8.4, 1.2 Hz, NH), 7.64–7.45 (5H,
m, Ph), 4.94 (2H, s, CH2@), 4.23 (1H, dd, J = 9.2, 7.6 Hz, CH–N), 1.98 (1H, m, CH),
1.76 (3H, s, CH3), 0.96 (3H, d, J = 6.8 Hz, CH3), 0.94 (3H, d, J = 7.2 Hz, CH3); 13C
NMR (100 MHz, CDCl3) d: 187.8 (C@O), 161.2 (C@O), 142.9 (C@), 134.5, 133.3,
131.2, 128.4 (Ph), 113.0 (CH2@), 60.4 (CN), 29.6 (CH3), 19.9 (CH3), 19.2 (CH),
21. (S)-N-(2-Methyl-1-phenylallyl)-2-oxo-2-p-methoxi-phenil-acetamide
(3d).
Liquid,1H NMR (400 MHz, CDCl3) d: 8.43 (1H, d, J = 8.8 Hz, NH), 7.54–7.26
(7H, m, Ph), 7.00 (2H, d, J = 9.28 Hz, Ph), 5.51 (1H, d, J = 8.8 Hz, CH–N), 5.07 (2H,
s, CH2@), 3.88 (3H, s, OCH3), 1.72 (3H, s, CH3); 13C NMR (100 MHz, CDCl3) d:
185.3 (C@O), 164.7 (C@O), 161.1 (Ph), 143.2 (C@), 139.0, 134.0, 128.8, 128.0,
127.3, 126.3, 113.8 (Ph), 112.2 (CH2@), 58.9 (C–N), 55.5 (OCH3), 20.2 (CH3); IR
17.8 (CH3); IR
m
max: 3269.4, 2964.8, 2952.2, 1685.8, 1663.1, 1630.7, 1555.6,
m
max: 3321.3, 2917.7, 1681.5, 1647.6, 1598.1, 1511.1, 1259.7, 1164.4, 801.7,
1450.3, 1220.6, 892.4, 704.9, 664.6 cmꢁ1; EI-HRMS: calculated for C15H19NO2,
245.1416; found, 245.1406.
700.0 cmꢁ1
.