Synthesis of new asymmetric phosphonylated thiazolines and their use in olefination reactions

Article abstract of DOI:10.1055/s-2000-6324

N-(2-Hydroxyalkyl)-2-phosphonoethanethioamides were prepared from a readily accessible phosphonodithioacetate and commercial chiral β-amino alcohols. Taking advantage of both the presence of the hydroxy group (nucleofuge) and of the C=S (nucleophile) in the same molecule, we obtained new chiral phosphonylated thiazolines by an intramolecular cyclisation using the Mitsunobu procedure. These thiazoline-phosphonates were then involved in Horner-Wadsworth-Emmons reaction to give asymmetric vinylic thiazolines.

Full text of DOI:10.1055/s-2000-6324

PAPER
1143
Synthesis of New Asymmetric Phosphonylated Thiazolines and their Use in
Olefination Reactions
Nicolas Leflemme, Patrice Marchand, Mihaela Gulea, Serge Masson*
Laboratoire de Chimie Moléculaire et Thioorganique UMR 6507 CNRS, ISMRA-Université de Caen, 6 Bd. Maréchal Juin, 14050 Caen,
France
Received 28 January 2000; revised 3 April 2000
This report describes a facile synthesis of chiral phospho-
Abstract:
N-(2-Hydroxyalkyl)-2-phosphonoethanethioamides
nylated thiazolines starting from readily accessible ethyl
phosphonodithioacetate12 and commercial b-amino alco-
hols. The Mitsunobu procedure13,14 was used to perform
were prepared from a readily accessible phosphonodithioacetate
and commercial chiral b-amino alcohols. Taking advantage of both
the presence of the hydroxy group (nucleofuge) and of the C=S (nu-
cleophile) in the same molecule, we obtained new chiral phospho- the internal cyclisation of intermediate hydroxy substitut-
nylated thiazolines by an intramolecular cyclisation using the
Mitsunobu procedure. These thiazoline-phosphonates were then in-
volved in Horner-Wadsworth-Emmons reaction to give asymmet-
synthesis of new vinylic chiral thiazolines.
ric vinylic thiazolines.
ed thioamides. Some of the resulting phosphonylated thi-
azolines were then involved in the H◊W◊E reaction for the
N-(2-Hydroxyalkyl)-2-phosphonoethanethioamides 3a-e
Key words: phosphonate, dithioester, thioamide, thiazoline,
Mitsunobu reaction, Horner-Wadsworth-Emmons reaction
were readily prepared by amination12,15 of the phosphon-
odithioacetate 1 with achiral or enantiopure amino alco-
hols 2a-e (Scheme 1). Phosphonylated thioamides 3a-e
were thus obtained in good yields after purification (Table
Although less studied than oxazolines,1 their sulfur ana-
logues, thiazolines, have recently seen an increasing inter-
1).
est due to the presence of this heterocycle in the structure
of many biologically active compounds including natural
products (such as anguibactin,2 curacin A,3 tantazoles and
mirabazoles4). For example, L-084 (1-b-methylcarbapen-
em carrying thiazoline ring) is a new oral antibiotic,5
arylvinyl thiazolines are antihelmintic and antifungal
agents6 and thiangazole alkaloid is the subject of particu-
lar attention because of its high potency in HIV inhibi-
tion.4,7 Used several years ago as an aldehyde source by A.
I. Meyers,8 thiazolines continued to find applications as
Scheme 1
synthetic intermediates.9 As well as phosphonylated ox-
azolines I,10 sulfur analogues II are convenient Horner-
The resulting thioamides 3a-e were then treated with 1.5
Wadsworth-Emmons (H. W. E.) reagents for the intro-
equivalents of PPh3/DEAD in toluene (Scheme 2). After
48 hours at room temperature, the reaction was complete
duction of a thiazoline ring into an organic structure.6,7
Nevertheless, to the best of our knowledge, only two
methods have been described for the synthesis of these
thiazolines. The first starts from cyanomethyl phospho-
nate and either a b-aminoethanethiol6 or a cysteine deriv-
ative.7 The second, developed in our laboratory, employed
phosphonodithioacetate and bromoethyl amine hydro-
chloride.11 However, these syntheses cannot be easily
generalised because of the limited availability of the start-
ing materials (b-amino thiols or bromides). Therefore, ef-
ficient routes are still needed for the preparation of new
phosphonylated thiazoline (especially with chiral thiazo-
line moiety).
Table 1
Prod- R
31P NMR Isolated [a]2D0
uct
3a
3b
3c
3d
3e
Amino alcohol
(CDCl3), Yield
(c, CHCl3)
d (ppm) (%)
H
23.2
23.2
23.5
23.3
22.9
87
83
79
71
80
–
ethanolamine
C2H5
+30.9 (c=0.5)
-36.2 (c=0.5)
-87.6 (c=0.5)
-72.1 (c=0.5)
R-(-)-2-aminobutanol
(CH3)2CH
S-(+)-valinol
C6H5
S-(-)-1-phenylglycinol
CH2C6H5
S-(-)-phenylalaninol
Synthesis 2000, No. 8, 1143–1147 ISSN 0039-7881 © Thieme Stuttgart · New York

1144
N. Leflemme et al.
PAPER
(as proved by 31P NMR spectroscopy). The expected
products 4a-e were isolated in satisfactory yields (Table
2). Although the cyclisation seems quantitative according
to 31P NMR spectra of the crude reaction products, sepa-
ration of these thiazolines from residual triphenylphos-
phine oxide by silica gel column chromatography proved
difficult. However, this problem of purification can be
easily solved by using PPh3 fixed on solid support.16 This
increases the yield for 4c and 4d to 90% and 78%, respec-
tively.
Table 3
Product
R
R1
R2
Isolated [a]2D0
Yield
(%)
(c, CHCl3)
5a
5b
5c
Et
Me
i-Pr
Ph
H
56
74
76
32
75
71
75
88
–
–
–
–
Et
H
Et
H
5d
5c*
6a
6b
6c
Et
Me
Ph
Me
Me
H
Et
+12.7 (c = 1.0)
-15.1 (c = 0.5 )
-12.2 (c = 1.3 )
- 8.8 (c = 0.8)
Bn
Bn
Bn
Me
i-Pr
Ph
H
H
Scheme 2
The use of these phosphonylated thiazolines as H.W.E re-
agents was examined using the racemic product 4b. With
NaH as a base,6 vinylthiazoline 5a was produced in very
low yield (18%). However, using DBU/LiCl in acetoni-
trile as the deprotonation agent,7 various aldehydes and
acetone could be successfully coupled. The reaction was
then performed with the chiral thiazoline phosphonates 4b
and 4e (Scheme 3). New racemic 5a-d and chiral 5c*,
6a-c vinylic thiazolines were thus obtained in good yields
(Table 3). No loss of enantiomeric purity of the products
under these basic conditions was confirmed by HPLC
analysis on a Chiralpak AD column of the racemic 5c and
enantiopure product 5c*. An excellent selectivity (>99%)
in favour of the trans-isomer was observed in each case.
In conclusion, this work describes an efficient synthesis of
new chiral phosphonylated thiazolines using readily
available starting materials (phosphonodithioacetate and
chiral amino alcohols). These compounds could be used
as Horner-Wadsworth-Emmons reagents and new vinyl-
ic thiazolines were obtained. Reactivity, complexing
properties, and utilisation of these chiral thiazolines deriv-
atives in asymmetric synthesis are under investigation.
The NMR spectra were recorded in CDCl3 with a Bruker AC 250
spectrometer; the chemical shifts (d) are expressed in ppm relative
to TMS for 1H, 13C nuclei and to H3PO4 for 31P nucleus (broad band
decoupling); the coupling constants (J) are given in Hz; convention-
al abbreviations are used. Signals corresponding to alcoholic pro-
tons are not reported. IR spectra were recorded on a Perkin-Elmer
684 spectrometer. A typical example of spectrum is given for each
series of compounds. Elemental microanalyses were obtained from
the "Service de Microanalyse ICSN" (Gif sur Yvette). Analyses of
sulfur were performed at Caen following Debal and Levy’s method
(Bull. Chem. Soc. Fr. 1968, 426). High resolution mass spectra
(HRMS) were obtained with a JEOL GCmate spectrometer.
N-(2-Hydroxyalkyl)(diethylphosphono)ethanethioamide (3);
Typical Procedure
Scheme 3
Table 2
A solution of phosphonodithioacetate 1 (1 mmol) in THF (5 mL)
was added to a stirred mixture of amino alcohol 2 (1 mmol) and
Et3N (1.5 mmol) in THF (15 mL). The mixture was allowed to react
for 24 h at r.t. The colour changed from orange to pale yellow. The
solvent was removed and the residual crude product was purified by
column chromatography on silica gel (EtOAc/MeOH, 95:5) to af-
ford phosphonothioamides 3. The 31P NMR data of 3 are recorded
Product
R
31P NMR
(CDCl3),
d (ppm)
Isolated [a]2D0
Yield
(%)
(c, CHCl3)
1
in Table 1 and H and 13C NMR data in Table 4. Satisfactory mi-
croanalyses were obtained for 3a, b, c, e C ± 0.40; H ± 0.20; N ±
0.20; P ± 0.02; S ± 0.19.
4a
4b
4c
4d
4e
H
23.1
22.9
23.3
22.7
22.8
51
78
–
3b
Et
+24.6 (c = 1.10)
IR (NaCl): n = 3450 (nOH), 3232 (nNH), 2972, 2936, 2878, 1554 (nN-
C=S), 1432, 1394, 1236 (nP=O), 1164 (nC=S), 1054, 1028, 972 cm-1.
iPr
Ph
Bn
76 (90)a -20.9 (c = 0.75)
55 (78)a -14.8 (c = 0.52)
1-[(Diethylphosphono)methyl]-(4,5-dihydro)thiazole (4); Gen-
eral Procedure
A solution of diethyl azodicarboxylate (1.5 mmol) in THF (5 mL)
was added dropwise to a stirred mixture of phosphonothioamide 3
(1 mmol) and triphenylphosphine (1.5 mmol) in THF (20 mL). The
61
-29.4 (c = 0.5)
a Yields obtained using PPh3 on solid support.
Synthesis 2000, No. 8, 1143–1147 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of New Asymmetric Phosphonylated Thiazolines and their Use in Olefination Reactions
1145
Table 4 1H and 13C NMR Data of Compounds 3
Producta
1H NMR (CDCl3),
13C{1H}NMR (CDCl3),
d , J (Hz)
d , J (Hz)
3a
1.35 [t, 6 H, J = 6.9, (CH3CH2O)2P], 3.50 (d, 2 H, J = 22.0,
PCH2), 3.62 (s, 4 H, NCH2CH2OH), 4.05-4.25 [m, 4 H,
(CH3CH2O)2P], 9.40 (br s, 1 H, NH)
16.3 [d, J = 6.3, (CH3CH2O)2P], 44.4 (d, J = 128.3, PCH2),
49.2 (CH2NH), 59.7 (CH2OH), 63.6 [d, J = 6.9,
(CH3CH2O)2P), 192.5 (d, J = 6.3, C=S)
3b
3c
3d
3e
0.99 (t, 3 H, J = 7.4, CH3CH2), 1.35 [t, 6 H, J = 6.9,
(CH3CH2O)2P], 1.72-1.82 (m, 2 H, CH3CH2), 3.45-3.65
(m, 2 H, PCH2), 3.75-3.95 (m, 2 H, CH2OH), 4.05-4.25
[m, 4 H, (CH3CH2O)2P], 4.30 (m, 1 H, CHNH), 8.60 (br s,
1 H, NH)
10.5 (s, CH3CH2), 16.3 [d, J = 6.1, (CH3CH2O)2P], 23.1
(CH3CH2), 44.6 (d, J = 126.9, PCH2), 59.4 (CHNH), 62.5
(s, CH2OH), 63.1 & 63.8 [2d, J = 6.9, (CH3CH2O)2P],
192.3 (d, J = 6.4, C=S)
1.01 & 1.02 [2d, 6 H, J = 6.8, (CH3)2CH], 1.30 [t, 6 H, J =
7.1, (CH3CH2O)2P], 2.10 [hept, 1 H, J = 6.8, (CH3)2CH],
3.45-3.65 (m, 2 H, PCH2), 3.75-3.95 (m, 2 H, CH2OH),
4.05-4.25 [m, 4 H, (CH3CH2O)2P], 4.30 (m, 1 H, CHNH),
8.60 (br s, 1 H, NH)
15.2 & 15.3 [2d, J = 6.2, (CH3CH2O)2P], 19.6 & 19.6 [2s,
(CH3)2CH], 26.5 [(CH3)2CH], 45.0 (d, J = 126.4, PCH2),
61.8 (CHNH), 62.8 & 63.1 [2d, J = 6.9, (CH3CH2O)2P],
63.9 (s, CH2OH), 192.8 (d, J = 6.5, C=S)
1.21 & 1.32 [2t, 6 H, J = 7.0, (CH3CH2O)2P], 3.45-3.65 (m,
2 H, PCH2), 3.85-4.35 [m, 7 H, CH2OH, (CH3CH2O)2P,
CHNH],; 7.15-7.30 (m, 5 H, C6H5), 8.60 (br s, 1 H, NH)
16.6 & 16.7 [2d, J = 6.8, (CH3CH2O)2P], 45.0 (d, J = 127.0,
PCH2), 62.4 (CHNH), 63.8 & 64.1 [2d, J = 6.4,
(CH3CH2O)2P]; 65.3 (d, J = 1.5, CH2OH), 127.6, 128.0,
128.9, (3s, CHarom), 138.2 (Carom), 192.7 (d, J = 6.6,
C=S)
1.30 [t, 6 H, J = 7.3, (CH3CH2O)2P], 2.90-3.10 (m, 2 H,
CH2C6H5), 3.35-3.55 (m 2 H, PCH2), 3.50-3.80 (m, 2 H,
CH2OH), 4.05-4.30 [m, 4 H, CH3CH2O)2P], 4.75 (m, 1 H,
CHNH), 7.15-7.35 (m, 5 H, C6H5), 8.95 (br s, 1 H, NH)
16.7 [d, J = 6.4, (CH3CH2O)2P], 35.7 (CH2C6H5), 44.9
(d, J = 128.0, PCH2), 59.6 (CHNH), 61.4 (CH2OH), 63.5
& 64.2 [2d, J = 6.8, (CH3CH2O)2P], 126.9, 128.9, 129.6 (3s,
CHarom), 138.2 (Carom), 192.2 (d, J = 6.5, C=S)
solution became pale yellow and a white precipitate of diethyl hy-
drazine-N,N’-dicarboxylate was formed. The mixture was stirred for
48 h at r.t. then pentane (20 mL) was added and the precipitate was
filtered off. The solvents were removed in vacuo and the crude mix-
ture was chromatographed on silica gel (Et2O/acetone, 80:20) to af-
ford the pure phosphonothiazoline 4. The 31P NMR data of 4 are
recorded in Table 2 and 1H and 13C NMR data in Table 5. Satisfac-
tory microanalyses were obtained for 4a-e C ± 0.40; H ± 0.36; N±
0.40; P ± 0.28; S ± 0.10.
4b
IR (NaCl): n = 2976, 2932, 2876, 1668, 1554, 1460, 1394, 1368,
1246 (nP = O), 1120, 1098, 1028, 970 cm-1.
Table 5 1H and 13C NMR Data of Compounds 4a
Product
1H NMR (CDCl3),
13C{1H}NMR (CDCl3),
d, J (Hz)
d, J (Hz)
4b
1.02 (t, 3 H, J = 7.4, CH3CH2), 1.34 [t, 6 H, J = 7.2,
(CH3CH2O)2P], 1.56-1.85 (m, 2 H, CH3CH2), 3.02-3.42
(m, 4 H, PCH2, CH2S), 4.05-4.25 [m, 4 H, (CH3CH2O)2P],
4.30-4.47 (m, 1 H, CHN)
11.2 (CH3CH2), 16.7 [d, J = 6.3, (CH3CH2O)2P], 28.2
(CH3CH2), 33.5 (d, J = 137.9, PCH2), 39.2 (SCH2), 62.9 &
63.0 [2d, J = 6.4, (CH3CH2O)2P], 78.9 (d, J = 1.6, CHN),
160.5 (d, J = 8.6, S-C=N)
4c
4d
4e
0.88 & 0.95 [2d, 6 H, J = 6.7, (CH3)2CH], 1.24 [t, 6 H, J =
7.1, (CH3CH2O)2P], 1.95 [hept, 1 H, J = 6.7, (CH3)2CH],
3.24-3.45 (m, 4 H, PCH2, CH2S), 4.05-4.25 [m, 4 H,
(CH3CH2O)2P], 4.30 (m, 1 H, CHN)
13.2 [2d, J = 5, (CH3)2CH], 15.3 [d, J = 6.2, (CH3CH2O)2P],
31.8 [d, J = 1.5, (CH3)2CH], 32.0 (d, J = 137.9, PCH2), 35.3
(SCH2), 61.3 & 61.5 [2d, J = 6.4, (CH3CH2O)2P], 73.4 (s,
CHN), 158.9 (d, J = 8.7, S-C=N)
1.26 & 1.35 [2t, 6 H, J = 7.2, (CH3CH2O)2P], 3.25 (d, 2 H,
JHP = 21.1, PCH2), 3.45 (m, 1 H, SCHH), 3.60 (m, 1 H,
SCHH), 4.05-4.15 [m, 4 H, (CH3CH2O)2P], 5.45 (m, 1 H,
CHN), 7.25-7.40 (m, 5 H, C6H5)
15.3 [d, J = 6.2, (CH3CH2O)2P], 32.2 (d, J = 137.6, PCH2),
41.1 (SCH2), 61.6 & 61.65 [2d, J = 6.4, (CH3CH2O)2P],
78.9 (d, J = 1.5, CHN), 126.8, 129.2, 129.6 (3s, CHarom),
137.8 (Carom), 161.6 (d, J = 8.5, S-C=N)
1.35 [t, 6 H, J = 7.1, (CH3CH2O)2P], 2.7 (m, 1 H,
C6H5CHH), 3.1 (d, 2 H, JHP = 21.6, PCH2), 3.05-3.45 (m,
3 H, C6H5CHH, CH2S), 4.05-4.25 [m, 4 H, (CH3CH2O)2P],
4.7 (m, 1 H, CHN), 7.00-7.25 (m, 5 H, C6H5)
16.4 [d, J = 6.2, (CH3CH2O)2P], 33.1 (d, J = 137.9, PCH2),
38.4 (SCH2), 39.9 (d, J = 2.2, CH2C6H5), 62.6 & 62.65 [2d,
J = 6.5, (CH3CH2O)2P], 78.4 (CHN), 126.8, 129.2, 129.6
(CHarom), 137.8 (Carom), 161.2 (d, J = 8.6, S-C=N)
a Description of 4a was already published.6
Synthesis 2000, No. 8, 1143–1147 ISSN 0039-7881 © Thieme Stuttgart · New York

1146
N. Leflemme et al.
PAPER
Table 6 1H and 13C NMR Data of Compounds 5 & 6
Product*
1H NMR (CDCl3),
13C{1H}NMR (CDCl3),
d , J (Hz)
d
5a
1.03 (t, 3 H, J = 7.4, CH2CH3), 1.59-1.86 (m, 2 H,
CH2CH3), 1.89 (d, 3 H, J = 5.3, CH3CH=CH), 2.92-3.33
(m, 2 H, CH2S), 4.40 (m, 1 H, CHN), 6.61-6.43 (m, 2 H;
HC=CH)
10.0 (CH2CH3), 17.5 (CH2CH3), 27.1 (CH3CH=CH), 35.8
(CH2S), 77.6 (CHN), 125.7 (CH3CH=CH), 138.9
(CH3CH=CH), 164.8 (S-C=N)
5b
5c
5d
6a
6b
6c
1.04 (t, 3 H, J = 7.5, CH2CH3), 1.07 [d, 6 H, J = 6.7,
CH(CH3)2], 1.62-1,89 (m, 2 H, CH2CH3), 2.48 [m, 1 H,
CH(CH3)2], 2.92-3.33 (m, 2 H, CH2S), 4.37-4.43 (m, 1 H,
CHN), 6.24-6.38 (m, 2 H, HC=CH)
11.6 (CH2CH3), 21.1 (CH2CH3), 21.9 [CH(CH3)2], 37.2
(CH2S), 31.5 [CH(CH3)2], 76.3 (CHN), 125.0 [(CH3)2CH-
HC=CH], 151.3 [(CH3)2CH-HC=CH], 163.7 (S-C=N)
1.07 (t, 3 H, J = 7.4, CH2CH3), 1.65-1.93 (m, 2 H,
CH2CH3), 3.01-3.42 (m, 2 H, CH2S), 4.47 (m, 1 H, CHN),
7.06 (d, 1 H, J = 16.1, Ph-CH=CH), 7.10 (d, 1 H; J = 16.1,
Ph-CH=CH), 7.32-7.51 (m, 5 H, C6H5)
11.8 (CH2CH3), 22.6 (CH2CH3), 37.8 (CH2S), 77.1 (CHN),
125.4 (Ph-CH=CH), 128.0, 129.2, 129.4 (CHarom.), 134.1
(Carom.), 145.1 (Ph-CH=CH), 164.7 (S-C=N)
1.04 (t, 3 H, J = 7.4, CH2CH3), 1.59-1.84 (m, 2 H,
CH2CH3), 1.87 & 2.06 [2d, 6 H, J = 6.8, (CH3)2C=CH],
2.98-3.34 (m, 2 H, CH2S), 4,39 (m, 1 H, CHN), 5.97 (s, 1
H, C=CH)
11.5 (CH2CH3), 21.0 (CH2CH3), 27.6 & 28.6 [2s,
(CH3)2C=CH], 38.0 (CH2S), 78.8 (CHN), 119,6
[(CH3)2C=CH], 146.7 [(CH3)2C=CH], 164.1 (S-C=N)
1.90 (d, 3 H, J = 5.0, CH3CH=CH), 2.75 (m, 1 H, CHHPh),
3.00 (m, 1 H, CHHS), 3.17 (m, 1 H, CHHS), 3.23 (m, 1 H,
CHHPh), 4.62-4.73 (m, 1 H, CHN), 6.30-6.44 (m, 2 H,
HC=CH), 7.26-7,31 (m, 5 H, C6H5)
18.5 (CH3-CH=CH), 36.4 (CH2S), 40.3 (CH2Ph), 78.0
(CHN), 126.5 (CH3-CH=CH), 126.6, 128.5 & 129.3 (3s,
CHarom), 138.6 (Carom), 140.2 (CH3-CH=CH), 166.6 (S-
C=N)
1.08 [d, 6 H, J = 6.8, CH(CH3)2], 2,49 [m, 1 H, CH(CH3)2],
2.75 (m, 1 H, CHHPh), 3.00 (m, 1 H, CHHS), 3.18 (m, 1
H, CHHS), 3.24 (m, 1 H, CHHPh), 4.70 (m, 1 H, CHN),
6.26-6.40 (m, 2 H, HC=CH), 7.26-7.32 (m, 5 H, C6H5)
21.9 [CH(CH3)2], 31.8 (CH(CH3)2), 36.8 (CH2S), 40.7
(CH2Ph), 78.4 (CHN), 122.9 [(CH3)2CH-CH=CH], 126.9,
129.0, 129.6 (3s; CHarom), 139.0 (Carom), 152.1
[(CH3)2CH-CH=CH], 167.6 (s, S-C=N)
2.81 (m, 1 H, CHHPh), 3.07 (m, 1 H, CHHS), 3.21-3.32
(m, 2 H, CHHS, CHHPh), 4.77-4.89 (m, 1 H, CHN), 7.07
(d, 1 H, J = 16,2, PhCH=CH), 7.10 (d, 1 H, J = 16,2,
PhCH=CH), 7.26-7.57 (m, 10 H, 2 ¥ C6H5)
37.1 (CH2S), 40.7 (CH2Ph), 78.6 (CHN), 123.2
(PhCH=CH), 126.9, 127.9, 129.0, 129.3, 129.7, 129.9 (6s,
CHarom), 135.8 & 138.9 (2s, Carom), 141.6 (PhCH=CH),
167.2 (S-C=N)
Vinylic Thiazolines 5 and 6; General Procedure
Acknowledgement
A solution of phosphonothiazoline 4 (1 mmol) dissolved in MeCN
(5 mL) was added dropwise to a stirred mixture of diazabicycloun-
decene (1.1 mmol) and LiCl (1.1 mmol). Aldehyde (1.2 mmol) in
MeCN (5 mL) was added and the mixture was stirred for 16 h at r.t.
In the case of (R1 = Me) pure acetaldehyde was added at 0 °C and
the reaction carried out at this temperature for 20 h. After filtration
of the salts and evaporation of the solvent, the crude mixture was
chromatographed on silica gel (EtOAc) to afford the pure vinylic
thiazoline 5 or 6. The 1H and 13C NMR data of 5 and 6 are recorded
in Table 6.
We warmly thank M. Lemarié who conducted the HPLC analysis.
This work was supported by the RINCOF (Contrat de plan Etat-
Bassin Parisien-Régions Haute-Normandie et Basse-Normandie)
which is gratefully acknowledged.
References
(1) Lutomski, K. A.; Meyers, A. I. Asymmetric Synthesis via
Chiral Oxazolines. In Asymmetric Synthesis, Vol. 3;
Academic Press: New York, 1984, p 213.
IR (NaCl): n = 2962, 2930, 2872, 1632, 1582, 1450, 1188, 960, 752,
692 cm-1.
Pfaltz, A. Synlett 1999, 835.
Reuman, M.; Meyers, A. I. Tetrahedron Lett. 1985, 41, 837
Gant, T. G.; Meyers, A. I. Tetrahedron 1994, 50, 2297.
(2) Jalal, M. A. F.; Hossain, M. B.; van der Helm, D.; Sanders-
Loehr, J.; Actis, L. A.; Crosa, J. H. J. Am. Chem. Soc. 1989,
111, 292.
(3) Gerwick, W. H.; Proteau, J.; Nagle, D. G.; Hamel, E.;
Blokhin, A.; Slate, D. L. J. Org. Chem. 1994, 59, 1243.
Muir, J. C.; Pattenden, G.; Ye, T. Tetrahedron Lett. 1998, 39,
2861.
Enantiopure thiazoline 5c* was analysed by HPLC (Chiralpak AD
analytical column (Daicel); eluting with hexane/propan-2-ol
(90:10), flow rate 1 mL/min, 234 nm, tR = 9.8 min). The HPLC sep-
aration was calibrated using racemic product 5c (tR1 = 6.7 min,
t
R2 = 9.8 min).
Satisfactory analyses were obtained for 5c.
HRMS (EI): m/z calcd for C13H15NS (M+) 217.0925. Found:
217.0948.
(4) Wipf, P.; Venkatraman, S. Synlett 1997, 1; and references
cited therein.
Anal. Calcd for C13H15NS: S, 13.86. Found: S, 13.69.
(5) Hayashi, K.; Sato, C.; Hiki, S.; Kumagai, T.; Tamai, S.; Abe,
T.; Nagao, Y. Tetrahedron Lett. 1999, 40, 3761.
Synthesis 2000, No. 8, 1143–1147 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of New Asymmetric Phosphonylated Thiazolines and their Use in Olefination Reactions
1147
(6) Caujolle, R.; Baziard-Mouysset; Favrot, J. D.; Payard, M.;
Loiseau, P. R. Eur. J. Med. Chem. Chim. Ther. 1993, 28, 29.
(7) Ehrler, J.; Farooq, S. Synlett 1994, 702.
(8) Meyers, A. I.; Munavu, R.; Durandetta, S Tetrahedron Lett.
1972, 37, 3929.
(9) Elliot, M. C.; Monk, A. E.; Kruiswijk, E.; Hibbs, D. E.;
Jenkins, L.; Jones, D. V. Synlett 1999, 1379.
(10) Meyers, A. I.; Shipman, M. J. Org. Chem. 1991, 56, 7098.
Chesney, A.; Bryce, M. R. Tetrahedron: Asymmetry 1996, 7,
3247.
Tamaru, Y.; Hioki, T.; Kawamura, S.; Satomi, H.; Yoshida, Z.
J. Am. Chem. Soc. 1984, 106, 3876.
Tanaka, T.; Hashimoto,T.; Iino, K.; Sugimura, Y.; Miyadera,
T. J. J. Chem. Soc., Chem. Commun. 1982, 713.
Takahata, H.; Ohkura, E.; Ikuro, K.; Yamazaky, T. Synth.
Commun. 1990, 20, 285.
(14) Galéotti, N.; Montagne, C.; Poncet, J.; Jouin, P. Tetrahedron
Lett. 1992, 33, 2807.
(15) Bulpin, A.; Le Roy-Gouvernnec, S.; Masson, S. Phosphorus,
Sulfur Silicon Relat. Elem. 1994, 89, 119.
Chesney, A.; Bryce, M. R. Batsanov, A. S.; Howard, J. A. K.;
Goldenberg, L. M. Chem. Commun. 1998, 677.
(11) The method is described with phosphonodithioformate and b-
bromoethylamine hydrochloride: see ref. (15).
(12) Le Roy-Gouvernnec, S.; Masson, S. Synthesis 1995, 1393.
(13) Nagasawa, H.; Mitsunobu, O. Bull. Chem. Soc. Jpn. 1981, 54,
2223.
(16) Bernard, M.; Ford, W. T. J. Org. Chem. 1983, 48, 326.
Article Identifier:
1437-210X,E;2000,0,08,1143,1147,ftx,en;P01100SS.pdf
Synthesis 2000, No. 8, 1143–1147 ISSN 0039-7881 © Thieme Stuttgart · New York