A trial toward the synthesis of γ-fluorinated β-amino-α-thiohydroxyamino acid: A finding of desulfurizative C-C bond formation in Thio-Wittig-Type rearrangement of S-(N-aryltrifluoroacetimidoyl)thioglycolates

Full text of DOI:10.1021/jo0010330

1
026
J . Org. Chem. 2001, 66, 1026-1029
A Tr ia l tow a r d th e Syn th esis of
Sch em e 1
γ-F lu or in a ted â-Am in o-r-th ioh yd r oxya m in o
Acid : A F in d in g of Desu lfu r iza tive C-C
Bon d F or m a tion in Th io-Wittig-Typ e
Rea r r a n gem en t of S-(N-Ar yl-
tr iflu or oa cetim id oyl)th ioglycola tes
Sch em e 2
Kenji Uneyama,* Hironari Ohkura, J ian Hao, and
Hideki Amii
Department of Applied Chemistry, Faculty of Engineering,
Okayama University, Okayama 700-8530, J apan
uneyamak@cc.okayama-u.ac.jp
Received J uly 10, 2000
The study of the chemistry and biological activity of
antibiotics and enzyme inhibitors of fluorinated â-amino
acids1 has gained considerable interest during the last
two decades. On this basis, unnatural and structurally
new fluorinated amino acids are current synthetic tar-
gets. Recently, we reported the synthesis of R-hydroxy-
â-amino acids via Wittig rearrangement3 of O-(N-
arylimidoyl)glycolates 1 to R-hydroxy-â-iminocarboxylates
,2
Sch em e 3
,4
3
(Scheme 1). As an extension of the O-Wittig rearrange-
ment (1 f 3), it is interesting to see whether the
corresponding thio-analogues 2 undergo the same type
of rearrangement to â-imino-R-thiohydroxycarboxylates
Ta ble 1. Effect of Tem p er a tu r e a n d Ba ses in th e
Con ver sion of 2a to 8a
5
, which would be promising precursors of R-thiohydroxy-
â-amino-γ,γ,γ-trifluorobutanoic acid, a new class of R-thio-
hydroxyamino acids (Scheme 1). Here, we describe the
preparation and the base-promoted reactions of thiogly-
colates 2 in which unexpected desulfurization5 and in-
tramolecular ring closure with N-aromatic rings were
discovered.
entry
base
T (°C)
time (h)
yield (%) of 8a
1
2
3
4
5
6
7
8
9
LTMP
NaH
KO Bu
-40
-40
-40
-20
-40
-60
-80
-40
-40
-40
-40
9
9
9
9
9
9
9
1
3
4
6
62
62
60
61
71
t
LDA
LDA
LDA
LDA
LDA
LDA
LDA
LDA
a
20
The thioglycolates 2 were prepared in good yields by
the nucleophilic displacement of the fluorinated imidoyl
chlorides 76 with the commercially available thioglyco-
a
no reaction
25
49
57
a
,7
a
a
1
9
10
1
lates under the basic conditions (Scheme 2). F NMR of
a
1
65
2
a showed two broad peaks for CF
3
group at 96.5 and
a
The amounts of recovered 2a were 75, 98, 69, 33, 17, and 11%
in entries 6, 7, 8, 9, 10, and 11, respectively.
1
00.0 ppm in DMSO-d at room temperature, which
6
(
1) (a) Banks, R. E. J . Fluorine Chem. 1998, 87, 1. (b) Surya, P. G.
K.; Yudin, A. K. Chem. Rev. 1997, 97, 757.
2) (a) Soloshonok, V. A.; Ono, T.; Soloshonok, I. V. J . Org. Chem.
997, 62, 7538. (b) Fustero, S.; Pina, B.; Torre, M. G.; Navarro, A.;
coalesced to one peak when the NMR temperature was
raised to 50 °C. This phenomenon may arise from the
stereoisomerism of an N-aryl group, anti or syn to the
trifluoromethyl group.
The thioglycolates 2 were subjected to the lithium
diisopropylamide (LDA)-promoted Wittig-type rearrange-
ment. Surprisingly, the reaction provided enamino esters
(
1
Arellano, C. R.; Simon, A. Org. Lett. 1999, 1, 977. (c) Fustero, S.; Torre,
M. G.; Pina, B.; Fuentes, A. S. J . Org. Chem. 1999, 64, 5551. (d) Knorr,
R.; Weiss, A. Chem. Ber. 1981, 114, 2104. (e) Fustero, S.; Pina., B.;
Simon-Fuentes, A. Tetrahedron Lett. 1997, 38, 6771. (f) Bartoli, G.;
Cimarelli, C.; Dalpozzo, R.; Palmieri, G. Tetrahedron. 1995, 51, 8613.
(
g) Soloshonok, V. A.; Kukhar, V. P. Tetrahedron 1996, 52, 6953. (h)
8
bearing no sulfur moiety and no expected â-imino-R-
Linderman, R. J .; Kirollos, K. S. Tetrahedron Lett. 1990, 19, 2689. (i)
Fustero, S.; Navarro, A.; Diaz, D.; Torre, M. G.; Asensio, A. J . Org.
Chem. 1996, 61, 8849. (j) Fustero, S.; Torre, M. G.; J ofre, V.; Carlon,
R. P.; Navarro, A.; Fuentes, A. S. J . Org. Chem. 1998, 63, 8825.
thiohydroxyesters 5 (Scheme 3). The effects of bases and
the reaction conditions for the yield of 8 are shown in
Table 1. The LDA was the best base for this enamine
formation in our estimation. The lower reaction temper-
ature (Table 1, entries 6 and 7) and the shorter reaction
time (Table 1, entries 8-10) resulted in mostly recovery
of 2a . Results of the desulfurizative rearrangement of
some ring-substituted compounds 2 are summarized in
Table 2. Both electron-withdrawing (Table 2, entries 4
and 5) and electron-donating substituents (Table 2,
entries 1 and 6) provided the products 8 in reasonable
yields, suggesting that the electronic effect in the rear-
(
(
3) Uneyama, K.; Hao, J .; Amii, H. Tetrahedron Lett. 1998, 39, 4079.
4) (a) Nakai, T.; Mikami, K. Chem. Rev. 1986, 86, 885. (b) Ono, T.;
Kukhar, V. P.; Soloshonok, V. A. J . Org. Chem., 1996, 61, 6563. (c)
Tomooka, K.; Shimizu, H.; Inoue, T.; Shibata, H.; Nakai, T. Chem. Lett.
1
999, 759. (d) Miyata, O.; Koizumi T.; Ninomiya, I.; Naito, T. J . Org.
Chem. 1996, 61, 9078. (e) Zimmerman, H. E. Molecular Rearrangement;
963; Chapter 6, p 345.
5) (a) Eschenmoser, A. Q. Rev. Chem. Soc. 1970, 24, 366. (b)
1
(
Loeloger, P.; Fluckiger, E. Organic Syntheses; Wiley: New York, 1973;
Collect. Vol. VI, p 776.
(
6) Uneyama, K. J . Fluorine Chem. 1999, 97, 11.
(7) Tamura, K.; Mizukami, H.; Maeda, K.; Watanabe, H.; Uneyama,
K. J . Org. Chem. 1993, 58. 32.
1
0.1021/jo0010330 CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/06/2001

Notes
J . Org. Chem., Vol. 66, No. 3, 2001 1027
Ta ble 2. Yield of 8 in Desu lfu r iza tive Rea r r a n gem en t of
2
Sch em e 5
entry
R1
R2
Ar
yield (%) of 8
1
2
3
4
5
6
7
Me
Bn
H
H
Me
H
H
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
3-ClC6H4
3,5-Cl2C6H3
3,5-Me2C6H3
4-NO2C6H4
8a (71)
8b (91)
8c (54 )
8d (90)
8e (77)
8f (70)
8g (7)
a
Me
Me
Me
Me
Me
H
H
a
A mixture of 8c and its tautomer (3-iminoester).
Sch em e 4
Sch em e 6
rangement is small. However, the nitro compound mostly
decomposed under the experimental conditions. Mean-
while, one-pot reaction (7a f 2a f 8a ) by using 2.5 equiv
of LDA also gave a reasonable yield of compound 8a
reaction of the solid with tributylphosphine produced the
phosphine sulfide 14 (Scheme 5).
9
Then, the trapping of thiolate intermediate 12 by
benzoylation was examined. After treating 2a with LDA
at -40 °C for 4 h, benzoyl chloride was added at once
into the reaction mixture, which was then stirred at -40
(59%).
In Wittig-type rearrangement of O-(N-arylimidoyl)-
glycolates 1 to R-hydroxy-â-iminocarboxylates 3, the best
result was obtained under the conditions of lithium
°
C for another 30 min. 2-Thiobenzoyloxy-3-(N-benzoyl-
amino)-2-butenoate 18 was isolated in 34% yield along
with compounds 8a (30%) and 2a (16%). Meanwhile,
when the reaction mixture was quenched with aqueous
2
(
-
,2,6,6-tetramethylpiperidide (LTMP) in a mixed solvent
DME/THF ) 3:1) at the temperature between -70 and
105 °C for 1 h. The reaction of 2 proceeded at the higher
NH
4
Cl under the same conditions, the yield of 8a was
temperature with a longer reaction time (-40 °C for 9
h) than that of oxygen compound 1. To clarify the relative
reactivities between 1 and 2, and the reaction mechanism
of the transformation of 2 to 8, several additional
experiments were conducted. At first, both 1a and 2a
were separately treated with LDA at -80 °C for 1 h and
5
7% (Table 1, entry 10) and the crude sample did not
show absorption of thiohydroxyl group in the IR spec-
trum. These experimental results suggest that desulfu-
rization occurs not only under the reaction conditions but
also under the workup conditions. Enamine 18 was
isolable as a final product, because of the high acidity of
R-methine proton of S-benzoyl compound of 12 and
thermodynamically more favorable trifluoromethyl enam-
ine form 18 rather than the imine form.10 Isolation of 18
clearly suggests that thiolate 12 is an initial rearrange-
ment intermediate that gradually undergoes desulfuri-
zation under the reaction conditions. Due to the strong
electron-withdrawing nature of both trifluoroiminyl and
carboalkoxyl groups, desulfurization as shown in 12
would occur easily. A similar type of desulfurization from
the reaction was quenched with D
revealed 1a provided the rearranged product 3a (Scheme
), but 2a was simply deuterated on R-carbon to carboxyl
2
O. This experiment
4
group and did not undergo the expected rearrangement
to 8. Next, a mixture of 1a (0.5 mmol) and 2a (0.5 mmol)
was treated with 0.5 mmol of LDA at -80 °C for 1 h and
then was added deuterium oxide. Surprisingly, deute-
rium was incorporated in 2a to give 9a , but 1a was
recovered intact. These results suggest that deprotona-
tion from 2a occurs much more easily than that from 1a ,8
but the carbanion of 2a rearranges more slowly at -80
1
2
,3-dicarbonyl-2-thiol is known.11 It is interesting that
-thiol compound 16 was isolated along with â-amino-
°
C as compared with 1a . It is plausible that the imino
cinnamate 17 in the reaction of 15 with LDA (Scheme
). The lower stability of 12 is presumably due to the
esters 2 undergo Wittig type rearrangement only at the
higher temperature. The next questions to be solved are
what the sulfur moiety is transformed to and when
desulfurization occurs. If the reaction proceeds stepwise
as shown in Scheme 5, elemental sulfur must be elimi-
nated. In fact, the crude product mixture in ether was
decanted and a slightly yellow solid was obtained. The
mass spectrum of the solid clearly revealed a typical
fragment of elemental sulfur that was consistent with
that of the authentic elemental sulfur. Moreover, the
6
stronger electron-withdrawing nature of trifluoromethyl
group in 12 than that of the phenyl group in 16.
The another interesting phenomenon observed in the
chemistry of thiolate 12 was the oxidative intramolecular
cyclization (2a f 12a f 19). Thiolate 12a could be
oxidized with elemental iodine to the corresponding
(
9) Hoffmann, H.; Schellenbeck, P. Chem. Ber. 1967, 100, 692.
(10) Methyl 4-imino-5,5,5-trifluoropentanoate isomerizes to methyl
4
-amino-5,5,5-trifluoro-3-pentenoate. Ohkura, H.; Uneyama, K. Un-
(
8) It is well-known that base-promoted deprotonation from R-carbon
published results.
of alkyl thioether is much faster than that of alkyl ether. Price, C. C.;
Oae, S, Sulfur Bonding; Ronald Press: New York, 1962. Oae, S.;
Takagi, W.; Ohno, A. J . Am. Chem. Soc. 1961, 83, 5036.
(11) (a) Roth, M.; Dubs, P.; Gotschi, E.; Eschenmoser, A. Helv. Chem.
Acta, 1971, 54, 710. (b) Rolfs, A.; Liebscher, J . J . Org. Chem. 1997,
62, 3480.

1
028 J . Org. Chem., Vol. 66, No. 3, 2001
Notes
Sch em e 7
then stirred at 0 °C (ice water bath) for 1 h. After all of the
imidoyl chloride was consumed (monitored by TLC), the reaction
was stopped and the insoluble salt formed in the reaction was
filtered off. The usual workup and distillation under reduced
pressure provided the product 2a (92%, 5.931 g) as a yellowish
product
Meth yl S-(1-((N-4-m eth oxyp h en yl)im in o)-2,2,2-tr iflu o-
-1 1
r oeth yl)th ioglycola te (2a ): IR (neat) 1746, 1634 cm ; H NMR
(
(
3
6
DMSO-d ) δ 7.2-6.9 (m, 4 H), 3.89 (s, 2 H), 3.78 (s, 3 H), 3.64
s, 3 H); 19F NMR (DMSO-d
, 60 °C) δ 96.5 (brs, CF
NO S: C, 46.90;
6
3
); MS m/z
+
07 (3) [M] , 202 (100). Anal. Calcd for C12
H
12
F
3
3
H, 3.94; N, 4.56. Found: C, 46.98; H, 4.21; N, 4.55.
Gen er a l P r oced u r e for Rea r r a n gem en t Rea ction of 2.
To a solution of diisopropylamine (0.75 mmol) in freshly distilled
THF (3 mL) cooled to -40 °C under argon atmosphere was added
dropwise n-BuLi in hexane (0.75 mmol), and then the mixture
was stirred for an additional 30 min. Trifluoromethylated imino
thioglycolate 2 (0.5 mmol, 0.156 g) in freshly distilled THF (2
mL) was added dropwise to the LDA solution over 10 min. The
reaction mixture was stirred for 9 h. After almost all the starting
material was gone (checked by TLC), 10 mL of diethyl ether was
added and the reaction was quenched with 10 mL of aqueous
Sch em e 8
NH
color of water layer became light yellowish and was dried over
MgSO . Purification through column chromatography (silica gel,
4
Cl. The organic layer was then washed with water until the
4
AcOEt/hexane ) 1:10) gave the yellowish product 8a (71%, 0.098
g).
thioalkoxyl radical which subsequently underwent in-
tramolecular cyclization via a radical addition to the aryl
ring, affording compound 19 (Scheme 7). The structure
of 19 was determined by X-ray crystallography of the
corresponding amide 20 (Figure 1, Supporting Informa-
tion), which was prepared by ester-amide exchange
reaction12 with benzylamine (Scheme 8).
Meth yl 3-(N-4-m eth oxyp h en yl)a m in o-4,4,4-tr iflu or o-2-
-
1
1
bu ten oa te (8a ): IR (neat) 3232, 1746, 1682 cm
CDCl ) δ 9.64 (brs, 1 H), 7.11 (d, J ) 9 Hz, 2 H), 6.84 (d, J ) 9
Hz, 2 H), 5.27 (s, 1 H), 3.79 (s, 3 H), 3.74 (s, 3 H); F NMR
; H NMR
(
3
1
9
+
(
(
CDCl
3
) δ 97.9 (s, CF
3
); MS m/z 275 (74) [M] , 206 (100), 149
NO : C, 52.37; H, 4.39; N, 5.09.
81). Anal. Calcd for C12
H
12
F
3
3
Found: C, 52.17; H, 4.62; N, 5.16.
P r ep a r a tion a n d P r oced u r e for Rea r r a n gem en t Rea c-
In conclusion, the base-catalyzed Wittig type rear-
rangement of S-(N-aryltrifluoroacetimidoyl)acetates 2
proceeded smoothly at -40 °C, affording 3-amino-4,4,4-
trifluoro-2-butenoates 8. The intermediate 3-amino-4,4,4-
trifluoro-2-thiohydroxybutanoates underwent a facile
desulfurization to give 3-amino-4,4,4-trifluoro-2-butenoate
tion of 15. To a solution of (N-4-methoxyphenyl)thiobenzanil-
1
3
ide (1.001 g, 4.12 mmol)/CH
flask under N were added methyl bromoacetate (0.702 g, 4.53
mmol) and Et N (1.3 mL, 12.4 mmol). The reaction mixture was
2 2
Cl (25 mL) in a 50 mL reaction
2
3
then stirred at 0 °C (ice water bath) for 3 h and concentrated,
and compound 15 was obtained in 92% (1.193 g) yield by column
chromatography (silica gel, AcOEt/hexane ) 1:5). The compound
15 (1.0 mmol, 0.317 g) in freshly distilled THF (2 mL) was added
dropwise to the LDA solution at -20 °C. The reaction mixture
was stirred for 9 h at -20 °C. After almost all of the starting
material was gone (checked by TLC), 10 mL of diethyl ether and
1
2
2. The same type rearrangement of the corresponding
-S-(N-arylbenzoimidoyl)acetate 15 proceeded likewise
under the same reaction conditions at -20 °C, where
-amino-2-thiohydroxycinnamate 16 was produced as a
3
4
aqueous NH Cl were added at once. The organic layer was then
washed with water until the color of the water layer became
major product. The facile desulfurization would arise
from the stronger electron-withdrawing nature of tri-
fluoromethyl group for 2 than that of phenyl group for
light red and was dried over MgSO . Purification by column
4
chromatography (silica gel, AcOEt/hexane) gave the yellowish
products 16 (53%, 0.168 g) and 17 (26%, 0.074 g).
1
5. This rearrangement provides us a possible synthethic
Met h yl S-(1-((N-4-m et h oxyp h en yl)im in o)p h en yl)t h io-
route to 3-amino-2-thiohydroxycarboxylic acid deriva-
tives.
-
1 1
glycola te (15): IR (neat) 1742, 1614 cm ; H NMR (DMSO-d
6
,
7
0 °C) δ 7.6-7.2 (m, 5H), 6.9-6.5 (m, 4 H), 3.88 (brs, 2 H), 3.68
+
(s, 3 H), 3.63 (s, 3 H); MS m/z 315 (10) [M] , 210 (100), 77 (12).
Exp er im en ta l Section
Anal. Calcd for C17H17NO S: C, 64.74; H, 5.43; N, 4.44. Found:
3
C, 64.43; H, 5.58; N, 4.74.
Meth yl 3-(N-4-m eth oxyp h en yl)a m in o-2-th ioh yd r oxycin -
Gen er a l Meth od s. All reactions were performed under a dry
argon atmosphere. THF was freshly distilled from sodium-
benzophenone ketyl under nitrogen. All other reagents were used
as obtained and without further purification. Glassware and
-
1 1
n a m a te (16): IR (neat) 3180, 2280, 1738, 1648 cm ; H NMR
CDCl
(
6
3
) δ 11.59 (brs, 1 H), 7.4-7.2 (m,5 H), 7.1 (brs, 1H), 6.7-
17
.5 (m, 4 H), 3.77 (brs, 3 H), 3.68 (s, 3 H). Anal. Calcd for C17H -
1
syringes used for the reaction were oven dried before use. H,
3
NO S: C, 64.74; H, 5.43; N, 4.44. Found: C, 64.37; H, 5.43; N,
1
3
19
C, and F NMR spectra were recorded at 200, 50.3, and 188
4
.18.
MHz, respectively. The chemical shifts are reported in δ (ppm)
1
Meth yl 3-(N-4-m eth oxyp h en yl)a m in ocin n a m a te (17): IR
values relative to CDCl
3
(δ 7.26 ppm for H NMR, δ 77.0 ppm
-
1 1
1
3
19
3
(neat) 3280, 1652, 1616 cm ; H NMR (CDCl ) δ 10.19 (brs, 1
for C NMR) and C
6
F
6
(δ 0 ppm for F NMR). For TLC and
H), 7.4-7.2 (m,5 H), 6.7-6.6 (m, 4 H), 4.93 (s, 1 H), 3.74 (s, 3
column chromatography E. Merck silica gel (Kieselegel 60 F254
and Kieselgel 60, 230-400 mesh) was used.
Gen er a l P r oced u r e for th e Rea ction of Im id oyl Ch lo-
r id es 7 w ith Th ioglycola tes. To a solution of thioglycolate
+
H), 3.70 (s, 3 H); MS m/z 283 (100) [M] , 251 (63), 210 (56). Anal.
Calcd for C17
3
H17NO : C, 72.07; H, 6.05; N, 4.94. Found: C, 71.80;
H, 6.31; N, 5.31.
A P r oced u r e for Tr a p p in g In ter m ed ia te 12 w ith Ben -
zoyl Ch lor id e. A mixture of 2a (0.154 g, 0.5 mmol) and LDA
(
N
2.440 g, 23 mmol)/THF (25 mL) in a 50 mL reaction flask under
were added trifluoroacetimidoyl chloride 7a (4.948 g, 21
mmol) and Et N (3.2 mL, 23 mmol). The reaction mixture was
2
(
0.75 mmol) was stirred at -40 °C for 4 h and was then added
3
benzoyl chloride (0.18 mL, 1.5 mmol) at once. After being stirred
(
12) (a) Otera, J .; Dan-oh, N.; Nozaki, H. J . Org. Chem. 1991, 56,
307. (b) Otera, J .; Yano, T.; Kawabata, A.; Nozaki, H. Tetrahedron
Lett. 1986, 21, 2383.
5
(13) Stevens, M. F. G.; McCall, C. J .; Lelieveld, P.; Alexander, P.;
Richter, A.; Davies, D. E. J . Med. Chem. 1994, 37, 1689.

Notes
J . Org. Chem., Vol. 66, No. 3, 2001 1029
at -40 °C for 30 min, 10 mL of diethyl ether and 10 mL of
2-Ben zylca r ba m oyl-3-tr iflu or om eth yl-7-m eth ylben zo[e]-
th ia zin e (20): mp ) 152-153 °C; IR (KBr) 3400, 1678, 1660
aqueous NH
MgSO
4
Cl were added. The ether solution was dried over
-
1 1
4
and concentrated. The residue was column chromato-
cm ; H NMR (CDCl
3
) δ 7.6-6.4 (m, 8 H), 4.43 (dd, J ) 15, 7
graphed (silica gel, AcOEt/hexane ) 1:5) to give 18 as colorless
crystal in 34% (0.088 g) yield.
Hz, 1 H), 4.34 (s, 1 H), 4.19 (dd, J ) 15, 7 Hz, 1 H), 3.80 (s, 3 H);
1
9
+
F NMR (CDCl ) δ 91.0 (s, CF ); MS m/z 380 (1) [M] , 247 (100),
3
3
Met h yl 3-(N-4-m et h oxyp h en yl-N-ben zoyl)a m in o-4,4,4-
tr iflu or o-2-ben zoylth io-2-bu ten oa te (18): mp ) 123-125 °C;
3 2 2
91 (34). Anal. Calcd for C18H15F N O S: C, 56.84; H, 3.97; N,
7.36. Found: C, 57.13; H, 4.18; N, 7.61.
-
1 1
IR (KBr) 1746, 1682, 1678 cm ; H NMR (CDCl
3
) δ 8.0-6.6 (m,
) δ 101.8 (s,
); MS m/z 515 (9) [M] , 484 (7), 456 (7), 378 (21) 105(100).
Anal. Calcd for C26 NO S: C, 60.58; H, 3.91; N, 2.72.
X-r a y cr ysta l d a ta for 20: C18H F N O S, M ) 380.38,
15 3 2 2
1
9
1
CF
4 H), 3.94 (s, 3 H), 3.73 (s, 3 H); F NMR (CDCl
3
orthorhombic, space group P212121 (#19), a ) 14.033(2) Å, b )
+
3
3
2
1
3
2.164(4) Å, c ) 5.5190(5) Å, V ) 1716.5(4) Å , Z ) 4, Dcalc )
H
20
F
3
5
-3
.47 (2) g cm , R ) 0.0790 for 1060 observed reflections [I >
.00σ(I)] and 235 variable parameters. All measurements were
made on a Rigaku RAXIS-IV imaging plate area detector with
Found: C, 60.42; H, 3.92; N, 2.83.
Syn th esis of 19 by Iod in e Oxid a tion of In ter m ed ia te 12.
After the reaction of 2a (0.1538 g, 0.5 mmol) with LDA (0.75
mmol) for 6 h as described above, the mixture was treated with
Mo KR radiation.
I
2
(0.2571 g, 1 mmol) in THF (2 mL). The reaction was quenched
with 10 mL of aqeous Na . After the usual workup and
chromatography (silica gel, Et O/hexane ) 1/2), 19 was isolated
as a red oil in 52% (0.0804 g) yield.
-Tr iflu or om eth yl-7-m eth oxy-2-m eth oxyca r bon ylben zo-
Ack n ow led gm en t. We are grateful to the Ministry
of Education, Science, Sports and Culture of J apan for
financial support (Grant No. 09305058 and Priority
Areas No. 706) and SC-NMR Laboratory of Okayama
University for F NMR analysis and VBL X-ray analy-
sis.
2
S
2
O
2
3
3
-
1 1
[
e]th ia zin e (19): IR (neat) 1746 cm ; H NMR (CDCl
3
) δ 7.50
1
9
(
3
d, J ) 10 Hz, 1 H), 6.9-6.7 (m, 2 H), 4.34 (s, 1 H), 3.82 (s, 3 H),
1
9
.68 (s, 3 H); F NMR (CDCl
3
) δ 90.0 (s, CF
3
); MS m/z 305 (13)
S: C, 47.21; H,
+
[M] , 246 (100). Anal. Calcd for C12
H
10
F
3
N
3
O
3
3
.30; N, 4.59. Found: C, 47.0; H, 3.20; N, 4.36.
P r ep a r a tion of 20. A mixture of 19 (0.6289 g, 2 mmol), 1,3-
Su p p or tin g In for m a tion Ava ila ble: Data of IR,
1
H and
19
F NMR, MS, and elemental analysis for compounds 2b-g
dichlorotetrabutyldistannoxane (0.4049 g, 0.5 mmol), and ben-
zylamine (0.25 mL, 2 mmol) in toluene (7 mL) was refluxed
and 8b-g and the detailed X-ray data for compound 20. This
material is available free of charge via the Internet at
http://pubs.acs.org.
under N
silica gel, AcOEt/hexane ) 1:2) gave product 20 as white
crystals in 82% (0.6232 g) yield.
2
for 1 day. Purification by column chromatography
(
J O0010330