Properties and reactions of substituted 1,2-thiazetidine 1,1-dioxides: Functionalization and reactions at C(4) of the β-sultam

Article abstract of DOI:10.1002/hlca.200490144

The introduction of functional groups at the 4-position of β-sultam ring was realized by the synthesis of mono- and disubstituted derivatives by reactions of N-silylated β-sultams with electrophiles in the presence of BuLi or LDA. As electrophiles, ketone

Full text of DOI:10.1002/hlca.200490144

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Properties and Reactions of Substituted 1,2-Thiazetidine 1,1-Dioxides:
Functionalization and Reactions at C(4) of the b-Sultam
by Herbert Plagge, Nico Manicone, and Hans-Hartwig Otto*
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Greifswald,
Friedrich-Ludwig-Jahn-Strasse 17, D-17487 Greifswald
(phone: ‡49-3834-864875; fax: ‡49-3834-864874; e-mail: ottohh@pharmazie.uni-greifswald.de)
The introduction of functional groups at the 4-position of the b-sultam ring was realized by the synthesis of
mono- and disubstituted derivatives by reactions of N-silylated b-sultams with electrophiles in the presence of
BuLi or LDA. As electrophiles, ketones, chlorosilanes, a b-sultam, CO2, chloroformiate, halogen, azodicarbox-
ylate, phenyltriazoledione, tosyl azide, 1,3,5-triazine, propyl nitrate, and phenyl isocyanate were used.
Furthermore, a number of derivatives of these substitution products were synthesized. All products were
characterized by standard spectroscopic methods, and conformations were studied, supported by calculation.
Introduction. The b-sultam ring (1,2-thiazetidine 1,1-dioxide) is a highly reactive
cyclic sulfonamide that can be used as a building block in drug synthesis. But, in
contrast to its less-reactive lactam analog, which can be easily functionalized, reactions
at the b-sultam ring are much more difficult due to the sulfonyl group. In preceding
papers, we have reported reactions at N(2) and at C(3) [1][2]. Here, we describe the
introduction of functional groups at C(4). This position causes special problems, as the
introduction of a heteroatom results in an unstable, aminal-like structure, which is
readily hydrolyzed. Therefore, until now, no derivatives with an N-substituent at C(4)
have been described.
After deprotonation, the C(4) atom of b-sultams can be attacked by electrophiles.
Thereby, a deprotonated intermediate is formed [3] that, by reaction with C-
electrophiles, yields relatively stable products, as demonstrated by silylation [4],
acylation [5], reactions with aromatic nitriles yielding enamino b-sultams [6], and by
the rearrangement of 2,3-disubstituted b-sultams into 2,4,1-dithiazine derivatives [7].
Results. Syntheses. When a solution of 0.6 1 equiv. of BuLi or LDA (lithium
diisopropylamide) was added to a solution of b-sultams 1a or 1b [4] at À 788, we
isolated, after hydrolytic workup, the −dimeric× (aminoethyl)sulfonyl b-sultams 2a and
2b in nearly quantitative yields (Scheme 1), probably formed by deprotonation of the
b-sultam, followed by an attack of the deprotonated intermediate at the sulfonyl group
of a second b-sultam molecule. A similar reaction was observed when a soln. of the N-
benzoyl b-sultam 3 [8] was added to a soln. of 1 equiv.of LDA, but the reaction did not
stop after the formation of the dimer. Rather, a second deprotonation and reaction with
a third b-sultam yielded the −trimeric× compound 4 as a mixture of two diastereoisom-
ers. On the other hand, the reaction between 1a and benzophenone, after deproto-
nation with 2 equiv. of BuLi, yielded the aldol adduct 5 [9]; and analogous reactions

Helvetica Chimica Acta Vol. 87 (2004)
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Scheme 1
occurred, when 1b was silylated after deprotonation with an excess of LDA, yielding 6,
which was transformed into the benzylidene derivative 7. Analogously, 8 [4], after
deprotonation with an excess of LDA, reacted with diethyl mesoxalate, yielding the
aldol adduct 9. These experiments clearly demonstrate that, for 1:1 reactions between
the b-sultam ring and electrophiles, an excess of base is necessary.
Until now, no b-sultam with an N-substituent at C(4) has been described. As the
Curtius rearrangement is known to be a mild and effective method to transform an
isocyanate into an amine, we intended to prepare first an isocyanate from 8, and then to

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Helvetica Chimica Acta Vol. 87 (2004)
rearrange it into the corresponding 4-amino-b-sultam. Deprotonation of 8 with BuLi,
followed by reaction with gaseous CO2, led to the carboxylic acid 10, which was isolated
as a stable, crystalline compound in 45% yield (Scheme 2). An analogous reaction with
1b did not yield the corresponding b-sultam, but the taurine derivative 11, formerly
prepared from the Cl derivative and cyclohexylamine [10]. The transformation of 10
into the acid chloride 12 was possible only when using SOCl2 in the presence of 1 equiv.
of pyridine. Then, 12 was obtained as a colorless viscous liquid in ca. 50% yield after
purification by Kugelrohr distillation. The formation of the azide 13 was not possible by
standard procedures, but when a solution of 12 in Et2O was reacted with an aqueous
solution of NaN3 at 08, 13 was obtained in yields of > 80%. Despite much effort, 13
could be rearranged only into the isocyanate 14 or the amine at exactly 858 in toluene,
where the reaction is complete within 10 min, as shown by 1H-NMR. Thus, we could not
isolate pure compound 14, which seems to be very unstable (probably due to the two
electron-withdrawing heteroatoms at C(4)).
Scheme 2

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When we tried the Curtius rearrangement of 13 in MeOH or EtOH to obtain the
alkyl carbamates, we observed no rearrangement, but alcoholysis of the azide, and we
isolated the esters 15a or 15b. These esters were obtained in higher yields from
reactions of 12 and the parent alcohol. Furthermore, 15a was synthesized by reaction of
10 with diazomethane, and was desilylated with TBAF on silica gel in MeOH at room
temperature, yielding 16. When 8, after deprotonation with BuLi, was acylated with
phenyl chloroformiate, a mixture of the diacylated product 17 and the monoacylated
compound 18 was always obtained, which was separated by column chroma-
tography (CC). Under similar conditions, the acylation of 1a with methyl chloro-
formiate yielded only the diacylated compound 19. While the monoacylated product 18
was obtained as a viscous liquid, all diacylated products were obtained as stable,
crystalline compounds.
To explore the possibility of halogenation at C(4), 8 was deprotonated with
equimolar amounts of BuLi and then reacted with Br2, leading to 20, which was isolated
as a stable crystalline product in yields of ca. 20%, formed by a trans-silylation reaction
followed by bromination of the intermediate silylated b-sultam (Scheme 3). Using an
excess of BuLi (1.5 2 equiv.) and Br2 (2 3 equiv.), we obtained in all experiments
from 8, 1a, or 1b mixtures of the mono- and dibrominated products. Separation by CC
was possible, when the N-atom was protected with a (t-Bu)Ph2Si group (21a, 22a) or a
cyclohexyl substituent (21b, 22b), but separation was not possible when we used the (t-
Bu)Me2Si group for protection. Experiments with the aim of introducing Cl instead of
Br failed. While analogous halogenations of b-lactams [11], depending on the
conditions, yield stable monohalogenated compounds, our experiments demonstrate
that the reactions of b-sultams with halogens yield mixtures of relatively unstable
mono- and dihalogenated compounds in low yields. Furthermore, halogen exchange by
Finkelstein reaction was not successful either. Finally, iodination of b-sultam was
Scheme 3

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Helvetica Chimica Acta Vol. 87 (2004)
possible when one C-substituent was present at C(4), as demonstrated by the reaction
of 15a with LDA and I2, yielding the crystalline compound 23 in 20% yield.
Unexpected results were obtained when we tried to introduce N-substituents at
position 4. Thus, the reaction between 1a, deprotonated with LDA at À 788, and an
excess of diethyl azodicarboxylate (DEAD) did not give the expected addition
product, but the carboxylate 24 and hydrazine-1,2-dicarboxylate. Apparently, in this
reaction, the azodicarboxylate did not serve as an N-electrophile, but, like chlor-
oformiate, as a C-electrophile, and the excess of azodicarboxylate was reduced by LDA
(Scheme 4). However, when we performed the reaction with C(4)-monosubstituted b-
sultams like 15a or 25, prepared from 8 and ethyl benzoate or benzonitrile, we obtained
the addition products in yields of 30 80%. Thus, from reactions of 15a, we isolated the
addition products 26a and 26b as stable crystalline compounds. The analogous products
27a c were obtained from the 4-benzoyl derivative 25. Even these products were
obtained as stable crystalline compounds. In another experiment, we tried first to
silylate 25, and then to replace the silyl group by an N-substituent, but we obtained the
silyl enol ethers 28a and 28b from the silylation reaction, and no further reaction with
DEAD occurred. Upon trying to desilylate these addition products by stirring with
TBAF (SiO2) in THF at room temperature, we noticed in all experiments complete
decomposition of the starting materials. In a detailed study with 27a, we found two
products, diethyl hydrazine-1,2-dicarboxylate and 3-amino-2-hydroxy-1-phenylprop-2-
en-1-one (29). (This reaction is best explained by fluoride-catalyzed desilylation,
followed by fluoride-catalyzed SO2 extrusion and elimination of the hydrazine-1,2-
dicarboxylate; the structure of 29 was established by spectroscopic methods, including
high-resolution MS). On the other hand, additions readily occurred between 15a or 25
and 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione, yielding the adducts 30a and 30b,
respectively.
When we tried to prepare an azido b-sultam from 25 according to the method of
K¸hlein and Jensen [12] in the presence of Me3SiCl, we did not isolate the desired azido
compound, but silylated 28a. By modifying the reaction conditions (warming the
reaction mixture to 08 before addition of Me3SiCl), we obtained 31a in low yield. Under
analogous conditions, we obtained from 15a two fractions of the azido derivative 31b
(see below). Both azido compounds were isolated after chromatographic purification
as viscous liquids. In the reaction between deprotonated 8 and 1,3,5-triazine, the latter
reacted as the C-electrophile, and we obtained the dihydrotriazinyl derivative 32 as a
crystalline compound (Scheme 5).
Finally, we prepared for the first time a 4-nitro b-sultam. For this purpose, 8 was
silylated at À 788 with LDA and Et3SiCl, yielding the C-monosilylated product 33 in
89% yield. The latter was deprotonated with BuLi, and then reacted with propyl nitrate
at À 788, leading to the strongly moisture-sensitive product 34 as an unstable yellow
liquid in 24% yield.
Reactions of 8 with phenyl isocyanate were similar to those with chloroformiates,
and yielded mixtures of mono- and disubstituted products like 35 and 36, which were
isolated as stable crystalline compounds (Scheme 6). The monoamide 35 was prepared
in higher yield from 12 and aniline in the presence of pyridine, and by the reaction of 12
in NH3-saturated CHCl3 at 08, giving rise to the b-sultam 4-carboxamide 37. Finally, we
prepared two substituted amides, 38a and 38b, bearing an aminothiazolyl substituent

Helvetica Chimica Acta Vol. 87 (2004)
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Scheme 4
known to increase the anti-infective activity of cephalosporins. Unfortunately, both
compounds exhibited no remarkable antibacterial activities in standard tests.
In conclusion, our experiments demonstrate that reactions at C(4) of b-sultam rings
significantly differ from analogous reactions of b-lactams, while reactions at positions 2
or 3 are comparable with those at the b-lactam ring [11]. The most-significant
difference concerns the introduction of a heteroatom at C(4). While a-halogeno and a-

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 5
Scheme 6
amino b-lactams are relatively stable compounds that can be prepared mostly by
standard methods [11], b-sultam derivatives are unstable, as demonstrated for
halogeno and nitro compounds. This explains why the synthesis of a-amino b-sultams
has not been described so far.
Spectroscopy and Stereochemistry. The IR spectra of all b-sultams are characterized
by the bands of the SO2 group at 1340 1295 (SO2, asym.) and 1200 1140 cmÀ1 (SO2,

Helvetica Chimica Acta Vol. 87 (2004)
1581
sym.), depending on the substituents. When comparing the data of the N-silyl
compound 8 with those of the N-benzoyl derivative 3, both lacking substituents at C(4),
a shift to higher wave numbers is observed for both bands. The data of the 4-substituted
derivatives show no or only a small shift of both bands, when the substituent is silyl, an
sp3-C-atom, or when C(4) is sp2 hybridized (7). When the substituent at C(4) is an
electron-withdrawing group as in 10, 15a, 13, 14, 31b, and 34, the shift to higher wave
numbers of v(SO2, asym.) is relatively small (0 30 cmÀ1), but the shift of v(SO2, sym.)
increases by up to 60 cmÀ1 (Table 1).
Table 1. IR Data of Selected b-Sultams
Compound
v(SO2, asym.)
v(SO2, sym.)
Other bands, literature
3
5
6
7
8
10
12
13
14
15a
16
17
21a
31b
33
34
1340
1310, 1295
1310
1300
1300
1315
1335
1330
1320
1320
1340
1320
1330
1300
1301
1328
1155
1175, 1140
1155
1150
1140
1170
1180
1200, 1170
1180
1170
1170
1180, 1160
1170
1180
1161
1660 (CˆO) [12]
[4]
1730 (CˆO)
1805, 1775 (CˆO)
2180 (N3), 1720 (CˆO)
2260 (NˆCˆO)
1750 (CˆO)
1745 (CˆO)
1750, 1730 (CˆO)
2140 (N3), 1760 (CˆO
1184
1570, 1359 (NO2)
1
All C(4)-monosubstituted b-sultams show in their H-NMR spectra an AB(M)X
system for HÀC(4) and HÀC(3). When the substituent at C(4) is electron withdrawing
(as in 10, 12, 13, 14, 15a, 18, or 34), the signal of one H-atom at C(3) shows a significant
downfield shift (Table 2). We interprete this effect by the anisotropy effect of the
substituent at C(4) on the vicinal proton in the cis position, while the trans proton is
nearly unaffected. This is in agreement with the coupling constants J3',4 ˆ Jcis ˆ 7 8 Hz,
and J3,4 ˆ Jtrans ˆ 4 5 Hz, and with the postulate of a favored pseudo-equatorial
orientation of the substituent at C(4) (Fig. 1,a), which is supported by an ab initio
Table 2. 1H-NMR Data of Selected b-Sultams. Solvent: CDCl3; d in ppm, J in Hz.
Compound
H'ÀC(3)
HÀC(3)
HÀC(4)
J(3,3')
J(3',4)
J(3,4)
10
12
3.47
3.50
2.93
2.72
3.44
3.53
3.69
3.65
3.70
3.50
3.16
3.67
3.76
3.94
5.25
5.57
4.70
4.86
5.18
5.40
6.42
6
6
6
6
5.7
6.3
8
8
5
7.6
7.6
7
7.5
7.7
7
4.5
4.5
5
4.5
4.6
4
13a)
14a)
15a
18
34
a) In (D8)toluene.

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Fig. 1. Favored conformation of a) 15a according to NMR data, and of b) (R)-15a, as derived by ab initio
calculation (Gauss STO-3G; Hyperchem 5.11)
calculation of 15a, showing a ×folding× of 188 for the b-sultam ring (Fig. 1,b). This
folding agrees with results from former X-ray analyses [4][8].
A remarkable observation was made when we reacted 15a with tosyl azide. The
purification of the crude product by CC (SiO2) yielded two fractions, 31ba and 31bb,
which showed identical IR spectra, 13C-NMR spectra, and elemental analyses, but
exhibited significant differences in the shifts of H'ÀC(3) and HÀC(3) in the 1H-NMR
spectra. While, in the spectrum of 31ba, the signal of H'ÀC(3) at d(H) 4.23 showed a
downfield shift compared to that of HÀC(3) at 3.93 ppm, in the spectrum of 31bb, the
effect was opposite. Here, the signal of HÀC(3) at 4.37 ppm showed a downfield shift
compared to that of H'ÀC(3) at 3.57 ppm. We suspect that we have isolated two
different conformers (Fig. 2) that are stable at room temperature. To estimate the free
1
energy of activation for their interconversion, we tried to record H-NMR spectra at
elevated temperature, but, unfortunately, the compound(s) completely decomposed on
warming.
Fig. 2. Favored conformers 31ba and 31bb of compound 31b, as deduced from NMR data
We wish to thank Novartis, Basel, for biological tests, Degussa AG for generous support with chemicals, E.
Merck KGaG, Darmstadt, for extended support with chemicals, with chromatography materials, and for HPLC
experiments, and we thank the ×Fonds der Chemischen Industrie×, Frankfurt a. Main, for continuous financial
support.
Experimental Part
General. Abbreviations: HMPT, hexamethylphosphortriamide; LDA, lithium diisopropylamide; PE,
petroleum ether; TBAF, tetrabutylammonium fluoride; THF, tetrahydrofuran. THF was stored over CaCl2,
refluxed over LiAlH4, and distilled prior to use. Other solvents were dried and purified according to literature
procedures. Compounds 1a [4], 1b [6], 3 [8], 8 [4], and 11 [10] were prepared according to lit. procedures.
Lithium diisopropylamide (LDA) was freshly prepared by mixing equivalent amounts of (i-Pr)2NH and BuLi

Helvetica Chimica Acta Vol. 87 (2004)
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(15% in hexane) in THF at À 788. Thin-layer chromatography (TLC): pre-coated silica-gel 60F254 plates
(Merck). Column (CC) and flash chromatography (FC): silica gel 60 (Merck). M.p.: Kofler apparatus;
uncorrected. IR Spectra (KBr): Perkin-Elmer IR-1310, Beckman IR-4240; in cmÀ1. 1H- and 13C-NMR Spectra:
Varian T-60 (1H, 60 MHz), Bruker WP-80 (80/20.15 MHz for 1H and 13C, resp.), WP-250, AM-400 (1H, 250/
400 MHz); d in ppm rel. to SiMe4 (ˆ0 ppm), J in Hz; in CDCl3, if not stated otherwise. MS: Finnigan GC-MS
4000, MAT-312, MAT-44-S; in m/z (rel. %); EI spectra at 2008 (70 eV), CI spectra with CH4, NH3, ca. 300 mbar.
Elemental analyses: Institute of Pharmacy, or Chemisches Laboratorium, University of Freiburg (Germany) or
Greifswald (Germany), resp. All compounds1) gave satisfactory elemental analyses or were analyzed by MS
and/or HR-MS.
2-[(tert-Butyl)diphenylsilyl]-4-[(2-{[(tert-butyl)diphenylsilyl]amino}ethyl)sulfonyl]-1,2-thiazetidine 1,1-
Dioxide (2a). BuLi (3.8 ml, 6 mmol) was added to a soln. of 1a (3.45 g, 10 mmol) in THF (100 ml) at À 788.
The mixture was stirred for 30 min at this temp. and hydrolyzed with aq. sat. NaCl soln. (200 ml). The org. layer
was dried (Na2SO4) and concentrated in vacuo: 1.55 g (45%) of 2a. Colorless crystals. M.p. 1508 (EtOH). IR:
3400 (NH), 3070, 3040, 2960, 2930, 2900, 2860 (CH), 1330, 1300, 1185, 1140, 1110 (SO2), 820, 745 (MeÀSi).
1H-NMR (80 MHz): 1.01 (s, t-Bu); 1.18 (s, t-Bu); 1.55 (s, NH); 3.15 3.60 (m, 2 CH2, HÀC(3), H'ÀC(3)); 5.36
‡
(dd, J ˆ 7.8, 4.4, HÀC(4)); 7.25 7.85 (m, 20 arom. H). EI-MS: 691 (0.8, M ), 135 (100). Anal. calc. for
C36H46N2O4S2Si2 (691.06): C 62.56, H 6.71, N 4.05, S 9.27; found: C 62.29, H 6.60, N 4.27, S 9.00.
2-Cyclohexyl-4-{[2-(cyclohexylamino)ethyl]sulfonyl}-1,2-thiazetidine 1,1-Dioxide (2b). Prepared from 1b
(950 mg, 5 mmol), as described for 2a. Some drops of Et2O were added to the residue, which was cooled for 24 h
to 08: 450 mg (48%) of 2b. M.p. 86 888 (Et2O). IR: 3290 (NH), 2920, 2850 (CH), 1330, 1295, 1170, 1120 (SO2).
1H-NMR (250 MHz): 0.98 2.04 (m, 10 CH2, NH); 2.46 (m, cyclohexyl CH); 3.08 3.34 (m, CHÀCH2,
cyclohexyl CH); 3.36 (dd, J ˆ 6.3, 7.7, H'ÀC(3)); 3.70 (m, CH); 3.78 (dd, J ˆ 4.3, 6.3, HÀC(3)); 5.74 (dd, J ˆ
7.7, 4.3, HÀC(4)). Anal. calc. for C16H30N2O4S2 (378.54): C 50.76, H 7.99, N 7.40, S 16.94; found C 50.71, H 7.89, N
7.28, S 16.81.
2-Benzoyl-4-[(2-(benzoylamino)-1-{[(benzoylamino)ethyl]sulfonyl}ethyl)sulfonyl]-1,2-thiazetidine 1,1-Di-
oxide1) (4). A soln. of 3 (2.1 g, 10 mmol) in THF (40 ml) was added to a soln. of LDA (10 mmol) in THF (30 ml)
at À 788 over 10 min at À 788 under stirring. Then, a mixture of an aq. sat. NaCl soln. (152 ml) and conc. HCl
soln. (8 ml) was added, the org. layer was separated, dried (Na2SO4), and evaporated in vacuo: 900 mg (43%) of
4. Colorless crystals. M.p. 204 2088 (EtOH; dec.). IR: 3420, 3320 (NH), 3060, 2990, 2960, 2940 (CH), 1680,
1640 (CˆO), 1535 (NH), 1350, 1330, 1310, 1290, 1190, 1160, 1140 (SO2). Anal. calc. for C27H27N3O9S3 (633.72):
C 51.17, H 4.29, N 6.63, S 15.17; found: C 50.94, H 4.39, N 6.50, S 15.01.
1
Isomer 1. H-NMR (250 MHz, (D6)DMSO): 3.76 (m, 2 CH2); 4.00 (dd, J ˆ 6.0, HÀC(7), H'ÀC(7)); 4.23
(dd, J ˆ 8.7, 5.2, H'ÀC(3)); 4.42 (dd, J ˆ 8.7, 8.7, HÀC(3)); 6.77 (t, J ˆ 6.0, HÀC(6)); 6.89 (dd, J ˆ 8.7, 5.2,
HÀC(4)); 7.4 8.0 (m, 15 arom. H); 8.84 (s, NH); 9.14 (t, J ˆ 6.0, NH).
Isomer 2. 1H-NMR (250 MHz, (D6)DMSO): 3.76 (m, 2 CH2); 4.09 (dd, J ˆ 6, HÀC(7), H'ÀC(7)); 4.23
(dd, J ˆ 8.7, 5.2, H'ÀC(3)); 4.42 (dd, J ˆ 8.7, 8.7, HÀC(3)); 6.55 (t, J ˆ 6.0, HÀC(6)); 6.89 (dd, J ˆ 8.7, 5.2,
HÀC(4)); 7.4 8.0 (m, 15 arom. H); 8.84 (s, NH); 9.06 (t, J ˆ 6.0, NH).
2-[(tert-Butyl)diphenylsilyl]-4-[hydroxy(diphenyl)methyl]-1,2-thiazetidine 1,1-Dioxide1) (5). BuLi
(12.5 ml, 20 mmol) was added to a soln. of 1a (3.45 g, 10 mmol) in THF (100 ml) at À 788, and after 45 s, a
soln. of benzophenone (4.5 g, 25 mmol) in THF (20 ml) was added. After stirring for 10 min at À 788, a sat. aq.
soln. of NaCl (200 ml) was added, the org. layer was separated, dried (Na2SO4), and evaporated in vacuo. Some
drops of MeOH were added to the residue, which, on cooling (24 h, 08), crystallized: 2.2 g (41%) of 5. Colorless
crystals. M.p. 66 808 (MeOH). IR: 3490 (OH), 3060, 3040, 3020, 2960, 2920, 2890, 2860 (CH), 1310, 1295, 1175,
1140 (SO2). 1H-NMR (80 MHz): 1.16 (s, t-Bu); 2.93 (dd, J ˆ 5.6, 8.6, H'ÀC(3)); 3.41 (dd, J ˆ 5.6, 5.6, HÀC(3));
4.40 (s, OH); 5.52 (dd, J ˆ 8.6, 5.6, HÀC(4)); 7.05 7.9 (m, 20 arom. H). Anal. calc. for C31H33NO3SSi (527.74): C
70.55, H 6.30, N 2.65, S 6.07; found: C 70.50, H 6.37, N 2.73, S 6.18.
4-[(tert-Butyl)dimethylsilyl]-2-cyclohexyl-1,2-thiazetidine 1,1-Dioxide (6). A soln. of 1b (1.89 g, 15 mmol)
in THF (70 ml) was added dropwise at À 788 to a mixture of a soln. of LDA (20 mmol) in THF (20 ml) and a
soln. of (t-Bu)Me2SiCl (2.26 g, 15 mmol) in THF (20 ml). The mixture was stirred for 1 h at À 788, and then
hydrolyzed with aq. sat. soln. of NaCl (100 ml). The org. layer was separated, dried (Na2SO4), and evaporated in
vacuo. Some drops of pentane were added to the residue to induce crystallization: 1.95 g (65%) of 6. Colorless
crystals. M.p. 798 (pentane). IR: 2930, 2900, 2850 (CH), 1310, 1155 (SO2), 1250 (MeÀSi). 1H-NMR (80 MHz):
1
)
For simplicity, all compounds were named taking the thiazetidine 1,1-dioxide core as the parent structure,
ignoring potentially higher-ranking side chains.

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0.21, 0.27 (2s, Me2Si); 0.95 (s, t-Bu); 1.10 2.13 (m, 5 CH2); 2.91 (dd, J ˆ 4.5, 6, H'ÀC(3)); 3.22 (m, CH); 3.29
(dd, J ˆ 8.5, 4.5, HÀC(3)); 3.95 (dd, J ˆ 8.5, 6, HÀC(4)). Anal. calc. for C14H29NO2SSi (303.54): C 55.40, H 9.63,
N 4.61, S 10.56; found: C 55.15, H 9.51, N 4.72, S 10.68.
4-(4-Chlorobenzylidene)-2-cyclohexyl-1,2-thiazetidine 1,1-Dioxide (7). A cooled soln. of 6 (1.5 g, 5 mmol)
in THF (40 ml) was added dropwise to a soln. of LDA (10 mmol) in THF (20 ml) at À 788. Then, a soln. of 4-
chlorobenzaldehyde (2.1 g, 15 mmol) in THF (10 ml) was added under stirring. Stirring was continued for 1 h,
the mixture was hydrolyzed with a sat. aq. soln. of NaCl (100 ml), the org. layer was separated, and stirred for
1.5 h with an aq. soln. of NaHSO3 (37%). The org. layer was again separated, dried (Na2SO4), and evaporated in
vacuo: 1 g (66%) of 7. Colorless crystals. M.p. 1778 (MeOH). IR: 2920, 2850 (CH), 1675 (CˆC), 1590 (arom.),
1300, 1150 (SO2). 1H-NMR (80 MHz; (Z)-Isomer): 1.05 2.15 (m, 5 CH2); 2.26 (m, CH); 3.75 (d, J ˆ 1.5,
H'ÀC(3), HÀC(3)); 6.58 (t, J ˆ 1.5, HÀC(a)); 7.10 7.62 (m, 4 arom. H). 1H-NMR (80 MHz; (E)-Isomer):
1.05 2.15 (m, 5 CH2); 2.26 (m, CH); 3.97 (d, J ˆ 2, H'ÀC(3), HÀC(3)); 7.10 (t, J ˆ 2, HÀC(a)); 7.10 7.62
(m, 4 arom. H). Anal. calc. for C15H18ClNO2S (311.83): C 57.78, H 5.82, Cl 11.37, N 4.49, S 10.28; found: C 57.58,
H 5.72, Cl 11.46, N 4.44, S 10.38.
2-[(tert-Butyl)dimethylsilyl]-4-[2-ethoxy-1-(ethoxycarbonyl)-1-hydroxy-2-oxoethyl]-1,2-thiazetidine 1,1-
Dioxide1) (9). A soln. of 8 (660 mg, 3 mmol) was added to a soln. of LDA (4.5 mmol) in THF (25 ml) at
À 788. Then, diethyl mesoxalate (ˆdiethyl 2-oxopropane-1,3-dioic acid; 1.4 ml, 9 mmol) was added. After
stirring for 10 min at À 788, the mixture was hydrolyzed with a sat. aq. soln. of NaCl (80 ml). The org. layer was
separated, dried (Na2SO4), and evaporated. The residue was purified by CC (CHCl3/acetone 95 :5; Rf 0.4):
200 mg (17%) of 9. Yellow liquid. IR (film): 3480 (OH), 2970, 2940, 2920, 2870 (CH), 1745 (CˆO), 1310, 1175
1
(SO2). H-NMR (80 MHz): 0.23 (s, Me2Si); 0.95 (s, t-Bu); 1.31 (t, Me); 1.36 (t, Me); 3.32 3.66 (m, H'ÀC(3),
HÀC(3)); 4.08 4.60 (m, 2 OCH2); 4.37 (s, OH); 5.22 (dd, J ˆ 8.0, 5.5, HÀC(4)). Anal. calc. for C15H29NO7SSi
(395.55): C 45.55, H 7.39, N 3.54; found: C 45.82, H 7.37, N 3.47.
2-[(tert-Butyl)dimethylsilyl]-1,2-thiazetidine-4-carboxylic Acid 1,1-Dioxide (10). BuLi (9.4 ml, 15 mmol)
was added to a soln. of 8 (2.2 g, 10 mmol) in THF (150 ml) at À 788. After 45 s, CO2 gas was bubbled through the
soln. for 10 15 min, and stirring was continued for 10 min at À 788. Then, a mixture of a sat. aq. soln. of NaCl
(114 ml) and conc. HCl (6 ml) was added, the org. layer was separated, dried (Na2SO4), and evaporated. The
residue was dissolved in a few milliliters of pentane, and cooled (08, 24 h): 1.2 g (45%) of 10. Colorless crystals.
M.p. 1008 (pentane). IR: 3200 2540 (OH), 2960, 2940, 2900, 2860 (CH), 1730 (CˆO), 1315, 1170 (SO2).
1H-NMR (80 MHz): 0.30 (s, Me2Si); 0.99 (s, t-Bu); 3.47 (dd, J ˆ 6, 8, H'ÀC(3)); 3.65 (dd(t), J ˆ 5, 6, HÀC(3));
5.25 (dd, J ˆ 8, 5, HÀC(4)); 8.82 (s, OH). Anal. calc. for C9H19NO4SSi (265.39): C 40.73, H 7.21, N 5.28, S 12.08;
found: C 40.47, H 7.10, N 5.41, S 12.18.
2-[(tert-Butyl)dimethylsilyl]-1,2-thiazetidine-4-carbonyl Chloride 1,1-Dioxide (12). Pyridine (0.4 ml,
5 mmol) was added at 08 to a soln. of 10 (1.32 g, 5 mmol) in Et2O (150 ml) under N2. Then, SOCl2 (0.38 ml,
5 mmol) was added dropwise, and stirring was continued for 30 min at 08, and then for 1 h at r.t. The precipitate
was filtered off, the filtrate was concentrated in vacuo, and the resulting residue was purified by Kugelrohr
distillation: 700 mg (49%) of 12. Colorless liquid. B.p. 1308/0.01 Torr. IR (film): 2960, 2940, 2910, 2900, 2870
(CH), 1805, 1775 (CˆO), 1335, 1180 (SO2), 1260 (MeÀSi). 1H-NMR (80 MHz): 0.31 (s, Me2Si); 1.00 (s, t-Bu);
3.50 (dd, J ˆ 6, 7.6, H'ÀC(3)); 3.70 (dd(t), J ˆ 4.5, 6, HÀC(3)); 5.57 (dd, J ˆ 7.6, 4.5, HÀC(4)). Anal. calc. for
C9H18ClNO3SSi (283.85): C 38.08, H 6.39, N 4.93; found: C 37.81, H 6.24, N 5.08.
2-[(tert-Butyl)dimethylsilyl]-1,2-thiazetidine-4-carbonyl Azide 1,1-Dioxide (13). A soln. of 11 (700 mg,
2.45 mmol) in Et2O (20 ml) was added under vigorous stirring at 08 to a soln. of NaN3 (580 mg, 9.3 mmol) in
H2O (3 ml). Stirring was continued for 1.5 h at 08, the org. layer was separated, dried (Na2SO4), and evaporated
in vacuo: 600 mg (85%) of 13. Colorless liquid. IR (film): 2970, 2940, 2920, 2900, 2880 (CH), 2180 (N3), 1720
(CˆO), 1330, 1200 1170 (SO2), 1265 (MeÀSi), 1210 1180 (N3). 1H-NMR (80 MHz): 0.31 (s, Me2Si); 1.00
(s, t-Bu); 3.45 (dd, J ˆ 6, 7.6, H'ÀC(3)); 3.67 (dd, J ˆ 4.5, 6, HÀC(3)); 5.17 (dd, J ˆ 7.6, 4.5, HÀC(4)); 1H-NMR
(80 MHz; (D8)toluene): 0.31 (s, Me2Si); 1.05 (s, t-Bu); 2.93 (dd, J ˆ 6, 7.6, H'ÀC(3)); 3.50 (dd, J ˆ 4.5, 6,
‡
HÀC(3)); 4.70 (dd, J ˆ 7.6, 4.5, HÀC(4)). EI-MS: 291 (3.4, [M ‡ 1] ), 100 (100), 233 (12), 141 (30), 136 (20),
129 (17), 113 (37), 102 (16), 101 (38), 99 (23), 86 (60), 75 (42), 74 (22), 73 (88), 72 (41), 59 (76), 58 (26), 57
‡
(82), 56 (30), 55 (91), 45 (30), 44 (12), 43 (44), 42 (11), 41 (19). CI-MS (CH4): 291 ([M ‡ H] ). Molecular
formula: C9H18N4O3SSi (290.41 g molÀ1).
2-[(tert-Butyl)dimethylsilyl]-1,2-thiazetidine-4-carbonyl Isocyanate 1,1-Dioxide (14). In an NMR tube, a
soln. of 13 (290 mg, 1 mmol) in [D8]toluene (1.5 ml) was warmed for 10 min to 808 in an NMR spectrometer.
Longer heating resulted in product decomposition. IR (film): 2960, 2940, 2910, 2900, 2860 (CH), 2260
(NˆCˆO), 1320, 1180 (SO2), 1260 (MeÀSi). 1H-NMR (80 MHz, (D8)toluene): 0.31 (s, Me2Si); 1.00 (s, t-Bu);

Helvetica Chimica Acta Vol. 87 (2004)
1585
2.72 (dd, J ˆ 6, 5, H'ÀC(3)); 3.16 (dd, J ˆ 7, 6, HÀC(3)); 4.86 (dd, J ˆ 7, 5, HÀC(4)). Molecular formula:
C9H18N2O3SSi (262.40 g molÀ1).
Methyl 2-[(tert-Butyl)dimethylsilyl]-1,2-thiazetidine-4-carboxylate 1,1-Dioxide (15a). Method A. A soln. of
¾
diazomethane prepared from Diazald (3 g), dissolved in Et2O (30 ml) and aq. KOH (2 ml, 65%), and
diethyleneglycolmonomethyl ether (5 ml) was distilled into a soln. of 10 (1.6 g, 6 mmol) in Et2O (200 ml)
under stirring at 08. Stirring was continued for 3 h at 08, the excess diazomethane was blown out with a stream of
N2, the solvent was evaporated in vacuo, and the residue was purified by Kugelrohr distillation: 1.2 g (72%) of
15a. Colorless liquid. B.p. 1108/0.01 Torr. IR (film): 2960, 2940, 2900, 2890, 2860 (CH), 1750 (CˆO), 1320, 1170
(SO2). 1H-NMR (250 MHz): 0.28, 0.30 (2s, Me2Si); 1.00 (s, t-Bu); 3.44 (dd, J ˆ 5.7, 7.5, H'ÀC(3)); 3.67 (dd, J ˆ
‡
4.5, 5.7, HÀC(3)); 3.89 (s, MeO); 5.18 (dd, J ˆ 7.5, 4.5, HÀC(4)). EI-MS: 222 (26, [M À t-Bu] ), 55 (100). Anal.
calc. for C10H21NO4SSi (279.39): C 42.99, H 7.57, N 5.01, S 11.47; found: C 42.76, H 7.47, N 5.12, S 11.22.
Method B. A soln. of 12 (1.6 g, 6 mmol) in MeOH (15 ml) was stirred for 30 min at r.t. The solvent was
evaporated, and the residue was purified as in Method A (see above): 1.1 g (65%) of 15a.
Ethyl 2-[(tert-Butyl)dimethylsilyl]-1,2-thiazetidine-4-carboxylate 1,1-Dioxide (15b). Method A. A soln. of
13 (600 mg, 2 mmol) in EtOH (15 ml) was refluxed for 15 min, the solvent was evaporated, and the residue was
purified by Kugelrohr distillation: 350 mg (60%) of 15b. Colorless liquid. B.p. 1658/0.02 Torr. IR (film): 2960,
2940, 2860 (CH), 1745 (CˆO), 1330, 1175 (SO2). 1H-NMR (80 MHz): 0.33 (s, Me2Si); 1.00 (s, t-Bu); 1.35
(t, Me); 3.45 (dd, J ˆ 5.8, 8.0, H'ÀC(3)); 3.70 (dd, J ˆ 4.5, 5.8, HÀC(3)); 4.36 (q, CH2); 5.17 (dd, J ˆ 8, 4.5,
HÀC(4)). Anal. calc. for C11H23NO4SSi (293.45): C 45.02, H 7.89, N 4.77; found: C 45.29, H 7.88, N 4.94.
Method B. A soln. of 12 (600 mg, 2 mmol) in EtOH (15 ml) was stirred for 30 min at r.t. Workup as
described for Method A: 360 mg (62%) of 15b.
Methyl 1,2-Thiezetidine-4-carboxylate 1,1-Dioxide (16). Under N2, 15a (270 mg, 1 mmol), and TBAF
(55 mg, 20% on SiO2) in MeOH (20 ml) were stirred for 14 h. The solvent was evaporated, and the residue was
purified by CC (acetone; Rf 0.64): 110 mg (70%) of 16. Colorless liquid. IR (film): 3300 (NH), 3000, 2960 (CH),
1745 (CˆO), 1340, 1170 (SO2). 1H-NMR (80 MHz): 3.3 3.8 (m, H'ÀC(3), HÀC(3)); 3.88 (s, MeO); 5.27
(dd, J ˆ 8.0, 5.6, HÀC(4)); 5.83 (s, NH). Anal. calc. for C4H7NO4S (165.16): C 29.09, H 4.27, N 8.48, S 19.41;
found: C 29.30, H 4.23, N 8.45, S 19.53.
Diphenyl 2-[(tert-Butyl)dimethylsilyl]-1,2-thiazetidine-4,4-dicarboxylate 1,1-Dioxide (17). Prepared from 8
(2.2 g, 10 mmol) in THF (100 ml), BuLi (9.4 ml, 15 mmol), and phenyl chloroformate (1.8 ml, 15 mmol) at
À 788, as described for 32. The product was purified by CC (CH2Cl2; Rf 0.54): 960 mg (21%) of 17. Colorless
crystals. M.p. 808 (pentane). IR: 3060, 2960, 2930, 2900, 2880, 2860 (CH), 1750, 1730 (CˆO), 1320, 1180, 1160
(SO2). 1H-NMR (80 MHz): 0.33 (s, Me2Si); 1.00 (s, t-Bu); 4.00 (s, H'ÀC(3), HÀC(3)); 7.12 7.60 (m, 10 arom.
H). Anal. calc. for C22H27NO6SSi (461.59): C 57.25, H 5.89, N 3.03, S 6.95; found: C 57.45, H 5.93, N 3.10, S 6.85.
Phenyl 2-[(tert-Butyl)dimethylsilyl]-1,2-thiazetidine-4-carboxylate 1,1-Dioxide (18). This compound was
obtained as a side product in the synthesis of 17 (Rf 0.40): 540 mg (16%). Colorless, viscous liquid. B.p. 1758/
0.01 Torr. IR (film): 3030, 2960, 2940, 2900, 2860 (CH), 1760 (CˆO), 1330, 1165 (SO2), 1260 (MeÀSi).
1H-NMR (250 MHz); 0.32, 0.33 (2s, Me2Si); 1.00 (s, t-Bu); 3.53 (dd, J ˆ 6.3, 7.7, H'ÀC(3)); 3.76 (dd, J ˆ 4.6, 6.3,
HÀC(3)); 5.40 (dd, J ˆ 7.7, 4.6, HÀC(4)); 7.14 7.47 (m, 5 arom. H). Anal. calc. for C15H23NO4SSi (341.49): C
52.76, H 6.79, N 4.10, S 9.39; found: C 52.85, H 6.72, N 4.01, S 9.25.
Dimethyl 2-[(tert-Butyl)diphenylsilyl]-1,2-thiazetidine-4,4-dicarboxylate 1,1-Dioxide (19). Prepared from
1a (3.45 g, 10 mmol) in THF (100 ml), BuLi (9.4 ml, 15 mmol), and ethyl chloroformate (1.2 ml, 15 mmol) at
À 788, as described for 32. Some drops of MeOH were added to the residue to induce crystallization: 1.2 g (26%)
of 19. Colorless crystals. M.p. 958 (MeOH). IR: 3090, 3060, 2970, 2940, 2900, 2880 (CH), 1780, 1760 (CˆO),
1
1335, 1320, 1175 (SO2). H-NMR (80 MHz): 1.19 (s, t-Bu); 3.63 (s, H'ÀC(3), HÀC(3)); 3.88 (s, MeO); 7.32
7.90 (m, 10 arom. H). Anal. calc. for C22H27NO6SSi (461.59): C 57.25, H 5.89, N 3.03, S 6.95; found: C 57.10, H
5.99, N 3.03, S 6.84.
4-Bromo-2,4-bis[(tert-butyl)dimethylsilyl]-1,2-thiazetidine 1,1-Dioxide (20).
A soln. of Br2 (0.5 ml,
10 mmol) in THF (20 ml) was added under stirring at À 788 to a soln. of 8 (2.2 g, 10 mmol) and BuLi
(6.25 ml, 10 mmol) in THF (100 ml), and stirring was continued for 45 min at À 788. Then, a sat. aq. soln. of
NaCl (150 ml) was added, the org. layer was separated, washed with aq. NaCl soln., dried (Na2SO4), and
evaporated in vacuo. The residue was dissolved in a few ml of MeOH, and cooled (08, 2 3 d): 370 mg (17%) of
20. Colorless crystals. M.p. 45 488 (MeOH). IR: 2950, 2920, 2880, 2860 (CH), 1305, 1160 (SO2). 1H-NMR
(250 MHz): 0.28, 0.30 (2s, Me2Si); 0.34 (s, Me2Si); 0.98 (s, t-Bu); 1.07 (s, t-Bu); 3.43 (d, J ˆ 6.5, H'ÀC(3)); 3.77
(d, J ˆ 6.5, HÀC(3)). 13C-NMR (20.15 MHz): À 6.28 (Me); À 5.91 (Me); 18.30 (Me3C); 18.49 (Me3C); 25.86
(Me3C); 27.83 (Me3C); 46.71 (C(3)); 75.37 (C(4)). Anal. calc. for C14H32BrNO2SSi (414.53): C 40.56, H 7.78, Br
19.28, N 3.38, S 7.73; found: C 40.80, H 7.88, Br 19.10, N 3.58, S 7.60.

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Helvetica Chimica Acta Vol. 87 (2004)
4,4-Dibromo-2-[(tert-butyl)diphenylsilyl]-1,2-thiazetidine 1,1-Dioxide (21a). A cooled soln. of Br2 (1.0 ml,
20 mmol) in THF (30 ml) was added under stirring at À 788 to a soln. of 1a (3.45 g, 10 mmol) and BuLi (9.4 ml,
15 mmol) in THF (100 ml). Stirring was continued for 1 h at À 788, and for 30 min at r.t. Then, a mixture of a sat.
aq. soln. of NaCl (70 ml) and an aq. soln. of NaHSO3 (70 ml, 37%) was added, the org. layer was separated,
washed twice with aq. NaCl soln., dried (Na2SO4), and evaporated. The residue was purified by CC (CHCl3; Rf
0.65): 1.5 g (29%) of 21a. Colorless crystals. M.p. 120 1228 (MeOH). IR: 3060, 3040, 2960, 2940, 2880, 2860
(CH), 1330, 1170 (SO2). 1H-NMR (80 MHz): 1.22 (s, t-Bu); 3.88 (s, H'ÀC(3), HÀC(3)); 7.30 7.87 (m, 10 arom.
H). Anal. calc. for C18H21Br2NO2SSi (503.30): C 42.95, H 4.20, Br 31.75, N 2.78, S 6.37; found: C 42.80, H 4.30, Br
31.58, N 2.72, S 6.38.
4,4-Dibromo-2-cyclohexyl-1,2-thiazetidine 1,1-Dioxide (21b). Prepared from 1b (1.9 g, 10 mmol), as
described for 21a (Rf 0.61): 680 mg (20%). Colorless crystals. M.p. 958 (MeOH). IR: 2930, 2860 (CH), 1330,
1
1180, 1170 (SO2). H-NMR (80 MHz): 1.0 2.1 (m, 5 CH2); 3.28 (m, CH); 3.96 (s, H'ÀC(3), HÀC(3)). Anal.
calc. for C8H13Br2NO2S (347.06): C 27.69, H 3.77, Br 46.05, N 4.03, S 9.24; found: C 27.89, H 3.72, Br 45.85, N 4.12,
S 9.14.
4-Bromo-2-[(tert-butyl)diphenylsilyl]-1,2-thiazetidine 1,1-Dioxide (22a). Obtained as a side product in the
synthesis of 21a (Rf 0.59): 530 mg (13%). Colorless crystals. M.p. 127 1298 (MeOH). IR: 3070, 3000, 2960,
2940, 2860 (CH), 1320, 1185 (SO2). 1H-NMR (80 MHz): 1.21 (s, t-Bu); 3.17 (dd, J ˆ 7.5, H'ÀC(3)); 3.63
(dd(t), J ˆ 7.5, 7.5, HÀC(3)); 5.77 (dd, J ˆ 7.5, 5, HÀC(4)); 7.30 7.80 (m, 10 arom. H). Anal. calc. for
C18H22BrNO2SSi (424.40): C 50.94, H 5.22, Br 18.82, N 3.30, S 7.55; found: C 50.27, H 4.99, Br 18.51, N 3.51, S 7.34.
4-Bromo-2-cyclohexyl-1,2-thiazetidine 1,1-Dioxide (22b). Obtained as a side product in the synthesis of 21b
(Rf 0.43): 400 mg (15%). Colorless crystals. M.p. 518 (MeOH; lit. 60 618 [13]). IR: 2940, 2860 (CH), 1330,
1320, 1180, 1170 (SO2). 1H-NMR (80 MHz): 1.1 2.1 (m, 5 cyclohexyl CH2); 3.22 (m, cyclohexyl CH); 3.21
(dd, J ˆ 7.0, 4.5, H'ÀC(3)); 3.76 (dd, J ˆ 7.0, 7.0, HÀC(3)); 5.57 (dd, J ˆ 7.0, 4.5, HÀC(4)). Anal. calc. for
C8H14BrNO2S (268.17): C 35.83, H 5.26, Br 29.80, N 5.22, S 11.95; found C 36.01, H 5.22, Br 29.79, N 5.25, S 11.80.
Methyl 2-[(tert-butyl)dimethylsilyl-4-iodo-1,2-thiazetidine-4-carboxylate 1,1-Dioxide (23). A soln. of 15a
(550 mg, 2 mmol) in THF (20 ml) was added at À 788 to a soln. of LDA (3 mmol) in THF (20 ml). Then, the
mixture was added dropwise via syringe to a soln. of I2 (1.0 g, 4 mmol) in THF (30 ml) at À 788. After warming
to r.t., a mixture of an aq. sat. soln. of NaCl (100 ml) and an aq. soln. of NaHSO3 (15 ml, 37%) was added, the
org. layer was separated, washed twice with aq. NaCl soln., dried (Na2SO4), and evaporated in vacuo. The
residue was purified by CC (CHCl3; Rf 0.59): 160 mg (20%) of 23. Colorless crystals. M.p. 538 (pentane). IR:
2980, 2950, 2910, 2880 (CH), 1750 (CˆO), 1330, 1305, 1290, 1170 (SO2). 1H-NMR (80 MHz): 0.29 (s, Me2Si);
0.99 (s, t-Bu); 3.56 (d, J ˆ 7, H'ÀC(3)); 3.90 (s, MeO); 4.35 (d, J ˆ 7, H ÀC(3)). Anal. calc. for C10H20INO4SSi
(405.28): C 29.63, H 4.97, N 3.46, S 7.91; found: C 29.53, H 4.89, N 3.37, S 8.12.
Ethyl 2-[(tert-Butyl)diphenylsilyl]-1,2-thiazetidine-4-carboxylate 1,1-Dioxide (24). A cooled soln. of 1a
(1.72 g, 5 mmol) in THF (30 ml) was added to a soln. of LDA (8 mmol) in THF (20 ml) at À 788. After 2 min, a
soln. of diethyl azodicarboxylate (DEAD; 1.4 g, 8 mmol) in THF (10 ml) was added dropwise under stirring,
and stirring was continued for 20 min. Then, a sat. aq. soln. of NaCl (100 ml) was added, the org. layer was
separated, dried (Na2SO4), and evaporated in vacuo. The residue was dissolved in a few milliliters of CHCl3, and
cooled (24 h, 08). The precipitate (diethyl hydrazine-1,2-dicarboxylate; m.p. 1308) was separated, and the filtrate
was purified by CC (CHCl3; Rf 0.52): 200 mg (10%) of 24. Colorless crystals. M.p. 938 (pentane). IR: 3070,
1
3050, 3000, 2960, 2940, 2900, 2860 (CH), 1740 (CˆO), 1320, 1170, 1150 (SO2). H-NMR (80 MHz): 1.80 (s, t-
Bu); 1.32 (t, Me); 3.20 (dd, J ˆ 6, 8, H'ÀC(3)); 3.52 (dd, J ˆ 4.4, 6, HÀC(3)); 4.31 (q, CH2); 5.11 (dd, J ˆ 8, 4.4,
HÀC(4)); 7.30 7.92 (m, 10 arom. H). Anal. calc. for C21H27NO4SSi (417.55): C 60.41, H 6.52, N 3.35, S 7.68;
found: C 60.35, H 6.56, N 3.27, S 7.87.
Methyl 2-[(tert-Butyl)dimethylsilyl]-4-[1,2-bis(ethoxycarbonyl)hydrazino]-1,2-thiazetidine-4-carboxylate
1,1-Dioxide1) (26a). A soln. of 15a (410 mg, 1.5 mmol) in THF (15 ml) was added to a soln. of LDA (1.6 mmol)
in THF at À 788, and the mixture was stirred for 15 min. Then, a soln. of diethyl azodicarboxylate (290 mg,
1.6 mmol) was added, and stirring was continued for 45 min at À 788. The mixture was hydrolyzed with a sat. aq.
soln. of NaHCO3, extracted with CH2Cl2 (2 Â 40 ml), and the combined org. layers were dried (Na2SO4) and
evaporated. The residue was purified by CC (CHCl3/acetone 95 :5; Rf 0.22): 260 mg (38%) of 26a. Colorless
crystals. M.p. 948 (pentane). IR: 3250 (NH), 2990, 2960, 2940, 2860 (CH), 1765, 1730 (CˆO), 1540 (amide),
1310, 1145 (SO2). 1H-NMR (250 MHz): 0.22, 0.29 (2s, Me2Si); 0.91 (s, t-Bu); 1.27 (t, Me); 1.30 (t, Me); 3.72
(d, J ˆ 11, H'ÀC(3)); 3.87 (s, MeO); 4.20 (d, J ˆ 11, HÀC(3)); 4.20 4.32 (m, 2 OCH2); 7.19 (s, NH). Anal. calc.
for C16H31N3O8SSi (453.58): C 42.37, H 6.89, N 9.26, S 7.07; found C 42.60, H 6.92, N 9.45, S 7.00.
Methyl 2-[(tert-Butyl)dimethylsilyl]-4-{1,2-bis[(2,2,2-trichloroethoxy)carbonyl]hydrazino}-1,2-thiazeti-
dine-4-carboxylate 1,1-Dioxide1) (26b). Prepared from 15a (410 mg, 1.5 mmol) and bis(2,2,2-trichloroethyl)

Helvetica Chimica Acta Vol. 87 (2004)
1587
azodicarboxylate (600 mg, 1.6 mmol), as described for 26a, and purified by CC (CHCl3/acetone 9 :1; Rf 0.68):
480 mg (49%) of 26b. Colorless crystals. M.p. 1628 (Et2O/pentane). IR: 3230 (NH), 2960, 2930, 2890, 2860
(CH), 1770, 1740 (CˆO), 1540 (amide), 1325, 1290, 1180, 1140 (SO2), 1260 (MeÀSi), 810, 720 (Cl3C).
1H-NMR (80 MHz): 0.22, 0.27 (2s, Me2Si); 0.90 (s, t-Bu); 3.81 (d, J ˆ 11.5, H'ÀC(3)); 3.82 (s, MeO); 4.26
(d, J ˆ 11.5, HÀC(3)); 4.76 (s, 2 CH2); 7.76 (s, NH). Anal. calc. for C16H25Cl6N3O8SSi (660.26): C 29.11, H 3.82,
Cl 32.22, N 6.36, S 4.86; found: C 29.31, H 3.85, Cl 32.03, N 6.47, S 4.98.
4-Benzoyl-2-[(tert-butyl)dimethylsilyl]-1,2-thiazetidine 1,1-Dioxide1) (25). A soln. of 8 (2.2 g, 10 mmol) in
THF (60 ml) was added to a soln. of LDA (20 mmol) in THF (30 ml) at À 788. Then, ethyl benzoate (3 ml,
20 mmol) was added dropwise. After stirring for 1 h, the mixture was hydrolyzed with a sat. aq. soln. of NaCl, the
org. layer was separated, dried (Na2SO4), and evaporated in vacuo. The residue was purified by CC
(cyclohexane/AcOEt 4 :1; Rf 0.27): 1.8 g (55%) of 25. Colorless crystals. M.p. 878 (cyclohexane; lit. 878 [6]).
Molecular formula: C15H23NO3SSi (325.49 g molÀ1).
Phenyl 2-[(tert-Butyl)dimethylsilyl]-4-[1,2-bis(ethoxycarbonyl)hydrazino]-1,2-thiazetidine-4-carboxylate
1,1-Dioxide1) (27a). Prepared from 25 (480 mg, 1.5 mmol) and ethyl diazodicarboxylate (290 mg, 1.6 mmol),
as described for 26a (Rf 0.5): 460 mg (63%). Colorless crystals. M.p. 858 (pentane). IR: 3250 (NH), 2990, 2940,
2870 (CH), 1750, 1720 (CˆO), 1530 (amide), 1325, 1180, 1160 (SO2). 1H-NMR (250 MHz): 0.08, 0.26
(2s, Me2Si); 0.86 (s, t-Bu); 1.09 (t, Me); 1.34 (t, Me); 3.65 (d, J ˆ 11.3, H'ÀC(3)); 4.08 (m, OCH2); 4.30
(m, OCH2); 4.30 (d, J ˆ 11.3, HÀC(3)); 7.3 7.6 (m, 3 arom. H, NH); 8.43 (d, 2 arom. H). Anal. calc. for
C21H33N3O7SSi (499.65): C 50.48, H 6.66, N 8.41, S 6.42; found: C 50.45, H 6.64, N 8.49, S 6.50.
Phenyl 2-[(tert-Butyl)dimethylsilyl]-4-{1,2-bis[(2,2,2-trichloroethoxy)carbonyl]hydrazino}-1,2-thiazeti-
dine-4-carboxylate 1,1-Dioxide1) (27b). Prepared from 25 (480 mg, 1.5 mmol) and bis(2,2,2-trichloroethyl)
azodicarboxylate (600 mg, 1.6 mmol), as described for 26a: 800 mg (77%). Colorless crystals. M.p. 1618 (Et2O/
pentane). IR : 3260 (NH), 2950, 2920, 2890, 2860 (CH), 1750, 1710 (CˆO), 1525 (amide), 1320, 1170 (SO2),
1265 (MeÀSi), 820, 720 (Cl3C). 1H-NMR (80 MHz): 0.15, 0.28 (2s, Me2Si); 0.90 (s, t-Bu); 3.85 (d, J ˆ 11.5,
H'ÀC(3)); 4.36 (d, J ˆ 11.5, HÀC(3)); 4.67 (s, CH2); 4.87 (s, CH2); 7.32 7.73 (m, 3 arom. H); 8.12 (s, NH);
8.22 8.47 (m, 2 arom. H). Anal. calc. for C21H27Cl6N3O7SSi (706.33): C 35.71, H 3.85, Cl 30.12, N 5.95, S 4.54;
found: C 35.63, H 3.80, Cl 30.22, N 6.07, S 4.63.
Phenyl 2-[(tert-Butyl)dimethylsilyl]-4-{1,2-bis[(tert-butoxy)carbonyl]hydrazino}-1,2-thiazetidine-4-car-
boxylate 1,1-Dioxide1) (27c). Prepared from 25 (480 mg, 1.5 mmol) and di(tert-butyl) azodicarboxylate
(370 mg, 1.6 mmol), as described for 26a, and purified by CC (CHCl3/acetone 95 :5; Rf 0.39): 240 mg (29%) of
27c. Colorless crystals. M.p. 818 (Et2O/pentane). IR: 3240 (NH), 2980, 2960, 2940, 2860 (CH), 1730, 1710
(CˆO), 1325, 1170, 1150 (SO2), 1260 (MeÀSi). 1H-NMR (80 MHz): 0.05, 0.27 (2s, Me2Si); 0.88 (s, t-Bu); 1.26
(s, (t-Bu)O); 1.55 (s, (t-Bu)O); 3.70 (d, J ˆ 11.5, H'ÀC(3)); 4.35 (d, J ˆ 11.5, HÀC(3)); 7.07 (s, NH); 7.40 7.70
‡
(m, 3 arom. H); 8.40 8.60 (m, 2 arom. H). MS: 491 (0.89, [M À SO2] ), 105 (100). DCI-MS (NH3): 573 ([M ‡
‡
‡
‡
NH4] ). HR-MS: 491.2831 (M À SO2] ), C25H41N3O5Si ; calc. 491.2816). Anal. calc. for C25H41N3O7SSi
(555.77): C 54.03, H 7.44, N 7.56, S 5.77; found: C 53.96, H 7.36, N 7.30, S 5.63.
2-(tert-Butyl)dimethylsilyl]-4-(a-(trimethylsilyl)oxy]benzylidene)-1,2-thiazetidine 1,1-Dioxide (28a). A
cooled soln. of 25 (480 mg, 1.5 mmol) in THF (15 ml) was added dropwise to a soln. of LDA (2 mmol) in
THF (15 ml) at À 788. After stirring for 15 min at À 788, Me3SiCl (0.4 ml, 3 mmol) was added, and stirring was
continued for 45 min at r.t., before the solvent was evaporated: 410 mg (70%) of 28a. Light-yellow liquid.
IR (film): 3060, 3020, 2940, 2920, 2860 (CH), 1685, 1660 (CˆC), 1320, 1295, 1175, 1145 (SO2), 1250
(MeÀSi). 1H-NMR (60 MHz): 0.13, 0.26 (2s, Me2Si, Me3Si); 0.96 (s, t-Bu); 3.86, 3.97 (2s, H'ÀC(3), HÀC(3));
‡
7.16 8.23 (m, 5 arom. H). EI-MS: 340 (29, [M À t-Bu] ), 73 (100, 268 (14), 205 (21), 204 (20), 203 (15), 147
‡
(68), 131 (20), 105 (27), 103 (26), 77 (29). CI-MS (CH4): 398 ([M ‡ H] ). Molecular formula: C18H31NO3SSi2
(397.67 g molÀ1).
2-[(tert-Butyl)dimethylsilyl]-4-(a-{[(tert-butyl)dimethylsilyl]oxy}benzylidene)-1,2-thiazetidine 1,1-Dioxide
(28b). Prepared from 25 (480 mg, 1.5 mmol), LDA (1.6 mmol) in THF (20 ml), and (t-Bu)Me2SiCl (240 mg,
1.6 mmol) in THF (5 ml) at À 788, as described for 28a, and purified by Kugelrohr distillation: 590 mg (90%) of
28b. Colorless liquid. B.p. 1708/0.01 Torr. IR: 3060, 2960, 2940, 2890, 2860 (CH), 1670 (CˆC), 1310, 1150 (SO2).
1H-NMR (80 MHz): 0.0 (s, Me2Si); 0.27 (s, Me2Si); 0.95 (s, t-Bu); 1.00 (s, t-Bu); 3.88 (s, H'ÀC(3), HÀC(3));
7.3 7.8 ( m, 5 arom. H). Anal. calc. for C21H37NO3SSi2 (439.76): C 57.36, H 8.48, N 3.19, S 7.29; found: C 57.31, H
8.40, N 3.30, S 7.43.
3-Amino-2-hydroxy-1-phenylprop-2-en-1-one (29). A soln. of TBAF (0.5 ml, 0.5 mmol) was added under
stirring to a soln. of 27a (250 mg, 0.5 mmol) in THF (20 ml) under N2. After 30 s, the mixture was hydrolyzed
with a sat. aq. soln. of NaCl (40 ml), extracted with CH2Cl2 (2 Â 50 ml), and the combined org. layers were dried
(Na2SO4) and evaporated. The residue was purified by CC (CHCl3/acetone 9 :2; Rf 0.32): 27 mg (33%). IR:

1588
Helvetica Chimica Acta Vol. 87 (2004)
3460, 3300, 3180 (NH2, OH), 1660 (CˆO), 1580 (CˆO). 1H-NMR (80 MHz; (D6)acetone): 5.60 (s, NH2); 6.65
‡
(s, HÀC(3)); 7.45 (m, 5 arom. H); 8.0 (s, OH). EI-MS: 163 (26, M ), 162 (22), 105 (41), 77 (81), 58 (43), 57
‡
‡
‡
(100), 51 (45), 50 (22). CI-MS (CH4): 164 ([M ‡ H] ). HR-EI-MS: 163.0647 (M , C9H9NO2 ; calc. 163.0633).
Methyl 2-[(tert-Butyl)dimethylsilyl]-4-(3,5-dioxo-4-phenyl-1,2,4-triazolidin-1-yl)-1,2-thiazetidine-4-carbox-
ylate 1,1-Dioxide1) (30a). Prepared from 15a (410 mg, 1.5 mmol) and 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione
(280 mg, 1.6 mmol), as described for 26a. Hydrolysis with a mixture of a sat. aq. soln. of NaCl (57 ml) and conc.
HCl (3 ml): 400 mg (60%) of 30a. Light-yellow crystals. M.p. 80 828 (dec.; pentane). IR: 3200 3100 (NH),
2950, 2920, 2850 (CH), 1760 1710, 1690 (CˆO), 1290, 1170, 1150 (SO2). 1H-NMR (80 MHz): 0.25, 0.32
(2s, Me2Si); 0.96 (s, t-Bu); 3.83 (s, MeO); 4.25 (d, J ˆ 12, H'ÀC(3)); 4.83 (d, J ˆ 12, HÀC(3)); 6.17 (s, NH); 7.47
(m, 5 arom. H). Anal. calc. for C18H26N4O6SSi (454.58): C 47.56, H 5.76, N 12.33, S 7.05; found: C 47.66, H 5.83, N
12.45, S 6.96.
4-Benzoyl-2-[(tert-butyl)dimethylsilyl]-4-(3,5-dioxo-4-phenyl-1,2,4-triazolidin-1-yl)-1,2-thiazetidine 1,1-Di-
oxide1) (30b). Prepared from 25 (480 mg, 1.5 mmol) and 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione (280 mg,
1.6 mmol), as described for 26a. The residue was recrystallized from pentane/Et2O: 310 mg (41%) of 30b. Light-
yellow crystals. M.p. 1108 (dec.). IR: 3200 (NH), 2960, 2940, 2890, 2860 (CH), 1730 (CˆO), 1300, 1180, 1160
1
(SO2). H-NMR (80 MHz): 0.25, 0.30 (2s, Me2Si); 0.97 (s, t-Bu); 4.52 (d, J ˆ 11.5, H'ÀC(3)); 4.73 (d, J ˆ 11.5,
HÀC(3)); 7.3 7.7 (m, 8 arom. H, NH); 8.14 (d, 2 arom. H). Anal. calc. for C23H28N4O5SSi (500.64): C 55.18, H
5.64, N 11.19, S 6.40; found: C 55.46, H 5.75, N 11.01, S 6.20.
4-Azido-4-benzoyl-2-[(tert-butyl)dimethylsilyl]-1,2-thiazetidine 1,1-Dioxide1) (31a). A soln. of 25 (480 mg,
1.5 mmol) in THF (15 ml) was added dropwise to a soln. of LDA (1.6 mmol) in THF (15 ml) at À 788. After
stirring for 15 min at À 788, a soln. of tosyl azide (310 mg, 1.6 mmol) in THF (5 ml) was added. After 10 min, the
mixture was warmed to 08, Me3SiCl (0.44 ml, 3.5 mmol) was added, and stirring was continued for 30 min at r.t.
The solvent was evaporated in vacuo, and the residue was purified by CC (1. cyclohexane/AcOEt 4 :1 (Rf 0.45);
2. CHCl3 (Rf 0.36)): 45 mg (8%) of 31a. Colorless, viscous liquid. IR (film): 2960, 2940, 2890, 2860 (CH), 2120
(N3), 1700 (CˆO), 1300, 1175, 1150 (SO2), 1260 (MeÀSi). 1H-NMR (80 MHz): 0.26 (s, Me2Si); 0.95 (s, t-Bu);
4.03 (d, J ˆ 11.5, H'ÀC(3)); 4.70 (d, J ˆ 11.5, HÀC(3)); 7.3 7.7 (m, 3 arom. H); 8.15 (d, 2 arom. H). Molecular
formula: C15H22N4O3SSi (366.51 g molÀ1).
Methyl 4-Azido-2-[(tert-butyl)dimethylsilyl]-1,2-thiazetidine-4-carboxylate 1,1-Dioxide (31b). A soln. of
15a (410 mg, 1.5 mmol) in THF (15 ml) was added dropwise to a soln. of LDA (1.6 mmol) in THF (15 ml) at
À 788. After stirring for 15 min at À 788, tosyl azide (310 mg, 1.6 mmol) in THF (5 ml), and after 45 min,
Me3SiCl (0.44 ml, 3.5 mmol), were added. The mixture was stirred for another 30 min, then hydrolyzed with a
sat. aq. soln. of NaCl (50 ml). The org. layer was separated, dried (Na2SO4), and evaporated in vacuo. The
residue was purified by FC (CH2Cl2), probably yielding two stable conformers (31ba and 31bb; see Fig. 2) with
distinct properties (spectral data not assigned): a) 170 mg (35%) and b) 90 mg (19%).
Data of Major Conformer: Colorless liquid. Rf 0.27 (CH2Cl2). IR (film): 2970, 2940, 2900, 2870 (CH), 2140
(N3), 1760 (CˆO), 1300, 1180 (SO2), 1260 (MeÀSi). 1H-NMR (80 MHz): 0.26, 0.30 (2s, Me2Si); 0.95 (s, t-Bu);
3.89 (s, MeO); 3.93 (d, J ˆ 11.5, HÀC(3)); 4.23 (d, J ˆ 11.5, H'ÀC(3)). 13C-NMR: À 5.57, À 5.42 (Me2Si); 18.80,
25.87 (t-Bu); 53.68 (MeO); 55.31 (C(3)); 98.36 (C(4)); 165.99 (CˆO). Anal. calc. for C10H20N4O4SSi (320.44): C
37.48, H 6.29, N 17.48, S 10.00; found: C 37.74, H 6.26, N 17.25, S 9.89.
Data of Minor Conformer. Colorless liquid. Rf 0.20 (CH2Cl2). IR (film): identical with major conformer.
1H-NMR (80 MHz): 0.31, 0.32 (2s, Me2Si); 0.97 (s, t-Bu); 3.57 (d, J ˆ 11.5, H'ÀC(3)); 3.90 (s, MeO); 4.37 (d, J ˆ
11.5, HÀC(3)). 13C-NMR: À 5.36 (Me2Si); 18.85, 25.84 (t-Bu); 53.86 (MeO); 55.03 (C(3)); 97.33 (C(4)); 165.43
(CˆO). Anal. calc. for C10H20N4O4SSi (320.44): C 37.48, H 6.29, N 17.48; found: C 38.47, H 6.69, N 16.06.
2-[(tert-Butyl)dimethylsilyl]-4-(1,2-dihydro-1,3,5-triazin-2-yl)-1,2-thiazetidine 1,1-Dioxide1) (32). BuLi
(4.7 ml, 7.5 mmol) was added at À 788 to a soln. of 8 (1.1 g, 5 mmol) in THF (80 ml). Then, a cooled soln. of
1,3,5-triazine (640 mg, 8 mmol) in THF (15 ml) was added, and the mixture was stirred for 10 min at À 788. The
mixture was hydrolyzed with a sat. aq. soln. of NaCl (100 ml). The org. layer was separated, the aq. layer was
washed with CH2Cl2 (2 Â 50 ml), and the combined org. layers were dried (Na2SO4) and evaporated in vacuo:
490 mg (33%) of 32. Colorless crystals. M.p. 1338 (Et2O). IR: 3360 3180 (NH), 2960, 2940, 2900, 2860 (CH),
1685 (CˆN), 1310, 1195, 1140 (SO2), 1260 (MeÀSi). 1H-NMR (250 MHz): 0.27 (s, Me2Si); 0.97 (s, t-Bu); 3.38
(dd(t), J ˆ 5.0, 5.0, H'ÀC(3)); 3.51 (dd, J ˆ 7.5, 5.0, HÀC(3)); 4.68 (ddd, J ˆ 9.7, 7.5, 5.0, HÀC(4)); 5.20 (d, J ˆ
9.7, triazinyl HÀC(2)); 7.26, 7.28 (2s, triazinyl HÀC(4), triazinyl HÀC(6)); 8.48 (s, NH). Anal. calc. for
C11H22N4O2SSi (302.47): C 43.68, H 7.33, N 18.52, S 10.60; found: C 43.42, H 7.27, N 18.73, S 10.75.
2-[(tert-Butyl)dimethylsilyl]-4-(triethylsilyl)-1,2-thiazetidine 1,1-Dioxide (33). A soln. of 8 (2.2 g, 10 mmol)
in THF (40 ml) was added dropwise under stirring to a mixture of LDA (15 mmol) and Et3SiCl (2.26 g,
15 mmol) in THFat À 788, and stirring was continued for 1 h at this temp. Then, a sat. aq. soln. of NH4Cl (50 ml)

Helvetica Chimica Acta Vol. 87 (2004)
1589
and AcOEt (50 ml) were added, the org. layer was separated, washed with a sat. aq. soln. of NH4Cl, dried
(Na2SO4), and evaporated. The resulting residue was purified by FC (cyclohexane/Et2O 9 :1; Rf 0.2): 3.0 g
(89%) of 33. Colorless liquid. IR (film): 2957, 2880, 2862 (CH), 1470 (Me), 1301, 1161 (SO2). 1H-NMR
(300 MHz): 0.20 (s, Me2Si); 0.63 0.87 (m, 3 SiCH2); 0.92 (s, t-Bu); 0.94 1.00 (m, 3 Me); 3.12 (dd, J ˆ 5.0, 6.0,
H'ÀC(3)); 3.34 (dd, J ˆ 5.0, 9.0, HÀC(3)); 4.17 (dd, J ˆ 6.0, 9.0, HÀC(4)). 13C-NMR: À 6.13, À 6.08
(2s, Me2Si); 2.27 (s, SiCH2); 7.23, 18.16 (s, Me); 25.88 (s, Me3C); 32.08 (s, C(3)); 62.23 (s, C(4)). Anal. calc.
for C14H33NO2SSi2 (335.65): C 50.10, H 9.91, N 4.17, S 9.55; found: C 50.22, H 9.87, N 4.12, S 9.62.
2-[(tert-Butyl)dimethylsilyl]-4-nitro-1,2-thiazetidine 1,1-Dioxide (34). Propyl nitrate (450 ml, 4.5 mmol) was
added at À 788 to a soln. of 33 (500 mg, 1.49 mmol) and BuLi (1.9 ml, 3 mmol) in THF (30 ml). The mixture was
warmed to r.t., and after 1 h, AcOH (0.6 ml) was added, and the mixture was stirred for 15 min. Then, Et2O
(50 ml) was added, the mixture was washed with a sat. aq. soln. of NH4Cl (50 ml), the org. layer was separated,
dried (Na2SO4), and evaporated in vacuo. The residue was purified by FC (Et2O/cyclohexane 1 :1; Rf 0.38):
1
97 mg (24%) of 34. Yellow liquid. IR: 2962, 2933, 2862 (CH), 1570, 1359 (NO2), 1328, 1184 (SO2). H-NMR
(300 MHz): 0.29, 0.31 (2s, Me2Si); 0.97 (s, t-Bu); 3.69 (dd, J ˆ 7.0, 8.0, H'ÀC(3)); 3.94 (dd, J ˆ 8.0, 4.0, HÀC(3));
6.42 (dd, J ˆ 7.0, 4.0, HÀC(4)). Anal. calc. for C8H18N2O4SSi (266.39): C 36.07, H 6.81, N 10.52; found: C 35.80, H
6.55, N 10.16.
2-[(tert-Butyl)dimethylsilyl]-N-phenyl-1,2-thiazetidine-4-carboxamide 1,1-Dioxide (35). A soln. of 12
(480 mg, 1.7 mmol) in Et2O (10 ml) was added dropwise at 08 to a soln. of aniline (0.15 g, 1.7 mmol) and pyridine
(0.13 ml, 1.7 mmol) in Et2O (50 ml). After 4 h, the precipitate was separated, and the solvent was evaporated.
The residue was purified by CC (acetone/AcOEt 1:1; Rf 0.73): 230 mg (14%). (Compound 35 was also obtained
(in higher yield!) as a −side product× in the synthesis of 36 from 8: 180 mg (31%)). Colorless crystals. M.p. 1138
(pentane). IR: 3340 (NH), 3080, 3060, 3020, 2950, 2920, 2900, 2880, 2860 (CH), 1700 (CˆO), 1540 (amide),
1300, 1160, 1150 (SO2), 1250 (MeÀSi). 1H-NMR (250 MHz): 0.32, 0.33 (2s, Me2Si); 1.00 (s, t-Bu); 3.56 (dd, J ˆ
5.8, 8.0, H'ÀC(3)); 3.75 (dd(t), J ˆ 4.6, 5.8, HÀC(3)); 5.29 (dd, J ˆ 8.0, 4.6, HÀC(4)); 7.11 7.64 (m, 5 arom. H);
8.77 (s, NH). Anal. calc. for C15H24N2O2SSi (340.50): C 52.91, H 7.10, N 8.23, S 9.41; found: C 52.99, H 7.14, N
8.33, S 9.30.
2-[(tert-Butyl)dimethylsilyl]-N,N'-diphenyl-1,2-thiazetidine-4,4-dicarboxamide 1,1-Dioxide (36). BuLi
(4.4 ml, 7 mmol) was added to a soln. of 8 (1.1 g, 5 mmol) in THF (60 ml), and the mixture was cooled to
À 788. A soln. of phenylisocyanate (0.75 ml, 7 mmol) in THF (10 ml) was added. The mixture was stirred for
30 min at À 788 and then hydrolyzed with a mixture of a sat. aq. soln. of NaCl (95 ml) and conc. HCl (5 ml). The
org. layer was separated, dried (Na2SO4), and evaporated in vacuo: 520 mg (22%) of 36. Colorless crystals. M.p.
1728 (toluene). IR: 3340 (NH), 3060, 2960, 2940, 2900, 2860 (CH), 1700, 1670 (CˆO), 1535 (amide), 1330, 1320,
1160 (SO2), 1260 (MeÀSi). 1H-NMR (80 MHz): 0.22 (s, Me2Si); 0.92 (s, t-Bu); 4.00 (s, H'ÀC(3), HÀC(3));
6.95 7.55 (m, 10 arom. H); 8.85 (s, 2 NH). Anal. calc. for C22H29N3O4SSi (459.62): C 57.62, H 6.36, N 9.14, S
6.97; found: C 57.76, H 6.25, N 9.30, S 7.19.
2-[(tert-Butyl)dimethylsilyl)-1,2-thiazetidine-4-carboxamide 1,1-Dioxide (37). A sat. soln. of NH3 in CHCl3
(10 ml) was added to a soln. of 12 (280 mg, 1 mmol) in CHCl3 (25 ml) at 08. After stirring for 1 h, the mixture
was hydrolyzed with an aq. sat. soln. of NaCl (40 ml). The org. layer was separated, dried (Na2SO4), and
evaporated in vacuo: 65 mg (25%) of 37. Colorless crystals. M.p. 123 1258 (pentane). IR: 3460, 3230 3180
(NH), 2990, 2960, 2940, 2900, 2890, 2860 (CH), 1690 (CˆO), 1300, 1170 (SO2), 1260 (MeÀSi). 1H-NMR
(80 MHz; (D6)acetone): 0.26 (s, Me2Si); 0.98 (s, t-Bu); 3.46 (dd, J ˆ 5.8, 7.8, H'ÀC(3)); 3.69 (dd(t), J ˆ 4.5, 5.8,
‡
HÀC(3)); 5.25 (dd, J ˆ 7.8, 4.5, HÀC(4)); 6.82 (s, NH); 7.38 (s, NH). EI-MS: 207 (73, [M À t-Bu] ), 128
‡
(100%). CI-MS (CH4): 265 ([M ‡ H] ). Anal. calc. for C9H20N2O3SSi (264.41): C 40.88, H 7.62, N 10.59, S 12.13;
found: C 40.46, H 7.24, N 10.20, S 12.33.
2-[(tert-Butyl)dimethylsilyl]-N-[4-(2-ethoxy-2-oxoethyl)-1,3-thiazol-2-yl]-1,2-thiazetidine-4-carboxamide1)
(38a). Prepared from 12 (480 mg, 1.7 mmol) and ethyl 2-amino-1,3-thiazol-4-acetate (320 mg, 1.7 mmol) in
Et2O (40 ml), as described for 35 (reaction time: 3 4 h). The residue crystallized, when some drops of MeOH
were added: 180 mg (25%) of 38a. Colorless crystals. M.p. 1868 (MeoH). IR: 3330 (NH), 2990, 2960, 2940, 2900,
2860 (CH), 1740, 1700 (CˆO), 1560 (amide), 1310, 1300, 1170 (SO2), 1260 (MeÀSi). 1H-NMR (80 MHz): 0.32
(s, Me2Si); 1.00 (s, t-Bu); 1.27 (t, Me); 3.52 (dd, J ˆ 6, 8, H'ÀC(3)); 3.71 (s, CH2); 3.80 (dd(t), J ˆ 4.4, 6,
HÀC(3)); 4.17 (q, OCH2); 5.42 (dd, J ˆ 8, 4.4, HÀC(4)); 6.85 (s, thiazolyl HÀC(5)); 7.32 (s, NH). Anal. calc.
for C16H27N3O5S2Si (433.61): C 44.32, H 6.28, N 9.69, S 14.79; found: C 44.22, H 6.27, N 9.44, S 14.74.
2-[(tert-Butyl)dimethylsilyl]-N-(4-{2-ethoxy-1-[(Z)-methoxyimino]-2-oxoethyl}-1,3-thiazol-2-yl)-1,2-thi-
azetidine-4-carboxamide1) (38b). Prepared from 12 (480 mg, 1.7 mmol) and ethyl (Z)-(methoxyimino)(1,3-
thiazol-4-yl)acetate (380 mg, 1.7 mmol) in Et2O (40 ml), as described for 35 (reaction time: 3 4 h at 08). The
residue was purified by CC (acetone/AcOEt 1 :1; Rf 0.73): 170 mg (21%). Colorless crystals. M.p. 868 (MeOH).

1590
Helvetica Chimica Acta Vol. 87 (2004)
IR: 3280 (NH), 2960, 2940, 2900, 2860 (CH), 1735, 1695 (CˆO), 1555 (amide), 1320, 1300, 1175 (SO2), 1265
1
(MeÀSi). H-NMR (80 MHz): 0.30 (s, Me2Si); 0.99 (s, t-Bu); 1.32 (t, Me); 3.50 (dd, J ˆ 5.8, 8, H'ÀC(3)); 3.72
(dd(t), J ˆ 4.6, 5.8, HÀC(3)); 3.97 (s, MeO); 4.37 (q, OCH2); 5.40 (dd, J ˆ 8, 4.6, HÀC(4)); 7.27 (s, thiazolyl,
‡
HÀC(5)); 10.3 (s, NH). EI-MS: 476 (5, M ), 421 (16), 420 (23), 419 (100), 355 (42), 340 (27), 326 (22), 251
‡
‡
(26), 236 (30), 99 (22), 75 (36), 73 (47), 59 (23), 55 (70). HR-EI-MS: 476.12135 (M , C17H28N4O6S2Si ; calc.
476.1220).
REFERENCES
[1] T. Rˆhrich, B. Abu Thaher, H.-H. Otto, Monatsh. Chem. 2004, 135, 55.
[2] A. Meinzer, A. Breckel, B. Abu Thaher, N. Manicone, H.-H. Otto, Helv. Chim. Acta 2004, 87, 90.
[3] N. Manicone, Ph.D. Thesis, University of Freiburg i.Br., 2000, and lit. cit. therein.
[4] M. M¸ller, E. Meyle, E. F. Paulus, H. Plagge, H.-H. Otto, Liebigs Ann. Chem. 1989, 975.
[5] M. M¸ller, H.-H. Otto, Liebigs Ann. Chem. 1991, 171.
[6] H. Plagge, H.-H. Otto, Heterocycles 1993, 35, 193.
[7] E. Meyle, H.-H. Otto, J. Chem. Soc., Chem. Commun. 1984, 1084; E. Meyle, P. Schwenkkraus, M.
Zsigmondy, H.-H. Otto, Arch. Pharm. 1989, 322, 17.
[8] E. Meyle, H.-H. Otto, C. Kratky, Monatsh. Chem. 1985, 116, 493.
[9] E. Meyle, Ph.D. Thesis, University of Freiburg i.Br., 1983.
[10] A. LeBerre, A. Etienne, J. Coquelin, Bull. Soc. Chim. Fr. 1974, 221.
[11] H. Wild, in ×The Organic Chemistry of b-Lactams×, Ed. G. I. Georg, Wiley-VCH, New York, 1992.
[12] K. K¸hlein, H. Jensen, Liebigs Ann. Chem. 1974, 369.
¬
[13] A. Champseix, J. Chanet, A. Etienne, A. LeBerre, J. C. Masson, C. Napierala, R. Vessiere, Bull. Soc. Chim.
Fr. 1985, 463.
Received January 26, 2004