1,2-Asymmetric induction in the ketene Claisen rearrangement of (2S,3E)-5-(isopropylsulfanyl)-3-pentenes

Article abstract of DOI:10.1016/S0040-4020(01)00465-3

The ketene Claisen rearrangement of chiral (2S,3E)-5-(isopropylsulfanyl)-3-penten-2-amines has been investigated by the semi-empirical AM1 method. The observed efficient direction of the 1,2-asymmetric induction in the ketene Claisen rearrangement has been modelled from comparison of the energies of the four possible transition states arising from two chair-like and two boat-like structures. The resulting trends of relative transition state energy are in reasonable agreement with experimental observations.

Full text of DOI:10.1016/S0040-4020(01)00465-3

TETRAHEDRON
Pergamon
Tetrahedron 57 +2001) 5607±5613
1,2-Asymmetric induction in the ketene Claisen rearrangement of
ꢀ2S,3E)-5-ꢀisopropylsulfanyl)-3-pentenes
a,p
Jozef Gonda, Miroslava Martinkova, Beat Ernst and Daniel Bellus
a
b
Â
Ïc
a
Ï
Department of Organic Chemistry, P.J. Safarik University, Moyzesova 11, 04167 Kosice, Slovak Republic
Ï
b
È
È
Department of Pharmacy, University of Basel, Totengasslein, CH-4051 Basel, Switzerland
cCiba Specialities Ltd, R-1059.5.15, CH-4002 Basel, Switzerland
Received 15 January 2001; revised 11 April 2001; accepted 26 April 2001
AbstractÐThe ketene Claisen rearrangement of chiral +2S,3E)-5-+isopropylsulfanyl)-3-penten-2-amines has been investigated by the semi-
empirical AM1 method. The observed ef®cient direction of the 1,2-asymmetric induction in the ketene Claisen rearrangement has been
modelled from comparison of the energies of the four possible transition states arising from two chair-like and two boat-like structures. The
resulting trends of relative transition state energy are in reasonable agreement with experimental observations. q 2001 Elsevier Science Ltd.
All rights reserved.
1. Introduction
2. Results and discussion
The Claisen rearrangement has become one of the most
powerful tools for stereoselective carbon±carbon bond
formation.1 Much of its current popularity is due to the
subsequent development of a series of new variants of this
+3,3)-sigmatropic rearrangement. In 1978, we reported2 a
ketene version of the Claisen rearrangement. Treatment of
allyl ethers with in situ prepared dichloroketene provided
rearrangement products in good yield.3 We showed that the
ketene Claisen rearrangement of allyl thioethers 1 and 2
proceeds diastereoselectively with a high preference for
syn-3 +de$94%) and syn-5 +de$90%) derivatives4 +Scheme
1).
The methyl ester of N-benzyl-l-alanine5 after reaction with
di-tert-butyl dicarbonate and reduction with diisobutyl-
aluminium hydride +DIBAL-H) afforded alcohol 9.6
A
Swern oxidation, and chain elongation via Wittig ole®nation
+Ph3PCHCOOCH3) led to ester 10.7 The second DIBAL-H
reduction led to allyl alcohol 11, the corresponding Mosher
ester8 of which was used to determine its optical purity
+de$95%).
Subsequently 11 was converted into thioacetate 12 by reac-
tion with thioacetic acid under Mitsunobu conditions.
Saponi®cation and in situ alkylation with 2-bromopropane
afforded thioether 13. Thioether 14 was easily prepared by
hydrolysis of 13 +with tri¯uoroacetic acid) and reaction of
the amine with p-toluenesulfonyl chloride +Scheme 2).
Dichloroketene, generated in situ by reductive elimination
of chlorine from trichloroacetyl chloride upon treatment
with activated zinc,3 was allowed to react with allyl
Here we report on the 1,2-asymmetric induction in the
ketene Claisen rearrangement of chiral +2S,3E)-5-+iso-
propylsulfanyl)-3-penten-2-amines 13 and 14 and the pos-
sible transition states of this reaction at semi-empirical AM1
SCF-MO level.
Scheme 1.
Keywords: rearrangements; semi-empirical; transition state; asymmetric induction.
Corresponding author. Tel.: 1421-95-62-28332; fax: 1421-95-62-22124; e-mail: jgonda@kosice.upjs.sk
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020+01)00 465-3

5608
J. Gonda et al. / Tetrahedron 57 72001) 5607±5613
Scheme 2. +a) BOC2O, DMPA, 87%; +b) DIBAH, hexane, 2788C +68±75%); +c) +i) +COCl)2, DMSO, Net3, 2788C, +ii) Ph3PˆCHCOOCH3, THF, CH2Cl2,
2788C!208C +64%); +d) AcSH, Ph3P, diethyl azodicarboxylate +DEAD), THF, 08C +71%); +e) NaOEt, EtOH, 208C, 1 h then i-PrBr, 12 h +99%); +f) +i) TFA,
K2CO3, +ii) TsCl, K2CO3 +80%).
thioethers 13 and 14. Compound 13 afforded diastereo-
isomers 17 and 18 in a ratio of 80:20 +deˆ60%) and oxazo-
lidones 21 and 22 as byproducts. Thioether 14 afforded 19
and 20 as a mixture of diastereoisomers, 90:10 +deˆ80%).
Examination of the con®guration in thioesters 17, 18 and 19,
20 was carried out using 1H NMR spectroscopy of the corre-
sponding cyclised products 24 and 26, which were obtained
by reductive cyclization with Zn/AcOH +Scheme 3). Irradia-
tion of the methyl protons in lactone 24 resulted in a 9%
NOE on the vinyl CH signal, indicating a cis relationship
between these two substituents which supports a threo
con®guration and syn selectivity in the formation of 17
and 19. Irradiation of the methyl protons in 26 led to 0%
NOE on the vinyl CH, indicating a trans relationship
between these substituents and thus the erythro con®gura-
tion of 18 and 20. Under non-reducing conditions, thioesters
17 and 18 afforded chlorolactones 23 and 25 +Scheme 3).
ment. Theoretical calculations were carried out at the semi-
empirical RHF AM1 SCF-MO level, as implemented in the
mopac 6.0program. 9±11 We obtained optimized geometries
for all molecules in the reactions using the BFGS optimi-
zation method with AM1 parameters. The energetics
reported are based upon the lowest energy reactant and
product conformations. We explored the conformation
space of reactant and product using a grid calculation imple-
mented in mopac.9 The resultant low-energy structures were
fully optimized at the AM1 level. The transition states for
the ketene Claisen rearrangement of compounds 1, 2 and 13
were located using the saddle routine12 implemented in
mopac and performing a grid calculation with bond distance
search on the active S±C5 and C2±C3 bonds +Fig. 1, Table
1). Further re®nements of these approximate transition-state
geometries were carried out by minimizing the energy12
using the eigenvector-following +EF) method. The resulting
geometries have one and only one negative vibration
freqency12 and veri®cation using intrinsic reaction coordi-
nate calculations for modes 1 and 21 led to the reactants
and products of the reactions.
It is worth noting that while high 1,2-stereoinduction
occurred upon dichloroketene addition to 1 and 2 +with 94
and 90%, respectively), reactions of 13 and 14 in the same
conditions led to only 60and 80% de. This fact prompted us
to investigate the models corresponding to this rearrange-
For the reaction of 1 with ketene to give syn-3 and anti-4,
Scheme 3. +a) CCl3COCl, Et2O, Zn/Cu, 408C, 3±6 h; +b) TFA, NaHCO3, 2 h; +c) AcOH, Zn, 1108C +17, 18 3 h; 19, 20 24 h).

J. Gonda et al. / Tetrahedron 57 72001) 5607±5613
5609
Figure 1. The transition structures of reaction of 1 with ketene +AM1 geometry; distances in angstroms).
Table 1. Heat of formation DHf +298 K) and some geometrical parameters for localized stationary structures
1
TS1A
TS2B
TS3C
TS4D
syn-3
anti-4
DHf +kJ/mol)
S±C5b
C2±C3
2501.24 +0.00)a
2470.28 +17.15)
2.108
2.244
2453.12 +20.37)
2.062
2.221
2449.90+23.84)
2.131
2.267
2446.43
2.146
2.274
2634.96
2623.49
2
TS1E
TS2F
TS3G
TS4H
syn-5
anti-6
DHf +kJ/mol)
S±C5
C2±C3
2537.76 +0.00)
2509.15 +25.43)
2.107
2.249
2483.71 +28.66)
2.062
2.227
2477.17 +29.28)
2.148
2.275
2479.86
2.132
2.267
2671.23
2650.52
13
TS1ITS2J
TS3K
TS4L
syn-17
anti-18
DHf +kJ/mol)
S±C5
C2±C3
2276.60
2240.49 +0.00)
2.107
2.239
2238.99 +1.50)
2.086
2.228
2239.40+1.08)
2.157
2.279
2227.48 +13.01)
2.185
2.287
2406.22
2401.49
a
Value in parentheses are relative energies in kJ/mol.
Distances are in angstroms.
b

5610
J. Gonda et al. / Tetrahedron 57 72001) 5607±5613
two chair-like transition states TS1A and TS2B with
DHfˆ2470.28 and 2453.12 kJ/mol and two boat-like tran-
sition structures TS3C and TS4D with DHfˆ2449.90and
2446.43 kJ/mol, respectively, were found +Table 1). The
calculated energy difference in favor of diastereoisomer
syn-3 +formed via TS1A) is 17.15 kJ/mol in comparison to
the anti-4 +via TS2B) and predicts exclusive formation of
this product +calculated diastereoselectivity, de$99.9%). In
the reaction of 2 with ketene to syn-5 and anti-6, the dia-
stereomeric chair-like TS1E, which leads to syn-5, is
preferred by 25.43 kJ/mol in comparison to the chair-like
TS2F +which led to anti-6) +Table 1). These results are in
good agreement with experimentally4 determined high +94
and 90%) syn selectivity. For the reaction of 13 with ketene
to give products syn-17 and anti-18, two chair-like tran-
sition states TS1I and TS2J with DHfˆ2240.49 and
2238.99 kJ/mol and two boat-like transition structures
TS3K and TS4L with DHfˆ2239.40and 2227.48 kJ/
mol, respectively, were found +Table 1). The transition
state TS1I, which led to syn-17, is favored by only
1.08 kJ/mol in comparison with TS3K and the calculated
diastereoselectivity, deˆ20%, is in resonable agreement
with the deˆ60% observed. This is indicative of more
complex electronic and steric interaction in transitions states
of the reaction.
layer was washed with brine +60mL), dried +MgSO 4) and
concentrated in vacuo. Puri®cation of the residue by column
chromatograpy on silica gel using hexane/AcOEt +7:3) as an
eluent afforded 11 +0.87 g, 75%) as a colourless oil.
21
[a]D ˆ217.42 +c 0.79, CHCl3). IR: 3600, 3450, 3030,
2980, 2930, 2827, 1730, 1680, 1600, 1490, 1450 1405,
1365, 1340, 1240, 1165, 1100, 1030, 1000, 980, 865. H
1
NMR: 1.21 +3H, d, Jˆ7.2 Hz, CH3CH), 1.37 +9H, b s,
+CH3)3C), 3.66 +1H, b s, OH), 4.02 +2H, d, Jˆ4.7 Hz,
CH2OH), 4.33±4.42 +1H, m, CHCH3), 4.50+1H, d, Jˆ
9.3 Hz, CHaHbPh), 4.59 +1H, d, Jˆ9.3 Hz, CHaHbPh),
5.65±5.71 +1H, m, CHvCHCH2), 5.95±6.01 +1H, m,
CHvCHCH2), 7.11±7.35 +5H, m, Ph). 13C NMR: 19.2,
24.4, 43.8, 46.5, 61.6, 80.1, 123.5, 123.6, 124.2, 126.3,
140.2, 153.3. Anal. calcd for C17H25NO3: C 70.07, H 8.65,
N 4.81; found: C 70.12, H 8.62, N 4.78.
4.1.2. ꢀE,4S)-4-[Benzylꢀtert-butoxycarbonyl)amino]-2-pen-
tenyl ethanethioate ꢀ12). To a stirred solution of triphenyl-
phosphine +3.25 g, 12.4 mmol) in THF was added dropwise
diethylazodicarboxylate +2.15 g, 12.3 mmol) at 08C. the
solution of 11 +2.39 g, 8.2 mmol) in THF +15 mL) was
added at the same temperature. To the mixture was added
thioacetic acid +0.94 g, 12.3 mmol) in THF +15 mL) and
stirring was continued at 08C for 1 h. The mixture was
allowed to warm to rt over 2 h and then quenched with
0.5 mL H2O and 100 mL n-pentane. The precipitate was
collected by ®ltration. The organic layer was concentrated
in vacuo. Puri®cation of the residue by column chroma-
tography on silica gel using hexane/AcOEt +95:5) as an
eluent afforded 12 +2.03 g, 71%) as a colourless oil.
3. Conclusion
Calculated transition states for the ketene Claisen rearrange-
ments of chiral +2S,3E)-5-+isopropylsulfanyl)-3-pentenes at
a semiempirical AM1 level are concerted but asynchronous.
Chair-like and boat-like structures are typical13 for +3,3)-
sigmatropic rearrangements. The simple AM1 model
presented for the ketene Claisen rearrangement of allyl
thioethers demonstrates that the diastereoselectivities
observed are entirely consistent with the energy difference
between such diastereomeric transition states.
21
[a]D ˆ239.29 +c 0.84, CHCl3). IR: 2970, 2930, 1685,
1492, 1450, 1400, 1365, 1340, 1240, 1165, 1135, 1112,
1
1020, 960. H NMR: 1.16 +3H, d, Jˆ6.91 Hz, CH3CH),
1.44 +9H, s, +CH3)3C), 2.31 +3H, s, CH3CO), 3.03 +2H, d,
Jˆ6.7 Hz, CH2S), 3.50±3.61 +1H, m, CHCH3), 4.25 +1H, d,
Jˆ9.3 Hz, CHaHbPh), 4.34 +1H, d, Jˆ9.3 Hz, CHaHbPh),
5.48±5.53 +1H, m, CHvCHCH2), 5.65±5.72 +1H, m,
CHvCHCH2), 7.19±7.32 +5H, m, Ph). 13C NMR: 17.9,
28.3, 30.8, 33.3, 47.1, 52.3, 79.6, 126.5, 126.8, 128.1,
128.2, 134.4, 139.3, 155.5, 194.5. Anal. calcd for
C19H27NO3S: C 65.33, 7.79, N 4.01, S 9.17; found: C
65.29, H 7.83, N 3.98, S 9.16.
4. Experimental
The reagents and solvents: purchased from Fluka AG in the
highest obtainable purity. CHCl3 and CDCl3 were passed
throgh basic alumina +Woelm, act. 1) immediately before
use. Optical rotations: Perkin±Elmer 241 MC. TLC: DC
Alufolien Kieselgel 60F254 +Merck), detection UV
+254 nm) and/or KMnO4 spray. Chromatography: Kieselgel
0.032±0.060 mesh +Merck). IR spectra +2±3%) in CHCl3:
4.1.3. tert-Butyl N-benzyl-N-[ꢀ1S,2E)-4-ꢀisopropylsul-
fanyl)-1-methyl-2-butenyl]carbamate ꢀ13). Compound
12 +3.5 g, 10mmol) in 5 mL of ethanol was added to
7 mmol of freshly prepared NaOEt in 1 mL of ethanol.
After stirring at rt for 1 h, the mixture was treated with
1.22 g +10mmol) of 2-bromopropane. After 12 h, the
mixture was diluted with 50mL of Et 2O and washed with
H2O +2£15 mL), brine +10mL), dried +MgSO 4), and con-
centrated in vacuo. The puri®cation of the residue by
column chromatography on silica gel using hexane/AcOEt
+7:3) as an eluent afforded 13 +3.40g, 99%) as a colourless
Perkin±Elmer 599 IR spectrometer; absorptions in cm21
.
NMR spectra: d in ppm relative to internal Me4Si
+ˆ0ppm) in CDCl 3 at rt, Bruckner WM 360+36.013,
90.56 MHz). All reactions were run under argon using
¯ame-dried glassware.
21
oil. [a]D ˆ212.29 +c 0.84, CHCl3). IR: 2972, 2930, 1680,
4.1. Data for compounds
1490, 1455, 1410, 1360, 1343, 1242, 1170, 1140, 1110,
1
1022, 963. H NMR: 1.16 +3H, d, Jˆ6.91 Hz, CH3CHN),
4.1.1. tert-Butyl N-benzyl-N-[ꢀ1S,2E)-4-hydroxy-1-methyl-
2-butenyl]carbamate ꢀ11). To a stirred solution of 10
+1.27 g, 4 mmol) in THF +50mL) was added dropwise
DIBAL-H +1 M in toluene, 8.1 mL, 8.1 mmol) at 08C. The
mixture was stirred for an additional 30min and quenched
with H2O and diluted with AcOEt +100 mL). The organic
1.19 +6H, d, Jˆ6.7 Hz, +CH3)2CHS), 1.45 +9H, b s,
+CH3)3C), 2.60±2.71 +1H, m, CHS), 3.03 +2H, d, Jˆ
6.6 Hz, CH2S), 3.50+1H, m, C HN), 4.25 +1H, d, Jˆ
9.3 Hz, CHaHbPh), 4.33 +1H, d, Jˆ9.3 Hz, CHaHbPh),
5.44±5.49 +1H, m, CHvCHCH2), 5.62±5.71 +1H, m,

J. Gonda et al. / Tetrahedron 57 72001) 5607±5613
5611
CHvCHCH2), 7.19±7.32 +5H, m, Ph). 13C NMR: 17.8,
28.5, 28.3, 32.1, 45.1, 53.2, 78.9, 126.4, 126.5, 128.5,
128.5, 134.5, 139.6, 155.6, 194.8. Anal. calcd for
C20H31NO2S: C 68.73, H 8.94, N 4.01, S 9.17; found: C
68.67, H 8.86, N 4.01, S 9.16.
C13H15NO2: C 71.87, H 6.96, N 6.45; found: C 71.85, H
6.99, N 6.43.
4.1.8. ꢀ4S,5S)-3-Benzyl-4-methyl-5-vinyl-1,3-oxazolan-2-
21
one ꢀ22). Colourless oil. [a]D ˆ14.6 +c 0.96 CHCl3). IR:
3080, 3060, 3020, 2970, 2920, 1740, 1492, 1410, 1380,
1360, 1320, 1325, 1200, 1175, 1100, 1020, 1025, 985,
955, 940, 760, 700. 1H NMR: 1.10+3H, d, Jˆ6.0Hz,
CH3), 3.53±3.61 +1H, m, CHN), 4.11 +1H, d, Jˆ9.3 Hz,
CHaHbPh), 4.80+1H, d, Jˆ9.3 Hz, CHaHbPh), 4.78±4.82
+1H, m, CHO), 5.24 +1H, m, CHaHbvCH), 5.43±5.47
+1H, m, CHaHbvCH), 5.79±5.83 +1H, m, CHvCH2),
7.22±7.39 +5H, m, Ph). 13C NMR: 17.0, 45.9, 55.9, 81.9,
119.5, 127.9, 128.1, 128.8, 133.6, 135.9, 157.8. Anal. calcd
for C13H15NO2: C 71.87, H 6.96, N 6.45; found: C 71.84, H
6.95, N 6.41.
4.1.4. Ketene Claisen rearrangement of allylthioether 13.
Allyl thioether 13 +0.501 g, 1.5 mmol) and about 15 mmol
Zn/Cu alloy were placed in 15 mL of vigorously stirred
diethylether under argon and the mixture was heated to
re¯ux. A solution of 0.55 g +3 mmol) of freshly distilled
trichloroacetylchloride in 5 mL of ether was added dropwise
to the solution over 4 h by means of a syringe pump. After
cooling, the reaction solution was decanted from the resi-
due. Chromatographic separation on silica gel +hexane/
AcOEt, 9:1) yield, 17 +0.52 g, 74%), 18 +0.12 g, 17%), 21
+0.003 g, 0.9%) and 22 +0.002 g, 0.6%).
4.1.9. ꢀ4R,5S)-1-Benzyl-3,3-dichloro-5-methyl-4-vinyl-
tetrahydro-1H-pyrrol-2-one ꢀ23). Thioester 17 +0.456 g,
1 mmol) in 69 mL CH3CN was treated slowly with 4 mL
of 48% HF in CH3CN with stirring at rt. After 2.5 h, the
mixture was poured on ice/solid NaHCO3 and extracted
with CH2Cl2 +5£25 mL). The organic layer was dried
+MgSO4) and concentrated to give a yellow oil. Rapid chro-
4.1.5. Isopropyl ꢀ3R)-3-ꢀꢀ1S)-1-benzylꢀtert-butoxycarbo-
nyl)amino)ethyl)-2,2-dichloropent-4-enethioate
ꢀ17).
21
Colourless oil. [a]D ˆ17.09 +c 0.76, CHCl3). IR: 2980,
2930, 2870, 1770, 1500, 1470, 1452, 1405, 1395, 1368,
1345, 1310, 1240, 1170, 1060, 1030, 1000, 940, 910, 800,
1
700, 650, 620. H NMR: 1.18 +d, 3H, Jˆ6.2 Hz, CH3CH),
1.31 +6H, d, Jˆ7.2 Hz, +CH3)2CH), 1.40+9H, s, +C H3)3C),
3.50±3.58 +1H, m, CHS), 3.64±3.70+m, 1H, C HCHvCH2),
4.11±4.20+m, 1H, C HN), 4.25 +1H, d, Jˆ9.3 Hz,
CHaHbPh), 4.38 +1H, d, Jˆ9.3 Hz, CHaHbPh), 5.15±5.20
+1H, m, CHaHbvCH), 5.23±5.25 +1H, m, CHaHbvCH),
5.67 +1H, m, CHvCH2), 7.20±7.35 +m, 5H, Ph). 13C
NMR: 18.4, 19.5, 23.0, 29.1, 51.8, 53.8, 58.2, 81.0, 92.8,
122.8, 127.5, 127.6, 128.0, 132.6, 140.0, 155.8, 194.0. Anal.
calcd for C22H31Cl2NO3S: C 57.39, H 6.79, N 3.04, S 6.96;
found: C 57.43, H 6.84, N 3.08, S 7.00.
matography on silica gel +ether/petroleum ether, 2:8)
21
yielded 23 +0.257 g, 90%) as a colourless oil. [a]D
ˆ
25.18 +c 0.89 CHCl3). IR: 3080, 3020, 2970, 2920, 2860,
1715, 1490, 1410, 1380, 1350, 1310, 1275, 1230, 1200, 850,
740, 695. 1H NMR: 1.22 +3H, d, Jˆ6.6 Hz, CH3), 3.23±3.27
+1H, m, CHN), 3.58±3.63 +1H, m, CHCCl2), 4.06 +1H, d,
Jˆ9.3 Hz, CHaHbPh), 5.08 +1H, d, Jˆ9.3 Hz, CHaHbPh),
5.28±5.34 +1H, m, CHaHbvCH), 5.41±5.45 +1H, m,
CHaHbvCH), 5.93±6.04 +1H, m, CHvCH2), 7.19±7.33
+5H, m, Ph). 13C NMR: 13.6, 45.4, 53.8, 57.7, 84.9, 123.0,
128.2, 129.0, 129.7, 135.1, 166.4. Anal. calcd for
C14H15Cl2NO: C 59.17, H 5.32, N 4.93; found: C 59.15, H
5.29, N 4.89.
4.1.6. Isopropyl ꢀ3S)-3-ꢀꢀ1S)-1-benzylꢀtert-butoxycarbo-
nyl)amino)ethyl)-2,2-dichloropent-4-enethioate
ꢀ18).
21
Colourless oil. [a]D ˆ22.91 +c 1.04 CHCl3). IR: 2978,
2930, 2860, 1685, 1495, 1465, 1450, 1405, 1390, 1340,
1240, 1160, 1120, 1080, 1060, 1030, 995, 930, 910, 860.
1H NMR: 1.09 +d, 3H, Jˆ6.3 Hz, CH3CH), 1.34 +6H, d,
Jˆ7.2 Hz, +CH3)2CH), 1.43 +9H, s, +CH3)3C), 3.62±3.71
+m, 1H, CHCHvCH2), 3.72±3.83 +1H, m, CHS), 4.13±
4.20+m, 1H, C HN), 4.29 +1H, d, Jˆ9.3 Hz, CHaHbPh),
4.43 +1H, d, Jˆ9.3 Hz, CHaHbPh), 5.21±5.22 +1H, m,
CHaHbvCH), 5.26±5.33 +1H, m, CHaHbvCH), 5.73 +1H,
m, CHvCH2), 7.19±7.33 +m, 5H, Ph). 13C NMR: 19.3,
20.3, 22.8, 28.8, 36.9, 54.0, 58.4, 80.3, 80.4, 92.0, 121.4,
121.5, 127.0, 129.0, 133.8, 133.9, 139.9, 156.0, 195.0. Anal.
calcd for C22H31Cl2NO3S: C 57.39, H 6.79, N 3.04, S 6.96;
found: C 57.41, H 6.82, N 3.09, S 7.01.
4.1.10. ꢀ4S,5S)-1-Benzyl-3,3-dichloro-5-methyl-4-vinyl-
tetrahydro-1H-pyrrol-2-one ꢀ25). Following the pro-
cedure described for the preparation of 23, 18 +0.456 g,
1 mmol) gave, after chromatography on silica gel +ether/
petroleum ether, 2:8), 25 +0.263 g, 93%) as a colourless
21
oil. [a]D ˆ15.25 +c 1.13, CHCl3). IR: 3030, 2970, 2920,
2860, 1710, 1440, 1420, 1380, 1350, 1250, 1150, 1110,
1
1070, 1040, 940, 890, 850. H NMR: 1.20+3H, d, Jˆ
6.0Hz, CH 3), 3.26±3.29 +1H, m, CHN), 3.55±3.61 +1H,
m, CHCCl2), 4.02 +1H, d, Jˆ9.3 Hz, CHaHbPh), 5.16 +1H,
d, Jˆ9.3 Hz, CHaHbPh), 5.35±5.40+1H, m, C HaHbvCH),
5.46±5.51 +1H, m, CHaHbvCH), 5.87±5.92 +1H, m,
CHvCH2), 7.20±7.34 +5H, m, Ph). 13C NMR: 15.9, 44.6,
53.5, 62.2, 85.1, 123.5, 127.9, 128.0, 128.9, 129.5, 135.1,
167.0. Anal. calcd for C14H15Cl2NO: C 59.17, H 5.32, N
4.93; found: C 59.18, H 5.28, N 4.90.
4.1.7. ꢀ4S,5R)-3-Benzyl-4-methyl-5-vinyl-1,3-oxazolan-2-
21
one ꢀ21). Colourless oil. [a]D ˆ29.4 +c 1.08 CHCl3). IR:
3080, 3060, 3020, 2870, 2820, 1740, 1490, 1410, 1480,
1460, 1420, 1235, 1200, 1175, 1100, 1060, 1025, 990,
4.1.11. N-ꢀBenzylꢀ4-toluenesulfonyl)-ꢀ2S,3E)-5-isopropyl-
thio)pent-3-en-2-amine ꢀ14). To a tri¯uoroacetic acid
+10mL) was added 13 +3.50g, 10mmol) at 0 8C and stirring
was continued for 2 h. The reaction mixture was evaporated
in vacuo and residue was triturated with sat. Na2CO3
+40mL). After addition of tosylchloride +1.90g, 10mmol)
in CH2Cl2 +15 mL) was reaction mixture stirred additional
12 h at rt. The organic layer was washed with 0.5 M HCl
1
955, 760, 700. H NMR: 1.08 +3H, d, Jˆ7.1 Hz, CH3),
3.70±3.76 +1H, m, CHN), 4.04 +1H, d, Jˆ9.2 Hz,
CHaHbPh), 4.84 +1H, d, Jˆ9.2 Hz, CHaHbPh), 4.85±4.88
+1H, m, CHO), 5.36 +1H, m, CHaHbvCH), 5.42±5.46
+1H, m, CHaHbvCH), 5.85 +1H, m, C±HvCH2), 7.23±
7.40+5H, m, Ph). 13C NMR: 13.7, 45.8, 53.2, 78.1, 120.0,
127.9, 128.1, 28.8, 131.2, 136.1, 157.6. Anal. calcd for

5612
J. Gonda et al. / Tetrahedron 57 72001) 5607±5613
+50mL), dried +MgSO 4) and concentrated in vacuo. The
residue was chromatographed on silica gel +hexane/
washed with 2N NaOH +30mL) and sat. NaHCO 3
+2£20mL), dried +MgSO 4), and concentrated. The residue
was chromatographed on silica gel +Et2O/petroleum ether,
2:8) to yield 24 +250mg, 95%) as a colourless oil.
21
AcOEt), 7:3) to yield 14 +3.2 g, 80%) as a oil. [ a]D
212.9 +c 1.02 CHCl3). IR: 3070, 3040, 2930, 2870, 1600,
ˆ
21
1500, 1450, 1380, 1360, 1340, 1300, 1200, 1160, 1100,
[a]D ˆ25.8 +c 0.89 CHCl3). IR: 3350, 3060, 2970, 2920,
1
1010, 980, 920, 860. H NMR: 1.08 +3H, d, Jˆ7.2 Hz,
1670, 1490, 1440, 1415, 1380, 1353, 1315, 1295, 1255,
1230, 1200, 1165, 1080, 1030, 1000, 925. H NMR: 1.03
1
CH3CHN), 1.19 +6H, d, Jˆ6.7 Hz, +CH3)2CH), 2.20+3H,
s, CH3Ph), 2.66 +1H, m, CH+CH3)2), 2.95 +2H, d, Jˆ
6.6 Hz, CH2S), 4.22 +1H, d, Jˆ9.3 Hz, CHaHbPh), 4.40
+1H, d, Jˆ9.3 Hz, CHaHbPh), 4.42±4.46 +1H, m, CHN),
5.20±5.26 +1H, m, CHvCHCH2), 5.41±5.44 +1H, m,
CHvCHCH2), 7.18±7.32 +5H, m, Ph), 7.87±7.94 +4H, m,
Ph). 13C NMR: 19.8, 21.9, 24.1, 32.4, 34.2, 48.0, 55.2,
127.8, 128.2, 128.3, 130.0, 131.8, 127.9, 130.8, 143.6.
Anal. calcd for C22H29NO2S2: C 65.47, H 7.24, N 3.47, S
15.89; found: C 65.45, H 7.22, N 3.40, S 15.86.
+3H, d, Jˆ6 Hz, CH3), 2.40±2.54 +2H, m, CH2CO), 2.94±
3.02 +m, 1H, CHCH2), 3.03±3.35 +1H, m, CH), 3.91 +1H, d,
Jˆ9.3 Hz, CHaHbPh), 4.64±4.69 +1H, m, CHaHbvCH),
5.38 +1H, d, Jˆ9.3 Hz, CHaHbPh), 5.47±5.63 +1H, m,
CHaHbvCH), 5.75±5.85 +1H, m, CH2vCH), 7.20±7.32
+5H, m, Ph). 13C NMR: 14.0, 35.2, 41.0, 44.0, 55.7, 117.3,
127.5, 128.0, 128.7, 136.0, 136.8 173.6. Anal. calcd for
C14H17NO: C 78.10, H 7.96, N 6.51; found: C 78.13, H
7.94, N 6.48.
4.1.16. ꢀ4S,5S)-1-Benzyl-5-methyl-4-vinyltetrahydro-1H-
pyrrol-2-one ꢀ26). Following the procedure described for
the preparation 24, compound 18 +0.46 g, 1 mmol) gave
after chromatography on silica gel +ether/petroleum ether,
4.1.12. Ketene Claisen rearrangement of allyl thioether
14. Folowing the procedure described for the rearrangement
of 13, thioether 14 +0.4 g, 1 mmol) gave, after chroma-
tography on silica gel +ether/petroleum ether, 2:9) 19
+0.458 g, 89%) and 20 +0.048 g, 9.5%).
21
2:8) 26 +193 mg, 90%) as a colourless oil. [a]D ˆ16.4 +c
0.77 CHCl3). IR: 3350, 3060, 3020, 2920, 1680, 1495, 1450,
1420, 1380, 1360, 1320, 1300, 1260, 1230, 1205, 1170,
4.1.13. Isopropyl ꢀ3R)-3-ꢀꢀ1S)-1-benzylꢀꢀ4-methylphenyl)-
sulfonyl)amino)ethyl)-2,2-dichloropent-4-enethioate ꢀ19).
1
1030, 1000, 925. H NMR: 1.16 +3H, d, Jˆ6 Hz, CH3),
21
2.40±2.47 +2H, m, CH2CO), 2.89±3.02 +m, 1H, CHCH2),
3.15±3.31 +1H, m, CH), 4.12 +1H, d, Jˆ9.3 Hz, CHaHbPh),
4.61±4.65 +1H, m, CHaHbvCH), 5.25 +1H, d, Jˆ9.3 Hz,
CHaHbPh), 5.59±5.64 +1H, m, CHaHbvCH), 5.73±5.81
+1H, m, CH2vCH), 7.19±7.31 +5H, m, Ph). 13C NMR:
17.8, 36.9, 44.0, 57.9, 116.7, 127.5, 128.0, 128.7, 136.7,
137.8, 173.9. Anal. calcd for C14H17NO: C 78.10, H 7.96,
N 6.51; found: C 78.15, H 7.93, N 6.47.
Colourless oil. [a]D ˆ13.2 +c 0.77 CHCl3). IR: 2960,
2920, 2860, 1680, 1595, 1495, 1450, 1340, 1300, 1160,
1090, 1055, 1000, 940, 920, 860, 810, 800, 760, 650. H
1
NMR: 1.21 +3H, d, Jˆ6.3 Hz, CH3CH), 1.32 +6H, d, Jˆ
6.7 Hz, +CH3)2CH), 2.42 +3H, s, CH3Ph), 3.31±3.35 +1H,
m, CHS), 3.85±3.91 +1H, m, CHCCl2), 4.14 +1H, d,
Jˆ9.3 Hz, CHaHbPh), 4.32±4.38 +1H, m, CHN), 4.45 +1H,
d, Jˆ9.3 Hz, CHaHbPh), 4.63±4.68 +1H, m, CHaHbvCH),
5.13±5.21 +1H, m, CHaHbvCH), 5.65±5.78 +1H, m,
CH2vCH), 7.19±7.32 +5H, m, Ph), 7.71±7.78 +4H, m,
Ph). 13C NMR: 18.8, 22.1, 37.0, 48.4, 56.9, 57.5, 92.0,
123.2, 127.5, 128.1, 128.2, 128.3, 128.7, 130.0, 131.2,
133.5. Anal. calcd for C24H29Cl2NO3S2: C 56.02, H 5.68,
N 2.72, S 12.46; found: C 56.05, H 5.71, N 2.75, S 12.43.
Acknowledgements
The present work was supported by a Grant Agency
+1/6080/99) from the Ministry of Education, Slovak
Republic.
4.1.14. Isopropyl ꢀ3S)-3-ꢀꢀ1S)-1-benzylꢀꢀ4-methylphenyl)-
sulfonyl)amino)ethyl)-2,2-dichloropent-4-enethioate ꢀ20).
21
Colourless oil. [a]D ˆ26.1 +c 0.57 CHCl3). IR: 2960,
References
2920, 2860, 1680, 1595, 1495, 1450, 1340, 1300, 1160,
1090, 1055, 1000, 940, 920, 860, 810, 800, 760, 650. H
1
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NMR: 1.18 +3H, d, Jˆ6.3 Hz, CH3CH), 1.36 +6H, d, Jˆ
6.7 Hz, +CH3)2CH), 2.37 +3H, s, CH3Ph), 3.42±3.48 +1H,
m, CHS), 3.75±3.88 +1H, m, CHCCl2), 4.14 +1H, d, Jˆ
9.3 Hz, CHaHbPh), 4.29±4.35 +1H, m, CHN), 4.42 +1H, d,
Jˆ9.3 Hz, CHaHbPh), 4.60±4.66 +1H, m, CHaHbvCH),
5.20±5.28 +1H, m, CHaHbvCH), 5.70±5.85 +1H, m,
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123.9, 127.6, 128.0, 128.8, 131.2, 138.2, 142.0, 194.0.
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