Asymmetric induction in a new domino reaction of [3,3]-sigmatropic rearrangement of allylic thiocyanates and intramolecular heterocyclisation

Article abstract of DOI:10.1016/S0040-4020(02)00026-1

A new synthetic route to diastereomerically pure (4S,5S)-4-vinyltetrahydro-1H-2-imidazolethiones via a novel domino reaction of [3,3]-sigmatropic rearrangement of chiral thiocyanates followed by stereoselective intramolecular amine addition to arising isothiocyanates is reported.

Full text of DOI:10.1016/S0040-4020(02)00026-1

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 1611±1616
Asymmetric induction in a new domino reaction of
[3,3]-sigmatropic rearrangement of allylic thiocyanates and
intramolecular heterocyclisation
p
Jozef Gonda, Miroslava Martinkova and Jan Imrich
Â
Â
Ï
Department of Organic Chemistry, P.J. Safarik University, Moyzesova 11, 04167 Kosice, Slovakia
Â
Received 17 September 2001;revised 30 November 2001;accepted 3 January 2002
AbstractÐA new synthetic route to diastereomerically pure (4S,5S)-4-vinyltetrahydro-1H-2-imidazolethiones via a novel domino
reaction of [3,3]-sigmatropic rearrangement of chiral thiocyanates followed by stereoselective intramolecular amine addition to arising
isothiocyanates is reported. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
The usefulness of chiral 1,2-diamines as auxiliaries and
controller groups in asymmetric dihydroxylation,1 con-
jugate addition,2 ole®nation,3 allylation,4 epoxidation,5 or
aldol condensation6 is well documented. Although the 1,2-
diamino unit is a constituent of natural products only an
astonishingly small number of stereocontrolled syntheses
have been developed for them.7 In a previous paper, we
have reported the excellent diastereoselectivity in 1,2-asym-
metric induction8 for the palladium(II) catalyzed aza-
Claisen rearrangement of allylic trichloroacetimidates 1
leading to anti-1,2-diamines 2 and (2S,3S)-diaminobutanoic
acids 3 (Scheme 1).
We wish to report now12 a new and highly stereoselective
preparation of (4S,5S)-4-vinyltetrahydro-1H-2-imidazol-
ethiones, as useful precursors for (2R,3S)-diaminoalkanoic
acids, by a novel domino reaction of [3,3]-sigmatropic
rearrangement of chiral allylic thiocyanates followed by
stereoselective intramolecular amine addition to arising
isothiocyanates.
The starting thiocyanates 6a±e were prepared by SN2
displacement of the O-mesyl group in 5a±e, derived from
allylic alcohols 4a±e,13 by thiocyanate group (KSCN/
CH3CN) in 85±90% overall yields (Scheme 2). The thermal
rearrangement of thiocyanate 6a was carried out at 808C in
xylene under N2 for 1 h with high yield of isothiocyanates
7a and 8a (92%), but without selectivity (anti-7a/syn-
8a<50:50). The prolonged heating of the reaction mixture
(26 h) unexpectedly led to the formation of tert-butyl
(4S,5S)-5-methyl-2-thioxo-4-vinyltetrahydro-1H-1-imida-
zolecarboxylate 9a as a single reaction product in 89%
Due to the biological importance of the a,b-diamino acids,
much effort has been directed toward their stereoselective
synthesis. Speci®cally, synthetic approaches have been
reported for preparing 2,3-diaminopropanoic9 and diamino-
butanoic8,10 acids as well as other 2,3-diaminoalkanoic
acids.11
Scheme 1.
Keywords: rearrangements;asymmetric induction;aminoacids.
Corresponding author. Tel.: 1421-95-62-28332;fax: 1421-95-62-22124;e-mail: jgonda@kosice.upjs.sk
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00026-1

1612
J. Gonda et al. / Tetrahedron 58 /2002) 1611±1616
26±44 to 3 h) with the conservation of the high diastereo-
selectivity of the reaction.
The reaction of imidazolidines 9a±e and 10a with TFA/H2O
afforded the corresponding cyclic thioureas 11a±e and 12a
(Scheme 2). The reaction stereochemistry was determined
by NOE difference experiments of cyclic thioureas 11a and
12a. Irradiation of the methyl protons in 12a resulted in a
9% NOE on vinyl CH signal, indicating a cis relationship
between these two substituents and thus 4R,5S con®gura-
tion. Irradiation of the methyl protons in 11a resulted in
almost 0% NOE on vinyl CH, indicating a trans relationship
between these substituents and thus the 4S,5Scon®guration
of 11a.
The observed stereochemistry of these reactions can be
rationalized by transition states A and B of the hetero-
cyclisation step in Fig. 1. Unfavorable interaction between
the R group and vinyl group in the transition state A is in
agreement with experimentally observed, very low yield of
cis-isomer. Consequently, the preferred product is formed
through transition state B in which the steric interactions
between R and vinyl moiety is signi®cantly reduced. The
reversible rearrangement thiocyanate$isothiocyanate14 is a
reason for complete conversion of diastereomers 7a±e to
8a±e via the corresponding thiocyanates 6a±e and preferred
formation of 9a±e. 2-Hydroxypyridine probably works as
proton transfer catalyst. This is indicative that the diastereo-
selectivity of the reaction may be explained by two-proton
transfer15 in the transition state C of the rate-determining
step (Fig. 1).
Scheme 2.
yield. To investigate the variability of this synthetic method,
different allylic thiocyanates 6b±e were examined. In all
cases the heating of thiocyanates 6b±e in xylene at 808C
for 3 h afforded the mixture of isothiocyanates 7b±e and
8b±e (50:50). Further heating at the same temperature for
26±44 h led to intramolecular addition of the amine to NCS
group with stereoselective formation of imidazolidines
9b±e (Table 1).
Figure 1. Proposed transition-state models of the heterocyclisation step.
In contrast with these results, treatment of anti-7a and syn-
8a (crude mixture ,50:50, obtained by rearrangement of
thiocyanate 6a) with sodium hydride in THF at 08C for
15 min afforded the mixture of diastereomers 10a and 9a
in essentially the same ratio. We have found that the
presence of catalytic amount of 2-hydroxypyridine
(0.10 mol%) signi®cantly reduces the reaction time (from
3. Conclusion
In summary, we have developed a novel domino reaction of
[3,3]-sigmatropic rearrangement of chiral allylic thio-
cyanates, followed by stereocontrolled intramolecular addi-
tion of amine to NCS group, leading to diastereomerically
pure (4S,5S)-4-vinyltetrahydro-1H-2-imidazolethiones. Ab
initio investigation of this reaction will be reported in due
course.
Table 1. tert-Butyl (4S,5S)-5-alkyl-2-thioxo-4-vinyltetrahydro-1H-1-
imidazolecarboxylates 9a±e produced via Scheme 2
4. Experimental
Entry Educt
R
Product Yield (%)a Period (h)a
Ratiob
Melting points are uncorrected. 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 60
F254 (Merck), detection UV (254 nm) and/or KMnO4 spray.
Chromatography: silica gel 0.032±0.060 mesh (Merck). IR
spectra (2±3%) in CHCl3: Perkin±Elmer 599 IR spectro-
meter;absorptions in cm 21. The elucidation of the structure
1
2
3
4
5
6a
6b
6c
6d
6e
Me
Et
i-Pr
Bn
9a
9b
9c
9d
89/89
87/90
84/89
80/85
84/88
26/3
30/3
36/3
29/3
44/3
98:2
99:1
99.5:0.5
99.5:0.5
99.5:0.5
i-Bu 9e
a
Method A/Method B. Method A: all reaction were carried out at 808C in
xylene. Method B: all reaction were carried out at 808C in xylene in the
presence of 0.10 mol% 2-hydroxypyridine.
b
Diastereoselectivities were determined by 1H NMR analysis.

J. Gonda et al. / Tetrahedron 58 /2002) 1611±1616
1613
and stereochemical arrangement of compounds 9a±e, 10a,
4.2. General procedure for the synthesis of the
thiocyanates 6a±e
11a±e followed from NMR studies incorporating a suite of
experiments. In addition to the 1D 1H, NOE difference, 1D
homonuclear selectively decoupled, 13C broadband-
decoupled, DEPT-90, and DEPT-135 spectra, 2D H,H-
COSY, and CHSHF experiments were acquired on a
JEOL Alpha 400 NMR spectrometer equipped with a
5 mm probe operating at 399.65 MHz for 1H, and
100.00 MHz for 13C. The spectra were recorded at
398.3 K in deuteriochloroform and both 1H and 13C spectra
were referenced internally to tetramethylsilane (0 ppm for
both).
To a solution of the mesylates 5a±e (1 mmol) in CH3CN
(10 mL) was added KSCN (1.2 mmol). After being stirred
for 2 h at room temperature, the reaction mixture was
concentrated under reduced pressure. The resulting residue
was diluted with diethyl ether and solid was removed by
®ltration. The organic phase was concentrated under
reduced pressure to afford the crude products, which were
puri®ed by silica gel chromatography (20% ethyl acetate/
hexane) to provide the thiocyanates 6a±e.
4.2.1. tert-Butyl N-[01S,2E)-1-methyl-4-thiocyanato-2-
pentenyl]carbamate
4.1. General procedure for the synthesis of the mesylates
5a±e
06a).
83%;colorless
oil;
25
[a]D ˆ260.4 (c 0.77 CHCl3);IR (CHCl ) 3443, 2150,
3
1
1685 cm21; H NMR (400 MHz, CDCl3) d 1.26 (3H, d,
To a solution of allylic alcohol 4a±e (1 mmol) in dry
CH2Cl2 (10 mL) were added Et3N (1.5 mmol) and
CH3SO2Cl (1.2 mmol) at 08C. After being stirred under
the same temperature for 1 h, the reaction mixture was
concentrated under reduced pressure. The resulting residue
was diluted with diethyl ether (15 mL) and solid was
removed by ®ltration. The organic phase was concentrated
under reduced pressure to afford the crude products, which
were puri®ed by ¯ash chromatography over silica gel (20%
ethyl acetate/hexane) to provide the mesylates 5a±e. This
material was used for the next reaction without further
puri®cation.
Jˆ6.5 Hz, CH3), 1.45 (9H, s, 3£CH3), 3.52±3.57 (2H, m,
H1), 4.34±4.42 (2H, m, NH, H4), 5.70±5.76 (2H, m, H2, H3);
13C NMR (100 MHz, CDCl3) d 14.8, 28.1, 35.7, 56.9, 79.6,
111.75, 123.1, 137.7, 155.0. Anal. Calcd for C11H18N2O2S:
C, 54.52;H, 7.49;N, 11.56;S, 13.23. Found: C, 54.63;H,
7.51;N, 11.45;S, 13.37.
4.2.2. tert-Butyl N-[01S,2E)-1-ethyl-4-thiocyanato-2-
25
hexenyl]carbamate 06b). 86%;colorless oil;[ a]D
ˆ
251.4 (c 1.1 CHCl3);IR (CHCl ) 3440, 2152, 1686 cm21
;
3
1H NMR (400 MHz, CDCl3) d 0.91 (3H, t, Jˆ7.5 Hz);1.45
(9H, s, 3£CH3), 1.53±1.58 (2H, m, H5), 3.53±3.59 (2H, m,
H1), 4.05 (1H, b s, NH), 4.52±4.58 (1H, m, H4), 5.70±5.76
(2H, m, H2, H3); 13C NMR (100 MHz, CDCl3) d 11.3, 23.3,
28.4, 35.8, 55.9, 80.1, 111.8, 122.6, 138.6, 155.2. Anal.
Calcd for C12H20N2O2S: C, 56.22;H, 7.86;N, 10.93;S,
12.51. Found: C, 56.31;H, 7.94;N, 10.73;S, 12.31.
4.1.1. 0E,4S)-4-[0tert-Butoxycarbonyl)amino]-2-pentenyl
methanesulfonate 05a). 92%;colorless oil; 1H NMR
(400 MHz, CDCl3) d 1.24 (3H, d, Jˆ6.7 Hz, CH3), 1.44
(9H, s, 3£CH3), 3.01 (3H, s, CH3SO2), 4.30±4.35 (1H, m,
H4), 4.71 (2H, d, Jˆ5.0 Hz, H1);5.76±5.82 (2H, m, H 2, H3).
4.2.3. tert-Butyl N-[01S,2E)-1-isopropyl-4-thiocyanato-2-
4.1.2. 0E,4S)-4-[0tert-Butoxycarbonyl)amino]-2-hexenyl
methanesulfonate 05b). 95%;colorless oil; 1H NMR
(400 MHz, CDCl3) d 0.98 (t, Jˆ7.2 Hz, CH3), 1.32±1.36
(2H, m, H5), 1.48 (9H, s, 3£CH3), 3.04 (3H, s, CH3SO2),
4.10±4.16 (1H, m, H4), 4.74 (2H, d, Jˆ5.1 Hz, H1),
5.77±5.83 (2H, m, H2, H3).
25
hexenyl]carbamate 06c). 85%;colorless oil;[ a]D
ˆ
260.4 (c 0.81 CHCl3);IR (CHCl
)
3445, 2152,
3
1
1683 cm21; H NMR (400 MHz, CDCl3) d 0.94 (3H, d,
Jˆ6.8 Hz, CH3), 0.95 (3H, d, Jˆ6.8 Hz, CH3), 1.46 (9H,
s, 3£CH3), 1.78±1.82 (1H, m, H5), 3.56±3.60 (2H, m,
H1), 4.03 (1H, b s, NH), 4.55±4.61 (1H, m, H4), 5.70±
5.76 (2H, m, H2, H3); 13C NMR (100 MHz, CDCl3) d
18.1, 18.7, 28.4, 32.3, 36.0, 57.1, 79.6, 111.9, 123.7,
137.1, 155.4. Anal. Calcd for C13H22N2O2S: C, 57.75;H,
8.20;N, 10.36;S, 11.86. Found: C, 57.64;H, 8.24;N, 10.41;
S, 11.73.
4.1.3. 0E,4S)-4-[0tert-Butoxycarbonyl)amino]-5-methyl-
2-hexenyl methanesulfonate 05c). 96%;colorless oil; 1H
NMR (400 MHz, CDCl3) d 0.91 (6H, d, Jˆ6.7 Hz, 2£CH3),
1.44 (9H, s, 3£CH3), 1.76±1.80 (1H, m, H5), 3.01 (3H, s,
CH3SO2), 4.00±4.10 (1H, m, H4), 4.73 (2H, d, Jˆ4.7 Hz,
H1), 5.76±5.78 (2H, m, H2, H3).
4.2.4. tert-Butyl N-[01S,2E)-1-benzyl-4-thiocyanato-2-
pentenyl]carbamate 06d). 87%;white solid: mp 58±
4.1.4. 0E,4S)-4-[0tert-Butoxycarbonyl)amino]-5-phenyl-
2-pentenyl methanesulfonate 05d). 91%;colorless oil; 1H
NMR (400 MHz, CDCl3) d 1.40 (9H, s, 3£CH3), 2.94 (3H,
s, CH3SO2) 2.94±2.96 (2H, m, H5), 4.45±4.51 (1H, m, H4),
4.67 (2H, d, Jˆ5.1 Hz, H1), 5.75±5.77 (2H, m, H2, H3),
7.22±7.26 (5H, m, Ph).
25
608C;[ a]D ˆ240.2 (c 0.91 CHCl3);IR (CHCl ) 3446,
3
2151, 1684 cm21
;
1H NMR (400 MHz, CDCl3) d 1.40
(9H, s, 3£CH3), 2.84±2.88 (2H, m, H5), 3.50±5.54 (2H,
m, H1), 4.09 (1H, b s, NH), 4.57±4.64 (1H, m, H4), 5.70±
5.76 (2H, m, H2, H3), 7.17±7.21 (2H, m, Ph), 7.27±7.33
(3H, m, Ph); 13C NMR (100 MHz, CDCl3) d 28.3, 35.7,
41.5, 52.6, 79.8, 111.8, 122.8, 126.7, 128.4, 129.5, 136.8,
137.7, 155.1. Anal. Calcd for C14H24N2O2S: C, 59.12;H,
8.51;N, 9.85;S, 11.27. Found: C, 59.18;H, 8.62;N, 9.79;S,
11.33.
4.1.5. 0E,4S)-4-[0tert-Butoxycarbonyl)amino]-6-methyl-
2-heptenyl methanesulfonate 05e). 95%;colorless oil; 1H
NMR (400 MHz, CDCl3) d 0.94 (3H, d, Jˆ6.6 Hz, CH3),
0.95 (3H, d, Jˆ6.6 Hz, CH3), 1.28±1.32 (2H, m, H5), 1.44
(9H, s, 3£CH3), 1.47±1.53 (1H, m, H6), 3.03 (3H, s,
CH3SO2), 4.18±4.22 (1H, m, H4), 4.71±4.75 (2H, m, H1),
5.75±5.81 (2H, m, H2, H3).
4.2.5. tert-Butyl N-[01S,2E)-1-isobutyl-4-thiocyanato-2-
heptenyl]carbamate
06e).
82%;colorless
oil;

1614
J. Gonda et al. / Tetrahedron 58 /2002) 1611±1616
25
[a]D ˆ282.4 (c 0.80 CHCl3);IR (CHCl ) 3445, 2151,
70.2, 83.5, 117.4, 136.4, 150.2, 180.4. Anal. Calcd for
C13H22N2O2S: C, 57.75;H, 8.20;N, 10.36;S, 11.86.
Found: C, 57.79;H, 8.13;N, 10.42;S, 11.79.
3
1
1683 cm21; H NMR (400 MHz, CDCl3) d 0.93 (3H, d,
Jˆ6.6 Hz, CH3), 0.94 (3H, d, Jˆ6.6 Hz, CH3), 1.46 (9H,
s, 3£CH3), 1.54±1.58 (3H, m, H5, H6), 3.53±3.59 (2H, m,
H1), 4.00 (1H, b s, NH), 4.50±4.52 (1H, m, H4), 5.71±5.75
(2H, m, H2, H3); 13C NMR (100 Hz, CDCl3) d 22.2, 22.7,
24.7, 28.4, 35.8, 44.4, 51.0, 79.6, 111.8, 122.2, 139.2, 155.2.
Anal. Calcd for C17H22N2O2S: C, 64.12;H, 6.96;N, 8.80;S,
10.07. Found: C, 64.23;H, 6.87;N, 8.83;S, 10.12.
4.3.4. tert-Butyl 04S,5S)-5-benzyl-2-thioxo-4-vinyltetra-
hydro-1H-1-imidazolecarboxylate 09d). 85%;colorless
25
oil;[ a]D ˆ255.6 (c 0.77 CHCl3);IR (CHCl 3) 3443,
1
1687 cm21; H NMR (400 MHz, CDCl3) d 1.60 (9H, s,
3£CH3), 2.80 (1H, dd, J8,8ˆ13.3 Hz, J8,5ˆ10.1 Hz, H8),
3.33 (1H, dd, J8,8ˆ13.3 Hz, J8,5ˆ3.4 Hz, H8), 3.94 (1H,
dd, J5,4ˆ7.0 Hz, J6,4ˆ6.5 Hz, H4), 4.35 (1H, ddd,
J5,4ˆ7.0 Hz, J8,5ˆ3.4 Hz, J8,5ˆ10.1 Hz, H5), 4.99 (1H, d,
J7trans,6ˆ17 Hz, H7trans), 5.05 (1H, d, J7cis,6ˆ10.3 Hz, H7cis),
5.55 (1H, ddd, J7trans,6ˆ17.1 Hz, J7cis,6ˆ10.3 Hz, J6,4ˆ
6.5 Hz, H6), 7.18±7.22 (2H, m, Ph), 7.29±7.33 (3H, m,
Ph), 7.53 (1H, b s, NH); 13C NMR (100 MHz, CDCl3) d
28.2, 38.9, 58.6, 66.7, 83.8, 117.5, 127.2, 128.9, 129.4,
135.4, 135.6, 150.0, 180.0. Anal. Calcd for C17H22N2O2S:
C, 64.12;H, 6.96;N 8.80;S, 10.07. Found: C, 64.15;H,
6.92;N 8.84;S, 10.11.
4.3. General procedure for the synthesis of the 04S,5S)-4-
vinyltetrahydro-1H-2-imidazolethiones 9a±e
A solution of thiocyanates 6a±e (1 mmol) and 2-hydroxy-
pyridine (0.1 mmol, Method B) in dry xylene (5 mL) was
heated at 808C for 3 h (26±44 h, without 2-hydroxypyridine,
Method A). The solvent was removed under reduced
pressure and the residue was puri®ed by silica gel chromato-
graphy (20% ethyl acetate/hexane) to provide the title
compounds 9a±e.
4.3.5. tert-Butyl 04S,5S)-5-isobutyl-2-thioxo-4-vinyltetra-
hydro-1H-1-imidazolecarboxylate 09e). 88%;white solid:
4.3.1. tert-Butyl 04S,5S)-5-methyl-2-thioxo-4-vinyltetra-
hydro-1H-1-imidazolecarboxylate 09a). 89%;colorless
25
25
mp 75±778C;[ a]D ˆ263.2 (c 0.80 CHCl3);IR (CHCl )
3
oil;[ a]D ˆ220.3 (c 1.2 CHCl3);IR (CHCl 3) 3445,
3446, 1689 cm21; 1H NMR (400 MHz, CDCl3) d 0.96 (3H,
d, Jˆ6.6 Hz, CH3), 0.98 (3H, d, Jˆ6.6 Hz, CH3), 1.55 (9H,
s, 3£CH3), 1.65±1.69 (3H, m, H8, H9), 3.90±3.94 (1H, m,
H5), 4.14±4.16 (1H, m, H4), 5.24 (1H, dd, J7cis,6ˆ10.3 Hz,
J7cis,4ˆ0.7 Hz, H7cis), 5.30 (1H, dd, J7trans,6ˆ17.0 Hz,
J7trans,4ˆ0.7 Hz, H7trans), 5.84 (1H, ddd, J7trans,6ˆ17.0 Hz,
J7cis,6ˆ10.1 Hz, J6,4ˆ7.5 Hz, H6), 7.45 (1H, b s, NH); 13C
NMR (100 MHz, CDCl3) d 21.4, 23.8, 24.5, 28.2, 42.2,
60.8, 64.4, 83.7, 117.9, 135.7, 149.9, 179.7. Anal. Calcd
for C14H24N2O2S: C, 59.12;H, 8.51;N, 9.85;S, 11.27.
Found: C, 59.21;H, 8.54;N, 9.83;S, 11.34.
1
1688 cm21; H NMR (400 MHz, CDCl3) d 1.53 (d, 3H,
Jˆ6.5 Hz, CH3CH), 1.64 (9H, s, 3£CH3), 3.89 (1H, ddt,
J6,4ˆ7.1 Hz, J5,4ˆ6.3 Hz, J7,4ˆ0.8 Hz, H4), 4.26 (1H, dq,
JMe,5ˆ6.5 Hz, J5,4ˆ6.3 Hz, H5), 5.33 (1H, dd, J7,6ˆ
10.3 Hz, J7,4ˆ0.8 Hz, H7cis), 5.39 (1H, dd, J7,6ˆ17.0 Hz,
J7,4ˆ0.8 Hz, H7trans), 5.89 (1H, ddd, J7trans,6ˆ17.0 Hz,
J7cis,6ˆ10.3 Hz, J6,4ˆ7.1 Hz, H6), 7.60 (1H, b s, NH); 13C
NMR (100 MHz, CDCl3) d 19.7, 28.1, 61.6, 62.8, 83.5,
118.4, 135.0, 150.0, 180.0. Anal. Calcd for C11H18N2O2S:
C, 54.52;H, 7.49;N, 11.56;S, 13.23. Found: C, 54.43;H,
7.52;N, 11.54;S, 13.26.
4.3.2. tert-Butyl 04S,5S)-5-ethyl-2-thioxo-4-vinyltetra-
hydro-1H-1-imidazolecarboxylate 09b). 90%;colorless
4.4. Preparation of a mixture of diastereomers of
imidazolidines 9a and 10a
25
oil;[ a]D ˆ231.4 (c 0.71 CHCl3);IR (CHCl 3) 3446,
1
1687 cm21; H NMR (400 MHz, CDCl3) d 0.97 (3H, t,
A solution of thiocyanate 6a (0.20 g, 0.83 mmol) in xylene
(5 mL) was heated at 808C for 1 h under a nitrogen atmo-
sphere. The organic phase was concentrated under reduced
pressure to afford the crude products, which were puri®ed
by ¯ash chromatography over silica gel (20% ethyl acetate/
hexane) to provide the isothiocyanates 7a/8a (50:50). This
material was used for the next reaction without further puri-
®cation. To NaH (0.032 g, 0.74 mmol) in THF (6 mL) at
08C was added mixture of isothiocyanates 7a/8a (0.18 g,
0.74 mmol). The reaction mixture was stirred at 08C for
15 min and concentrated under reduced pressure. Puri®ca-
tion of the residue by ¯ash chromatography (20% ethyl
acetate/hexane) afforded the title compounds 9a and 10a
(50:50, 0.16 g, 88.9% combined yield).
Jˆ7.5 Hz, CH3CH2), 1.45±1.49 (1H, m, H8), 1.56 (3H, s,
3£CH3), 1.80±1.84 (1H, m, H8), 3.90 (1H, dd, J6,4ˆ7.0 Hz,
J5,4ˆ6.8 Hz, H4), 4.06 (1H, ddd, J8,5ˆ7.9 Hz, J5,8ˆ7.2 Hz,
J5,4ˆ6.8 Hz, H5), 5.24 (1H, d, J7cis,6ˆ10.2 Hz, H7cis), 5.29
(1H, d, J7trans,6ˆ17.0 Hz, H7trans), 5.83 (1H, ddd,
J7trans,6ˆ17.0 Hz, J7cis,6ˆ10.2 Hz, J6,4ˆ7.0 Hz, H6), 6.91
(1H, b s, NH); 13C NMR (100 MHz, CDCl3) d 8.6, 27.3,
28.1, 60.1, 66.7, 83.5, 117.9, 135.9, 150.1, 180.3. Anal.
Calcd for C12H20N2O2S: C, 56.22;H, 7.86;N, 10.93;S,
12.51. Found: C, 56.32;H, 7.96;N, 10.84;S, 12.41.
4.3.3. tert-Butyl 04S,5S)-5-isopropyl-2-thioxo-4-vinyl-
tetrahydro-1H-1-imidazolecarboxylate 09c). 89%;color-
25
less oil;[ a]D ˆ241.5 (c 0.97 CHCl3);IR (CHCl ) 3444,
3
1
1689 cm21; H NMR (400 MHz, CDCl3) d 0.92 (3H, d,
4.4.1. tert-Butyl 04S,5R)-5-methyl-2-thioxo-4-vinyltetra-
hydro-1H-1-imidazolecarboxylate 010a). Colorless oil;
Jˆ6.9 Hz, CH3CH), 0.98 (3H, d, Jˆ6.9 Hz, CH3CH), 1.55
(9H, s, 3£CH3), 2.35 (1H, dseptet, J8,Meˆ6.9 Hz,
J8,Meˆ6.9 Hz, J8,5ˆ7.2 Hz, H8), 3.97 (1H, dd, J6,4ˆ6.7 Hz,
J5,4ˆ6.6 Hz, H4), 4.08 (1H, dd, J8,5ˆ7.2 Hz, J4,5ˆ6.6 Hz,
H5), 5.22 (1H, d, J6,7cisˆ10.0 Hz, H7cis), 5.28 (1H, d,
J7trans,6ˆ17.0 Hz, H7trans), 5.82 (1H, ddd, J7trans,6ˆ17.0 Hz,
J7cis,6ˆ10.0 Hz, J6,4ˆ6.7 Hz, H6), 7.33 (1H, b s, NH); 13C
NMR (100 MHz, CDCl3) d 15.2, 17.8, 28.1, 30.1, 55.8,
25
[a]D ˆ134.0 (c 0.86 CHCl3);IR (CHCl
) 3445,
3
1680 cm21; H NMR (400 MHz, CDCl3) d 1.17 (3H, d,
Jˆ6.8 Hz, CH3), 1.62 (9H, s, 3£CH3), 4.03 (1H, dd,
J5,4ˆ7.2 Hz, J5,Meˆ6.8 Hz, H5), 4.40 (1H, dddd, J6,4ˆ
7.9 Hz, J5,4ˆ7.2 Hz, J7trans,4ˆ1.1 Hz, J7cis,4ˆ0.8 Hz, H4),
1
5.32 (1H, ddd, J7cis,6ˆ10.3 Hz, J7trans,7cisˆ1.1 Hz, J7cis,4
ˆ
ˆ
0.8 Hz, H7cis), 5.33 (1H, ddd, J7trans,6ˆ17.1 Hz, J7trans,7cis

J. Gonda et al. / Tetrahedron 58 /2002) 1611±1616
1615
1.1 Hz, J7cis,4ˆ1.0 Hz, H7trans), 5.73 (1H, ddd, J7trans,6
ˆ
J6,4ˆ8.3 Hz, H4), 5.30 (1H, d, J7cis,6ˆ10.1 Hz, H7cis), 5.32
17.1 Hz, J7cis,6ˆ10.6 Hz, J6,4ˆ7.9 Hz, H6), 5.92 (1H, b s,
NH), 6.05 (1H, b s, NH); 13C NMR (100 Hz, CDCl3) d
9.6, 27.3, 28.1, 56.1, 63.0, 119.5, 132.8, 152.0, 183.5.
Anal. Calcd for C11H18N2O2S: C, 54.52;H, 7.49;N,
11.56;S, 13.23. Found: C, 54.46;H, 7.50;N, 11.53;S,
13.28.
(1H, d, J7trans,6ˆ17.1 Hz, H7trans), 5.92 (1H, ddd, J7trans,6ˆ
17.1 Hz, J7cis,6ˆ10.1 Hz, J6,4ˆ8.3 Hz, H6), 6.33 (1H, b s.
NH), 6.49 (1H, b s, NH); 13C NMR (100 MHz, CDCl3) d
19.4, 19.6, 27.8, 62.8, 67.4, 119.8, 131.9, 184.2. Anal. Calcd
for C8H14N2S: C, 56.43;H, 8.29;N, 16.45;S, 18.83. Found:
C, 56.47;H, 8.30;N, 16.51;S, 18.78.
4.5.4. 04S,5S)-4-Vinyl-5-benzyltetrahydro-1H-2-imida-
zolethione 011d). 94%;white solid: mp 126±128 8C;
4.5. General procedure for the synthesis of 11a±e
and 12a
25
[a]D ˆ260.3 (c 0.84 CHCl3);IR (CHCl ) 3442, 3451,
3
1
1678 cm21; H NMR (400 MHz, CDCl3) d 2.85 (1H, dd,
The imidazolidines 9a±e and 10a (1 mmol) were dissolved
in the mixture of CF3COOH and H2O (95:5, 5 mL). The
reaction mixture was stirred at room temperature for
15 min and then concentrated under reduced pressure. The
resulting residue was diluted with diethyl ether and washed
with saturated aq. sodium hydrogen carbonate and brine.
After being dried, evaporation of the solvent gave the
crude products, which were puri®ed by silica gel chromato-
graphy with a mixture ethyl acetate±cyclohexane (20%
ethyl acetate/hexane) to provide the products 11a±e and
12a.
J8,8ˆ13.5 Hz, J8,5ˆ8.9 Hz, H8), 2.95 (1H, dd, J8,8ˆ13.5 Hz,
J8,5ˆ5.1 Hz, H8), 3.89 (1H, dddd, J8,5ˆ8.9 Hz, J5,4ˆ7.2 Hz,
J8,5ˆ5.1 Hz, J7trans,5ˆ1.0 Hz, H5), 4.18 (1H, ddd, J6,4ˆ
7.4 Hz, J5,4ˆ7.2 Hz, J7,4ˆ0.9 Hz, H4), 5.21 (1H, ddd,
J7,6ˆ10.1 Hz, J7,4ˆ0.9 Hz, J7,7ˆ0.9 Hz, H7cis), 5.25 (1H,
ddd, J7trans,6ˆ17.3 Hz, J7,5ˆ1.0 Hz, J7,7ˆ0.9 Hz, H7trans),
5.78 (1H, ddd, J7trans,6ˆ17.3 Hz, J7cis,6ˆ10.1 Hz, J6,4ˆ
7.4 Hz, H6), 6.18 (1H, b s, NH), 6.35 (1H, b s, NH), 7.16±
7.20 (2H, m, Ph), 7.28±7.32 (3H, m, Ph); 13C NMR
(100 MHz, CDCl3) d 40.3, 64.9, 65.4, 118.8, 127.3, 129.0,
129.1, 135.1, 136.0, 183.1. Anal. Calcd for C12H14N2S: C,
66.02;H, 6.46;N, 12.83;S, 14.69. Found: C, 66.08;H, 6.40;
N, 12.85;S, 14.74.
4.5.1. 04S,5S)-4-Vinyl-5-methyltetrahydro-1H-2-imida-
zolethione 011a). 96%;white solid: mp 115±117 8C;
25
[a]D ˆ2110.0 (c 0.63 CHCl3);IR (CHCl ) 3452, 3441,
3
1680 cm21; H NMR (400 MHz, CDCl3) d 1.17 (3H, d,
1
4.5.5. 04S,5S)-4-Vinyl-5-isobutyltetrahydro-1H-2-imida-
zolethione 011e). 93%;white solid: mp 128±131 8C;
Jˆ6.6 Hz, CH3), 4.19 (1H, dq, J5,4ˆ7.1 Hz, J5,Meˆ6.6 Hz,
25
[a]D ˆ290.3 (c 0.93 CHCl3);IR (CHCl ) 3452, 3439,
3
H5), 4.46 (1H, dddd, J6,4ˆ7.7 Hz, J5,4ˆ7.1 Hz, J7trans,4
ˆ
1680 cm21; H NMR (400 MHz, CDCl3) d 0.92 (3H, d,
1
1.0 Hz, J7cis,4ˆ0.9 Hz, H4), 5.32 (1H, ddd, J7cis,6ˆ10.3 Hz,
J7trans,7cisˆ1.1 Hz, J7cis,4ˆ0.9 Hz, H7cis), 5.34 (1H, ddd,
J7trans,6ˆ17.1 Hz, J7trans,7cisˆ1.1 Hz, J7cis,4ˆ1.0 Hz, H7trans),
5.82 (1H, ddd, J7trans,6ˆ17.1 Hz, J7cis,6ˆ10.3 Hz,
J6,4ˆ7.7 Hz, H6), 6.03 (1H, b s, NH), 6.19 (1H, b s, NH);
13C NMR (100 Hz, CDCl3) d 16.0, 56.1, 63.1, 119.7, 132.1,
183.6. Anal. Calcd for C6H10N2S: C, 50.67;H, 7.09;N,
19.70;S, 22.54. Found: C, 50.72;H, 7.11;N, 19.75;S,
22.46.
Jˆ6.3 Hz, CH3), 0.94 (3H, d, Jˆ6.3 Hz, CH3), 1.48±1.52
(3H, m, H8, H9), 3.77±3.79 (1H, m, H5), 4.09 (1H, dd,
J6,4ˆ7.2 Hz, J5,4ˆ6.8 Hz, H4), 5.27 (1H, dd, J7cis,6
ˆ
10.1 Hz, J7,7ˆ0.7 Hz, H7cis), 5.32 (1H, dd, J7trans,6ˆ17.0 Hz,
J7,7ˆ0.7 Hz, H7trans), 5.81 (1H, ddd, J7trans,6ˆ17.0 Hz,
J7cis,6ˆ10.1 Hz, J6,4ˆ7.2 Hz, H6), 6.24 (1H, b s, NH), 6.48
(1H, b s, NH); 13C NMR (100 MHz, CDCl3) d 23.0, 25.0,
43.4, 62.2, 66.6, 119.1, 135.2, 182.5. Anal. Calcd for
C9H16N2S: C, 58.65;H, 8.75;N, 15.20;S, 17.40. Found:
C, 58.59;H, 8.78;N, 15.14;S, 17.44.
4.5.2. 04S,5S)-4-Vinyl-5-ethyltetrahydro-1H-2-imida-
zolethione 011b). 98%;white solid: mp 147±149 8C;
25
4.5.6. 04S,5R)-4-Vinyl-5-methyltetrahydro-1H-2-imida-
zolethione 012a). 96%;white solid: mp 212±213 8C;
[a]D ˆ2106.7 (c 0.71 CHCl3);IR (CHCl ) 3450, 3440,
3
1679 cm21; H NMR (400 MHz, CDCl3) d 0.98 (3H, t,
1
25
[a]D ˆ164.0 (c 0.86 CHCl3);IR (CHCl ) 3440, 3451,
3
Jˆ7.5 Hz, CH3), 2.36±2.40 (2H, m, H8), 3.61 (1H, ddd,
1683 cm21; H NMR (400 MHz, CDCl3) d 1.15 (3H, d,
1
J5,4ˆ7.3 Hz, J8,5ˆ6.8 Hz, J8,5ˆ5.9 Hz, H5), 4.08 (1H,
Jˆ6.7 Hz, CH3), 4.03 (1H, dq, J5,4ˆ7.0 Hz, J5,Meˆ6.7 Hz,
dddd, J6,4ˆ7.6 Hz, J5,4ˆ7.4 Hz, J7trans,4ˆ1.1 Hz, J7c,4
0.8 Hz, H4), 5.23 (1H, ddd, J7cis,6ˆ10.1 Hz, J7cis,7trans
0.9 Hz, J7cis,4ˆ0.8 Hz, H7cis), 5.30 (1H, ddd, J7trans,6
ˆ
ˆ
ˆ
H5), 4.40 (1H, dddd, J6,4ˆ7.9 Hz, J5,4ˆ7.0 Hz, J7trans,4
ˆ
1.0 Hz, J7cis,4ˆ0.8 Hz, H4), 5.32 (1H, ddd, J7cis,6ˆ10.3 Hz,
J7trans,4ˆ1.1 Hz, J7cis,4ˆ0.8 Hz, H7cis), 5.30 (1H, ddd,
J7trans,6ˆ17.1 Hz, J7trans,4ˆ1.1 Hz, J7cis,4ˆ1.0 Hz, H7trans),
5.78 (1H, ddd, J7trans,6ˆ17.1 Hz, J7cis,6ˆ10.3 Hz, J6,4ˆ
7.9 Hz, H6), 5.98 (1H, b s, NH), 6.11 (1H, b s, NH); 13C
NMR (100 Hz, CDCl3) d 15.9, 56.1, 63.0, 119.3, 132.3,
183.0. Anal. Calcd for C6H10N2S: C, 50.67;H, 7.09;N,
19.70;S, 22.54. Found: C, 50.72;H, 7.11;N, 19.75;S,
22.46.
17.1 Hz, J7trans,4ˆ1.1 Hz, J7,7ˆ0.9 Hz, H7trans), 5.84 (1H,
ddd, J7trans,6ˆ17.1 Hz, J7cis,6ˆ10.1 Hz, J6,4ˆ7.6 Hz, H6),
6.14 (1H, b s, NH), 6.30 (1H, b s, NH); 13C NMR
(100 MHz, CDCl3) d 9.8, 27.2, 65.1, 65.6, 118.5, 135.7,
183.0. Anal.Calcd for C7H12N2S: C, 53.81;H, 7.74;N,
17.93;S, 20.52. Found: C, 53.83;H, 7.84;N, 17.80;S,
20.56.
4.5.3. 04S,5S)-4-Vinyl-5-isopropyltetrahydro-1H-2-imida-
zolethione 011c). 94%;white solid: mp 127±130 8C;
25
[a]D ˆ2100.3 (c 0.68 CHCl3);IR (CHCl ) 3439, 3451,
Acknowledgements
3
1678 cm21; H NMR (400 MHz, CDCl3) d 0.89 (3H, d,
1
JMe,8ˆ6.6 Hz, CH3), 1.00 (3H, d, JMe,8ˆ6.6 Hz, CH3), 1.84
(1H, dseptet, J8,5ˆ9.3 Hz, J8,Meˆ6.6 Hz, H8), 3.69 (1H, dd,
J8,5ˆ9.3 Hz, J5,4ˆ8.4 Hz, H5), 4.35 (1H, dd, J5,4ˆ8.4 Hz,
A possibility to realize selected NMR experiments during
the visit of J. I. to the Department of Chemistry, University
of Turku, Finland (a Professor Kalevi Pihlaja's Group) is

1616
J. Gonda et al. / Tetrahedron 58 /2002) 1611±1616
Williams, D. J. J. Chem. Soc., Chem. Commun. 1986, 755±
757. Natsugari, H.;Whittle, R. R.;Weinreb, S. M. J. Am.
Chem. Soc. 1984, 106, 7867±7872.
gratefully acknowledged. The present work was supported
by Grant Agency (No. 1/6080/99) from the Ministry of
Education, Slovak republic.
Ï
8. Gonda, J.;Helland, A.-Ch.;Ernst, B.;Bellus , D. Synthesis
1993, 729±733.
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