Resolution of (4RS,5RS)-4,5-diphenylimidazolidine-2-thione using pentafluorophenyl active esters

Article abstract of DOI:10.1016/j.tetlet.2010.10.157

(4RS,5RS)-4,5-Diphenylimidazolidine-2-thione is resolved efficiently by treatment with NaHMDS and an enantiomerically pure pentafluorophenyl active ester. The levels of diastereocontrol were excellent (up to 90% de).

Full text of DOI:10.1016/j.tetlet.2010.10.157

Tetrahedron Letters 51 (2010) 6935–6938
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Resolution of (4RS,5RS)-4,5-diphenylimidazolidine-2-thione
using pentafluorophenyl active esters
⇑
Anna Andreou, Najla Al Shaye, Hannah Brown, Jason Eames
Department of Chemistry, University of Hull, Cottingham Road, Kingston upon Hull HU6 7RX, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 July 2010
Revised 15 October 2010
Accepted 29 October 2010
Available online 4 November 2010
(4RS,5RS)-4,5-Diphenylimidazolidine-2-thione is resolved efficiently by treatment with NaHMDS and an
enantiomerically pure pentafluorophenyl active ester. The levels of diastereocontrol were excellent (up to
90% de).
Ó 2010 Elsevier Ltd. All rights reserved.
The separation of enantiomeric substrates1 using parallel reso-
lution is becoming an increasingly popular method.2 Over the last
few years, we have been interested in the kinetic resolution of
oxazolidine-2-ones3 and oxazolidine-2-thiones,4 such as 4-phenyl-
oxazolidine-2-thione (rac)-1, using an enantiomerically pure
ibuprofen-derived active ester, 2-(4-isobutylphenyl)propanoate
(S)-2, to give the corresponding oxazolidine-2-thione adduct
(S,R)-syn-3 in 32% yield with 92% de (Scheme 1).3 The levels of
diastereocontrol were found to be excellent for a wide range of
structurally related profen-based active esters. This methodology
has more recently been applied to the resolution of racemic alco-
hols, such as 1-phenylethanol,5 and carboxylic acids.6
fluorophenyl 2-phenylbutanoate (rac)-5 was recovered in 41%
yield with 38% ee.13
With this information in hand, we next investigated the com-
plementary resolution of racemic 4,5-diphenylimidazolidine-2-
thione (4RS,5RS)-4 using enantiomerically pure pentafluorophenyl
2-phenylbutanoate (R)-5, formed in 78% yield by DCC coupling of
(R)-2-phenylbutanoic acid with pentafluorophenol (Scheme 3).
Deprotonation of racemic 4,5-diphenylimidazolidine-2-thione
(4RS,5RS)-4 (1 equiv) with NaHMDS (1.1 equiv) in THF at ꢀ78 °C,
followed by the addition of pentafluorophenyl 2-phenylbutanoate
(R)-5 (1.1 equiv) gave, after 2 h at ꢀ78 °C, 4,5-diphenylimidazoli-
dine-2-thione (2R,4S,5S)-syn,anti-6 in 28% yield with 78% de. The
resolved 4,5-diphenylimidazolidine-2-thione (4R,5R)-5 was recovered
Using our standard protocol,3 we were interested in studying
the resolution of C2-symmetric 4,5-diphenylimidazolidine-2-
thione (4RS,5RS)-4, as this substrate contained all the essential
features7 for efficient molecular recognition with our profen-based
pentafluorophenyl active esters.8 We first studied the resolution of
pentafluorophenyl 2-phenylbutanoate (rac)-5 using the enantio-
merically pure 4,5-diphenylimidazolidine-2-thione (4S,5S)-4
(Scheme 2). Treatment of (4S,5S)-4 (1 equiv) with sodium hexam-
ethyldisilazane (NaHMDS; 1.1 equiv) in THF at ꢀ78 °C, followed by
the addition of pentafluorophenyl 2-phenylbutanoate (rac)-5
(1.1 equiv) gave, after stirring for 2 h, the corresponding 4,5-diph-
enylimidazolidine-2-thione (2R,4S,5S)-syn,anti-6 in 24% yield with
80% de (Scheme 2). The stereochemical outcome of this resolution
was confirmed through stereospecific synthesis,9 and the diastere-
oselectivity was determined by 400 MHz 1H NMR spectroscopy.10
Formation of this product, 4,5-diphenylimidazolidine-2-thione
(2R,4S,5S)-syn,anti-6, is intrinsically low yielding (ꢁ25% yield)11
due to its being more acidic than its starting 4,5-diphenylimidaz-
olidine-2-thione, (4S,5S)-4, and the inherent enantiomeric
composition of the active ester (rac)-5.12 The remaining penta-
S
S
O
1. n-BuLi
THF, -78 oC
Ar
HN
Ph
O
N
O
2.
O
Me
Ar
Ph
OC6F5
Me
(rac)-1
(S,R)-syn-3
32%; 92% de
Ar = 4-i-BuC6H4
(S)-2
Scheme 1. Resolution of oxazolidine-2-thione (rac)-1 using active ester (S)-2.
O
S
S
O
1. NaHMDS
THF, -78 oC
Ph
Ph
OC6F5
HN
Ph
NH
Ph
N
NH
Ph
O
2.
Et
Et
Ph
Ph
OC6F5
Et
(rac)-5
(R)-5
41%; 38% ee
(2R,4S,5S)-syn,anti-6
(4S,5S)-4
24%; 80% de
⇑
Corresponding author. Tel.: +44 1482 466401; fax: +44 1482 466410.
E-mail address: j.eames@hull.ac.uk (J. Eames).
Scheme 2. Resolution of active ester (rac)-5 using 4,5-diphenylimidazolidine-2-
thione (4S,5S)-4.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.157

6936
A. Andreou et al. / Tetrahedron Letters 51 (2010) 6935–6938
S
S
We next turned our attention to the parallel resolution of race-
S
O
1. NaHMDS
THF, -78 oC
mic 4,5-diphenylimidazolidine-2-thione (4RS,5RS)-4 using a com-
bination of quasi-enantiomeric active esters (R)-5 and (S)-7
(Scheme 5). Deprotonation of (4RS,5RS)-4 (1 equiv) using NaHMDS
(1.1 equiv) in THF at ꢀ78 °C followed by the addition of an equivm-
olar amount of quasi-enantiomeric active esters (R)-5 (0.55 equiv)
and (S)-7 (0.55 equiv) gave, after 2 h, a mixture of two quasi-enan-
tiomeric 4,5-diphenylimidazolidine-2-thiones (2R,4S,5S)-syn,anti-6
and (2S,4R,5R)-syn,anti-8 in 24% and 28% yields, with 90% de and
82% de, respectively (Scheme 5).
Increased separation of the 4,5-diphenylimidazolidine-2-thione
adducts can be achieved using two quasi-enantiomeric active
esters, (R)-5 and (S)-9, which have different polarity.16 Treatment
of 4,5-diphenylimidazolidine-2-thione (4RS,5RS)-4 (1 equiv) with
NaHMDS (1.1 equiv) in THF at ꢀ78 °C, followed by the addition
of an equimolar amount of (R)-5 (0.55 equiv) and (S)-917
Ph
HN
Ph
NH
Ph
N
NH
Ph
HN
Ph
NH
Ph
O
2.
Et
Ph
Ph
OC6F5
Et
(R)-5
(4R,5R)-5
35%; 32% ee
(2R,4S,5S)-syn,anti -6
(4RS,5RS)-4
28%; 78% de
S
S
S
O
1. NaHMDS
THF, -78 oC
Ar
HN
Ph
NH
Ph
N
NH
Ph
HN
Ph
NH
Ph
2.
O
Me
Ar
Ph
OC6F5
Me
(2S,4R,5R)-syn,anti-8
(4S,5S)-4
32%; 37% ee
(4RS,5RS)-4
Ar = 4-i-BuC6H4
31%; 76% de
(S)-7
Scheme 3. Kinetic resolution of 4,5-diphenylimidazolidine-2-thione (4RS,5RS)-4
using active esters (R)-5 and (S)-7.
(0.55 equiv)
gave
the
4,5-diphenylimidazolidine-2-thiones
(2R,4S,5S)-syn,anti-6 and (2S,4R,5R)-syn,anti-1018 in 24% yield with
86% de and 26% yield with 80% de, respectively (Scheme 6). These
adducts were easily separated by column chromatography;
DRF
[CH2Cl2] = 0.10.19
S
S
O
1. NaHMDS
THF, -78 oC
However, attempts at separating the enantiomers of (4RS,5RS)-4
using a pair of quasi-enantiomeric pentafluorophenyl propanoates,
(R)-1120 and (S)-9, gave the corresponding 4,5-diphenylimidazoli-
dine-2-thiones (2R,4S,5S)-syn,anti-1221 and (2S,4R,5R)-syn,anti-10
in higher yields, 29% and 30%, respectively, but with decreased
levels of diastereoselectivity, 80% de and 84% de, respectively
(Scheme 7). These pentafluorophenyl propanoates, (R)-11 and
(S)-9, were less diastereoselective than the pentafluorophenyl
Ph
HN
Ph
NH
Ph
N
NH
Ph
2.
O
Et
Ph
Ph
OC6F5
Et
(rac)-5
(2SR,4RS,5RS)-syn,anti-6
(4RS,5RS)-4
41%; 90% de
S
S
1. NaHMDS
THF, -78 oC
O
Ar
HN
Ph
NH
Ph
N
NH
Ph
2.
O
Me
Ar
Ph
OC6F5
S
S
S
1. NaHMDS
THF, -78 oC
O
O
Me
(2SR,4RS,5RS)-syn,anti-8
(4RS,5RS)-4
Ph
Ar
Ar = 4-i-BuC6H4
41%; 90% de
HN
Ph
NH
Ph
N
NH
Ph
N
NH
Ph
O
2.
(rac)-7
Et
Me
Ph
OC6F5
Ph
Ph
Scheme 4. Mutual resolution of 4,5-diphenylimidazolidine-2-thione (4RS,5RS)-4
using active esters (rac)-5 and (rac)-7.
Et
(4RS,5RS)-4
(2R,4S,5S)-syn,anti-6
(2S,4R,5R)-syn,anti-8
(R)-5
24%; 90% de
28%; 82% de
O
Ar
OC6F5
with the predicted stereochemistry in 35% yield with 32% ee
(Scheme 3). The enantiomeric 4,5-diphenylimidazolidine-2-thione
(4S,5S)-4 was synthesised in 32% yield with 37% ee by treatment
of the parent 4,5-diphenylimidazolidine-2-thione (4RS,5RS)-4
(1 equiv) with NaHMDS (1.1 equiv), followed by the addition of
pentafluorophenyl 2-(4-isobutylphenyl)propanoate (S)-7 (1.1 equiv)
(Scheme 3). The complementary 4,5-diphenylimidazolidine-2-thione
adduct (2S,4R,5R)-syn,anti-8 was formed in 31% yield with 76% de
(Scheme 3).
Me
Ar = 4-i-BuC6H4
(S)-7
Scheme 5. Parallel resolution of 4,5-diphenylimidazolidine-2-thione (4RS,5RS)-4
using active esters (R)-5 and (S)-7.
S
O
In an attempt to improve the efficiency of this resolution, we
next chose to resolve 4,5-diphenylimidazolidine-2-thione
(4RS,5RS)-4 in parallel2,14 using two complementary quasi-enantio-
meric15 pentafluorophenyl active esters, (R)-5 and (S)-7. As a pre-
liminary model study, we first investigated the mutual resolution
of 4,5-diphenylimidazolidine-2-thione (4RS,5RS)-4, using the race-
mic active esters, (rac)-5 and (rac)-7 (Scheme 4). Deprotonaton of
racemic 4,5-diphenylimidazolidine-2-thione (4RS,5RS)-4 (1 equiv)
with NaHMDS (1.1 equiv) in THF at ꢀ78 °C, followed by addition
of racemic active esters, (rac)-5 (1.1 equiv) and (rac)-7 (1.1 equiv),
gave the 4,5-diphenylimidazolidine-2-thione adducts (2SR,4RS,
5RS)-syn,anti-6 (in 41% yield with 90% de) and (2SR,4RS,5RS)-
syn,anti-8 (in 41% yield with 90% de), respectively (Scheme 4). In
both cases, the diastereoselectivity for these mutual resolutions
was higher2 than their corresponding kinetic resolutions; 90% de
for both (rac)-5 and (rac)-7 versus 78% de for (R)-5 and 76% de
for (S)-7 (Schemes 3 and 4).
Ph
N
NH
Ph
Et
Ph
S
1. NaHMDS
THF, -78 oC
(2R,4S,5S)-syn,anti-6
24%; 86% de
HN
Ph
NH
Ph
O
2.
MeO
Ph
S
O
OC6F5
Et
(4RS,5RS)-4
N
NH
Ph
(R)-5
Me
MeO
Ph
O
(2S,4R,5R)-syn,anti-10
OC6F5
26%; 80% de
Me
(S)-9
Scheme 6. Parallel resolution of 4,5-diphenylimidazolidine-2-thione (4RS,5RS)-4
using active esters (R)-5 and (S)-9.

A. Andreou et al. / Tetrahedron Letters 51 (2010) 6935–6938
6937
S
O
References and notes
Ph
N
NH
Ph
1. For representative reviews, see: (a) Fu, G. Acc. Chem. Res. 2000, 33, 412; (b)
Spivey, A. C.; Maddaford, A.; Redgrave, A. J. Org. Prep. Proced. Int. 2000, 32, 331;
(c) Miller, S. J. Acc. Chem. Res. 2004, 37, 601; (d) France, S.; Guerin, D. J.; Miller, S.
J.; Lectka, T. Chem. Rev. 2003, 103, 2985; (e) Spivey, A. C.; Arseniyadis, S. Angew.
Chem., Int. Ed. 2004, 43, 5436.
2. Reviews, see: (a) Eames, J. Angew. Chem., Int. Ed. 2000, 39, 885; (b) Eames, J. In
Organic Synthesis Highlights; VCH-Wiley, 2003; Vol. v, Chapter 17; (c) Dehli, J.
R.; Gotor, V. Chem. Soc. Rev. 2002, 31, 365; (d) Dehli, J. R.; Gotor, V. ARKIVOC
2002, v, 196.
Me
Ph
S
1. NaHMDS
THF, -78 oC
(2R,4S,5S)-syn,anti-12
29%; 80% de
HN
Ph
NH
Ph
O
2.
MeO
Ph
S
O
OC6F5
3. Boyd, E.; Coulbeck, E.; Coumbarides, G. S.; Chavda, S.; Dingjan, M.; Eames, J.;
Flinn, A.; Motevalli, M.; Northen, J.; Yohannes, Y. Tetrahedron: Asymmetry 2007,
18, 2515.
4. Al Shaye, N.; Broughton, T. W.; Coulbeck, E.; Eames, J. Synlett 2009, 960.
5. (a) Coulbeck, E.; Eames, J. Tetrahedron Lett. 2009, 50, 4449; (b) Coulbeck, E.;
Eames, J. Synlett 2008, 333.
6. Al Shaye, N.; Boa, A. N.; Coulbeck, E.; Eames, J. Tetrahedron Lett. 2008, 49, 4661.
7. For high levels of molecular recognition, the nucleophilic component must
contain a PhCH(alkyl)-XM motif, where X is O and N.
Me
(4RS,5RS)-4
N
NH
Ph
(R)-11
Me
MeO
Ph
O
(2S,4R,5R)-syn,anti-10
OC6F5
30%; 84% de
Me
(S)-9
8. Addition of racemic sodiated trans-4,5-tetramethylene-imidazolidine-2-thione
to (S)-pentafluorophenyl 2-(4-isobutylphenyl)propanoate leads to the
corresponding (4R,5R)-3-[2S-(4-isobutylphenyl)propanoyl]-4,5-tetramethyl-
eneimidazolidine-2-thione in 36% yield with 40% de.
Scheme 7. Parallel resolution of 4,5-diphenylimidazolidine-2-thione (4RS,5RS)-4
using active esters (R)-11 and (S)-9.
9. The 4,5-diphenylimidazolidine-2-thione (2R,4S,5S)-syn,anti-6 was formed in
54% yield by the addition of lithiated 4,5-diphenylimidazolidine-2-thione
(4S,5S)-4 to (R)-2,4-dichlorophenyl 2-(4-isobutylphenyl)propanoate.
10. For 4,5-diphenylimidazolidine-2-thione (2R,4S,5S)-syn,anti-6, the PhCHNC@O
doublet is at 5.37 ppm (1H, d, J = 5.4). Whereas, for (2R,4R,5R)-anti,anti-6, the
PhCHNC@O doublet is at 5.22 ppm (1H, br d, J = 2.2).
S
S
O
LiAlH4
THF
Ar
Ar
OH
N
NH
Ph
HN
Ph
NH
Ph
11. Trace amounts (<2%) of dipropanonyl thioureas can be detected in the crude
Me
Me
mixture by 1H NMR spectroscopy.
Ph
12. Dipropanonyl thioureas can be formed using an excess of Brønsted base and
active ester. Under our standard conditions, treatment of thiourea (4S,5S)-4
(1 equiv) with n-BuLi (2.2 equiv) and active ester (rac)-7 (4.4 equiv) gave the
(4R,5R)-4
90%; 98% ee
(S)-13
(2S,4R,5R)-syn,anti-8
98% de
90%; >95% ee
Ar = 4-i-BuC6H4
propanoyl thioureas syn,anti- and anti,anti-8 in 25% yield in
a
diastereoisomeric ratio of 56:44 and the di-propanoyl thioureas syn,anti,syn-,
syn,anti,anti- and anti,anti,anti- in 48% yield with a diastereoisomeric ratio of
35:45:20. The relative ratio of the propanoyl and di-propanoyl thioureas was
38:62 (by 1H NMR spectroscopy).
Scheme 8. LiAlH4 reduction of 4,5-diphenylimidazolidine-2-thione (2S,4R,5R)-8.
13. The enantiomeric excess was determined by comparison with the known
specific rotation, and through hydrolysis to give the corresponding carboxylic
acid. The enantiomeric excess of this carboxylic acid was determined by self-
coupling to form the corresponding anhydride, see: Coulbeck, E.; Eames, J.
Tetrahedron: Asymmetry 2009, 20, 635.
14. Recent examples of parallel kinetic resolutions: (a) Vedejs, E.; Chen, X. J. Am.
Chem. Soc. 1997, 119, 2584; (b) Liao, L.; Zhang, F.; Dmitrenko, O.; Bach, R. D.;
Fox, J. M. J. Am. Chem. Soc. 2004, 126, 4490; (c) Davies, S. G.; Garner, A. C.; Long,
M. J.; Smith, A. D.; Sweet, M. J.; Withey, J. M. Org. Biomol. Chem. 2004, 2, 3355.
15. Zhang, Q. S.; Curran, D. P. Chem. Eur. J. 2005, 4866.
butanoate (R)-7, due to their increased electrophilicity and less
sterically demanding nature.
Access to the resolved parent 4,5-diphenylimidazolidine-2-
thione, such as (4R,5R)-4, was achieved by LiAlH4 reduction of
4,5-diphenylimidazolidine-2-thione (2S,4R,5R)-syn,anti-8 (Scheme
8). Addition of LiAlH4 to a stirred solution of (2S,4R,5R)-syn,anti-8
in THF at RT, and stirring the resulting solution for 2 h, gave the re-
quired enantiomerically pure 4,5-diphenylimidazolidine-2-thione
(4R,5R)-422 in 90% yield with 98% ee and the primary alcohol (S)-
135b,6 in 90% yield with >95% ee (Scheme 8).
16. The 2-(6-methoxynaphthalen-2-yl)propanoyl transfer group, in (S)-9, is more
polar than the 2-phenylbutanoyl transfer group in (R)-7.
17. The mutual resolution using (rac)-9, gave (2RS,4SR,5SR)-syn,anti-10 in 31%
yield with 72% de.
18. (2S,4R,5R)-syn,anti-10; ½a D25
ꢂ
+166.8 (c 4.0, CHCl3).
In conclusion, we have shown23 that four pentafluorophenyl
active esters, (R)-5, (S)-7, (S)-9 and (R)-11, can be used to efficiently
resolve racemic 4,5-diphenylimidazolidine-2-thione, (4RS,5RS)-4
in good yields. The levels of diastereocontrol were found to be good
to excellent (78% de?90% de) favouring formation of the corre-
19. (2R,4S,5S)-syn,anti-6: RF[CH2Cl2] 0.66; (2S,4R,5R)-syn,anti-10; RF[CH2Cl2] 0.56.
20. The mutual resolution using (rac)-11, gave (2RS,4SR,5SR)-syn,anti-12 in 35%
yield with 80% de.
21. (2R,4S,5S)-syn,anti-12; ½a D25
ꢀ134.2 (c 2.4, CHCl3).
ꢂ
22.
½
a 2D5
ꢂ
+62.7 (c 2.2, CHCl3) {lit. ½a D25
ꢂ
+65.0 (c 0.25, CHCl3); Davies, S. G.; Mortlock,
A. A. Tetrahedron 1993, 49, 4419}.
*
*
*
sponding (2R ,4S ,5S )-syn,anti-4,5-diphenylimidazolidine-2-thi-
ones 6, 8, 10 and 12. The nearest analogy to this work is the
desymmetrisation of meso-(4R,5S)-diphenylimidazolidine-2-thi-
one24 using profen-based pentafluorophenyl active esters. The lev-
els of molecular recognition between the PhCHN(Na)C@S motif of
meso-(4R,5S)-4,5-diphenylimidazolidine-2-thione and the enantio-
merically pure active ester, (R)-5, were similarly high (92% de). In
comparison, formation of the complementary diastereoisomeric
anti-4,5-diphenylimidazolidine-2-thiones can be achieved using a
deprotonation–methylation strategy developed by Davies25
involving a related C2-symmetric N-propanoyl 4,5-diphenylimi-
dazolidine-2-thione.
23. Representative experimental procedure: Synthesis of (4S,5S)-3-[2R-
phenylbutanoyl]-4,5-diphenylimidazolidine-2-thione (2R,4S,5S)-syn,anti-6;
NaHMDS (0.43 mL, 1.0 M in THF, 0.43 mmol) was added to a stirred solution
of enantiomerically pure 4,5-diphenylimidazolidine-2-thione (4S,5S)-4 (0.1 g,
0.39 mmol) in THF at ꢀ78 °C. After stirring for 1 h, a solution of racemic
pentafluorophenyl 2-phenylbutanoate (rac)-5 (0.14 g, 0.43 mmol) in THF
(5 mL) was added. The resulting mixture was stirred for 2 h at ꢀ78 °C. The
reaction was quenched with H2O (10 mL). The organic layer was extracted with
Et2O (2 ꢃ 10 mL), dried (over MgSO4) and evaporated under reduced pressure
to give
a separable mixture of two diastereoisomeric oxazolidine-2-ones
(2R,4S,5S)-syn,anti-6 and (2S,4S,5S)-anti,anti-6 (ratio 90:10). The crude mixture
was purified by flash column chromatography on silica gel eluting with light
petroleum (bp 40–60 °C)/CH2Cl2 (1:9), to give (2R,4S,5S)-syn,anti-6 (33 mg,
21%) and (2S,4S,5S)-anti,anti-6 (4 mg, 3%) as a separable diastereoisomeric
mixture (90:10—syn,anti-/anti,anti-); and pentafluorophenyl 2-phenylbutanoate
(R)-5 (26 mg, 41%) as a colourless oil with ꢁ38% ee; {½a D25
ꢂ
+26.4 (c 1.0, CHCl3)};
{(R)-; >98% ee ½a D25
ꢂ
+69.5 (c 5.3, CHCl3)}.
Characterisation data for: (2S,4S,5S)-anti,anti-6; colourless oil; RF [CH2Cl2]
max (CHCl3) cmꢀ1 3022 (N–H), 1216 (C@S) and 1705 (C@O); ½a 2D5
ꢂ
+7.4 (c
Acknowledgements
0.52;
m
1.1, CHCl3); dH (400 MHz; CDCl3) 7.42–7.38 (3 H, m, 3 ꢃ CH; Ph), 7.30–7.25 (5H,
m, 5 ꢃ CH; Ph), 7.23–7.18 (5 H, m, 5 ꢃ CH; Ph), 6.84 (2 H, d, J 8.8, 2 ꢃ CH; Ph),
6.19 (1H, t, J 7.5, PhCHEt), 5.22 (1H, br d, J 2.2, PhCHNCO), 4.38 (1H, br s,
PhCHN), 2.20–2.10 (1H, ddq, J 13.7, 7.5 and 7.3, CHAHBCH3), 1.89–1.80 (1H,
ddq, J 13.7, 7.5 and 7.3, CHAHBCH3) and 0.74 (3H, t, J 7.3, CHCH2CH3); dC
We are grateful to the Saudi Government for financial support
(to N.A.S.) and the EPSRC National Mass Spectrometry Service
(Swansea) for accurate mass determinations.

6938
A. Andreou et al. / Tetrahedron Letters 51 (2010) 6935–6938
(100 MHz; CDCl3) 180.4 (C@S), 175.1 (C@O), 140.5 (i-C; Ph), 139.2 (i-C; Ph),
7.5 and 7.3, CHAHBCH3) and 0.79 (3H, t, J 7.3, CHCH2CH3); dC (100 MHz; CDCl3)
180.4 (C@S), 175.2 (C@O), 138.9 (i-C; Ph), 138.7 (i-C; Ph), 138.4 (i-C; Ar), 129.32
(2C, 2 ꢃ CH; Ph), 129.03 (3C, 3 ꢃ CH; Ph), 128.82 (2C, 2 ꢃ CH; Ph), 128.22 (2C,
2 ꢃ CH; Ph), 128.11 (1 ꢃ CH; Ph), 126.91 (1 ꢃ CH; Ar), 125.92 (2C, 2 ꢃ CH; Ph),
125.72 (2C, 2 ꢃ CH; Ar), 71.6 (PhCHNCO), 64.9 (PhCHN), 51.2 (PhCHEt), 26.8
139.1 (i-C; Ph), 129.32 (2C, 2 ꢃ CH; Ph), 129.22 (2C, 2 ꢃ CH; Ar), 128.82 (2 ꢃ CH;
Ph), 128.41 (1 ꢃ CH; Ph), 128.41 (1 ꢃ CH; Ph), 128.32 (2C, 2 ꢃ CH; Ph), 127.11
(1 ꢃ CH; Ph), 125.42 (2C, 2 ꢃ CH; Ph), 125.22 (2C, 2 ꢃ CH; Ar), 71.7 (PhCHNCO),
64.8 (PhCHN), 50.2 (PhCHEt), 27.1 (CH2CH3) and 11.9 (CH2CH3) (found MH+,
401.1678;
C
25H25O1N2S1 requires MH+, 401.11682); (2R,4S,5S)-syn,anti-6;
(CH2CH3) and 12.0 (CH2CH3) (found MH+, 401.1678; C25H25O1N2S1 requires
þ
þ
colourless oil; RF [CH2Cl2] 0.44;
m
max (CHCl3) cmꢀ1 3020 (N–H), 1215 (C@S) and
MH+, 401.1682).
1705 (C@O); ½a 2D5
ꢂ
ꢀ161.0 (c 0.8, CHCl3); dH (400 MHz; CDCl3) 7.35–7.27 (4H, m,
24. Andreou, A.; Eames, J.; Motevalli, M.; Prior, T. J.; Watkinson, M. Tetrahedron
4 ꢃ CH; Ph), 7.23–7.06 (9H, m, 9 ꢃ CH; Ph), 6.77 (2H, d, J 8.8, 2 ꢃ CH; Ph), 6.14
(1H, t, J 7.5, PhCHEt), 5.37 (1H, d, J 5.4, PhCHNCO), 4.42 (1H, d, J 5.4, PhCHN),
2.04–1.93 (1 H, ddq, J 13.7, 7.5 and 7.3, CHAHBCH3), 1.70–1.58 (1H, ddq, J 13.7,
Lett. 2010, 51, 1423.
25. Davies, S. G.; Evans, G. B.; Mortlock, A. A. Tetrahedron: Asymmetry 1994, 5,
585.