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H. Villar et al. / Tetrahedron: Asymmetry 13 (2002) 1465–1475
4.1.6. SmI2-induced cyclisation of racemic (4R*,5S*) and
enantiomerically enriched (4R,5S)-5-iodo-4-methylhex-
(2E)-enoic acid benzyl ester. 0.1N solution of SmI2 in
THF. In a graduated Schlenk tube under an argon
atmosphere, 1,2-diiodoethane (2.82 g, 10 mmol) was
diluted to a volume of 100 mL in anhydrous and
degassed THF. This solution was slowly transferred,
through a cannula into a second Schlenk tube contain-
ing metallic samarium (1.8 g, 1.19 mmol) and a stirring
bar. The yellow suspension was magnetically stirred at
room temperature for 2 h to give a deep blue solution.
This solution was stored for not more than a week
under argon and in the dark.
4.2. NMR spectroscopy in oriented solvents
The chiral and non chiral liquid crystalline NMR sam-
ples were prepared using the homopolypeptide (ca. 100
mg, commercially available from Sigma), the deuterated
solutes (ca. 10 mg) and organic co-solvent (ca. 400 mg)
directly weighed into a 5 mm o.d. NMR tube. The
exact compositions of each oriented NMR sample are
given in Table 2. All NMR tubes were sealed to avoid
solvent evaporation and centrifuged back and forth
until an optically homogeneous birefringent phase was
obtained. Various experimental details on the method
can be found in Ref. 6a. The 2H-{1H} 1D and 2D
experiments were performed at 9.4 T on a Bruker DRX
400 high-resolution spectrometer equipped with an
inverse multinuclear probe (BBI) operating at 61.4
MHz for deuterium and with a standard variable tem-
perature unit (BVT 3000). In order to remove the
proton–deuterium scalar and dipolar couplings, the
protons were broadband decoupled using WALTZ-16
composite pulse sequence. Other experimental NMR
parameters or details are given in the figure captions.
Cyclisation: Either (4R*,5S*)- or enantiomerically
enriched (4R,5S)-5-iodo-4-methylhex-(2E)-enoic acid
benzyl ester (200 mg, 0.58 mmol) together with tert-
butanol (165 mL, 1.75 mmol), were diluted with THF (2
mL). The resulting solution was added dropwise over a
period of 1 min and under stirring in a Schlenk tube
(argon atmosphere) containing a solution of SmI2 in
THF (0.1 M, 14.5 mL, 2.5 equiv.). After 2 h, during
which the deep blue colour of the SmI2 solution pro-
gressively discharged, the reaction mixture was
quenched with 0.1N HCl and extracted with diethyl
ether. The organic phase was washed with aqueous
sodium thiosulfate solution and dried over magnesium
sulfate.
References
1. David, H.; Afonso, C.; Bonin, M.; Doisneau, G.;
Guillerez, M.-G.; Guibe´, F. Tetrahedron Lett. 1999, 40,
8557.
2. Frohn, M.; Dalkiewicz, M.; Tu, Y.; Wang, Z.-X.; Shi, Y.
NMR and HRMS characterisation of cyclised propanes:
The crude products were directly purified by column
chromatography (silica gel, 80:20 cyclohexane/ethyl
acetate) to give 100 mg (80% overall yield) of a ca. 1:2
mixture of unseparated meso 2-(trans-2-trans-3-
dimethylcyclopropyl)acetic acid benzyl ester 2 and d,l-
2-(cis-2-trans-3-dimethylcyclopropyl)acetic acid benzyl
ester [3+ent-3].
J. Org. Chem. 1998, 63, 2948.
3. David, H.; Dupuis, L.; Guillerez, M.-G.; Guibe´, F. Tet-
rahedron Lett. 2000, 41, 3335.
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5. Kainosho, M.; Ajisaka, K.; Pirkle, W.; Beare, S. D. J.
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6. (a) Sarfati, M.; Lesot, P.; Merlet, D.; Courtieu, J. Chem.
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tiomer 2001, 6, 281.
1H NMR (CDCl3, 400 MHz): peak assignments to
respectively the d,l- and the meso-isomers were estab-
lished using COSY 2D proton NMR experiments d,l-2-
(cis-2-trans-3-dimethyl-cyclopropyl)acetic acid benzyl
ester 3: l 7.33–7.27 (m, 5H); 5.15 (s, 2H); 2.33 (d,
3J=7.35 Hz, 2H); 1.01–0.96 (two d, 3J= 6.45 Hz, 3H+3
H); 0.76–0.71 (m, 1H); 0.59–0.54 (m, 1H); 0.20–0.16 (m,
1H). meso-2-(cis-2-trans-3-Dimethylcyclopropyl)acetic
acid benzyl ester 2: 7.33–7.27 (m, 5H); 5.13 (s, 2H); 2.24
7. Meddour, A.; Canlet, C.; Blanco, L.; Courtieu, J. Angew.
Chem., Int. Ed. 1999, 38, 2391.
8. (a) Lesot, P. D.; Merlet, D. A.; Loewenstein, A. J.;
Courtieu, J. Tetrahedron: Asymmetry 1998, 9, 1871; (b)
Merlet, D.; Ancian, B.; Courtieu, J.; Lesot, P. J. Am.
Chem. Soc. 1999, 121, 5249.
9. Meddour, A.; Canet, I.; Loewenstein, A.; Pe´chine´, J.-M.;
Courtieu, J. J. Am. Chem. Soc. 1995, 116, 9652.
10. (a) Merlet, D.; Emsley, J. W.; Lesot, P.; Courtieu, J. J.
Chem. Phys. 1999, 111, 6890; (b) Aroulanda, C.; Merlet,
D.; Courtieu, J.; Lesot, P. J. Am. Chem. Soc. 2001, 123,
12059.
11. Theoretical considerations on spin-1 COSY 2D experi-
ments will be published elsewhere.
12. Canlet, C.; Merlet, D.; Lesot, P.; Meddour, A.; Loewen-
stein, A.; Courtieu, J. Tetrahedron: Asymmetry 2000, 11,
1911.
3
(d, J=7.15 Hz, 2H); 0.99 (s, 6H); 0.59-0.54 (m, 2H);
0.39–0.33 (m, 1H). Electrospray (ESI, positive mode) 2
and 3: 219.3 (23%, MH+); 236.3 (34%, M+NH4 ); 241.3
+
(75%, M++Na); 242.3.
4.1.7. Reduction of esters to deuterated alcohols. The
crude (unchromatographed) products of cyclisation
(theoretical amount: 0.58 mmol) were dissolved in THF
(1 mL) and added to a solution of LiAlD4 (20 mg, 0.48
mmol) in THF (1 mL) at 0°C. After stirring for 1 h the
reaction mixture was hydrolysed with 1N aqueous HCl
and extracted several times with ethyl acetate. The
organic phases were washed with water, dried over
MgSO4 and the solvent was evaporated. 1H and 2H
NMR analyses were carried out directly on the crude
residue.
13. Molander, G. A.; Harris, C. R. J. Org. Chem. 1997, 62,
7418.
14. See also: (a) Bennett, S. M.; Biboutou, R. K.; Zhou, Z.;
Pion, R. Tetrahedron 1998, 54, 4761; (b) see Ref. 15c, pp.
767–768.