4856
J. R. Al-Dulayymi et al. / Tetrahedron 62 (2006) 4851–4862
17.3 mmol) in dry tetrahydrofuran (15 ml) was added drop-
wise to a stirred suspension of lithium aluminium hydride
(1.32 g, 34.7 mmol) in tetrahydrofuran (50 ml) at room tem-
perature under nitrogen. The mixture was refluxed for 1 h,
when TLC showed no starting material, then cooled to
for 266 refined parameters, final difference map within
ꢃ0.27 eAꢀ3. Software: Bruker SMART, SAINT and
˚
SHELXTL. Crystallographic data (excluding structure fac-
tors) for the structure in this paper have been deposited
with the Cambridge Crystallographic Data Centre as sup-
plementary publication number CCD283460. Copies of the
data can be obtained free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax:
ꢁ
0 C and quenched with satd aq sodium sulfate decahydrate
(20 ml) until a white solid formed. The precipitate was fil-
tered off and washed with tetrahydrofuran (2ꢂ20 ml). The
filtrate was evaporated to give a crude product; chromatogra-
phy (1:1 petroleum/ethyl acetate) gave (S)-3-[(1R,2R)-2-
((S)-2,2-dimethyl[1,3]dioxolan-4-yl)cyclopropyl]-butan-1-ol
(13) as a colourless oil (3.26 g, 88%) [Found M+ꢀCH3:
199.1344; C11H19O3 requires: 199.1334], [a]2D2 ꢀ8.9 (c
1.53, CHCl3), which showed dH (500 MHz, CDCl3): 4.19
(1H, dd, J 5.65, 7.55 Hz), 3.88 (1H, dt, J 6, 7.86 Hz), 3.71
(2H, t, J 7.9 Hz), 3.67–3.62 (1H, br m), 1.75 (1H, br s),
1.67–1.59 (2H, m), 1.53–1.46 (1H, m), 1.45 (3H, s), 1.36
(3H, s), 1.04 (3H, d, J 6.6 Hz), 0.95 (1H, dq, J 5.65,
8.5 Hz), 0.85 (1H, dt, J 4.4, 8.5 Hz), 0.74–0.68 (1H, m),
0.28 (1H, br q, J 5.65 Hz); dC (125 MHz, CDCl3): 108.5,
77.1, 70.1, 60.6, 40.3, 29.64, 26.78, 25.7, 23.87, 20.35,
2.1.8. 2-{(S)-3-[(1R,2R)-2-((S)-2,2-Dimethyl[1,3]-dioxo-
lan-4-yl)cyclopropyl]butylsulfanyl}benzothiazole (14).
Diethyl azodicarboxylate (2.56 g, 14.7 mmol) in dry tetrahy-
drofuran (5 ml) was added to a stirred solution of alcohol 13
(3 g, 14.0 mmol), triphenylphosphine (4.04 g, 15 mmol) and
2-mercaptobenzthiazole (2.46 g, 14.7 mmol) in tetrahydro-
ꢁ
furan (20 ml) at 5 C under nitrogen. The mixture was al-
lowed to reach room temperature, stirred for 24 h, then the
solvent was evaporated. The residue was dissolved in ethyl
acetate (50 ml) and petroleum (50 ml), stirred for 15 min,
filtered through Celite and evaporated to give a yellow oil.
This was dissolved in ether, suspended on silica and then
columned (1:1 petroleum/ether) to give 2-{(S)-3-[(1R,2R)-2-
((S)-2,2-dimethyl[1,3]-dioxolan-4-yl)cyclopropyl]butylsul-
fanyl}benzothiazole (14) as a pale yellow oil (4.5 g, 89%)
[Found M+: 363.1317; C19H25O2S2N requires: 363.1327],
[a]2D2 ꢀ45.05 (c 1.485, CHCl3), which showed dH
(250 MHz, CDCl3): 7.88 (1H, br dd, J 0.9, 7.6 Hz), 7.76
(1H, br dd, J 0.9, 8 Hz), 7.42 (1H br dt, J 1.2, 7.3 Hz),
7.27 (1H, br dt, J 1.2, 8 Hz), 4.09 (1H, dd, J 5.8, 7.6 Hz),
3.76 (1H, br dt, J 5.8, 8.25 Hz), 3.63 (1H, br t, J 7.6 Hz),
3.52–3.24 (2H, m), 1.95–1.83 (1H, m), 1.81–1.65 (1H, m),
1.43 (3H, s), 1.33 (3H, s), 1.29–1.19 (1H, m), 1.10 (3H, d,
J 6.4 Hz), 1.04–0.71 (4H, m), 0.31 (1H, br q, J 6.4 Hz); dC
(62.5 MHz, CDCl3): 166.6, 153.2, 135.1, 126.1, 124.2,
121.5, 120.9, 108.3, 77.2, 70, 36.7, 32.65, 31.1, 26.8, 25.6,
23.5, 19.6, 19.4, 8.9; nmax: 3062, 2982, 1461, 1427,
19.1, 8.3; nmax: 3432, 2983 cmꢀ1
.
2.1.6. 3,5-Dinitrobenzoic acid (S)-3-[(1R,2R)-2-((S)-2,2-
dimethyl[1,3]dioxolan-4-yl)cyclopropyl]butyl ester. 3,5-
Dinitrobenzoyl chloride (0.42 g, 1.82 mmol), was added
to
a stirred solution of (S)-3-[(1R,2R)-2-((S)-2,2-di-
methyl[1,3]dioxolan-4-yl)cyclopropyl]butan-1-ol (13) (0.3 g,
1.4 mmol) and pyridine (1.5 ml) in toluene (5 ml) at room
temperature. The mixture was refluxed for 4 h then cooled
to room temperature and the solvent was evaporated. The
residue was treated with water (10 ml) and extracted with
ether (3ꢂ20 ml). The combined organic layers were washed
with brine, dried and evaporated to give a thick yellow
oil; chromatography (1:1 petroleum/ether) gave a white
solid, 3,5-dinitrobenzoic acid (S)-3-[(1R,2R)-2-((S)-2,2-dime-
thyl[1,3]dioxolan-4-yl)cyclopropyl]butyl ester (0.32 g, 56%),
mp 77–79 C [Found C, 56.0, H, 5.8, N, 6.9; C19H24O8N2
1060 cmꢀ1
.
ꢁ
requires: C, 55.88, H, 5.92, N, 6.85], [a]2D2 ꢀ26 (c 0.4,
CHCl3), which showed dH (250 MHz, CDCl3): 9.23 (1H,
br t, J 2.1 Hz), 9.14 (2H, br d, J 2.1 Hz), 4.56–4.42 (2H,
m), 4.18–4.08 (1H, m), 3.81–3.68 (2H, m), 2.10–1.88
(1H, m), 1.81–1.67 (1H, m), 1.42 (3H, s), 1.38–1.29 (1H,
m), 1.28 (3H, s), 1.13 (3H, d, J 6.4 Hz), 1.08–0.79 (3H,
m), 0.33 (1H, br q, J 5 Hz); dC (62.5 MHz, CDCl3): 162.5,
148.7, 133.8, 129.3, 122.38, 108.56, 70.1, 65.2, 33.8, 30.4,
28.75, 25.7, 23.5, 20.03, 19.1, 8.73; nmax: 2923, 2853,
2.1.9. 2-{(S)-3-[(1R,2R)-2-((S)-2,2-Dimethyl[1,3]dioxo-
lan-4-yl)cyclopropyl]-butane-1-sulfonyl}benzothiazole
(15). A solution of ammonium heptamolybdate(VI) tetra-
hydrate (1.34 g, 1.1 mmol), in 35%ꢁH2O2 (w/w) (5.3 ml,
54.4 mmol) was added dropwise at 5 C to a stirred solution
of compound 14 (4.2 g, 11.5 mmol) in methylated spirit
(100 ml). The resulting yellow solution was stirred for 1 h
at this temperature and then for 16 h at room temperature.
The solvent was evaporated to give a yellow solid which
was treated with water (50 ml) and extracted with dichloro-
methane (3ꢂ50 ml); the combined organic layers were
washed with brine (50 ml), dried and evaporated to give
the crude product. This was purified by chromatography
(1:1 petroleum/ethyl acetate) to give 2-{(S)-3-[(1R,2R)-
2-((S)-2,2-dimethyl[1,3]-dioxolan-4-yl)cyclopropyl]-butane-
1-sulfonyl}benzothiazole as a thick yellow oil (15) (3.08 g,
67.4%) [Found M+: 395.123; C19H25O4S2N requires:
395.1225], [a]2D2 ꢀ34.1 (c 1.36, CHCl3), which showed dH
(250 MHz, CDCl3): 8.23 (1H, br d, J 8.2 Hz), 8.04 (1H, br
d, J 8 Hz), 7.66 (1H, dt, J 1, 7.3 Hz), 7.61 (1H, dt, J 1,
8.2 Hz), 4.04 (1H, dd, J 6, 7.9 Hz), 3.76 (1H, br q, J
7.6 Hz), 3.63–3.56 (2H, m), 3.54–3.48 (1H, m), 2.03–1.96
(1H, m), 1.81–1.73 (1H, m), 1.41 (3H, s), 1.37–1.33 (1H,
m), 1.31 (3H, s), 1.06 (3H, d, J 6.4 Hz), 0.99–0.92 (1H, dt,
1732, 1544 cmꢀ1
.
2.1.7. Crystal structure determination for the 3,5-dinitro-
benzoate of (13). Crystal data: C19H24N2O8, M¼408.4,
orthorhombic, space group P212121, a¼5.6009(3), b¼
3
˚
˚
16.6472(8), c¼21.3374(10) A, V¼1989.48(17) A , Z¼4,
Dc¼1.364 g cmꢀ3, m¼0.11 mmꢀ1 (Mo Ka, l¼0.71073 A),
˚
T¼150 K. Of 14,574 reflections measured on a Bruker
AXS SMART CCD diffractometer, 2057 were unique
(q<25ꢁ, Rint¼0.038). The structure was solved by standard
direct methods and refined on F2 values; H atoms were con-
strained with a riding model. In the absence of significant
anomalous scattering, Friedel pairs were merged, and the ab-
solute configuration was assigned on the basis of the known
configuration of compound 8. R¼0.033 (F values, F2>2s),
Rw¼0.079 (F2 values, all data), goodness-of-fit¼1.125