(2R,4R)-Di-O-(3,3-p en tylid en e)-3-O[(m eth ylth io)th ioca r -
bon yl]a r a bitol (en t-12). To a solution of ent-5 (12.03 g, 41.7
mmol) in THF (150 mL) and CS2 (32.0 mL, 0.53 mol) at 0 °C
was added NaH (2.0 g of a 60% dispersion in mineral oil, 50
mmol) and the reaction was stirred for 1 h at 0 °C. After being
stirred overnight at room temperature, the reaction was cooled
to 0 °C and MeI (3.3 mL, 54.21 mmol) was added. The reaction
was warmed to room temperature and stirred for 6 h, then
quenched by the slow addition of saturated aqueous NH4Cl (200
mL) followed by diethyl ether (200 mL). The aqueous phase was
extracted with diethyl ether (2 × 200 mL). The combined organic
phases were dried over anhydrous Na2SO4, filtered, and con-
centrated in vacuo to give a yellow oil. Purification by chroma-
tography (hexane/ethyl acetate 9:1) yielded a yellow oil (15.47
g, 98%). [R]D +56.1 (c 0.53, CHCl3, 20 °C); IR 2973 (s), 2940 (s),
after 30, 60, and 90 min. The solvent was then removed in vacuo
and the crude material purified by chromatography (hexane/
EtOAc 95:5). A second purification by chromatography was
required, which yielded ent-6b as a colorless oil (1.39 g, 97%).
(C) Red u ction of en t-13: As above for ent-12. ent-13 (2.0 g,
5.02 mmol), Et3SiH (38 mL, 0.24 mol), Bz2O2 (0.24 g, 1.0 mmol).
Yield 1.27 g (93%).
(2S,4S)-P en ta n e-1,2,4,5-tetr a ol (en t-14). To a stirred solu-
tion of ent-6b (10.65 g, 39.11 mmol) in ethanol (50 mL) was
added aqueous 0.5 M H2SO4 (50 mL) and the reaction was stirred
at reflux for 4 h. The reaction was quenched by addition of
powdered BaCO3 until neutral. After stirring at reflux for
another 10 min the reaction mixture was cooled and filtered.
The residue was stirred again with hot methanol, filtered, and
washed with methanol. The filtrate was concentrated in vacuo
to give a white solid. This was purified by chromatography (CH2-
Cl2/MeOH 7:3) to give a white solid (5.092 g, 96%). Mp 104-
106 °C (EtOH/hexane) [lit.13 mp 106-107 °C]; [R]D -47.7 (c 0.5,
EtOH, 20 °C) [lit.13 [R]D -46.0 (c 1.03, EtOH, 22 °C)]; the 1H
and 13C NMR spectra corresponded to the literature values.13
Data for 14: mp 105-107 °C; [R]D +47.2 (c 0.4, EtOH, 20 °C);
the 1H and 13C NMR correspond to those of ent-14.
1
2882 (m), 1463 (m), 1357 (w), 1209 (s), 1077 (s) cm-1; H NMR
(400 MHz, CDCl3) δ 6.14 (1H, dd, J ) 5.8, 2.8 Hz), 4.45-4.38
(2H, m), 4.11 (1H, dd, J ) 8.8, 6.3 Hz), 4.03 (1H, dd, J ) 8.3, 6.8
Hz), 4.00 (1H, dd, J ) 8.8, 6.3 Hz), 3.70 (1H, t, J ) 8.0 Hz), 2.60
(3H, s), 1.71-1.57 (8H, m), 0.95-0.87 (12H, m) ppm; 13C NMR
(100 MHz, CDCl3) δ 217.2 (C), 113.3 (C), 113.2 (C), 79.4 (CH),
75.6 (CH), 75.4 (CH), 66.4 (CH2), 65.6 (CH2), 29.6 (CH2), 29.3
(CH2), 29.0 (CH2), 28.95 (CH2), 19.3 (CH3), 8.09 (2 × CH3), 8.05
(2 × CH3) ppm; CIMS m/z (%) 349 ((M - Et)+, 36), 293 (100),
263 (46), 241 (66); HRMS (ES+) calcd for C17H30O5S2Na (M +
Na)+ 401.1427, found 401.1426. Data for 12: [R]D -56.1 (c 0.60,
CHCl3, 20 °C); 1H and 13C NMR, CIMS and IR data correspond
to those for ent-12; HRMS (ES+) calcd for C17H30O5S2Na (M +
Na)+ 401.14269, found 401.14267.
(2S,4S)-2,4-Dih yd r oxyp en ta n e-1,5-d iyl Bis-(2,4,6-tr iiso-
p r op yl-1-ben zen esu lfon a te) (en t-15). To a stirred solution of
ent-14 (2.5 g, 18.36 mmol) in dry pyridine (22 mL) at 0 °C was
added 2,4,6-tri-isopropyl benzenesulfonyl chloride (12.24 g, 40.41
mmol). The reaction was stirred overnight at room temperature
and the solvent removed under high vacuum rotary evaporation.
The resulting pale yellow solid was purified by chromatography
(hexane/acetone 75:25) to give a white solid. Recrystallization
(CH2Cl2/hexane) gave a fluffy white solid (10.43 g, 85%). Mp
154-156 °C (CH2Cl2/hexane) [lit.13 mp 154-155 °C (CH2Cl2/light
petroleum)]; [R]D -7.5 (c 0.6, EtOH, 20 °C) [lit.13 [R]D -8.8 (c
0.2, EtOH, 22 °C)]; the 1H and 13C NMR spectra corresponded
to the literature values.13 Data for 15: mp 153-154 °C (CH2-
(2R,4R)-1,2:4,5-Di-O-(3,3-pen tyliden e)-3-O-[(N-im idazolyl)-
th ioca r bon yl]a r a bitol (en t-13). To a solution of ent-5 (2.0 g,
6.94 mmol) in dry 1,2-dichloroethane (25 mL) was added N,N′-
thiocarbonyldi-imidazole (2.16 g, 12.14 mmol) and the mixture
was stirred for 6 h at reflux. The resultant orange/brown solution
was concentrated in vacuo and purified by chromatography
(hexane/EtOAc 85:15) to give a yellow oil (2.76 g, 100%). [R]D
+40.8 (c 0.90, CHCl3, 23 °C); IR 3127 (w), 2973 (s), 2940 (s),
1
Cl2/hexane); [R]D +7.7 (c 0.4, EtOH, 22 °C); the H and 13C NMR
2882 (s), 1532 (m), 1464 (s), 1390 (s), 1080 (s) cm-1 1H NMR
;
correspond to those of ent-15.
(400 MHz, CDCl3) δ 8.36 (1H, s), 7.64 (1H, m), 7.06 (1H, m),
6.04 (1H, dd, J ) 5.0, 3.5 Hz), 4.48-4.41 (2H, m), 4.15 (1H, dd,
J ) 8.8, 6.5 Hz), 4.10 (1H, dd, J ) 8.7, 6.6 Hz), 4.04 (1H, dd, J
) 8.8, 6.8 Hz), 3.74 (1H, t, J ) 8.2 Hz), 1.69-1.45 (8H, m), 0.895
(3H, t, J ) 7.4 Hz), 0.888 (3H, t, J ) 7.5 Hz), 0.882 (3H, t, J )
7.5 Hz), 0.77 (3H, t, J ) 7.4 Hz) ppm; 13C NMR (100 MHz, CDCl3)
δ 184.5 (C), 137.1 (CH), 131.1 (CH), 118.0 (CH), 113.5 (C), 113.4
(C), 80.1 (CH), 75.6 (CH), 75.1 (CH), 66.1 (CH2), 65.5 (CH2), 29.4
(2 × CH2), 28.6 (2 × CH2), 8.2 (CH3), 8.1 (CH3), 8.0 (CH3), 7.7
(CH3) ppm; CIMS m/z (%) 421.3 ((M + Na)+, 12), 399.2 (100);
HRMS (ES+) calcd for C19H30N2O5S (M + H)+ 399.1948, found
399.1949.
(2S,4S)-1,2:4,5-Diep oxyp en ta n e (en t-1). To a stirred solu-
tion of ent-15 (14.51 g, 21.7 mmol) in dry THF (600 mL) was
added NaH (9.5 g, 60% dispersion in mineral oil, washed with
pentane, 0.24 mol) and the reaction was stirred vigorously for 1
h. The reaction was then filtered through MgSO4 and washed
with pentane, and the solvent was removed by fractional
distillation yielding a yellow slurry. Purification by chromatog-
raphy (diethyl ether/pentane 4:1) and subsequent concentration
by distillation gave a colorless oil that was purified by Kugelrohr
distillation (90 °C, 18 mmHg) to yield a colorless oil (1.46 g, 67%).
[R]D -56.5 (c 0.6, CHCl3, 20 °C) [lit.2a [R]D -55.5 (c 0.92, CHCl3)];
the 1H and 13C NMR spectra corresponded to the literature
values. Data for 1: [R]D +55.9 (c 0.6, CHCl3, 20 °C) [lit.2a [R]D
+57.6 (c 2.2, CHCl3)]; the 1H and 13C NMR spectra corresponded
to the literature values.2a
(2S,4S)-Di-O-(3,3-p en tylid en e)-3-d eoxya r a bitol (en t-6b).
(A) Tin h yd r id e r ed u ction of en t-12: AIBN (0.4 g, 2.5 mmol)
and 11 (23.25 g, 61.42 mmol) were dissolved in degassed toluene
(350 mL). Bu3SnH (18.50 mL, 67.56 mmol) was added and the
reaction was refluxed for 4 h. The reaction was allowed to cool,
and concentrated in vacuo. Purification by chromatography
(hexane/EtOAc 9:1) yielded ent-6b as a colorless oil (14.92 g,
89%). [R]D +10.0 (c 0.46, CHCl3, 20 °C); IR 2973 (s), 2941 (s),
Ack n ow led gm en t. We thank the EPSRC and the
Royal Society for support. E.B. thanks Prof. J . Engels
for the opportunity to undertake research at Southamp-
ton University. We are indebted to J oan Street and Neil
Wells for NMR support, and to Dr. J ohn Langley and
J ulie Herniman for MS support. We wish to acknowl-
edge the use of the EPSRC’s Chemical Database Service
at Daresbury.15
1
2881 (s), 1173 (s), 1078 (s) cm-1; H NMR (400 MHz, CDCl3) δ
4.18 (2H, ddd, J ) 12.3, 7.7, 6.3 Hz), 4.11 (2H, dd, J ) 7.8, 6.0
Hz), 3.52 (2H, t, J ) 7.8 Hz), 1.81 (2H, t, J ) 6.4 Hz), 1.67-1.58
(8H, m), 0.894 (6H, t, J ) 7.4 Hz), 0.891 (6H, t, J ) 7.4 Hz)
ppm; 13C NMR (100 MHz, CDCl3) δ 112.6 (2 × C), 74.0 (2 ×
CH), 70.5 (2 × CH2), 37.7 (CH2), 29.9 (2 × CH2), 29.7 (2 × CH2),
8.2 (2 × CH3), 8.0 (2 × CH3) ppm; CIMS, m/z (%) 273 ((M +
H)+, 30), 243 (22), 157 (100). Anal. Calcd for C15H28O4: C, 66.14;
H, 10.36. Found: C, 66.43; H, 10.23. Data for 6b: [R]D -11.5 (c
0.60, CHCl3, 20 °C). Anal. Calcd for C15H28O4: C, 66.14; H, 10.36.
Found: C, 66.20; H, 10.08. 1H and 13C NMR, CIMS, and IR data
all correspond to that for ent-6b.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of all novel compounds. Experimental procedures and
characterization for compounds 10 and en t-11. This material
J O034374X
(B) Sila n e r ed u ction of en t-12: To en t-12 (2.0 g, 5.28 mmol)
was added Et3SiH (40 mL, 0.25 mol) and the reaction was
brought to reflux. Benzoyl peroxide (0.26 g, 1.1 mmol) was added
and the reaction refluxed for 2 h, with a similar quantity added
(15) The United Kingdom Database Service. Fletcher, D. A.; Mc-
Meeking, R. F.; Parkin, D. J . Chem. Inf. Comput. Sci. 1996, 36, 746.
J . Org. Chem, Vol. 68, No. 21, 2003 8255