2032
M.L. Bode et al. / Tetrahedron 66 (2010) 2026–2036
(12) (7.00 g, 20.0 mmol) in THF (120 mL) at ꢀ78 ꢁC. The reaction
mixture was stirred at ꢀ78 ꢁC for 1 h, and then quenched by
careful addition of saturated NH4Cl solution at ꢀ78 ꢁC. The re-
action was allowed to warm to rt and worked-up as described for
compound (13a) above. Column chromatography of the oily res-
idue using EtOAc as eluent gave the hydroxysulfoxide (13b)
(4.69 g, 67%) as a white solid, mp 104–106 ꢁC. Rf¼0.35 (EtOAc);
3.10. (S(R),2R,4S)-1-(p-Tolylsulfinyl)-5-
(triphenylmethyloxy)pentane-2,4-diol (15a)
4-Dimethylaminopyridine (DMAP) (0.36 g, 2.96 mmol) and tri-
phenylmethyl chloride (4.64 g, 16.31 mmol) were added to a solu-
tion of (S(R),2R,4S)-1-(p-tolylsulfinyl)-pentane-2,4,5-triol (14a)
(3.83 g, 14.82 mmol) in CH2Cl2 (60 mL) and pyridine (4.8 mL,
59.3 mmol) and the reaction mixture stirred at rt for 2 days (TLC
control). The reaction mixture was washed with 1 M HCl
(4ꢂ100 mL) and then with brine (100 mL). The organic layer was
dried (Na2SO4) and evaporated to leave a yellow, viscous oil, which
was purified by column chromatography (elution hexane–EtOAc
1:4) to afford (S(R),2R,4S)-1-(p-tolylsulfinyl)-5-(triphenylmethy-
loxy)pentane-2,4-diol (15a) (7.26 g, 98%) as a white solid, mp 74–
[
a]
þ197.4 (c, 0.5, CHCl3); nmax 3359, 2975, 2921, 2886, 1376,
D
1362, 1048 (vs) cmꢀ1 1H NMR (300 MHz, CDCl3):
; d 7.48–7.29 (m,
4H, ArH), 4.69 (d, 1H, 2-OH), 4.31 (m, 1H, H-2), 4.15 (dddd,1H, J
7.5, 7.2, 6.0, 4.7, H-4), 4.02 (dd, 1H, J 8.0, 6.0, H-5a), 3.51 (dd, 1H, J
8.0, 7.2, H-5b), 2.98 (dd, 1H, J 13.4, 9.0, H-1a), 2.79 (dd, 1H, J 13.4,
2.2, H-1b), 2.38 (s, 3H, ArCH3), 1.76 (ddd, 1H, J 14.0, 8.0, 4.7, H-3a),
1.69 (ddd, 1H, J 14.0, 7,5, 4.1, H-3b), 1.32 (s, 3H, (CH3)2C), 1.21 (s,
3H, (CH3)2C); 13C NMR (75 MHz, CDCl3):
d
141.5S, 139.7S, 130.0D,
76 ꢁC. Rf¼0.38 (hexane–EtOAc 1:4); [
a
]
þ89.3 (c 0.98, CHCl3); 1H
D
123.9D (ArC), 108.7S ((CH3)2C), 73.2D (C-4), 69.5T (C-5), 64.5D (C-
2), 62.5T (C-1), 40.3T (C-3), 26.8Q and 25.6Q ((CH3)2C), 21.3Q
(ArCH3). HRMS (FAB): m/z 299.1317 (MþH)þ; calcd for C15H22SO4:
299.1317.
NMR (300 MHz, CDCl3): d 7.61–7.18 (m, 19H, ArH), 4.34 (m, 2H, H-2
and OH), 4.02 (m, 1H, H-4), 3.26 (br s, 1H, OH), 3.10 (m, 2H, H-5),
3.02 (dd, 1H, J 13.2, 8.0, H-1b), 2.77 (dd, 1H, J 13.2, 3.6, H-1a), 2.39 (s,
3H, ArCH3), 1.69 (dd, 2H, J 6.2, 6.2, H-3); 13C NMR (75 MHz, CDCl3):
d
143.7S, 141.8S, 140.4S, 130.0D, 128.6D, 127.8D, 127.0D and 124.0D
(ArC), 86.7S (Ph3CO), 70.4D (C-4), 68.1D (C-2), 67.4T (C-5), 63.0T (C-
1), 39.4T (C-3), 21.3Q (ArCH3); HRMS (FAB): m/z 501.2099 (MþH)þ;
calcd for C31H33SO4: 501.2100.
3.8. (S(R),2R,4S)-1-(p-Tolylsulfinyl)-pentane-2,4,5-triol (14a)
(S(R),2R,4S)-4,5-O-isopropylidene-1-(p-tolylsulfinyl)-pentane-
2,4,5-triol (13a) (5.05 g, 16.9 mmol) was dissolved in MeOH
(150 mL) and water (50 mL) and p-TsOH (0.32 g) were added. The
reaction was heated under reflux for 1.5 h, after which TLC in-
dicated that no starting material remained. Et3N (1 mL) was
added to neutralize the acid and the solvents were removed
under reduced pressure. The residue was dissolved in water
(60 mL) and extracted with EtOAc (50 mL) to remove any starting
material. The aqueous layer was then continuously extracted
with EtOAc for 2 days. The EtOAc solution was dried (Na2SO4)
and evaporated to leave (S(R),2R,4S)-1-(p-tolylsulfinyl)-pentane-
2,4,5-triol (14a) (3.93 g, 90%) as an oil that solidified after drying
3.11. (S(R),2S,4S)-1-(p-Tolylsulfinyl)-5-
(triphenylmethyloxy)pentane-2,4-diol (15b)
DMAP (0.26 g, 2.14 mmol) and triphenylmethyl chloride (3.21 g,
11.5 mmol) were added to a solution of the triol (14b) in CH2Cl2
(60 mL) and pyridine (4.2 mL, 54.2 mmol). The reaction mixture
was refluxed for 6 h, allowed to cool and washed with 3 M HCl
(100 mL) and then with brine (2ꢂ100 mL). The organic layer was
dried (Na2SO4) and concentrated. Column chromatography of the
residue using EtOAc as eluent yielded the O-trityl derivative (15b)
(4.98 g, 95%) as a white solid, mp 143–145 ꢁC; Rf¼0.58 (EtOAc);
under high vacuum, mp 140–142 ꢁC. [
a
]
þ186.8 (c 0.53, CHCl3),
D
[a
]
þ112.6 (c, 1.03, CHCl3); nmax 3356 (br), 2919, 1490, 1439, 1011
D
[
a
]
þ82.4 (c 1.0, MeOH); 1H NMR (300 MHz, CDCl3):
d 7.52–7.24
D
(vs) cmꢀ1 1H NMR (300 MHz, CDCl3):
; d 7.51–7.17 (m, 19H, ArH),
(m, 4H, ArH), 4.32 (m, 1H, H-2), 3.90 (m, 1H, H-4), 3.56 (dd, 1H,
J 11.4, 3.6, H-5b), 3.45 (dd, 1H, J 11.4, 6.2, H-5a), 3.08 (dd, 1H, J
13.3, 7.4, H-1b), 2.82 (dd, 1H, J 13.3, 4.3, H-1a), 2.35 (s, 3H,
ArCH3), 1.77 (m, 1H, H-3b), 1.71 (m, 1H, H-3a); 13C NMR (75 MHz,
4.65 (d, 1H, J 4.1, 2-OH), 4.47 (m, 1H, H-2), 4.03 (m, 1H, H-4), 3.29
(d, 1H, J 3.9, 4-OH), 3.09 (d, 2H, J 5.4, H-5), 3.01 (dd, 1H, J 13.3, 9.8,
H-1a), 2.75 (dd, 1H, J 13.3, 2.2, H-1b), 2.39 (s, 3H, ArCH3), 1.62 (ddd,
1H, J 14.0, 9.1, 3.6, H-3a), 1.54 (ddd, 1H, J 14.0, 8.3, 2.8, H-3b); After
D2O exchange: 4.47 (dddd, 1H, J 9.8, 8.3, 3.6, 2.2, H-2), 4.03 (dddd,
1H, J 9.1, 6.5, 4.9, 2.8, H-4), 3.10 (dd, 1H, J 9.6, 4.9, H-5a), 3.07 (dd,
1H, J 9.6, 6.5, H-5b); 13C NMR (75 MHz, CDCl3): 143.8S, 141.5S,
139.6S, 130.0D, 128.6D, 127.7D, 126.9D, 124.0D (ArC), 86.5S
(Ph3CO), 67.7T (C-5); 67.4D (C-4), 63.5T (C-1), 63.3D (C-2), 40.1T
(C-3), 21.3Q (ArCH3); HRMS (FAB): m/z 501.2098 (MþH)þ; calcd for
C31H33SO4: 501.2100.
CDCl3):
d 141.9S, 139.9S, 130.1D and 124.2D (ArC), 71.1D (C-4),
67.2D (C-2), 66.3T (C-5), 62.6T (C-1), 39.1T (C-3), 21.4Q (ArCH3);
HRMS (FAB): m/z 259.1004 (MþH)þ; calcd for C12H19SO4:
259.1004.
3.9. (S(R),2S,4S)-1-(p-Tolylsulfinyl)-pentane-2,4,5-triol (14b)
p-TsOH (0.15 g) was added to a solution of the protected sulf-
oxide (13b) (3.70 g, 12.0 mol) in MeOH (90 mL) and water (30 mL).
The reaction was heated under reflux for 1.5 h, neutralised by ad-
dition of Et3N (0.5 mL) and concentrated under reduced pressure.
The residue was dissolved in water (30 mL) and the product con-
tinuously extracted with EtOAc to yield (14b) (2.84 g, 89%) as
3.12. (S(R),2R,4S)-2,4-O-isopropylidene-1-(p-tolylsulfinyl)-5-
(triphenylmethyloxy)pentane-2,4-diol (16a)
p-TsOH (25 mg) was added to a stirred solution of (S(R),2R,4S)-
1-(p-tolylsulfinyl)-5-(triphenylmethyloxy)pentane-2,4-diol (15a)
(1.00 g, 1.997 mmol) in 2,2-dimethoxypropane (5 mL) and acetone
(20 mL). Et3N (1 mL) was added after 35 min and the solvent re-
moved under reduced pressure. Column chromatography of the
residue with hexane–EtOAc (1:1) as eluent afforded (S(R),2R,4S)-
2,4-O-isopropylidene-1-(p-tolylsulfinyl)-5-triphenylmethyloxypen-
tane-2,4-diol (16a) (0.96 g, 89%) as a white solid, mp 167–168 ꢁC.
a white solid, mp 139–141 ꢁC; Rf¼0.43 (CHCl3–MeOH 4:1); [
a]
D
þ196.8 (c 0.53, MeOH); nmax 3364, 3281, 2947, 2910, 2863, 1497,
1434, 1402, 1345, 1274, 1223, 1105, 1066 (vs) cmꢀ1
;
1H NMR
(300 MHz, CDCl3): 7.42–7.30 (m, 4H, ArH), 4.20 (dddd, 1H, J 10.2,
d
9.3, 3.6, 2.8, H-2), 3.78 (dddd, 1H, J 9.6, 6.5, 4.1, 4.1, H-4), 3.45 (dd,
1H, J 11.6, 4.1, H-5a), 3.35 (dd, 1H, J 11.6, 6.5, H-5b), 3.01 (dd, 1H, J
13.7, 2.8, H-1a), 2.81 (dd, 1H, J 13.7, 10.2, H-1b), 2.24 (s, 3H, ArCH3),
1.54 (ddd, 1H, J 14.6, 9.3, 4.1, H-3a), 1.45 (ddd, 1H, J 14.6, 9.6, 3.6, H-
Rf¼0.51 (hexane–EtOAc 1:1). [
2878, 1596, 1489, 1447, 1382, 1199, 1077 (vs) cmꢀ1
(300 MHz, CDCl3): 7.42–7.26 (m, 19H, ArH), 4.09 (m, 1H, H-2),
a]
D
þ25.2 (c 1.08, CHCl3); nmax 2923,
;
1H NMR
3b); 13C NMR (75 MHz, D2O):
d
143.8S, 137.8S, 130.8D, 125.0D (ArC);
d
68.6D (C-4); 66.2T (C-5); 64.3D (C-2); 62.8T (C-1); 39.9T (C-3);
21.0Q (ArCH3); HRMS (FAB): m/z 259.1004 (MþH)þ; calcd for
C12H18SO4: 259.1004.
3.96 (m, 1H, H-4), 3.22 (dd, 1H, J 9.3, 5.2, H-5b), 3.14 (dd, 1H, J 13.2,
6.9, H-1b), 2.96 (dd, 1H, J 9.3, 6.0, H-5a), 2.75 (dd, 1H, J 13.2, 5.4, H-
1a), 2.40 (s, 3H, ArCH3), 1.74 (ddd, 1H, J 12.7, 2.3, 2.3, H-3), 1.37