To a
3-L, three-necked, round-bottomed flask equipped with a
mechanical stirrer and
two glass stoppers at room temperature are added
(E)-1,2-diphenylethene (trans-stilbene) (180.25 g, 1.0 mol, 1.0 equiv) (Note
1),
4-methylmorpholine N-oxide (NMO) [260 mL of a 60% by wt. aqueous solution (1.5 mol, 1.5 equiv) (Note 1) and (Note 2)],
dihydroquinidine 4-chlorobenzoate (23.25 g, 0.05 mol, 0.05 equiv) (Note
3) and (Note
4),
375 mL of acetone and 7.5 mL water. [The solution is 0.1 M in alkaloid (Note
5), 2 M in olefin, and the solvent is 25% water/75%
acetone (v/v) (Note
6)]. The flask is immersed in a 0°C cooling bath and stirred for 1 hr.
Osmium tetroxide (1.0 g, 4.0 mmol, 4.0 × 10−3 equiv) is added in one portion, producing a milky brown-yellow suspension (Note
7). The reaction mixture is then stirred at 0°C for 33 hr and monitored by silica TLC (3:1 CH
2Cl
2:Et
2O v/v) until complete. At this point, the mixture is warmed to room temperature, diluted with
500 mL of dichloromethane, and
sodium metabisulfite (285 g, 1.5 mol) is added in several portions while the internal temperature is maintained at room temperature with an
ice bath as needed. After addition is complete and the exothermic reaction has subsided, stirring is continued at room temperature for 1 hr (Note
8). Anhydrous
sodium sulfate (50 g) is added and the mixture is stirred at room temperature overnight (Note
9). The suspension is filtered through a
20-cm Büchner funnel, the filtrand is rinsed thoroughly with
acetone (3 × 250 mL), and the filtrate is concentrated to a brown paste (Note
10). The paste is dissolved in
3.5 L of ethyl acetate, transferred to a
6-L separatory funnel, and washed sequentially with water (2 × 500 mL) (Note
11), 0.25 M
sulfuric acid (2 × 500 mL) (Note
12), and
brine (1 × 500 mL). The initial, aqueous washes are kept separate from the subsequent acid washes which are retained for alkaloid recovery (Note
13) and (Note
14). The organic layer is dried (Na
2SO
4), and concentrated to give the crude diol in quantitative yield (2
22.7 g, 1.04 mol,
104%). The ee of the crude product is determined by
1H NMR analysis of the derived bis-Mosher ester to be 90%. One recrystallization
3 from hot aqueous
95% ethanol (3 mL/g) affords
155–162 g (
72–75%) of enantiomerically pure
stilbene diol as a white solid, mp
144.5–146.5°C, [α]
25D 90.0° (abs EtOH,
c 1.96) (Note
15).