Page 175 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

162 hydrolysis, oxidation and reduction

Procedure

1. (S)-a, a-Diphenylpyrrolidinemethanol (127 mg) was placed in a 25 mL
three-necked flask equipped with a magnetic stirrer bar, under nitrogen. A
solution of trimethyl borate (62 mg) in dry tetrahydrofuran (5 mL) was
added. The mixture was stirred for 1 hour at room temperature.
2. 10 M Borane±dimethylsulfide complex (2.0 mL) was added to the resulting
solution. The mixture was cooled to 0±5 8C with an ice-bath, and then a
solution of 2,3-butadione monoxime trityl ether (1.72 g) in dry tetrahydro-
furan (5 mL) was added dropwise via a syringe pump over 1 hour at that
temperature.
3. After being stirred for 0.5 hour at 0±5 8C, the mixture was allowed to warm
to room temperature and heated under reflux for 18 hours. The resulting
mixture was cooled to room temperature and cautiously transferred into 2 N
hydrochloric acid (15 mL) in a 200 mL round-bottomed flask equipped with
a magnetic stirrer bar using diethyl ether (10 mL).
4. After being stirred for 5 hours at room temperature, the mixture was made
basic with sodium hydroxide (2.4 g). The organic solvents were removed
under reduced pressure using a rotary evaporator. The aqueous residue was
washed with diethyl ether (2 10 mL) and then benzyl chloroformate (3.41 g)
was added. The mixture was stirred for 20 hours at room temperature.
5. The resulting mixture was transferred into a separating funnel with methyl-
ene chloride (20 mL) and the phases were separated. The aqueous layer was
extracted with methylene chloride (2 20 mL). The combined organic layers
were dried over magnesium sulfate, filtered and concentrated using a rotary
evaporator.
6. The residue was purified by silica gel column chromatography using n-
hexane±ethyl acetate (3:1 ! 1:1) as an eluent to give as a white solid 3-
benzyloxyamino-2-butanol (1.03 g, 92 %) as a mixture of diastereomers.
The anti/syn ratio (86:14) and the respective ee (anti 99 %, syn 97 %) were
determined by HPLC (Chiralcel OJ chiral column (i.d. 4.6 250 mm), flow
0.5 mL/min, eluent n-hexane±isopropanol 9:1, detection UV 230 nm);
22.9 min for (2S, 3S)-isomer, 26.8 min for (2S, 3R)-isomer, 29.8 min for
(2R, 3R)-isomer, 36.1 min for (2R, 3S)-isomer.
1 H NMR (270 MHz, CDCl 3 ) for anti isomer d 1.11 (d, J 6.7 Hz, 3H), 1.15
(d, J 6.7 Hz, 3H), 2.18 (br, 1H), 3.74 (m, 1H), 3.88 (m, 1H), 4.94 (br, 1H), 5.10
(s, 2H), 7.35 (m, 5H); for syn isomer d 1.18 (d, J 6.7 Hz, 3H), 1.20 (d, J 6.1 Hz,
3H), 1.88 (br, 1H), 3.70 (m, 2H), 4.94 (br, 1H), 5.10 (s, 2H), 7.35 (m, 5H).