Page 190 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

178 hydrolysis, oxidation and reduction

. Anhydrous methanol degassed for 20 minutes with nitrogen, 5 mL
. Ethyl acetate, diethyl ether
. Silica gel 60 (0.063±0.04 mm)

. 10 mL Glass liner adapted to the high pressure reactor
. Magnetic stirrer hot plate with a thermostatically controlled oil-bath and
thermometer
. 25 mL High pressure reactor
The reaction can be performed at atmospheric pressure using a low-
pressure hydrogenation apparatus fitted with a gas burette system.

Procedure

1. A 10 mL glass liner equipped with a magnetic stirrer bar was dried in an
oven at 120 8C overnight, cooled in a desiccator under vacuum and then
flushed with nitrogen.
2. The liner was filled under nitrogen with dimethyl itaconate (177 mL, 200 mg)
and the catalyst [(COD)Rh(S,S)-Me-BPE] (0.7 mg) and then placed in a
25 mL high pressure reactor.
3. The reactor was flushed six times with hydrogen (the bomb was pressurized
at 200 psi, then the gas inlet was closed before the hydrogen was slowly
vented off). Degassed anhydrous methanol (5 mL) was added and the re-
actor was pressurized to an initial pressure of 50 psi H 2 . The reaction was
allowed to stir at 20 8C until no further hydrogen uptake was observed (2
hours).
4. The reaction was followed by chiral GC (SE 30, 100 8C isotherm, nitrogen
mobile phase). R t (dimethyl itaconate): 6.8 min; R t (dimethyl methylsucci-
nate): 5.7 min.
5. The reaction was then concentrated and the residue was passed through a
short column of silica gel eluting with ethyl acetate±diethyl ether (1:1) to
remove the catalyst. The (S)-dimethyl methylsuccinate does not need any
further purification (190 mg, 95 %).
. The ee (95 %) was determined by chiral GC (Lipodex 1 E, 25 m, 0.25 mm
ID, temperatures: column 75 8C isotherm, injector 250 8C, detector
250 8C, mobile phase helium, sample dissolve in methanol) R t (R)-enan-
tiomer: 39.3 min R t (S)-enantiomer: 41.2 min.
. 1 H NMR(200 MHz, CDCl 3 ): d3:70 (s, 3H, CO 2 CH 3 ); 3.69 (s, 3H,
CO 2 CH 3 ); 2.92 (m, 1H, CH); 2.76 (dd, J 16.5 Hz, J 8.2 Hz, 1H,
CH a H b ); 2.42 (dd, J 16.5 Hz, J 6.0 Hz, 1H, CH a H b ); 1.23 (d, J 7.1 Hz,
3H, CH 3 ).
ÿ1
. IR (CHCl 3 , cm ): 3031, 2957 (C±H aliphatic), 1727 (CˆO), 1463, 1437,
1353, 1280 (C±O), 1167, 1059, 1007.
‡
. Mass: calculated for C 7 H 13 O 4 : m/z 161.08138; found [MH] 161:08154.