A flame-dried, 500-mL Schlenk flask equipped with a magnetic stirring bar, dropping funnel sealed with a rubber septum, and an argon balloon is loaded under an atmosphere of argon with 18.7 g (90 mmol) of (−)-(S)-ethyl 2-(benzyloxy)propanoate and the compound is dissolved in anhydrous diethyl ether (180 mL). The reaction mixture is cooled to −78°C by means of a cooling bath (dry ice/ethanol). A 1 M solution of diisobutylaluminum hydride (DIBAH) in hexane (126 mL, 126 mmol) is added very slowly dropwise to the solution of the ester and stirring is continued for at least 1 hr after the complete addition of the DIBAH solution. Upon complete consumption of the ester, the crude reaction mixture is poured directly with vigorous stirring into 360 mL of ice cold 4 N hydrochloric acid. The aqueous phase is extracted with diethyl ether (4 × 180 mL) and the combined organic extracts are washed with 50 mL of aqueous saturated NaCl solution. After drying over MgSO 4 , filtration and removal of the solvents under reduced pressure by means of a rotary evaporator, 14.4 g (98%) of the crude aldehyde is obtained.

    A flame-dried, 1-L, round-bottomed flask equipped with a Teflon-coated magnetic stirring bar is charged with 2.95 g (73.9 mmol) of 95% lithium aluminum hydride under a nitrogen atmosphere. The flask is sealed with a rubber septum containing a needle adapter to an argon-filled balloon and is charged with 170 mL of hexanes. The septum is removed and the flask is equipped with an oven-dried, 25-mL, pressure-equalizing addition funnel sealed with a rubber septum containing a needle adapter to an argon-filled balloon. The reaction flask is cooled to 0°C in an ice-water bath, the addition funnel is charged with 10.7 mL (109 mmol) of ethyl acetate, and slow, dropwise addition of ethyl acetate is initiated and completed within 1.25 hr. Upon completion of the addition, the addition funnel is removed, the reaction vessel is sealed with a rubber septum containing a needle adapter to an argon-filled balloon, and the reaction flask is cooled to −78°C in a dry ice-acetone bath. A solution of 10.0 g (32.1mmol) of (1S,2S)-pseudoephedrine-(R)-2-methylhydrocinnamamide in 110 mL of tetrahydrofuran is added to the cold suspension of lithium triethoxyaluminum hydride [LiAlH(OEt) 3 ] via cannula over 5 min. Upon completion of the addition, the dry ice-acetone bath is removed and the reaction mixture is warmed to 0°C in an ice-water bath. During the course of warming, substantial gas evolution is observed and vented using a needle as necessary. The reaction mixture is stirred at 0°C for 1 hr, then transferred via a wide-bore cannula into a vigorously stirring solution of 400 mL of 1 N aqueous hydrochloric acid solution and 25 mL (325 mmol) of trifluoroacetic acid in an argon-purged, three-necked, 2-L, round-bottomed flask equipped with a mechanical stirrer and two rubber septa on the side-arms, one containing a needle adapter to an argon-filled balloon. A quantitative transfer is effected with 10 mL of tetrahydrofuran, and the biphasic hydrolysis mixture is stirred vigorously for 5 min at 23°C, then is poured into a 2-L separatory funnel containing 700 mL of 1 N aqueous hydrochloric acid solution. After the layers are shaken vigorously, they are separated and the aqueous layer is further extracted with three 150-mL portions of ethyl acetate. The combined organic layers are extracted with 250 mL of saturated aqueous sodium bicarbonate solution with care to avoid excessive build-up of pressure in the separatory funnel. The aqueous phase is separated and extracted with 100 mL of ethyl acetate. This ethyl acetate extract is combined with the other organic extracts, and the resulting solution is dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by flash column chromatography (230-400 mesh silica gel, 270 g, packed with hexanes and eluted with 7.5% ethyl acetate-hexanes) to afford 3.64 g (76%) of (R)-α-methylbenzenepropanal as an oil. The enantiomeric excess (ee) of this product is determined to be 95%.