As shown in
f.htmigure 1, a dry,
1-L, three-necked flask is equipped with an
overhead stirrer bearing a
four-bladed propeller of ca. 2.5-cm diameter driven by a strong, safely connected motor A (Note
1), a
rubber septum, and a
three-way stopcock. The air in the flask is replaced by dry
argon or
nitrogen, the pressure of which is maintained during the reaction at ca. 50 mm above atmospheric pressure with a mercury bubbler (Note
2). A second stirrer (
m.htmotor B, Figure 1) to agitate the bath is attached next to the flask with the propeller just below the bottom of the flask. Finally, a
4.5-cm × 20-cm test tube is held next to the bath stirrer. The entire apparatus
(.htmFigure 1) is mounted well above the bench to allow for immersion of the flask,
bath stirrer, and tube into
cooling baths and for exchange of bulky
bath containers with the aid of a lab jack. The flask is charged (Note
3) with
400 mL of 2-methylbutane (isopentane) (Note
4) and
24.6 g (27.5 mL, 0.12 mol) of (S,S)-( + )-N,N,N',N'-tetramethyl-1,4-diamino-2,3-dimethoxybutane (DDB) (Note
5). A
methanol–dry ice bath is raised to immerse the flask and cool the contents to −78°C with slow stirring, whereupon
0.021 mol of butyllithium (13.5 mL of a 1.56 M solution in hexane) (Note
6) is added within a few minutes. A second cooling bath is prepared in a ca.
7-L Dewar cylinder (Note
7) by pouring liquid
nitrogen into a stirred (
glass rod) mixture of
methylcyclohexane/
isopentane (3 : 2) (Note
8) until about half of the liquid has solidified and a slush has been formed, the temperature of which is ca. −140°C (Note
9). The reaction flask is cooled to the lower temperature by exchanging baths and waiting for 15 min with bath stirring. The bath is temporarily lowered and cooled until again half frozen by pouring in liquid
nitrogen and manual agitation (Note
10). From then on, cooling is kept constant by filling the tube in the stirred bath at intervals with liquid
nitrogen (Note
10). A solution of
2.12 g (0.020 mol) of benzaldehyde (Note
11) in
20 mL of isopentane (Note
4) is added dropwise (Note
12) over 15 min to the vigorously stirred (ca. 1000 rpm) reaction mixture. After completion of the addition (ca. 0.5 hr), the bath is removed, the flask is warmed to ca. 0°C (Note
13), and the contents are poured into a
1-L separatory funnel containing
150 mL of ice-cold 2 N aqueous hydrochloric acid. The aqueous layer is extracted twice with
70 mL of hexane and saved for recovery of the chiral auxiliary agent
DDB (Note
14). The combined organic layers are sequentially washed with saturated aqueous bicarbonate and
sodium chloride solutions and concentrated in a
rotary evaporator to ca. 200 mL. The solution is then transferred to a
500-mL separatory funnel and vigorously shaken with
40 mL of a saturated aqueous sodium bisulfite solution to precipitate the bisulfite adduct of unreacted
benzaldehyde (Note
15). After filtration (if necessary) the residue and the aqueous phase are washed with
hexane. The combined organic solution is dried over anhydrous
magnesium sulfate and concentrated by rotary evaporation. Simple distillation yields
2.60–2.95 g (
80–90%) of
1-phenyl-1-pentanol, bp
54–56°C (0.02 mm),
[α]D = 6.13° (neat), (Note
16), optical yield
30% (Note
17).