Page 183 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

170 hydrolysis, oxidation and reduction

Procedure

1. The 100 mL round-bottomed flask, equipped with a magnetic stirrer bar,
was dried in an oven at 120 8C overnight. The flask was removed, sealed,
cooled and flushed with nitrogen.
2. l-Histidine (50 mg) was placed in the flask. The flask was again flushed with
nitrogen. Tetrahydrofuran (30 mL) was added and the mixture was stirred.
l-Histidine is sparingly soluble in tetrahydrofuran.
3. To this stirring mixture at ambient temperature was added n-butyllithium
(0.32 mL of a 2 M solution in hexane) dropwise. The resulting solution was
stirred at ambient temperature for 30 minutes.
4. The clear mixture was cooled to 0 8C, and freshly distilled tetramethylene
diamine (1 mL) was added. The system was stirred for 10 minutes after the
addition.
Tetramethylethylene diamine is hygroscopic.
5. Trimethoxysilane (0.38 mL) was added and the solution allowed to stir for
an additional 10 minutes.

Triethoxysilane and especially trimethoxysilane are rather toxic com-
pounds (they may cause blindness if allowed to get into contact with
eyes) and therefore care must be taken in their handing. Both need to be
manipulated very carefully with suitable gloves, eyes face protection, in a
well ventilated fume-hood. However, both can be handled without prob-
lems via syringe techniques.
Although both triethoxysilane and trimethoxysilane are useful in these
reactions, the latter reacts much more rapidly and, therefore is more con-
venient than the former.
6. Acetophenone (0.35 mL) was added and the resulting system was allowed to
stir overnight at 0 8C.
7. The reaction was removed from the cooling bath and quenched with the
addition of sodium hydrogen carbonate (20 mL), with vigorous stirring that
was continued for 30 minutes at room temperature.
Care must be taken in controlling the quenching time of the reaction.
It was found that longer quenching times resulted in crude reaction mix-
tures that were difficult to effectively separate (lower product yields were
obtained).
8. The biphasic system was transferred to a separatory funnel (250 mL) and
extracted with ether (3 40 mL). The organic fractions were combined. The
solvent was removed using a rotary evaporator, to produce a yellow oil and
a white solid (polymerized trimethoxysilane).
9. The crude material was purified using flash silica gel chromatography
eluting with pentane/ether (3:1). This provided 0.31 g (85 %) phenethanol.
1 19
H NMR and/or F NMR analysis of the Mosher ester of the resulting
alcohol was used to determine the ee (25±30 %).