Page 162 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

asymmetric reduction using nonmetallic catalysts 149

. Oxazaphosphinamide (N-(di-p-anisylphosphoryl)-(S)-a, a-diphenyl-2-pyr-
rolidine methanol), 50 mg, 0.1 mmol, 0.1 eq*
The catalyst was prepared by reaction of (S)-diphenylprolinol with
dimethylphosphinite and triethylamine in the presence of carbon tetrachlor-
ide. The N-(O,O-dimethylphosphoryl) derivative obtained was treated with
an excess of p-anisylmagnesium bromide to give the oxazaphosphinamide
catalyst [13] .
. Borane dimethyl sulfide complex 2 M solution in tetrahydrofuran, 0.5 mL,
1 mmol, 1 eq
. Petroleum ether, ethyl acetate, triethylamine
. Saturated aqueous solution of NH 4 Cl, 10 mL
. Brine
. Magnesium sulfate
. Silica gel 60 (0.063±0.04 mm)
. p-Anisaldehyde dip

. 50 mL Two-necked dry round-bottomed flask with a magnetic stirrer bar
. Magnetic stirrer hot plate with a thermostatically controlled oil bath and
thermometer
. Dean and Stark apparatus
. Condenser
. Syringe, 3 mL
. Syringe pump
. Separating funnel, 250 mL
. Rotary evaporator
. Kugelrohr apparatus

Procedure
1. A 50 mL two-necked round-bottomed flask (dried overnight at 150 8C and
cooled under vacuum) was equipped with a Dean and Stark apparatus and
flushed with nitrogen.
2. The flask was filled with the catalyst (50 mg) and anhydrous toluene (4 mL).
The mixture was refluxed until 3.5 mL of solvent was recovered. The catalyst
was azeotroped twice with toluene (4 mL) and then cooled to room tempera-
ture under argon.
Precautions were taken whilst azeotroping the catalyst with toluene: thus
the use of freshly dried toluene and flame-dried glassware were necessary to
ensure anhydrous conditions.
3. The Dean and Stark apparatus was removed, replaced by a condenser (the
solution was flushed continuously with nitrogen) and the catalyst dissolved in
anhydrous toluene (2 mL). Borane±dimethylsulfide (0.5 mL of a 2 M solution
in tetrahydrofuran) was added to the mixture, which was heated to 110 8C.

* The catalyst was kindly provided by Prof. M. Wills (University of Warwick, Coventry, UK).