Catalysis of Organic..

464 Chiral 2-Amino-1-Phenylethanolparameters the reduction was run at 65°C using a BH 3 : ketone : catalyst ratio of0.6 : 1 : 0.003. Reduction of a 0.9 M solution of 2 in THF under these conditionsgave the chiral chloroalcohol (4) with 95-96% ee at 100% conversion. Theaminoalcohol (1) was produced by treating a methanol solution of 4 with a largeexcess of 30% NH 4 OH at room temperature for 2-3 days. After evaporation of themethanol, 1 was isolated as a crude product having an ee of 95% in 85% yield.O2ClPh PhON B H OHH OH3 CH 3ClNH 2(Eqn. 1)BH 3NH 4 OH41Even though 2 was successfully converted to 4 by a chiral transferhydrogenation (10), attempts at running a classic Noyori hydrogenation of 2 wereunsuccessful. Trying to hydrogenate a primary aminoketone would only lead toproblems arising from self condensation. A blocked amine group was needed. Thephthalimido ketone (5) could easily be prepared by reaction of 2 with potassiumphthalimide. It has been reported that 5 could be hydrogenated enantioselectivelyusing a chiral rhodium catalyst but the reaction only took place at high pressures(11). Another problem with the use of 5 as a precursor in the preparation of 1 wasthe very low solubility of 5 in methanol or i-propanol which are the solvents we usedin the Noyori hydrogenations. However, the analogous succinimide, 6, wassufficiently soluble under the hydrogenation conditions and was, therefore, used inthe screening of the various ligands, diamines and bases used in the Noyorihydrogenation (Eqn. 2).The ligands tested were: tol-binap, dipamp, P-phos, xyl-P-phos, binam, phanephosand xyl-phanephos with the results lised in Table 1. Table 2 shows the effect whichO2ClON - K +OON - K +OO5ONOON6OONoyoriHydrogenationHHOOH7NAq. NaOHOOHNH 21(Eqn. 2)