Development of dynamic kinetic resolution on large scale for (±)-1-phenylethylamine

• Lisa K. Thalén and
• Jan-E. Bäckvall

Beilstein J. Org. Chem. 2010, 6, 823–829, doi:10.3762/bjoc.6.97

• -phenylethyl)acetamide (3) in good yield and high ee when alkyl methoxyacetates were used as acyl donors compared to when isopropyl acetate was used as the acyl donor. The catalyst loading could be decreased to 1.25 mol % Ru-catalyst 4 and 10 mg CALB per mmol 1 when alkyl methoxyacetates were used as the acyl

• were observed when the reaction mixture was concentrated from 0.06 M to 0.13 M (Table 1, entries 1 and 7, respectively). The parameters were then changed concurrently to find a balance between the rate of acylation and racemization at lower catalyst loadings. When the Ru-catalyst loading was decreased

• to 2 mol % and the reaction concentration was increased to 0.25 M, the amide 2 could be obtained in 77% yield with 99% ee (Table 2, entry 1). When the Ru-catalyst loading was further decreased to 1 mol%, and the amount of CALB or acyl donor was increased, a decrease in the enantioselectivity of the

Large- scale ruthenium- and enzyme- catalyzed dynamic kinetic resolution of (rac)-1-phenylethanol

• Krisztián Bogár,
• Belén Martín-Matute and
• Jan-E. Bäckvall

Beilstein J. Org. Chem. 2007, 3, No. 50, doi:10.1186/1860-5397-3-50

• larger scale and the results are summarized in Table 1. On a 10 mmol-scale, 1 mol% of Ru-catalyst 1 can be used to achieve 90% yield of acetate 3 (99% ee) after 18 h at room temperature (entry 1). A decrease of the catalyst loading to 0.5 mol% afforded 87% of enantiopure acetate, although a longer

• high efficiency of the latter reaction suggests that the racemization catalyst loading can be further decreased, and that an increased reaction temperature may facilitate this decrease. Indeed, a DKR reaction at 70°C on a 1 mol-scale employing only 0.05 mol% Ru-catalyst in a more concentrated reaction

• . Under optimized reaction conditions, DKR of 1-phenylethanol (2) was performed delivering 159 g (97% yield) of enantiomerically pure (R)-1-phenylethanol acetate (3) in a short reaction time (20 h) using 0.05 mol% of Ru-catalyst 1, and small amounts of enzyme. The employed heterogeneous biocatalyst