Large-scale ruthenium- and enzyme-catalyzed dynamic kinetic resolution of (rac)-1-phenylethanol.
The scale-up of the ruthenium- and enzyme-catalyzed dynamic kinetic resolution (DKR) of (rac)-1-phenylethanol (2) is addressed. The immobilized lipase Candida antarctica lipase B (CALB) was employed for the resolution, which shows high enantioselectivity in the transesterification. The ruthenium catalyst used, (eta 5-C5Ph5)RuCl(CO)2 1, was shown to possess very high reactivity in the "in situ" redox racemization of 1-phenylethanol (2) in the presence of the immobilized enzyme, and could be used in 0.05 mol% with high efficiency. Commercially available isopropenyl acetate was employed as acylating agent in the lipase-catalyzed transesterifications, which makes the purification of the product very easy. In a successful large-scale DKR of 2, with 0.05 mol% of 1, (R)-1-phenylethanol acetate (3) was obtained in 159 g (97% yield) in excellent enantiomeric excess (99.8% ee).
Bogár
Krisztián
K
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden. krisztian.bogar@astrazeneca.com
Martín-Matute
Belén
B
Bäckvall
Jan-E
JE