Asymmetric synthesis of bicyclic diol derivatives through metal and enzyme catalysis: application to the formal synthesis of sertraline.
Enzyme- and ruthenium-catalyzed dynamic kinetic asymmetric transformation (DYKAT) of bicyclic diols to their diacetates was highly enantio- and diastereoselective to give the corresponding diacetates in high yield with high enantioselectivity (99.9 % ee). The enantiomerically pure diols are accessible by simple hydrolysis (NaOH, MeOH), but an alternative enzyme-catalyzed ester cleavage was also used to give the trans-diol (R,R)-1 b in extremely high diastereomeric purity (trans/cis=99.9:0.1, >99.9 % ee). It was demonstrated that the diols can be selectively oxidized to the ketoalcohols in a ruthenium-catalyzed Oppenauer-type reaction. A formal enantioselective synthesis of sertraline from a simple racemic cis/trans diol 1 b was demonstrated.
Krumlinde
Patrik
P
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 106 91 Stockholm, Sweden.
Bogár
Krisztián
K
Bäckvall
Jan-E
JE
D000438:Alcohols / Q000737:chemistry*; D055162:Biocatalysis; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D006868:Hydrolysis; D007700:Kinetics; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D020280:Sertraline / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000438:Alcohols; D001643:Bridged Bicyclo Compounds; D009942:Organometallic Compounds; D012428:Ruthenium; D020280:Sertraline