Enzymatic kinetic resolution and chemoenzymatic dynamic kinetic resolution of delta-hydroxy esters. An efficient route to chiral delta-lactones.
A successful kinetic resolution of a racemic mixture of delta-hydroxy esters 1 was obtained via lipase-catalyzed transesterification (E value up to 360). The combination of the enzymatic kinetic resolution with a ruthenium-catalyzed alcohol racemization led to an efficient dynamic kinetic resolution (ee up to 99% and conversion up to 92%). The synthetic utility of this procedure was illustrated by the practical syntheses of delta-lactones (R)-6-methyl- and (R)-6-ethyl-tetrahydropyran-2-one and (S)-5-(tert-butyldimethylsiloxy)heptanal. The former are important building blocks in the synthesis of natural products and biologically active compounds, and the latter is a key intermediate in the synthesis of widely used commercial insecticide Spinosyn A.
Pàmies
Oscar
O
Arrhenius Laboratory, Department of Organic Chemistry, Stockholm University, SE-106 91 Stockholm, Sweden.
Bäckvall
Jan-E
JE
D001230:Aspergillus / Q000201:enzymology; D002175:Candida / Q000201:enzymology*; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D004951:Esterification; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D005561:Formates / Q000737:chemistry; D005656:Fungal Proteins; D007700:Kinetics; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D008049:Lipase / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012428:Ruthenium / Q000378:metabolism*; D013237:Stereoisomerism
D004952:Esters; D005561:Formates; D005656:Fungal Proteins; D007783:Lactones; C030544:formic acid; D012428:Ruthenium; D008049:Lipase; C431349:lipase B, Candida antarctica