The thio-adduct facilitated, enzymatic kinetic resolution of 4-hydroxycyclopentenone and 4-hydroxycyclohexenone.
The addition of 3,4-dimethoxybenzyl thiol 8, as a benzyl thiol surrogate, to racemic 4-hydroxycyclopent-2-enone 2 and 4-hydroxycyclohex-2-enone 15 gave the corresponding cis-adducts (+/-)-3-(3,4-dimethoxybenzylthio)-4-hydroxycyclopentanone 4b and (+/-)-3-(3,4-dimethoxybenzylthio)-4-hydroxycyclohexanone 16 with good diastereocontrol. In both cases, subsequent treatment with vinyl acetate, in the presence of a lipase enabled enantiomer resolution. Thus, (+)-16 and the acetate of its enantiomer, (-)-(1R,2S)-2-(3,4-dimethoxybenzylthio)-4-oxocyclohexyl acetate, (-)-17 were isolated in 98% enantiomeric excess. Based on the 1,4-dioxygenation pattern, (-)-17 can be used to prepare both enantiomers of 4-(tert-butyldimethylsilyloxy)cyclohex-2-enone 19. Firstly, saponification, with a sub-stoichiometric amount of NaOMe, followed by a one-pot silyl ether formation-sulfide elimination sequence gave (+)-19. Then using the same starting material a 6-step sequence, featuring a diastereoselective NaBH4 reduction and a Cope-type sulfoxide elimination, gave (-)-19.
O'Byrne
Aisling
A
Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Dublin 4, Ireland.
Murray
Cian
C
Keegan
Dearbhla
D
Palacio
Carole
C
Evans
Paul
P
Morgan
Ben S
BS
D002175:Candida / Q000201:enzymology; D018360:Crystallography, X-Ray; D003512:Cyclohexanones / Q000737:chemistry* / Q000378:metabolism*; D003517:Cyclopentanes / Q000737:chemistry* / Q000378:metabolism*; D007659:Ketones / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013455:Sulfur / Q000737:chemistry*
C548047:4-hydroxycyclohexenone; C548046:4-hydroxycyclopentenone; D003512:Cyclohexanones; D003517:Cyclopentanes; D007659:Ketones; D013455:Sulfur; D008049:Lipase