Asymmetric Synthesis of Novel gem-Difluorinated Compounds Using Chemo-Enzymatic Methodology

摘要

Asymmetric synthesis of two types of partly difluorinated compounds has been accomplished based on the chemo-enzymatic reaction strategy. Optically active 1,1-difluoro-2,3-(bishydroxymethyl) cyclopropane has been synthesized through lipase-catalyzed reaction;prochiral diacetate of s-1,1-difluoro-2,3-bis(hydroxymethyl)cyclopropane was converted to the corresponding monoacetate through Alcaligenes sp. lipase-catalyzed hydrolysis with >99% enantiomeric excess. Racemic acetate of trans-1,1-difluoro-2,3-bis(hydroxymethyl) cyclopropane was resolved by Pseudomonas sp. lipase-catalyzed hydrolysis successfully. Lipase-catalyzed reaction was employed to resolve bis-difluorocyclopropane derivatives; the first synthesis of optically pure (trans, trans)-2,2,5,5-tetrafluoro-1,6-bis(hydroxymethyl) bicyclopropane has thus been accomplished. Carbon radicals from allyl O-trimethylsilyl-#alpha#-bromo-#alpha#,#alpha#-difluoroacetal can cyclize onto the olefinic part regiospecifically to give #gamma#-lactols in good yields. The lactols are then converted to the corresponding #alpha#,#alpha#-difluoro-#gamma#-lactones. Systematic synthesis of multifluorinated-#alpha#,#alpha#-difluoro-#gamma#-lactones has been accomplished through intramolecular radical cyclization as a key reaction. The synthesis of difluorinated analogue of an insect sex pheromone has been accomplished through intramolecular radical cyclization and lipase-catalyzed reaction.