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

Abstract

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 cis-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-α-bromo-α, α-difluoroacetal can cyclize onto the olefinic part regiospecifically to give γ-lactols in good yield. The lactols are then converted to the corresponding α, α-difluoro-γ-lactones. Systematic synthesis of multifluorinated-α, α-difluoro-γ-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.