Highly Stereoselective Synthesis of Trifluoromethylated Compounds via Ester-Enolate [2,3]-Wittig and [3,3]-Ireland−Claisen Rearrangements

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Abstract
γ-Trifluoromethylated propargylic alcohols have been obtained in optically pure forms via effective enzymatic kinetic resolution and then converted into (E)- or (Z)-allylic alcohols. [2,3]-Wittig rearrangement of the corresponding [[γ-(trifluoromethyl)allyl]oxy]acetic acid methyl esters afforded α-hydroxy-β-(trifluoromethyl)-γ,δ-unsaturated carboxylic acid methyl esters in good yields. The rearrangement of (Z)-substrates proceeded in a highly stereoselective manner to give anti-isomers with E configuration at a newly created olefinic bond via complete chirality transfer. (E)-Substrates, however, showed relatively low stereoselectivities resulting in mixtures of syn- and anti-products. The trifluoromethylated allylic alcohols were also converted into the corresponding α-methoxyacetic acid γ-(trifluoromethyl)allyl esters and evaluated as substrates for [3,3]-Ireland−Claisen rearrangement. (E)-Substrates were efficiently transformed into syn-products while (Z)-substrates exhibited relatively low stereoselectivities. The two complementary methods provide facile routes to highly functionalized trifluoromethyl-containing molecules with a high degree of stereocontrol.