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

gamma-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 [[gamma-(trifluoromethyl)allyl]oxy]acetic acid methyl esters afforded alpha-hydroxy-beta-(trifluoromethyl)-gamma,delta-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 alpha-methoxyacetic acid gamma-(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.