CsF-catalyzed nucleophilic trifluoromethylation of trans-enones with trimethyl(trifluoromethyl)silane: A facile synthesis of trans-α-trifluoromethyl allylic alcohols

Abstract

(matrix presented) Reactions of trans-enones, R-C=C-COR′ (R = Ph, Me, -C=CH-CH=C-S; R′ = Ph, Me, Et, CF3) (1a-e), with TMS-CF3 in the presence of catalytic amounts of cesium fluoride (CsF) in ethylene glycol dimethyl ether led to the formation of the corresponding trans-α-trifluoromethyl silyl ethers, R-C=C-C(OSiMe3)(CF3)R′ (R = Ph, Me, -C=CH-CH=C-S; R′ = Ph, Me, Et, CF3) (2a-e), in essentially quantitative yield. On hydrolysis with aqueous HCI, the corresponding trans-α-trifluoromethyl allylic alcohols, R-C=C-C(OH)(CF3)R′ (R = Ph, Me, -C=CH-CH=C-S; R′ = Ph, Me, Et, CF3) (3a-e), were formed in >90% isolated yield. Under similar reaction conditions, 2-cyclohexen-1-one (1f) also gave trifluoromethyl allylic alcohols (3f) in 92% yield. The intermediates (2a-f) and products (3a-f) are liquids and were characterized by IR, 1H, 19F and 13C NMR, MS, and high-resolution mass spectroscopy (HRMS).