New Method for Trifluoromethylation of Enolate Anions and Applications to Regio-, Diastereo- and Enantioselective Trifluoromethylation

Article abstract of DOI:10.1021/jo00098a030

Assessment was made of the effectiveness of different boron Lewis acids in mediating the trifluoromethylation of reactive enolate anions with S- and Se-(trifluoromethyl)chalcogen salts.Treatment of potassium or lithium enolates derived in situ from carbonyl compounds or enol trimethylsilyl ethers with S-(trifluoromethyl)dibenzothiophenium triflate (1) in the presence of 2-phenyl-1,3,2-benzodioxaborole (4) produced trifluoromethylated carbonyl compounds in high yields.In this manner, various α-CF3 ketones, γ-CF3-α,β-unsaturated ketones, and an α-CF3 ester were synthesized.Perfluorooctylation was similarly conducted using S-(perfluorooctyl)dibenzothiophenium triflate and 4.Thus, a balance of the reactivity of the reactants was essential for these electrophilic perfluoroalkylations.The deprotonation of 2-methylcyclohexanone with KN(SiMe3)2 followed by trifluoromethylation gave the 6-trifluoromethylated product regioselectively.In the trifluoromethylation of potassium enolate 16 of 4,4a,5,6,7,8-hexahydro-4a-methyl-2(3H)-naphthalenone, the use of bulky 2-mesitylphenanthro<9,10-d>-1,3,2-dioxaborole (15) led to the diastereoselective formation of the thermodynamically less stable CF3-isomer 17β.For enantioselective trifluoromethylation, optically active (S)-4-phenyldinaphtho<2,1-d:1',2'-f><1,3,2>dioxaborepin (19) and its 3,3'-diphenyl derivative 20 were synthesized.The trifluoromethylation of the potassium enolate of propiophenone with 1 in the presence of 20 afforded optically active α-CF3-propiophenone in 45percent ee yield.Thus, a new and versatile method for selective trifluoromethylation has been developed.