NEW METHOD FOR TRIFLUOROMETHYLATION OF ENOLATE ANIONS AND APPLICATIONS TO REGIOSELECTIVE, DIASTEREOSELECTIVE AND ENANTIOSELECTIVE TRIFLUOROMETHYLATION

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. Iq this manner, various alpha-CF3 ketones, gamma-CF3-alpha,beta-unsaturated ketones, and an alpha-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(SiMe(3))(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 diastereo-selective formation of the thermodynamically less stable CF3-isomer 17 beta. 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 alpha-CF3-propiophenone in 45% ee yield. Thus, a new and versatile method for selective trifluoromethylation has been developed.