✍ Scribed by Russell J. Linderman; Kirollos S. Kirollos
No coin nor oath required. For personal study only.
Tritluoromethyl substituted quinolines have been prepared by 1,2-or 1,4-addition of anilines to trifluoroacetyl acetylenes followed by intramolecular acid catalyzed ring closure.
Recently considerable interest has been dimcted toward the synthesis of trifluorometbyl substituted heteroaromatic compoundsl. due in part to the unique biological properties imparted by fluorine.2 For example, mefloquine, a trifluoromethylated quinoline, has been developed as an antimalarial agent in response to increased resistance to existing drugs. 3 Several non-regiospecific approaches to CF3 substituted quinolines are known, typically providing access to 2-CF3 substituted quinolines4 or quinolones5 in modest yields. More recently, Pastor and co-worker& achieved improved yields for 2-Rf substituted quinolines from Rf alkynyl esters. Methods for the regioselective synthesis of 4-CF3 substituted quinolines have not been reported. We now wish to report preliminary data on the regiocontrolled synthesis of 4-CF3 substituted quinolines from trifluoroacetyl (TPA) acetylenes.
Significantly, the CF3 group ultimately is derived from trifluoroacetic acid rather than an expensive CF3 substituted aniline.
Regioselective 1,4-addition of a wide variety of anilines to TPA acetylenes is a facile reaction, providing the p-TFA enamine in good yield, see Table . Only the Z-isomer was observed for 1" amines, while 2' amines or thiols produced a mixture of E and Z isomers.7a Hojo et a17b recently reported an addition/elimination sequence leading to p-TFA enamines from p-TFA enol ethers. To prepare aunsubstituted enamines such as 2, we also employed the addition/elimination sequence.7 The yields for isomerically pure enamines l-7 are given in the Table.
📜 SIMILAR VOLUMES