Synthesis of Perfluoroalkyl-1H-benzo[c]quinolizin-l-one Derivatives from 2-Methylquinolines

Abstract

As an extension of our synthetic investigation on heterocycles using silicon reagents, preparation of perfluoroalkyl-1 H-benzo[ c ]quinolizin-1-onesw as studied. An addition-cyclization reaction of perfluoro(2-methyl-2-pentene) [ 2 ] with a 2-quinolylmethyl carbanion generated from 2-(trimethylsilylmethyl)quinoline [3 a] in the presence of a catalytic amount of tetrabutylammonium fluoride (TBAF) afforded 3-pentafluoroethyl-2-trifluoromethyl-1 Hbenzo[c ]quinolizin-1-one [6 a] in 36% yield, accompanied with the corresponding adduct [4 a] and E/Z alkenes [5 a] (1, 29 and 11% yields, respectively). These intermediate compounds [4 a] and E/Z-[5 a] were effectively transformed into the final product [6 a] on heating in wet xylene. An equilibrium constant K_E-Z for E-Z isomerization of [5 a] was 2.44 in refluxing dry tetrahydrofuran (THF) and the calculated ΔG_E→Z was 2.5 x 10³ J⋅ K^-1mol^-1. Under the optimized conditions ([3]:[2]: [KF] =1: 3: 1; at -5°C for 3 h in THF, then refluxed for 6 h in xylene after quenching with water and replacement of the solvent), the reaction of [3a] or the methyl- or chloro-substituted analogs gave the corresponding 1 Hbenzo[c ]quinolizin-1-one derivatives [6a]-[6e] in 93 (substituent R =H), 92 (R =6-CH_, ), 83(R = 8 -CH₃), 90(R =8-Cl), 86%, (R =10-Cl) yields, respectively, and 5-methyl-3-pen tafluoroethyl2-trifluoromethyl-1 H-benzo[ c ]quinoxalizin-1-one [6 f] in 35% yield.