Enantioselective construction of quaternary stereogenic centres possessing a fluorine atom

Abstract

Fluorination of methyl (1R,3R,4S)-8-phenylmenthyl methylmalonates 2 using lithium hexamethyl-disilazide and 1-fluoro-2,4,6-trimethylpyridinium triflate (trifluoromethanesulfonate), gave the (R)-3 and (S)-4 isomers in a 3.8 : 1 ratio, while fluorination of ethyl-, propyl- and benzyl-malonates 10, 11 and 12 provided the (R)-13, 15 and 17 and (S)-14, 16 and 18 isomers in a 1 : 1.6–2.0 ratio. On the other hand, alkylation of (1R,3R,4S)-8-phenylmenthyl hydrogen fluoromalonates 26 in the presence of lithium hexamethyldisilazide, followed by esterification with diazomethane, produced the (R)-3,13,15,17- and 27 and (S)-4,14,16,18 and 28 isomers in a 1 : 5.7–35 ratio.