Spontaneous Resolution of Julia-Kocienski Intermediates Facilitates Phase Separation to Produce <i>Z</i>- and <i>E</i>‑Monofluoroalkenes

The monofluoroalkene motif is important in drug development as it serves as a peptide bond isostere and is found in a number of biologically active compounds with various pharmacological activities. Direct olefination of carbonyl compound is a straightforward way to prepare monofluoroalkenes; however, these methods often result in a mixture of Z- and E-isomers that cannot be easily separated. We discovered a unique spontaneous resolving reaction that simultaneously addresses the problems in the synthesis and separation of Z- and E-monofluoroalkenes. The reaction is accompanied by a highly efficient spontaneous kinetic resolution and phase labeling of monofluoroalkene precursors which allows the separation of Z- and E-monofluoroalkenes by liquid–liquid extraction. The application of the method is demonstrated by the synthesis and separation of potential anticancer agents, which are inseparable by HPLC.