Stereoselective Carbonyl Olefination with Fluorosulfoximines: Facile Access to Z or E Terminal Monofluoroalkenes

Terminal monofluoroalkenes are important structural motifs in the design of bioactive compounds, such as homeostasis regulators and mechanism‐based enzyme inhibitors. However, it is difficult to control the stereoselectivity of known carbonyl olefination reactions, and olefin metathesis is limited to disubstituted terminal monofluoroalkenes. Although sulfoximines have been used extensively in organic synthesis, reports on their use in carbonyl olefination reactions have not appeared to date. Herein, we report highly stereoselective carbonyl monofluoroolefination with a fluorosulfoximine reagent. The potential of this method is demonstrated by the synthesis of MDL 72161 and by the late‐stage monofluoromethylenation of complex molecules, such as haloperidol and steroid derivatives. Showing off new skills: Fluorinated sulfoximines, which are known to be fluoroalkylation reagents for the asymmetric synthesis of organofluorine compounds, have now been found to act as carbonyl‐olefination reagents. This newly discovered reactivity was used to tackle the long‐standing challenge of the stereoselective synthesis of terminal monofluoroalkenes from the corresponding aldehydes or ketones (see scheme).