Phosphonates have garnered considerable attention for years owing to both their singular biological properties and their synthetic potential. State‐of‐the‐art methods for the preparation of mixed phosphonates, phosphonamidates, phosphonothioates, and phosphinates rely on harsh and poorly selective reaction conditions. We report herein a mild method for the modular preparation of phosphonylated derivatives, several of which exhibit interesting biological activities, that is based on chemoselective activation with triflic anhydride. This procedure enables flexible and even iterative substitution with a broad range of O, S, N, and C nucleophiles.

suggesting a stepwise process. In addition, no cis−trans isomerization was observed under the reaction conditions. Moreover, key information was obtained when the reaction with the diethylbenzylidene malonate was conducted and quenched at −20 °C (Scheme 3).This experiment led to a mixture of the cis-fluorocyclopropane as a single stereoisomer and the product A resulting from a Michael addition and an interrupted cyclization. In addition, when this reaction was allowed to reach room temperature, the Michael adduct A was not detected and the trans-Scheme 2. Scope of the Michael-Initiated Cyclopropanation Reaction Using Br 2 FCCO 2 Et Scheme 3. Proposed Mechanism for the Michael-Initiated Cyclopropanation Reaction Using Br 2 FCCO 2 Et Scheme 4. Synthesis of Fluorinated Cyclopropyl Amino Acid Analogues and Fluoro Analog of Simeprevir Accounts of Chemical Research pubs.acs.org/accounts Article