Concise Synthesis of (+)‐[13C4]‐Anatoxin‐a by Dynamic Kinetic Resolution of a Cyclic Iminium Ion

An asymmetric total synthesis of [13C4]‐anatoxin‐a ([13C4]‐1) has been developed from commercially available ethyl [13C4]‐acetoacetate ([13C4]‐15). The unique requirements associated with isotope incorporation inspired a new, robust, and highly scalable route, providing access to 0.110 g of this internal standard for use in the detection and precise quantification of anatoxin‐a in freshwater. A highlight of the synthesis is a method that leverages a cyclic iminium ion racemization to achieve dynamic kinetic resolution in an enantioselective Morita–Baylis–Hillman (MBH) cyclization. Label it! Reported here is an asymmetric total synthesis of the isotopically labelled cyanotoxin [13C4]‐anatoxin‐a. A critical feature of the synthesis is the unique enantioselective Morita–Baylis–Hillman cyclization that leverages a cyclic iminium ion racemization to achieve dynamic kinetic resolution. The substantial quantities of this internal standard with 99.1 % isotope incorporation will enable the development of an analytical method for the precise quantification of anatoxin‐a in freshwater.