Expansion of the scope of the 1,3-diaza-Claisen rearrangement beyond bridged-bicyclic tertiary allylic amines has been investigated through a tethering strategy. Isothioureas tethered to tertiary allylic amines are converted to carbodiimides through a reaction with AgOTf/Et 3 N. Intramolecular cyclization of the tertiary allylic amine to the carbodiimide equilibrates with a zwitterionic intermediate. Heating the carbodiimide/zwitterion affords a rearrangement product. Heating carbodiimide/zwitterion with a deuterated allyl group results in the scrambling of the deuterium label, which is consistent with an ionic mechanism involving heterolytic cleavage of the allylic C−N bond, followed by trapping of the allyl cation at either terminal carbon. The ionic mechanism is attributed to silver salt contamination since pushing deuterium-labeled carbodiimide/zwitterion through silica gel prior to heating results in clean deuterium transposition consistent with a sigmatropic mechanism, and adding back silver salts results in deuterium scrambling. Overall, the tethering strategy broadens the scope of the rearrangement to simpler allylic substrates. Density functional theory (DFT) calculations of the sigmatropic rearrangement are in agreement with reactivity trends observed with reactions run under silver-free conditions.

Vinyl pyrrolidines tethered to isothioureas are activated to the corresponding carbodiimides with AgOTf and Et 3 N. Intramolecular addition of the vinyl pyrrolidine amine to the carbodiimide followed by a 1,3-diaza-Claisen rearrangement affords [9,5]-and [9,6]-bicyclic guanidines depending on the tether length in good to excellent yields. Density functional theory calculations reveal that the pathway involving intramolecular addition of the amine to carbodiimide to afford a zwitterionic intermediate followed by the zwitterionic 1,3-diaza-Claisen rearrangement was consistently a higher energy pathway than the path involving protonation of the zwitterionic intermediate followed by the cationic 1,3-diaza-Claisen rearrangement.