Investigation of the 1,3-diaza-Claisen Rearrangements in Ring Expansion of Vinyl N-heterocycles

Electron-deficient isothioureas tethered to vinyl tertiary N-heterocycles can afford carbodiimides upon desulfurization with thiophilic metals and non-nucleophilic amine bases. Addition of the N-heterocycles to the carbodiimdes form zwitterionic spiro-cycles which then undergo zwitterionic 1,3-diaza-Claisen rearrangements to afford guanidine containing macro-cycles. Variation of the N-heterocycles and the tether lengths influences the different reactivity in the rearrangement. Solvent effect and stereoselectivity are also explored. The method provides easy access to novel guanidines that would be difficult to synthesize through conventional pathways