The synthesis of 2-amino-dihydropyrimidines and a new model for 6-endo selectivity in intramolecular alkyne hydroaminations

Propargylguanidines, accessible in three synthetic steps, when treated with metal catalysts undergo hydroaminations. Judicious choice of metal catalyst can lead to regioselective hydroaminations. Silver has been shown to catalyze a 5-exo-dig pathway, whereas rhodium catalyzes a 6-endo-dig pathway. Computational and kinetic data are used to identify potential reaction mechanisms and transition states of the Rh(II)- catalyzed hydroamination. The propargylguanidine hydroamination methodology has been expanded to include the cyclization of bis-propargylguanidines, to produce bicyclic guanidine structures.