Titanium-Catalyzed, One-Pot Synthesis of 2-Amino-3-cyano- pyridines

Earth-abundant and inexpensive titanium can catalyze alkyne iminoamination, which generates tautomers of 1,3-diimines. Upon treatment with base (DBU) and malononitrile, the multicomponent coupling product is converted to 2-amino-3-cyanopyridines in a one-pot procedure in good to modest yields. There is substantial control of regioselectivity for the substituents on the pyridine ring and on the 2-amino group. Several studies were done that provide significant evidence for a Dimroth rearrangement mechanism for 2-aminopyridine formation, including isolation of a 2-imino-1,2-dihydropyridine intermediate that undergoes rearrangement under the reaction conditions.