Inverse electron demand Diels–Alder reaction of tetrazines and functionalized alkynes: convenient way to heterocycles and noncanonical amino acids

A simple preparative synthesis of the heterocyclic system tetrahydropyrido[3,4-c]pyridazine has been developed within the framework of the IEDDA reaction of sym-tetrazine with methyl 2-(tert-butoxycarbonylamino)pent-4-ynoate. A series of pyridazinyl-α-alanines with diff erent numbers of carboxyl groups — new non-canonical amino acids for bioengineering — have been obtained by its stepwise hydrolysis.