Silver-Catalyzed [3 + 3] Dipolar Cycloaddition of Trifluorodiazoethane and Glycine Imines: Access to Highly Functionalized Trifluoromethyl-Substituted Triazines and Pyridines

Herein
we disclose a silver-catalyzed [3 + 3] 1,3-dipolar cycloaddition
reaction of trifluorodiazoethane with glycine imines. This reaction
exhibits manifold remarkable features, such as easily available substrates,
high regio- and diastereoselectivities, mild reaction conditions,
and good yields across a broad spectrum of substrates. Moreover, swift
transformations of the obtained tetrahydrotriazines provide efficient
access to a diverse set of highly functionalized trifluoromethyl-substituted
triazines and pyridines. Particularly noteworthy is that such trifluoromethylated
1,2,4-triazines demonstrate competent reactivity toward trans-cyclooctene (TCO) derivatives with second-order rate constants (k2) up to 99.24 M–1 s–1, which represents the highest value involving 1,2,4-triazines to
date.