Asymmetric Approach for the Synthesis of Triazine Derivatives via a Cooperative Catalysis

The cooperative catalysis employing chiral ligands and transition metals has proved to be an efficient
approach in the asymmetric synthesis of a wide range of heterocyclic scaffolds. Numerous examples of
(3+2) cycloadditions were reported over the past years, however, it is peculiar that (3+3)
cycloadditions have largely been neglected. To this end, herein we report our efforts leading to a
stereoselective (3+3) cycloaddition of substituted isocyanoacetate esters and azomethines
affording 1,2,4-triazines and analogous structures with two contiguous fully substituted carbon stereocenters
– the aforementioned reaction has been promoted by a system assembled from chinchona-derived
amino phosphine ligand and a silver (I) salt.
We selected azomethine 1 and isocyanoacetate 2 as a model reaction –the reaction in toluene at room
temperature delivered the desired product with high atom economy, excellent yield and promising
enantioselectivity. With these encouraging results, our efforts are focused on the improvement of the
enantioselectivity of this transformation.