Highly Diastereoselective Switchable Enantioselective Mannich Reaction Of Glycine Derivatives With Imines

摘要

Chiral α,β-diamino acid derivatives are an important class of compounds because of their biological activities and their usefulness in organic synthesis. Many synthetic approaches have been developed for them, as exemplified by an assemblage employing asymmetric Mannich type reaction of glycine derivatives with imines and nitro compounds under metallo- and organocatalysis. The chiral quarter-nary carbon center at the a-position was also established. However, only a few reports realized both diastereo- and enantioselectivities and no paper dealt with the tuning of diastereoselectivity. In some cases the substrates were limited. Thus, challenges still remain regarding diastereo- and enantioselectivities and/or substrate scope for the reaction. On the other hand, tuning of diastereoselectivity by using different approaches have been well documented; few reports accomplished it by changing the electronic factor of the ligand. In the studies of chiral ligands in asymmetric catalysis, we found a dramatic effect of the electronic property of ligands on the switch of regio- and diastereoselectivities in the Heck reaction and 1,3-dipolar cycloaddition. Here we report our preliminary results showing that the same strategy can be applied to Lewis acid catalyzed Mannich reaction of glycine esters with both aromatic and aliphatic imines, achieving excellent diastereo- and enantioselectivities for both syn and anti products.