New Entries in Lewis Acid−Lewis Base Bifunctional Asymmetric Catalyst: Catalytic Enantioselective Reissert Reaction of Pyridine Derivatives

Abstract
The first catalytic enantioselective Reissert reaction of pyridine derivatives that affords products with excellent regio- and enantioselectivity is described. The key for success is the development of new Lewis acid−Lewis base bifunctional asymmetric catalysts containing an aluminum as a Lewis acid and sulfoxides or phosphine sulfides as a Lewis base. These reactions are useful for the synthesis of a variety of chiral piperidine subunits, and catalytic enantioselective formal synthesis of CP-293,019, a selective D4 receptor antagonist, was achieved. Preliminary mechanistic studies indicated that both sulfoxides and phosphine sulfides can activate TMSCN as a Lewis base. In addition, the sulfoxides with appropriate stereochemistry might stabilize a highly enantioselective bimetallic complex (a presumed active catalyst) through internal coordination to aluminum.