Stereoselection in the preparation of alpha-OXY-beta-amino esters : revealing the mechanism

Due to their significant pharmaceutical applications, the development of efficient, stereoselective synthetic routes for the preparation of α-substituted-β-amino esters has become increasingly important. We demonstrated that the titanium enolates (47) of a.alkoxy acetate esters (48) add cleanly to imines (49), and predominately afford the anti diastereomer of the a.-oxy-f3-amino ester product (50). Furthermore, by altering the electronic properties of the ether oxygen, sterics of the ester and temperature conditions, we changed the anti:syn product ratio. We rationalized the origin of these effects, and proposed a mechanism of imine addition