The Development of a Highly Stereoselective Zn-Catalyzed (3 + 2) Cycloaddition of Azomethine Ylides and Nitroalkenes

We present a high-yielding, highly diastereoselective, and highly enantioselective synthesis of 4-nitropyrrolidines via a Zn(II)-UCD-Imphanol-catalyzed (3 + 2) cycloaddition of imino esters and nitroalkenes. Fifteen 4-nitropyrrolidines were synthesized with isolated yields of up to 96%, diastereoselectivities of up to 99:1 exo/endo, and enantioselectivities of up to 99% ee. This study, combined with previous work in our group, establishes this family of (N,O) ligands as a versatile and relatively general chiral scaffold to afford substituted pyrrolidines in excellent yields and stereoselectivities. However, the work described herein remains inferior to previously reported Cu- or Ag-catalyzed methods as the present reaction remains mainly limited to aryl-substituted imino esters and aryl nitroalkenes. We have demonstrated that these 4-nitropyrrolidines can be converted into the valuable 4-aminopyrrolidines in a single step. We have also shown the utility of these compounds in accessing complex structures suggesting the potential of this method in constructing large libraries of chiral pyrrolidine-containing molecules.