Enantioselective Narasaka–Heck cyclizations: synthesis of tetrasubstituted nitrogen-bearing stereocenters

Abstract

The first examples of highly enantioselective Narasaka–Heck cyclizations are described. A SPINOL-derived P,N-ligand system enables Pd-catalyzed 5-exo cyclization of a range of oxime esters with sterically diverse trisubstituted alkenes to generate dihydropyrroles containing tetrasubstituted nitrogen-bearing stereocenters in 56 to 86% yield and 90 : 10 to 95 : 5 e.r. These processes are rare examples of reactions that proceed via enantioselective migratory insertion of alkenes into Pd–N bonds, and the first where trisubstituted alkenes are used to generate tetrasubstituted stereocenters with high enantioselectivity.