Organocatalytic dynamic kinetic resolution of N-arylindole lactams: atroposelective construction of axially chiral amino acids bearing a C-N chiral axis

Organocatalytic dynamic kinetic resolution of configurationally labile cyclic molecules represents one of the most efficient methods for the atroposelective construction of axially chiral molecules bearing a tetra-ortho-substituted chiral axis. Notably, this privileged strategy is limited to constructing a C-C chiral axis. Herein, organocatalytic dynamic kinetic resolution of configurationally labile N-arylindole lactams has been successfully achieved at the first time, allowing for access to a structurally diverse set of axially chiral N-arylindole amino esters with a tetra-ortho-substituted C-N chiral axis in excellent yields and atroposelectivities. In addition to the N-arylindole skeleton, N-aryl thieno[3,2-b]pyrrole, furo[3,2-b]pyrrole, and pyrrolo[2,3-b] pyridine skeletons are also compatible with this transformation. This transition-metal-free facile strategy features a broad substrate scope, mild reaction conditions, easy scale-up and excellent atom economy. Several potentially valuable molecules, such as axially chiral peptides, were efficiently generated from the resulting configurationally stable axially-chiral N-arylindole amino esters, demonstrating the power of this strategy. [Figure not available: see fulltext.]