Enantioselective [3+2] Annulation of Aldimines with Alkynes by Scandium-Catalyzed C−H Activation

Abstract

The enantioselective [3+2] annulation of readily accessible aldimines with alkynes via C−H activation is, in principle, a straightforward and atom-efficient route for synthesizing chiral 1-aminoindenes, which are important components in a wide array of natural products, bioactive molecules, and functional materials. However, such asymmetric transformation has remained undeveloped to date due to the lack of suitable chiral catalysts. Here, we report for the first time the enantioselective [3+2] annulation of aldimines with alkynes via C−H activation using chiral half-sandwich scandium catalysts. This protocol enabled the synthesis of diverse multi-substituted chiral 1-aminoindene derivatives with 100 % atom-efficiency, broad substrate scope, and high regio- and enantioselectivity. Density functional theory (DFT) analyses have revealed that a noncovalent C−H⋅⋅⋅π interaction between a tert-Bu substituent in the chiral cyclopentadienyl (Cp) ligand and the phenyl ring of an aromatic aldimine substrate played an important role in achieving a high level of enantioselectivity. This work not only offers an efficient and selective route for synthesizing a new family of chiral 1-aminoindene derivatives but also offers unprecedented insights into enantioselectivity control in chiral Cp-ligated metal catalysts.