Enantioselective Synthesis of 1-Aminoindanes via [3+2] Annulation of Aldimines with Alkenes by Scandium-Catalyzed C-H Activation

Multisubstituted chiral 1-aminoindanes are importantcomponentsin many pharmaceuticals and bioactive molecules. Therefore, the developmentof efficient and selective methods for the synthesis of chiral 1-aminoindanesis of great interest and importance. In principle, the asymmetric[3 + 2] annulation of aldimines with alkenes through C-H activationis the most atom-efficient and straightforward route for the constructionof chiral 1-aminoindanes, but such a transformation has remained undevelopedto date probably due to the lack of suitable catalysts. Herein, wereport for the first time the enantioselective [3 + 2] annulationof a wide range of aromatic aldimines and alkenes via ortho-C(sp(2))-H activation by chiral half-sandwich scandiumcatalysts, which provides a straightforward route for the synthesisof multisubstituted chiral 1-aminoindanes. This protocol features100% atom-efficiency, broad functional group compatibility, and highregio-, diastereo-, and enantioselectivity (up to >19:1 dr and99:1er). Remarkably, by fine-tuning the sterics of the chiral ligand aroundthe catalyst metal center, the diastereodivergent asymmetric [3 +2] annulation of aldimines and styrenes has been achieved with a highlevel of diastereo- and enantioselectivity, offering an efficientmethod for the synthesis of both the trans and cis diastereomers of a novel class of chiral 1-aminoindanederivatives containing two contiguous stereocenters from the sameset of starting materials. Moreover, the asymmetric [3 + 2] annulationof aldimines with aliphatic & alpha;-olefins, norbornene, and 1,3-dieneshas also been achieved.

Automated summary

Multisubstituted chiral 1-aminoindanes are important components in pharmaceuticals and bioactive molecules. The synthesis of chiral 1-aminoindanes is of great interest and importance, and the asymmetric[3 + 2] annulation of aldimines with alkenes through C-H activation is a promising method. This study reports the enantioselective [3 + 2] annulation of aromatic aldimines and alkenes via ortho-C(sp(2))-H activation using chiral half-sandwich scandium catalysts, which provides a straightforward route for the synthesis of multisubstituted chiral 1-aminoindanes.