SPA-PNN ligand for the kinetic resolution of carbocyclic and heterocyclic spiranes by asymmetric hydrogenation

The chiral carbocyclic and heterocyclic spirane scaffolds are widely present in natural products and pharmaceutical molecules. Efficient, concise, and enantioenriched synthesis of these structures is a significant objective in both academic and industrial fields. Here, we design and synthesize a series of chiral SPA-PNN ligands, which are used to kinetically resolve racemic spirocyclic 1,3-diketones and their analogs via Ir-catalyzed asymmetric direct hydrogenation to afford the corresponding chiral spirocyclic 1,3-diketones and chiral hydroxyspiroketones. This asymmetric transformation features broad substrate scope (four different types of spirocycle), low catalyst loading (S/C = 5000), and an excellent kinetic resolution efficiency (selectivity factor of up to 207). Notably, the resulting chiral products are successfully used in the total and formal synthesis of four natural products, and in the preparation of key synthetic intermediates for structurally attractive ligands. Furthermore, control experiments and DFT calculations enable the origin of the observed enantioselectivity to be elucidated.