Catalytic Asymmetric Synthesis of (N, N)-Spiroketal via Pd-Catalyzed Enantioconvergent Aminocarbonylation and Dearomative Nucleophilic Aza-Addition

Chiral spirocyclic skeletons have found widespread applications in asymmetric catalysis, drug discovery, and functional materials due to their rigid three-dimensional architecture and excellent stereochemical stability. However, the structural diversity of accessible spiro frameworks remains limited, constraining their broader utility and functional development. For instance, chiral (N, N)-spiroketals represent a promising class of scaffolds with potential application in asymmetric catalysis and are frequently encountered in natural products and biologically active compounds, yet their efficient synthesis is still underdeveloped. Herein, we present a novel Pd-catalyzed cascade enantioconvergent aminocarbonylation and intramolecular dearomative nucleophilic aza-addition that enables the efficient synthesis of chiral (N, N)-spiroketal. This formal [3+1+1] spiroannulation employs racemic quinazoline-derived heterobiaryl triflates, carbon monoxide, and amines to deliver an array of (N, N)-spiroketal in high yields and excellent enantioselectivities. The protocol exhibits wide functional group tolerance, scalability, and downstream synthetic utility, providing access to structurally diverse spirocyclic derivatives. Mechanistic studies revealed that the stereochemical outcome of (N, N)-spiroketal was determined by the atroposelective DyKAT aminocarbonylation step, rather than the subsequent spiroannulation. Moreover, the resulting spiroketal structure was developed into chiral carbene ligand, as demonstrated by the successful synthesis of its corresponding Rh, Ir, Au and Pd complexes.