Palladium-Catalyzed Enantioselective Cycloadditions of Aliphatic 1,4-Dipoles: Access to Chiral Cyclohexanes and Spiro [2.4] heptanes

Design and exploration of new intermediates for chemo-, regio-, and stereoselective cycloadditions remain a formidable challenge in modern organic synthesis. Compared to the well-developed 1,3-dipolar cycloadditions, Pd-catalyzed1,4-dipolar cycloadditions are generally limited to specialized substrates due to the inherent nature of the thermodynamically driven intramolecular transformations and undesired isomerizations. Herein, we demonstrate the use of ligated palladium catalysts to control and modulate the intermolecular reactivity of aliphatic 1,4-dipoles, enabling two distinctive cycloaddition pathways with a broad scope of acceptors. This atom-economic process also features an eco-friendly in situ deprotonation strategy to generate the corresponding active palladium-mediated dipoles. Overall, a diverse array of chiral 6-membered rings and spiro [2.4] heptanes were prepared in high yield and selectivity. In addition, an unexpected property of cyano-stabilized carbanions was discovered and investigated, which can be useful in designing and predicting future transformations.