Synthesis of Chiral Carbocycles via Enantioselective β,γ-Dehydrogenation

Enantioselective dehydrogenation of prochiral C-H bonds could provide a powerful method for constructing chiral centers attached to synthetically versatile vinyl groups. Herein, we describe the realization of enantioselective β,γ-dehydrogenation of cycloalkyl amides enabled by chiral oxazoline-pyridone ligands to afford a wide range of highly elaborated carbocycles with exceptional enantioselectivity (>99% ee). Notably, the resulting chiral β,γ-unsaturated carbocycles are difficult to access via inverse electron demand Diels-Alder reaction. Through ligand control, tandem dehydrogenation and C-H olefination sequence also led to the formation of chiral β-alkylidene-γ-lactam. Remarkably, this catalyst is also compatible with complex biologically significant natural products, including diterpenes and pentacyclic triterpenes, where each enantiomer of our chiral ligand enables site-selective modification at four distinct sites within the E ring.