Synthesis of New Chiral 2,2‘-Bipyridine Ligands and Their Application in Copper-Catalyzed Asymmetric Allylic Oxidation and Cyclopropanation

A series of modular bipyridine-type ligands 1 and 3−9 has been synthesized via a de novo construction of the pyridine nucleus. The chiral moieties of these ligands originate from the isoprenoid chiral pool, namely, β-pinene (10 → 1), 3-carene (14 → 3 and 5), 2-carene (28 → 4), α-pinene (43 → 6-8), and dehydropregnenolone acetate (48 → 9), respectively. Copper(I) complexes, derived from these ligands and (TfO)2Cu (1 mol %) upon an in situ reduction with phenylhydrazine, exhibit good enantioselectivity (up to 82% ee) and unusually high reaction rate (typicaly 30 min at room temperature) in allylic oxidation of cyclic olefins (52 → 53). Copper-catalyzed cyclopropanation proceeded with ≤76% enantioselectivity and ∼3:1 to 99:1 trans/cis-diastereoselectivity (54 → 55 + 56). The level of the asymmetric induction is discussed in terms of the ligand architecture that controls the stereochemical environment of the coordinated metal.