Direct Synthesis of Benzhydryl-Functionalized 3,4-Dihydropyridin-2-ones from 2-Pyridones and Their Use in the Formation of Bridged δ-Lactams

A method for the synthesis of C4-benzhydryl-functionalized 3,4-dihydropyridin-2-ones using complementary addition of benzhydryllithium and/or benzhydrylmagnesiate reagents to 2-pyridones, with high regioselectivity triggered by substituents, is described. A partially stereoselective cyclization was successfully demonstrated using TfOH and/or TIPSOTf as Brønsted and Lewis acids, respectively, leading to C6-phenyl-functionalized 7,8-benzomorphanones. It is also shown that the use of functionalized δ-enelactams obtained with an active methoxy-substituted benzyl group at C3 enabled the preparation of a new C3-C6 bridged system within the δ-lactam framework.