Synthesis of β-, γ-, and δ-Lactams via Pd(II)-Catalyzed C-H Activation

Significance

Reported is the Pd(II)-catalyzed synthesis of β-, γ-, and δ-lactams via an intra­molecular C-H amination strategy. Cyclization of O-methylhydroxamic acids 1 proceeds smoothly under the reaction conditions to deliver γ- and δ-lactams 2 in excellent yields. Although the electronic nature of the arene has little effect on the reaction, the presence of ortho-hydrogens (R^²,R^³ = H) greatly retards the reaction. The α,β-double bond in 3 is tolerated, allowing access to oxindoles 4 suitable for further functionalization. The reaction was also extended to the synthesis of 2-quinolone derivatives 6. Attempted formation of a β-lactam under the standard conditions led instead to a β-chlorination product, which was converted into the corresponding lactam on treatment with CsF. Cleavage of the N-methoxy protecting group was readily achieved by hydrogenolysis.