Transition-Metal-Free Selective Halocyclization of N -Alkoxy Amides: Synthesis of N -Alkoxy Lactams and Oximinolactones

A new method for the synthesis of N-alkoxy lactams and ox-iminolactones, involving the selective N-cyclization and O-cyclization ofunsaturated N-alkoxy amides, is presented. This approach features mildreaction conditions and no requirement for transition-metal catalysts.The protocol demonstrates a wide range of applicability in 5-exo-trigand 6-exo-trig cyclization, accommodating chloro, bromo, and iodoelectrophiles. The N-cyclization process can be achieved in the presenceof strong lithium base such as LiHMDS or n-BuLi, while the O-cyclizationoccurs spontaneously without the addition of any base. Mechanisticstudies reveal the N-cyclization reactions proceed through cyclic lithi-um intermediates, as confirmed by FT-IR studies and control experi-ments, which contribute to the N-selectivity. The current methodologywas successfully used in synthesis of natural product (E/Z) des-hydroxytriticone A and B.