Rapid Synthesis of Weinreb Amides via Titanium‐Mediated Direct Amidation at Room Temperature

Reported herein is a mild, rapid, and operationally simple protocol for the direct synthesis of N ‐methoxy‐ N ‐methylamides (Weinreb amides) from carboxylic acids in the presence of TiCl ₄ . The reaction proceeds under ambient conditions, overcoming the challenges encountered by existing amidation methodologies. The protocol accommodates a broad range of substrates, delivering both aliphatic and aromatic Weinreb amides in good to excellent yields. Notably, the simple workup procedure eliminates the need for column chromatography, further enhancing the practical appeal.