Copper‐Mediated ortho ‐C–H Etherification of Arylaldehydes Enabled by a Transient Directing Group

Key Points

• This research investigates a novel strategy for C–H functionalization using transient directing groups for etherification reactions.
• Utilized transient directing groups for in situ generation of imines from amino acids and aromatic aldehydes.
• Conducted copper-mediated ortho-C–H etherification reaction using phenols and alcohols.
• Demonstrated multiple applications, including late-stage diversification of drug analogs.
• Successfully achieved ortho-C–H etherification between aromatic aldehydes and phenols/alcohols under copper-mediated conditions.
• Established the first example of a TDG-based reaction using phenol substrates.
• Showed the method's utility in the late-stage modification of drug molecules.