Modifications of Phenols with β-Lactam via Ring-Opening Reaction.

We report a K2CO3-mediated modification of phenols via the ring-opening of β-lactams under mild conditions. This method is compatible with a broad range of substituted substrates, affording the corresponding amino acid-introducing phenolic products in good to excellent yields. The protocol is also successfully applied to the modification of various phenol-containing small-molecule drugs and peptides. Importantly, a preliminary attempt to employ β-lactam as a linkage for constructing conjugates between a phenolic drug and another drug was also achieved. The extremely mild reaction conditions make this work as a potential easily handled modification protocol for phenol drugs.