Chelating Picolinaldehyde Hydrazone Amides as Protecting Groups for Carboxylic Acids: Orthogonal Reactivities of Hydrazone Amides and Esters in Hydrolysis

We report a chelating hydrazone amide as a protecting group for carboxylic acids. Unlike most esters, 2picolinaldehyde hydrazone amides are stable under acidic or basic hydrolytic conditions. However, hydrazone amides can be easily converted to the corresponding carboxylic acids via Ni-mediated hydrolysis. Orthogonal reactivities of the hydrazone amides and representative protecting groups were verified by control experiments and peptide synthesis, demonstrating that chelating hydrazone amides are highly useful protecting groups.

Automated summary

A chelating hydrazone amide was reported as a protecting group for carboxylic acids. Unlike most esters, 2picolinaldehyde hydrazone amides are stable under acidic or basic hydrolytic conditions. However, they can be easily converted to carboxylic acids via Ni-mediated hydrolysis. Control experiments and peptide synthesis confirmed the orthogonal reactivities of hydrazone amides and other protecting groups, demonstrating the utility of chelating hydrazone amides as protecting groups.