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, 2-picolinaldehyde 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.

Site-Selective Acylations of α- and β-Hydroxyamides in Complex Molecules: Application of Template-Driven Acylation to Disaccharides and a Glycopeptide.

Site-selective acylations of α-and β-hydroxyamides in complex polyols are described. The combination of a pyridine aldoxime ester and Zn(OTf) facilitates the acylation of two types of -glycolyl disaccharides, namely, Gal-GlcNGc and Neu5Gc-Gal, both of which are partial structures of polysaccharides responsible for biological actions, with highly site-selective modifications achieved. Furthermore, biotinylation, one of the most important techniques in chemical biology, is used to site-selectively acylate the β-hydroxyl group in a glycopeptide.

Site-Selective Esterifications of Polyol β-Hydroxyamides and Applications to Serine-Selective Glycopeptide Modifications.

The site-selective acylations of β-hydroxyamides in the presence of other hydroxyl groups are described. Central to the success of this modification is the metal-template-driven acylation using pyridine ketoxime esters as acylating reagents in combination with CuOTf. This strategy enables β-hydroxyl groups to be site-selectively acylated in various derivatives, including sterically hindered secondary β-alcohol.

Metal Template Assisted Proximal Arrangement of a Nucleophile and an Electrophile: Site-Selective Acylation of α-Hydroxyamides in Polyols.

Site-selective acylation of α-hydroxyl groups in amides has been achieved in the presence of other primary hydroxyl groups with intrinsic high reactivity. In this methodology, a relatively stable pyridine aldoxime ester was exploited as an acyl donor to suppress undesired acylation. The catalytic activation of a pyridine aldoxime ester with a Lewis acid produced a cationic complex, which preferentially attracted the Lewis basic α-hydroxyamide via a template effect, to thus facilitate o-acylation.