Reactions of N-Benzyloxycarbamate Derivatives with Stabilized Carbon Nucleophiles: A New Synthetic Approach to Polyhydroxamic Acids and Other Hydroxamate-Containing Mixed Ligand Systems

• Published in: Journal of organic chemistry 2009-01, Vol.74 (2), p.782-788
• Main Authors: Liu, Yuan, Jacobs, Hollie K, Gopalan, Aravamudan S
• Format: Article
• Language: English
• Subjects: Carbamates - chemistry; Carbon - chemistry; Catalysis; Catalysts: preparations and properties; Chelating Agents - chemistry; Chemistry; Exact sciences and technology; General and physical chemistry; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Hydroxamic Acids - chemical synthesis; Hydroxamic Acids - chemistry; Ligands; Organic chemistry; Polymers - chemical synthesis; Polymers - chemistry; Preparations and properties; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo802410u

Hydroxamic acids are an important class of chelators of hard metal ions such as Fe(III), which have found applications in therapeutic, diagnostic, and separation chemistry. Hence, methods for their preparation and incorporation into various matrices are important. A new strategy for the preparation of hydroxamic acids that uses readily available N-benzyloxy carbamic acid ethyl ester, 1, has been developed. N-Alkylation of 1 occurs readily to give N-alkyl-N-benzyloxy carbamates, 2, which react with a variety of stabilized carbon nucleophiles to give functionalized protected hydroxamic acids, 3, in good to excellent yields. The O-protected hydroxamate intermediates 3 can be further alkylated with halides to access a variety of potential metal binding hosts. The usefulness of this methodology has been demonstrated by the synthesis of a novel trihydroxamic acid 6, mixed ligand systems 9 and 12, and the macrocyclic dihydroxamic acid 16.