One-Step Synthesis of O-Benzyl Hydroxamates from Unactivated Aliphatic and Aromatic Esters

Abstract

We have developed a simple and high yielding one-step method for the synthesis of hydroxamate derivatives directly from a broad range of unactivated esters and the anion of O-benzyl-hydroxylamine generated in situ. The reaction takes place in minutes at -78 degrees C. Very importantly, the method was successfully employed with enolizable esters, including chiral alpha-amino acid esters and peptides, with no trace of racemization/epimerization at the alpha carbon detected.

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

“…O-Benzyl hydroxamate 2a could also be prepared via direct amidation of the methyl ester of amino acid 4 using LiHMDS base in THF. 24 A slight reduction in yield and a shorter reaction time are observed in this instance (Scheme 1, entry 2a). The direct amidation route could also be applied to more complex substrates as exemplified below in Scheme 3.…”

Synthesis of β- and γ-oxa isosteres of fosmidomycin and FR900098 as antimalarial candidates

“…β-Oxa analogue 11 proved to be stable in H 2 O for more than two weeks, as revealed by 1 H-NMR. 16 The synthesis of the N-hydroxy carbamates 14 and 15 is depicted in Scheme 3. Treatment of dimethylhydroxyethyl phosphonate (34) with carbonyldiimidazole and benzylhydroxyl amine afforded 37.…”

Hydroxamic Acids: Chemistry, Bioactivity, and Solutionand Solid‐Phase Synthesis

“…This historic and extremely effective method was subsequently used to synthesize a vast array of different hydroxamic acids [85][86][87][88][89][90]. Hydroxylamine is generally generated by adding KOH or NaOH to an aqueous or methanolic solution of hydroxylamine hydrochloride.…”