A Novel Transformation of Primary Amines to N-Monoalkylhydroxylamines

Abstract

A novel transformation of primary amines to the corresponding N-monoalkylhydroxylamines is described. The three-step protocol involves selective mono-cyanomethylation of primary amines, regioselective formation of nitrones by m-CPBA oxidation, and hydroxylaminolysis of the nitrones with hydroxylamine hydrochloride. The method is applicable for a wide range of primary amines, including alkyl, benzyl, and chiral.

A New Three‐Component Cascade Reaction to Yield 3‐Spirocyclopropanatedβ‐Lactams

“…NMR spectra were recorded with Bruker AM 250 (250 MHz for 1 H and 62.9 MHz for 13 [6] bicyclopropylidene (2), [6] N-benzhydrylhydroxylamine hydrochloride (8c), [16] and methylglyoxylate (10-Me), [17] were prepared according to published procedures. All operations in anhydrous solvents were performed under an argon atmosphere in flame-dried glassware.…”

Chemical Protein Synthesis with the KAHA Ligation

“…As it is desirable to introduce other functionalized N-hydroxyl aminoacids, we have developed a method to prepare nitrone-protected N-hydroxy aminoacid building blocks amenable to direct incorporation into peptides by standard Fmoc SPPS without the loss of stereochemical integrity (Scheme 18) [41]. By following a modification of the procedure reported by Fukuyama [42], O-protected aminoacids were alkylated in good yields to afford the cyanomethyl amines. Following a one-pot oxidation to the corresponding nitrones and subsequent hydrolysis with hydroxylamine hydrochloride, the free N-hydroxylamino acids were obtained.…”

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

“…In addition to the oxidation of amines with BPO [136,[138][139][140][141], there are four alternative routes for synthesizing hydroxylamines from amines as outlined in Scheme 3.21: (a) oxidation of primary and secondary amines using oxone over silica gel or, in certain instances, alumina [142], (b) oxidation of amines using dimethyldioxirane in acetone to give the acetonederived nitrone, followed by acid hydrolysis or hydroxylaminolysis [143], (c) selective mono-cyanomethylation of primary amines, followed by meta-chloroperoxybenzoic acid (m-CPBA) oxidation to give the nitrone and subsequent hydroxylaminolysis with hydroxylamine hydrochloride [144], and (d) reaction of an amine and an aromatic aldehyde to give an imine, followed by oxidation with m-CPBA to give the corresponding oxaziridine and hydrolysis to the hydroxylamine under acid-catalyzed conditions [145][146][147]. …”