Alkoxylamines

N-Alkoxylamines 88 are a class of initiators in "living" radical polymerization (Scheme 14). A new methodology for their synthesis mediated by (TMSlsSiH has been developed. The method consists of the trapping of alkyl radicals generated in situ by stable nitroxide radicals. To accomplish this simple reaction sequence, an alkyl bromide or iodide 87 was treated with (TMSlsSiH in the presence of thermally generated f-BuO radicals. The reaction is not a radical chain process and stoichiometric quantities of the radical initiator are required. This method allows the generation of a variety of carbon-centered radicals such as primary, secondary, tertiary, benzylic, allylic, and a-carbonyl, which can be trapped with various nitroxides. 

In 2002, Kanno and Taylor successfully developed a simple one-pot procedure using MnOi/NHiOMe-HCl for the conversion of activated primary alcohols into O-methyl oximes (Scheme 11). They also developed a modification using Amberlyst 15-supported alkoxylamines, which can be employed to prepare other types of 0-aUcyl oximes as well as the parent hydroxylamines. This latter procedure has been used as the cornerstone of an efficient synthesis of the antifungal natural product citaldoxime 11 (Scheme 11). Citaldoxime is an antifungal natural product first obtained as a radiation-induced stress metabolite of Citrus sinensis , and later isolated from the roots of several different citrus plants. ... 

Primary amines (RNH2) also add reversibly to ketones or aldehydes to give imines (Schiff bases) and related compounds via the intermediate hemiaminals. The position of the equilibrium depends on the structure of the amine and the carbonyl compound. With alkylamines, the equilibrium favors the carbonyl compound, but it can be driven to the imine by removal of H20. With hydrazines (R2NNH2) and hydroxyl-and alkoxylamines (RONH2), the equilibrium greatly favors the hydrazone, oxime, or oxime ether, and it is difficult to drive the reaction in the reverse direction. Secondary amines (R2NH) can form hemiaminals, but they cannot form imines. 

We will focus here on a simple hydroxylation process of enolate radicals generated from ester enolates via SET oxidation. Ferrocenium ion was used as the oxidizing agent, and the radical intermediate was trapped with TEMPO [48]. In a second step, the alkoxylamine was reduced with zinc to the corresponding a-hydroxyester. The hydroxylation of ethyl 3-hydroxybutyrate gave the ethyl 2,3-dihydroxybutyrate with moderate stereocontrol (Scheme 17). 

N-Alkoxy - s. Alkoxylamines Alkoxydiazenium salts s. O-Alkylnitrosimmonium salts 20... 

M -butyllithium added dropwise to a soln. of o-bromo-N-methyl-N-propoxy-aniline in tetrahydrofuran under argon at — 105°, the mixture stirred for 1.5 h, treated dropwise with benzyl bromide, stirring continued for 30 min, and the mixture allowed to warm to room temp, over 1.5 h intermediate (Y 78%), and W-2 Raney Ni (pre-washed to pH 7 with distilled water) in ethanol stirred at room temp, under argon until reaction complete by t.l.c. (ca. 1 h) - o-benzyl-N-methylaniline (Y 86%). The intermediate o-lithiated alkoxylamine thus serves as an o-lithio-N-alkylaniline equivalent. F.e. and electrophiles s. J. Sisko, S.M. Weinreb, Synth. Commun. 18, 1035-41 (1988). 

Magnesium cerium(III) chloride Synthesis of alkoxylamines from alkoximes with asym. induction Chiral a-(alkoxylamino)ketals... 

---