Reactions Neber rearrangement

Nazarov Cyclization Reaction Neber Rearrangement Nef Reaction Nef Synthesis Negishi Cross Coupling Nencki Reaction... 

One of the more important approaches to 1-azirines involves a similar base-induced cycloelimination reaction of a suitably functionalized ketone derivative (route c. Scheme 1). This reaction is analogous to route (b) (Scheme 1) used for the synthesis of aziridines wherein displacement of the leaving group at nitrogen is initiated by a -carbanionic center. An example of this cycloelimination involves the Neber rearrangement of oxime tosylate esters (357 X = OTs) to 1-azirines and subsequently to a-aminoketones (358) (71AHC-(13)45). The reaction has been demonstrated to be configurationally indiscriminate both syn and anti ketoxime tosylate esters afforded the same product mixture of a-aminoketones... 

Unlike the Beckmann rearrangement, the outcome of the Neber rearrangement does not depend on the configuration of the starting oxime derivative E- as well as Z-oxime yield the same product. If the starting oxime derivative contains two different a-methylene groups, the reaction pathway is not determined by the configuration of the oxime, but rather by the relative acidity of the a-methylene protons the more acidic proton is abstracted preferentially. ... 

Isolation of an Intermediate. It is sometimes possible to isolate an intermediate from a reaction mixture by stopping the reaction after a short time or by the use of very mild conditions. For example, in the Neber rearrangement (18-12)... 

Miscellaneous PTC Reactions The field of PTC is constantly expanding toward the discovery of new enantioselective transformations. Indeed, more recent applications have demonstrated the capacity of chiral quaternary ammonium salts to catalyze a number of transformations, including the Neber rearrangement (Scheme 11.19a), ° the trifluoromethylation of carbonyl compounds (Scheme 11.19b), ° the Mannich reaction (Scheme 11.19c), and the nucleophilic aromatic substitution (SnAt)... 

Both oximes (10) and their ester (11) or ether derivatives can be used in the classical Beckmann rearrangement and the reaction usually proceeds under acidic or neutral conditions (although basic conditions may also be used). In sharp contrast, only 0-oxime esters can be used as starting materials for the Neber rearrangement and basic conditions are always necessary. The Neber rearrangement is not stereospecific, as the stereochemistry of the starting material E or Z) does not influence the outcome of the reaction. In... 

Although both the Beckmann and Neber reactions can use oxime derivatives as starting materials, O-unsubstituted oximes cannot undergo the Neber rearrangement. The latter occurs only in strongly alkaline reaction conditions while the former can also proceed in both acid and basic media. As a consequence, the Neber rearrangement will only be a possible side reaction of base-induced Beckmann rearrangements. 

The Neber rearrangement is usually performed with ketoxime tosylates but ketone trimethylhydrazonium halides (519), iV,iV-dichloro-5ec-alkyl amines (520), N-chloroimines (521) and A-chloroimidates (522) may also be precursors for the reaction. Only the Neber rearrangement of oxime derivatives will be analysed in this chapter. 

Both cyclic and acyclic ketoximes may be used in this transformation and the reaction is usually performed in an alcohol solution containing equimolar quantities of alkoxide. For a successful reaction, the starting material usually contains at least an a-methylene group but the presence of only one a-hydrogen may suffice. When treated with base the 0-acylated aldoximes do not react via the Neber rearrangement and instead they undergo an E2 elimination to cyanides or isocyanides. 

Similar Neber rearrangements were used to produce 528, an intermediate for an efficient synthesis of 2-imidazol-2-yl acetates 530 (equation 234). Condensation of the a-amino ketals 528 with imidates 529, followed by cyclization in refluxing acidic dioxane, yielded 2-imidazol-2-yl acetates 530 in a one-pot reaction. 

This reaction, like all Neber rearrangements, is limited by availability... 

In a reinvoetigation of the Neber rearrangement 77 of oxiiiu-toeyl tes to aminoketonee it has been conclusively demonstrated that a l-azirine is an intermediate ( q. 70). When the reaction was run under slightly different conditions, an unstable aUtoxyaesridine v-i obtained. 2.105... 

Another significant preparative pathway to the 2i/-azirine system is the Neber rearrangement of oxime sulfonates. The presence of strong electron-withdrawing groups in the a-position to the oxime increases the acidity of those protons, and thus favors the cycloelimination reaction under mild conditions. The Neber reaction occurs either through an internal concerted nucleophilic displacement or via a vinyl nitrene (Scheme 213) <2001EJ02401>. 

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