The Polonovski Reaction

摘要: In connection with their interest in the isolation and medicinal properties of “gen alkaloids” (N-oxides), Max Michel Polonovski reported 1927 discovery that treatment a tertiary amine N-oxide acetic anhydride or acetyl chloride results rearrangement which one alkyl groups attached to nitrogen is cleaved, N-acetyl derivative corresponding secondary aldehyde are obtained. As original work by Polonovskis was mainly carried out on bicyclic tropane derivatives, products reaction were demethylated amides formaldehyde. The thus looked upon as means effecting N-demethylation amines. As such it was, still remains, viable alternative use cyanogen bromide, chloroformates, azocarboxylic esters, nitrous acid for this purpose. These methods often require more drastic conditions and/or promote unwanted side reactions. The central feature transformation an iminium ion intermediate. Depending structure substrate other activating reagent employed, formation can occur through loss α hydrogen, fragmentation Cαcarbon bond. Again, depending conditions, will either stop at stage ions become products, proceed give enamines amines aldehydes. close relationship between determine both product types regiochemistry, discussed. In its initial stages resembles reactions oxidized interaction pair electrons agent X followed elimination elements HX. Reagents like lead tetraacetate, N-bromosuccinimide particular mercuric acetate have been employed However, offer certain advantages selectivity experimental ease. In principle, any capable oxygen could reaction. three major agents, anhydrides chlorides (including chloroformate esters), iron salts complexes, sulfur dioxide, usually employed. Perhaps most important contribution modern organic synthesis 1960s replacing trifluoroacetic be stopped stage. Considering rich chemistry ions, many applications modified, Polonovski–Potier, appeared literature, spectacular first successful approach indole antitumor agents vinblastine group. In chapter discussion limited examples abovementioned reagents employed. coverage restricted oxides least substituents group. Both acyclic cyclic piperidine fall into category, whereas heteroaromatic N-oxides do not. With exception special case, nitrones also omitted from discussion. The literature includes articles appearing before end August 1988. Keywords: Polonovski reaction; scope; limitations; acylating agents; iron-based reagents; sulfur dioxide; carbon-hydrogen eliminations; synthetic applications; CC fragmentations; iron salts; silicon; selenium; experimental procedures; indole alkaloids