The use of the β-amino-alcohol-n-oxide derivatives in the synthesis of 2,3 or 4-alkyl substituted nh pyrrolidines

✍ Scribed by Georges Roussi; Jidong Zhang

• Publisher: Elsevier Science
• Year: 1991
• Tongue: French
• Weight: 775 KB
• Volume: 47
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(01)87128-3

✦ Synopsis

Nonstabilized azomethme ylides generated from the various B-amino alcohols N-oxides 13,17, 23 and 24 undergo [3+2] cycloadditron reactions with unactivated alkenes to afford the corresponding pyrrolidines 14a-g, 18a-g, 25 and 27 in moderate to good yields. These compounds are precursors of NH pyrrolidines substituted m position 2,3 or 4. We have discovered an efficient access to nonstabilized azomethine ylides Yl by lithium base deprotonation of tertiary amine N-oxides.2a These entities are so reactive that they undergo 3+2 intermolecular cycloaddition reaction to unactivated olefins leading to the corresponding N-alkylated pyrrolidines 2a in 60-70% yields.2 By using acetylenic derivatives, imines or thiones as dipolarophiles, pyrroles or pyrrolines, tmidazolidines 2b and thiazolidines 2c were respectively obtained (Scheme 1).2b 2 a z=c b EN c z=s Scheme 1 Because it is possible to build complex systems from the NH fonction and because some NH pyrrolidines are important derivatives from a biological point of view3, we report here various attempts to reach these compounds by the N-oxide deprotonation route Attempts from N-alkylated pyrrolidines. Several methods to N-demethylate tertiary amines or piperidines are repowhich rted (Polonovski and von Braun type reactions, KMn04 oxidanon, for exemple)4 and we tested them, since no specific method could be found in the literature, for N-demethylation of N-methyl pyrrolidines. In no case did we obtain the expected derivative, and we could only caracterise trace amounts of compounds resulting from nng opening. This 5161