Synthesis of 3,3-dimethylazetidine-2-carboxylic acid and some derivatives

✍ Scribed by Norbert De Kimpe; Marc Boeykens; Dirk Tourwé

• Book ID: 104208452
• Publisher: Elsevier Science
• Year: 1998
• Tongue: French
• Weight: 591 KB
• Volume: 54
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(98)00024-6

✦ Synopsis

~,-Chloro-a-(N-alkylimino)esters were reduced by sodium cyanoborohydride in methanol in the presence of acetic acid with complete selectivity to give rise to either ~,-chloro-a-(N-alkylamino)esters (reaction at 0°C) or 1-alkyl-3,3-dimethylazetidine-2-carboxylic esters (reaction at reflux). The isolable ~,-cMoro-a-(N-alkylamino)esters are suitable sources for l-(N-alkylamino)-2,2-dimethylcycloprupane-1-carboxylic esters via base-induced 1,3-dehydrochlorination, while the former substrates as transient species undergo 1,4-dehydrocMorination to the corresponding azetidines. The latter process was used for the synthesis of 3,3-dimethylazetidine-2-carboxylic acid, a new non-proteinogenic sterically hindered c~-amino acid, via hydrogenolysis of methyl 1-benzyl-3,3-dimethylazetidine-l-carboxylate and subsequent acidic hydrolysis. Reduction of alkyl 4-chloro-3,3-dimethyl-a-(N-alkylimino)butanoates with lithiumaluminiumhydride in diethyl ether afforded 1-alkyl-3,3-dimethyl-2-(hydroxymethyl)azetidines.