Non-natural azetidine-based amino acids (Aze) present interesting features in protein engineering. A simple organometallic route toward unsaturated carboxylic acid precursors is presented. Subsequent metal-catalyzed asymmetric reduction allowed for the synthesis of a new library of 2-azetidinylcarboxylic acids, which were finally employed in the formation of small peptide chains.

The addition of nucleophilic organometallic species onto in situ generated azabicyclobutanes enables the selective formation of 3-arylated azetidine intermediates through strain-release. Single pot strategies were further developed for the N-arylation...

Recent progress on four-membered ring building blocks has led us to investigate the formation of non-natural azetidine-based amino acids (<i>Aze</i>). A simple organometallic route was developed to access unsaturated carboxylic acids, which were further engaged in metal catalyzed asymmetric reduction. Functionalized <i>Aze</i> derivatives were finally employed in the formation of small peptide chains.

The addition of nucleophilic organometallic species onto in situ generated azabicyclobutanes enables the selective formation of 3-arylated azetidine intermediates through strain-release. Single pot strategies were further developed for the N-arylation of resulting azetidines, employing either SNAr reactions or Buchwald-Hartwig couplings.

Recent progress on four-membered ring building blocks has led us to investigate the formation of non-natural azetidine-based amino acids (<i>Aze</i>). A simple organometallic route was developed to access unsaturated carboxylic acids, which were further engaged in metal catalyzed asymmetric reduction. Functionalized <i>Aze</i> derivatives were finally employed in the formation of small peptide chains.