N,N'-carbonyldiimidazole-mediated cyclization of amino alcohols to substituted azetidines and other N-heterocycles.
Amino alcohols are important synthons for N-heterocycles. We have developed an efficient method to activate hydroxyl groups, which avoids the use of toxic reagents and tolerates a wide variety of functional groups. Our strategy has been applied to the synthesis of functionalized p-methoxyphenyl-protected azetidines, pyrrolidines, and piperidines. The required amino alcohols were synthesized according to an optimized proline-catalyzed Mannich protocol. An azetidine analogue of ezetimibe was synthesized to demonstrate the potential for the synthesis of drug-like molecules.
de Figueiredo
Renata Marcia
RM
Institut für Organische Chemie der RWTH Aachen, Landoltweg 1, 52074 Aachen, Germany.
Fröhlich
Roland
R
Christmann
Mathias
M
D000605:Amino Alcohols / Q000737:chemistry*; D001384:Azetidines / Q000138:chemical synthesis*; D002384:Catalysis; D007093:Imidazoles / Q000737:chemistry*; D015394:Molecular Structure
D000605:Amino Alcohols; D001384:Azetidines; D007093:Imidazoles; C006900:N,N-carbonyldiimidazole