Synthesis of stereodefined piperidines from aziridines and their transformation into conformationally constrained amino acids, amino alcohols and 2,7-diazabicyclo[3.3.1]nonanes.
2-(2-Cyano-2-phenylethyl)aziridines were converted into novel cis- and trans-2-chloromethyl-4-phenylpiperidine-4-carbonitriles via alkylation with 1-bromo-2-chloroethane followed by microwave-assisted 6-exo-tet cyclization and regiospecific ring opening. The latter piperidines were used as eligible substrates for the synthesis of stereodefined 2-chloromethyl-, 2-hydroxymethyl-, and 2-carboxymethyl-4-phenylpiperidine-4-carboxylic acids, 2-hydroxymethyl-4-phenylpiperidine-4-carbonitriles, 3-hydroxy-5-phenylazepane-5-carbonitriles, and 5-phenyl-2,7-diazabicyclo[3.3.1]nonanes.
Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
Karel
K
Vervisch
Matthias
M
D'hooghe
Karl W
KW
Törnroos
Norbert
N
De Kimpe
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D001388:Aziridines / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D009570:Nitriles / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000596:Amino Acids; D000605:Amino Alcohols; D001388:Aziridines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D009570:Nitriles; D010880:Piperidines