Mitsunobu approach to the synthesis of optically active alpha,alpha-disubstituted amino acids.
Chiral tertiary alpha-hydroxy esters of known stereochemical configuration were transformed to alpha-azido esters by Mitsunobu reaction with HN3. Optimization of this reaction was shown to proceed at room temperature with high chemical yield using 1,1-(azodicarbonyl)dipiperidine (ADDP) and trimethylphosphine (PMe3). Complete inversion of configuration was observed at the alpha-carbon. Several alpha,alpha-disubstituted amino acids were synthesized in high overall chemical yield and optical purity.
Green
Jonathan E
JE
Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Bender
David M
DM
Jackson
Stona
S
O'Donnell
Martin J
MJ
McCarthy
James R
JR
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D004952:Esters; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry; D013237:Stereoisomerism
C538981:1,1-(azodicarbonyl)dipiperidine; D000596:Amino Acids; D004952:Esters; D010880:Piperidines