Allkyl Substituent Effects on Pipecolyl Amide Isomer Equilibrium: Efficient Methodology for Synthesizing Enantiopure 6-Alkylpipecolic Acids and Conformational Analysis of Their N-Acetyl N’-Metylamides.
Martin E. Swarbrick, Francis Gosselin, and William D. Lubell. J. Org. Chem. 1999, 64, 1993-2002
Our investigation has provided effective means for preparing novel alkylpipecolates and better understanding of their conformational effects in peptide structures. Enantiopure 6-alkylpipecolates were synthesized by employment of α-tert-butyl N-(PhF) aspartate β-aldehyde in an aldol condensation, dehydration, reductive amination sequence. Primary, secondary, and tertiary alkyl as well as aromatic groups all were stereoselectively introduced at the 6-position of pipecolic acid. Furthermore, extension of this methodology offers potential to provide pipecolates with other substitution patterns.