# A versatile route towards 6-arylpipecolic acids

## TL;DR

This paper introduces a new method to create enantiomerically pure pipecolic acid derivatives with aryl groups in the C6 position using chiral amino acids and metal-catalyzed reactions.

## Contribution

A novel route for synthesizing 6-arylpipecolic acids using chiral amino acids and transition metal-catalyzed cross-coupling.

## Key findings

- Enantiomerically pure pipecolic acid derivatives with aryl modifications in C6 position were successfully synthesized.
- NMR analysis revealed conformational constraints and dihedral angles consistent with coupling constants.
- The method utilizes a chiral pool and transition metal catalysis for efficient synthesis.

## Abstract

Pipecolic acid is known as a non-proteinogenic amino acid with a secondary amine. It contains a six-membered ring and is, like its five-membered correlate, known for its secondary structure inducing properties, which are particularly useful in the design of peptide conformations. We present a new and improved way to generate enantiomerically pure pipecolic acid derivatives with aryl modifications in C6 position by utilising the chiral pool of a non-proteinogenic amino acid in combination with transition metal-catalysed cross-coupling reactions. Moreover, we present an in-depth NMR analysis of the key intermediate steps, which illustrates the conformational constraints in accordance with coupling constants and resulting dihedral angles.