Synthesis of novel pipecolic acid derivatives: a multicomponent approach from 3,4,5,6-tetrahydropyridines

A simple approach to several derivatives of pipecolic acid is via a multico mponent reaction starting from cyclic imines 2, which are synthesized on a large scale and with different substitution patterns. The protected amino a cids 3 are formed in high yields. In cases where chiral imines are used the target compounds are obtained with remarkable diastereoselectivity. Bisami des 3 serve as versatile precursors for the preparation of a wide range of amino acid derivatives. Different methods of hydrolysis of 3 lead to the fr ee pipecolic acids or its derivatives. Employment of methanol or ethanethio l as a nucleophile in the acid-mediated conversion of enamides 3 results in N-acylated amino acid esters 5. Furthermore a method for the resolution of the obtained racemic alpha-amino acids via diastereomeric salt formation i s described.