Practical method for the synthesis of (R)-homopipecolinic acid and (R)-homoproline esters from ω-chloroalkanoic acids and available chiral amines

A practical synthesis of (R)-homopipecolinic acid methyl ester and (R)-homoproline methyl ester was performed utilizing (i) a direct intramolecular cyclization of ω-chloro-β-enamino esters and , which were prepared from available (S)-1-phenylethylamine or (S)-1-(1-naphthyl)ethylamine and ω-chloro-β-keto esters and , respectively and (ii) a highly diastereoselective NaBH4 reduction followed by hydrogenolysis. The present method is a short-step process using inexpensive and readily available substrates and reagents with fewer wasted materials.