Synthesis of α-amino acids using amino acid γ-anion equivalents: synthesis of 5-oxo α-amino acids, homophenylalanine derivatives and pentenylglycines

Abstract

Treatment of protected iodohomoalanine 7 with Rieke copper leads to the formation of an organocopper reagent 10 which reacts with electrophiles in moderate yield to give enantiomerically pure α-amino acid derivatives 11, 12 and 13. Alternatively, reaction of the fully protected iodohomoalanine derivative 15 with activated zinc gives the corresponding alkylzinc iodide 14, which reacts under palladium catalysis with a range of electrophiles (aryl iodides and acid chlorides) to give the corresponding adducts 19 and 22. While the reactions with aryl iodides provide acceptable yields in THF as solvent, the corresponding reactions with acid chlorides requires dimethoxyethane or, preferably, a combination of toluene and dimethylacetamide under ultrasonication, for good results. The alkylzinc iodide 14 can be transformed into a zinc–copper reagent 16 which reacts with allylic halides, and with reactive acid chlorides, to give the corresponding adducts 22l, 24–26 in reasonable yields.