Direct synthesis of Fmoc-protected amino acids using organozinc chemistry: application to polymethoxylated phenylalanines and 4-oxoamino acids

The new N-Fmoc 3-iodoalanine tort-butyl ester derived organozinc reagent 1, obtained in 7 steps from optically pure L-serine. was coupled to a range of electrophiles under palladium catalysis to give substituted phenylalanines and 4-oxoamino acids in variable yields (21 59%). Transformation into the organocopper reagent 13 allowed coupling with allyl chloride and ethyl oxalyl chloride. Removal of the tort-butyl group gives Fmoc-protected amino acids (63-95%), suitable for use in automated solid phase peptide synthesis.