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 o f electrophiles under palladium catalysis to give substituted phenylalanine s and 4-oxoamino acids in variable yields (21 59%). Transformation into the organocopper reagent 13 allowed coupling with allyl chloride and ethyl oxa lyl chloride. Removal of the tort-butyl group gives Fmoc-protected amino ac ids (63-95%), suitable for use in automated solid phase peptide synthesis.