Reaction of N-t-Boc, Z or Fmoc protected 4-iodo-L-phenylalanine with t-BuSH was explored as a direct approach to the preparation of the corresponding novel 4-thiophenylalanine derivatives. It was found that Pd (0), additive, and Et₃N are all essential to bring about the desired coupling reaction. Of the two sources of Pd (0) employed, Pd₂dba₃. CHCl₃ was found to be more satisfactory and of the six additives screened DPPF was the most efficient reagent to bring about a clean coupling reaction in 3 h at 70-75 °C. While the t-Boc and Z protected 4-iodophenylalanines provided the corresponding thiophenylalanine derivatives in good yields the Fmoc protected derivative underwent base promoted cleavage of the Fmoc group. However, the desired N-Fmoc protected 4-S-t-butyl thiophenylalanine was obtained from the corresponding Boc-protected thiophenylalanine derivative via a sequential deprotection- reprotection approach. Finally, stability of the S-t-butyl group in these N-protected thiophenylalanine derivatives to the conditions of peptide synthesis was evaluated.