Thiol vs carboxylic acid reactivity to acyl chlorides?

Question

I want to form a thioester between some acyl chlorides and NBoc-cysteine. Is the free thiol so much more reactive than the carboxylic acid in cysteine that the side product formation of carboxylic anhydrides is negligible?

Answer 1

I think so that's the case according to Ref.1. For example:

Your $\ce{R^1}$-group can be one you wish to have. A typical procedure to prepare S-Acylation of N-protected-cysteines is given in the reference as follows:

To a solution of N-protected-L-cysteine ($\bf{4a-c}$; $\pu{1 mmol}$) in THF ($\pu{5 mL}$) was added a solution of acyl 1-benzotriazolyl $\bf{5}$ ($\pu{1 mmol}$) in THF ($\pu{5 mL}$) in the presence of $\ce{KHCO3}$ ($\pu{1 mmol}$). The heterogeneous mixture was then stirred at room temperature for $\pu{12 h}$. THF was evaporated, and the solution was acidified with $\ce{HCl}$, and the solid formed was taken in ethyl acetate and washed with $\ce{HCl}$ ($\pu{1N}$, 3×) and brine (3×) and then dried over sodium sulfate. Evaporation of ethyl acetate under reduced pressure afforded N-protected S-acyl cysteine.

References:

1. Tarek S. Ibrahim, Srinivasa R. Tala, Said A. El-Feky, Zakaria K. Abdel-Samii, and Alan R. Katritzky, "Cysteinoyl- and Cysteine-containing Dipeptidoylbenzotriazoles with Free Sulfhydryl Groups: Easy Access to N-terminal and Internal Cysteine Peptides," Chemical Biology & Drug Design 2012, 80(2), 194-202 (DOI: https://doi.org/10.1111/j.1747-0285.2011.01303.x).