Open-Flask Protocol for the Removal of Alloc Carbamate and Allyl Ester Protecting Groups. Application to In-solution and On-resin Peptide Synthesis

The standard protocol for Alloc group removal during peptide synthesis still presents limitations, including low reaction yields, <i>N</i>-allylated byproducts, and the use of air-sensitive Pd(PPh₃)₄. We addressed these challenges by developing a novel protocol using the air-stable Pd(PPh₃)₂Cl₂ catalyst, Meldrum's acid (MA), and triethylsilane (TES-H). This combination ensured high yields, eliminated <i>N</i>-allylated byproducts, and is compatible with automated synthesis. This cost-effective and efficient method shows promise for widespread use in peptide chemistry applications and beyond.