Year: 2026
Type: preprint
Abstract: Investigation of hydrogenolytic removal of N -benzyloxycarbonyl ( N -Cbz) protecting groups from amino acid and dipeptide derivatives mediated by spherical SiliaCat Pd(0) under mild conditions using an H 2 -filled balloon allowed to optimize reaction parameters including solvent composition, substrate concentration, Pd loading, temperature, and catalyst particle size. The spherical catalyst enabled efficient N -Cbz deprotection at Pd loadings as low as 0.25–0.50 mol% under selected conditions, with high conversions, isolated yields, and selectivities across a broad range of amino acid derivatives. The methodology was successfully extended to N -Cbz-protected dipeptides, although substrate-specific optimization of solvent composition and Pd loading was required for more challenging substrates. Catalyst particle size primarily influenced reaction kinetics, with smaller particles providing faster deprotection, and larger particles advantageous for packed-bed continuous-flow applications. The catalyst showed useful chemoselectivity in the presence of Boc and tert -butyl ester protecting groups, while selective N -Cbz removal in the presence of benzyl esters could be achieved through appropriate control of reaction conditions. Comparison with commercial heterogeneous Pd catalysts showed that the spherical organosilica catalyst provided a favorable combination of complete conversion, high isolated yields, and consistently low Pd leaching. Overall, these results establish spherical SiliaCat Pd(0) as a practical, non-pyrophoric, and versatile heterogeneous catalyst for N -Cbz deprotection of amino acid and dipeptide derivatives, supporting its application in peptide-oriented synthesis.
Source: ChemRxiv
Institution: Institute of Nanostructured Materials
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7223186284