Nickel-Catalyzed Deallylation for Sustainable Solution and Solid-Phase Peptide Synthesis
We report a one-step, nickel-catalyzed allyl/alloc deprotection compatible with solid-phase peptide synthesis (SPPS) to address the reliance on costly palladium conditions and limited on-resin compatibility of base-metal alternatives. Our two-component system employs an air-stable Ni(PPh<sub>3</sub>)<sub>2</sub>Br<sub>2</sub> precatalyst and NH<sub>3</sub>BH<sub>3</sub> reductant and operates rapidly in SPPS-compatible solvents under inertion. This protocol efficiently and chemoselectively deprotects allyl- and alloc-protected amino acids, small molecules, and peptides in solution and has been extended to on-resin deprotection, showing promise for SPPS applications.
Authors
- Sam Crossley (ORCID: https://orcid.org/0000-0002-4187-5079)
- Kyle E. Ruhl (ORCID: https://orcid.org/0009-0008-2073-7444)
- Brittany M. Armstrong (ORCID: https://orcid.org/0000-0002-6049-4781)
- Yangzhong Qin (ORCID: https://orcid.org/0000-0002-2450-521X)
- Serge Ruccolo (ORCID: https://orcid.org/0000-0002-4297-2751)
- Renee J. Sifri (ORCID: https://orcid.org/0000-0003-0315-5158)
- Omer Ad
- Maria Camila Aguilera
Institutions
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Analytical Services (US)
- Materials Processing (United States) (US)
Publication Details
- Journal
- Organic Letters
- Published
- 2026-02-25
- DOI
- https://doi.org/10.1021/acs.orglett.6c00213
- Primary Topic
- Chemical Synthesis and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00