2026-10-11T10:39:17Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33973080 2026-09-23T12:11:21Z category_4 category_19 category_21 category_873 category_734 category_106 portal_63 item_type_3 month_year_09_2026

Nickel as a Competitive Drop-In Alternative to Palladium in Thermal C–O Cross-Couplings of Aliphatic Alcohols with Heteroaryl Halides: A High-Throughput Experimentation Study Kathleen M. Morrison (11285224) Emily C. Jackson (25097181) Alexis Lavallée (14510591) Faral Akhtar (20468437) Martin Priester (25097184) Devin Deussen (25097187) Philipp M. Holstein (1701724) Mark Stradiotto (1887670) Biochemistry Pharmacology Biotechnology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Science Policy offer catalytic performance ancillary ligand design thermal c – catalyzed c – class palladium catalysts ligated nickel precatalysts aryl ether formation alkyl heteroaryl ethers tertiary aliphatic alcohols tertiary alcohols aliphatic alcohols catalyzed processes aryl chloride heteroaryl halides heteroaryl chlorides thermal palladium throughput experimentation otherwise challenging otherwise best ligation ). g ., emerged owing disclose herein choice methodologies bromide electrophiles biological relevance appropriate dalphos Palladium-catalyzed thermal C–O cross-coupling reactions represent first-choice methodologies for alkyl (hetero)aryl ether formation in both academia and industry, especially when commencing from otherwise challenging (hetero)aryl chloride or bromide electrophiles and aliphatic alcohol coupling partners. While highly effective thermal nickel-catalyzed processes of this type have emerged owing to advances in ancillary ligand design, their use as competitive drop-in alternatives to palladium in such applications in the context of high-throughput experimentation (HTE) has not been demonstrated. In targeting the formation of alkyl heteroaryl ethers of biological relevance, we disclose herein a comparative HTE screening study focused on thermal palladium- or nickel-catalyzed C–O cross-couplings of primary, secondary, or tertiary aliphatic alcohols with heteroaryl chlorides or bromides. We demonstrate that appropriate DalPhos-ligated nickel precatalysts can offer catalytic performance in such transformations that is competitive with (e.g., for primary and secondary alcohols) or superior to (e.g., for tertiary alcohols) that achieved by use of otherwise best-in-class palladium catalysts (e.g., featuring biarylmonophosphine, JosiPhos, or other ligation). 2026-09-23T00:00:00Z Dataset Dataset 10.1021/acs.oprd.6c00228.s001 https://figshare.com/articles/dataset/Nickel_as_a_Competitive_Drop-In_Alternative_to_Palladium_in_Thermal_C_O_Cross-Couplings_of_Aliphatic_Alcohols_with_Heteroaryl_Halides_A_High-Throughput_Experimentation_Study/33973080 CC BY-NC 4.0