Nickel‐catalyzed P ‐arylation of HP(= O)(R/OR) 2 nucleophiles with (hetero)aryl chlorides enabled by DalPhos ligation

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Cotnam, Michael J. and Redpath, T. Kieran and Weetman, Catherine E. and DeRoy, Patrick L. and Nelson, David J. and Stradiotto, Mark (2025) Nickel‐catalyzed P ‐arylation of HP(= O)(R/OR) 2 nucleophiles with (hetero)aryl chlorides enabled by DalPhos ligation. Chemistry - A European Journal, 31 (59). e02189. ISSN 1521-3765 (https://doi.org/10.1002/chem.202502189)

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Abstract

Herein we disclose our development of broadly useful C-P cross-couplings of (hetero)aryl chlorides and HP(O)(R)2 or HP(O)(OR)2 nucleophiles, enabled by use of nickel/DalPhos-based catalysts. These typically use 5 mol% nickel at 110 °C for 18 hours, but the feasibility of shorter or milder reactions was demonstrated with one specific example. The ability to apply such transformations on gram scale, and in the P-arylation of active pharmaceutical ingredients (APIs) (i.e., chloroquine and clozapine) was also shown. Also described are our findings arising from the computational modelling of such cross-coupling reactions by use of density functional theory (DFT) calculations, which confirmed the clear preference for C-P bond formation involving three-centered reductive elimination through substrate PV pathways.

ORCID iDs

Cotnam, Michael J., Redpath, T. Kieran, Weetman, Catherine E. ORCID logoORCID: https://orcid.org/0000-0001-5643-9256, DeRoy, Patrick L., Nelson, David J. ORCID logoORCID: https://orcid.org/0000-0002-9461-5182 and Stradiotto, Mark;
  • Item type:Article
    ID code:94193
    Dates:
    Date
    Event
    22 October 2025
    Published
    15 September 2025
    Published Online
    9 September 2025
    Accepted
    2 July 2025
    Submitted
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:17 Sep 2025 08:49
    Last modified:07 Aug 2026 06:34
    URI:https://strathprints.strath.ac.uk/id/eprint/94193
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