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PreprintCC BYChemRxiv

Zirconium-Mediated C–O Bond Cleavage of Alkenyl Ethers Enables Nickel-Catalyzed C(sp3)–C(sp3) and C(sp3)–C(sp2) Cross-Coupling

  • Haowen Xu1,2,3
  • Songlin Bai3
  • Bin Yang1,2,3
  • Yijie Huang1,2,3
  • Gen Li3
  • Xiangbing Qi3,4
4 affiliations
  1. 1School of Life Sciences
  2. 2Tsinghua University
  3. 3National Institute of Biological Sciences, Zhongguancun Life Science Park, Beijing, China, 102206
  4. 4Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University
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Abstract

Inert aliphatic C–O bonds are ubiquitous in both natural and synthetic feedstocks, yet their direct functionalization remains a formidable challenge in sustainable synthesis. Here we report a tandem strategy that merges thermal zirconium-mediated deoxygenation of alkenyl ethers with visible-light-induced nickel-catalyzed cross-coupling. Through β-oxygen elimination and chain walking, readily available ethers are transformed into alkylzirconocene nucleophiles, enabling efficient C(sp3)–C(sp3) and C(sp3)–C(sp2) bond formation with alkyl and aryl iodides. The method exhibits broad functional group tolerance, late-stage applicability to pharmaceuticals and natural products, gram-scale scalability, and an enantioselective variant (94% ee). Notably, the oxygen-retentive reaction of dihydropyran and the dual functionalization of PMB-protected ethers highlight the atom-economical potential of this protocol. Mechanistic studies elucidate the preference for β-oxygen elimination over β-hydride elimination and reveal the role of a special Zr (III) species as a single-electron donor in the catalytic cycle. This work provides a direct route from unactivated aliphatic C–O bonds to functionalized alkanes, advancing the sustainable valorization of renewable biomass feedstocks.

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Cite

BibTeXRIS
BibTeX
@misc{xu2026zirconiummediated,
  title = {{Zirconium-Mediated C–O Bond Cleavage of Alkenyl Ethers Enables Nickel-Catalyzed C(sp3)–C(sp3) and C(sp3)–C(sp2) Cross-Coupling}},
  author = {Haowen Xu and Songlin Bai and Bin Yang and Yijie Huang and Gen Li and Xiangbing Qi},
  howpublished = {ChemRxiv},
  year = {2026},
  month = sep,
  doi = {10.26434/chemrxiv.15008196/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008196/v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Zirconium-Mediated C–O Bond Cleavage of Alkenyl Ethers Enables Nickel-Catalyzed C(sp3)–C(sp3) and C(sp3)–C(sp2) Cross-Coupling
AU  - Haowen Xu
AU  - Songlin Bai
AU  - Bin Yang
AU  - Yijie Huang
AU  - Gen Li
AU  - Xiangbing Qi
PY  - 2026
DA  - 2026/09/02
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15008196/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008196/v1
AB  - Inert aliphatic C–O bonds are ubiquitous in both natural and synthetic feedstocks, yet their direct functionalization remains a formidable challenge in sustainable synthesis. Here we report a tandem strategy that merges thermal zirconium-mediated deoxygenation of alkenyl ethers with visible-light-induced nickel-catalyzed cross-coupling. Through β-oxygen elimination and chain walking, readily available ethers are transformed into alkylzirconocene nucleophiles, enabling efficient C(sp3)–C(sp3) and C(sp3)–C(sp2) bond formation with alkyl and aryl iodides. The method exhibits broad functional group tolerance, late-stage applicability to pharmaceuticals and natural products, gram-scale scalability, and an enantioselective variant (94% ee). Notably, the oxygen-retentive reaction of dihydropyran and the dual functionalization of PMB-protected ethers highlight the atom-economical potential of this protocol. Mechanistic studies elucidate the preference for β-oxygen elimination over β-hydride elimination and reveal the role of a special Zr (III) species as a single-electron donor in the catalytic cycle. This work provides a direct route from unactivated aliphatic C–O bonds to functionalized alkanes, advancing the sustainable valorization of renewable biomass feedstocks.
ER  -