NHC Compound for the Redox Activation of Aliphatic Alcohols

C(sp²)-C(sp³) cross-coupling reactions allow the direct introduction of alkyl groups to aromatic rings. sp³-Carbon-rich compounds have attracted much attention in drug discovery research because they can improve water solubility and off-targets.¹⁾ They are also effective for introducing bioisosteres, which are the biological equivalents of aromatic rings.
Deoxazole (1), an N-heterocyclic carbene (NHS) salt, reacts with aliphatic alcohols to give redox-active alkyl compounds.²⁾ The synthetic reaction of redox-active alkyl compounds is so fast that it is completed in about 5 minutes at room temperature. Without purification, the product can then be used in cross-coupling reactions with aryl bromides under Ir/Ni metallaphotoredox conditions to give alkylated aromatic compounds. This reaction can be applied to complex compounds such as sugars, APIs, and natural products such as paclitaxel. 1 has also been reported to be used in parallel synthesis using an automated synthesis apparatus³⁾ and as a catalyst for Mitsunobu-type ether synthesis.⁴⁾

References

• 1) Expanding the Medicinal Chemist Toolbox: Comparing Seven C(sp²)-C(sp³) Cross-Coupling Methods by Library Synthesis
  • A. W. Dombrowski, N. J. Gesmundo, A. L. Aguirre, K. A. Sarris, J. M. Young, A. R. Bogdan, M. C. Martin, S. Gedeon, Y. Wang, ACS Med. Chem. Lett. 2020, 11, 597.
• 2) Metallaphotoredox-enabled deoxygenative arylation of alcohols
  • Z. Dong, D. W. C. MacMillan, Nature 2021, 598, 451.
• 3) Enabling Deoxygenative C(sp²)-C(sp³) Cross-Coupling for Parallel Medicinal Chemistry
  • W. Liu et al., ACS Med. Chem. Lett. 2023, 14, 853.
• 4) Deoxygenative alcohol-nucleophile coupling via carbocations
  • L. Thai-Savard, J. R. Zbieg, J. A. Terrett, Chem Catal. 2025, 5, 101187.

Related Products

D4887

(4,4'-Di-tert-butyl-2,2'-bipyridine)bis[(2-pyridinyl)phenyl]iridium(III) Hexafluorophosphate (= Ir(ppy)₂(dtbbpy)PF₆)

Q0062

Quinuclidine

Page Top