Correlation Engine 2.0
Clear Search sequence regions


  • 1 adamantanol (1)
  • 2 2′- bipyridyl (1)
  • acetals (1)
  • acid (21)
  • acids vitamin (1)
  • acyl (3)
  • adducts (1)
  • alcohols n- dodecyl (2)
  • alkyl (3)
  • appears (1)
  • artemisinins (1)
  • benzoates (15)
  • benzoic acids (2)
  • benzyl alcohol (1)
  • benzyl alcohol (1)
  • bht (1)
  • bromide (5)
  • carbamates (1)
  • carbonates (1)
  • catalysis (2)
  • cross- reaction (9)
  • cyclobutanol (1)
  • cyclohexanol (1)
  • d 53 (1)
  • d c (1)
  • dppf (13)
  • drug design (2)
  • esters (4)
  • ethanol (1)
  • ethers (17)
  • ethyl acetate (5)
  • glycol (1)
  • gram (1)
  • isopropanol (1)
  • ligand (10)
  • light (1)
  • magnesium (1)
  • menthol (2)
  • methanol (1)
  • molecular structures (1)
  • nad (1)
  • nitrogen (3)
  • OAc 2 (3)
  • oxygen (1)
  • palladium (1)
  • peer review (1)
  • potassium (3)
  • powder (2)
  • PPh3 (4)
  • protocols (6)
  • reagent (2)
  • reductases (1)
  • salts (1)
  • scale (2)
  • signals (1)
  • solvent (6)
  • tempo (5)
  • vinyl compounds (1)
  • vitamin e (1)
  • zinc (5)
  • Sizes of these terms reflect their relevance to your search.

    gem-Difluoroalkene is a bioisostere of carbonyl group for improving bioavailability of drug candidates. Herein we develop structurally diverse 2,2-difluorovinyl benzoates (BzO-DFs) as versatile building blocks for modular synthesis of gem-difluoroenol ethers (44 examples) and gem-difluoroalkenes (2 examples) by Ni-catalyzed cross coupling reactions. Diverse BzO-DFs derivatives bearing sensitive functional groups (e.g., C = C, TMS, strained carbocycles) are readily prepared from their bromodifluoroacetates and bromodifluoroketones precursors using metallic zinc as reductant. With Ni(COD)2 and dppf [1,1'-bis(diphenylphosphino)ferrocene] as catalyst, reactions of BzO-DFs with arylboronic acids and arylmagnesium/alkylzinc reagents afforded the desired gem-difluoroenol ethers and gem-difluoroalkenes in good yields. The Ni-catalyzed coupling reactions features highly regioselective C(vinyl)-O(benzoate) bond activation of the BzO-DFs. Results from control experiments and DFT calculations are consistent with a mechanism involving initial oxidative addition of the BzO-DFs by the Ni(0) complex. By virtue of diversity of the BzO-DFs and excellent functional group tolerance, this method is amenable to late-stage functionalization of multifunctionalized bioactive molecules.

    Citation

    Bingnan Du, Chun-Ming Chan, Pui-Yiu Lee, Leong-Hung Cheung, Xin Xu, Zhenyang Lin, Wing-Yiu Yu. 2,2-difluorovinyl benzoates for diverse synthesis of gem-difluoroenol ethers by Ni-catalyzed cross-coupling reactions. Nature communications. 2021 Jan 18;12(1):412

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 33462244

    View Full Text