Research ArticleORGANIC CHEMISTRY

A remote C–C bond cleavage–enabled skeletal reorganization: Access to medium-/large-sized cyclic alkenes

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Science Advances  03 Nov 2017:
Vol. 3, no. 11, e1701487
DOI: 10.1126/sciadv.1701487
  • Fig. 1 Radical-initiated C–C bond cleavage via remote carbon-based functional group migration.

    (A) Reported remote radical aryl, carbonyl, and cyano migration and challenging vinyl migration process. (B) Proposed mechanism for remote radical vinyl migration process. (C) Our designed remote radical vinyl migration and synthetic application.

  • Fig. 2 Representative natural products containing medium-sized cyclic alkenes and bridged rings.

    Several natural products of eight- and nine-membered cyclic alkenes and bridged ring are shown.

  • Fig. 3 Substrate scope of linear substrates.

    1,3-, 1,4-, and 1,5-vinyl migration processes all provided desired products in moderate to good yields.

  • Fig. 4 Scope for medium- and large-sized cyclic alkenes.

    Diverse medium- and large-sized cyclic alkenes are constructed. (A) Remote 1,3-vinyl migration process. (B) Remote 1,4-vinyl migration process. (C) Synthesis of external cyclic alkenes. (D) Functional group diversity at alkenyl position.

  • Fig. 5 Scope for other radical precursors and polar alkenes.

    More fluoroalkyl-containing eight-membered cyclic alkenes are formed. (A) Applicability of other radical precursors. (B) Applicability of electron-rich vinyl ether substrate.

  • Fig. 6 Versatile transformations.

    The medium-sized cyclic alkenes are applicable for diverse transformation. (A) Dihydroxylation of cyclic alkene. (B) Epoxidation of cyclic alkenes. (C) Reduction of carbonyl group. NMO, N-methylmorpholine N-oxide; rt, room temperature; dr, diastereomeric ratio.

  • Table 1 Screening of the reaction conditions.

    Reaction conditions: 1A (0.2 mmol), 2 (1.5 equiv.), and Cu(I) (10 mol %) under argon atmosphere. Conversion (c) and yield (y) were determined by 1H nuclear magnetic resonance (NMR) spectroscopy using CH2Br2 as an internal standard. 2 (1.2 equiv.) was added for entry 6. 2 (1.8 equiv.) was added for entry 7. 2 (2.4 equiv.) was added in two portions with a time interval of 10 hours for entry 15. EtOAc, ethyl acetate; DCE, 1,2-dichloroethane; THF, tetrahydrofuran.


    Embedded Image
    Entry[Cu]SolventT (°C)Time (hours)c (%)y (%)
    1CuIEtOAc80249055
    2CuBrEtOAc80249546
    3CuClEtOAc80249054
    4CuOAcEtOAc802410055
    5CuCNEtOAc80249058
    6CuCNEtOAc80247034
    7CuCNEtOAc802410052
    8CuCNEtOAc60243020
    9CuCNEtOAc80188561
    10CuCNEtOAc1002410040
    11CuCNDCE801810032
    12CuCNCH3CN801810038
    13CuCNTHF80184030
    14CuCN1,4-Dioxane80187058
    15CuCN1,4-Dioxane80209569

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/3/11/e1701487/DC1

    scheme S1. Control experiments.

    fig. S1. Speculated energy profiles for carbonyl, aryl, and vinyl migration process.

    fig. S2. X-ray structures of 5I and 6.

    Experimental procedure

    Mechanistic study

    NMR spectra

    CIF Files 1 and 2

  • Supplementary Materials

    This PDF file includes:

    • scheme S1. Control experiments.
    • fig. S1. Speculated energy profiles for carbonyl, aryl, and vinyl migration process.
    • fig. S2. X-ray structures of 5I and 6.
    • Experimental procedure
    • Mechanistic study
    • NMR spectra

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    Other Supplementary Material for this manuscript includes the following:

    Files in this Data Supplement:

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