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Deconstructive fluorination of cyclic amines by carbon-carbon cleavage

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Science  13 Jul 2018:
Vol. 361, Issue 6398, pp. 171-174
DOI: 10.1126/science.aat6365
  • Fig. 1 Development of a deconstructive fluorination of cyclic amines.

    (A) Well-established deconstructive functionalization. (B) An elusive deconstructive functionalization. (C) A blueprint for deconstructive fluorination of cyclic amines. (D) Optimization of silver-mediated deconstructive fluorination of N-Bz piperidine 1a. R, any functional group; Me, methyl; Ph, phenyl; equiv, equivalents; h, hour.

  • Fig. 2 Deconstructive fluorination: cyclic amine scope.

    Only isolated yields are shown. Reaction conditions: 1 (0.1 mmol), AgBF4 (4 equivalents), Selectfluor (4 equivalents), acetone:H2O (1:9), 40°C, 1 hour. *Deformylated product obtained. dr, diastereomeric ratio.

  • Fig. 3 Diversification of pipecolic acid and proline residues in peptides.

    Isolated yields are shown. Isolated yields of recovered starting material (RSM) are given in parentheses. Reaction conditions: 3 (0.1 mmol), AgBF4 (4 equivalents), Selectfluor (4 equivalents), acetone:H2O (1:9), room temperature, 15 hours.

  • Fig. 4 Mechanistic studies.

    (A) Proposed mechanism for 1a oxidation. (B) Possible mechanisms for fluorination of B. (C) Mechanistic studies. Reaction conditions: (a) starting material (0.1 mmol), AgBF4 (4 equivalents), Selectfluor (4 equivalents), acetone:H2O (1:9), 40°C, 1 hour; (b) 1a (0.5 mmol), AgBF4 (4 equivalents), Selectfluor (4 equivalents), acetone:H2O (1:9), room temperature, 16 hours. (D) Mechanistically driven gem-fluorination of enamide 10. Reaction conditions: 10 (0.1 mmol), AgBF4 (0.25 equivalents), Selectfluor (4 equivalents), acetone:H2O (1:1), room temperature, 15 hours. Phth, phthaloyl.

Supplementary Materials

  • Deconstructive fluorination of cyclic amines by carbon-carbon cleavage

    Jose B. Roque, Yusuke Kuroda, Lucas T. Göttemann, Richmond Sarpong

    Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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    • Materials and Methods 
    • Figs. S1 to S3
    • NMR Spectra
    • References 

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