Research ArticlePHYSICAL SCIENCES

In situ generation of N-unsubstituted imines from alkyl azides and their applications for imine transfer via copper catalysis

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Science Advances  09 Aug 2017:
Vol. 3, no. 8, e1700826
DOI: 10.1126/sciadv.1700826
  • Fig. 1 Azides derived synthons and transition metal imine complexes.

    (A) Transition metal–catalyzed C–N bond formation from azides. (B) Isolated transition metal imine complexes.

  • Fig. 2 The construction of C–N bonds through imine transfer reactions using azides as nitrogen source.

    (A) Modulating ligands enables imine transfer reactions using azides. (B) This work.

  • Scheme 1 Isotope study.
  • Scheme 2 Proposed mechanism.
  • Scheme 3 Key NOESY correlations of 14cll.
  • Scheme 4 Construction of unsymmetrical 2,3,5-triaryl pyridine 14cgd.
  • Table 1 Optimization of reaction conditions for the construction of 3,5-diaryl pyridines.

    Reaction conditions: 1a (0.1 mmol, 1 equiv.), catalyst (0.01 mmol, 0.1 equiv.), ligand (0.01 mmol, 0.1 equiv.), and additive (0.02 mmol, 0.2 equiv.) in solvent (1.0 ml) at T (°C) for 48 hours. MS, molecular sieves; phen, 1,10-phenanthroline; bpy, bipyridine; THF, tetrahydrofuran; n.r., no reaction.


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  • Table 2 Substrate scope for the construction of 3,5-diaryl pyridines.

    Reaction conditions: 1 (0.5 mmol, 1 equiv.), CuBr2 (0.05 mmol, 0.1 equiv.), L1* (0.05 mmol, 0.1 equiv.), AgSbF6 (0.01 mmol, 0.2 equiv.), 4 Å MS (150 mg), and HFIP (5.0 ml). Yields were that of isolated products.


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  • Table 3 Substrate molecules for the construction of unsymmetrical 3,5-diaryl pyridines.

    Reaction conditions: 1 (0.2 mmol, 1 equiv.), 1′ (0.8 mmol, 4 equiv.), CuBr2 (0.04 mmol, 0.2 equiv.), L1* (0.04 mmol, 0.2 equiv.), AgSbF6 (0.08 mmol, 0.4 equiv.), 4 Å MS (60 mg), and HFIP (2.0 ml). Yields were that of isolated products.


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  • Table 4 Optimization of reaction conditions for the construction of indoles.

    Reaction conditions: 3a (0.1 mmol, 1 equiv.), catalyst [x mole percent (mol %)], ligand (0.01 mmol, 0.1 equiv.), AgSbF6 (0.01 mmol, 0.1 equiv.), 4 Å MS (30 mg), and base (0.2 mmol, 2.0 equiv.) in solvent (1.0 ml) for 48 hours at 110°C. DME, dimethoxyethane; NMP, N-methyl-2-pyrrolidone.


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  • Table 5 Substrate scope for the construction of indoles.

    Reaction conditions: 3 (0.5 mmol, 1 equiv.), CuI (0.2 mmol, 0.4 equiv.), L1* (0.05 mmol, 0.1 equiv.), AgSbF6 (0.05 mmol, 0.1 equiv.), 4 Å MS (150 mg), and NaOtBu (0.1 mmol, 2.0 equiv.) in HFIP/dioxane [3:7 (v/v), 5.0 ml] for 24 to 80 hours at 110°C. Yields were that of isolated products.


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  • Table 6 Construction of 2,3,5-triaryl pyridines.

    Reaction conditions: 13 (0.2 mmol, 1 equiv.), 1 (0.6 mmol, 3 equiv.), CuBr2 (0.04 mmol, 0.2 equiv.), L1* (0.04 mmol, 0.2 equiv.), AgSbF6 (0.08 mmol, 0.4 equiv.), and 4 Å MS (60 mg) in HFIP (2.0 ml) for 24 hours at 100°C. Yields were that of isolated products.


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Supplementary Materials

  • Supplementary Materials

    This PDF file includes:

    • Supplementary Materials and Methods
    • Substrate structure
    • Experimental sections
    • NMR spectra
    • References (65–77)

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