Unified Synthesis of 1,2-Oxy-aminoarenes via a Bio-inspired Phenol-Amine Coupling Kenneth Virgel N. Esguerra, Wenbo Xu, Jean-Philip Lumb Chem Volume 2, Issue 4, Pages 533-549 (April 2017) DOI: 10.1016/j.chempr.2017.03.003 Copyright © 2017 Elsevier Inc. Terms and Conditions
Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Figure 1 Representative Examples of 1,2-Oxy-aminoarenes Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Figure 2 Scope of Symmetric Phenols Reaction conditions for the synthesis of 20 and 21: (i) 1.0 mmol of phenol, CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) 11 (2.0 equiv) for 2 hr at 23°C. Reaction conditions for the synthesis of 22: (i) 1.0 mmol of phenol, CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) BnNH2 (2.0 equiv) and O2 (1 atm) for 2 hr at 23°C. See Figures S212–S217 for the corresponding 1H and 13C NMR spectra. Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Figure 3 Scope of Non-symmetric Phenols Benzoxazole synthesis: (i) phenol (1 mmol), CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) benzylamine (2.0 equiv) and O2 (1 atm) for 2 hr at 23°C. Benzoxazinone synthesis: (i) phenol (1 mmol), CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) phenylglycine methyl ester (2.0 equiv) in MeOH (5 mL) for 4 hr at 50°C. N-Aryl pyrrole synthesis: (i) phenol (1.0 mmol), CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) 3-pyrroline (2.0 equiv) for 2 hr at 23°C. Isolated yields are reported for each entry. 1H and 13C NMR spectra can be found in Figures S219–S263. Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Scheme 1 Representative Syntheses of 1,2-Oxy-aminoarenes (A) Synthesis of benzoxazole and benzoxazinone heterocycles from aminophenols. (B) Complementary conditions for cross-coupling of halogenated arenes and nitrogen coupling partners. Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Scheme 2 Lysyl Oxidase-Mediated Oxidation of Amines Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Scheme 3 Bio-inspired Aerobic Oxidation of Amines Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Scheme 4 Dehydrogenative Phenol-Amine Coupling Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Scheme 5 Unified Strategy for the Synthesis of Benzoxazoles and Benzoxazinones Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Scheme 6 Scope of Benzoxazoles and Benzoxazinones Benzoxazoles: (i) 1.0 mmol of 1, CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) amine (2.0 equiv) for 2 hr at 23°C. For entries 21, 27, and 38, reaction time decreased to 1 hr. Benzoxazinones: (i) 1.0 mmol of 1, CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) amine (2.0 equiv) in MeOH (5 mL) for 4 hr at 50°C. tBu deprotection: benzoxazinone (1.0 mmol) and H3PO4 (2 mL) at 220°C. Synthesis of 7: benzoxazole (1 mmol), AlCl3 (4 equiv), and PhMe for 5 hr at 40°C. Synthesis of 8: benzoxazole (1 mmol), AlCl3 (12 equiv), and PhMe for 2 hr at 80°C. Isolated yields are reported for each entry. See Figures S71–S167 for the corresponding 1H and 13C NMR spectra. Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Scheme 7 Scope of 2° or α-Branched Amines Entries 1 and 2: (i) 1.0 mmol of 1, CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) amine (2.0 equiv) for 2 hr at 23°C. Entries 3–8: (i) 1.0 mmol of 1, CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; (ii) amine (2.0 equiv) for 2 hr at 50°C; and (iii) NaBH4 (2.0 equiv) in MeOH (2 mL) for 2 hr at 0–23°C or Grignard reagent (3.0 equiv) for 2 hr at 0–23°C. Synthesis of 13: N-aryl pyrrole (entry 2, 0.05 mmol), AlCl3 (12 equiv) and toluene for 2 hr at 80°C. Synthesis of 14: aminophenol (entry 3, 1.0 mmol) and H3PO4 (2 mL) at 220°C. See Figures S168–S183 for the corresponding 1H and 13C NMR spectra. Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Scheme 8 Coupling with Pyrrolidine Synthesis of 16: (i) 1.0 mmol of 1, CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) 15 (2.0 equiv) for 2 hr at 23°C. Entries 1–5: (i) 1.0 mmol of 1, CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; (ii) 15 (2.0 equiv) for 2 hr at 23°C; and (iii) NaBH4 (2.0 equiv) in MeOH (2 mL) for 2 hr at 0–23°C (for entry 1) or Grignard reagent (3.0 equiv) for 2 hr at 0–23°C (for entries 2–5). Entries 6–8: N-aryl pyrrolidine (1.0 equiv), NaIO4 (3.0 equiv), and CH2Cl2/H2O (1:1) for 4 hr at 23°C. Entries 9–14: substrate (0.01–1.0 mmol) and H3PO4 (2 mL) at 220°C. Synthesis of 18 and 19: (i) 1.0 mmol of 1, CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) 17 (2.0 equiv) for 2 hr at 23°C. Entry 15: (i) 1.0 mmol of 1, CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) 17 (2.0 equiv) in MeOH for 4 hr at 50°C. See Figures S184–S211 for the corresponding 1H and 13C NMR data. Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Scheme 9 Studies on the Regiochemistry of ortho-Oxygenation and C–N Bond Formation Synthesis of A, D, and E: phenol (1 mmol), CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C. Synthesis of B, F, and G: quinone (1 mmol), benzylamine (2.0 equiv), and O2 (1 atm) for 2 hr at 23°C. 1H and 13C NMR spectra for ortho-quinone products can be found in Figures S264–S273 and S278–S280. Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions
Scheme 10 Linearly Fused Heterocycles Benzoxazole synthesis: (i) phenol (1 mmol), CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) benzylamine (2.0 equiv) and O2 (1 atm) for 2 hr at 23°C. Benzoxazinone synthesis: (i) phenol (1 mmol), CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) phenylglycine methyl ester (2.0 equiv) in MeOH (5 mL) for 4 hr at 50°C. N-Aryl pyrrole synthesis: (i) phenol (1.0 mmol), CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; and (ii) 3-pyrroline (2.0 equiv) for 2 hr at 23°C. Synthesis of aminophenols: (i) 1.0 mmol of 1, CuPF6 (8 mol %), DBED (15 mol %), O2 (1 atm), and CH2Cl2 (0.1 M) for 4 hr at 23°C; (ii) amine (2.0 equiv) for 12 hr at 50°C; and (iii) NaBH4 (2.0 equiv) in MeOH (2 mL) for 2 hr at 0–23°C. Isolated yields are reported for each entry. See Figures S289–S318 for 1H and 13C NMR spectra. Chem 2017 2, 533-549DOI: (10.1016/j.chempr.2017.03.003) Copyright © 2017 Elsevier Inc. Terms and Conditions