Selective Aerobic Oxidation of Primary Alcohols to Aldehydes

Abstract

The 2-azaadamantane-N-oxyl (AZADO)- and 9-azanoradamantane-N-oxyl (nor-AZADO)-catalyzed selective oxidation of primary alcohols to the corresponding aldehydes is described. The use of tert-butyl nitrite as the co-catalyst enables efficient aerobic oxidation in MeCN instead of previously reported AcOH; this is important for the selectivity of the reaction. The addition of a solution of saturated aqueous NaHCO₃ after the completion of the reaction was effective to suppress the overoxidation of the product to the corresponding carboxylic acid during the workup.

Key words

oxidation - nitroxyl radical - primary alcohols - aldehydes - chemoselectivity

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• 15 4-Phenylbutanal (7b); Typical Procedure To a solution of 4-phenylbutan-1-ol (7a, 45.8 mg, 0.305 mmol) and AZADO (2, 2.36 mg, 15.5 μmol) in MeCN (1.5 mL) was added TBN (92%, 7.9 μL, 61 μmol). The reaction mixture was stirred under an air atmosphere at r.t for 10 h. After the addition of a saturated aqueous NaHCO₃ solution (3 mL), the resulting mixture was extracted with EtOAc (3 × 5 mL). The combined organic layer was dried over MgSO₄, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (hexane–EtOAc, 20:1) to give 4-phenylbutanal (7b) as a colorless oil; 42.0 mg (93%). ¹H NMR (400 MHz, CDCl₃): δ = 9.56 (t, J = 1.6 Hz, 1 H), 7.34–7.25 (m, 2 H), 7.24–7.16 (m, 3 H), 2.66 (t, J = 7.6 Hz, 2 H), 2.45 (dt, J = 7.6, 1.6 Hz, 2 H), 1.97 (quint, J = 7.6 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 201.3, 140.2, 127.5, 125.1, 42.2, 34.0, 22.7. 3-Pentafluorophenylpropanal (11b) Colorless oil; 66.4 mg (80%). ¹H NMR (400 MHz, CDCl₃): δ = 9.81 (s, 1 H), 3.03 (t, J = 7.2 Hz, 2 H), 2.80 (t, J = 7.2 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 199.4, 145.0 (dm, J = 245 Hz), 140.0 (dm, J = 243 Hz), 137.5 (dm, J = 251 Hz), 113.3 (td, J = 18.1, 3.8 Hz), 42.5, 15.1. HRMS (DART): m/z calcd for C₁₈H₁₄F₁₀NO₃·NH₄ [2M + NH₄]⁺: 466.0865; found: 466.0858. 4-Methoxyphenylacetaldehyde (16b) Pale yellow oil; 56.8 mg (86%). ¹H NMR (400 MHz, CDCl₃): δ = 9.72 (t, J = 2.0 Hz, 1 H), 7.17–7.09 (m, 2 H), 6.95–6.85 (m, 2 H), 3.80 (s, 3 H), 3.62 (d, J = 2.0 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 199.6, 158.9, 130.6, 123.7, 114.4, 55.2, 49.7.