A Versatile Iron-Catalyzed Protocol for the One-Pot Synthesis of Isoxazoles or Isoxazolines from the Same Propargylic Alcohols

• Published in: Chemistry : a European journal Vol. 16; no. 40; pp. 12207 - 12213
• Main Authors: Debleds, Olivier, Gayon, Eric, Ostaszuk, Emilie, Vrancken, Emmanuel, Campagne, Jean-Marc
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 25-10-2010; WILEY‐VCH Verlag; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Subjects: Alcohol; Alcohols; alkynes; Catalysts; Chemical Sciences; Chemistry; cyclization; Gold; heterocycles; Iron; Organic chemistry; Pyridines; Synthesis; Triethylamine; Tuning; gold; iron; heterocycles; cyclization; alkynes
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201001461

The use N‐sulfonyl‐protected hydroxylamines as bi‐nucleophiles in iron‐catalyzed propargylic substitutions allows the selective one‐pot synthesis of four classes of substituted isoxazoles or isoxazolines from the same propargylic alcohols (21 examples) by simply tuning the nature of the base. By using an iron(III) catalyst and a base such as triethylamine (3 equiv), isoxazoles 3 are obtained in good isolated yields (56–95%), whereas N‐sulfonyl‐protected isoxazolines 6 are selectively obtained (77–93% yield) by using iron and gold catalysts in the presence of a catalytic amount of pyridine (10 mol%).
Strike while the iron is hot! Iron‐catalyzed protocols for the selective, one‐pot synthesis of four classes of substituted isoxazoles or isoxazolines from the same propargylic alcohols, with yields of up to 94 %, are described (21 examples; see scheme).