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DOI: 10.1055/s-2008-1078610
Synthesis of Pyridines via Rh-Catalyzed Ring Expansion of Isoxazoles
Contributor(s):Victor Snieckus, Timothy HurstUniversity of Buffalo, The State University of New York, USA
One-Pot Synthesis of Highly Functionalized Pyridines via a Rhodium Carbenoid Induced Ring Expansion of Isoxazoles
J. Am. Chem. Soc. 2008, 130: 8602-8603
Publication History
Publication Date:
22 August 2008 (online)
Key words
pyridines - rhodium carbenoids - ring expansion - isoxazoles
Significance
Reported is the one-pot synthesis of highly functionalized pyridines via the ring expansion of isoxazoles using Rh catalysis. Optimal conditions were found to be slow addition of the diazo compound 1 to a toluene solution of the catalyst and isoxazole 2 at 60 ˚C to ensure complete formation of the Rh carbenoid. Intermediate 3 may be isolated. Increasing the temperature to reflux effects cyclization to the dihydropyridines 4, which were oxidized with DDQ to the aromatic derivatives 5 in moderate to excellent yield. The substrate scope was widely studied, with the lower yields observed for the more electron-rich heteroaromatic vinyldiazoacetates.
Comment
Functionalized pyridines and dihydropyridines demonstrate a wide range of important biological activity. Typical methods for their preparation include the classical Hantzsch synthesis, cycloaddition and electrocyclization processes and multicomponent condensations. The current method represents a rapid and efficient synthesis of pyridine derivatives starting from 3,5-disubstituted isoxazoles, which themselves may be readily prepared in good yield from oximes and alkynes under copper catalysis. Expansion of this reaction to involve N-O-bond carbenoid insertion to form other heterocycles may be envisaged.