Brønsted acid catalyzed intramolecular benzylic cyclizations of alkylpyridines
Ashabha I Lansakara1, Daniel P Farrell, F Christopher Pigge
1Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, USA. chris-pigge@uiowa.edu.
Abstract:
Aldehyde and ketone electrophiles incorporated into the side chains of 2- and 4-alkylpyridines participate in intramolecular aldol-like condensations with pyridine benzylic carbons in the presence of Brønsted acid catalysts. Pyridines featuring β-ketoamide side chains undergo cyclization in the presence of 10 mol% TfOH to afford pyridyl-substituted hydroxy lactams in good yield. These products were found to be resistant to further dehydration under a variety of conditions, however treatment with thionyl chloride elicited an unusual dehydration/oxidation reaction sequence. In contrast, acid-catalyzed cyclization of pyridines tethered to aliphatic aldehydes with amine linkers gives pyridyl-substituted dehydro-piperidine products. Similarly, intramolecular condensation of salicylaldehyde- and salicylketone-substituted pyridines affords pyridyl-substituted benzofurans.
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