title: Brønsted acid catalyzed intramolecular benzylic cyclizations of alkylpyridines.
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.
authors.affiliation: Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, USA. chris-pigge@uiowa.edu.
authors.forename: Ashabha I
authors.initials: AI
authors.lastname: Lansakara
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Farrell
authors.forename: F Christopher
authors.initials: FC
authors.lastname: Pigge
mesh_terms: D000143:Acids / Q000737:chemistry*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry*
chemical_list: D000143:Acids; D001572:Benzofurans; D007769:Lactams; D010880:Piperidines; D011725:Pyridines