Highly regioselective Friedländer annulations with unmodified ketones employing novel amine catalysts: Syntheses of 2-substituted quinolines, 1,8-naphthyridines, and related heterocycles

Peter G. Dormer, Kan K. Eng, Roger N. Farr, Guy R. Humphrey, J. Christopher McWilliams, P. J. Reider, Jess W. Sager, R. P. Volante

Research output: Contribution to journalArticle

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Abstract

Catalysts were evaluated on the preparation of 2-substituted quinolines, 1,8-naphthyridines, and chromone derivatives from unmodified methyl ketones and o-aminoaromatic aldehydes. While oxide catalysts yielded the 2,3-dialkyl substituted products, cyclic secondary amines provided the 2-alkylsubstutited products regioselectively. In particular, pyrrolidine derivatives provided the highest regioselectivity favoring the 2-substituted products. The most reactive and regioselective catalyst was the bicyclic pyrrolidine derivative, TABO (1,3,3-trimethyl-6-azabicyclo [3.2.1] octane), yielding 1,8-naphthyridines with as high as 96:4 regioselectivity. Regioselectivity increased with slow addition of the methyl ketone substrate to the reaction mixture, and was positively related to temperature. Isolated yields of single regioisomers were typically 65-84%, while observed regioselectivities were ≥90:10 for 1,8-naphthyridines and ≥84:16 for quinolines.

Original languageEnglish (US)
Pages (from-to)467-477
Number of pages11
JournalJournal of Organic Chemistry
Volume68
Issue number2
DOIs
StatePublished - Jan 24 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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