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DOI: 10.1055/s-0028-1083481
One-Pot Synthesis of Tetrahydroquinolines by an Imino-Diels-Alder Reaction
Contributor(s):Victor Snieckus, Dmitry N. KorolevWyeth Research, New York, USA
Practical One-Pot Procedure for the Synthesis of 1,2,3,4-Tetrahydroquinolines by the Imino-Diels-Alder Reaction
Synth. Commun. 2008, 38: 796-802
Publication History
Publication Date:
23 October 2008 (online)
Key words
tetrahydroquino-lines - imino-Diels-Alder reaction -
Significance
Reported is a synthesis of 1,2,3,4-tetrahydroquinolines by the Diels-Alder reaction of alkenes with iminium salts formed in situ from N-methylaniline and different sources of formaldehyde. The influence of the source of formaldehyde, Lewis acid and alkene structure on yield and stereochemistry of the products obtained was moderately investigated. The formation of both syn and anti products suggests the competition of pericyclic [4+2] cycloaddition with a stepwise mechanism involving cationic species.
Comment
Recently, many tetrahydroquinolines with biologically interesting properties have been investigated as drug candidates against cancer (N. B. Perry et al. J. Org. Chem. 1986, 51, 5476), inflammation (N. M. Williamson et al. Tetrahedron Lett. 1995, 36, 7721), and heart failure (T. Kimura J. Cardiovasc. Pharmacol. 1989, 49, 245), among other indications. In comparison to the known methods based on imino-Diels-Alder reaction (K. D. Hesse Justus Liebigs Ann. Chem. 1970, 741, 117; H. Posson et al. Synlett 2000, 209; R. Chen et al. Synth. Commun. 2002, 16, 2543) the present procedure appears to have the advantage of mild conditions, convenience, and broad scope in terms of variety of alkenes used.