Palladium-Catalyzed Synthesis of Quinolines From Cyclopropanols

Significance

Reported is the palladium-catalyzed synthesis of substituted quinolines using 2-bromoanilines and cyclopropanols. It was hypo­thesized that bromoaniline serves as the terminal oxidant in the reaction, which was confirmed by isolation of dehalogenated aniline from the reaction and by deuterium-labelling studies. As a result of these investigations, a plausible mechanism was proposed. The synthesis of quinolines substituted at the 3-position can be difficult; however, the current method provides these when 2-substituted cyclopropanols are used as starting materials. Such cyclopropanols are either readily available or easily accessible, so this method should prove especially useful for the synthesis of 3-substituted quinolines.

Comment

Quinolines are important synthetic targets and intermediates with a wide range of previous methods for their synthesis (see Book below). The current method provides a useful extension of the palladium-catalyzed cross-coupling of cyclopropanols and aromatic halides previously optimized and utilized by the same group. This extension provides substituted quinolines and is optimized with respect to base, base stoichiometry, and reagent stoichiometry. The palladium catalysis was previously optimized and needed no further work. The scope of the reaction was investigated well and, as would be expected, tolerated a wide range of functionality on the aniline with modest to good yields. Monosubstituted cyclopropanols provided good yields of quinolines, and bicyclic cyclopropanols gave tricyclic quinolines in modest yields.

Book

R. D. Larson, D. Cai, In Science of Synthesis, Vol. 15; D. StC. Black, Ed.; Georg Thieme Verlag: Stuttgart, New York, 2005, 389–496.