An easy route to atropoisomeric bipyridine N,N′-dioxides and allylation of aldehydes

Axially chiral bipyridine N,N′-dioxides (Lewis basic organocatalysts) are easily accessible in three steps from commercially available material. The key step of this reaction sequence is cobalt-catalyzed heterocyclotrimerization of 1-pyridyl-1,7-octadiynes with nitriles. Our effort was focused on the synthesis of unsymmetrically substituted bipyridines. The scope of the cyclotrimerization reaction was tested under thermal and microwave conditions. Two of the synthesized bipyridine N,N′-dioxides were successfully resolved into enantiomers and tested in enantioselective allylation of aldehydes.

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(S)-5,6,7,8-Tetrahydro-1-(3-methylpyridin-2-yl)-3-phenylisoquinoline N,N′-dioxideC21H20N2O2[α]D = −350 (c 0.01, CHCl3)Source of chirality: chiral HPLC separationAbsolute configuration: (S)

(S)-5,6,7,8-Tetrahydro-1-(3-methylpyridin-2-yl)-3-phenylisoquinolineC21H17F3N2O2[α]D = +39 (c 0.01, CHCl3)Source of chirality: chiral HPLC separationAbsolute configuration: (S)