Synthesis of axially chiral bipyridine N,N'-dioxides and enantioselective allylation of aldehydes

Abstract

N-oxides possessing the pyridine framework are strong Lewis bases that can activate the C–Si bond of allylhalosilanes to such an extent that they catalyze reactions with aldehydes. N-oxides embedded in chiral scaffolds are usually capable of highly selective chirality transfer to the derived products. Our goal was to develop a general synthetic method allowing the preparation of structurally varied N,N'-dioxides suitable for enantioselective organocatalysis. The underlying synthetic strategy was based on [2 + 2 + 2]-cyclotrimerization of suitably substituted diynes with nitriles catalyzed by Co-complexes to generate the desired bipyridines, their further oxidation and resolution of which furnished the corresponding chiral N,N'-dioxides. The prepared compounds were used in catalytic allylation of aromatic aldehydes to homoallyl alcohols with high enantioselectivity (up to 96 % ee). Enantioselectivity, enantiodiscrimination, and the reaction mechanism are controlled by the choice of solvent.