Copper-catalyzed Chemoselective Reduction of α,β-unsaturated Flavone Olefin and It's Glycosides.

The chemoselective reduction of flavones to flavanones remains a significant synthetic challenge in the total synthesis of bioactive flavonoid glycosides. This chemoselective reduction of flavone olefin requires precise control over reactivity to reduce the conjugated α,β-unsaturated carbonyl system without affecting the functional groups commonly present in the complex carbohydrate derivatives. We report a straightforward copper-catalyzed reduction method using ammonia borane (NH3•BH3) as a hydrogen source. The catalytic system, based on a Cu(II) combination with bipyridine ligand, exhibited highly chemoselective hydrogenation of the C═C bond in the enone moiety of flavones to flavanones, whereas the Cu(I) without ligand reduced both functional groups to furnish flavanols. Notably, this methodology demonstrated a broad substrate scope with a wide range of functional group tolerance, including various sugar-derived substituents. The synthetic utility and versatility of the protocol were further highlighted through the useful synthesis of a library of mono- and disaccharide-conjugated flavonoid glycosides. Interestingly, this catalytic system displayed distinct reactivity by efficiently reducing carbonyl compounds to alcohols while inhibiting over-reduction to alkanes. Additionally, we performed a series of control experiments to gain a deeper insight into the mechanism and revealed that the reaction proceeds through the in situ generation of CuH in the reaction.