Versatile and Enantioselective Preparation of Planar-Chiral Metallocene-Fused 4‑Dialkylaminopyridines and Their Application in Asymmetric Organocatalysis

A series of ferrocene-fused planar-chiral N-tosyl-4-pyridones (S)-2b–d were prepared in enantiomerically pure forms. Starting with the chiral ferrocenyl acetals, 1-[(2S,4S)-4-methoxymethyl-1,3-dioxan-2-yl]-1′,2′,3′,4′,5′-R5-ferrocenes ((−)-3b, R = Me; (−)-3c, R = Ph; (−)-3d, R = Bn), N-tosylamino and formyl groups were introduced at the 1- and 2-positions of the ferrocene cores in (S)-11b–d with control of the planar chirality. After the reaction with ethynylmagnesium bromide, generated propargyl alcohol derivatives (S)-17 were treated with MnO2 and catalytic tetrabutylammonium iodide to give the planar-chiral pyridones by the iodide-catalyzed cyclization. This method is highly practical with a shorter and higher-yield sequence without using noble metal catalysts. Planar-chiral ferroco-pyridones (S)-2b–d were reacted with various Me3SiNR2 compounds to give a library of ferrocene-fused 4-dialkylaminopyridines ((S)-1, DAAPs) in high yields as single enantiomers by the detosylative amination. The cymantrene-fused DAAPs were also prepared in the same way. The library of chiral DAAPs was examined in the two asymmetric reactions as organocatalysts, and some newly prepared Fc-DAAPs showed better enantioselectivity than the known species.