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

Abstract

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 TBAI 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 Me3Si-NR'2 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 the chiral DAAPs were examined in the two asymmetric reactions as organocatalysts, and some newly prepared Fc-DAAPs showed better enantioselectivity than the known species.