A method for the synthesis of pyridine-based C2-symmetrical chiral nucleophilic organocatalysts via Pd-catalyzed coupling

A one step Pd-catalyzed coupling methodology involving a reaction between a chiral diamine and a 2-bromo-4-(alkylamino)pyridine, was developed for the synthesis of novel C2-symmmetrical chiral compounds with chemical yields of up to 87%. The organocatalytic performance was tested as an alternative to the enzymatic kinetic resolution of 1-phenylethanol and a promising result of 76% ee was obtained. We observed that the catalysts synthesized had their own characteristics in terms of enantioselectivity; for example, non-nucleophilic heterogeneous auxiliary bases and ether solvents proved to be more efficient.

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N2,N2′-((9R,10R,11S,12S)-9,10-dihydro-9,10-ethanoanthracene-11,12-diyl)bis(N4,N4-dimethylpyridine-2,4-diamine)C30H32N6[σ]D27=-46.0(c0.2,CHCl3)Source of chirality: (9R,10R,11S,12S)-9,10-dihydro-9,10-ethanoanthracene-11,12-diamineAbsolute configuration: (9R,10R,11S,12S)

N2,N2′-((1R,2R)-Cyclohexane-1,2-diyl)bis(N4,N4-dimethylpyridine-2,4-diamine)C20H30N6[σ]D27=-41.0(c1.0,CHCl3)Source of chirality:(1R,2R)-cyclohexane-1,2-diamineAbsolute configuration: (1R,2R)

N2,N2′-((1R,2R)-1,2-Diphenylethane-1,2-diyl)bis(N4,N4-dimethylpyridine-2,4-diamine)C28H32N6[σ]D27=+35.6(c1.0,CHCl3)Source of chirality: (1R,2R)-1,2-diphenylethane-1,2-diamineAbsolute configuration: (1R,2R)

(R)-N2,N2′-([1,1′-Binaphthalene]-2,2′-diyl)bis(N4,N4-dimethylpyridine-2,4-diamine)C34H32N6[σ]D22=+232.8(c0.5,CHCl3)Source of chirality: (R)-[1,1’-binaphthalene]-2,2’-diamineAbsolute configuration: (R)

(R)-N2-(4-(Dimethylamino)pyridin-2-yl)-N2-(2′-((4-(dimethylamino)pyridin-2-yl)amino)-[1,1′-binaphthalen]-2-yl)- (N4,N4-dimethylpyridine-2,4-diamineC41H40N8[σ]D22=-35.5(c1.0,CHCl3)Source of chirality: (R)-[1,1’-binaphthalene]-2,2’-diamineAbsolute configuration: (R)

(9R,10R,11S,12S)-N11,N12-Bis(4-(pyrrolidin-1-yl)pyridin-2-yl)-9,10-dihydro-9,10-ethanoanthracene-11,12-diamineC34H36N6[σ]D23=-93.9(c1.0,CHCl3)Source of chirality: (9R,10R,11S,12S)-9,10-dihydro-9,10-ethanoanthracene-11,12-diamineAbsolute configuration: (9R,10R,11S,12S)