Modular iminopyridine ligands. Application to the enantioselective copper(II)-catalyzed Henry reaction

Chiral iminopyridines prepared in a modular fashion from monoterpenic (camphor-derived) ketones and pyridinylalkylamines catalyze the enantioselective Henry (nitro aldol) reaction between nitromethane and o-anisol in the presence of copper(II) acetate, with high yields and good ee (up to 86%) under straightforward experimental conditions without the need for air or moisture exclusion.

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(E)-N-((1R,4R)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-ylidene)(pyridin-2-yl)methanamineC16H22N2[α]D25 = −24.2 (c 0.91, CHCl3)Source of chirality: (1R)-(+)-camphor

(E)-N-((1R,4R)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-ylidene)-2-(pyridin-2-yl)propan-2-amineC18H22N2[α]D25 = −5.6 (c 0.99, CHCl3)Source of chirality: (1R)-(+)-camphor

(E)-N-((1R,4R)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-ylidene)(6-methylpyridin-2-yl)methanamineC17H24N2[α]D25 = −23.9 (c 0.92, CHCl3)Source of chirality: (1R)-(+)-camphor

(E)-N-((1R,4R)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-ylidene)-2-(pyridin-2-yl)ethanamineC17H24N2[α]D25 = −28.4 (c 1.00, CHCl3)Source of chirality: (1R)-(+)-camphor

((E,1S,4R)-2-[(Pyridin-2-yl)methylimino]-7,7-dimethylbicyclo[2.2.1]heptan-1-yl)diphenylmethanolC28H30N2[α]D25 = +163.7 (c 0.97, CHCl3)Source of chirality: (1S)-(+)-ketopinic acid

(Z)-N-(1R,4S-1,3,3,7,7-Pentamethylbicyclo[2.2.1]heptan-2-ylidene)(pyridin-2-yl)methanamineC18H27N3O2S[α]D25 = −70.9 (c 0.38, CHCl3),Source of chirality: (1R)-(−)-fenchone