Novel tridentate ligands derived from (+)-camphoric acid for enantioselective ethylation of aromatic aldehydes

Novel tridentate ligands were prepared from (+)-camphoric acid, using simple synthetic sequences. The synthesized ligands were used in enantioselective ethylations of benzaldehydes, showing enantioselectivities up to 92%, at room temperature. Extending the reaction to other aromatic aldehydes, very good results (almost quantitative yields and ee up to 97%, for m-anisaldehyde) were obtained. Structural features such as no substitution in the salicylaldehyde moiety of the Schiff base and an ethyl group in the nitrogen at the C1 position of the cyclopentane ring seem to be essential for obtaining high enantioselectivities.

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(1R,3S)-N1,N1-Dimethyl-N3-salicylidene-1,2,2-trimethylcyclopentane-1,3-diamineC27H48N4OEe = 100%[α]D20 = +108 (c 1, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1R,3S)

(1R,3S)-N1,N1-Dimethyl-N3-(3-methoxysalicylidene)-1,2,2-trimethylcyclopentane-1,3-diamineC18H28N2O2Ee = 100%[α]D20 = +110 (c 1, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1R,3S)

(1R,3S)-N1,N1-Dimethyl-N3-(3,5-di-t-butylsalicylidene)-1,2,2-trimethylcyclopentane-1,3-diamineC25H42N2OEe = 100%[α]D20 = +75 (c 1, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1R,3S)

(1R,3S)-N1,N1-Dimethyl-N3-(5-bromosalicylidene)-1,2,2-trimethylcyclopentane-1,3-diamineC17H25BrN2OEe = 100%[α]D20 = +60 (c 1, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1R,3S)

(1R,3S)-N1,N1-Dimethyl-N3-(2-hydroxyacetophenylidene)-1,2,2-trimethylcyclopentane-1,3-diamineC18H28N2OEe = 100%[α]D20 = +145 (c 1, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1R,3S)

(1R,3S)-N1,N1-Dimethyl-N3-(phenylidene)-1,2,2-trimethylcyclopentane-1,3-diamineC17H26N2OEe = 100%[α]D20 = +85 (c 1, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1R,3S)

(1R,3S)-N1,N1-Dimethyl-N3-(2-hydroxybenzyl)-1,2,2-trimethylcyclopentane-1,3-diamineC17H28N2OEe = 100%[α]D20 = +65 (c 1, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1R,3S)

(1R,3S)-N1,N1-Dimethyl-N3-(5-bromo-2-hydroxybenzyl)-1,2,2-trimethylcyclopentane-1,3-diamineC17H27BrN2OEe = 100%[α]D20 = +40 (c 1, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1R,3S)

(1R,3S)-N1-Ethyl-N3-salicylidene-1,2,2-trimethylcyclopentane-1,3-diamineC17H26N2OEe = 100%[α]D20 = +72 (c 1, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1R,3S)

(1R,3S)-N1-Ethyl-N3-(3-bromosalicylidene)-1,2,2-trimethylcyclopentane-1,3-diamineC17H25BrN2OEe = 100%[α]D20 = +64 (c 1, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1R,3S)