Evaluation of cobalt(III) tetramethylchiroporphyrin as an analytical reagent for the determination of enantiomer composition of primary amines and aziridines by 1H NMR spectroscopy

Abstract

The irreversible reaction of chlorocobalt(III) tetramethylchiroporphyrin CoCl(TMCP), 1, with nitrogen donor ligands L, such as primary amines and aziridines, in deuterated chloroform solution at room temperature gives cationic bis-adducts of the type [Co(L)₂(TMCP)]⁺Cl⁻ in quantitative yields. Upon binding to the chiral host 1, the protons of L experience a shielding by the porphyrin, and several of their ¹H NMR signals are shifted to a vacant spectral window upfield of tetramethylsilane (0 > δ > −6.5). The coordinated (R) and (S) enantiomers show well-resolved signatures at 200 MHz, allowing their relative concentrations to be readily determined by peak integration. Racemic amine derivatives such as 2-butylamine, 1-aminoindane, α-amino-γ-butyrolactone, 1-phenylethylamine, 2-aminomethoxypropane and 1-(1-naphthyl)ethylamine bind to 1 in CDCl₃ solution without detectable kinetic resolution, affording a 1:1 concentration ratio of the two cobalt-bound enantiomers (R_Co) and (S_Co), as measured by ¹H NMR. Aziridines such as ethyl 2-aziridinecarboxylate and 2-aziridinemethanol behave in an analogous manner. Standard solutions of 1-(1-naphthyl)ethylamine covering a range of enantiomer compositions x  = (R)/[(R) + (S)] (x  = 0, 0.1, 0.25, 0.5, 0.75, 0.9, 1) were analyzed using 1 as a chiral NMR shift reagent. The bound enantiomer composition values y  = (R_Co)/[(R_Co) + (S_Co)] measured by NMR were in good agreement with those of the standard solutions, and the calibration curve y  =  f(x) was linear in the range 0⩽x⩽1, within experimental error. These features of 1 as a chiral analytical reagent may prove suitable for the accurate determination of a wide range of enantiomeric excesses of amines and aziridines. The crystal structures of {Co[(R)-1-(1-naphthyl)ethylamine]₂(TMCP)}⁺Cl⁻ and {Co[(R)-2-butylamine]₂(TMCP)}⁺Cl⁻ are described.