Point-to-Axial Chirality Transmission: A Highly Sensitive Triaryl Chirality Probe for Stereochemical Assignments of Amines

Abstract

A readily available stereodynamic and the electronic circular dichroism (ECD)-silent 2,5-di(1-naphthyl)-terephthalaldehyde-based probe has been applied for chirality sensing of primary amines. The chiral amine (the inductor) forces a change in the structure of the chromophore system through the point-to-axial chirality transmission mechanism. As a result, efficient induction of optical activity in the chromophoric system is observed. The butterflylike structure of the probe, with the terminal aryl groups acting as changeable "wings", allowed for the generation of exciton Cotton effects in the region of ¹B_b electronic transition in the naphthalene chromophores. The sign of the exciton couplets observed for inductor-reporter systems might be correlated with an absolute configuration of the inductor, whereas the linear relationship between amplitudes of the specific Cotton effect and enantiomeric excess of the parent amine gives potentiality for quantitative chirality sensing. Despite the structural simplicity, the probe turned out to be unprecedentedly highly sensitive to even subtle differences in the inductor structure (i.e., O vs CH₂).

Chart 1. (a) Porphyrin-Based Noncovalent Probes for Chirality Sensing and (b) Exemplary Sterodynamic Probes for the Covalent Binding and Chirality Sensing of Amines

Figure 1

Schematic representation of the designed stereodynamic triaryl probe. Red arrows indicate polarizations of the electronic transition of the highest oscillator strengths within anthracene and naphthalene chromophores.

Chart 2. (a) Structures of Compounds under Study, (b) Oak Ridge Thermal Ellipsoid Plot (ORTEP) Drawing Showing an X-ray-Determined Structure of Dialdehyde 2 with Atom Numbering, and (c) Torsion Angles That Characterize a Molecular Conformation

Figure 2

UV (upper panels) and ECD (lower panels) spectra of (a) 3a (solid black lines) and 3b (dashed black lines), (b) 4a, (c) 4c, and (d) 4f (blue lines), measured in cyclohexane and calculated at the TD-CAM-B3LYP/6-311++G(d,p) level and ΔΔG-based Boltzmann-averaged UV and ECD spectra of 4a, 4c, and 4f (red lines). The calculated spectra were wavelength-corrected to match the UV maximum. Only the 185–350 nm region is shown. Experimental and calculated ECD spectra of 4f were multiplied by a factor of 4 to increase their visibility.

Figure 3

Overlays of X-ray diffraction-determined solid-state structures of (a) 4a (green) and 6a (orange), (b) 4b (aquamarine) and 6b (red), (c) 4c (deep yellow) and 6c (blue), and (d) 4f (deep yellow) and 6f (deep blue). For the disordered molecules, the fragments with lower occupancy factors are shown as a thin line. C-bound hydrogen atoms have been omitted for clarity, and the nitrogen and oxygen atoms are shown as balls.

Figure 4

(a) Molecular energy of 5 as a function of angles α₁ and α₂. (b) Computed at the TD-CAM-B3LYP/6-311++G(d,p) level, long- (R_long) and short-wavelength (R_short) rotatory strengths corresponding to experimental exciton couplets of the ¹B_b electronic transition as a function of angles α₁ and α₂. (c) Deconvolution of the ECD spectrum of the low-energy conformer of 5. The ECD spectrum calculated for the whole conformer is in black, the spectrum calculated for the AB part is represented by the blue solid line, the spectrum calculated for the AC part of the molecules is shown as the red line, and the effect of summation (S = 2 × AB + AC) is shown as a brown dashed line. Wavelengths were not corrected. Insets indicate the position of the low-energy electronic transition in 5. (d) Main molecular orbitals involved in the low-energy electronic transitions in the low-energy conformer of 5.

Scheme 1. Low-Energy C- and S-Type Conformers of Imine 5 and the Relationship between the Twist of the α Angles and Symmetry of the Molecule

Figure 5

(a) Overlay of low-energy conformers of 4a calculated at the B3LYP/6-311++G(d,p) level of individual conformers of 4a. (b) ECD spectra calculated at the TD-CAM-B3LYP/6-311++G(d,p) level for the individual low-energy conformers of 4a. Wavelengths were not corrected. Structural and spectral data for a given conformer are shown in the same color: conf. no 1, green; conf. no. 2, blue; conf. no. 4, black; and conf. no. 6, red.

Figure 6

Top (upper panel) and side (lower panel) views of the low-energy conformers of (a) 4d (conf. no. 14) and (b) 4h (conf. no. 1). The naphthyl rings closer to the observer are in green, whereas the naphthyl rings away from the observer are in red.

Figure 7

(a) ECD spectra of the crude imine samples, obtained from 2 and 3,3-dimethylbutan-2-amine of varying ee. (b) Linear relationships between CE amplitude at 227 nm (blue line) and 215 nm (red line) and the sample ee.

Chart 3. Exemplary Sterodynamic Inductor–Reporter Systems and Their Calculated Sensitivity Factors G