Enantioselective Recognition of Helicenes by a Tailored Chiral Benzo[ghi]perylene Trisimide π‐Scaffold

Abstract Enantioselective molecular recognition of chiral molecules that lack specific interaction sites for hydrogen bonding or Lewis acid–base interactions remains challenging. Here we introduce the concept of tailored chiral π‐surfaces toward the maximization of shape complementarity. As we demonstrate for helicenes it is indeed possible by pure van‐der‐Waals interactions (π–π interactions and CH–π interactions) to accomplish enantioselective binding. This is shown for a novel benzo[ghi]perylene trisimide (BPTI) receptor whose π‐scaffold is contorted into a chiral plane by functionalization with 1,1′‐bi‐2‐naphthol (BINOL). Complexation experiments of enantiopure (P)‐BPTI with (P)‐ and (M)‐[6]helicene afforded binding constants of 10 700 M−1 and 550 M−1, respectively, thereby demonstrating the pronounced enantiodifferentiation by the homochiral π‐scaffold of the BPTI host. The enantioselective recognition is even observable by the naked eye due to a specific exciplex‐type emission originating from the interacting homochiral π‐scaffolds of electron‐rich [6]helicene and electron‐poor BPTI.


Synthesis and Compound Characterization
The syntheses of precursors 2, 3, 4, 5 and 8 are described in the literature. S1  (M)-7 Scheme S1. Synthesis of literature known precursor 5 and new BPTI 6 and BPTI 7, with EtOH as ethanol, n-BuLi as n-butyllithium, THF as tetrahydrofuran and DMF as N, N-dimethylformamide.

Single Crystal X-ray Analysis
The crystal of rac-BPTI 7 was obtained by very slow diffusion ( > 6 weeks) of n-pentane in a solution of rac-BPTI 7 in MeCN and CHCl3. Figure S9. a) Photograph of crystal rac-BPTI 7. b) Side view of molecular structure of BPTI 7 obtained by single-crystal X-ray analysis and two perspectives on the crystal unit cell in c) side view and d) top view with (P)-and (M)-enantiomers shown in blue and red, respectively. Hydrogen atoms and solvent molecules are omitted for clarity. Figure S10. Molecular structure of rac-BPTI 7 obtained by single-crystal X-ray analysis. Hydrogen atoms are omitted for clarity in a) top view (distance between the two imide substituents shown, 28.3° as dihedral angle of bay position) b) side view (angles of 13.4° and 11.2° show the alignment of the successive π-planes to each other). and DFT-optimized geometry at the wb97xd/6-31g(d) level of theory of [6]helicene (G5) in c) top view (size of 9.7 Å with hydrogen atoms included, 27.8° as dihedral angle of helical planes) and d) side view (angles of 13.1° and 9.6° show the alignment of the successive π-planes to each other).

Activation Parameters for the Racemization of BPTI 7
To determine the activation parameters of BPTI 7 the racemization was monitored by time-dependent CD spectroscopy at different temperatures. Because of the high activation barrier, temperatures of 473-523 K were chosen and therefore the high boiling diphenylether was used as solvent. All samples were prepared in a temperature-resistant vial and heated to the respective temperature with an oil bath that has already been heated to the desired temperature. For each measurement, the solution was rapidly cooled with cold water and then a CD spectrum recorded. Afterwards, the vial with solution was again placed in the oil bath with the respective temperature. An uncertainty for the temperature of σT = ±5 K was assumed. The timer for racemization was started each time before heating and stopped before cooling the sample. It was assumed that no racemization takes place during the CD measurement at 293 K. Figure S11. Racemization of (P)-BPTI 7 in diphenylether at a) 473 K b) 483 K c) 493 K d) 503 K e) 513 K and f) 523 K monitored by time dependent CD spectroscopy.
Racemization follows a first order kinetic, so that the rate law for the racemization between (P)-and (M) enantiomer is given by: Where A is the concentration of the enantiomer present in excess and A0 is the initial concentration of this enantiomer. Due to the linear relationship between CD amplitude and the enantiomer concentration, A/A0 was calculated globally from the integrals (325-550 nm) of the time-dependent CD spectra ( Figure S11).
The rate constant k at certain temperatures can be determined by plotting the ln of A/A0 versus the time, which gives −k as the slope of the linear fit of the data points ( Figure S12). Figure S12. The logarithmic plot of A/A0 versus time shows the racemization rates of (P)-BPTI 7 in diphenylether at 473 K (black), 483 K (red), 493 K (blue), 503 K (green), 513 K (purple) and 523 K (yellow).
The racemization rate allows to calculate the half-life t½: With the Eyring equation (S5) the rate constant is related at different temperatures to the racemization barrier ∆G ‡ : Where κ is a transmission coefficient and for the racemization process κ = 0.5 since the probability of the transition state to transform into the one or the other enantiomer is equal. S8 h is Planck´s constant (6.63 × 10 −34 J s), kB the Boltzmann constant (1.38 × 10 −23 J K −1 ), T the temperature and R the gas constant (8.314 J mol −1 K −1 ). By rearranging the Eyring equation (S6) ∆G ‡ as well as the enthalpy ∆H ‡ and the entropy ∆S ‡ can be determined by plotting ln (k/T) versus 1/T ( Figure S13a): Likewise, the activation energy EA can be determined according to Arrhenius (S8) by plotting ln(k) versus 1/T with (−EA/R) as the slope and ln(A) as the y axis intercept of the plot ( Figure S13b). Figure S13. a) Eyring plot ln(k/T) versus 1/T for (P)-BPTI 7 at 473 K, 483 K, 493 K, 503 K, 513 K and 523 K. b) Arrhenius plot ln(k) versus 1/T for the racemization of (P)-BPTI 7 at 473 K, 483 K, 493 K, 503 K, 513 K and 523 K.
The uncertainty σ of all values were determined by the Gaussian error propagation law (S10). E.g. σ∆G ‡ was calculated via equation (S11).  Figure S12) and σT = ±5 K and is calculated with the equation (S11).
[d] Error calculated from the error of the linear regression ( Figure S13a).
[f] Error calculated from the error of the linear regression ( Figure S13b).
[g] Calculated with temperature dependent CD spectroscopy ( Figure S11) and an exponential fit via equation (S2).
[h] For the error of k, the error of the exponential fit ( Figure S12) was used.     Table S3. Optical properties of BPTI 7 in MCH solution determined by UV/vis, CD, fluorescence spectroscopy and CPL.

Titration Studies
For the titration experiments a solution of enantiomerically pure or racemic BPTI 7 and the respective guest in excess was titrated to a solution of the pure BPTI 7 solution by keeping the concentration of BPTI 7 constant. As the titrations were all carried out in MCH the concentration of the guest solution was limited by solubility. Theoretical spectra (black dotted lines) for each titration end point (corresponding to 1:1 complex) were calculated by using the following equations: With AH as the absorbance of the host molecule (BPTI 7), AHG as the absorbance of the host-guest complex and Arel as the measured absorption of a mixture of host and host-guest complex. The coefficients xH and xHG represent the mole fraction of the host and the host-guest complex, respectively. Both mole fractions were calculated from the experimental data via the global 1:1 fit of bindfit. S10 The respective binding constants Ka were calculated by a 1:1 nonlinear curve fit for specific wavelengths and a global 1:1 fit via the program bindfit. S10 Since the values obtained were by both approaches within the expected error range, the binding constants of the global fit were used in the discussion in the main section. For the studies using racemic mixtures of the host and [4]-to [6]helicene it was assumed, that only the respective homochiral complex will form in solution, so for the calculation of Ka the concentration of host and guest was divided by two.        Figure S30. 1 H NMR spectra of rac-BPTI 7 in a MCH-d14 and toluene-d8 mixture (24:1) at 293 K (c = 3.4 x 10 −4 M) upon the addition of rac-[6]helicene (G5) as a guest, b) an excerpt of the molecular structure of BPTI 7 and the resulting plots of the normalized shift of c) a scaffold proton marked with a red star and d) a BINOL proton marked with a blue star with nonlinear curve fit (1:1 binding model, red curve).