Subcomponent Self‐Assembly of a Cyclic Tetranuclear FeII Helicate in a Highly Diastereoselective Self‐Sorting Manner

Abstract An enantiomerically pure diamine based on the 4,15‐difunctionalized [2.2]paracyclophane scaffold and 2‐formylpyridine self‐assemble into an optically pure cyclic metallosupramolecular Fe4L6 helicate upon mixing with iron(II) ions in a diastereoselective subcomponent self‐assembly process. The cyclic assembly results from steric strain that prevents the formation of a smaller linear dinuclear triple‐stranded helicate, and hence, leads to the larger strain‐free assembly that fulfils the maximum occupancy rule. Interestingly, use of the racemic diamine also leads to a racemic mixture of the homochiral cyclic helicates as the major product in a highly diastereoselective narcissistic chiral self‐sorting manner given the fact that the assembly contains ten stereogenic elements, which can in principle give rise to 149 different diastereomers. The metallosupramolecular aggregates could be characterized by NMR, UV/Vis and CD spectroscopy, mass spectrometry, and X‐ray crystallography.


General experimental information
All reactions with air and moisture sensitive compounds were performed under argon atmosphere using standard Schlenk techniques, oven-dried glassware and dry solvents.
The following chemicals were synthesized according to known literature synthesis procedures : 4,15diiodo[2.2]paracyclophane (rac)-A, [1] iron(II) triflate hexahydrate. [2] All solvents were obtained from commercial sources. Dry solvents were obtained from the solvent purification system MS-SPS 800 from MBraun. Other reaction solvents and solvents for specific rotation value, UV-Vis or CD measurements were solvents of p.a. grade. For flash column chromatography freshly destilled solvents of technical grade and for high performance liquid chromatography solvents of HPLC grade were used.
Thin-layer chromatography was performed on silica gel-coated aluminum plates with fluorescent indicator F254 from Merck. Detection was done by UV-light (254 and 366 nm).
Products were purified by flash column chromatography on silica gel 60 (particle size 0.040-0.063 mm) from Merck or on reversed phase silica gel (C18-RP, 17% C, 0.048-0.065 mm) from Acros Organics. 1 H, 13 C, H,H-COSY, HSQC, HMBC and 1 H-2D-DOSY NMR experiments were performed on a Bruker Avance I 500 spectrometer or a Bruker Avance III HD 700 spectrometer with a cryo probe. 1 H NMR chemical shifts are reported relative to residual non-deuterated solvent as internal standard. 13 C NMR chemical shifts are reported relative to deuterated solvent as internal standard. All shifts are reported on the  scale in ppm and NMR multiplicities are abbreviated as s (singlet), d (doublet), t (triplet), dd (doublet of doublets), ddd (doublet of doublet of doublets) or m (multiplet). Coupling constants J are reported in Hertz. All spectra were processed using the MestReNova 8.0.1 program from Mestrelab. 1 H-2D-DOSY NMR spectra were evaluated using the software Topspin 3.5 from Bruker and the Stokes-Einstein equation, normally used for spherical particles, with a correction factor for ellipsoids (Equation S1). [

S3
UV-Vis spectra were measured on a Specord 200 instrument from Analytik Jena and analyzed using the software WinASPECT 1.7.2.0. Quartz glass cuvettes from Hellma Analytics with a layer thickness of 10 mm (solutions of ligand precursors/ligands) and 0.01 mm (complex solutions) were used.
Circular dichroism (CD) spectra were measured on a J-810 spectrometer from Jasco. Quartz glass cuvettes from Hellma Analytics with a layer thickness of 1 mm (solutions of ligand precursors/ligands) and 0.01 mm (complex solutions) were used.
Specific rotation values were measured on an Anton Paar Model MCP 150 polarimeter with a standard wavelength of 589 nm using a cuvette with a layer thickness of 100 mm.
High performance liquid chromatography on analytical scale was performed on a PLATINblue HPLC system from Knauer, equipped with two pumps, an online degasser and a photodiode array detector PDA-1 with a deuterium and tungsten-halogen lamp (190-1000 nm), and a CHIRALPAK ® IB column (4.6 mm Ø, 250 mm) by Daicel was used. High performance liquid chromatography on semipreparative scale was performed on an Azura HPLC system from Knauer, equipped with a binary HPG pump P 6.1L, an online degasser, a multi wavelength detector MWL 2.1L with deuterium lamp (190-700 nm) and a fraction collector, and a CHIRALPAK ® IB column (20 mm Ø, 250 mm) by Daicel was used.

(R p )-, (S p )-and (rac)-4,15-Bis-(4-aminophenyl)[2.2]paracyclophane ((R p )-, (S p )-and (rac)-1)
Under an atmosphere of argon, (rac)-B (200 mg, 339 µmol, 1.00 eq.) was dissolved in dry dichloromethane (10 mL) and trifluoroacetic acid (5.22 mL, 7.73 g, 67.8 mmol, 200 eq.) was added. The reaction solution was stirred at room temperature for 18 h. Then, it was concentrated under reduced pressure, the residue was dissolved in ethyl acetate and neutralized with saturated potassium hydrogen carbonate solution. The mixture was extracted with ethyl acetate. The combined organic layers were washed with brine, dried with anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The crude product was dissolved in warm acetonitrile and precipitated as hydrochloride by adding hydrochloric acid (37%, 60.0 µL, 70.8 mg, 678 µmol, 2.00 eq.). The white solid was filtered off, washed with acetonitrile and dissolved in water. After the addition of saturated potassium hydrogen solution, the mixture was extracted with ethyl acetate. The combined organic layers were washed with brine, dried with anhydrous magnesium sulfate and the solvent was removed under reduced pressure to give (rac)-1 (110 mg, 282 µmol, 83%) as a yellow solid.      ). When upscaling to semipreparative mode, the flow rate was increased to 18 mL min